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Öğe Cardiovascular effects of resveratrol and atorvastatin treatments in an H2O2-induced stress model(Spandidos Publ Ltd, 2014) Soner, Burak Cem; Sahin, Ayse SaideOxidative stress has been implicated in the pathophysiology of several types of cardiovascular disease (CVD). Statins are widely used to inhibit the progression of atherosclerosis and reduce the incidence of CVD. Certain over-the-counter products, including resveratrol, show similar effects to statins and may thus be used in conjunction with statins for the treatment of the majority of patients with CVD. The aim of the present study was to evaluate the effects of atorvastatin, resveratrol and resveratrol + atorvastatin (R+A) pretreatment on myocardial contractions and vascular endothelial functions in the presence of 11209 as an experimental model of oxidative stress in rats. Four groups were established and referred to as the control, atorvastatin, resveratrol and R+A groups. Atorvastatin (40 mg/kg, per oral) and/or resveratrol (30 mg/kg, intraperitoneal) treatments were administered for 14 days. On the 15th day, the thoracic aortas and hearts of the rats were dissected and placed into isolated organ baths. Vascular responses to cumulative doses of H2O2 (1x10(-8)-1x10(-4) M H2O2) with and without N (G)-nitro-L-arginine methyl ester (L-NAME) incubation were measured. In addition, myocardial electrical stimulation (ES) responses to various H2O2 concentrations (1x10(-7)-1x10(-5) M H2O2) were evaluated. In the control and atorvastatin groups, H2O2 application caused a significant dose-dependent decrease in the ES-induced contractions in the myocardial tissue of rats. In the resveratrol and R+A groups, H2O2 application did not significantly affect myocardial contraction at any dose. In all groups, incubatibn with L-NAME caused a significant augmentation in the H2O2 response, revealing that this effect was mediated via the vascular endothelium. In conclusion, pretreatment with R+A for CVD appears to be superior to pretreatment with either agent alone.Öğe Effect of Agomelatin on Rat Model of Parkinson's Disease(Dr Behcet Uz Cocuk Hastaliklari Ve Cerrahisi, 2019) Ayvat, Pinar; Sahin, Aye Saide; Soner, Burak CemObjective: Parkinson's disease is one of the most frequently seen neurodegenerative disorders. A definite cure for this disease is not available yet. Agomelatin is the synthetic analog of melatonin hormone that is synthesized in, and released from the pineal gland . Agomelatin shows its antidepressant effects on central nervous system (CNS) by activating melatonin receptors MT1 and MT2 and antagonizing serotonin 5-HT2C receptors stimulated by monoamine transmitters. In this study, we examined the effects of oral agomelatin administration on Parkinson disease-induced experimental rats by using 6-OHDA. Methods: We administered unilateral intrastriatal 6-OHDA to 45 rats weighing 270-330 gr, in three different groups. We applied dissolver on control group; in other two groups we administered agomelatin at daily doses of 5 mg/kg and 20 mg/kg, respectively, for 15 days. At the end of this treatment process, motor coordination and skills were tested with sticky band test, open-field test and cylinder test, whereas, the severity of dopaminergic damage was tested with apomorphine induced rotation test. Results: in our study, we found out that in both doses of agomelatin (5 mg/kg/day and 20 mg/kg/day respectively), prevented progression of experimental Parkinson disease induced with 6-OHDA in rats. Conclusion: Agomelatin protected striatal neurons from destructive effects in experimental Parkinson's Disease model.