Person: ÖZKAN YENAL, NAZİYE
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ÖZKAN YENAL
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NAZİYE
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Publication Open Access BRAFV600E Immunohistochemistry in Papillary Thyroid Carcinomas: Relationship Between Clinical and Morphological Parameters(FEDERATION TURKISH PATHOLOGY SOC, 2019) UĞURLU, MUSTAFA ÜMİT; Kombak, Faruk Erdem; Ozkan, Naziye; Ugurlu, Mustafa Umit; Kaya, HandanObjective: To investigate the association of the BRAFV600E mutation with papillary thyroid carcinoma using clinical, morphological and prognostic parameters. We also intend to assess the utility of the BRAFV600E immunohistochemistry and compare it with BRAF polymerase chain reaction (RT-PCR). Material and Method: We applied BRAFV600E immunohistochemistry in a cohort of 107 papillary carcinomas, 19 adenomas and 13 normal thyroid tissues that was chosen retrospectively between 2011 and 2015. Statistical analysis was based on semiquantitative immunohistochemistry findings. We also applied BRAF RT-PCR in a subgroup of 14 papillary carcinomas, 13 metastatic lymph nodes and 4 adenomas that was chosen randomly. Results: In regard to the comparison of BRAFV600E immunohistochemistry and BRAF RT-PCR, a 3+ nuclear and cytoplasmic immunoexpression was considered 'positive The BRAFV600E mutation was most frequently observed in classic variant cases. No mutation was detected in follicular variant cases. The mutational status of the primary tumour and the lymph node metastasis was consistent. A significant relationship of the BRAFV600E mutation was found with prognostic factors such as higher pT stage, classic variant, lymphatic invasion, perineural invasion, lower mitotic index, lack of tumour capsule, intrathyroidal spread and extrathyroidal extension. Conclusion: Immunohistochemistry, using the VE1 clone, is a reliable technique for detection of the BRAFV600E mutation. Our results with immunohistochemistry are consistent with a previous effort. In our study, despite the correlation between some pathological prognostic parameters and the BRAFV600E mutation; poor prognosis was found to be irrelevant overall. Morphological parameters seem to be keener than the BRAFV600E mutation. Nevertheless, different series display different results, possibly due to environmental factors. Considering this and the proven success of targeted therapies against the BRAFV600E mutation a thorough assessment would be important.Publication Open Access The effects of resveratrol treatment on caveolin-3 expression and Na+/K+ ATPase activity in rats with isoproterenol-induced myocardial injury(KARE PUBL, 2020) YEGEN, BERRAK; Sehirli, Ahmet Ozer; Aykac, Asli; Tetik, Sermin; Yiginer, Omer; Cetinel, Sule; Ozkan, Naziye; Akkiprik, Mustafa; Kaya, Zehra; Yegen, Berrak Caglayan; Tezcan, Mehmet; Sener, GoekselOBJECTIVE: The present study aims to investigate the therapeutic effects of resveratrol (RES) on isoproterenol (ISO) induced myocardial injury rat model. METHODS: Catecholamine-induced heart damage was induced by ISO treatment for 30 days. The rats were divided into four groups as follows: the control group received saline, the ISO group received 5.0 mg/kg ISO, the RES group received 10 mg/kg RES, and the ISO-RES group received 10 mg/kg RES and 5 mg/kg ISO treatments for 30 days. Following echocardiographic measurements and body weight recorded, the rats were decapitated. Plasma and cardiac tissue samples obtained by decapitation were analyzed using biochemical, histopathological, molecular and immunohistochemical methods. RESULTS: In the ISO group, Na+/K+ ATPase activity and ATP content, GSH, and caveolin-3 levels were low. LDH, CK and lysosomal enzyme activities, MDA level, and MPO activity were found to be high. It was determined that GSH and MDA levels and MPO, Na+/K+ ATPase