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AKKAN, AHMET GÖKHAN

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AHMET GÖKHAN
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  • PublicationMetadata only
    Cardiac Troponin-I (cTnI) a Biomarker of Cardiac Injuries Induced by Doxorubicin Alone and in Combination with Ciprofloxacin, Following Acute and Chronic Dose Protocol in Sprague Dawley Rats
    (2014-07-01T00:00:00Z) Shahzadi, Andleeb; Sonmez, Ikbal; Allahverdiyev, Oruc; Onal, Burak; Kandaz, Cemre; Ozyazgan, Sibel Ozmen; Akkan, Ahmet Gökhan; Yazici, Zeliha; AKKAN, AHMET GÖKHAN
    The present study investigates the release of cardiac troponin-I (cTnI) as a biomarker of cardiac injuries induced by doxorubicin (Doxo) alone and along with ciprofloxacin (Cipro), following acute and chronic dose protocol in Sprague Dawley rats. In chronic protocol, rats were given multiple intra-peritoneal (i.p) injections of Doxo (1 or 2.5 mg kg(-1)) alone or in combination with Cipro (20 mg kg(-1) daily) and a placebo control. Whereas in acute protocol, rats were subjected to receive single i.p. injection of Doxo (6 or 15 mg kg(-1)) alone or along with Cipro (20 mg kg(-1)) and placebo treatment with saline (control). The plasma levels of cTnI were measured by using Enzyme-linked Immuno Sorbent Assay (ELISA) technique. All the treated groups, following acute or chronic dose protocol showed significant increase in cTnI plasma level from 137-248% in comparison to control (p<0.0001). The cTnI plasma levels increased in dose dependent manner after following acute and chronic dose protocol. The difference between two doses following chronic (1 mg kg(-1) vs. 2.5 mg kg(-1)) and acute (6 vs. 15 mg kg(-1)) administration was 34.6 and 31.5%, respectively. Results of this investigation suggest that Doxo alone and in combination with Cipro from both the chronic and acute groups showed cardio-toxicity (release of cTnI). To our knowledge this is the first description towards Doxo-Cipro is induced cardiotoxicity and could be a bridge between preclinical and clinical practice for physicians in making an expert opinion dealing with above mentioned group.
  • PublicationMetadata only
    The Effects of Potassium Channels in Human Internal Mammary Artery
    (2016-01-01T00:00:00Z) Afsar, Selim; Hemsinli, Dogus; Ozyazgan, Sibel; Akkan, Ahmet Gökhan; Arslan, Caner; AKKAN, AHMET GÖKHAN
    Background: Structural and functional changes in potassium channels of vascular smooth muscle cells may contribute to the development of diseases such as hypertension. We aim to investigate the vascular effects of potassium channel openers and blockers in human internal mammary artery (HIMA). Methods: Remaining segments of HIMA from 18 consecutive patients undergoing coronary artery bypass surgery were obtained to examine the vascular effects of various potassium channel openers (staurosporine, hydrochlorothiazide and cromakalim) and potassium channel blockers (4-aminopyridin [4-AP], charybdotoxin [CTX] and glibenclamide [GLBC]). Results: Noradrenaline (NA)-induced maximal contractions were inhibited by all 3 K+-channel blockers but only fully inhibited by 4-AP (95.6%). Only NA-induced contractions were reversed by CTX. Only K+-induced maximal contractions were significantly inhibited by 4-AP (95.6%, p < 0.05). Only acetylcholine-induced relaxation was fully inhibited by CTX. Only sodium nitroprusside-induced relaxations in potassium chloride-precontracted strips could be reversed by GLBC. Conclusions: Drugs affecting potassium channels may be useful in the treatment of hypertension and management of perioperative vasospasm during the coronary artery bypass surgery. (C) 2015 S. Karger AG, Basel
  • PublicationMetadata only
    The Anti-Inflammatory Effects of Anacardic Acid on a TNF-alpha Induced Human Saphenous Vein Endothelial Cell Culture Model
    (2020-01-01T00:00:00Z) DURSUN, Erdinç; Onal, Burak; Ozen, Deniz; Demir, Bulent; Ak, Duygu Gezen; Demir, Caner; Akkan, Ahmet Gökhan; Ozyazgan, Sibel; AKKAN, AHMET GÖKHAN
    Background and Objective: Coronary bypass operations are commonly performed for the treatment of ischemic heart diseases. Coronary artery bypass surgery with autologous human saphenous vein maintains its importance as a commonly used therapy for advanced atherosclerosis. Vascular inflammation-related intimal hyperplasia and atherosclerotic progress have major roles in the pathogenesis of saphenous vein graft disease.
