Browsing by Author "Yavasoglu, A"
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Item Role of intercellular communications in breast cancer multicellular tumor spheroids after chemotherapyOktem, G; Bilir, A; Ayla, S; Yavasoglu, A; Goksel, G; Saydam, G; Uysal, ATumor heterogeneity is an important feature that is especially involved in tumor aggressiveness. Multicellular tumor spheroids (MTS) may provide some benefits in different steps for investigation of the aggregation, organization, differentiation, and network formation of tumor cells in 3D space. This model offers a unique opportunity for improvements in the capability of a current strategy to detect the effect of an appropriate anticancer agent. The aim of this study was to investigate the cellular interactions and morphological changes following chemotherapy in a 3D breast cancer spheroid model. Distribution of the gap junction protein connexin-43 and the tight junction protein occludin was investigated by immunohistochemistry. Cellular interactions were examined by using transmission and scanning electron microscopies as well as light microscopy with Giemsa staining after treating cells with doxorubicin, docetaxel, and doxorubicin/docetaxel combination. Statistical analyses showed significant changes and various alterations that were observed in all groups; however, the most prominent effect was detected in the doxorubicin/docetaxel combination group. Distinct composition as a vessel-like structure and a pseudoglandular pattern of control spheroids were detected in drug-administered groups. Immunohistochemical results were consistent with the ultrastructural changes. In conclusion, doxorubicin/docetaxel combination may be more effective than the single drug usage as shown in a 3D model. The MTS model has been found to be an appropriate and reliable method for the detection of the changes in the expression of cellular junction proteins as well as other cellular proteins occurring after chemotherapy. The MTS model can be used to validate the effects of various combinations or new chemotherapeutic agents as well as documentation of possible mechanisms of new drugs.Item Histopathological and apoptotic changes on marine mussels Mytilus galloprovincialis (Lamark, 1819) following exposure to environmental pollutantsYavasoglu, A; Özkan, D; Güner, A; Katalay, S; Oltulu, F; Yavasoglu, NÜKMarine bivalve mussels, especially Mytilus species are an earlywarning system used for determining of damage caused by the various aquatic pollutions. In the present study, Mytilus galloprovincialis L. (black mussel) have been utilised as a biomonitoring organism to reveal environmental pollution in the Aliaga, Foca and Urla where located along the Izmir Coast of Turkey. Mussels were collected at these areas and gill and hepatopancreas (digestive gland) tissues were excised. mRNA expressions of initiator (caspase-2 and -8) and executioner (caspase -3/7-1, -3/7-2, -3/7-3 and -3/7-4) caspases of mussels tissues in areas exposed to pollution agent have been observed. TUNEL immunoreactivity in paralel to histopathological changes in both Aliaga and Foca areas were compared with Urla. This study is the first report to reveal the pollution with apoptotic expression on mussels in the coast of Turkey. (C) 2016 Elsevier Ltd. All rights reserved.Item The effects of botulinum-A toxin on bladder function and histology in spinal cord injured rats: Is there any difference between early and late application?Temeltas, G; Tikiz, C; Dagci, T; Tuglu, I; Yavasoglu, APurpose: We explored the effects of early and late application of botulinum-A toxin (BTX-A) on reservoir function and histological bladder changes in spinal cord injured rats. Materials and Methods: The study was done in 30 Sprague-Dawley rats randomly allocated into 5 groups. Group 1 of 6 rats underwent sham operation only. Group 2 of 6 rats underwent spinal cord transection. Group 3 of 6 rats underwent spinal cord transection followed by BTX-A application into the detrusor muscle 7 days later. Group 4 of 6 rats underwent spinal cord transection, followed by BTX-A application into the detrusor muscle 28 days later. Group 5 of 6 rats underwent spinal cord transection followed by saline injection into the detrusor muscle after 28 days. Spinal cord injury was created by transecting the cord at the T9 to T10 level. All rats underwent cystometric examination initially and on day 42 before sacrifice. The bladders were removed and examined histologically for fibrosis and hyperplasia. Results: On cystometric examination BTX-A caused an improvement in baseline pressure, and the frequency and amplitude of uninhibited detrusor contractions (p < 0.001). No significant differences were observed in maximal bladder capacity or urethral opening pressure (p > 0.05). Histologically BTX-A led to decreased fibrosis and hyperplasia (p < 0.001). No significant