The role of metformin response in lipid metabolism in patients with recent-onset type 2 diabetes: HbA1c level as a criterion for designating patients as responders or nonresponders to metformin

Background: In this study, we investigated whether response to metformin, the most frequently drug for diabetes treatment, influences the therapeutic effects of antilipidemic medication in newly diagnosed patients with type 2 diabetes mellitus (T2DM). Methods: A total of 150 patients with T2DM were classified into two groups following 3 months of metformin therapy (1000mg twice daily): responders (patients showing >1% reduction in HbA1c from baseline) and nonresponders (patients showing <1% reduction in HbA1c from baseline). The patients received atorvastatin 20 mg, gemfibrozil 300 mg, or atorvastatin 20 mg and gemfibrozil 300 mg daily. Principal Findings: HbA1c and fasting glucose levels were significantly different between baseline and 3 months among responders receiving atorvastatin; however, these differences were not statistically significant in nonresponders. Atherogenic ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C; p = 0.002), total cholesterol to HDL-C (TC/HDL-C; p<0.001) and AIP (the atherogenic index of plasma; p = 0.004) decreased significantly in responders receiving atorvastatin than in nonresponders. Moreover, responders receiving atorvastatin showed a significant increase in HDL-C levels but nonresponders receiving atorvastatin did not (p = 0.007). The multivariate model identified a significant association between metformin response (as the independent variable) and TG, TC, HDL-C and LDL-C (dependent variables; Wilk's λ = 0.927, p = 0.036). Conclusions: Metformin response affects therapeutic outcomes of atorvastatin on atherogenic lipid markers in patients newly diagnosed with T2DM. Metformin has a greater impact on BMI in responders of metformin compared to nonresponders. Adoption of better therapeutic strategies for reducing atherogenic lipid markers may be necessary for metformin nonresponders. © 2016 Kashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Semi-quantitative analysis of endometrial receptivity marker mRNA expression in the mid-secretory endometrium of patients with uterine fibromas

In fertile women, expression of molecular marker of endometrial receptivity, HOXA11, leukemia inhibitory factor (LIF) and basic transcriptional element binding protein 1 (BTEB1), rises during the luteal phase with the peak occurring during the implantation window. We evaluated the transcript levels of HOXA-11, LIF and BTEB1 in the mid-secretory endometrium of infertile patients with uterine fibroid infertility (n = 8) and from normal fertile women (n = 8). Expression levels of HOXA11, LIF and BTEB1 mRNA were measured in endometrium during the mid-secretory phase using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Endometrial HOXA11, LIF and BTEB1 mRNA expression levels (normalized to ß-actin expression) were significantly decreased in endometrium of infertile patients with uterine fibroid as compared with healthy fertile controls at the time of implantation (P&lt;0.05). The results suggest that the alteration in expression pattern of some genes could account for some aspects of infertility in patients with uterine fibroma.Key words: Myoma, fibromas, implantation, HOXA11, leukemia inhibitory factor, basic transcriptional element binding protein 1

Role of circ-FOXO3 and miR-23a in radiosensitivity of breast cancer

Identifying the radiosensitivity of cells before radiotherapy (RT) in breast cancer (BC) patients allows appropriate switching between routinely used treatment regimens and reduces adverse side effects in exposed patients. In this study, blood was collected from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC and 20 healthy women. To predict cellular radiosensitivity, a standard G2-chromosomal assay was performed. From these 60 samples, 20 BC patients were found to be radiosensitive based on the G2 assay. Therefore, molecular studies were finally performed on two equal groups (20 samples each) of patients with and without cellular radiosensitivity. QPCR was performed to examine the expression levels of circ-FOXO3 and miR-23a in peripheral blood mononuclear cells (PBMCs) and RNA sensitivity and specificity were determined by plotting Receiver Operating Characteristic (ROC) curves. Binary logistic regression was performed to identify RNA involvement in BC and cellular radiosensitivity (CR) in BC patients. Meanwhile, qPCR was used to compare differential RNA expression in the radiosensitive MCF-7 and radioresistant MDA-MB-231 cell lines. An annexin -V FITC/PI binding assay was used to measure cell apoptosis 24 and 48 h after 2 Gy, 4 Gy, and 8 Gy gamma-irradiation. Results indicated that circ-FOXO3 was downregulated and miR-23a was upregulated in BC patients. RNA expression levels were directly associated with CR. Cell line results showed that circ-FOXO3 overexpression induced apoptosis in the MCF-7 cell line and miR-23a overexpression inhibited apoptosis in the MDA-MB-231 cell line. Evaluation of the ROC curves revealed that both RNAs had acceptable specificity and sensitivity in predicting CR in BC patients. Binary logistic regression showed that both RNAs were also successful in predicting breast cancer. Although only circ-FOXO3 has been shown to predict CR in BC patients, circ-FOXO3 may function as a tumor suppressor and miR-23a may function as oncomiR in BC. Circ-FOXO3 and miR-23a may be promising potential biomarkers for BC prediction. Furthermore, Circ-FOXO3 could be a potential biomarker for predicting CR in BC patients.</p

