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Öğe Cardiac protection by mitoK(ATP) channels is dependent on akt translocation from cytosol to mitochondria during late preconditioning(Amer Physiological Soc, 2006) Ahmad, Nauman; Wang, Yigang; Haider, Khawaja Husnain; Wang, Boyu; Pasha, Zeeshan; Uzun, Özge; Ashraf, MuhammadThis investigation elucidates the Akt/mitochondrial ATP-sensitive K+ (mitoK(ATP)) channel signaling pathway in late pharmacological preconditioning, using the mitoK(ATP) channel openers BMS-191095 (BMS) and diazoxide (DE). BMS (1 mg/kg ip) and DE (7 mg/kg ip) alone or BMS plus wortmannin (WTN, 15 mu g/kg ip), an inhibitor of phosphatidylinositol 3-kinase, and BMS plus 5-hydroxydecanoic acid (5-HD, 5 mg/kg ip), an inhibitor of mitoK(ATP) channels, were administered to male mice. Twenty-four hours later, hearts were isolated and subjected to 40 min of ischemia and 120 min of reperfusion via Langendorff's apparatus. Both BMS and DE reduced left ventricular end-diastolic pressure and increased left ventricular developed pressure as well as reduced LDH release. Coadministration of BMS and WTN abolished the beneficial effects of BMS on cardiac function. Moreover, BMS and DE accelerated Akt phosphorylation in cardiac tissue as determined by Western blot analysis and also significantly reduced apoptosis compared with ischemic control. WTN significantly suppressed BMS-induced Akt phosphorylation, whereas 5-HD had no effect on Akt phosphorylation in cytosol, and the effect of BMS on apoptosis was abolished. It is concluded that the cardioprotective effect by mitoK(ATP) channels is attributed to the translocation of phosphorylated Akt from cytosol to mitochondria.Öğe Case report showed Beau's lines or onychomadesis, not Muehrcke's lines(Sage Publications Ltd, 2016) Polat, Mualla; Uzun, ÖzgeTo the Editor, We wrote for the case report entitled ‘Muehrcke’s lines (Leukonychia striata) due to transretinoic acid therapy for acute promyelocytic leukemia’ presented by Dasanu et al.1 Our assessment is based on clinical photographs submitted by the researchers. It is well known that drug-induced nail abnormalities may result from toxicity to the matrix, the nail bed, or the periungual tissues. The most common symptoms include Beau’s lines, onychomadesis, melanonychia, onycholysis, periungual pyogenic granulomas, and Muehrcke’s lines. Nail changes usually affect several nails and in most cases are asymptomatic. Drugs that most frequently produce nail abnormalities include retinoids, indinavir, and cancer chemotherapeutic agents. In this case, it should be considered all differential diagnosis such as Muehrcke’s lines, Beau’s lines, or onychomadesis occurs due to drugs. In the presented case, we saw transverse white band on her nail plates after receiving 16-week transretinoic acid therapy for acute promyelocytic leukemia. But this cannot identify as a Muehrcke’s line. Because it does not appear the two horizontal white lines that run parallel to the lunula across the width of the nail which are specific for Muehrcke’s lines. Otherwise Muehrcke’s lines are nonpalpable.4 Moreover, we detected broken nail and grooves or furrows on the white nail plate. As a result, these are characteristic of Beau’s lines or onychomadesis not Muehrcke’s lines.