activity, ATP content caveolin-3 levels changes that arose from ISO treatment were suppressed by RES treatment. CONCLUSION: RES treatment has ameliorated all the functional and biochemical parameters. The results obtained in this study suggest that RES is a promising supplement against catecholamine exposure as it improves antioxidant defense mechanisms in the heart. In the light of above-mentioned data, RES can be assumed as a promising agent in ameliorating the oxidative injury of the myocardium.Publication Open Access Protective effects of St. John's wort in the hepatic ischemia/reperfusion injury in rats(AVES, 2018-09-28) VELİOĞLU ÖĞÜNÇ, AYLİZ; Atalay, Suleyman; Soylu, Belkis; Aykac, Asli; Ogunc, Ayliz Velioglu; Cetinel, Sule; Ozkan, Naziye; Erzik, Can; Sehirli, Ahmet OzerObjectives: The purpose of this study was to investigate possible protective effects of St. John's wort in the hepatic ischemia/reperfusion injury. Material and Methods: The hepatic artery, portal vein, and bile duct were all clamped for 45 minutes to induce ischemia in rats, and after that reperfusion for 1 hour. SJW was administrated orally, once a day for 3 days before ischemia/reperfusion. The aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and interleukin levels were measured in the serum samples. Luminol chemiluminescence, lucigenin luminol chemiluminescence levels; myeloperoxidase. The sodium-potassium ATPase (Na+/K+ ATPase) activity was determined in the liver tissue, and caspase-3 and caspase-9 activity with the bcl-2/bax ratio were measured by the western blot analysis. Results: The St. John's wort administration recovered the aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and IL-1 beta levels serum parameters meaningfully, while ischemia/reperfusion caused an increase in luminol chemiluminescence, lucigenin luminol chemiluminescence, myeloperoxidase, caspase-3, and caspase-9 activity and led to a decrease in the B-cell lymphoma-2/bcl-2-associated X protein (bcl-2/bax) ratio and the Na+/K+ ATPase activity. Conclusion: The obtained results indicate protective effects of St. John's wort on the ischemia/reperfusion injury through various mechanisms, and we are able to suggest that St. John's wort can clinically create a new therapeutic principle.Publication Open Access The potency of obestatin in improving kidney functions and apoptosis in rats with cisplatin-induced acute kidney injury(2022-01-01) ÖZDEMİR KUMRAL, ZARİFE NİGAR; BULUT, ALİSİNA; ÖZKAN YENAL, NAZİYE; YEGEN, BERRAK; KOÇ, MEHMET; ÖZDEMİR KUMRAL Z. N. , BULUT A., Üzülmez B., Vezirhüyük M., Kök Z., ÖZKAN YENAL N., YEGEN B., KOÇ M.© 2022 Marmara University Press.Cisplatin (CP), which is the most commonly used anticancer agent to treat several solid tumors, may cause acute kidney injury (AKI) as the major limiting factor for its clinical use. Obestatin (OB) is a ghrelin gene-derived peptide produced in several tissues and has shown anti-oxidant, anti-apoptotic, and anti-inflammatory effects in many experimental models. This study investigated the effect of OB treatment on nephrotoxicity induced by CP. Rats were divided into 4 groups as two control (1 ml/kg, saline, intraperitoneal (ip), single dose) and two CP-induced (7 mg/kg, ip, single dose) AKI groups (8 rats in each group). Immediately after the CP injection and the following two days, injections of OB (10 µg/kg, ip) were performed. Rats were decapitated at the end of 72 hours. Blood and kidney tissue samples were taken for biochemical and histopathological measurements. The results of the present study revealed that serum creatinine and BUN levels were significantly increased in the CP-induced AKI group when compared to the control group. Treatment with OB improved kidney functions and ameliorated renal oxidative injury and maintained oxidative balance in the CP-induced AKI model, which was revealed by elevated