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Öğe DRUG RESISTANCE RESTRICTS THE EFFICACY OF SHORT TERM LOW DOSE MITOMYCIN-C TREATMENT IN UMUC-3 BLADDER CANCER CELLS(Iniestares, S.A., 2018) Gul, Murat; Goktas, Serdar; Kars, Meltem Demirel; Kaynar, MehmetOBJECTIVE: Mitomycin-c (MMC) is the most used intravesical adjuvant agent in non-muscle invasive bladder cancer to prevent recurrence. However, a consensus on about appropriate dosage and treatment schedule of MMC is lacking. We, therefore, aimed to evaluate the most appropriate MMC dosage using an in vitro model of high-grade human bladder cancer. METHODS: UMUC-3 cells, a model for high-grade bladder cancer, were exposed to MMC in different time courses to assess its toxicological effects. XTT cell proliferation kit was used to evaluate the effect of MMC on the proliferation of UMUC-3 cell line. Gene expression analysis for the MDR1, BCL2 and ANXA5 genes was performed by Real-time PCR and flow cytometry analysis were conducted to evaluate the cell death mechanism and acquired resistance after MMC exposure. An ANXA5 kit was used to detect apoptotic cells, and 7-AAD was used to detect necrotic cells. RESULTS: Cell proliferation was prevented to a large extent (IC50, 0.175-0.081 mg/mL) and cytotoxic effects were observed after 5 mu g/mL and 10 mu g/mL MMC administrations for 1 and 2-h, after the 4th and 2nd dose cycles, respectively. Moreover, cell death was observed at 5 mu g/mL and 10 mu/mL MMC applications for 1-h and 2-h by the sixth and second week, respectively. Flow cytometry exhibits increased subpopulation of drug-extruding UMUC-3 cells after a single dose of MMC for 1-h. MMC did not increase the number of apoptotic or necrotic cells; yet, MDR1 (multiple drug resistance) and ANXA5 (apoptotic) expression levels were increased and BCL2 (anti-apoptotic) expression was decreased. Limitations: In-vitro nature of the study and working with only one cell culture are inherit limitations of this project. CONCLUSION: A single dose of MMC administration for 1 or 2-h results in drug-resistance. If maintenance treatment is administered for one hour, it should be continued throughout a 6-week period.Öğe Dynamic changes in aortic stiffness after substantial weight loss by laparoscopic sleeve gastrectomy in patients with obesity: a 1-year follow-up study(Sage Publications Ltd, 2021) Gul, Murat; Inci, Sinan; Aktas, Halil; Yildirim, Oguz; Alsancak, Yakup; Ozkan, NamikArterial stiffness has been identified as a powerful and independent risk factor for cardiovascular disease. Obesity is associated with an increased risk of aortic stiffness (AS) and adverse cardiovascular events. Herein, we aimed to evaluate the effects of weight loss after laparoscopic sleeve gastrectomy (LSG) on AS in individuals with morbid obesity by using the transthoracic echocardiography (TTE). A total of 53 patients with obesity (17 males, 36 females) who underwent LSG and did not have any known heart disease were included in the study. The AS parameters were measured with TTE. The demographic and echocardiographic data of the patients were studied before, at 1 month and 12 months after surgery. The mean age of the study group was 34.41 +/- 11.62, 68% of whom were female. There were no significant differences in terms of the standard echocardiography and Doppler measurements as compared with preoperative values (all p>0.05). When the elastic parameters of the aorta were compared, no significant differences were detected regarding aortic strain (%) ((16.28 +/- 4.11) vs (16.68 +/- 4.56), p=(0.998)), distensibility (cm(2)/dyn) ((6.74 +/- 1.78) vs (7.03 +/- 2.31), p=(0.997)) and Aortic Stiffness Index values ((10.73 +/- 3.84) vs (10.63 +/- 3.34), p=0.998) between baseline and first month after surgery. In the 12-month follow-up, it was determined that the aortic strain ((16.28 +/- 4.11) vs (22.74 +/- 5.79), p <= 0.001) and distensibility ((6.74 +/- 1.78) vs (10.34 +/- 3.059), p<0.001)) values increased at significant levels. Weight loss by LSG improves arterial stiffness parameters in patients with obesity over a 1-year follow-up.