Öğe Effect of metformin on the human T98G glioblastoma multiforme cell line(Spandidos Publ Ltd, 2014) Üçbek, Ali; Özünal, Zeynep Güneş; Uzun, Özge; Gepdiremen, AkçahanMetformin is a guanidine derivative found in Galega officinalis that is commonly used to treat diabetes mellitus. The mechanism of action of metformin involves regulation of the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin signaling pathway, which is implicated in the control of protein synthesis and cell proliferation. This led to the hypothesis that metformin reduces the risk of cancer and slows tumor growth. Thus, in the present study, the effectiveness of metformin as an antiglioma agent was evaluated using the human T98G glioblastoma multiforme cell line. The viability of the T98G cells was assessed using a 3-(4,5-dimethylthiazol-2-yL)-2,5-diphenyltetrazolium bromide assay. Apoptosis was monitored by measuring caspase-3 levels, as well as by terminal deoxynucleotidyl transferase dUTP nick end labeling and staining with acridine orange and ethidium bromide. The results demonstrate that metformin reduced cell viability and caused apoptotic morphological changes in the T98G cells. Furthermore, the caspase-3 levels in the metformin-treated T98G cells were higher than those in the control cells. Metformin induced apoptosis in the T98G cell line in a concentration-dependent manner. Metformin may provide an important contribution to the treatment of glioblastoma multiforme.Öğe The effect of NF-kappa B and angiotensin II on the proliferation in human breast adenocancer cell line(2013) Özünal, Zeynep Güneş; Bayram, Recep; Yavuz, Muhsine Zeynep; Ucbek, Ali; Aydoğar, A.; Uzun, Özge; Gepdíremen, Akçahan AkçahanThere are many in-vitro studies implicating that Angiotensin (Ang)II stimulates solid organ cancer growth. Effect of AngII on cell proliferation can be related to nuclear factor NFkB. The aim of the present study is to examine the effects of pyrithione, an NFkB inhibitor and AngII on breast cancer cell proliferation. MCF-7 is treated with AII (10?M) and NFkB inhibitor, pyrithione sodium (0,1-100?M). Cells are counted and photographed. WST-1 is used to measure viability in 48h after treatment and groups are fluorescent dyed with ethidium bromide. The results of cell count showed that cell proliferation was increased in AngII treated group when compared with control group. However, this increase did not show statistically significance. Cell count was decreased in pyrithione (10 and 100?M) treated group. Morphologic changes were most apparent in 100?M pyrithione group. We concluded that pyrithione alone or in combination with AngII decreased MCF-7 cell proliferation.Öğe Effect of resveratrol in acute hypoxic pulmonary vasoconstriction in isolated lamb pulmonary arteries and veins(2009) Sılan, Coşkun; Kuşcuoğlu, Evren; Uzun, Özge; Balbay, Öner AbidinResveratrol (RSV), antioksidan, antitrombositik, antiaterojenik, antienflamatuar, immunomodülatör, kimyasallara karşı koruyucu ve östrojenik özellikleri dahil olmak üzere çeşitli biyolojik etkileri olan doğal bir fitoleksindir. Kardiyovasküler sistemdeki etkileri incelendiğinde damar düz kaslarında gevşetici etkisi; çeşitli damar yataklarında endotele bağımlı ve endotelden bağımsız mekanizmalarla vazodilatatör etkilere sebep olduğu bildirilmiştir. Bu çalışmada önkasılım oluşturulmuş izole kuzu pulmoner arter ve venlerinde, hipoksinin damar yanıtlarına etkisi ile hipoksiye bağlı vazokonstriksiyonda resveratrolun etkisi araştırıldı. Krebs-Heinseleit solusyonu ile doldurulmuş organ banyosuna asılmış izole kuzu pulmoner damarları izometrik transduser aracılığı ile bilgisayarlı poligraf sisteminde sürekli kayıt edilmiştir. Çözelti oda havasıyla (normoksik) veya %95 N2 + %5 CO2 karışımıyla (hipoksik) havalandırılmıştır. İzole organ banyosundaki solüsyonun oksijen konsantrasyonu oksijen elektrodu ile ölçülmüştür. Ön kasılım oluşturmak için arterlerde Serotonin (5-HT), (10-5 M) ve venlerde de bir tromboksan analogu olan U46619 kullanılmıştır. Sonuçlarımız; RSV (20 ?M)’ün, U46619 ile önkasılım oluşturulmuş pulmoner venlerde hipoksik pulmoner vazokonstriksiyonu anlamlı şekilde inhibe ettiğini, ancak 5-HT ile önkasılım oluşturulmuş pulmoner arterlerde damar yanıtlarını anlamlı olarak etkilemediğini göstermiştir.Öğe The effects of no and cylooxygenase inhibition on hypoxic vasoconstriction of sheep pulmonary vein rings(Wiley-Blackwell, 2001) Uzun, Özge; Demiryürek, Abdullah T.