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Öğe Cilostazol induces angiogenesis and regulates oxidative stress in adose-dependent manner: A chorioallantoic membrane study(2021) Etli, Mutlu; Karahan, Oğuz; Akkaya, Özgür; Savaş, Hasan BasriBackground: In this study, we aimed to investigate the effects ofcilostazol on angiogenesis and oxidative stress using the chorioallantoicmembrane model. Methods: In this experimental study, the Ross 308 chick embryos wereused. The negative control group (n=10) received no intervention. Thepositive control group (n=10) consisted of eggs treated with epidermalgrowth factor for inducing angiogenesis. Three cilostazol groups weredesigned with 10-7 (n=10), 10-6 (n=10), and 10-5 (n=10) M concentrations.Each egg was punctured on the sixth day of incubation, and drugpellets were introduced to the positive control and drug groups at theprespecified doses. Vascular development was evaluated on the eighthday of application. The total oxidant status, total antioxidant capacity,and oxidative stress index levels were determined from albumen liquidsobtained with a syringe before and after drug application. Results: Lower oxidative stress index levels were obtained fromthe positive control and cilostazol groups compared to the negativecontrol albumens (p=0.001). The increments in vascular junctions andnewly developed vascular nodules were evaluated in drug-free anddrug-applied chorioallantoic membranes. The highest activity wasobtained in the 10-7 M concentration cilostazol group. An increasedangiogenic activity was detected in all drug groups in each concentrationcompared to the negative control group (p=0.001). Angiogenic activitywas similar in all the cilostazol-treated groups (p=0.43).Conclusion: Cilostazol has a positive stimulant effect on angiogenesisand it seems to suppress oxidative stress during embryonic growth.Cilostazol exerts these effects significantly and similarly at differentdoses.Öğe Farklı Konsantrasyonlardaki Monosodyum Glutamatın Koryoallantoik Membran Modelinde Anti-Anjiyojenik ve Oksidan Etkileri(Muğla Sıtkı Koçman Üniversitesi, 2023) Sözen, Mehmet Enes; Savaş, Hasan Basri; Akkaya, Özgür; Karahan, OğuzMonosodyum glutamat (MSG), lezzet artırıcı bir gıda katkı maddesidir. İşlenmiş gıda tüketimindeki yükselişe bağlı olarak MSG maruziyeti her geçen gün artmaktadır. MSG maruziyeti çeşitli doku ve organlara zarar vermektedir. Bu çalışmanın amacı, MSG'nin anjiyogenez ve oksidan-antioksidan dengesi üzerindeki etkilerini araştırmaktır. Üç farklı konsantrasyonda MSG (10-4 M, 10-5 M ve 10-6 M), kontrol ve bevasizumab (10-6 M) hazırlanıp, embriyoların korioallantoik membranına (CAM) yerleştirildi. Deneyden önce ve sonra tavuk yumurtalarından sıvı alındı. Yumurta kabuğu üzerinde açılan pencereden anjiyogenez araştırıldı. Kontrol ve 10-6 M MSG grubunda (ortalama skor: 0.3) anjiyogenez normal bulundu. Anti-anjiyojenik etkilerin, 10-5 M MSG grubunda (ortalama puan: 0.5) ve 10-4 M MSG grubunda (ortalama puan: 0.7) orta düzeyde ve bevasizumab grubunda (ortalama puan: 1.1) güçlü olduğu tespit edildi. Sonuçlarımıza göre MSG daha yüksek dozlarda antianjiyogenik özellikler göstermektedir. Araştırmamızın sonuçlarına göre MSG'nin CAM modelinde anjiyogenezi doza bağımlı bir şekilde inhibe ettiği ve oksidan-antioksidan dengesini bozarak oksidatif hasarda artışa neden olabileceği görülmektedir. MSG'nin CAM modelinde anjiyogenez ve oksidan-antioksidan denge üzerindeki etkilerine ilişkin literatürde daha önce yapılmış bir çalışma tespit edilemediği için araştırma sonuçlarımızın literatürdeki önemli bir eksikliği gidereceğini düşünmekteyiz.