  • PublicationMetadata only
    Delta(9)-tetrahydrocannabinol treatment improved endothelium-dependent relaxation on streptozotocin/nicotinamide-induced diabetic rat aorta
    (2015-03-01T00:00:00Z) Altinok, A.; Coskun, Z. M.; Karaoglu, K.; BOLKENT, Şehnaz; Akkan, Ahmet Gökhan; Ozyazgan, S.; AKKAN, AHMET GÖKHAN
    Objective: In this study, we investigated the possible effect of Delta(9)-tetrahydrocannabinol (THC), a peroxisome proliferator-activated receptor gamma (PPAR.) agonist, on metabolic control and vascular complications of diabetes in streptozotocin/nicotinamide (STZ/NIC) induced type 2 diabetes mellitus. Material and methods: Type 2 diabetes was induced with 65 mg/kg STZ, 15 minute later 85 mg/kg NIC was given intraperitoneally (i.p.) to rats. Three days after diabetes induction, THC (3 mg/kg/day, i.p.) was given for 7 days to diabetic rats. Body weight and plasma glucose levels of rats were measured in all groups before and at the end of 3 weeks after diabetes induction. Acetylcholine (Ach) and sodium nitroprusside (SNP) potency and maximum relaxant effects were calculated on aortic rings pre-contracted with noradrenaline (NA). Results: At the end of 3 weeks, blood glucose levels of diabetic group significantly increased in comparison with the control group. Increased plasma glucose levels were significantly decreased by the treatment of THC. Ach induced relaxation was impaired whereas endothelium-independent relaxation to SNP was unaffected on isolated diabetic rat aorta. THC treatment enhanced Ach induced relaxation on diabetic rat aortas. Discussion: These results suggested that THC improved endothelium-dependent relaxation in STZ/NIC induced diabetic rat aorta and that these effects were mediated at least in part, by control of hyperglycemia and enhanced endothelial nitric oxide bioavailability.
  • PublicationMetadata only
    Does Inflammation Have a Role in the Pathogenesis of Cardiac Syndrome X? A Genetic-Based Clinical Study With Assessment of Multiple Cytokine Levels
    (2016-04-01T00:00:00Z) Demir, Bulent; Onal, Burak; Ozyazgan, Sibel; Kandaz, Cemre; UZUN, Hafize; Aciksari, Gonul; Uygun, Turgut; Opan, Selcuk; Karakaya, Osman; Akkan, Ahmet Gökhan; AKKAN, AHMET GÖKHAN
    We compared Turkish patients with cardiac syndrome X (CSX) and controls with respect to serum pro- and anti-inflammatory cytokine levels, as well as the single-nucleotide polymorphisms located in the promoter regions of their related genes. This study included 111 consecutive patients angiographically diagnosed with CSX and 111 healthy controls with similar demographic characteristics. Serum interleukin (IL) 6, tumor necrosis factor (TNF-), and IL-10 levels were measured, and the genotypes of the patients and controls were determined using standard methods. Serum IL-6 and IL-10 levels were significantly higher in the CSX group than in the control group (P < .01, respectively). Serum TNF- level was lower in the CSX group than in the control group (P < .001). On the other hand, participants with CSX and healthy controls were not significantly different with respect to the genotype distributions of IL-6, TNF-, and IL-10 genes. As a result of our study, both pro-inflammatory and anti-inflammatory cytokines may play a role in the pathogenesis of CSX. In contrast, the studied gene polymorphisms did not influence CSX pathogenesis.
