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We examine the problem of optimally maintaining a stochastically degrading system using preventive and reactive replacements. The system's rate of degradation is modulated by an exogenous stochastic environment process, and the system fails when its cumulative degradation level first reaches a fixed deterministic threshold. The objective is to minimize the total expected discounted cost of preventively and reactively replacing such a system over an infinite planning horizon. To this end, we present and analyze a Markov decision process model. It is shown that, for each environment state, there exists an optimal threshold-type replacement policy. Additionally, empirical evidence suggests that, when the environment process is monotone, and the state-dependent degradation rates are totally ordered, the optimal threshold is monotone. Lastly, we derive closed-form bounds on the optimal thresholds. [ABSTRACT FROM AUTHOR]

We report a 20 year old case of partial androgen insensitivity syndrome, referred to our clinic with complaints concerning external genital organs and left undescended testicle. The phenotypically male case was first evaluated for secondary sex development. Axillary hair was scanty and no pubic hair was found. There was no breast development. In the gynecological examination, the clitoris was hypertrophic (4.6 cm) and a blind vagina with intact hymen was seen. Abdominopelvic ultrasonography revealed the absence of an uterus and adnexes which was supported by magnetic resonance imaging (MRI). There was a palpable mass in the left inguinal canal (cryptorchism), seen as atrophic tissue under the skin in MRI. Although the other testis was in the labioscrotal fold, it was atrophic. The Karyotype was 46 XY after genetic investigation. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to determine the presence of deep infiltrative endometriosis (DIE) in the surgical management of endometriosis., Material and Methods: Operation notes and histopathological reports of women with endometriosis were retrospectively analyzed in the Ege University Hospital between 2008 and 2018. A total of 191 women with suspicious of endometriosis but without clinical signs of DIE were enrolled in the study. Laparoscopic diagnosis of DIE was compared with histopathological reports. There was no histopathology before surgery. Endometriosis was suspected only based on symptoms., Results: A total of 213 lesions that were thought to be DIE were removed from 191 women with endometriosis. Among these 213 lesions, 179 specimens were reported as endometriosis and 34 lesions as fibro-adipose tissue. Forty-nine right uterosacral ligaments were excised, and endometriosis was detected in 44 out of 49 specimens. Histopathological examination of 45 left uterosacral ligaments revealed endometriosis in 35 specimens. Finally, 25 endometriotic nodules were removed from the recto-vaginal space, and 22 of these were verified as endometriosis by a pathologist. The positive predictive value of laparoscopic visualization for DIE in the group suspected of endometriosis but without any clinical findings of DIE was 84%., Conclusions: Women with the suspicious of endometriosis, qualified to surgery, because of infertility or pain, should be prudently investigated to confirm or to exclude coexistence of DIE even if no preoperative sign of DIE was observed to provide complete resection. Otherwise, DIE continues to grow, causes pain postoperatively, and complicates subsequent surgery.

To evaluate the potential effect of Ankaferd Blood Stopper (ABS) and oxytocin (OT) in an experimental endometriosis model, 18 female Sprague Dawley rats were used in this study. The animals were divided randomly into three groups after surgical induction of endometriosis: group 1: control group (isotonic NaCl, 1 mL/kg/day, intramuscular, n=6); group 2: OT group (OT, 80 U/kg/day, intramuscular, n=6); group 3: ABS group (ABS, 1.5 mL/kg/day, intraperitoneal, n=6). Each group was treated for four weeks (two times per week). Volumes of endometriotic explants were measured in biopsy samples for histopathological analysis. Vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and tumour necrosis factor (TNF-α) levels were measured in plasma and peritoneal fluid. Endometriotic explant volumes were significantly decreased after OT administration (P<0.0001). The epithelial score was significantly decreased in both treatment groups compared to the control group (P<0.05). TUNEL immunohistochemistry showed more apoptotic changes in the endometriosis foci (gland epithelium and surrounding tissue) in the OT group than in the control group (P<0.05). The levels of VEGF, MCP-1, and TNF-α were significantly reduced in the OT group (P<0.05), whereas no significant changes in protein levels were found in the ABS-applied group. The results indicate that OT has greater potential as a therapeutic agent in experimentally induced peritoneal endometriosis, where ABS, which is a VEGF modulator, appears to act through different mechanisms to show its palliative effects on a rat model of peritoneal endometriosis.

