Researcher: Yalçın, Özlem
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Yalçın, Özlem
Yalçın, Özlem Seyhan
Yalçın, Özlem Seyhan
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Publication Metadata only A structured mechanical risk sensitivity assessment system using red cell deformability and fragmentation parameters(Ios Press, 2021) Yalçın, Özlem; Uğurel, Elif; Göktaş, Polat; Göksel, Evrim; Çilek, Neslihan; Atar, Dila; Faculty Member; Researcher; Researcher; PhD Student; PhD Student; Undergraduate Student; School of Medicine; School of Medicine; School of Medicine; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; 218440; N/A; N/A; N/A; N/A; N/AN/APublication Metadata only A micropillar-based microfluidic viscometer for newtonian and non-newtonian fluids(Elsevier, 2020) Tanyeri, Melikhan; Erten, Ahmet; Department of Physics; N/A; N/A; N/A; N/A; Kiraz, Alper; Yalçın, Özlem; Mustafa, Adil; Aksu, Ali Cenk; Eser, Ayşenur; Faculty Member; Faculty Member; PHD Student; PHD Student; Master Student; Department of Physics; College of Sciences; School of Medicine; Graduate School of Sciences and Engineering; School of Medicine; Graduate School of Sciences and Engineering; 22542; 218440; N/A; N/A; N/AIn this study, a novel viscosity measurement technique based on measuring the deflection of flexible (poly) dimethylsiloxane (PDMS) micropillars is presented. The experimental results show a nonlinear relationship between fluid viscosity and the deflection of micropillars due to viscoelastic properties of PDMS. A calibration curve, demonstrating this nonlinear relationship, is generated, and used to determine the viscosity of an unknown fluid. Using our method, viscosity measurements for Newtonian fluids (glycerol/water solutions) can be performed within 2-100 cP at shear rates gamma = 60.5-398.4 s(-1). We also measured viscosity of human whole blood samples (non-Newtonian fluid) yielding 2.7-5.1 cP at shear rates gamma = 120-345.1 s(-1), which compares well with measurements using conventional rotational vis-cometers (3.6-5.7 cP). With a sensitivity better than 0.5 cP, this method has the potential to be used as a portable microfluidic viscometer for real-time rheological studies. (C) 2020 Elsevier B.V. All rights reserved.Publication Metadata only Activation of protein kinase a cascade increases deformability of sickle red blood cells(Ios Press, 2021) Connes, Philippe; Boisson, Camille; Renoux, Celine; Gauthier, Alexandra; Fort, Romain; Nader, Elie; Poutrel, Solene; Göksel, Evrim; Yalçın, Özlem; PhD Student; Faculty Member; School of Medicine; School of Medicine; N/A; 218440Publication Metadata only Calcium/protein kinase C signaling mechanisms in shear-induced mechanical responses of red blood cells(Academic Press Inc Elsevier Science, 2021) N/A; N/A; N/A; N/A; N/A; N/A; Uğurel, Elif; Kısakürek, Zeynep Büşra; Aksu, Yasemin; Göksel, Evrim; Çilek, Neslihan; Yalçın, Özlem; Researcher; Undergraduate Student; Undergraduate Student; PhD Student; PhD Student; Faculty Member; School of Medicine; School of Medicine; School of Medicine; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; N/A; N/A; N/A; N/A; N/A; 218440Red blood cell (RBC) deformability has vital importance for microcirculation in the body, as RBCs travel in narrow capillaries under shear stress. Deformability can be defined as a remarkable cell ability to change shape in response to an external force which allows the cell to pass through the narrowest blood capillaries. Previous studies showed that RBC deformability could be regulated by Ca2+/protein kinase C (PKC) signaling mechanisms due to the phosphorylative changes in RBC membrane proteins by kinases and phosphatases. We investigated the roles of Ca2+/PKC signaling pathway on RBC mechanical responses and impaired RBC deformability under continuous shear stress (SS). A protein kinase C inhibitor Chelerythrine, a tyrosine phosphatase inhibitor Calpeptin, and a calcium channel blocker Verapamil were applied into human blood samples in 1 micromolar concentration. Samples with drugs were treated with or without 3 mM Ca2+. A shear stress at 5 Pa level was applied to each sample continuously for 300 s. RBC deformability was measured by a laser-assisted