Fakülteler / Faculties

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    Ozone Prevents Cochlear Damage From Ischemia-Reperfusion Injury in Guinea Pigs
    (2017) Onal, Merih; Elsurer, Cagdas; Selimoglu, Nebil; Yilmaz, Mustafa; Erdogan, Ender; Celik, Jale Bengi; Kal, Oznur; Onal, Ozkan; https://orcid.org/0000-0002-7751-4961; 28261890; AAJ-7586-2021
    The cochlea is an end organ, which is metabolically dependent on a nutrient and oxygen supply to maintain its normal physiological function. Cochlear ischemia and reperfusion (IR) injury is considered one of the most important causes of human idiopathic sudden sensorineural hearing loss. The aim of the present study was to study the efficacy of ozone therapy against cochlear damage caused by IR injury and to investigate the potential clinical use of this treatment for sudden deafness. Twenty-eight guinea pigs were randomized into four groups. The sham group (S) (n=7) was administered physiological saline intraperitoneally (i.p.) for 7 days. The ozone group (O) (n=7) was administered 1mg/kg of ozone i.p. for 7 days. In the IR + O group (n=7), 1 mg/kg of ozone was administered i.p. for 7 days before IR injury. On the eighth day, the IR + O group was subjected to cochlear ischemia for 15min by occluding the bilateral vertebral artery and vein with a nontraumatic clamp and then reperfusion for 2h. The IR group was subjected to cochlear IR injury. After the IR procedure, the guinea pigs were sacrificed on the same day. In a general histological evaluation, cochlear and spiral ganglionic tissues were examined with a light microscope, and apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The apoptotic index (AI) was then calculated. Blood samples were sent for analyses of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase, malondialdehyde (MDA), the total oxidant score (TOS), and total antioxidant capacity (TAC). Data were evaluated statistically using the Kruskal-Wallis test. The AI was highest in the IR group. The AI of the IR + O group was lower than that of the IR group. The biochemical antioxidant parameters SOD and GSH-Px and the TAC values were highest in the O group and lowest in the IR group. The MDA level and TOS were highest in the IR group and lowest in the O group. Controlled ozone administration stimulated endogenous antioxidant defense systems, thereby helping the body to combat IR injury. Although this study revealed a statistically significant decrease in cochlear IR damage following ozone therapy, further studies will be necessary to explain the protective mechanisms of ozone therapy in cochlear IR injury.
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    Comparison of the Apoptotic Effects of Topically Applied Papaverine, Diltiazem, and Nitroprusside to Internal Thoracic Artery
    (2020) Unal, Orcun; Ulukan, Mustafa Ozer; Bakuy, Vedat; Kaytaz, Behiye; Artan, Sevilhan; Aral, Erinc; Oztas, Didem Melis; Beyaz, Metin Onur; Ugurlucan, Murat; Sevin, Behcet; 33118726
    Objective: To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside. Methods: Internal thoracic artery segments of ten patients were obtained during coronary bypass grafting surgery. Each internal thoracic artery segment was divided into four pieces and immersed into four different solutions containing separately saline (Group S), diltiazem (Group D), papaverine (Group P), and nitroprusside (Group N). Each segment was examined with both hematoxylin-eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in order to determine and quantify apoptosis. Results: Apoptotic cells were counted in 50 microscopic areas of each segment. No significant difference was observed among the four groups according to hematoxylin-eosin staining. However, the TUNEL method revealed a significant increase in mean apoptotic cells in the diltiazem group when compared with the other three groups (Group S=4.25 +/- 1.4; Group D=13.31 +/- 2.8; Group N=9.48 +/- 2.09; Group P=10.75 +/- 2.37). The differences between groups were significant (P=0.0001). No difference was observed between the samples of the diabetic and non-diabetic patients in any of the study groups. Conclusion: The benefit of topically applied vasodilator drugs must outweigh the potential adverse effects. In terms of apoptosis, diltiazem was found to have the most deleterious effects on internal thoracic artery graft segments. Of the analyzed medical agents, nitroprusside was found to have the least apoptotic activity, followed by papaverine. Diabetes did not have significant effect on the occurrence of apoptosis in left internal thoracic artery grafts.
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    An answer to colon cancer treatment by mesenchymal stem cell originated from adipose tissue
    (2018) Kozanoglu, Ilknur; Iplik, Elif Sinem; Ertugrul, Baris; Baran, Yusuf; Cakmakoglu, Bedia; 0000-0002-5268-1210; 29922425; AAE-1241-2021
    Objective(s): Colon cancer is risen up with its complex mechanism that directly impacts on its treatment as well as its common prevalence. Mesenchymal stem cells (MSCs) have been considered as a therapeutic candidate for conventional disease including cancer. In this research, we have focused on apoptotic effects of adipose tissue-derived MSCs in colon cancer. Materials and Methods: MSCs were obtained from adipose tissue and characterized by Flowcytometer using suitable antibodies. MSCs, HT-29, HCT-116, RKO and healthy cell line MRC5 were cultured by different seeding procedure. After cell viability assay, changes in caspase 3 enzyme activity and the level of phosphatidylserine were measured. Results: For cell viability assay, a 48 hr incubation period was chosen to seed all cells together. There was a 1.36-fold decrease in caspase 3 enzyme activity by co-treatment of RKO and MSCs in addition to 2.02-fold decrease in HT-29 and MSCs co-treatment, and 1.103-fold increase in HCT-116 and MSCs. The results demonstrated that HCT-116 led to the highest rate of apoptotic cell death (7.5%) compared with other cells. Conclusion: We suggest that MSCs might remain a new treatment option for cancer by its differentiation and repair capacity.