Study Objective: To demonstrate a new technique of isthmocele repair via laparoscopic surgery., Design: Case report (Canadian Task Force classification III). The local Ethics Committee waived the requirement for approval., Setting: Isthmocele localized at a low uterine segment is a defect of a previous caesarean scar due to poor myometrial healing after surgery [1]. This pouch accumulates menstrual bleeding, which can cause various disturbances and irregularities, including abnormal uterine bleeding, infertility, pelvic pain, and scar pregnancy [2-6]. Given the absence of a clearly defined surgical method in the literature, choosing the proper approach to treating isthmocele can be arduous. Laparoscopy provides a minimally invasive procedure in women with previous caesarean scar defects., Intervention: A 28-year-old woman, gravida 2 para 2, presented with a complaint of prolonged postmenstrual bleeding for 5 years. She had undergone 2 cesarean deliveries. Transvaginal ultrasonography revealed a hypoechogenic area with menstrual blood in the anterior lower uterine segment. Magnetic resonance imaging showed an isthmocele localized at the anterior left lateral side of the uterus, with an estimated volume of approximately 12 cm 3 . After patient preparation, laparoscopy was performed. To repair the defect, the uterovesical peritoneal fold was incised and the bladder was mobilized from the lower uterine segment. During this surgery, differentiating the isthmocele from the abdomen can be challenging. Here we used a Foley catheter to identify the isthmocele. To do this, after mobilizing the bladder from the lower uterine segment, we inserted a Foley catheter into the uterine cavity through the cervical canal. We then filled the balloon of the catheter at the lower uterine segment under laparoscopic view, which allowed clear identification of the isthmocele pouch. The uterine defect was then incised. The isthmocele cavity was accessed, the margins of the pouch were debrided, and the edges were surgically reapproximated with continuous nonlocking single layer 2-0 polydioxanone sutures. We believed that single-layer suturing could provide for proper healing without necrosis due to suturation. During the procedure, the vesicouterine space was dissected without difficulty. A urine bag was collected with clear urine, and there was no gas leakage; thus, we considered a safety test for the bladder superfluous. Based on concerns about the possible increased risk of adhesions, we did not cover peritoneum over the suture. The patients experienced no associated complications, and she reported complete resolution of prolonged postmenstrual bleeding at a 3-month follow-up., Conclusion: Even though the literature is cloudy in this area, a laparoscopic approach to repairing an isthmocele is a safe and minimally invasive procedure. Our approach described here involves inserting a Foley catheter in the uterine cavity through the cervical canal, then filling the balloon in the lower uterine segment under laparoscopic view to identify the isthmocele., (Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.)

Endometriosis is a common chronic gynecological disease that is classically defined by the presence of endometrial stromal and glandular tissues outside the uterine cavity. Pelvic pain and infertility are the nonspecific but the most common symptoms of the disease; however, no currently definitive treatment has been developed since its pathogenesis has not been completely understood. Currently, none of the proposed conventional theories can explain all aspects of endometriosis. Recent evidence supports the presence of endometrial stem/progenitor cells and their possible involvement in endometrial regeneration and differentiation. The stem cell theory is a new hypothesis which may clarify the underlying pathophysiologic mechanisms of endometriosis. However, this theory could not only account for an alternative pathogenic mechanism of endometriosis but could also be involved in all conventional theories. This article will review the evidence for the presence of endometrial stem/progenitor cells, their possible sources and their possible involvement in the pathogenesis of endometriosis.

Objectives: To determine whether there exists a relationship between age and side dominance of tubal ectopic pregnancies., Material and Methods: One hundred twenty patients were retrospectively analyzed. The sides of the tubal ectopic pregnancies were recorded on the basis of laparoscopy or laparotomy findings. Five age groups were created: 20-24, 25-29, 30-34, 35-39, and > or = 40 years., Results: Of the patients who were > 30 years of age, 46 (69%) and 21 (31%) had tubal ectopic pregnancies on the right and left sides, respectively (p = 0.002). In the 35-39 years of age group, 17 of 20 patients (85%) had tubal ectopic pregnancies on the right, and 3 of 20 patients (15%) on the left side (p = 0.002). In the 30-34 years of age group, 26 of 39 patients (67%) and 13 of 39 patients (33%) had tubal ectopic pregnancies on the right and left sides, respectively (p = 0.037). In the > or = 40 years of age group, 3 of 8 patients (37%) had tubal ectopic pregnancy on the right side, while 5 patients (63%) on the left side (p = 0.48)., Conclusions: Patients who are between the age of 30-40 years have a right-sided dominance of tubal ectopic pregnancy however studies that involve larger numbers of subjects are needed to make definitive conclusions about women older than 40 years of age.