[No Abstract Available]Öğe Erdosteine protects rat testis tissue from hypoxic injury by reducing apoptotic cell death(Wiley, 2014) Güven, Aysel; İçkin, Meltem; Uzun, Özge; Bakar, Coşkun; Balbay, Ege GüleçThe purpose of this study was to examine the effects of hypobaric hypoxia on testis morphology and the effects of erdosteine on testis tissue. Caspase-3 and hypoxia-inducible factor 1 expressions were detected by immunohistochemistry. Adult male Wistar rats were placed in a hypobaric hypoxic chamber. Rats in the erdosteine group were exposed to the same conditions and treated orally with erdosteine (20mgkg(-1) daily) at the same time from the first day of hypoxic exposure for 2weeks. The normoxia group was evaluated as the control. The hypoxia group showed decreased height of spermatogenic epithelium in some seminiferous tubules, vacuolisation in spermatogenic epithelial cells, deterioration and gaps in the basal membrane and an increase in blood vessels in the interstitial area. The erdosteine group showed amelioration of both epithelial cell vacuolisation and basal membrane deterioration. Numbers of hypoxia-inducible factor 1-immunostained Sertoli and Leydig cells were significantly higher in the hypoxia group than in the erdosteine group. The number of seminiferous tubules with caspase-3-immunostained germ cells was highest in the hypoxia group and decreased in the erdosteine and normoxia groups respectively. Based on these observations, erdosteine protects testis tissue from hypoxic injury by reducing apoptotic cell death.Öğe Evaluation of Sense of Smell in Onychomycosis Patients Receiving Terbinafine Treatment(Duzce University Medical School, 2021) Polat, Mualla; Karapinar, Tekden; Küçükyangöz, Belgin; Biçer, Yusuf Özgür; Uzun, Özge; Sezer, TunaAim: The most common side effects of terbinafine are gastrointestinal symptoms. Loss of taste and smell side effects are presented in a small number of case reports. We aimed to measure the effect of terbinafine on the sense of smell and the degree of change in the sense of smell in this study. Material and Methods: Odor identification test (OIT), odor threshold test (OTT), and odor discrimination test (ODT) were applied to the patients treated with terbinafine and the control group. It was applied with “Sniffin Sticks” test pens. Smell test was performed on the patient group just before the start of terbinafine treatment and at the end of 3 months of treatment. Results: There was no statistical difference between the patient and control groups in terms of age (p=0.991) and gender (p=0.811). There was no statistical difference when the initial odor tests of the patient group and the control group were compared. The OIT value of the patient group was 10.15±1.43 at the beginning and 10.10±1.15 at the end of the treatment (p=0.743). The OTT values were 6.23±1.08 at the beginning and 6.21±0.85 at the end of the treatment (p=0.811). The ODT values were 9.71±1.44 at the beginning and 9.69±1.34 at the end of the treatment (p=0.767). There was no statistical difference in the results of the tests performed at the beginning and end of the treatment. Conclusion: There was no adverse effect on the sense of smell associated with the use of systemic terbinafine treatment for 3 months. © 2021, Duzce University Medical School. All rights reserved.