Öğe Favorable electrocardiographic changes after substantial weight loss in patients with morbid obesity Results of a prospective study(Urban & Vogel, 2021) Gul, Murat; Inci, Sinan; Ozkan, Namik; Alsancak, YakupBackground Obese patients have an increased risk of arrhythmias and sudden death, even in the absence of structural heart disease and cardiac dysfunction. This study aimed to determine whether weight loss by bariatric surgery has an effect on arrhythmia-related electrocardiographic (ECG) variables in morbidly obese patients. Methods In this prospective study, the data of 48 patients were analyzed. All ECG variables that have the potential to predict ventricular arrhythmia were evaluated before surgery, and were compared with the 1-month and 6-month follow-up results. Results The mean body mass index was 45.74 +/- 5.60 kg/m(2) before surgery. There was a statistically significant decline in body mass index in the first and sixth month after surgery (39.26 +/- 5.00 kg/m(2) and 31.71 +/- 4.49 kg/m(2), respectively; p < 0.001). Furthermore, notable reduction was found in terms of heart rate measurements-QTc-d, JTc, JTc-d, Tp-e, TP-e/QT, TP-e/QTc-in the first month and sixth month compared with baseline (p < 0.001 for all comparisons). Several ECG variables, such as heart rate (r = 0.369, p = 0.001), QTc-d (r = 0.449, p = 0.001), JTc-d (r = 0.324, p = 0.002), Tp-e (r = 0.592, p = 0.001), Tp-e/QTc (r = 0.543, p = 0.001), Tp-e/JTc (r = 0.515, p = 0.001), exhibited a positive and significant correlation with weigh loss. Moreover, a negative and weakly significant correlation was found between the index of cardiac electrophysiological balance (r = -0.239, p = 0.004) and body mass index. Conclusion Substantial weight loss following laparoscopic sleeve gastrectomy in obese patients is accompanied by a significant improvement in ventricular repolarization. Therefore, this effect may lead to a decrease in the incidence of lethal ventricular arrhythmia and sudden cardiac death.Öğe A Google Trends Analysis: Change in internet searches related to cardiovascular disease during COVID-19 outbreak(Czech Soc Cardiology & Czech Soc Cardiovascular Surgery, 2020) Alsancak, Yakup; Gul, MuratAim: A rapidly grown up information about coronavirus (COVID-19) has been regularly broadcast on internet websites or social media. We investigated the Google research trends in searches regarding cardiovascular system diseases or symptoms such as chest pain, hypertension, hyperlipidemia, heart attack during the COVID-19 pandemic in two countries, Turkey and Italy, which are most affected by this disease. Methods: The Google Trends (TM) (GT (TM)) was used to retrieve data on Internet user search activities and patterns of Google search queries. We searched most known keywords related to cardiovascular disease and symptoms such as chest pain, heart attack, heart diseases, hypertension, high cholesterol in GTTM between January 1, 2020 and May 5, 2020 in Turkish and Italian. Results: Search interest about coronavirus in Turkey and Italy appeared to have an increasing pattern and it has gradually tended to fall after a short time. Searching trends were higher both of countries about chest pain, hypertension, ACE inhibitor and death between January and May 2020. Searching rates about heart attack was not different for all year, but a significant decrease was remarkable for cholesterol. It was also revealed that as the duration of the pandemic increases in both countries, these research rates decrease. Conclusion: Internet could be used to determine behaviours of people for searching cardiovascular disease and their symptoms during the outbreak. These data illustrate that internet users in both countries conducted an intense research on cardiac symptoms or diseases during the COVID-19 pandemic.