Objective: To determine the effects of oxytocin (OT) on surgically induced endometriosis in a rat model., Study Design: Twelve female Sprague-Dawley rats were included. After the implantation and establishment of autologous endometrium onto the abdominal wall peritoneum, the rats were randomly divided into two groups, treated with intramuscular oxytocin (OT group, 160μgkg/day, n=6) or isotonic NaCl solution (control group, 1mLkg/day, n=6) for 28 days. To evaluate the therapeutic effects of OT, the explant volumes were calculated and the levels of vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1, and TNF-α were measured in plasma and peritoneal fluid. Endometriotic explants were examined histologically by semiquantitative analysis., Results: After treatment, the mean endometriotic explant volume was decreased in the OT group (p=0.016). The histopathological score and VEGF immunoexpression of endometriotic explants were significantly lower in the OT group (p=0.007) than in controls (p=0.000). Inflammatory cytokine levels in plasma and peritoneal fluid were considerably decreased in the OT group. Moreover, TUNEL immunohistochemistry clearly demonstrated more apoptotic changes in the mononuclear cells of the OT group compared with controls., Conclusion: We suggest that oxytocin might be considered as a potential candidate therapeutic agent for endometriosis., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

We aimed to compare the effects of different types of hormone treatment (HT) on endothelial function by means of brachial artery ultrasonographic examination in postmenopausal women. Sixty-two healthy postmenopausal women were included in this study. Subjects were assigned to one of the five groups receiving 6 months of treatment [estrogen (conjugated estrogen), estrogen (conjugated estrogen) plus progesterone (medroxyprogesterone acetate; MPA), raloxifene, tibolone or control]. Endothelial function was assessed by measurement of flow-mediated dilatation (FMD) and nitrate-dependent dilatation in the brachial artery. At the end of 6 months, FMD values were found to be significantly increased in women with HT use than the control group (p = 0.001). In subgroups, FMD increased significantly in the estrogen [12 ± 7 versus 25 ± 8, p = 0.001] and raloxifene groups [7 ± 5 versus 11 ± 3, p < 0.01] compared to tibolone and estrogen plus progesterone groups. In conclusion, endothelial function is impaired in postmenopausal women. Both estrogen and raloxifene regimens may improve endothelial functions in healthy postmenopausal women. The direct protective effects of these HT on the healthy endothelium may be more remarkable than the favorable effects on lipid profile.

Objective: To investigate that endometrioma is an asymmetric disease with left lateral predisposition as compared to other benign ovarian cyst and also, whether endometrioma side is related with endometriosis severity., Methods: Operative and histopathologic findings of 340 women who underwent cystectomy for treatment of endometriotic (n = 239) and nonendometriotic ovarian cysts (n = 101) by laparoscopy (n = 268) or laparotomy (n = 72) between January 2005 and August 2009 were evaluated retrospectively. We compared left and right sided distribution of endometriotic and nonendometriotic ovarian cysts, and we also investigated the extent of endometriotic foci, obliteration of pouch of Douglas and endometriosis stage according to the revised American Fertility Society classification of endometriosis to assess whether endometrioma side is related with the severity of endometriosis., Results: Of 239 women with endometriosis, endometrioma was found in the left ovary (n = 109), right ovary (n = 58) and bilaterally (n = 72). Of 101 control group women functional and dermoid cysts were found in the left ovary (n = 48), right ovary (n = 43) and bilaterally (n = 10). Among women with unilateral ovarian endometrioma (n = 167) a left cyst (63.3%) was found more frequently than a right cyst (34.7%) (P < 0.0001). In women with a left ovarian endometrioma pouch of Douglas was open in 99 (90.8%) cases. However, it was partially obliterated in 3 (2.8%) and completely obliterated in 7 (6.4%) cases. On the other hand, in women with a right endometrioma it was open in 44 (75.9%) cases and partially obliterated in 2 (3.4%) and completely obliterated in 12 (20.7%) cases. In women with a right endometrioma, the possibility of the pouch of Douglas obliteration is significantly higher than the women with a left endometrioma (P = 0.006)., Conclusion: Moreover, we also showed that in women with a right endometrioma, incidence of the pouch of Douglas obliteration is higher and the endometriosis tends to be more severe compared to women with a left endometrioma. Our most relevant observation is obliteration of Douglas pouch which was found to be more extensive in women with right ovarian endometrioma. Our results showing left lateral predisposition of endometriomas are in agreement with the previous reports and highlight the retrograde menstruation theory for the pathogenesis of this enigmatic disorder.