Öğe Hypobaric-hypoxia-induced pulmonary damage in rats ameliorated by antioxidant erdosteine(Elsevier Gmbh, Urban & Fischer Verlag, 2006) Uzun, Özge; Balbay, Öner; Çomunoğlu, Nil Üstündağ; Yavuz, Özlem; Annakkaya, Ali Nihat; Güler, Selver; Sılan, CoşkunFree radical-mediated injury to lung and pulmonary vasculature is an important mechanism in hypoxia-induced lung damage. In this study, we aimed to investigate the potential protective effects of erdosteine as an antioxidant agent on hypobaric hypoxia-induced pulmonary hypertension. Adult mate rats were assigned randomly to three groups. The first group of rats was exposed to hypobaric-hypoxia and the second group was treated with erdosteine (20 mg/kg, daily) for 2 weeks, during which time they were in a hypoxic chamber. These groups were compared with normoxic controls. All. rats were sacrificed after 2 weeks. The hypoxia-induced increase in right ventricle to left ventricle plus septum weight ratio (from 0.20+/-0.01 to 0.26+/-0.01) was reduced significantly in the erdosteine-treated group (0.23+/-0.01). Malondialdehyde levels were elevated (from 0.33+/-0.11 to 0.59+/-0.02) and total antioxidant status was not changed significantly (from 1.77+/-0.42 to 2.61+/-0.23) by hypoxia. In contrast to the hypoxia-exposed group, malondialdehyde levels were significantly decreased in the erdosteine-treated group (0.37+/-0.02). Total antioxidant status (4.03+/-0.22) was significantly higher in erdosteine-treated rats when compared to non-treated rats. Histopathotogical examination demonstrated that erdosteine prevented inflammation and protected lung parenchyma and pulmonary endothelium of hypoxia-exposed rats.Öğe Involvement of tyrosine kinase pathway in acute hypoxic vasoconstriction in sheep isolated pulmonary vein(Elsevier Science Inc, 2003) Uzun, Özge; Demiryürek, A. TuncayTyrosine kinase pathway has been shown to be involved in the effects of hypoxia in pulmonary arteries, but its role in pulmonary vein is not known. The aims of this study were to determine the effect of hypoxia in sheep isolated pulmonary veins and to identify the role of tyrosine kinase pathway in hypoxic response. Genistein and tyrphostin were used as selective tyrosine kinase inhibitors, and sodium orthovanadate was administered for tyrosine kinase activation. Hypoxia (95% N-2 to 5% CO2) caused a vasoconstriction either under resting tone or in U46619-precontracted pulmonary veins. Genistein and tyrphostin inhibited hypoxia-induced vasoconstriction both under resting tone and in precontracted veins, while sodium orthovanadate increased these hypoxic contractions. Our findings suggest that tyrosine kinase pathway is involved in hypoxic pulmonary vasoconstriction in sheep isolated pulmonary vein rings.Öğe Kuzu izole pulmoner arterlerinde gelişen hipoksik pulmoner vazokonstriksiyonda Gi ve Gs proteinlerinin rolü(2014) Erbaş, Mete; Balbay, Öner Abidin; Balbay, Ege Güleç; Uzun, Özge; Sılan, CoşkunHipoksik pulmoner vazokonstriksiyon akciğerlerde ventilasyon perfüzyon dengesini sağlayan fizyolojik uyum mekanizmasıdır. Hipoksemi ile seyreden progressif akciğer hastalıklarının patogenezinde önemli rol oynamakla birlikte sağlıklı bireylerde de görülmektedir. Yoğun çalışmalara rağmen, hipoksik pulmoner vazokonstriksiyonun mekanizması henüz bulunamamıştır. G proteinleri vasküler endotel ve düz kas hücrelerinde reseptör aracılıklı sinyal iletimine aracılık ederek vasküler tonusun düzenlenmesinde önemli rol oynayan membrana bağlı protein ailesidir. Biz bu çalışmada, kuzu izole pulmoner arterlerinde izlenen hipoksik vazokonstriksiyonun oluş mekanizmasında Gi ve Gs proteinlerinin rolünü saptamayı amaçladık. Pulmoner arterler yeni kesilmiş kuzuların sol akciğer alt loblarından izole edildi. Arterler Krebs-Henseleit solüsyonu ile dolu olan izole organ banyosuna asıldı ve izometrik kontraksiyonlar bilgisayarlı poligrafi sistemi ile bağlantılı olan izometrik transdüsır yoluyla devamlı olarak kaydedildi. Solüsyon %75 N2 - %20 O2 - %5 CO2 (Normoksik) ve %95 N2 - %5 CO2 (Hipoksik) karışımı içeren gazlar ile havalandırıldı. Organ banyosundaki parsiyel oksijen konsantrasyonu oksijen elektrodu kullanılarak sürekli olarak ölçüldü. Gi ve Gs proteinlerin rolünü araştırmak için kolera ve pertusis toksini kullanıldı. Çalışmada, dinlenme gerimindeki geniş çaplı pulmoner