Browsing by Author "Akar, A. R."

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Open Access
Apoptotic vascular smooth muscle cell depletion via BCL2 family of proteins in human ascending aortic aneurysm and dissection
(Blackwell Publishing Ltd, 2012) Durdu, S.; Deniz, G. C.; Balci, D.; Zaim, C.; Dogan, A.; Can, A.; Akcali, K. C.; Akar, A. R.
Aims: This study investigates the expression patterns of BCL2 (B-cell CLL/lymphoma2) family of proteins and the extent of vascular smooth muscle cell (VSMC) apoptosis in thoracic aortic aneurysms (TAA), type-A aortic dissections (TAD), and nondilated ascending aortic samples. Methods: Aortic wall specimens were obtained from patients undergoing surgical repair for TAA (n = 24), TAD (n = 20), and normal aortic tissues from organ donors (n = 6). The expression pattern of BCL2, BCL2L1 (BCL2-like1), BAK1 (BCL2-antagonist/killer1), and BAX (BCL2-associated X protein) proteins was investigated by immunohistochemistry. Furthermore, colocalization of alpha smooth muscle actin (ACTA2) and caspase3 (CASP3) in aortic VSMCs was analyzed by double-immunofluorescence staining. Onset of DNA fragmentation was measured by TUNEL assay. Results: Apoptotic index was significantly increased in both TAD group (31.3 ± 17.2, P < 0.001) and TAA group (21.1 ± 12.7, P = 0.001) relative to control aortas (2.0 ± 1.2). Anti-CASP3 and ACTA2 double-immunostaining confirmed apoptosis in VSMCs in TAA and TAD groups but not in controls. Proapoptotic BAX expression was significantly elevated in VSMCs of TAA patients, compared with that of controls (OR = 20; P = 0.02; 95% CI, 16-250). In contrast, antiapoptotic BCL2L1 expression was higher in controls compared with that of TAA group (OR = 11.2; P = 0.049; 95% CI, 1.0-123.9). Furthermore, BAX/BCL2 ratio was significantly increased in both TAA (1.2 ± 0.7, P < 0.001) and TAD (0.6 ± 0.4, P = 0.05) groups relative to controls (0.2 ± 0.1, P < 0.001). Conclusions: Apoptotic VSMC depletion in human TAA/TAD is associated with disturbance of the balance between proapoptotic and antiapoptotic members of the BCL2 family proteins, which may have a role in the pathogenesis of vascular remodelling in aortic disease. In light of the future studies, targeting apoptotic pathways in TAA and TAD pathogenesis may provide therapeutic benefits to patients by slowing down the progression and even possibly preventing the TAD. © 2012 Blackwell Publishing Ltd.
Open Access
A prescription fraud detection model
(Elsevier Ireland Ltd., 2012) Aral, K. D.; Güvenir H. A.; Sabuncuoğlu, T.; Akar, A. R.
Prescription fraud is a main problem that causes substantial monetary loss in health care systems. We aimed to develop a model for detecting cases of prescription fraud and test it on real world data from a large multi-center medical prescription database. Conventionally, prescription fraud detection is conducted on random samples by human experts. However, the samples might be misleading and manual detection is costly. We propose a novel distance based on data-mining approach for assessing the fraudulent risk of prescriptions regarding cross-features. Final tests have been conducted on adult cardiac surgery database. The results obtained from experiments reveal that the proposed model works considerably well with a true positive rate of 77.4% and a false positive rate of 6% for the fraudulent medical prescriptions. The proposed model has the potential advantages including on-line risk prediction for prescription fraud, off-line analysis of high-risk prescriptions by human experts, and self-learning ability by regular updates of the integrative data sets. We conclude that incorporating such a system in health authorities, social security agencies and insurance companies would improve efficiency of internal review to ensure compliance with the law, and radically decrease human-expert auditing costs. © 2011 Elsevier Ireland Ltd.
Open Access
Timing of induction of cardiomyocyte differentiation for in vitro cultured mesenchymal stem cells: a perspective for emergencies
(NRC Research Press, 2009) Tokçaer-Keskin, Zeynep; Akar, A. R.; Ayaloğlu-Bütün, Fatma; Terzioğlu-Kara, Ece; Durdu, S.; Özyurda, U.; Uğur, M.; Akçalı, Kamil C.