Endometriosis is a benign and common disorder that is characterized by ectopic endometrium outside the uterus. Extrapelvic endometriosis, like of the vulva, is rarely seen. We report a case of a 47-year-old woman referred to our clinic due to complaints of a vulvar mass and periodic swelling of the mass at the time of menstruation. During surgery, the cyst ruptured and a chocolate-colored liquid escaped onto the surgical field. The cyst was extirpated totally. Hipstopathological examination showed findings compatible with endometriosis. She was asked to follow-up after three weeks. The patient had no complaints and the incision field was clear at the follow-up.

Purpose of Investigation: To evaluate the prevalence and effects of inherited thrombophilia caused by factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T mutations in women with recurrent pregnancy loss., Methods: A study group of 97 women with recurrent miscarriages and a control group of 71 healthy pregnant women were included in the study. Genotype analyses for factor V Leiden, prothrombin G20210A and MTHFR C677T polymorphisms were performed by real-time polymerase chain reaction (RT-PCR)., Results: The frequency of factor V Leiden, prothrombin G20210A and MTHFR C677T mutations were similar in both the study and control group. There were eight patients (8.2%) who had more than one gene mutation in the study group and one patient in the control group (1.4%). This difference was not statistically significant. Study group patients (n = 97) were compared in terms of the number of miscarriages and the abortion week, in addition to being a carrier of factor V Leiden and MTHFR C677T gene mutations. No statistically significant correlation was found between being a factor V Leiden and MTHFR C677T mutation carrier with either the number of miscarriages or the abortion week., Conclusion: Factor V Leiden, prothrombin G20210A and MTHFR C677T gene mutations are not individually related with recurrent pregnancy loss. However, combined gene mutation status may be associated with recurrent miscarriages.

The main aim of this study is to describe the in vivo temporal and spatial expression of monocyte chemotactic protein 1 (MCP-1) in human endometrial endothelial cells (HEECs) and to compare the in vitro regulation of MCP-1 expression by sex steroids in HEECs from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to the menstrual cycle phase and were examined by immunohistochemistry for MCP-1 expression. No significant difference was observed for MCP-1 immunoreactivity in the endothelial cells of eutopic endometrium of women with endometriosis when compared to endometrium of women without endometriosis and to endometriosis implants. For in vitro studies, the purity of cultured HEECs (90%-95%) was confirmed by immunocytochemistry using endothelium-specific markers CD31 and CD146. The effects of estradiol (5 x 10(- 8) mol/L), progesterone (10(-7) mol/L), or both on MCP-1 messenger RNA (mRNA) and protein levels were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent serologic assay (ELISA), respectively. Sex steroids did not have significant effect on MCP-1 mRNA and protein expression in HEECs from women without endometriosis. However, we observed that the sex steroid treatment stimulated MCP-1 mRNA and protein expression in HEECs from women with endometriosis (P < .05). We postulate that the stimulation of chemokine expression by sex steroids in the endometrial endothelial cells in women with endometriosis may play a central role in recruiting mononuclear cells, therefore contributing to the inflammatory aspect of endometriosis.