arterlerde hipoksiye bağlı bir gerim artışı izlenmedi ancak hipoksi 3 mM 5-HT ile prekontrakte edilmiş dokularda kontraksiyona (1.7±0.5 mN/mm2, n=10) sebep oldu. Hipoksik vazokonstriksiyon 2 mg/ml kolera toksini ile inkübasyon sonrası inhibe (2.6±0.4 mN/mm2’den 1.0±0.4 mN/mm2’ye kadar, n=6) ve 2 mg/ml pertusis toksini ile inkübasyon sonrası potansiyalize (0.6±0.4 mN/mm2’den 1.7±0.3 mN/mm2’ye kadar, n=6) oldu. Bu sonuçlar Gi ve Gs proteinleri ile ilişkili sinyal iletiminin geniş çaplı kuzu izole pulmoner arterinde gelişen hipoksik vazokonstriksiyonda önemli bir mekanizma olabileceğini gösterdi.Öğe Nuclear factor-kappa B inhibitors abolish hypoxic vasoconstriction in sheep-isolated pulmonary arteries(Elsevier Science Bv, 2003) Uzun, Özge; Demiryürek, A. TuncayThe aim of this study was to determine the role of nuclear factor-kappaB (NF-kappaB) in hypoxic constriction of isolated pulmonary arteries. Rings were suspended in an organ bath filled with Krebs-Henseleit solution and isometric contractions were recorded continuously. Hypoxia (%95 N-2-%5 CO2) had no marked effect on resting force in artery rings. However, hypoxia caused further contractions in serotonin-precontracted arteries. Hypoxia-induced vasoconstrictions were abolished by preincubation with NF-kappaB inhibitors, pyrrolidine dithiocarbamate (100 muM) or pyrithione (10 muM). These results suggest that reactive oxygen species and/or NF-kappaB activation may be involved in the hypoxia-induced vasoconstriction in sheep-isolated pulmonary arteries.Öğe Pityriasis rosea-like drug eruption due to bupropion : a case report(Sage Publications Ltd, 2014) Polat, Mualla; Uzun, Özge; Örs, İsmail; Boran, ÇetinPityriasis rosea (PR) is a common, acute, and self-limited inflammatory skin disease. The typical clinical presentation includes the appearance of a primary "herald" patch followed within days to weeks by the onset of secondary scaly skin eruptions distributed along the skin tension line in most cases. Although PR is a well-known and relatively common disease, its cause is still not completely understood. However, viral agents, autoimmunity, psychogenic status, and numerous drugs have been proposed as possible factors to PR. Bupropion is known to cause hypersensitivity reactions. We present a clinical case of PR eruption caused by the use of bupropion. To the best of our knowledge, this is the first published case of PR associated with bupropion use.Öğe Pyrrolidine dithiocarbamate attenuates the development of monocrotaline-induced pulmonary arterial hypertension(Elsevier Gmbh, Urban & Fischer Verlag, 2013) Yavuz, Taner; Uzun, Özge; Macit, Aslı; Çomunoğlu, Cem; Yavuz, ÖzlemWe aimed to demonstrate the potential protective effects of pyrrolidine dithiocarbamate (PDTC) on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Adult male rats were randomly assigned to 4 groups: control group, MCT-treated rats only, MCT-injected rats treated with PDTC, and PDTC-treated rats only. Blood and tissue samples were collected after the sacrifice. Levels of malondialdehyde (MDA) were measured by using the thiobarbituric acid method. Total antioxidant status (TAS) was determined using a commercially available ImAnOx kit. A histopathological evaluation was accomplished by scoring the degree of severity. Endothelial damage of the main pulmonary artery was evaluated by immunohistochemical labeling of endothelial cells using anti-rat endothelial cell antigen 1 (RECA-1) antibody. MCT-induced right ventricular hypertrophy (RVH) was reduced significantly in the MCT + PDTC-treated group. MDA levels were significantly lowered in the MCT + PDTC-treated group. TAS was significantly higher in the MCT + PDTC-treated group when compared with the rats with PAH. Histopathological examination demonstrated that PDTC treatment reduced the development of inflammation, hemorrhage and congestion, and collagen deposition. In conclusion, PDTC attenuated PAH and protected pulmonary endothelium in rats administered MCT. These findings suggest that PDTC treatment may provide a new effective therapeutic approach in the treatment of PAH. (C) 2013 Elsevier GmbH. All rights reserved.