Öğe Effects of Different Drug Treatments on The Proliferation of Human Ovarian Carcinoma Cell Line Mdah-2774(2018) Ayla, Şule; Bilir, Ayhan; Ertürkoğlu, Şenol; Tanrıverdi, Gamze; Soner, Burak Cem; Sofuoğlu, Kenan; Ghisolfi, Laura; Öktem, GülperiBackground/aim: In this study, the effects of resveratrol as a natural polyphenol compound, gemcitabine as an antimetabolite thathas nucleoside structure analogous to deoxycytidine, and para-aminophenol-derived paracetamol were investigated with single andcombined applications in monolayers of the MDAH-2774 human ovarian cancer cell line.Materials and methods: Drugs were evaluated in cell culture with respect to cell proliferation, cell cytotoxicity (trypan blue dyeexclusion test), synthesis phase of cell cycle, and cell structure in 24, 48, 72, and 96 h.Result: Resveratrol and gemcitabine diminished both cell proliferation and cell cycle synthesis phase indication in monolayer cellcultures (P 0.05). All combination groups showed similar effects that were mainly more effective in respect to single usage of resveratroland gemcitabine in monolayer cell cultures.Conclusion: The effects of gemcitabine, resveratrol, and paracetamol were investigated in monolayers of the MDAH-2774 humanovarian cancer cell line and a decrease in cell number in cell cycle synthesis phase, prevention of cell proliferation, and destruction ofcell structure were observed.Öğe Enhanced G2/M Arrest, Caspase Related Apoptosis and Reduced E-Cadherin Dependent Intercellular Adhesion by Trabectedin in Prostate Cancer Stem Cells(Public Library Science, 2015) Acikgoz, Eda; Guven, Ummu; Duzagac, Fahriye; Uslu, Ruchan; Kara, Mikail; Soner, Burak Cem; Oktem, GulperiTrabectedin (Yondelis, ET-743) is a marine-derived tetrahydroisoquinoline alkaloid. It is originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and currently produced synthetically. Trabectedin is active against a variety of tumor cell lines growing in culture. The present study focused on the effect of trabectedin in cell proliferation, cell cycle progression, apoptosis and spheroid formation in prostate cancer stem cells (CSCs). Cluster of differentiation (CD) 133(+high)/CD44(+high) prostate CSCs were isolated from the DU145 and PC-3 human prostate cancer cell line through flow cytometry. We studied the growth-inhibitory effects of trabectedin and its molecular mechanisms on human prostate CSCs and non-CSCs. DU-145 and PC-3 CSCs were treated with 0.1, 1, 10 and 100 nM trabectedin for 24, 48 and 72 h and the growth inhibition rates were examined using the sphere-forming assay. Annexin-V assay and immunofluorescence analyses were performed for the detection of the cell death. Concentration-dependent effects of trabectedin on the cell cycle were also evaluated. The cells were exposed to the different doses of trabectedin for 24, 48 and 72 h to evaluate the effect of trabectedin on the number and diameter of spheroids. According to the results, trabectedin induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspase-3, caspase-8, caspase-9, p53 and decrease expression of bcl-2 in dose-dependentmanner. Cell cycle analyses revealed that trabectedin induces dose-dependent G2/M-phase cell cycle arrest, particularly at high-dose treatments. Three-dimensional culture studies showed that trabectedin reduced the number and diameter of spheroids of DU145 and PC3 CSCs. Furthermore, we have found that trabectedin disrupted cell-cell interactions via E-cadherin in prostasphere of DU-145 and PC-3 CSCs. Our results showed that trabectedin inhibits cellular proliferation and accelerates apoptotic events in prostate CSCs; and may be a potential effective therapeutic agent against prostate cancer.Öğe Enhanced G2/M Arrest, Caspase Related Apoptosis and Reduced E-Cadherin Dependent Intercellular Adhesion by Trabectedin in Prostate Cancer Stem Cells(Public Library Science, 2015) Acikgoz, Eda; Guven, Ummu; Duzagac, Fahriye; Uslu, Ruchan; Kara, Mikail; Soner, Burak Cem; Oktem, GulperiTrabectedin (Yondelis, ET-743) is a marine-derived tetrahydroisoquinoline alkaloid. It is originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and currently produced synthetically. Trabectedin is active against a variety of tumor cell lines growing in culture. The present study focused on the effect of trabectedin in cell proliferation, cell cycle progression, apoptosis and spheroid formation in prostate cancer stem cells (CSCs). Cluster of differentiation (CD) 133(+high)/CD44(+high) prostate