THE EFFECTS OF ETANERCEPT AND CABERGOLINE ON ENDOMETRIOTIC IMPLANTS, UTERUS AND OVARIES IN RAT ENDOMETRIOSIS MODEL.

The pathophysiology of endometriosis is still unknown and treatment options remain controversial. Searches focus on angiogenesis, stem cells, immunologic and inflammatory factors. This study investigated the effects of etanercept and cabergoline on ovaries, ectopic, and eutopic endometrium in an endometriosis rat model. This randomized, placebo-controlled, blinded study included 50 rats, Co(control), Sh(Sham), Cb(cabergoline), E(etanercept), and E + Cb(etanercept + cabergoline) groups. After surgical induction of endometriosis, 2nd operation was performed for endometriotic volume and AMH level. After 15 days of treatment: AMH level, flow cytometry, implant volume, histologic scores, immunohistochemical staining of ectopic, eutopic endometrium, and ovary were evaluated at 3rd operation. All groups had significantly reduced volume, TNF-α, VEGF, and CD 146/PDGF-Rß staining of endometriotic implants comparing to the Sh group (p < 0.05).TNF-α staining of eutopic endometrium in all treatment groups was similar to Sh and Co groups (p > 0.05). E and E + Cb groups significantly decreased TNF-α staining in the ovary comparing to Sh, Co, and Cb groups (p < 0.05). All treatment groups had significantly higher AFC compared to the Sh group. CD25+ Cells' median percentage was significantly increased in the E + Cb group compared to Co, Sh, Cb, and E group. E + Cb group had a significantly higher CD5+ Cells' level than the Co group (p = 0.035). In conclusion; Etanercept and/or Cabergoline decreased volume, TNF-α, VEGF, and CD 146/PDGF-Rß staining of the ectopic endometrial implant. E and E + Cb treatment decreased TNF-α levels in the ovary. E + Cb also increased peripheral blood CD25+ & CD5+ Cell's.

The association of seminal oxidation reduction potential with sperm parameters in patients with unexplained and male factor infertility

ABSTRACT Purpose: Understanding the effects of high oxidation reduction potential (ORP) levels on sperm parameters will help to identify patients with unexplained and male factor infertility who may have seminal oxidative stress and determine if ORP testing is needed. This study aimed to evaluate the association between seminal ORP and conventional sperm parameters. Materials and Methods: A total of 58 patients who provided a semen sample for simultaneous evaluation of sperm parameters and ORP between January and September 2019 were enrolled in this retrospective study. To identify normal and high ORP levels, a static ORP (sORP) cut-off value of 1.36mV/106sperm/mL was used. Sperm parameters were compared between infertile men with normal sORP (control group, n=23) and high sORP values (study group, n=35). Results: Men with sORP values >1.36mV/106sperm/mL had significantly lower total sperm count (TSC) (p <0.001), sperm concentration (p <0.001) and total motile sperm count (TMSC) (p <0.001). In addition, progressive motility (p=0.04) and fast forward progressive motility (p <0.001) were significantly lower in the study group. A negative correlation was found between sORP and TSC (r=-0.820, p <0.001), sperm concentration (r=-0.822, p <0.001), TMSC (r=-0.808, p <0.001) and progressive motility (r=-0.378, p=0.004). Non-progressive motility positively correlated with sORP (r=0.344, p=0.010). Conclusions: This study has shown that TSC, sperm concentration, progressive motility and TMSC are associated with seminal oxidative stress, indicated by a sORP cut-off of 1.36mV/106sperm/mL. Presence of oligozoospermia, reduced progressive motilty or low TMSC in sperm analysis should raise the suspicion of oxidative stress and warrants seminal ROS testing.

The association of seminal oxidation reduction potential with sperm parameters in patients with unexplained and male factor infertility.