Protein kinase B (PKB/Akt), a serine/threonine kinase, regulates the function of many cellular proteins involved in apoptosis and proliferation. It was postulated that there is a higher Akt activity in endometriosis compared with normal endometrium, and that oestrogen may be one of the factors responsible for the high Akt activation in endometriotic cells. Phospho-Akt (pAkt) concentrations in normal, eutopic and ectopic endometrial tissues were compared by immunohistochemistry, and a higher pAkt immunoreactivity was revealed in eutopic and ectopic endometrium compared with normal endometrium, in vivo. Higher Akt phosphorylation in stromal cells from eutopic endometrium was observed, when compared with normal, in vitro (P < 0.05). Akt phosphorylation was rapidly (2-10 min) stimulated when endometrial stromal cells from normal and endometriosis patients were treated with 17 beta-oestradiol. In endometrial stromal cells from the endometriosis group, ICI 182,780 (ICI, a specific oestrogen receptor antagonist) failed to antagonize the effect of oestradiol when combined with oestradiol, and revealed a stimulatory effect on Akt phosphorylation when given alone (P < 0.05). In conclusion, since Akt affects cell survival, it is suggested that increased Akt phosphorylation may be related to the altered apoptosis/proliferation harmony in endometriosis, and therefore Akt may play a critical role in the pathogenesis of endometriosis.

Objective: To investigate the expression and localization of interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in women with and without endometriosis., Design: Comparative immunohistochemical study., Setting: Academic medical center., Patient(s): Ectopic (n = 24) and homologous eutopic endometrium (n = 24) from women with endometriosis and endometrium from women without endometriosis (n = 27) were used for immunohistochemical analysis of IL-8 and MCP-1., Intervention(s): Tissue sections were immunostained with antihuman IL-8 and MCP-1 antibodies., Main Outcome Measure(s): Microscopic evaluation to assess the presence and localization of IL-8 and MCP-1 throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with endometriosis and comparison with normal endometrium., Result(s): In normal endometrium, secretory phase samples expressed higher levels of epithelial IL-8 than in proliferative phase samples. Epithelial MCP-1 expression was similar in both proliferative and secretory phases. Proliferative phase samples showed higher epithelial IL-8 and MCP-1 expressions in eutopic endometrium of women with endometriosis compared with that of normal women. Immunoreactivities of both chemokines were significantly increased in the epithelial cells of ectopic endometrial tissues compared with those of normal endometrium., Conclusion(s): These findings suggest that IL-8 and MCP-1 may be involved in the pathogenesis of endometriosis.

Objective: The purpose of this study was to compare the clinical symptoms and histopathological findings in subjects with adenomyosis uteri., Method: Infiltration depth and spread of adenomyotic foci together with clinical symptoms and findings were compared in a total of 103 subjects who had undergone hysterectomy and were diagnosed with adenomyosis uteri through histopathological examinations., Results: The spread of adenomyotic foci in myometrial tissues was observed to significantly increase as the depth of myometrial infiltration increased in subjects with adenomyosis (p < 0.05). It was observed that there was significantly higher myometrial infiltration depth in subjects with dysmenorrhea and severe anemia, and diffuse adenomyotic foci in subjects with menometrorrhagia (p < 0.05)., Conclusion: Increased infiltration depth and spread of adenomyotic foci in myometrial tissues in subjects with adenomyosis uteri were studied. When clinical symptoms and findings in subjects with adenomyosis, such as dysmenorrhea, anemia and menometrorrhagia are compared with these histopathological findings, infiltration depth and spread of adenomyotic foci appear to determine the clinical severity of adenomyosis.

Objective: This prospective study investigated the prevalence of adenomyosis in histopathological examinations of patients who had undergone hysterectomy due to various indications in our clinic. Epidemiological characteristics, predisposing risk factors, symptoms and clinical findings of adenomyosis were evaluated., Method: A total of 298 subjects who had undergone abdominal, vaginal or laparoscopic hysterectomy with/without salpingooophorectomy between October 2003 and April 2004 in our clinic were included. Uterine specimens obtained through hysterectomy were weighed and histopathologically examined in the Pathology Department of Ege University. The study group (n = 103), cases with adenomyosis, was compared with the control group (n=195), cases without adenomyosis, with respect to the epidemiological, clinical and histopathological characteristics., Results: The prevalence of adenomyosis in 298 subjects was 36.2% (103). Duration of the reproductive period in patients with adenomyosis was found to be significantly longer than for those in the control group (p < 0.05). Prevalence of pelvic pain, dysmenorrhea and dyspareunia was also significantly higher in the study group (p < 0.05). Moreover, the number of cases requiring blood transfusion before the operation was significantly higher in the study group (p < 0.05) as were the rates of smoking, previous uterine surgery and nulliparity (p < 0.05). The most common gynecological condition accompanying adenomyosis was found to be uterine myoma in both groups, but the difference was not significant., Conclusion: Adenomyosis is not a rare histopathological finding. Due to diagnostic and therapeutic methods which are being developed as an alternative to hysterectomy, the clinical effects of adenomyosis and its association with other gynecological conditions, adenomyosis appears to be an issue which will be more intensively investigated in the future.