CSCs were isolated from the DU145 and PC-3 human prostate cancer cell line through flow cytometry. We studied the growth-inhibitory effects of trabectedin and its molecular mechanisms on human prostate CSCs and non-CSCs. DU-145 and PC-3 CSCs were treated with 0.1, 1, 10 and 100 nM trabectedin for 24, 48 and 72 h and the growth inhibition rates were examined using the sphere-forming assay. Annexin-V assay and immunofluorescence analyses were performed for the detection of the cell death. Concentration-dependent effects of trabectedin on the cell cycle were also evaluated. The cells were exposed to the different doses of trabectedin for 24, 48 and 72 h to evaluate the effect of trabectedin on the number and diameter of spheroids. According to the results, trabectedin induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspase-3, caspase-8, caspase-9, p53 and decrease expression of bcl-2 in dose-dependentmanner. Cell cycle analyses revealed that trabectedin induces dose-dependent G2/M-phase cell cycle arrest, particularly at high-dose treatments. Three-dimensional culture studies showed that trabectedin reduced the number and diameter of spheroids of DU145 and PC3 CSCs. Furthermore, we have found that trabectedin disrupted cell-cell interactions via E-cadherin in prostasphere of DU-145 and PC-3 CSCs. Our results showed that trabectedin inhibits cellular proliferation and accelerates apoptotic events in prostate CSCs; and may be a potential effective therapeutic agent against prostate cancer.Öğe Farmakogenetik Yönden Bireyler Arası Farmakokinetik Varyasyonlar(2017) Al, Mevra; Kılıç, Mehmet; Şahin, Ayşe Saide; Soner, Burak CemFarmakogenetik (PGx), genetik varyasyonlar ve bunların bireyler arasında oluşturduğu ilaç yanıtı farklılıkları ile ilgilenir. İlaç metabolizmasından sorumlu enzimlerin keşfi ve bu enzimleri kodlayan DNA dizilimlerinin araştırılması bireysel tedavi stratejilerinin oluşturulmasını sağlar. İlaç metabolizmasından sorumlu sitokrom 2B6, sitokrom 2C9, sitokrom 2C19, sitokrom 2D6, sitokrom 3A4, N-asetil transferaz, dihidropirimidin dehidrogenaz, tiopurin metiltransferaz, 5’-difosfat (UDP)-glukuronoziltransferaz ve katekol-O-metil transferaz enzim polimorfizleri ilacın farmokokinetik özelliğini etkileyerek bireyler arası ilaç yanıtı farklılıklarına neden olabilirler. PGx çalışmaların temelini oluşturan ilk örnekler N- asetil transferaz ve sitokrom 2D6 polimorfizmleridir. İlaç seçiminde ciddi farmakokinetik farklılıklara neden olan enzim polimorfizmlerinin göz önünde bulundurulması tedavi başarısını artırmak ve advers/toksik reaksiyon riskini önlemek açısından önemlidir. Yaklaşık 50 yıl önce temelleri atılan farmakogenetik ile ilgili çalışmalar gen teknolojisinin gelişmesi ile günümüzde daha önemli bir hale gelmiştir. Teknolojik gelişmeler sayesinde hızlanan farmakogenetik çalışmalar ile bireye özgü ilaç seçimi farmakogenetiğin ikinci 50 yılı içerisinde daha fazla gelişme kaydederek önemli bir parametre olacaktır.Öğe Induced growth inhibition, cell cycle arrest and apoptosis in CD133+/CD44+ prostate cancer stem cells by flavopiridol(Spandidos Publ Ltd, 2014) Soner, Burak Cem; Aktug, Huseyin; Acikgoz, Eda; Duzagac, Fahriye; Guven, Ummu; Ayla, Sule; Cal, CagFlavopiridol is a flavone that inhibits several cyclin-dependent kinases and exhibits potent growth-inhibitory activity, apoptosis and G(1)-phase arrest in a number of human tumor cell lines. Flavopiridol is currently undergoing investigation in human clinical trials. The present study focused on the effect of flavopiridol in cell proliferation, cell cycle progression and apoptosis in prostate cancer stem cells (CSCs). Therefore, cluster of differentiation 133 (CD133)(+high)/CD44(+high) prostate CSCs were isolated from the DU145 human prostate cancer cell line. The cells were treated with flavopiridol in a dose- and time-dependent manner to determine the inhibitory effect. Cell viability and proliferation were analyzed and the efficiency of flavopiridol was assessed using the sphere-forming assay. Flavopiridol was applied to monolayer cultures of