PURPOSE: Understanding the effects of high oxidation reduction potential (ORP) levels on sperm parameters will help to identify patients with unexplained and male factor infertility who may have seminal oxidative stress and determine if ORP testing is needed. This study aimed to evaluate the association between seminal ORP and conventional sperm parameters. MATERIALS AND METHODS: A total of 58 patients who provided a semen sample for simultaneous evaluation of sperm parameters and ORP between January and September 2019 were enrolled in this retrospective study. To identify normal and high ORP levels, a static ORP (sORP) cut-off value of 1.36mV/106sperm/mL was used. Sperm parameters were compared between infertile men with normal sORP (control group, n=23) and high sORP values (study group, n=35). RESULTS: Men with sORP values >1.36mV/106sperm/mL had significantly lower total sperm count (TSC) (p <0.001), sperm concentration (p <0.001) and total motile sperm count (TMSC) (p <0.001). In addition, progressive motility (p=0.04) and fast forward progressive motility (p <0.001) were significantly lower in the study group. A negative correlation was found between sORP and TSC (r=-0.820, p <0.001), sperm concentration (r=-0.822, p <0.001), TMSC (r=-0.808, p <0.001) and progressive motility (r=-0.378, p=0.004). Non-progressive motility positively correlated with sORP (r=0.344, p=0.010). CONCLUSIONS: This study has shown that TSC, sperm concentration, progressive motility and TMSC are associated with seminal oxidative stress, indicated by a sORP cut-off of 1.36mV/106sperm/mL. Presence of oligozoospermia, reduced progressive motilty or low TMSC in sperm analysis should raise the suspicion of oxidative stress and warrants seminal ROS testing.

Hormonal and functional biomarkers in ovarian response.

PURPOSE: Success rates of any artificial reproduction techniques depend on a correct protocol for ovarian stimulation. This can be decided only by proper assessment of ovarian reserve before commencing ovarian stimulation. This study has been conducted to investigate the role of hormonal and functional biomarkers in the prediction of ovarian response. METHODS: A total of 689 women between July 2012 and July 2013 undergoing IVF at Kocaeli University have been enrolled in the study. Patients have been categorized into three groups according to the number of oocytes retrieved: 0-3 oocytes (poor responders), 4-15 oocytes (normoresponders), and >16 oocytes (hyperresponders). Groups have been compared according to follicle-stimulating hormone (FSH), E2, luteinizing hormone (LH) levels, antral follicle counts, and E2 levels on hCG days. Furthermore, regression analysis has been performed with parameters such as age, FSH, LH, E2, anti-mullerian hormone (AMH) and antral follicle counts (AFC) that can affect the total number of oocytes retrieved and pregnancy rates and their interactions with each other have been investigated. RESULTS: FSH, age, hCG day LH level, cycle cancellation rate, total gonadotropin dose were significantly higher in the poor responder group, but in this group, AFC, AMH, hCG day E2 level, and the number of MII oocytes were significantly lower. Cut-off values of normal responders for FSH, AMH, and AFC were 8.43 area under curve [AUC: 0.541 (0.491-0.590)], 0.62 [AUC: 0.704 (0.638-0.764)], and 6 [AUC: 0.715 (0.667-0.760)], respectively. Cut-off values for the absolute poor response group (cycle cancellation) were 12.75 for FSH [AUC: 0.533 (0.49-0.57)], 0.23 for AMH [AUC: 0.678 (0.618-0.733)], and 6 for AFC [AUC: 0.576 (0.531-0.613)]. AMH and AFC were the best markers for the prediction of total oocyte count, independent of age, FSH, and LH levels. CONCLUSIONS: AMH and AFC were found to be the best ovarian reserve tests that can determine the total oocyte count retrieved, without any significant effects on pregnancy rates.

Is sildenafil citrate affect endometrial receptivity? An immunohistochemical study.

The authors aimed to investigate the effect of sildenafil citrate (Sc) on expressions of ß(3) integrin and vascular endothelial growth factor (VEGF), which is taking part in endometrium receptivity in implantation window period in controlled ovarian hyperstimulation (COH) performed rats. In this study, Wistar albino female rats were used and were divided into four groups as control, COH, Sc, and COH + Sc groups. They were sacrificed on the third, fourth, and fifth day of pregnancy, uteruses were resected, and uteri sections were stained with immunohistochemical method and evaluated. ß(3) integrin immunoreactivity was most intensely observed in the endometrial glandular epithelium (GE) and stromal cells in the Sc group on the third day, whereas immunoreactivity was most intensely detected in the luminal epithelium (LE), GE, and stromal cells in the Sc group on the fourth day. VEGF immunoreactivity was most intensely observed in the endometrial LE in the Sc group on the third day, in the Sc and COH + Sc groups on the fourth day, and in the COH + Sc group on the fifth day. Our results indicated that Sc plays a role in both implantation and decidualization by affecting ß(3) integrin and VEGF expressions in implantation window period in rats.

Chronic ethanol-induced glial fibrillary acidic protein (GFAP) immunoreactivity: an immunocytochemical observation in various regions of adult rat brain.

