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    Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats
    (Co-Action Publishing, 2015) Kip, Gulay; Celik, Ali; Bilge, Mustafa; Alkan, Metin; Kiraz, Hasan Ali; Ozer, Abdullah; Sivgin, Volkan
    Objective: Diabetic complications and lipid peroxidation are known to have a close association. Lipid peroxidation commonly occurs at sites exposed to ischaemia, but distant organs and tissues also get damaged during ischaemia/reperfusion (I/R). Some of these targets are vital organs, such as the lung, liver, and kidney; the lung is the most frequently affected. The aim of our study was to investigate the effects of dexmedetomidine on I/R damage in lung tissue and on the oxidant/anti-oxidant system in diabetic rats. Material and methods: Diabetes was induced with streptozotocin (55 mg/kg) in 18 Wistar Albino rats, which were then randomly divided into three groups (diabetes control (DC), diabetes plus ischaemia-reperfusion (DIR), and diabetes plus dexmedetomidine-ischaemia/reperfusion (DIRD)) after the effects of diabetes were clearly evident. The rats underwent a left thoracotomy and then ischaemia was produced in the myocardium muscle by a left anterior descending artery ligation for 30 min in the DIRand DIRD groups. I/Rwas performed for 120 min. The DIRD group received a single intraperitoneal dose of dexmedetomidine (100 mu g/kg); the DIR group received no dexmedetomidine. Group DC was evaluated as the diabetic control group and also included six rats (C group) in which diabetes was not induced. These mice underwent only left thoracotomy and were closed without undergoing myocardial ischaemia. Histopathological changes, activities of catalase (CAT) and glutathione-S-transferase anti-oxidant enzymes, and malondialdehyde (MDA) levels were evaluated in the lung tissues of all rats. Results: Neutrophil infiltration/aggregation was higher in the DIR group than in the C, DC, and DIRD groups (p = 0.001, p = 0.013, and p = 0.042, respectively). The lung injury score was significantly higher in the DIR group than in the C and DC groups (p < 0.0001 and p = 0.024, respectively). The levels of MDA were significantly higher in the DIR group than in the C and DIRD groups. CATactivity was significantly higher in the DIR group than in the DIRD and C groups. Conclusion: Our results confirm that dexmedetomidine has protective effects against the lung damage resulting from I/R in diabetic rats. Future studies conducted to evaluate the effects of the use of dexmedetomidine on damage to various organs following different I/R durations may help understanding possible protective effects of dexmedetomidine and underlying mechanisms in tissue damage related to I/R injury.
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    Öğe
    Effect of Low and High Dose Sugammadex on Erythrocyte Deformability in Streptozotocin- Induced Diabetic Rats
    (2015) Kiraz, Hasan Ali; Turgut, Hüseyin Cihad; Kartal, Seyfi; Çomu, Faruk Metin; Kip, Gülay; Alkan, Metin; Aydın, Muhammed Enes
    Amaç: Eritrosit deformabilitesi eritrosit membranının özel yapısı ile ilgili bir fonksiyon olup, hücrenin dağılmadan oksijen taşımasına olanak sağlar. Diyabette görülen bozulmuş eritrosit deformabilitesi eritrosit agregasyonu ve mikrovasküler düzeydeki dolaşım bozukluğunun etkenlerinden biridir. Bu çalışmada sıçanlarda streptozosinle indüklenen diyabette yüksek ve düşük doz sugammadeksin eritrosit deformabilitesi üzerindeki etkisini araştırmayı amaçladık. Yöntemler: Ağırlıkları 225-300 gram arasında değişen 24 erkek Wistar albino sıçan rasgele 4 gruba ayrıldı. Grup K (kontrol; n=6), Grup DK (diyabet kontrol; n=6), Grup DR-16S (diyabet-rokuronyum-16mg sugamadeks; n=6) ve Grup DR96S (diyabet- rokuronyum-96mg sugammadeks; n=6). Kontrol ve diyabet gruplarındaki sıçanlara aynı hacimde %0.9 NaCl verildi. Diyabet oluşturmak için tek intraperitoneal enjeksiyonla 55 mg.kg-1 streptozosin (Sigma Chemical, St. Louis, MO, USA) uygulandı. Hayvanlar 30 gün süre ile izlendi ve takip süresinin sonunda kan örneklerinden eritrosit deformabilitesi ölçümü yapıldı. Bulgular: Kontrol grubundaki serum glukoz düzeyi DK, DR-16S ve DR-96S gruplarındakilerden anlamlı olarak düşük bulundu (p<0.0001). Diyabet oluşturulan sıçanlarda deformabilite indeksi anlamlı düzeyde yüksek bulundu (p<0.0001). Eritrosit deformabilitesi DR-96S grubunda Kontrol ve DK gruplarındakinden anlamlı olarak yüksek bulundu (p<0.0001 ve p=0.028). Sonuç: Bu çalışmada diyabetik sıçanlarda düşük doz sugammadeksin güvenli olduğunu gösterdik. Çalışmamazın sonuçları sugammadeksin eritrosit deformabilitesi ve mikro/makrosirkülasyon üzerindeki etkilerini araştıracak insan ve hayvan çalışmaları için yol gösterici olabilir