CD133(high)/CD44(high) human prostate CSCs at the following final concentrations: 100, 300, 500 and 1000 nM. The cultures were incubated for 24, 48 and 72 h. The half maximal inhibitory concentration (IC50) value of the drug was determined as 500 nM for monolayer cells. Dead cells were analyzed prior and subsequent to exposure to increasing flavopiridol doses. Annexin-V and immunofluorescence analyses were performed for the evaluation of apoptotic pathways. According to the results, flavopiridol treatment caused significant growth inhibition at 500 and 1000 nM when compared to the control at 24 h. G(0)/G(1), analysis showed a statistically significant difference between 100 and 500 nM (P<0.005), 100 and 1000 nM (P<0.001), 300 and 1000 nM (P<0.001), and 500 and 1000 nM (P<0.001). Flavopiridol also significantly influenced the cells in the G(2)/M phase, particularly at highldose treatments. Flavopiridol induced growth inhibition and apoptosis at the IC50 dose (500 nM), resulting in a significant increase in immunofluorescence staining of caspase-3, caspase-8 and p53. In conclusion, the present results indicated that flavopiridol could be a useful therapeutic agent for prostate CSCs by inhibiting tumor growth and malignant progression, and inducing apoptosis.Öğe Leptin Prevents U46619- and Angiotensin II-Elicited Contraction in Isolated Human Umbilical Vessels(Erciyes Univ Sch Medicine, 2022) Duman, Ipek; Soner, Burak Cem; Irian, Salim Yalcin; Sahin, Ayse SaideObjective: This study investigated the vasoactive responses of quiescent and pre-contracted isolated human umbilical veins and arteries to cumulative leptin. Materials and Methods: The vasoactive response of umbilical vessels pre-contracted with U46619 (10(-10)M) and angiotensin II (10(-6)M) to cumulative leptin (10(-11)-10(-7)M) were recorded in vitro. Results: Leptin did not affect the artery or vein basal tonus (p=1). The leptin-elicited relaxation in U46619-contracted vessels was greater in veins than in arteries (p<0.001). Incubation with N (omega)-nitro-L-arginine methyl ester (L-NAME) (10(-4)M) prevented the leptin-induced relaxation of the U46619 contraction response in the artery. The E-max and pD(2) values of the L-NAME-incubated veins were lower than those of the non-incubated veins (p<0.001 and p=0.001, respectively). The relaxation in angiotensin II-contracted veins was greater than that of the arteries (p<0.001). Incubation with L-NAME prevented leptin-induced relaxation in angiotensin II-contracted arteries. The E-max of leptin-induced relaxation of L-NAME-incubated veins was significantly lower than that of non-incubated veins (p=0.027); the pD(2) was similar. Conclusion: Leptin did not alter the resting tension of isolated umbilical vessels; however, the results indicated that leptin caused concentration-dependent relaxation in umbilical vessels pre-contracted with U46619 or angiotensin II. The maximum relaxation was greater in veins compared with arteries. Incubation with L-NAME completely inhibited leptin-induced relaxation in arteries and resulted in a significant inhibition in veins.Öğe Leptin Prevents U46619- and Angiotensin II-Elicited Contraction in Isolated Human Umbilical Vessels(Erciyes Univ Sch Medicine, 2022) Duman, Ipek; Soner, Burak Cem; Irian, Salim Yalcin; Sahin, Ayse SaideObjective: This study investigated the vasoactive responses of quiescent and pre-contracted isolated human umbilical veins and arteries to cumulative leptin. Materials and Methods: The vasoactive response of umbilical vessels pre-contracted with U46619 (10(-10)M) and angiotensin II (10(-6)M) to cumulative leptin (10(-11)-10(-7)M) were recorded in vitro. Results: Leptin did not affect the artery or vein basal tonus (p=1). The leptin-elicited relaxation in U46619-contracted vessels was greater in veins than in arteries (p<0.001). Incubation with N (omega)-nitro-L-arginine methyl ester (L-NAME) (10(-4)M) prevented the leptin-induced relaxation of the U46619 contraction response in the artery. The E-max and pD(2) values of the L-NAME-incubated veins were lower than those of