Öğe Investigation of the Antiangiogenic Properties of Zoledronic Acid by Using Chorioallantoic Membrane Model(2022) Gülcü, Anıl; Akkaya, ÖzgürObjective: Zoledronic acid (ZA) is a bisphosphonate-derived agent used in osteoporotic clinical pathologies to prevent the development of complications such as fractures and hypercalcemia by regulating bone metabolism. Studies have been conducted on the antiangiogenic efficacy of this agent, which also has other systemic side effects. In this study, the dose-dependent antiangiogenic activity of ZA was investigated on the chorioallantoic membrane model (CAM). Methods: Three doses (10?4, 10?5, and 10?6 M concentrations) of drug pellets were prepared with ZA and another pellet was prepared as the positive control group with vascular endothelial growth factor (VEGF) inhibitor agent bevacizumab (10?6 M concentration). Thereafter all pellets were placed on chorioallantoic membranes on the fourth day of egg incubation. All eggs were evaluated for capillary development four days after the drug application. Results: The highest antiangiogenic effect was detected in the positive control group. Moreover, incremental antiangiogenic effects were detected with average scores of.9, 1.1, 1.2 in 10?6, 10?5, and 10?4 M concentrations of ZA groups respectively. Conclusion: Our findings supported that ZA has dose-dependent antiangiogenic effects. This result suggests that different dosing may be required in cases where angiogenesis is therapeutic.Öğe Investigation of the Antiangiogenic Properties of Zoledronic Acid by Using Chorioallantoic Membrane Model(2022) Gülcü, Anıl; Akkaya, ÖzgürObjective: Zoledronic acid (ZA) is a bisphosphonate-derived agent used in osteoporotic clinical pathologies to prevent the development of complications such as fractures and hypercalcemia by regulating bone metabolism. Studies have been conducted on the antiangiogenic efficacy of this agent, which also has other systemic side effects. In this study, the dose-dependent antiangiogenic activity of ZA was investigated on the chorioallantoic membrane model (CAM). Methods: Three doses (10-4, 10-5, and 10-6 M concentrations) of drug pellets were prepared with ZA and another pellet was prepared as the positive control group with vascular endothelial growth factor (VEGF) inhibitor agent bevacizumab (10-6 M concentration). Thereafter all pellets were placed on chorioallantoic membranes on the fourth day of egg incubation. All eggs were evaluated for capillary development four days after the drug application. Results: The highest antiangiogenic effect was detected in the positive control group. Moreover, incremental antiangiogenic effects were detected with average scores of .9, 1.1, 1.2 in 10-6, 10-5, and 10-4 M concentrations of ZA groups respectively. Conclusion: Our findings supported that ZA has dose-dependent antiangiogenic effects. This result suggests that different dosing may be required in cases where angiogenesis is therapeutic.Öğe Predicting Postoperative Atrial Fibrillation Using HARMS2-AF Score(2024) Öncel, Can Ramazan; Köseoğlu, Cemal; Dagasan, Goksel; Çoner, Ali; Ayhan, Selçuk; Akkaya, Özgür; Karahan, OğuzBackground: Postoperative atrial fibrillation (POAF) remains a common complication after cardiac surgery. The ability to accurately identify patients at risk through previous risk scores is limited. This study aimed to evaluate the new HARMS2-AF risk score to pre- dict POAF after coronary artery bypass grafting (CABG) surgery. Methods: In this retrospective cohort study, we included 265 patients undergoing CABG surgery from 2022-2023. Data were obtained from the medical files of the patients and hospital records. Each patient was assigned a HARMS2-AF risk score. A univariate and multivariate regression analyses were done to analyze independent predictors of POAF. Results: Of 265 patients, 49 had postoperative atrial fibrillation. HARMS2-AF score was significantly higher in patients with POAF. Age, sleep apnea, left atrial diameter (LAd), and HARMS2-AF score were independently associated with POAF. A HARMS2-AF score ? 4.5 predicted POAF with 91% sensitivity and 64% specificity (AUC = 0.787, 95% CI = 0.731- 0.842, P < .001). Conclusion: The HARMS2-AF score is a strong predictor of atrial fibrillation (AF) develop- ment after isolated CABG surgery. It can be used as a novel stratification tool to estimate AF after cardiac surgery.