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    Investigation of the Protective Effects of Acetyl L-Carnitine on Cisplatin-Induced Uterus Toxicity
    (2018) Goktas, Guleser; Seyhan, Sermin; Saribas, Gulistan Sanem; Akcay, Neslihan Coskun; Gurgen, Seren Gulsen; Akyol, Seda Nur; Hirfanoglu, Ibrahim Murat; Erdogan, Deniz; Ozogul, Candan
    Objective: The aim of the study was to investigate the prophylactic effects of acetyl L-carnitine against to uterus induced by cisplatin. Methods: Twenty-four female Wistar albino rats were divided into four groups: group I (control) was administered with saline; group II was administered with acetyl L-carnitine; group III was administered with cisplatin; group IV was pretreated with acetyl L-carnitine before cisplatin intraperitoneal injection. After 72h of cisplatin injection uterine tissue was removed. Histological and immunohistochemical investigations were performed, respectively. Results: We found that the number of TUNEL and caspases positive cells were increased in the endometrial epithelium, subepithelial connective tissue, endometrial glands and stroma in group III compare to the other groups. Furthermore inflammation and edema were observed in uterus of rats in group III. Conclusion: We can concluded that pretreatment of acetyl L-carnitine administration has protective effect on histological alteration of uterus caused by cisplatin.
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    Both Granulocytic and Non-Granulocytic Blood Cells Are Affected in Patients with Severe Congenital Neutropenia and Their Non-Neutropenic Family Members: An Evaluation of Morphology, Function, and Cell Death
    (2018) Olcay, Lale; Unal, Sule; Onay, Huseyin; Erdemli, Esra; Ozturk, Aysenur; Billur, Deniz; Metin, Ayse; Okur, Hamza; Yildirmak, Yildiz; Buyukasik, Yahya; İkinciogullari, Aydan; Falay, Mesude; Ozet, Gulsum; Yetgin, Sevgi; 30040071
    Objective: To examine granulocytic and non-granulocytic cells in children with severe congenital neutropenia (SCN) and their non-neutropenic parents. Materials and Methods: Fifteen patients with SCN and 21 non-neutropenic parents were evaluated for a) CD95, CD95 ligand, annexin V, propidium iodide, cell cycle, and lymphocyte subsets by flow cytometry; b) rapid cell senescence (of leukocytes) by senescence-associated beta-galactosidase stain; c) aggregation tests by aggregometer; d) in vitro bleeding time by PFA-100 instrument; e) mepacrine-labeled dense granule number of thrombocytes by fluorescence microscope; and f) hematomorphology by light and electron microscope. HAX1, ELANE, G6PC3, CSF3R, and JAGN1 mutations associated with SCN were studied in patients and several parents. Results: Significant increase in apoptosis and secondary necrosis in monocytes, lymphocytes, and granulocytes of the patients and parents was detected, irrespective of the mutation type. CD95 and CD95 ligand results implied that apoptosis was non-CD95-mediated. Leukocytes of 25%, 12.5%, and 0% of patients, parents, and controls showed rapid cell senescence. The cell cycle analysis testable in four cases showed G1 arrest and apoptosis in lymphocytes of three. The patients had HAX1 (n=6), ELANE (n=2), G6PC3 (n=2), and unidentified (n=5) mutations. The CD3, CD4, and NK lymphocytes were below normal levels in 16.6%, 8.3%, and 36.4% of the patients and in 0%, 0%, and 15.4% of the parents (controls: 0%, 0%, 5.6%). The thrombocytes aggregated at low rates, dense granule number/thrombocyte ratio was low, and in vitro bleeding time was prolonged in 37.5%-66.6% of patients and 33.3%-63.2% of parents (vs. 0% in controls). Under electron and/or light microscope, the neutrophils, monocytes, lymphocytes, and thrombocytes in the peripheral blood of both patients and parents were dysplastic and the bone marrow of patients revealed increased phagocytic activity, dysmegakaryopoiesis, and necrotic and apoptotic cells. Ultrastructurally, thrombocyte adhesion, aggregation, and release were inadequate. Conclusion: In cases of SCN, patients' pluripotent hematopoietic stem cells and their non-neutropenic parents are both affected irrespective of the genetic defect.