the non-incubated veins (p<0.001 and p=0.001, respectively). The relaxation in angiotensin II-contracted veins was greater than that of the arteries (p<0.001). Incubation with L-NAME prevented leptin-induced relaxation in angiotensin II-contracted arteries. The E-max of leptin-induced relaxation of L-NAME-incubated veins was significantly lower than that of non-incubated veins (p=0.027); the pD(2) was similar. Conclusion: Leptin did not alter the resting tension of isolated umbilical vessels; however, the results indicated that leptin caused concentration-dependent relaxation in umbilical vessels pre-contracted with U46619 or angiotensin II. The maximum relaxation was greater in veins compared with arteries. Incubation with L-NAME completely inhibited leptin-induced relaxation in arteries and resulted in a significant inhibition in veins.Öğe Neuroprotective Effect of Intrastriatal Caffeic Acid Phenethyl Ester Treatment in 6-OH Dopamine Model of Parkinson's Disease in Rats(Hindawi Ltd, 2021) Soner, Burak Cem; Acikgoz, Eda; Inan, Salim Yalcin; Ayla, Sule; Sahin, Ayse Saide; Oktem, GulperiParkinson's disease (PD) is the second most common neurodegenerative disorder, and the main cause of PD is still not known. Until now, no cure for Parkinson's disease is yet in sight. Caffeic acid phenethyl ester (CAPE) is a polyphenolic component of the propolis, which can be derived from honeybee hive propolis. We aimed to determine the effect of intrastriatal CAPE administration as a neuroprotective agent on 6-hydroxydopamine (6-OHDA)-induced PD model. Adult male Wistar rats weighing 280-320 g were used. The PD model was induced with unilateral intrastriatal 6-OHDA injection. Treatment groups received 20 mu mol/5 mu L/4 day and 80 mu mol/5 mu L/4 day CAPE 24 h after 6-OHDA injection. Eight days after 6-OHDA application, behavioral studies (adhesive tape removal test, open-field test, cylinder test, and apomorphine-induced asymmetric rotational behavior) were performed once more to compare the effects of CAPE on behavior tests. Striatal histological verifications, immunohistochemistry, and stereological quantitation were performed. Our results for the first time showed that, besides improving the motor performance, CAPE treatment also prevents 6-OHDA-induced loss of TH-positive neurons. From our results, CAPE may be a promising clinical agent in the treatment of PD.Öğe Protective effects of Hawthorn (Crataegus oxyacantha) extract against digoxin-induced arrhythmias in rats(2015) Baysal, Tamer; Şahin, Ayşe Saide; Alp, Hayrullah; Soner, Burak CemObjective: Digitalis preparations are commonly used by children and adults with heart diseases worldwide, although excessive doses may cause cardiac effects. The aim of the study is to evaluate the antiarrhythmic effect of Crataegus oxyacantha extract on digoxin-induced arrhythmias in anesthetized Wistar rats. Methods: Control and experimental groups were evaluated for arrhythmias induced by digoxin. Fifteen rats (7 as controls and 8 as the experimental group) were included in the study. The dry fruits of 100 mg Crataegus oxyacantha were extracted by percolation method. Digoxin, at a dose of 40 ?g/kg/min, was infused to form the arrhythmias in all rats. Simultaneously, the extract was infused into the experimental group, while 0.9% NaCl was infused into control group. Electrocardiographic QRS prolongation and arterial blood pressure changes were analyzed.Results: The experimental group lived longer (62.13 2.20 min) than the controls (p0.002). On the other hand, the time to beginning of QRS prolongation did not differ between the two groups (p0.812). Bradycardia was significant in the control group (288.01 10.54 beat/min and p0.01). The maximum QRS duration was observed in the control group during the digoxin and 0.9% NaCl infusion period (53.29 3.99 ms and p0.001). Also, the durations of atrial and ventricular arrhythmias were shorter in the experimental group. However, arterial blood pressure dipping was significant in the experimental group (23.67 10.89 mm Hg and p0.001).Conclusion: Crataegus oxyacantha alcoholic extract produced an antiarrhythmic effect that was induced by digoxin in Wistar rats. However, in the clinical use of this extract, the hypotensive effect should be considered. Also, the alcoholic extract of Crataegus oxyacantha may be an alternative treatment medication for arrhythmias induced by digoxin toxicity in humans.