Person: YILDIRIM, ALPER
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YILDIRIM
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ALPER
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Publication Metadata only Apigenin’in hafif travmatik beyin hasarı modelinde olası antienflamatuar, antioksidan ve nöroprotektif etkisinin incelenmesi(2021-11-21) AKAKIN, DİLEK; PEKER EYÜBOĞLU, İREM; YILDIRIM, ALPER; YÜKSEL, MERAL; KURU BEKTAŞOĞLU P., DEMİR D., KOYUNCUOĞLU T., YÜKSEL M., KARAGÖZ KÖROĞLU A., AKAKIN D., PEKER EYÜBOĞLU İ., YILDIRIM A., ÇELİKOĞLU E., GÜRER B.Publication Open Access Comparative design improvement of the growing rod for the scoliosis treatment considering the mechanical complications(2023-01-01) AKGÜN, GAZİ; YILDIRIM, ALPER; DEMİR, UĞUR; DEMİR U., AKGÜN G., KOCAOĞLU S., Okay E., Heydar A., AKDOĞAN E., YILDIRIM A., Yazi S., Demirci B., Kaplanoglu E.In this study, the focus is on an implant used in the treatment of early-onset scoliosis called magnetically controlled growing rods (MCGR). The primary goal of the study is to address and propose solutions for the mechanical problems reported in the literature concerning MCGR. The problems of the MCGR are mainly due to excessive stress and mechanical bearing problems. Therefore, an MCGR removed from a patient is teardown and geometrically modeled. Then, eleven design parameters are determined on the MCGR for the mechanical problems experienced and these are evaluated by mechanical analysis over 14 control points. In this study, analysis processes are carried out with L12 orthogonal array for eleven design parameters and 2 levels using Taguchi’s experimental design method (DoE). With the obtained data by analyzing the experiments in L12, the fitness functions depending on the design parameters are created for 14 control points. Since the problem is multi-objective, a non-dominated sorting genetic algorithm (NSGA II) and multi-objective particle swarm optimization (MOPSO) are used to minimize stress and displacement in existing mechanical problems using fitness functions. The obtained design models from NSGA II and MOPSO are analyzed and evaluated in comparison with the existing mechanical model obtained through pre-optimization teardown study of MCGR.Publication Metadata only Phosphodiesterase-5 inhibition by sildenafil citrate in a rat model of bleomycin-induced lung fibrosis(ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2010) YILDIRIM, ALPER; Yildirim, Alper; Ersoy, Yasemin; Ercan, Feriha; Atukeren, Pinar; Gumustas, Koray; Uslu, Unal; Alican, InciSildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)-dependent mechanism. This study aimed to investigate the possible protective effect of sildenafil citrate on the extent of tissue integrity, oxidant-antioxidant status and neutrophil infiltration to the inflamed organ in a rat model of bleomycin-induced lung fibrosis. Lung fibrosis was induced by intratracheal administration of 0.1 ml of bleomycin hydrochloride (5 mg/kg in 0.9% NaCl) under anesthesia to Sprague-Dawley rats (200-250 g; n =7-8 per group). Control rats received an equal volume of saline intratracheally. In the treatment groups, the rats were treated with either sildenafil citrate (10 mg/kg per day; subcutaneously) or saline for 14 days. Another group of rats were administered subcutaneously with N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg in 0.9% NaCI) 5 min after sildenafil injections. After decapitation, the lungs were excised and taken for microscopic evaluation or stored for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity, and for the assessment of apoptosis. Trunk blood was collected for the assessment of serum tumor necrosis factor (TNF)-alpha and interleukin (1)-1 beta levels. In the group with lung fibrosis, the lung tissue was characterized by microscopic lesions, increased lipid peroxidation with a concomitant reduction in GSH content, increased MPO activity and apoptosis. Serum TNF-alpha and