malondialdehyde and depleted glutathione levels. TUNEL scores also demonstrated that CP increased the apoptotic response, while OB treatment abolished it. CP-induced medullary and cortical injuries were also partially reversed by OB treatment. Thus, our findings show that OB alleviates CP-induced nephrotoxicity in rats through the abolishment of oxidative stress and apoptosis.Publication Open Access How prenatal environmental factors affect rat molar enamel formation(2022-10-01) ÖZKAN YENAL, NAZİYE; MENTEŞ, ALİ RECAİ; Duman C., ÖZKAN YENAL N., MENTEŞ A. R.Amelogenin (AMELX) and ameloblastin (AMBN) are crucial for enamel formation, and interruptions in the production of these proteins may cause enamel defects. We investigated how prenatal environmental factors (chronic stress, bisphenol A (BPA), amoxicillin, and lipopolysaccharide (LPS)) affect AMELX and AMBN production of ameloblasts. Fifteen pregnant Sprague-Dawley rats were divided into four experimental groups and a control group. Chronic-stress group rats were exposed to a 12:12 light/light cycle (LL) from day E18 until delivery. BPA group rats were orally administered 5 mu g/kg BPA daily from day E1 until delivery. Amoxicillin group rats were injected 100 mg/kg amoxicillin daily from day E18 until delivery. LPS-infection group rats were injected 125 mu g/kg bacterial LPS once on day E18. Seven pups from the control group and ten pups from the experimental groups were euthanized on P10. Sections were stained with hematoxylin and eosin (H&E) and Gomori\"s one-step trichrome staining (GT) and incubated with rabbit polyclonal antibodies to AMELX and AMBN, to evaluate staining intensity at ameloblast stages. The surface morphology was evaluated with a stereomicroscope. AMELX (p = 0.008, p = 0.0001, p = 0.009) and AMBN (p = 0.002, p = 0.001, p = 0.0001) staining of all groups were significantly lower than that of the control group in the secretory, transitional, and maturation stages. Abnormal enamel matrix formation was observed in the H&E and GT staining sections of all experimental groups. Yellowish coloration of the amoxicillin group was observed in morphologic evaluation.Publication Open Access Evaluation of the wound healing potential of Aloe vera-based extract of Nerium oleander(KARE PUBL, 2017) YÜKSEL, MERAL; Akgun, Sevcan Gul; Aydemir, Sezgin; Ozkan, Naziye; Yuksel, Meral; Sardas, SemraOBJECTIVE: Nerium oleander (Apocynaceae) and Aloe vera (Liliaceae) are among the widely used herbal remedies for treating skin diseases and possess numerous activities such as antibacterial, antiviral, antifungal, and antioxidant. The aim of this study was to investigate the possible wound healing effect of Aloev era-based extract of the N. oleander leaf (NAE-8 (R)) based on its antioxidant, anti-inflammatory, and DNA repair capacity along with histological changes and to compare them with the traditional silver sulfadiazine treatment (SSD). METHODS: Twenty-four Wistar albino rats were randomly grouped as follows: i) control, ii) burn alone (burn), iii) burn with topical NAE-8 (R) (burn+ NAE-8 (R)) treatment, and iv) burn with topical 1% silver sulfadiazine (burn+ SSD) treatment. All groups received their related topical application twice a day for 14 consecutive days. Upon completion of the experimental protocol, trunk blood and skin tissues were collected for measuring malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-a), interleukin-1 beta (IL-1 beta), % DNA in the tail (% DNAT) levels along with histological examinations. RESULTS: Thermal injury-induced alterations in MDA, GSH, MPO, TNF-a, IL-1 beta, and % DNAT levels were significantly reversed by NAE-8 (R) treatment. These ameliorative effects were also supported by histological findings. CONCLUSION: Findings of the present study suggest that NAE-8 (R) is a promising remedy for treating skin burn injury.Publication Open