  • PublicationMetadata only
    Dexmedetomidine induces conditioned place preference in rats: Involvement of opioid receptors
    (2016-01-01T00:00:00Z) Uskur, Tugce; Barlas, M. Aydin; Akkan, Ahmet Gökhan; Shahzadi, Andleeb; Uzbay, Tayfun; AKKAN, AHMET GÖKHAN
    Dexmedetomidine (DEX) is an alpha-2 adrenergic agonist drug recently introduced to anesthesia practice. Certain agents used in anesthesia practice have been associated with abuse and addiction problems; however, few studies have investigated the role of DEX on addictive processes. Here, the effects and possible mechanisms of action of DEX on conditioned place preference (CPP), a model used for measuring the rewarding effects of drug abuse in rats, was investigated. The CPP apparatus was considered -biased- as the animals preferred the grid side to the mesh side. Male Wistar albino rats weighing 250-300 g were divided into several groups, including control (saline), morphine (10 mg/kg), DEX (2.5-20 mu g/kg), naloxone alone (0.5 mg/kg) and a combination (0.5 mg/kg naloxone plus 20 mu g/kg DEX) (n=7-8 for each group). The CPP effects of morphine, DEX, saline and the combination were evaluated. All the drug and saline administrations except naloxone were performed by intraperitoneal (ip) injections. Naloxone was injected subcutaneously (Sc) when given alone or in combination with DEX. Morphine (10 mg/kg) and DEX (5-20 mu g/kg) produced CPP that were statistically significant relative to saline-injected rats. DEX-induced CPP was significantly reversed by pretreatment with naloxone, an opioid antagonist. Naloxone alone treatment did not cause any significant effect on CPP. Our results suggest that DEX produces CPP effects similar to morphine in rats and that opioidergic mechanism may be responsible for DEX-induced CPP. Thus, DEX might have the potential to be addictive, and this possibility should be considered during clinical application of this drug. (C) 2015 Elsevier B.V. All rights reserved.
  • PublicationMetadata only
    Investigation of MTHFR gene C677T polymorphism in cardiac syndrome X patients
    (2018-02-01T00:00:00Z) Kandaz, Cemre; Onal, Burak; Ozen, Deniz; Demir, Bulent; Akkan, Ahmet Gökhan; Ozyazgan, Sibel; AKKAN, AHMET GÖKHAN
    BackgroundDefinition of Cardiac Syndrome X (CSX) refers to groups of patients with positive exercise stress test and normal epicardial coronary arteries on coronary angiography accompanied by chest pain. Although the etiology of CSX is not completely understood, there is a common consensus that its pathophysiology may be associated with endothelial dysfunction resulting in impaired coronary flow. Some polymorphisms observed on the MTHFR gene cause inactivation of the MTHFR enzyme, leading to hyperhomocysteinemia and homocysteinuria, which are prominent risk factors of cardiovascular and cerebrovascular diseases. It was aimed to explain the association of the endothelial dysfunction, which is thought to play a role in the pathophysiology of CSX, with C677T polymorphism on MTHFR gene based on genetic basis.
  • PublicationMetadata only
    The Effect of Orphenadrine on Rewarding Property of Morphine-Induced Conditioned Place Preference
    (2020-05-01T00:00:00Z) Köse, Çağla; Bukharı, Andleeb; Akkan, Ahmet Gökhan; Özyazgan, Sibel; AKKAN, AHMET GÖKHAN
  • PublicationMetadata only
    Vascular responses disrupted by fructose-induced hyperinsulinemia improved with delta-9- tetrahydrocannabinol
    (2021-02-01T00:00:00Z) Todurga Seven, Zeynep Gizem; Bolkent, Sema; Köse, Çağla; Çoşkun, Zeynep Mine; Gökdemir, Selim; Akkan, Ahmet Gökhan; Özyazgan, Sibel; AKKAN, AHMET GÖKHAN