IL-1 beta levels were higher in the lung fibrosis group compared to control values. Sildenafil reversed tissue MDA levels, MPO activity and serum pro-inflammatory cytokine levels, and preserved GSH content although its effect on the extent of tissue lesion and apoptosis was not statistically significant. Treatment with L-NAME reversed the effect of sildenafil on GSH content. In conclusion, sildenafil citrate administration to rats with bleomycin-induced lung fibrosis seems to be beneficial via prevention of lipid peroxidation, cytokine production and/or release and neutrophil accumulation. (C) 2009 Elsevier Ltd. All rights reserved.Publication Metadata only The ameliorative effects of melatonin on acetic acid-induced gastric ulcer in rats via its modulatory effects on gut microbiota(CUKUROVA UNIV, FAC MEDICINE, 2021) YILDIRIM, ALPER; Tamer, Sevil Arabaci; Yildirim, Alper; Cevik, Ozge; Aksu, Burak; Yuksel, Meral; Dertsiz, Ekin Kuntsal; Sirvanci, Serap; Yegen, Berrak C.Purpose: The aim of this study was of observe the possible protective effects of melatonin pretreatment on oxidative damage and microbiota alteration due to gastric ulcer in rats. Materials and Methods: Wistar-albino rats were given (n=32) melatonin (4 mg/kg/day), antibiotic mixture (AB; 1g/L ampicillin + 1g/L neomycin + 1g/L metronidazole), melatonin+AB in drinking water for 12 days or tap water for 15 days (control group; n=8). Subsequently, ulcer was induced. All treatments were continued for three days. Gastric tissues were obtained for biochemical and histopathological examinations, and fecal samples from the rectum were stored for bacteriological measurements. Results: MPO and MDA levels were increased in untreated ulcer groups compared to the control group. In addition, the levels of luminol-lucigenin chemiluminescence (CL) and 8-OHdG and TNF-alpha and IL-8 protein expressions were also increased, while TNF-alpha, IL-8, MDA, 8-OHdG, luminol and lucigenin CL levels were significantly decreased in the melatonin-treated ulcer groups. However, melatonin+AB pretreatment increased antioxidant GSH levels and anti-inflammatory IL-10 levels, and suppressed caspase-3 activity and reduced MPO back to control level. Conclusion: We anticipate that melatonin treatment, which is an effective antioxidant and radical scavenger, can accelerate ulcer healing along with antibiotics and increase the variety of bacteria impaired by antibiotics in the colon.Publication Open Access Cerrahi menopoz oluşturulmuş sıçanların karaciğer ve böbrek dokularında oksidan/antioksidan dengenin korunmasında egzersizin ve östrojenin yararlı etkileri(2022-09-01) YÜKSEL, MERAL; ERCAN, FERİHA; YILDIRIM, ALPER; YEGEN, BERRAK; Tamer S. A. , Levent N., Yüksel M., Ercan F., Yıldırım A., Yegen B.Amaç: Bu çalışmanın amacı cerrahi olarak menopoz oluşturulan sıçanların böbrek ve karaciğerlerinde gözlenen histopatolojik ve fonksiyonel değişiklikleri ve östrojen veya egzersizin ya da östrojen-egzersiz kombinasyonunun oksidan hasar üzerine etkilerini araştırmaktır.Materyal ve Metot: Anestezi altında Sprague Dawley dişi sıçanlara (n=32) bilateral overiektomi uygulandı ve tüm sıçanlar rastgele olarak iki gruba ayrıldı. Sıçanların yarısına normal içme suyu, diğer yarısının içme sularına östrojen (1mg/kg/gün) eklendi. İki hafta sonra gruplar kendi içlerinde sedanter ve egzersiz (5 gün/hafta, 30 daki-ka, 8 hafta) gruplarına ayrıldı. Deney protokolünün sonun-da serum, karaciğer ve böbrek örnekleri biyokimyasal ve histopatolojik incelemeler için alındı. Femurda da histopa-tolojik değerlendirme yapıldı.Bulgular: Cerrahi olarak menopoz oluşturulan sıçan-larda östrojenin böbrek dokusunda nötrofil infiltrasyonunu ve reaktif oksijen türlerinin üretimini baskılayarak koruyu-cu etki gösterdiği, kemik kütlesinde hafif düzeyde artışa neden olduğu, ancak karaciğerin antioksidan glutatyon düzeyinde azalmaya yol açtığı belirlenmiştir. Buna karşın, östrojen uygulaması menopozda yapılan egzersiz nedeniy-le karaciğerde