optical rotational cell analyzer (LORRCA) and was calculated as the change in elongation index (EI) of RBC upon a range of shear stress (SS, 0.3-50 Pa). RBC mechanical stress responses were evaluated before and after continuous SS through the parameterization of EI-SS curves. The drug administrations did not produce any significant alterations in RBC mechanical responses when they were applied alone. However, the application of the drugs together with Ca2+ substantially increased RBC deformability compared to calcium alone. Verapamil significantly improved Ca2+-induced impairments of deformability both before and after 5 Pa SS exposure (p < 0.0001). Calpeptin and Chelerythrine significantly ameliorated impaired deformability only after continuous SS (p < 0.05). Shear-induced improvements of deformability were conserved by the drug administrations although shear-induced deformability was impaired when the drugs were applied with calcium. The blocking of Ca2+ channel by Verapamil improved impaired RBC mechanical responses independent of the SS effect. The inhibition of tyrosine phosphatase and protein kinase C by Calpeptin and Chelerythrine, respectively, exhibited ameliorating effects on calcium-impaired deformability with the contribution of shear stress. The modulation of Ca2+/ PKC signaling pathway could regulate the mechanical stress responses of RBCs when cells are under continuous SS exposure. Shear-induced improvements in the mechanical properties of RBCs by this signaling mechanism could facilitate RBC flow in the microcirculation of pathophysiological disorders, wherein Ca2+ homeostasis is disturbed and RBC deformability is reduced.Publication Metadata only Nitrite may serve as a combination partner and a biomarker for the anti-cancer activity of RRx-001(Ios Press, 2019) Cirrik, Selma; Oronsky, Bryan; Cabrales, Pedro; N/A; Uğurel, Elif; Aksu, Ali Cenk; Yalçın, Özlem; Researcher; PhD Student; Faculty Member; School of Medicine; Graduate School of Health Sciences; School of Medicine; N/A; N/A; 218440Background: RRx-001 is an anti-cancer immunotherapeutic that increases the sensitivity of drug resistant tumors via multiple mechanisms which involve binding to hemoglobin and enhancing nitrite reductase activity of deoxyhemoglobin. Objective: In the present study, the effect of clinically used doses of RRx-001 on erythrocyte deformability was examined. Methods: A dose dependent effect of RRx-001 (1-1000 micro molar) on erythrocyte deformability was measured by ektacytometer under hypoxia (n = 8). Low dose RRx-001 (20 micro molar) in the presence of ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one), L-NAME (L-NG-Nitroarginine methyl ester) or nitrite were examined both in normoxia and hypoxia. Intracellular nitric oxide (NO) levels were measured fluorometrically with DAF-FM-DA. Results: Higher doses of RRx-001 (100, 1000 micro molar) significantly decreased erythrocyte deformability under hypoxia (p < 0.01; p < 0.05, respectively). RRx-001 (20 micro molar), alone or in combination with ODQ or L-NAME, did not change deformability. However, RRx-001 and nitrite caused an increase in deformability (p < 0.01) under hypoxia. RRx-001 induced NO production was more pronounced in the presence of nitrite (p < 0.05). Conclusions: Co-administration of RRx-001 and nitrite under hypoxic conditions results in a significant increase in erythrocyte deformability that is related to increased NO production. We suggest that measurement of serum nitrite level in RRx-001 treated cancer patients should be routinely undertaken and supplemented if levels are low for maximal activity.Publication Metadata only Differential effects of adenylyl cyclase-protein kinase a cascade on shear-induced changes of sickle cell deformability(IOS Press, 2019) Connes, Philippe; Renoux, Celine; Joly, Philippe; Gauthier, Alexandra; Hot, Arnaud; Bertrand, Yves; Cannas, Giovanna; N/A; N/A; N/A; N/A; N/A; N/A; Uğurel, Elif; Yalçın, Özlem; Yavaş, Gökçe; Eğlenen, Buse; Aksu, Ali Cenk; Turkay, Mine; Researcher; Faculty Member; Undergraduate Student; Undergraduate Student; PhD Student; Undergraduate Student; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Graduate School of Health Sciences; School of