differences were found between histological or cystometric among the groups with respect to receiving BTX-A in the early and late periods (p > 0.05). Conclusions: BTX-A has a functional and histological healing effect on detrusor hyperreflexia subsequent to spinal cord injury in rats. Although administering BTX-A in the early period had better quantifiable functional and histological outcomes compared to the late period, the difference was not statistically significant.Item The Protective Effect of Granulocyte Colony-Stimulating Factor on Endometrium and Ovary in a Rat Model of Diabetes MellitusPala, HG; Pala, EE; Ulkumen, BA; Aktug, H; Yavasoglu, A; Korkmaz, HA; Erbas, OAims: To evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on the endometrium and ovaries in an experimental diabetes mellitus (DM) rat model. Methods: A total of 18 female Sprague-Dawley albino mature rats (8 weeks, 200-220 g) were used in this study. Diabetes was induced by intra peritoneal (i.p.) injection of streptozocin randomly in 12 rats. No drug was administered to the remainder of the rats (control group, group 1, n = 6). The other 12 rats were randomly divided into 2 groups; 1 ml/kg i.p. saline was given as vehicle to group 2 (diabetic nontreated control group, n = 6) and 100 mu g/kg/day of i.p. G-CSF was given to group 3 (G-CSF-treated group, n = 6) for 4 weeks. After 4 weeks, blood samples were collected and hysterectomy with bilateral oophorectomy was performed for histopathological examination. Results: The mean endometrial gland degeneration and stromal fibrosis scores were significantly higher in group 2 compared with groups 1 and 3. Ovarian follicle degeneration, stromal degeneration and stromal fibrosis scores were significantly higher in group 2 compared with groups 1 and 3. Plasma TGF-beta and malondialdehyde levels were significantly lower in groups 1 and 3 compared with group 2. Antimullerian hormone levels were significantly lower in group 2 compared with groups 1 and 3. Conclusion: Glucose toxicity occurred severely in the ovaries and endometrium of the DM rats. After G-CSF treatment, ovarian and endometrial injury and fibrosis scores decreased significantly. The effects of G-CSF in rat models give hope to improved treatment of human DM complications such as premature ovarian failure and endometrial dysfunction. (C) 2014 S. Karger AG, BaselItem Ovarian failure in diabetic rat model: Nuclear factor-kappaB, oxidative stress, and pentraxin-3Erbas, O; Pala, HG; Pala, EE; Oltulu, F; Aktug, H; Yavasoglu, A; Taskiran, DObjective: The aim of the present study was to investigate the effects of diabetes mellitus (DM) on ovarian reserve and injury by considering laboratory and histopathological parameters in rat models. Materials and methods: An experimental DM model was created in 16 rats. Eight rats with normal blood glucose levels were included in the control group. Diabetic rats were divided randomly into two groups: nontreated and resveratrol-treated groups. Histopathological examination and nuclear factor (NF)-kappa B immunoexpression level determination were performed. Plasma malondialdehyde, glutathione, pentraxin-3, and anti-Mullerian hormone levels were measured. Relations between the variables were compared by Student t test, analysis of variance, and Mann-Whitney U and X-2 tests. Results: We found statistically significantly lower glutathione and anti-Mullerian hormone levels, and higher malondialdehyde and pentraxin-3 levels in nontreated diabetic group when compared with the control and resveratrol-treated diabetic groups. Stromal degeneration, follicle degeneration. stromal fibrosis scores, and NF-kappa B immunoexpression levels were significantly higher in nontreated diabetic rats. Primordial and primary follicle counts were significantly lower in the nontreated diabetic group when compared with the control and resveratrol-treated groups. There was no statistically significant difference in secondary and tertiary follicles between these groups. Conclusion: These findings provide strong evidence that the ovarian follicle pool in nontreated diabetic rats is affected in the early stages of the follicle development process. We precluded negative effects of DM on ovaries by inhibiting the NF-kappa B pathway with resveratrol. We thought that the NF-kappa B pathway plays a role in the pathophysiology of ovarian failure in diabetic rats. Further studies should evaluate this precise mechanism that leads to a decline in the anti-Mullerian hormone levels. In addition, the relationship between this abnormality and reproductive function in diabetic patients should be analyzed further. Copyright (C) 2014, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.Item Therapeutic effect of sunitinib on diabetes mellitus related ovarian injury: an experimental rat model studyErbas, O; Pala, HG; Pala, EE; Ulkumen, BA; Akman, L; Akman, T; Oltulu, F; Aktug, H; Yavasoglu, AThe