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus. Several theories have been proposed to explain the pathogenesis of this disease. According to Sampson's retrograde menstruation theory, endometrial cells are refluxed through the fallopian tubes during the menstruation and implant onto peritoneum or pelvic organs. Since retrograde menstruation is a very common phenomenon among women of reproductive age, there must be other factors that may contribute to the pathophysiology and/or pathogenesis of endometriosis. Genetic predisposition, environmental factors, and alterations in immune and endocrine functions are believed to play significant roles in the establishment and maintenance of endometriosis. Although the eutopic endometriums of women with and without endometriosis are histologically similar, studies revealed that there are many fundamental differences between these two tissues. Invasive properties, decreased apoptosis, alterations in expression of specific gene and proteins, and increased steroid and cytokine production have been identified in eutopic endometrium of women with endometriosis. Furthermore, significant biochemical differences exist even between ectopic and autologous eutopic endometrium. These differences can be explained by the direct effects of an inflammatory peritoneal environment.

Objective: To investigate the expression of interleukin-8 (IL-8) receptors CXCR1 and CXCR2 in adenomyosis., Design: Comparative immunohistochemical study., Setting: Academic medical center., Patient(s): Thirty women who had undergone hysterectomy and were proved histopathologically to have adenomyosis, and 27 women without adenomyosis who had a hysterectomy for nonendometrial pathology such as leiomyomata or benign ovarian cysts., Intervention(s): Tissue sections were immunostained with murine monoclonal anti-human CXCR1 and CXCR2 antibodies., Main Outcome Measure(s): Microscopic evaluation to assess the presence and localization of CXCR1 and CXCR2 throughout the menstrual cycle in both eutopic endometrial and adenomyotic tissues of women with adenomyosis and compare it with normal endometrium., Result(s): In eutopic endometrium of women with adenomyosis, proliferative phase samples showed higher epithelial CXCR1 and CXCR2 staining intensity compared with proliferative phase samples of normal endometrium. Adenomyosis foci expressed higher epithelial CXCR1 compared with the homologous eutopic endometrium and normal endometrium. On the other hand, adenomyosis foci and the homologous eutopic endometrium showed similar epithelial CXCR2 staining intensity, and this expression was higher than the normal controls., Conclusion(s): Intrinsic abnormalities concerning IL-8 and its receptor system may be present in the eutopic endometrium of women affected by adenomyosis. These findings suggest that IL-8 receptors may be involved in the pathogenesis and/or pathophysiology of adenomyosis.

Background: The present study evaluates the efficacy of a broad-spectrum chemokine inhibitor, NR58-3.14.3, in the prevention of adhesion formation after i.p. surgery in mice., Methods: A total of 110 eight week old female Balb/c mice underwent laparotomy. Forty animals were randomly assigned to receive daily i.p. injections of either vehicle (control) or NR58-3.14.3. Time-course of adhesion formation was assessed. A titration of NR58-3.14.3 was conducted for i.p. and s.c. administrations. The effectiveness of a single intra-operative dose of NR58-3.14.3 was evaluated. Number, extent, location and type of adhesions were recorded. Immunohistochemistry of adhesions was done with leukocyte common antigen, CD45., Results: Adhesion scores peaked on post-operative days 6-8. On both days 6 and 8, there were smaller adhesion size and lower cumulative adhesion scores in NR58-3.14.3-treated group. Moreover, on day 8, there were significantly fewer adhesions in NR58-3.14.3-treated group compared to controls. The least effective dose for i.p. administration of NR58-3.14.3 was 0.45 mg/animal. Subcutaneous and single intra-operative i.p. administrations were also effective in the prevention of i.p. adhesions. Although NR58-3.14.3 decreased the number of CD45+ inflammatory cells in the adhesions by 22.5% compared to control group, this was not significant., Conclusions: Our results show that this broad-spectrum chemokine inhibitor prevents post-operative adhesions in mice and may have a potential clinical use.