    : In recent years, cannabinoids have been shown to have beneficial effects on diabetic vascular complica tions. Vascular complications due to fructose-induced hyperinsulinemia (HI) and diabetic vascular complications have similar mechanisms. The aim of this experimental study was to observe whether the cannabinoid agonist delta-9-te trahydrocannabinol (THC) has an ameliorating effect on fructose-induced HI and vascular responses in the aortic ring of rats with HI. Methods: A total of 24 rats were categorized into 4 groups: control (standard food pellets and water), HI (water contain ing 10% fructose provided for 12 weeks), THC (1.5 mg/kg/day intraperitoneal administration for 4 weeks), and THC+HI. Body weight was measured again on the last day of the study and the serum insulin level was measured with an en zyme-linked immunosorbent assay. The acetylcholine (ACh) maximum relaxant effect in aortic rings pre-contracted with noradrenaline (NA) was evaluated. Results: The body weight of THC and THC+HI groups was lower compared with that of the controls (p<0.01). Increased insulin level as a result of fructose consumption decreased with THC administration (p<0.01) while the glucose level increased in all other groups compared with the control group (p<0.01, p<0.05). The NA Emax value decreased in the group receiving THC treatment (p<0.01). The increased ACh pD2 value in the HI groups also decreased in the THC treatment group (p<0.0001). The decreased maximum inhibition value in the HI group increased significantly with THC administration (p<0.001). Conclusion: THC demonstrated beneficial effects on fructose-induced HI. THC improved ACh-induced endothelial dependent relaxation in HI rat aortic rings. Keywords: Endothelial-dependent relaxation, hyperinsulinemia, tetrahydrocannabinol, vascular response
  • PublicationMetadata only
    TNF-α ile Oluşturulan in Vitro İnsan Safen ven Ateroskleroz Modelinde Atorvastatin ve Pitavastatinin Matriks Metalloproteinaz 2 Üzerine Etkilerinin Karşılaştırılması
    (2021-08-01T00:00:00Z) Özen, Deniz; Önal, Burak; Gezen Ak, Duygu; Dursun, Erdinç; Akkan, Ahmet Gökhan; AKKAN, AHMET GÖKHAN
    Giriş: Ateroskleroz, arteryal duvarda kolesterol içeren düşük dansiteli lipoprotein parçacıklarının birikmesi ile tetiklenen farklı tip hücreler ve ekstraselüler matriks birikiminin kalınlaşmaya sebep olduğu kronik inflamatuvar bir hastalıktır. Aterosklerotik süreçte subendotelyal matriks modifikasyonuna dahil olan başta matriks metalloproteinazları (MMP) olmak üzere birçok yapısal proteinlerin ve enzimlerin sentezi ile salınımında artışlar görülür. Patolojik vasküler dokularda özellikle MMP-2, -3 ve -9 ekspresyonunda ve bu enzimlerin proteolitik aktivitelerinde artış meydana gelir. Statinler, 3-hidroksi-3-metilglutaril-koenzim A redüktaz enzimini inhibe ederek kolesterol sentezini azaltan lipid düşürücü ajanlardır, ateroskleroz ve vasküler endotelyal hasara karşı koruyucu etkilere sahiptir. Statinler, direkt olarak vasküler ve immün hücrelerinin inflamatuvar fonksiyonlarını etkileyerek pleiotropik anti-inflamatuvar etki gösterirler. Gereç ve Yöntemler: Çalışmamızda, insan safen ven endotelyal hücrelerinde (HSaVEC) tümör nekroz faktörü alfa (TNF-α) ile uyararak oluşturduğumuz aterosklerozun inflamatuvar süreci modelinde, koroner bypass cerrahisi sonrası sıklıkla reçetelenen statinlerden atorvastatin ve pitavastatinin anti-inflamatuvar etkilerini karşılaştırdık. HSaVEC’lere 10 ve 50 µM atorvastatin ve 1 ve 2 µM pitavastatin uygulamalarının ardından, TNF-α ile inflamasyon oluşturduk, laktat dehidrogenazı (LDH) spektrofotometrik olarak ölçerek sitotoksisiteleri belirledik. MMP-2 ekspresyon seviyelerini qRT-PCR ile tespit ettik. Bulgular: DMSO grubu ile karşılaştırıldığında, her iki ilaç uygulamasının yapıldığı gruplardaki LDH düzeylerinin daha düşük olduğunu belirledik. TNF- uygulaması sonucunda, MMP-2 ekspresyon seviyesinin kontrol grubuna göre anlamlı olarak azaldığını gözlemledik (p<0.05). Buna karşın farklı dozlarda atorvastatin ve pitavastatin uygulamasının ardından TNF- ile uyarılan hücrelerde MMP-2 ekspresyon seviyesinin anlamlı düzeyde arttığını tespit ettik (p<0.05). Tartışma: Düşük sitotoksik etki gösteren bu iki statin uygulamasının, in vitro ateroskleroz modelinde MMP-2 ekspresyonu üzerindeki etkileri saptanarak, inflamasyonda düzenleyici etkilere sahip oldukları gözlemlenmiştir. Anahtar Kelimeler: Ateroskleroz, safen ven, statin