In the present study, the effects of chronic ethanol (ETOH) treatment on the glial fibrillary acidic protein (GFAP) immunoreactivity was investigated in adult rat brains. ETOH were administered as increasing concentrations of 2.4%-7.2% (v/v) gradually for 21 days. Immunocytochemistry revealed that chronic-ETOH treatment increased synthesis of GFAP. The increase in the diameter and the number of GFAP (+) cells were statistically significant compared with the control group (p <. 05). An increase of GFAP immunoreactivity was evident in various white matter and gray matter structures. We concluded that functional astrocytic cells responded to chronic ETOH exposure by increasing the synthesis of GFAP.

Placental expression of insulin-like growth factor-I, fibroblast growth factor-basic, and neural cell adhesion molecule in preeclampsia.

OBJECTIVE: To investigate placental expression of insulin-like growth factor-I (IGF-I), fibroblast growth factor-basic (FGF-b), and neural cell adhesion molecule (N-CAM) in preeclampsia. STUDY DESIGN: An immunohistochemical analysis using IGF-I, FGF-b, and N-CAM antibodies was conducted on 4% paraformaldehyde-fixed placental tissues of preeclamptic patients (N = 14) and normotensive pregnant subjects (N = 10). Immunostaining patterns of chorionic villi and amniochorionic membranes were assessed. RESULTS: Significantly increased FGF-b and N-CAM immunoreactivities in cytotrophoblasts and increased FGF-b immunoreactivity in capillary endothelium of chorionic villi of preeclamptic subjects were noted. Significantly increased FGF-b and decreased N-CAM immunoreactivities in extravillous trophoblasts and decidual cells of amniochorionic membranes obtained from preeclamptic subjects were demonstrated. Additionally, a significantly increased IGF-I immunoreactivity was shown in decidual cells of preeclamptic cases. CONCLUSION: Investigation of the regional distribution of IGF-I, FGF-b, and N-CAM at the maternal-fetal interface establishes a better understanding of cell-specific altered growth processes, which may be associated with the pathogenesis of preeclampsia.

Efficacies of caspofungin and a combination of caspofungin and meropenem in the treatment of murine disseminated candidiasis.

Disseminated candidiasis is relatively common in immunocompromised patients. The treatment protocol of these patients usually includes broad-spectrum antibiotics and also emprical antifungals initiated due to unresponsiveness to antibiotics. In this study the efficacies of caspofungin and meropenem - separately and together - in mice with disseminated candidiasis were studied. Immunocompetent mice were infected intravenously with 2x10(6) CFU of Candida albicans. At 24 h postinfection, intraperitoneal therapy was initiated and was continued for 7 days. Therapy groups included those given caspofungin (0.5, 1.25, 5 mg/kg/day), meropenem (20 mg/kg/day), and a combination of the two drugs. The outcome of therapy was evaluated by kidney tissue burden studies and histologic examination. In vitro, drug susceptibilities were tested by checkerboard analysis. Kidney CFU counts showed that mice that had received both drugs had lower residual burdens. Caspofungin was effective at doses of 0.5, 1.25, 5 mg/kg compared to infected untreated controls. In vitro, MICs of caspofungin and meropenem were <0.075 micro g/ml and >64 micro g/ml, respectively. Synergism was observed with the combination. Histopathology showed that the degree of inflammation was 25% less and tubular necrosis was more restricted in combined therapy than monotherapy. The results indicate that concurrent caspofungin and meropenem therapy may be beneficial.

Effects of chronic ethanol treatment on glial fibrillary acidic protein expression in adult rat optic nerve: an immunocytochemical study.

Glial fibrillary acidic protein (GFAP) is used as a marker of astrocyte response to various central nervous system injuries. In the present study, the effects of chronic ethanol administration on GFAP immunoreactivity were evaluated in astrocytes of the adult optic nerve head. The results demonstrated that ethanol exposure significantly and dramatically increases GFAP immunoreactivity and the number of immunoreactive astrocytes (p<0.001). In addition, GFAP immunoreactive cells in the optic nerve showed extensive hypertrophy (p<0.001).

Localization of neural cell adhesion molecule and pan-cadherin immunoreactivity in intrauterine growth-retarded newborn rat kidneys.

To examine the expression and distribution pattern of neural cell adhesion molecule (N-CAM) and pan-cadherin immunoreactivity in intrauterine growth retardation (IUGR) newborn kidneys, we used a rat model of maternal protein restriction throughout pregnancy. Weak or moderate immunoreactivity for N-CAM and pan-cadherin was seen in some proximal tubules, in the thick segments of Henle, and in the collecting tubules of the control sections. However, the number of tubules expressing N-CAM and pan-cadherin was increased in the IUGR group compared with the control group. Increased density of N-CAM and pan-cadherin immunoreactivity was observed mostly in the proximal tubules, in the thick segments of Henle, and in the collecting tubules of IUGR newborn rat kidneys. Furthermore, N-CAM and pan-cadherin immunoreactivity was present in the thin limb of Henle in the IUGR group, whereas it was absent in the control group. Glomeruli were negative in both groups except for some glomeruli that showed very weak N-CAM staining in the IUGR group. Thus it was demonstrated for the first time that IUGR newborn rat kidneys express N-CAM and cadherin adhesion molecules at specific sites of the nephron.