oluşan oksidan stresi engellemiştir. Egzer-sizle veya egzersize östrojen tedavisinin eklenmesiyle böbrek fonksiyonları önemli ölçüde etkilenmezken, kemik yapısında tek başına östrojene kıyasla daha olumlu deği-şiklikler gözlenmiştir.Sonuç: Östrojen replasmanı kemik dokusundaki olum-lu etkilerinin yanı sıra karaciğer ve böbrekte oksidan stresi azaltmakta ve özellikle karaciğerde egzersize bağlı gelişen oksidan stresi baskılayarak koruyucu etki göstermektedir.Publication Metadata only Sleeve gastrectomy-induced endocrine changes in the remnant stomachs of premenopausal and postmenopausal rats: role of the estrogen receptors(ELSEVIER SCIENCE INC, 2021) YILDIRIM, ALPER; Babayev, Hayyam; Arabaci-Tamer, Sevil; Yildirim, Alper; Kayali, Damla; Ercan, Feriha; Yegen, Cumhur; Ugurlu, M. Umit; Yegen, Berrak C.Background: Although alterations in the plasma levels of leptin, glucagon-like peptide-1, and gastrin were linkedwith bariatric surgery outcomes, gastric production of these peptides was not elucidated before. Objective: The aim was to evaluate the impact of estrogen depletion and estrogen receptors (ERs) on sleeve gastrectomy (SG)-induced alterations in gastric hormone production, gastric mucosal integrity, and bone mass. Setting: Physiology Research Lab at the University. Methods: Female Sprague-Dawley rats underwent ovariectomy or sham operation (control), and 2 months later SG or sham SG was performed. Rats received either nonselective agonist 17 beta, ER-alpha agonist, ER-beta agonist, or vehicle for 3 weeks. Trunk blood and gastric tissues were collected for biochemicalmeasurements, while histopathologic examination was performed in gastric and femur samples. Results: In the presence of intact ovaries, SG-induced weight loss was accompanied by reductions in the gastric synthesis of leptin and gastrin, while gastric glucagon-like peptide-1 was additionally decreased when SG was performed at the postmenopausal state. SG elevated the depleted serum estradiol levels of menopause, implicating a beneficial effect, but the occurrence of severe gastric mucosal injury was triggered. On the other hand, using ER agonists upregulated gastrinexpressing cells, ameliorated gastric injury, and improved bone loss. Conclusions: SG, either at premenopausal or postmenopausal state, resulted in considerable loss in bone mass, along with reductions in the gastric levels of gastrin and leptin. Functional status of the ovaries needs to be taken into consideration when monitoring the outcomes of SG, and ER agonists could be of value in controlling SG-induced complications. (C) 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.Publication Metadata only Nesfatin-1 ameliorates testicular injury and supports gonadal function in rats induced with testis torsion(ELSEVIER SCIENCE INC, 2018) YILDIRIM, ALPER; Tamer, Sevil Arabaci; Yildirim, Alper; Koroglu, M. Kutay; Cevik, Ozge; Ercan, Feriha; Yegen, Berrak C.Testicular torsion causes ischemia-reperfusion injury and an increased risk of infertility. Nesfatin-1 is a novel peptide with antioxidant, anti-inflammatory and anti-apoptotic properties. In the present study, we aimed to investigate the putative beneficial effects of nesfatin-1 on oxidative injury and impaired testicular function induced by testis torsion. Under anesthesia, male Sprague-Dawley rats (180-230 g; n = 24) had sham-operation or they underwent testicular torsion by rotating the left testis 720 degrees and fixing it for 2 h, followed by a 2-h detorsion. Rats in each group were treated intraperitoneally with either nesfatin-1 (0.3 mu g/kg) or saline prior to the torsion or sham-torsion. At the end of the 4-h experimental period, tissue samples were removed for evaluation of spermatozoa, molecular and histochemical analyses. In saline-treated torsion/detorsion group, a high percentage of abnormal spermatozoa with head defects was observed, which was abolished in nesfatin-1 -treated torsion/detorsion group. The levels of 