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    Öğe
    Effect of Low and High Dose Sugammadex on Erythrocyte Deformability in Streptozotocin-Induced Diabetic Rats
    (Gazi Univ, Fac Med, 2015) Kiraz, Hasan Ali; Turgut, Huseyin Cihad; Kartal, Seyfi; Comu, Faruk Metin; Kip, Glay; Alkan, Metin; Aydin, Muhammed Enes
    Objective: Erythrocyte deformability is a function of specially designed erythrocyte membrane properties and allows for the oxygen delivery without cell fragmentation. Impaired erythrocyte deformability in diabetes is one of the suspected factors that result in erythrocyte aggregation and the microvascular circulatory arrest. In this study, we aimed to investigate low versus high doses of sugammadex on erythrocyte deformability in streptozototocin-induced diabetic rats. Methods: Twenty-four male Wistar albino rats weighing between 225 and 300 gr were randomly divided into 4 groups. Group C (control; n=6), Group DC (diabetes control; n=6), Group DR-16S (diabetes-rocuronium-16mg sugammadex; n=6) and Group DR-96S (diabetes- rocuronium-96mg sugammadex; n=6). Rats in control and diabetes groups received a 0.9% NaCl solution at the same volume. Diabetes was induced by a single IP injection of streptozotocin (Sigma Chemical, St. Louis, MO, USA) at a dose of 55 mg.kg(-1) body weight, and animals were kept alive for 30 days. At the end of the follow-up period animals erythrocyte deformability was measured from blood samples. Results: Serum glucose was significantly lower in Group C as compared to Groups DC, DR-16S and DR-96S (p<0.0001). The deformability index was significantly increased in the diabetic rats (p<0.0001). It was significantly increased in Group DR-96S as compared to Group C and DC (p<0.0001, p=0.028, respectively). Conclusion: In this study, we showed the safety profile of low dose sugammadex in diabetic rats in terms of the erythrocyte deformability. Our findings may lead to future animal and human studies investigating sugammadex effects on erythrocyte deformability and micro/macrovascular circulation.
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    The effect of dexmedetomidine on myocardial ischemia reperfusion injury in streptozotocin induced diabetic rats
    (Anaesthesia Pain & Intensive Care, 2015) Arslan, Mustafa; Poyraz, Fatih; Kiraz, Hasan Ali; Alkan, Metin; Kip, Gulay; Erdem, Ozlem; Ozer, Abdullah
    Objective: Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio-protective effects of dexmedetomidine in a diabetic rat model of myocardial I/R injury. Methodology: A total of 18 streptozotocin (55 mg/kg) induced diabetic Wistar Albino rats were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced by ligating the left anterior descending (LAD) coronary artery for 30 min, followed by 2 hours of reperfusion following left thoracotomy, the diabetic I/R dexmedetomidine group (DIRD) which were given 100 mu g/kg dexmedetomidine intraperitoneally 30 min before I/R induction by the same method and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), 6 healthy age-matched Wistar Albino rats underwent sham operations similar to DC group. After the operation the rats were sacrificied and the myocardial tissues were histopathologically examined. Results: Microscopic myonecrosis findings were significantly different among groups (p= 0.008). Myonecrosis findings were significantly higher in DIR compared to C, DC and DIRD groups (p= 0.001, p=0.007 and p=0.037 respectively). Similarly microscopic inflammatory cell infiltration degrees showed significant differences among groups (p<0.0001). Compared to C, DC and DIRD groups, the microscopic inflammatory cell infiltration was significantly higher among DIR group (p<0.0001, p<0.0001 and p=0.009 respectively). Also myocardial tissue edema was significantly different among groups (p=0.002). The microscopic myocardial tissue edema levels were significantly higher in DIR group than C and DIRD groups (p<0.0001 and p=0.022 respectively). Tissue edema was also more prominent in DC compared to C group (p=0.022) Conclusion: Taken together our data indicate that dexmedetomidine may be helpful in reducing myocardial necrosis, myocardial inflammation and myocardial tissue edema resulting from ischemia/reperfusion injury.