Öğe Stem cell and extracellular matrix-related molecules increase following melatonin treatment in the skin of postmenopausal rats(Wiley, 2014) Uslu, Serap; Oktem, Gulperi; Uysal, Aysegul; Soner, Burak Cem; Arbak, Serap; Ince, UmitThe menopause has a negative effect in the skin. Melatonin affects skin functions and structures through actions mediated by cell-surface and putative-nuclear receptors expressed in skin cell. We have therefore determined the effects of melatonin treatment on stem cell in the epidermis and extracellular matrix related molecules in the dermis the skin of postmenopausal rats. A total of 45 female rats were divided into 5 groups: control group, group A [ ovariectomy (OVX)], group B (OVX +10 mg/kg/day melatonin), group C (OVX +30 mg/kg/day melatonin), group S (sham operated +10 mg/kg/day melatonin). Ventral skin samples were excised at 12th week after ovariectomy. Hematoxylin-eosin, periodic acid- methylamine silver, elastic van Gieson staining techniques were used to measure histomorphometrically the thickness of elastic fibers and basement membrane, depths of the epidermis, dermis, and subcutaneous fat layer. Immunohistochemical staining methods were used for fibroblast growth factor beta (FGF beta), collagen type I, fibronectin, beta-catenin, c-kit, c-Myc evaluation. Epidermal thickness, subcutaneous fat layer, and elastic fibers were significantly decreased in group C, and there was a significant increase after melatonin treatment. Although there was no difference in dermal thickness of group C, melatonin also significantly increased the dermal thickness. High FGF beta, type I collagen, fibronectin, beta-catenin, c-Myc immunoreactivity developed following melatonin in all groups. Thus melatonin treatment of postmenopausal rats was mostly due to the decrease of stem cell and extracellular matrix-related molecules in the skin.Öğe A survey of Turkish hospital patients' use of herbal medicine(Elsevier Science Inc, 2013) Soner, Burak Cem; Sahin, Ayse Saide; Sahin, Tahir KemalIntroduction: Herbal medicines (HMs) are generally considered safe due to their natural origin and long standing use. Although the use of HMs is common in Turkey, no detailed studies concerning the use or knowledge-attitudes towards HMs have been performed. This study aimed to describe the prevalence, types, reasons, attitudes and possible adverse effects related with HM use in population of Turkish hospital patients. Methods: Patients over 18 years of age were included in the study. Information was collected from a questionnaire completed by both out- and in-patients admitted to the Meram Faculty of Medicine Hospital in Konya between October 1st and December 31st 2012. Questions included herb use, reasons, attitudes and adverse effects. Results: Data from 927 questionnaires, conducted by face to face interviews identified that 48.8% of the study population used HM. Women, government officials (p<0.001), higher education level (p<0.05) and a higher family income (p<0.001) were more likely to use HMs. The most frequently used herbal medicines were Camellia sinensis (14.2%), Rosmarinus officinalis (10.2%) and Zingiber officinale (9.1%). Conclusion: Increased patient awareness about safe HM use is important considering that most HM users are being informed by friends or the media. Depending on the quality of the product, or in the case of being taken in conjunction with other medicines, traditional medicines can cause harmful adverse reactions. HMs have become a part of traditional medicine and healthcare providers need to be aware of how they are used by patients and ensure that health care policies exist to improve their safety and efficacy. (C) 2013 Elsevier GmbH. All rights reserved.