8-OHdG, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, caspase-3 were increased in the saline-treated torsion/detorsion group as compared to sham-operated group, while nesfatin-1 pre-treatment significantly decreased the expressions of the pro-inflammatory cytokines, depressed apoptosis, and also reduced the tubular degeneration. In addition, nesfatin-1 in torsion/detorsion group elevated expressions of transforming growth factor (TGF)-beta and reduced expressions of protein kinase B (AKT) and cAMP response element binding protein (CREB) in the testis tissue. The present findings show that nesfatin-1, by regulating AKT and CREB signaling pathways and pro-inflammatory/anti-inflammatory cytokine balance, preserves the spermatogenic cells and ameliorates torsion-detorsion-induced tubular degeneration.Publication Open Access Melatonin alleviates ovariectomy-induced cardiovascular inflammation in sedentary or exercised rats by upregulating SIRT1(2022-12-01) ERCAN, FERİHA; YILDIRIM, ALPER; YEGEN, BERRAK; Arabacı Tamer S., Altınoluk T., Emran M., Korkmaz S., Yüksel R. G., Baykal Z., Dur Z. S., Levent H. N., Ural M. A., Yüksel M., et al.© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.We aimed to evaluate the impact of hormone replacement, melatonin, or exercise alone or their combination on oxidative damage and functional status of heart, brain, and aorta of ovariectomized (OVX) rats and to determine whether the signaling pathway is dependent on sirtuin-1 (SIRT1). Ovariectomized Sprague Dawley rats were orally given either a hormone replacement therapy (1 mg/kg/day,17β estradiol; HRT) or melatonin (4 mg/kg/day) or HRT + melatonin treatments or tap water, while each group was further divided into sedentary and exercise (30 min/5 days/week) groups. After the heart rate measurements and memory tests were performed, trunk blood was collected at the end of the 10th week to determine metabolic parameters in serum samples. Tissue samples of abdominal aorta, heart, and brain were taken for biochemical measurements and histopathological evaluation. Heart rates and memory performances of the OVX rats were not changed significantly by none of the applications. Melatonin treatment or its co-administration with HRT upregulated the expressions of IL-10 and SIRT1, reduced the expressions of IL-6 and TNF-α, and reduced DNA damage in the hearts and thoracic aortae of non-exercised rats. Co-administration of melatonin and HRT to exercised OVX rats reduced inflammatory response and upregulated SIRT1 expression in the aortic and cardiac tissues. The present study suggests that melatonin treatment, either alone or in combination with exercise and/or HRT, upregulates SIRT1 expression and alleviates oxidative injury and inflammation in the hearts and aortas of OVX rats. Melatonin should be considered in alleviating cardiovascular disease risk in postmenopausal women.Publication Metadata only Intraluminal fluid infusion in a rat jejunum ischemia/reperfusion model is associated with improved tissue perfusion and less mucosal damage(ELSEVIER SCI LTD, 2020) YILDIRIM, ALPER; Yalcin, Dogus; Sacak, Bulent; Yalcin, Muge; Yildirim, Alper; Karademir, Betul; Ercan, Feriha; Celebiler, OzhanObjective: This study used an experimental model mimicking early postoperative enteral feeding after the transfer of free jejunal flap and tested the hypothesis that jejunal infusion with dextrose or saline is associated with improved tissue perfusion and/or less mucosal damage after ischemia/reperfusion (IR) injury. Methods: Thirty-five male Sprague Dawley rats were randomly divided into five groups: sham group (no IR and no intraluminal infusion); IR control group (IR but not intraluminal infusion); IR plus intraluminal 0.9% NaCl infusion or 5% dextrose or 10% dextrose infusion groups. A jejunal segment of each rat was isolated. The animals had jejunal ischemia for 40 min, reperfusion, and intestinal infusion on the basis of their allocation. Jejunal tissue