Medicine; N/A; 218440; N/A; N/A; N/A; N/ABackground: Erythrocyte deformability is impaired in sickle cell disease (SCD). The regulation of cytoskeletal protein organization plays a key role in erythrocyte deformability. The activation of adenylyl cyclase (AC)/cAMP/Protein kinase A (PKA) signaling pathway was associated with increased deformability in healthy erythrocytes, however the role of this pathway in SCD is unknown. Objective: We evaluated mechanical responses of sickle red blood cells under physiological levels of shear stress and the possible link between their deformability and AC/cAMP/PKA signaling pathway. Methods: The shearing of sickle red blood cells at physiological level (5 Pa) and the measurement of deformability were performed by a laser assisted optical rotational cell analyzer (LORRCA). Results: Red blood cell deformability increased of 2.5-6.5% by blocking the activity of phosphodiesterase with Pentoxifylline (10 mu M) (p < 0.05). The inhibition of AC with SQ22536 (100 mu M) produced more significant rise in deformability (+4.8-12%, p < 0.01). No significant change was observed by the inhibition of PKA with H89 (10 mu M). Conclusion: Pentoxifylline and SQ22536 increased the deformability of sickle red blood cells under fluid shear stress. Modulation of the AC/cAMP/PKA pathway could have the potential to be an effective therapeutic approach for SCD through shear-induced improvements of RBC deformability.Publication Metadata only A short-term in vivo evaluation of the Istanbul heart left ventricular assist device in a pig model(Middle East Society for Organ Transplantation, 2019) Küçükaksu, Deniz Süha; Bakuy, Vedat; Arat, Nurcan; Erkasap, Pelin Çelikbilek; Aksoy, Emin; Department of Mechanical Engineering; N/A; N/A; N/A; N/A; N/A; Lazoğlu, İsmail; Öztürk, Çağlar; Aka, İbrahim Başar; Yalçın, Özlem; Uğurel, Elif; Ruacan, Ahmet Şevket; Faculty Member; PhD Student; PhD Student; Faculty Member; Researcher; Faculty Member; Department of Mechanical Engineering; Manufacturing and Automation Research Center (MARC); College of Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; School of Medicine; School of Medicine; School of Medicine; 179391; N/A; N/A; 218440; N/A; N/AObjectives: a continuous-flow centrifugal blood pump system has been recently developed as an implantable left ventricular assist device for patients with endstage heart failure. The objective of this study was to evaluate the initial in vivo performance of a newly developed left ventricular assist device (iHeart or Istanbul heart; Manufacturing and Automation Research Center, Koc University, Istanbul, Turkey) in an acute setting using a pig model. Materials and Methods: three pigs (77, 83, 92 kg) received implants via a median sternotomy, with animals supported for up to 6 hours. An outflow cannula was anastomosed to the ascending aorta. Anticoagulation was applied by intravenous heparin administration. During the support period, pump performance was evaluated under several flow and operating conditions. All pigs were humanely sacrificied after the experiments, and organs were examined macroscopically and histopathologically. Results: flow rate ranged between 1.5 and 3.6 L/min with pump speeds of 1500 to 2800 revolutions/min and motor current of 0.6 to 1.3 A. Initial findings confirmed thatthe iHeart ventricular assist device had sufficient hydraulic performance to support the circulation. During the experimental period, plasma free hemoglobin levels were found to be within normalranges. Thrombus formation was not observed inside the pump in all experiments. Conclusions: the iHeart ventricular assist device demonstrated encouraging hemodynamic performance and good biocompatibility in the pig model for use as an implantable left ventricular assist device. Further acute in vivo studies will evaluate the short-term pump performance prior to chronic studies for long-term evaluation.Publication Metadata only Image-based flow cytometry and angle-resolved light scattering to define the sickling process(Wiley, 2019) Sukharevsky, Ilya O.; Larkin, Sandra; Kuypers, Frans A.; Yalcin, Ozlem; Altintas, Ayhan; Yalçın, Özlem; Göktaş, Polat; Faculty Member; Researcher; School of Medicine; School of