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    The effect of levosimendan on lung damage after myocardial ischemia reperfusion in rats in which experimental diabetes was induced
    (Academic Press Inc Elsevier Science, 2015) Alkan, Metin; Celik, Ali; Bilge, Mustafa; Kiraz, Hasan Ali; Kip, Gulay; Ozer, Abdullah; Sivgin, Volkan
    Background: It is known that diabetic complications and lipid peroxidation are closely associated. During ischemia and reperfusion (IR), injury may occur in distant organs, as well as in tissues next to the region exposed to the ischemia, and the lungs can be one of the most affected of these organs. Therefore, this study investigated the effects of levosimendan on lung tissue and the oxidant-antioxidant system in diabetic rats. Materials and methods: The study was conducted in 24 Wistar albino rats that were separated into four groups (C, control; DC, diabetic control; DIR, diabetic IR; and DIRL, diabetic IR levosimendan). Diabetes was induced in 18 rats using streptozotocin (55 mg/kg), and the animals were randomly separated into three groups after the effects of the diabetes became apparent. After a left thoracotomy, ischemia was performed on the myocardial muscle with the left main coronary artery (LAD) for 30 min in the DIR and DIRL groups. After ischemia, the LAD ligation was removed, and reperfusion was applied for 120 min. Single-dose intraperitoneal 12 mg/kg levosimendan was administered to group DIRL before the ischemia. Group DC was evaluated as the diabetic control group, and six rats were considered to be the control group (group C), in which thoracotomy was performed and then closed with no induction of myocardial ischemia. We measured the levels of malondialdehyde, as a lipid peroxidation end product, as well as catalase and glutathione S-transferase activities, as antioxidant enzymes in the lung tissue. Tissue samples were also examined histopathologically. Results: Neutrophil infiltration or aggregation in lung tissue was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.003, P = 0.026, and P = 0.026, respectively). Alveolar wall thickening in lung tissue was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.002, P = 0.002, and P = 0.006, respectively). In addition, the lung tissue damage score was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.001, P = 0.004, and P = 0.007, respectively). Finally, catalase and glutathione S-transferase activity levels were significantly higher in the DIR group compared with those observed in the C, DC, and DIRL groups. Conclusions: Although diabetes increases lipid peroxidation, it suppresses antioxidant activity. Our results showed that levosimendan had a protective effect against lung damage secondary to IR in the rats with induced diabetes. We recommend that experimental and clinical studies be conducted to examine the effects of levosimendan at different doses and different IR durations on various organs for clinical use. (C) 2015 Elsevier Inc. All rights reserved.
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    The effect of levosimendan on myocardial ischemia[1] reperfusion injury in streptozotocin-induced diabetic rats
    (Co-Action Publishing, 2015) Kiraz, Hasan Ali; Poyraz, Fatih; Kip, Gülay; Erdem, Özlem; Alkan, Metin; Arslan, Mustafa; Özer, Abdullah
    Objective: Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods: A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 mg kg-1; and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matchedWistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results: Myonecrosis findings were significantly different among groups (p = 0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p = 0.001, p = 0.007 and p = 0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001). Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively). Also, myocardial tissue edema was significantly different among groups (p=0.006). The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively). Conclusion: Taken together, our data indicate that levosimendan may be helpful in reducing myocardial necrosis, myocardial inflammation, and myocardial tissue edema resulting from ischemia-reperfusion injury. © 2015 Hasan Ali Kiraz et al.
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    Öğe
    The effect of levosinnendan on myocardial ischemia reperfusion injury in streptozotocin-induced diabetic rats
    (Co-Action Publishing, 2015) Kiraz, Hasan Ali; Poyraz, Fatih; Kip, Gulay; Erdem, Ozlem; Alkan, Metin; Arslan, Mustafa; Ozer, Abdullah
    Objective: Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods: A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 mu g kg(-1); and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results: Myonecrosis findings were significantly different among groups (p = 0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p = 0.001, p = 0.007 and p = 0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p < 0.0001). Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p < 0.0001, p < 0.0001, and p = 0.020, respectively). Also, myocardial tissue edema was significantly different among groups (p = 0.006). The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p = 0.001, p = 0.037, and p = 0.014, respectively). Conclusion: Taken together, our data indicate that levosimendan may be helpful in reducing myocardial necrosis, myocardial inflammation, and myocardial tissue edema resulting from ischemia reperfusion injury.