Expression of cell adhesion molecules in the adriamycin-induced esophageal atresia rat model.

Cell adhesion molecules are well-known membrane glycoproteins widely expressed during embryonic development that play a crucial role in cell division, migration and differentiation. We investigated the cell-matrix relationship using N-CAM and pan-cadherin adhesion molecules in the adriamycin-induced esophageal atresia (EA) rat model in the hope of finding a clue to the mechanisms of this unique anomaly.Time-mated pregnant Sprague-Dawley rats were given either saline or adriamycin on days 8 and 9 of gestation. Embryos were harvested on the 18th day of gestation. Esophageal specimens obtained from adriamycin-exposed embryos with (EA+) or without esophageal atresia (EA-) and from saline-exposed embryos were immunostained with N-CAM and pan-cadherin primary antisera. The esophageal specimens from control and EA- groups revealed similar immunostaining properties: weak N-CAM and pan-cadherin immunoreactivity. In contrast, the EA+ group showed intense immunoreactivity. Our study demonstrated an increased synthesis of N-CAM and pan-cadherin in the epithelial cells of the atretic esophagus and trachea. These results suggest that embryonic cell-cell and cell-matrix interactions may play a crucial role in the development of adriamycin-induced EA.

Immunohistochemical analysis of neural cell adhesion molecule (N-CAM) and pan-cadherin in the small intestine of intrauterine growth-retarded newborn rats caused by maternal protein malnutrition.

Cell-cell and cell-matrix adhesion molecules play an important role in morphogenesis, cell signaling and are involved in cell proliferation, cell death, cell polarization and differentiation. In the present study, we investigated N-CAM and pan-cadherin expression in small intestine of intrauterine growth-retarded (IUGR) newborn rats after maternal protein malnutrition during pregnancy. N-CAM and pan-cadherin immunostaining was increased in small intestine of IUGR newborn rats. This increase was evident in epithelial cells on villi, lamina propria, submucosa, muscularis mucosa and muscularis externa. The increase in numbers of villous N-CAM-positive and pan-cadherin-positive epithelial cells was statistically significant (p < 0.001). In most areas, crypts did not show any immunopositive epithelial cells or showed decreased expression of the adhesion molecules. Although the villous height was decreased in IUGR rats, the decrease was statistically not significant. Expression and recruitment of N-CAM and pan-cadherin in small intestine of newborn IUGR rats may indicate a direct or indirect involvement of adhesion mechanisms or signaling in the growth retardation process.

Localization of pan-cadherin immunoreactivity in adult rat tissues.

Cadherins, being responsible for selective cell recognition and normal tissue integrity in adults, regulate morphogenesis in a variety of organs during development. In this study, anti-rat pan-cadherin antibody, specific to all subgroups of the cadherin family, was used to map the distribution of the pan-cadherin immunoreactivity in adult rat organs. Pan-cadherin immunoreactivity positive tissues were: secretory cells of the adenohypophysis, autonomic nerve, corneal epithelium, oesophageal nerve plexus, stomach and pyloric glandular cells, epithelium of the ileum and its nerve plexus, alveolar cells of the lung, proximal convoluted tubules of the kidney, islet cells of Langerhans, and the acinar cells of the exocrine pancreas. For the first time, positive pan-cadherin immunoreactivity was demonstrated in the epithelial cells of the corpus ciliaris and in the nerve plexus of corpus cavernosum of the penis. In conclusion, our results suggest that cells in many tissues and organs of the adult rat synthesize cadherins.

A rare multiple variation of the greater omentum.

In a dissection performed in our department, we observed multiple variations of the greater omentum. The unusual attachments of the greater omentum were identified. While the right upper part combined with ligamentum teres hepatis, the left upper part had connection with the anterolateral abdominal wall. In addition, the free lower margin of the greater omentum was bound to the front of the abdomen wall. These unusual attachments contained vessels and nerves. The greater omentum is used in reconstructive surgery of the chest wall. And its ligaments are important in abdominal surgery. Therefore, it is important to keep in mind the different attachments of the greater omentum, so that caution is required during intraabdominal surgery and also in appropriately interpreting the radiographs.