Access Tacrolimus-Eluting Suture Inhibits Neointimal Hyperplasia: An Experimental In Vivo Study in Rats(W B SAUNDERS CO LTD, 2017-03) AK, KORAY; Ak, K.; Ak, E.; Dericioglu, O.; Canak, T.; Akbuga, J.; Ozkan, N.; Cetinel, S.; Isbir, S.; Arsan, S.; Cobanoglu, A.Objective/Background: Neointimal hyperplasia (NIH) remains one of the leading causes of graft failure after vascular anastomoses. Cytotoxic drugs, such as rapamycin and tacrolimus, have been shown to inhibit the development of NIH. In this study, the aim was to test the impact of a sustained releasing tacrolimus-chitosan-eluting suture on the development of NIH in a rat model. Methods: After tacrolimus-chitosan coating of a 7/0 polyvinylidene difluoride (PVDF) Trofilen (R) suture, the tacrolimus concentration on the coated suture and in vitro release trials were performed spectrophotometrically. Twelve Wistar rats were included. After midline laparotomy, a 7-8 mm longitudinal aortotomy in the infrarenal aorta was made and then closed by a bare 7/0 PVDF (group C, n = 6) and a 7/0 tacrolimus-chitosan coated PVDF suture (0.65 mu g/cm tacrolimus [0.9 wt%] + 1.82 mu/cm chitosan [2.28 wt%]) (group T, n = 6). After 1 month, rats were sacrificed and aortotomy sites were examined histologically by ratio of intimal area (including neointima) and immunohistochemically by alpha-smooth muscle actin (ASMA) and proliferating cell nuclear antigen (PCNA) immunostaining. The PCNA positive cells were indexed to total cell number and expressed as percentage. Results: In vitro tacrolimus release tests for a 7/0 tacrolimus-chitosan coated PVDF suture were confirmed for 1 month without an initial burst release. Endothelialisation over the aortotomy line occurred in both groups. The area of neointima was significantly reduced in group T compared with group C (ratio 0.22 +/- 0.12 vs. 0.42 +/- 0.11; p =.017) 1 month post-operatively. Likewise, the percentage of PCNA immunostaining significantly decreased in group C compared with group T (3.83 +/- 2.85% vs. 11.17 +/- 7.78%; p =.026). The cells constituting NIH were positive for ASMA immunostaining. Conclusions: Tacrolimus-chitosan-eluting suture is shown to be an effective way to reduce NIH without interfering with normal endothelialisation. (C) 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.Publication Open Access Are histomorphologic changes in the fimbrial ends more to blame for primary epithelial ovarian carcinomas than initially thought(2022-01-01) ERBARUT SEVEN, İPEK; ÖZKAN YENAL, NAZİYE; Askan G., ERBARUT SEVEN İ., ÖZKAN YENAL N., Eren F.Objective: To investigate the relationship between primary epithelial ovarian tumors and histomorphologic changes in the fimbrial ends (FEs) of the fallopian tubes. Materials and Methods: Twenty-eight serous carcinomas (SCs) and 12 non-serous carcinomas (NSC) were studied. Ovarian and concomitant invasive tumors in FEs were labeled with PAX8, WT-1 and Calretinin. Results: Eighty-six percent of SCs were high grade (HG), 14% of were low grade (LG). 71% of SCs (85% HG, 15% LG) had concomitant invasive tumors in FEs. Serous tubal intraepithelial carcinoma (STIC) was seen in 29% (75% HG, 25% LG), all had concomitant invasive tumors in FEs. The presence of tumors in FEs was statistically significant in SCs (p=0.03). 33% of NSCs had concomitantly invasive tumors in FEs. 67% of endometrioid tumors, 33% of clear cell carcinomas had endometriosis. 50% of mucinous tumors, 67% of endometrioid tumors, 50% of benign Brenner tumors had Walthard nest. Except for mucinous carcinomas, ovarian and concomitant invasive tumors in FEs displayed tubal phenotype (Calretinin-/PAX8+). Conclusion: The results of our study suggest that, invasive tumors and STIC in FEs are not only limited to HGSCs, but can also be seen in LGs. FEs could also be a site of origin for NSCs, however, future studies with more cases are needed.