perfusion was measured with laser Doppler flowmetry at one hour and two hours after reperfusion, after which the animals were sacrificed and tissue samples were obtained for the scoring of histological damage at superficial and cryptic epithelium, villus structure, and inflammatory cell infiltration and tissue nitric oxide (NO), interleukin (IL)-1, IL-6, and matrix metalloproteinase-1 (MMP) level measurements. Results: At 1 h of reperfusion, IR plus 5% dextrose and 10% dextrose groups both had significantly higher perfusion rates than the IR control group (384.8 +/- 26.7 and 462.4 +/- 44.7 versus 270.3 +/- 34.2 PU, respectively, p < 0.05 for both). These differences were maintained at 2 h of reperfusion (p < 0.05 for both). Saline infusion, however, resulted in improved tissue perfusion only at the early phase of reperfusion. Intraluminal infusion with dextrose solution, either 5% or 10%, was associated with higher tissue NO, IL-1, and IL-6 levels than that in the sham group (p < 0.05 for all). In addition, intraluminal infusion of any fluid resulted in less severe histo-logical damage (8.1 +/- 0.9 versus 5.8 +/- 1.0, 5.4 +/- 0.9, and 5.2 +/- 1.9, for IR plus saline, 5% dextrose and 10% dextrose groups, respectively, p < 0.05 for all). Conclusions: Intraluminal infusion of fluids, particularly dextrose solutions, may be protective against IR injury as demonstrated by improved tissue perfusion and less histological damage. In addition, increases in tissue NO, IL-1, and IL-6 levels in association with dextrose infusion may be explained by the activation of pro-inflammatory and anti-inflammatory protective pathways. These support early enteral feeding after free jejunum flap transfers; however, further studies are warranted. (C) 2019 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.Publication Metadata only Estrogen receptor agonists protect against acetaminophen-induced hepatorenal toxicity in rats(PERGAMON-ELSEVIER SCIENCE LTD, 2020) YILDIRIM, ALPER; Koyuncuoglu, Turkan; Yildirim, Alper; Dertsiz, Ekin K.; Yuksel, Meral; Ercan, Feriha; Yegen, Berrak C.Aims: Acetaminophen-induced hepatorenal toxicity varies among sexes with controversial results among species. The aim was to compare the impact of sex and ovarian hormones on hepatorenal toxicity and to elucidate protective effects of estrogen and estrogen receptor (ER) agonists. Main methods: Under anesthesia, female rats underwent ovariectomy (OVX) or sham-OVX. Starting at postsurgical 40th day, OVX-rats received subcutaneously (each, 1 mg/kg/day) 17 beta-estradiol (E2), ER beta-agonist (DPN) or ER alpha-agonist (PPT) for 10 days, while male and sham-OVX rats received vehicle for 10 days. Then, rats received either acetaminophen (3 g/kg) or saline by orogastric gavage and were decapitated at 24th h. Blood samples were obtained to measure serum ALT, AST, BUN, creatinine levels. Liver and kidney samples were obtained for histopathologic examination and for analyzing levels of luminoland lucigenin-chemiluminescence, glutathione and myeloperoxidase activity. Key findings: Compared to their control groups, levels of AST, ALT, BUN, creatinine, hepatic and renal myeloperoxidase activity and chemiluminescence levels were increased, and hepatic glutathione level was decreased in acetaminophen-administered male groups, while ALT and hepatic chemiluminescence levels were not elevated in sham-OVX-rats. Both ER-agonists and E2 reduced BUN, creatinine and reversed all oxidative parameters in renal tissues of OVX-rats. Additionally, ER alpha-agonist reversed all hepatic injury parameters, while ER beta-agonist elevated hepatic glutathione level. Significance: Acetaminophen toxicity in female rats presented with a more preserved hepatic function, while renal toxicity was not influenced by sex or by the lack of ovarian hormones. Pretreatment with estrogen or ER agonists, via their antioxidant actions, provided protective effects on acetaminophen-induced hepatorenal toxicity.