Background: To clarify the inflammatory nature of adenomyosis, we aimed to investigate the expression of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) by immunohistochemistry to determine their putative role in pathophysiology of adenomyosis., Methods: Adenomyosis samples, with their eutopic endometrium, were collected from 30 women undergoing hysterectomy. Endometrium from 27 women without adenomyosis were also collected as a control group. Samples were grouped according to the menstrual cycle phase and examined by immunohistochemistry for IL-8 and MCP-1., Results: In normal endometrium, secretory phase samples expressed higher levels of epithelial IL-8 than in proliferative phase samples (P = 0.01), and we observed a trend for an increased epithelial MCP-1 expression in the secretory phase samples compared with the proliferative phase samples (P = 0.07). Endometrial samples of women with adenomyosis did not show the same cyclic variation. In the secretory phase, eutopic endometrium of women with adenomyosis expressed lower levels of epithelial IL-8 and MCP-1 compared with normal endometrium (P < 0.05). The expression of epithelial IL-8 and MCP-1 was higher in the adenomyosis foci than the eutopic endometrium (P < 0.05)., Conclusions: These findings may indicate that an intrinsic abnormality of inflammatory response may be present in eutopic endometrium of women with adenomyosis, and IL-8 and MCP-1 may contribute to the pathophysiology of adenomyosis.

Endometriosis is classically described as the presence of both endometrial glandular and stromal cells outside the uterine cavity, mainly in the pelvis. The pathogenesis of this enigmatic disorder still remains controversial despite extensive research. Although multiple theories have been put forth to explain the pathophysiology and pathogenesis of endometriosis, the retrograde menstruation theory of Sampson is the most widely accepted. However, since retrograde menstruation occurs in most of the reproductive age women, it is clear that there must be other factors which may contribute to the implantation of endometrial cells and their subsequent development into endometriotic disease. There is substantial evidence to support that the alterations in both cell-mediated and humoral immunity contribute to the pathogenesis of endometriosis. Increased number and activation of peritoneal macrophages, decreased T cell and natural killer (NK) cell cytotoxicities are the alterations in cellular immunity and result in inadequate removal of ectopic endometrial cells from the peritoneal cavity. Moreover, increased levels of several cytokines and growth factors which are secreted by either immune and endometrial cells seem to promote implantation and growth of ectopic endometrium by inducing proliferation and angiogenesis. In addition to the impaired capacity of the immune cells to mediate endometrial cell removal, inherent resistance of the ectopic endometrial cells against immune cells is another interesting concept in the pathogenesis of endometriosis. Endometriosis has also been considered to be an autoimmune disease, since it is often associated with the presence of autoantibodies, other autoimmune diseases, and possibly with recurrent immune-mediated abortion.

It is believed that ovarian endometriosis may be generated by a celomic metaplastic process from existing epithelium in the ovary. However, no morphologic evidence of metaplastic process has been described. In this study, we intended to identify the earliest morphologic changes of endometriosis within the ovary to examine if evidence of metaplasia exists. Included in this study were 110 ovarian endometriosis cases and 30 benign ovaries without endometriosis but with ovarian epithelial inclusions (OEIs). Among the 110 well-established ovarian endometriosis cases, 34 cases showed areas of initial endometriosis (IE), which is defined as lesions showing direct transitions from normal-looking ovarian tissue to areas of minimal formation of endometriosis and/or to areas of full-blown endometriosis. We further divided IE into two types: type I IE was present on the ovarian surface, which was associated with ovarian surface epithelia; type II was located within the ovarian cortex, which was associated with OEIs. Sections containing IE, OEIs, and well-formed endometriosis were subject to CD10 and aromatase immunostaining. In IE lesions, the number of CD10-positive cells were significantly higher than the number of that in OEIs, but lower than that of well-formed endometriosis areas (p < 0.05). Aromatase expression was detected in both epithelial and stromal components of the IE lesions, indicating that estrogen local production may be involved in this initial process of endometriosis. Microvessel density was higher in IE lesions than in areas of OEI (p < 0.05). Based on the morphologic characteristics of IE, we believe that IE represent a spectrum of the earliest morphologic changes of endometriosis identifiable by routine microscopy. The morphologic transitions from ovarian surface epithelium or OEI to IE lesions provide direct metaplastic evidence for the pathogenesis of ovarian endometriosis. This metaplastic process may not only involve the ovarian epithelial cells, but also stromal components. Local production of estrogen, probably in high-levels, may be related to the initial process of endometriosis, although detailed mechanisms remain to be clarified.