Medicine; 218440; N/ARed blood cells (RBCs) from sickle cell patients exposed to a low oxygen tension reveal highly heterogeneous cell morphologies due to the polymerization of sickle hemoglobin (HbS). We show that angle-resolved light scattering approach with the use of image-based flow cytometry provides reliable quantitative data to define the change in morphology of large populations of RBCs from sickle cell patients when the cells are exposed for different times to low oxygen. We characterize the RBC morphological profile by means of a set of morphological and physical parameters, which includes cell shape, size, and orientation. These parameters define the cell as discocyte, sickle, elongated, as well as irregularly or abnormal RBC shaped cells, including echinocytes, holly-leaf, and granular structures. In contrast to microscopy, quick assessment of large numbers of cells provides statistically relevant information of the dynamic process of RBC sickling in time. The use of this approach facilitates the understanding of the processes that define the propensity of sickle blood samples to change their shape, and the ensuing vaso-occlusive events in the circulation of the patients. Moreover, it assists in the evaluation of treatments that include the use of anti-sickling agents, gene therapy-based hemoglobin modifications, as well as other approaches to improve the quality of life of sickle cell patients.Publication Metadata only Identification of diagnostic and prognostic indicators of hypercoagulability in patients with pseudoexfoliation syndrome(Association for Research in Vision and Ophthalmology (ARVO), 2021) N/A; N/A; Narimanfar, Ghazal; Uğurel, Elif; Kesim, Cem; Zibandeh, Noushin; Albayrak, Özgür; Şahin, Afsun; Yalçın, Özlem; PhD Student; Resercher; Doctor; Resercher; Resercher; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; N/A; N/A; School of Medicine; School of Medicine; N/A; N/A; Koç University Hospital; N/A; N/A; 387367; N/A; N/A; 171267; 218440N/APublication Metadata only Can rotational thromboelastometry be a new predictive tool for retinal vein occlusion development?(Taylor & Francis, 2019) Şahin, Deniz Gören; Özkaya, Abdullah; Bayraktutar, Betül; Taş, Ayşe Yıldız; Akay, Olga Meltem; Yalçın, Özlem; Şahin, Afsun; Doctor; Faculty Member; Faculty Member; Faculty Member; Faculty Member; N/A; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; N/A; 200905; 170966; 218440; 171267Purpose: To evaluate clotting dynamics by a new tool called rotational tromboelastometry (ROTEM) in retinal vein occlusion.Materials and methods: Thirty-six patients who were diagnosed with retinal vein occlusion and 43 age and sex matched healthy controls were included in this study. Diabetes and use of anticoagulant therapy were exclusion criteria. All study participants underwent detailed ophthalmologic and systemic medical examination, including blood pressure measurement, hemoglobin-hematocrit levels, platelet count, coagulation parameters including prothrombin time, activated partial thromboplastin time, fibrinogen levels, and D-dimer levels. Peripheral blood samples were collected and analyzed with ROTEM Coagulation Analyzer (Tem International, Munich, Germany).Results: The RVO patients and controls did not differ with respect to age, sex, hemoglobin, hematocrit, platelet numbers, prothrombin time, activated partial thromboplastin time, fibrinogen levels, D-dimer levels, and glucose levels. When extrinsic thromboelastometry results were analyzed, RVO patients showed a significantly decreased clotting time (76.515.0 vs. 95.0 +/- 21s, respectively; p =0.01) and clot formation time (83.3 +/- 22 vs. 99.7 +/- 24s; p =0.01) as compared with healthy controls. Other ROTEM parameters did now show any difference between two groups.Conclusion: Patients with retinal vein occlusion showed faster clotting time and shorter clotting formation time as compared with healthy controls. ROTEM detects the altered clotting dynamics and may be a useful tool to elucidate the disease pathophysiology. Further studies are needed to investigate if it can be used as a screening test for individuals who are under risk to develop RVO or as a first step test to evaluate hypercoagulable state in RVO.