Öğe The Dose-Dependent Antiangiogenic Potential of Apixaban: An Experimental Outlook(2022) Akkaya, Özgür; Aydoğan, EyüpAim: Direct oral anticoagulants (DOACs) are good alternatives to conventional medical regimens for the treatment and prevention of thromboembolism. Apixaban is one of the more popular variations of these newly developed drugs. Aside from its anticoagulant potential, possible cellular effects remain a topic for future studies. The object of this study was to investigate the possible antiangiogenic effects of apixaban in the chorioallantoic membrane (CAM) model. Method: Drug pellets were prepared at 10-4, 10-5, and 10-6 M concentrations of apixaban and were placed in the chorioallantoic membrane on the fourth day of egg incubation. On the eighth day, all vascular densities of the membranes were compared with a 10-6 M concentration of bevacizumab, which is a known monoclonal, humanized, vascular endothelial growth-factor inhibitor. Results: We find that a 10-4 M concentration of apixaban has strong antiangiogenic potential similar to that of bevacizumab. However, there was moderate antiangiogenic potential at a lower dose of apixaban (10-5 M, 10-6 M). A comparison of the higher doses of antiangiogenic potential (10-4 M concentration) with lower doses of apixaban (10-5 M, 10-6 M) revealed significant statistical differences (p < 0.05). Conclusion: Our results indicate that a high dose of apixaban has strong antiangiogenic potential. The exact mechanism of this effect remains unknown. These pilot results should be confirmed with further studies to obtain an updated look at DOACs.Öğe The Investigation of Endomyocardial Biopsy Results, Plasma pro-BNP Levels and Non-invasive Parameters for Diagnosing of Acute Rejection in Patients Who Undergo Cardiac Transplantation(2021) Akkaya, ÖzgürAim: Heart failure is a disease with high mortality and morbidity, reducing the patient's quality of life. Each year 10% of heart failure patients progress to end-stage heart failure. Cardiac transplantation is the gold standard treatment method in these patients, however acute rejection is the most important factor affecting the success of this treatment. In this study, it was aimed to evaluate endomyocardial biopsy results, serum pro-BNP and non-invasive parameters in patients with acute rejection following cardiac transplantation. Patients and Methods: Twenty patients who underwent cardiac transplantation in our center were included in the study. The patients were divided into two groups, namely acute rejection (n: 10) and without rejection (n: 10). Echocardiography, electrocardiography (ECG), endomyocardial biopsy results, serum reactive proteins (CRP), sedimentation rate and serum pro-BNP levels, were evaluated among the patients and compared between the groups. Results: Endomyocardial biopsies obtained from patients with acute rejection revealed grade 1 rejection in 6 (60%) patients, grade 2 in 3 (30%) patients and grade 3 rejection in 1 (10%) patients. CRP and sedimentation rate were found to be similar between the groups (p> 0.05). High pro-BNP levels were found in patients with rejection (4843.20 ± 6690.10 pg / ml) when compared to the control group (496.30 ± 216.20 pg / ml) (p: 0.001). In addition, higher pro-BNP levels were detected with progressing of rejection grade (p: 0.03). The highest pro-BNP level was found in a patient with Grade-3 rejection (15211 pg / ml, p: 0.000). Conclusion: Our results show that serum pro-BNP levels are associated with acute rejection. In addition, higher pro-BNP levels were found to be associated with advanced rejection levels.Öğe The investigation of possible beneficial effects of gabapentin on adverse cardiac effects of high dose zoledronic acid: An experimental study(2022) Gülcü, Anıl; Akkaya, ÖzgürZoledronic acid (ZA) is prescribed for different kinds of clinic conditions to suppress osteoclastic activity and protect bone mineral density. However, some reports claim that ZA treatment can lead to adverse cardiac events. Gabapentin (GP), a widely prescribed agent for neuropathic pain, can ameliorate some other medical agents’ cardiac side effects, through its anti-inflammatory and antioxidant properties. This study aimed to experimentally investigate the combined effect of ZA and GP on the myocardium. Four different groups were created with rats, as follows: I. Control (n:3): investigating the normal myocardial tissue in rat genus. II. Sham (n:4): weekly intraperitoneal (i.p.) saline injection and daily 30 mg/ kg GP (oral gavage) for obtaining possible cardiac side effects of i.p. injection. III. ZA (n: 7): weekly 100 mg/kg i.p. ZA infusion for four weeks. IV. ZA+ GP (n : 7): weekly 100 mg/kg ZA (i.p.) and daily 30 mg/kg GP (oral gavage) utilized for four weeks. Histopathological examinations were made to obtain cardiac tissues at the end of the four weeks. A severe myocardial injury was detected in the ZA group. Regarding injury grade, high dose ZA leads to significant myocardial edema and cellular damage when compared with control subjects (p = 0.000). On the other hand, reduced damage was detected in ZA + GP Group when compare with ZA alone treated group (p = 0.030). Our results suggest that the possible cardiac side effects of ZA can be prevented or reduced by GP. However, more comprehensive studies are needed to elucidate this potential effectÖğe The Oxidative and Anti-Angiogenic Effects of Acrylamide in Chorioallantoic Membrane Model(2023) Sozen, Mehmet Enes; Akkaya, Özgür; Savas, Hasan Basri; Karahan, OguzObjective: Acrylamide (ACR) is formed spontaneously during the preparation of carbohydrate-containing foods by exposure to high heat and can be found in large amounts in processed ready-made foods like potato crisps, biscuits, crackers, and bread. ACR is a toxic substance and increases oxidative stress. The aim of the study is to show the effects of ACR exposure at different doses on angiogenesis and oxidant-antioxidant balance in the chorioallantoic membrane (CAM) model. Methods: Two different concentrations of ACR were prepared (10-3 M and 10-4 M). Pellets were placed on the CAM of the embryos. Liquid samples were taken from fertilized chicken eggs before and after the experiment. Anti-angiogenic effects were evaluated through the window that was opened on the eggshell. Results: The 10-4 M ACR group caused anti-angiogenic effects (average score 0.3) which were higher than the control group, but these changes were not statistically significant. The 10-3 M ACR group caused moderate anti-angiogenic effects (average score 0.6). The 10-6 M Bevacizumab group caused powerful anti-angiogenic effects (average score 1). There is a significant increase in total oxidant capacity (TOC) and oxidative stress index (OSI) values in 10-3 M ACR and 10-4 M ACR groups, compared to the control group. Although there was a numerical increase in TOC and OSI values in 10-3 M ACR group compared to 10-4 M ACR group, this increase was not statistically significant. Conclusion: This study is the first to investigate the anti-angiogenic effects of ACR and is one of the first to investigate oxidative stress in the CAM model. ACR exposure increased oxidative stress in the CAM model and showed a dose-dependent anti-angiogenic effect.Öğe Vascular effects of continuous hyperbaric oxygen exposure: experimental outlook(2023) Yavuz, Celal; Karahan, Oğuz; Akkaya, ÖzgürHyperbaric oxygen (HBO) treatment aims to restore tissue oxygenation by inhaling 100% oxygen in pressure rooms. Although beneficial effects have been reported with regard to re-oxygenated ischemic tissues, conflicting findings have been presented concerning the paradoxical tissue response following reperfusion and/or the different responses of non-ischemic normal tissues to increased oxygen exposure. The present study sought to experimentally investigate the impact of continuous HBO treatments on normal aortic tissue. New Zealand rabbits were placed in pressure rooms for 90 minutes per day under 2.5 atmospheric pressure and exposed to HBO for 28 days. Normal structural histology was obtained in the control group. Foam cells were detected in the aortic intimae, thickening and undulation were visualized in the endothelium, and localized separations were observed in the tunica media in the study group compared with the control group. Moreover, salient vasa vasorum was detected in the study group via histopathology. These findings suggest that continuous HBO exposures disrupt the normal vascular structure of a healthy aorta. © 2023 Wolters Kluwer Medknow Publications. All rights reserved.