Mesenchymal stem cells (MSCs) have the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, myocytes, and cardiomyocytes. Several established methods are presently available for in vitro isolation of MSCs from bone marrow. However, the duration necessary to culture them can be a major handicap to cell-based therapies needed for such urgent cardiovascular conditions as acute myocardial infarction and acute hindlimb ischemia. The best timing of car- diomyocyte differentiation induction after MCS isolation and expansion is still an unresolved issue. Our goal was to investigate the possibility of obtaining functional cardiomyocytes from rat MSC within a shorter time period. We examined MSCs' colony-forming capacity, CD90 and CD34 immunoreactivity during the 14 days of culturing. Cardiomyocyte differentiation was induced by 5-azacytidine. Immunohistochemic staining, together with intracellular Ca2+ measurement experiments, revealed that MSCs do not differentiate into any specific cell lineage but show the characteristics of MSCs on both the 9th and 14th days of the culture. To check the potential for differentiation into cardiomyocytes, experiments with caffeine application and depolarization with KCl were performed. The cells possessed some of the specific biochemical features of contracting cells, with slightly higher capacities on the 14th day. Cells from 9th and 14th days of the culture that were treated with 5-azacytidine had a higher expression of cardiac-specific markers such as troponin I, α-sarcomeric actin, and MEF2D compared with the control groups. This study illustrates that it is possible to get functional cardiomyocytes from in vitro MSC culture in a shorter time period than previously achieved. This reduction in time may provide emergency cases with access to cell-based therapies that may have previously been unavailable.
Open Access
Validation of the EuroSCORE risk models in Turkish adult cardiac surgical population
(Oxford University Press, 2011) Akar, A. R.; Kurtcephe, M.; Sener, E.; Alhan, C.; Durdu, S.; Kunt, A. G.; Güvenir, H. A.
Objective: The aim of this study was to validate additive and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) models on Turkish adult cardiac surgical population. Methods: TurkoSCORE project involves a reliable web-based database to build up Turkish risk stratification models. Current patient population consisted of 9443 adult patients who underwent cardiac surgery between 2005 and 2010. However, the additive and logistic EuroSCORE models were applied to only 8018 patients whose EuroSCORE determinants were complete. Observed and predicted mortalities were compared for low-, medium-, and high-risk groups. Results: The mean patient age was 59.5 years (±12.1 years) at the time of surgery, and 28.6% were female. There were significant differences (all p< 0.001) in the prevalence of recent myocardial infarction (23.5% vs 9.7%), moderate left ventricular function (29.9% vs 25.6%), unstable angina (9.8% vs 8.0%), chronic pulmonary disease (13.4% vs 3.9%), active endocarditis (3.2% vs 1.1%), critical preoperative state (9.0% vs 4.1%), surgery on thoracic aorta (3.7% vs 2.4%), extracardiac arteriopathy (8.6% vs 11.3%), previous cardiac surgery (4.1% vs 7.3%), and other than isolated coronary artery bypass graft (CABG; 23.0% vs 36.4%) between Turkish and European cardiac surgical populations, respectively. For the entire cohort, actual hospital mortality was 1.96% (n = 157; 95% confidence interval (CI), 1.70-2.32). However, additive predicted mortality was 2.98% (p< 0.001 vs observed; 95%CI, 2.90-3.00), and logistic predicted mortality was 3.17% (p< 0.001 vs observed; 95%CI, 3.03-3.21). The predictive performance of EuroSCORE models for the entire cohort was fair with 0.757 (95%CI, 0.717-0.797) AUC value (area under the receiver operating characteristic, AUC) for additive EuroSCORE, and 0.760 (95%CI, 0.721-0.800) AUC value for logistic EuroSCORE. Observed hospital mortality for isolated CABG was 1.23% (n = 75; 95%CI, 0.95-1.51) while additive and logistic predicted mortalities were 2.87% (95%CI, 2.82-2.93) and 2.89% (95%CI, 2.80-2.98), respectively. AUC values for the isolated CABG subset were 0.768 (95%CI, 0.707-0.830) and 0.766 (95%CI, 0.705-0.828) for additive and logistic EuroSCORE models. Conclusion: The original EuroSCORE risk models overestimated mortality at all risk subgroups in Turkish population. Remodeling strategies for EuroSCORE or creation of a new model is warranted for future studies in Turkey. © 2011 European Association for Cardio-Thoracic Surgery.