Predicting the outcome in patients with unexplained syncope and suspected cardiac cause: Role of electrophysiologic studies Kalp nedenli oldu�undan ��phe edilen ve a�ıklanamayan senkoplu bir hastada sonucun kestirilmesi

Objective: Unexplained syncope is a challenge facing electrophysiologists. The prognosis varies widely depending on underlying causes, specially, cardiac ones. We sought to determine the abnormal electrophysiolgic (EP) study results as predictors of prognosis in syncope patients with suspected cardiac cause and risk factors associated with mortality. Methods: A total of 227 consecutive patients with unexplained syncope were prospectively enrolled in this study. EP study was performed in 177 patients in base of inclusion criteria. These patients, in whom a cardiac cause of syncope was suspected, underwent EP study and if negative, head-up tilts test (HUTT). Complete follow-up was obtained for 132 patients for 20.0�10.8 months. Results: A cardiac cause of syncope was established in 35, a neurally mediated syncope in 35.6, and in the rest 29.4 the cause of syncope remained unexplained despite a throughout neurologic and cardiologic evaluation. Logistic analysis revealed that the significant predictors of a cardiac cause of syncope were the absence of prodromal symptoms, left bundle branch block (LBBB), sever left ventricle (LV) dysfunction and male gender. At logistic analysis, the presence of LBBB (OR=6.63; 95 CI: 1.09-40) was significantly associated with outcome of death. Conclusion: The present study provides evidence that presence of LBBB, abnormal EP study result and structural heart disease (SHD) have prognostic value in patients with suspected cardiac cause of syncope. The patients with SHD and unexplained syncope who had a negative EP study have a good long-term prognosis even in the presence of LV dysfunction. � 2015 by Turkish Society of Cardiology

Predicting the outcome in patients with unexplained syncope and suspected cardiac cause: Role of electrophysiologic studies

Objective: Unexplained syncope is a challenge facing electrophysiologists. The prognosis varies widely depending on underlying causes, specially, cardiac ones. We sought to determine the abnormal electrophysiolgic (EP) study results as predictors of prognosis in syncope patients with suspected cardiac cause and risk factors associated with mortality. Methods: A total of 227 consecutive patients with unexplained syncope were prospectively enrolled in this study. EP study was performed in 177 patients in base of inclusion criteria. These patients, in whom a cardiac cause of syncope was suspected, underwent EP study and if negative, head-up tilts test (HUTT). Complete follow-up was obtained for 132 patients for 20.0±10.8 months. Results: A cardiac cause of syncope was established in 35, a neurally mediated syncope in 35.6, and in the rest 29.4 the cause of syncope remained unexplained despite a throughout neurologic and cardiologic evaluation. Logistic analysis revealed that the significant predictors of a cardiac cause of syncope were the absence of prodromal symptoms, left bundle branch block (LBBB), sever left ventricle (LV) dysfunction and male gender. At logistic analysis, the presence of LBBB (OR=6.63; 95 CI: 1.09-40) was significantly associated with outcome of death. Conclusion: The present study provides evidence that presence of LBBB, abnormal EP study result and structural heart disease (SHD) have prognostic value in patients with suspected cardiac cause of syncope. The patients with SHD and unexplained syncope who had a negative EP study have a good long-term prognosis even in the presence of LV dysfunction. © 2015 by Turkish Society of Cardiology