Öğe Role of G(s) proteins in hypoxic constriction of sheep pulmonary artery rings(Karger, 2002) Uzun, Özge; Demiryürek, Abdullah T.; Kanzık, İlhanThe introduction of hypoxia is well known to cause contraction of pulmonary artery rings in vitro. Despite intensive studies, the cellular mechanisms of hypoxic pulmonary vasoconstriction are still not well defined. In this study, we aimed to determine the contribution of G(S) proteins in hypoxia-induced vasoconstriction in large-diameter sheep pulmonary arteries using cholera toxin (CT). Hypoxia caused further contractions in serotonin but not in NaF-precontracted pulmonary artery rings. However, hypoxic vasoconstriction due to lowering Of pO(2) from 97 to 5 mm Hg was totally abolished by preincubation with CT in serotonin-precontracted arteries. These preliminary results indicate that signal transduction mediated by G(S) proteins may be an important mechanism in the hypoxic vasoconstriction of isolated pulmonary arteries of sheep.Öğe Role of NO and prostaglandins in acute hypoxic vasoconstriction in sheep pulmonary veins(Karger, 2006) Uzun, Özge; Demiryürek, Abdullah T.The aim of this study was to investigate the effect of hypoxia on and the role of nitric oxide (NO) and cyclooxgenase inhibition in hypoxia-induced vasoconstriction in sheep isolated pulmonary veins. We used the potent pulmonary vasoconstrictor U46619, a thromboxane analog, as a precontractile agent. Our results showed that hypoxia caused a vasoconstriction both under resting tone and in U46619 (10(-6) mol/l) precontracted pulmonary veins. In the presence of the nonselective NO synthase inhibitior N omega-nitro-L-arginine methyl ester (L-NAME; 3 x 10(-5) mol/l), the hypoxic pulmonary vasoconstriction (HPV) was significantly increased in veins under resting force. However, there was a decrease in HPV in pulmonaryveins precontracted with U46619 in the presence of L-NAME. Moreover, L-NAME markedly augmented the U46619-induced pulmonary contractions under normoxic conditions. Cyclooxygenase inhibition with indomethacin (10(-5) mol/l) significantly reduced the HPV both under resting tone and in precontracted veins. Indomethacin also significantly decreased the U46619-induced pulmonary contractions prior to the induction of hypoxia. Our findings suggest that NO and prostaglandins can act as a modulators of the hypoxic vasoconstriction in isolated pulmonary veins.Öğe The use of calcium channel blockers in skin diseases(Turkish Soc Dermatology Venerology, 2013) Polat, Mualla; Uzun, ÖzgeCalcium channel blockers are a group of drugs often used to treat cardiovascular diseases, such as hypertension, angina, peripheral vascular disorders and some arrhythmias. These drugs may suppress the growth and proliferation of vascular smooth muscle cells and fibroblasts, and inhibit the synthesis of extracellular-matrix proteins,such as collagen, fibronectin, proteoglycans. Some calcium channel blockers also have immunomodulatory or dysregulatory effects on lymphocytes and can suppress superoxide generation and phagocytic activity of neutrophils. Moreover, mast cell degranulation and platelet aggregation may also be impaired. On account of these properties, calcium channel blockers have also been used for the prevention and treatment of various dermatologic diseases. In this review, we evaluated the use of calcium channel blockers in various dermatologic diseases, such as Raynaud's phenomenon, chilblains, chronic anal fissures, vulvodynia, keloids and burn scars, calcinosis cutis, and leiomyoma.