aim of our study is to investigate the effect of sunitinib on diabetes mellitus related-ovarian injury and fibrosis in rat models. An experimental diabetes mellitus model was created in 16 rats, and eight rats with normal blood glucose levels were included in control group (Group-1). The diabetic rats were divided into two groups:diabetic control group (water given) - Group-2 and sunitinib treatment group - Group-3. After four weeks, bilateral oophorectomy was performed and ovaries were examined histologically. The groups were compared by Student's t-test, analysis of variance (ANOVA) and Mann Whitney's U-test. There was a significant increase in no-medication (water given) diabetic rat's ovary (Group-2) in terms of follicular degeneration, stromal degeneration, stromal fibrosis and NF-kappaB immune-expression compared with control group normal rats' ovary (Group-1) (p < 0.0001). Stromal degeneration (p = 0.04), stromal fibrosis (p = 0.01), follicular degeneration (p = 0.02), NF-kappaB immune-expression (p = 0.001) significantly decreased in sunitinib-treated diabetic rat's ovary (Group-3) when compared with no-medication (water given) diabetic rat's ovary (Group-2) (p < 0.05). When we used sunitinib in the treatment of diabetic rats, ovarian injury, fibrosis and NF-kappaB immunoexpression decreased significantly. The effects of sunitinib in rat models give hope to the improved treatment of premature ovarian failure due to diabetes mellitus in humans.Item Immunoexpressions of embryonic and nonembryonic stem cell markers (Nanog, Thy-1, c-kit) and cellular connections (connexin 43 and occludin) on testicular tissue in thyrotoxicosis rat modelOltulu, F; Aktug, H; Uysal, A; Turgan, N; Oktem, G; Erbas, O; Yavasoglu, NUK; Yavasoglu, AIn this study, possible thyrotoxicosis-related histological changes in testicular tissues of rats with experimentally induced thyrotoxicosis model were evaluated on cellular connections and stem cell markers. Two experimental groups, thyrotoxicosis and control, each consisting of eight animals were used. Rats in the thyrotoxicosis group were injected intraperitoneally with 3,3,5-triiodo-l-thyronine (50 mu g/100 g body weight/day) for 10 days. At the end of the study, animals in both groups were anesthetized, and blood samples were collected for biochemical analyses. Their testes were dissected out and histological procedure was conducted to perform further histochemical, immunohistochemical analyses and tissue expression analysis by real-time polymerase chain reaction. Expression of the stem cell markers such as c-kit and Thy-1 significantly decreased in the testes of the thyrotoxicosis group compared with the control group; however, Nanog expression was not detected in any of the groups. Similarly, connexin 43 and occludin expressions were also found to be significantly lower in the thyrotoxicosis group. These results on cellular connections are supported with the tissue expression analysis. Our findings are indicative of supporting microenvironmental tissue decay rather than parenchyma damage, which has been actually ignored in the literature. In conclusion, experimental thyrotoxicosis model may have adverse effects on the cell junctional complexes, cell-cell interactions, and pluripotency capacity.Item Exenatide improves ovarian and endometrial injury and preserves ovarian reserve in streptozocin induced diabetic ratsArtunc-Ulkumen, B; Pala, HG; Pala, EE; Yavasoglu, A; Yigitturk, G; Erbas, OWe aimed to evaluate: (1) endometrial and ovarian tissue injury caused by the glucose toxicity in diabetic rat model and (2) the effect of GLP-1 analog (exenatide) on endometrial and ovarian diabetes induced injury with emphasizing the underlying mechanism. The study group composed of 24 female rats assigned randomly into 3 groups. Group 1 was the control group (n = 8) and received no treatment. Diabetes was induced by intraperitoneal injection of streptozocin for 16 rats which are further assigned randomly into 2 groups: 1 ml/kg intraperitoneal saline was given to Group-2 (diabetic non-treated control group, 8 rats) and 10 mu g/kg/day of intraperitoneal exenatide was given to Group 3 (exenatide treated group, 8 rats) for four weeks. After four weeks, blood samples were collected and hysterectomy with bilateral oophorectomy was performed for histopathological examination. Diabetes caused endometrial and ovarian tissue injury in rats (p < 0.0001). Serum transforming growth factor beta (TGF-beta), malonylaldehyde (MDA), pentraxin-3 (PTX-3) levels were higher in diabetic rats (p < 0.0001), whereas antimullerian hormone (AMH) was lower (p < 0.001). Serum levels of these markers reflected that Diabetes induced injury in the reproductive tract occured via oxidative stress, fibrosis and severe inflammation. Diabetes diminished ovarian reserve. Exenatide treatment improved the histological