Öğe Hidden danger of COVID-19 outbreak: evaluation of subclinical myocardial dysfunction in patients with mild symptoms(Springer, 2021) Gul, Murat; Inci, Sinan; Aktas, Halil; Yildirim, Oguz; Alsancak, YakupThe COVID-19 infection, which is caused by the novel coronavirus SARS-CoV-2, has rapidly emerged as a global public health issue. Cardiac complications secondary to this infection are common and associated with mortality. This study aimed to evaluate whether subclinical myocardial dysfunction exists in non-hospitalized mildly symptomatic COVID-19 patients using left ventricular global longitudinal strain (LVGLS). In this cross-sectional, single-center study, data were collected from non-hospitalized mildly symptomatic COVID-19 patients between January 01 and February 01, 2021. Fifty (26 male, 24 female) COVID-19 patients and 50 age- and sex-matched healthy volunteers were included in the study. Apical four-, three-, and two-chamber images were analyzed longitudinally by conventional methods and speckle tracking echocardiography (STE) for left ventricle functions. The mean age of the COVID-19 patients was 39.5 +/- 8.96, and 52% of them were male. The most prevalent presenting symptoms were fever [in 34 (68%)], asthenia [in 30 (60%)], loss of appetite [in 21 (42%)], myalgia [in 20 (40%)], and cough [in 13 (26%)]. Plasma levels of C-reactive protein (CRP) were significantly higher in the COVID-19 patients than in the controls (10.84 +/- 12.44 vs. 4.50 +/- 2.81, p < 0.001). There was no significant difference between the groups in terms of standard echocardiography and Doppler parameters (p > 0.05). Left ventricular longitudinal strain and strain velocity parameters were significantly decreased in COVID-19 patients compared to healthy individuals. LV-GLS values (- 21.72 +/- 3.85% vs. - 23.11 +/- 4.16%; p = 0.003) were significantly lower in COVID-19 patients compared with the healthy controls. Mildly symptomatic COVID-19 patients also have subclinical myocardial dysfunction similar to hospitalized patients. STE has the potential for detecting subclinical LV systolic dysfunction, and can provide useful information regarding cardiac status in mildly symptomatic COVID-19 population.Öğe Short- and mid-term effects of sleeve gastrectomy on Left Ventricular Functions with Two-Dimensional Speckle Tracking Echocardiography in obese patients(Wiley, 2019) Inci, Sinan; Gul, Murat; Alsancak, Yakup; Ozkan, NamikAim This study aimed to investigate left ventricular functions of obese patients with no known heart disease who underwent laparoscopic sleeve gastrectomy by speckle tracking echocardiography in their early and medium-term postoperative follow-up. Patients and Method Thirty-seven obese patients (10 M, 27 F) without coronary artery disease or heart failure who had undergone LSG were included in the study. Apical four-, three-, and two-chamber images were analyzed longitudinally by conventional methods and speckle tracking echocardiography (STE) for left ventricle functions preoperatively, at the postoperative Month 1 and at the postoperative Month 6 (QLAB 6.0), using current software. Results No difference was found between standard echocardiography and Doppler parameters in terms of the 1-month versus 6-month follow-up values compared to baseline. Left ventricular STE longitudinal measurements demonstrated significantly higher longitudinal strain and strain velocity parameters in the follow-up values at Month 6 compared to the values at Month 1 and at baseline. Global longitudinal strain (GLS) was -17.48 +/- 1.09% in 6-month follow-up, -16.16 +/- 1.26% in 1-month follow-up, and -16.06 +/- 1.25% at baseline (P < .001). A significant correlation was found between delta GLS, which represents patients' GLS change in 6 months, and delta weight, which represents patients' body weight change in 6 months. Conclusion Obese patients who had undergone LSG were observed to have improved left ventricular function in the mid-term.
