Glucagon-like peptide-1 enhances cardiac L-type Ca2+ currents via activation of the cAMP-dependent protein kinase A pathway

<p>Abstract</p> <p>Background</p> <p>Glucagon-like peptide-1 (GLP-1) is a hormone predominately synthesized and secreted by intestinal L-cells. GLP-1 modulates multiple cellular functions and its receptor agonists are now used clinically for diabetic treatment. Interestingly, preclinical and clinical evidence suggests that GLP-1 agonists produce beneficial effects on dysfunctional hearts via acting on myocardial GLP-1 receptors. As the effects of GLP-1 on myocyte electrophysiology are largely unknown, this study was to assess if GLP-1 could affect the cardiac voltage-gated L-type Ca²⁺current (I_Ca).</p> <p>Methods</p> <p>The whole-cell patch clamp method was used to record I_Caand action potentials in enzymatically isolated cardiomyocytes from adult canine left ventricles.</p> <p>Results</p> <p>Extracellular perfusion of GLP-1 (7-36 amide) at 5 nM increased I_Caby 23 ± 8% (<it>p </it>< 0.05, n = 7). Simultaneous bath perfusion of 5 nM GLP-1 plus 100 nM Exendin (9-39), a GLP-1 receptor antagonist, was unable to block the GLP-1-induced increase in I_Ca; however, the increase in I_Cawas abolished if Exendin (9-39) was pre-applied 5 min prior to GLP-1 administration. Intracellular dialysis with a protein kinase A inhibitor also blocked the GLP-1-enhanced I_Ca. In addition, GLP-1 at 5 nM prolonged the durations of the action potentials by 128 ± 36 ms (<it>p </it>< 0.01) and 199 ± 76 ms (<it>p </it>< 0.05) at 50% and 90% repolarization (n = 6), respectively.</p> <p>Conclusions</p> <p>Our data demonstrate that GLP-1 enhances I_Cain canine cardiomyocytes. The enhancement of I_Cais likely via the cAMP-dependent protein kinase A mechanism and may contribute, at least partially, to the prolongation of the action potential duration.</p

Experimental Investigation of the Nature of the Knee in the Primary Cosmic Ray Energy Spectrum with the GAMMA experiment

We present preliminary results obtained by a novel difference method for the study of the nature of the knee in the energy spectrum of the primary cosmic radiation. We have applied this method to data from the GAMMA experiment in Armenia. The analysis provides evidence for the possible existence of a nearby source of primary cosmic rays in the Southern hemisphere.Comment: 17 pages, 5 figure

FEATURES OF THE PLACEMENT OF DUMPS DURING THE DEVELOPMENT OF UPLAND DEPOSITS: QUALITY MANAGEMENT IN INDUSTRIAL AND MANUFACTURING ENGINEERING

The purpose of this paper was to determine the specifics of the placement of dumps during the development of upland deposits and to develop recommendations to improve quality management in industrial and manufacturing engineering during the development of mineral resource deposits. As a result of the performed research, it was proved that the placement of dumps during the development of upland deposits requires more calculations for planning and ensuring stability than for dumps located on a horizontal surface. Assessment of the stability of dumps on the slope is a key component of ensuring the safety of dumps. One of the main factors affecting the stability of dumps on an inclined base is the bearing capacity of the base. When planning the area for the dump, the bearing capacity and strength of the base rocks are calculated. The article describes a method for determining the loading of the dump depending on the bearing capacity of the base of the dump of overburden rocks. The features of the placement of overburden dumps during the development of upland deposits are revealed, taking into account the planning of the base for the dump, depending on the strength characteristics of the base and the slope angle. The theoretical significance of the results obtained is due to their rethinking of the essence of the development of mineral resource deposits from the position of quality management in industrial and manufacturing engineering. The practical significance of the authors’ developments is that the authors’ methodology of determining the load of the dump depending on the carrying capacity of the base dump of overburden rocks will allow improving quality management in industrial and manufacturing engineering of the development of mineral resource deposits

Indexed left atrial volume, C-reactive protein and erythrocyte sedimentation rate as predictors of recurrence of non-valvular atrial fibrillation after successful cardioversion

Indexed left atrial volume, C-reactive protein and erythrocyte sedimentation rate as predictors of recurrence of non-valvular atrial fibrillation after successful cardioversio

Indexed left atrial volume is superior to left atrial diameter in predicting nonvalvular atrial fibrillation recurrence after successful cardioversion: a prospective study.

BACKGROUND: Although indexed left atrial volume (iLAV) is the most accurate measure of left atrial size, it has not been evaluated prospectively as predictor of recurrence of atrial fibrillation (AFib) after successful cardioversion (CV). METHODS: We prospectively selected 76 patients (mean age 66.1 ± 13.6 years, 65.8% men) with AFib who underwent successful CV. Baseline clinical and echocardiographic characteristics were obtained before CV. LAV was measured using Simpson's method and indexed to body surface area. All patients were scheduled for follow-up visit at 1, 6, 12 months, and then annually. A 24-hour Holter ECG was performed within 6 months and each time the patients reported symptoms suggestive of arrhythmia. RESULTS: The 52 patients (68.4%) with AFib recurrence had larger iLAV (35.5 ± 8.9 mL/m(2) vs 27.0 ± 6.7 mL/m(2) , P < 0.001). Anteroposterior LA diameter was not associated with AFib relapse (OR 1.08, 95% CI: 0.96-1.21, P = 0.09). Each unit increase in iLAV was associated with a 1.15-fold increased risk of recurrence (OR 1.15, 95% CI: 1.06-1.25, P < 0.001). In a multivariable model, iLAV remained the only independent predictor of relapse (adjusted OR 1.14, 95% CI: 1.02-1.28, P = 0.02). The area under ROC curves, generated to compare LA diameter, and iLAV as predictors of AFib recurrence were 0.56 (SE 0.07) versus 0.78 (SE 0.05), respectively (P = 0.003). CONCLUSION: This is the first prospective study to show that larger iLAV, as a more accurate measure of LA remodeling than anteroposterior diameter, is strongly and independently associated with a higher risk of AFib recurrence after CV

Innovative quality improvements in hotel services

The paper is devoted to the development of approaches for the improvement of quality of hotel services on innovative basis. It has been established that in the market of hotel services, innovations are being introduced successfully for the purpose of attracting as many customers as possible. All this ensures development of new technologies of constructing hotels, appearance of new market segments satisfying a diverse demand of visitors. It has been proved that to improve the quality of hotel services, it is necessary to develop a strategy and tactics of development of hotel business on innovative basis. It has been determined that introduction of innovations must be realised both at the level of the state and at the level of separate hotels. Further innovative growth will allow improving the quality of hotel services in the world market of hotel real estate. However, this is possible in case of normalization of the economic and political situation in the country and creation of conditions for investment attractiveness in hotel business.peer-reviewe