degeneration and fibrosis in the endometrium and ovary with concomitant decrease in inflammatory and oxidative stress markers (p < 0.05). Exenatide also improved ovarian reserve (p < 0.05). Glucose toxicity occured severely in ovary and endometrium in DM. After exenatide treatment; ovarian and endometrial injury and fibrosis seems to decrease significantly. The effects of exenatide in rat models give hope to prevent the women with DM from premature ovarian failure and endometrial dysfunction.Item HISTOLOGICAL EFFECTS OF POLLUTION ON GILL AND HEPATOPANCREAS TISSUES OF BLACK MUSSELS (M. GALLOPROVINCIALIS L.) FROM IZMIR BAY OF TURKEYKatalay, S; Yavasoglu, A; Yigitturk, G; Oltulu, F; Sari, G; Yavasoglu, NUKIn the present study, the histological examination of the hepatopancreas (digestive gland) and gills of black mussels, Mytilus galloprovincialis was performed as a part of the biomonitoring programs carried out to assess the biological effects of the Izmir Bay (Western coast of Turkey). Mussels collected from five stations; Urla in the outer Bay and Inciralti, Goztepe, Konak, Pasaport in the inner Bay of Izmir Bay. While normal histology on hepatopancreas tissue was observed in Urla samples, vacuolar degenerations and hemocytic infiltrations were abundant in hepatopancreas throughout the other four stations. Also breakdown of digestive epithelium was determined in only Pasaport station. In gill tissues, while hemocytic infiltration was observed in Urla samples, gradually increasing cilia erosion, fusion, cell loss and necrosis was observed in Inciralti, Goztepe, Konak, Pasaport samples. Lumen was determined as normal in Urla and Goztepe samples and enlarged in Inciralti samples. The lumen in each filament was thinner and in some parts adjoined to each other and in Konak and Pasaport samples. Also the gills abfrontal tissue integrity was disturbed in these two stations.Item Oxidative stress-induced apoptotic changes after acute exposure to antifouling agent zinc pyrithione (ZnPT) in Mytilus galloprovincialis Lamark (Mediterranean mussels) tissuesKatalay, S; Guner, A; Dagdeviren, M; Yigitturk, G; Yavasoglu, A; Gunal, AC; Yavasoglu, NUK; Oltulu, FZinc pyrithione (ZnPT) is one of the components used in antifouling paints and can be an alternative to classical toxic chemicals such as organotin. However, there is still remarkable concern about the environmental safeness of ZnPT due to rapid transchelation and degradation into several metabolites that have their own toxicity. The effect after acute exposure of ZnPT is investigated on Mediterranean mussels exposed to 20 and 40 mu g/L concentrations for 48 and 96 h and antioxidant responses [superoxide dismutase (SOD), and reduced glutathione (GSH)], genotoxicity [micronuclei (MN) frequency], apoptotic and histological changes were determined. Severe histological changes in hepatopancreas and gill tissues of mussels were observed in ZnPT exposed groups due to dose-dependent increase. ZnPT also caused a dose-dependent increase of TUNEL-positive cell count in the mussel tissues, especially in the hepatopancreas. Increasing in SOD activities and decreasing in GSH levels in both ZnPT concentrations compared to the control were observed. MN and binuclei numbers in all exposure groups were significantly increased. The results of the present study demonstrate that acute exposure to ZnPT could cause an adverse effect on mussel tissues at especially higher concentrations.Item The effects of sunitinib on endometriosisPala, HG; Erbas, O; Pala, EE; Ulkumen, BA; Akman, L; Akman, T; Oltulu, F; Yavasoglu, AThe aim of the present study was to evaluate the effect of sunitinib on endometriotic implants and adhesions in a rat endometriosis model. An experimental endometriosis model was created in 21 rats. These rats were randomly divided into three groups: Group 1 (control group, 7 rats) was given no medication; Group 2 (sunitinib group, 7 rats) was given 3 mg/kg per day of oral sunitinib; and Group 3 (danazol group, 7 rats) was given 7.2 mg/kg per day of oral danazol. The volume of endometriotic implants was calculated. The extent and severity of adhesions were evaluated. The groups were compared by the Student's t-test, analysis of variance (ANOVA) and the Mann-Whitney U test. There was no statistically significant difference in the mean volume of endometriotic implants before medication between three groups. The volume of implants and extent, severity, total score of adhesions were significantly decreased after medication in Group 2 and Group 3. We noted that the volume of the endometriotic implants and adhesion formation were decreased both after sunitinib and danazol treatment. As a result, sunitinib seems to be effective for endometriotic peritoneal lesions. The effects of sunitinib in rat models give hope for improving the treatment of human endometriosis and prevention of pain symptoms.