Background: Although the etiology of endometriosis is not well understood, chemokines and their receptors are believed to play a role in its pathogenesis. Therefore, we aimed to investigate the expression and localization of interleukin-8 (IL-8) receptors CXCR1 and CXCR2 in eutopic and ectopic endometrial tissues of women with endometriosis, and in endometrium of women without endometriosis., Methods: Ectopic (n = 27) and homologous eutopic endometrium (n = 25) from women with endometriosis and endometrium from women without endometriosis (n = 27) were used for immunohistochemical analysis of CXCR1 and CXCR2., Results: In normal endometrium, epithelial CXCR1 and CXCR2 immunostaining intensities were similar in the proliferative and secretory phase. Stromal CXCR1 expression was less then epithelial expression and did not show cyclical difference. No stromal CXCR2 expression was observed. In eutopic endometrium of women with endometriosis compared to endometrium of women without endometriosis, there was a significant increase in both proliferative and secretory phases for epithelial CXCR2 expression, and in proliferative phase for CXCR1 expression (P < 0.05). Both receptor immunoreactivities were significantly increased in the epithelial cells of ectopic endometrial tissues compared to that of normal endometrium (P < 0.05)., Conclusions: These findings suggest that IL-8 and its receptors may be involved in the pathogenesis of endometriosis.

The elevation of the proinflammatory chemoattractant cytokine levels in ectopic and eutopic endometrium of endometriosis implies an inflammatory basis for this disease. The relationship between endothelial cells and leukocytes is likely to be important in the regulation of inflammatory mediators of endometriosis. The aim of this study was to describe the temporal and spatial expression of IL-8 in human endometrial endothelial cells (HEEC) in vivo and to compare the in vitro regulation of IL-8 expression by sex steroids in HEEC from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to menstrual cycle phase and examined by immunohistochemistry for IL-8 expression. Endothelial cells of endometriotic implants expressed higher IL-8 immunoreactivity compared with endothelial cells of eutopic endometrium from women with or without endometriosis (P < 0.02). For in vitro studies, HEEC were isolated from women with or without endometriosis and grown to preconfluence. The purity of cultured HEEC (90-95%) was confirmed by immunocytochemistry using endothelium-specific markers, CD31 and CD146. The effects of estradiol (5 x 10(-8) m), progesterone (10(-7) m), or both on IL-8 mRNA and protein levels were analyzed by RT-PCR and ELISA, respectively. Sex steroids reduced the expression of IL-8 mRNA and protein in HEEC from women without endometriosis. In contrast, both estradiol and progesterone stimulated IL-8 mRNA and protein expression in HEEC from women with endometriosis. We postulate that the stimulation of chemokine expression by sex steroids in HEEC of women with endometriosis may play a role in the inflammatory aspect of this disease.

Objective: The aim of the present study was to assess the incidence of endometrial polyps in women presenting with different symptoms to Ege University Hospital., Material and Methods: Patient records were retrospectively scanned and patients with a histopathological diagnosis of endometrial polyps were included in the analysis., Results: 53 patients had been diagnosed with endometrial polyps. Sixty-four percent of the patients were postmenopausal and the most common presenting symptom was postmenopausal vaginal bleeding (26.4%). Forty-nine percent of the diagnoses were made by endometrial sampling., Conclusion: In a university hospital setting the majority of the endometrial polyp cases diagnosed were in postmenopausal women. Standard endometrial sampling failed to detect almost half of the cases.