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The purpose of this mini-review is to highlight the recent findings associating large artery stiffness with deleterious brain outcomes, with a specific focus on causative evidence obtained from animal models. We will also discuss the gaps in knowledge that remain in our understanding of how large artery stiffness affects brain function and disease outcomes.Heart failure (HF) post-myocardial infarction (MI) presents with increased vulnerability to monomorphic ventricular tachycardia (mmVT). To appropriately evaluate new therapies for infarct-mediated reentrant arrhythmia in the preclinical setting, chronologic characterization of the preclinical animal model pathophysiology is critical. This study aimed to evaluate the rigor and reproducibility of mmVT incidence in a rodent model of HF. We hypothesize a progressive increase in the incidence of mmVT as the duration of HF increases. Adult male Sprague-Dawley rats underwent permanent left coronary artery ligation or SHAM surgery and were maintained for either 6 or 10 wk. At end point, SHAM and HF rats underwent echocardiographic and invasive hemodynamic evaluation. Finally, rats underwent electrophysiologic (EP) assessment to assess susceptibility to mmVT and define ventricular effective refractory period (ERP). In 6-wk HF rats (n = 20), left ventricular (LV) ejection fraction (EF) decreased (P 0.05). Electrophysiology studies revealed an increase in incidence of mmVT between SHAM and 6-wk HF (P = 0.0016) and ERP prolongation (P = 0.0186). The incidence of mmVT and ventricular ERP did not differ between 6- and 10-wk HF (P = 1.0000), (P = 0.9831). Findings from this rodent model of HF suggest that once the ischemia-mediated infarct stabilizes, proarrhythmic deterioration ceases. Within the 6- and 10-wk period post-MI, no echocardiographic, invasive hemodynamic, or electrophysiologic changes were observed, suggesting stable HF. This is the necessary context for the evaluation of experimental therapies in rodent HF.NEW & NOTEWORTHY Rodent model of ischemic cardiomyopathy exhibits a plateau of inducible monomorphic ventricular tachycardia incidence between 6 and 10 wk postinfarction.Adequate adaptation of ventricular repolarization (VR) duration to changes in heart rate (HR) is important for cardiac electromechanical function and electrical stability. We studied the QT and QTpeak adaptation in response to abrupt start and stop of atrial and ventricular pacing on two occasions with an interval of at least 1 mo in 25 study subjects with permanent pacemakers. Frank vectorcardiography was used for data collection. Atrial or ventricular pacing was performed for 8 min aiming at a cycle length (CL) of 500 ms. MGCD0103 We measured the immediate response (IR), the time constant (τ) of the exponential phase, and T90 End, the time to reach 90% change of QT and QTpeak from baseline to steady state during and after pacing. During atrial pacing, the CL decreased on average 45% from mean (SD) 944 (120) to 518 (46) ms and QT decreased on average 18% from 388 (20) to 318 (17) ms. For QT, T90 End was 103 (24) s and 126 (15) s after start versus stop of atrial pacing; a difference of 24 (27) s (P = 0.006). The resping.In healthy and overweight/obese adults, interrupting prolonged sitting with activity bouts mitigates impairment in vascular function. However, it is unknown whether these benefits extend to those with type 2 diabetes (T2D), nor whether an optimal frequency of activity interruptions exist. We examined the acute effects on vascular function in T2D of interrupting prolonged sitting with simple resistance activities (SRA) at different frequencies. In a randomized crossover trial, 24 adults with T2D (35-70 yr) completed three 7-h conditions 1) uninterrupted sitting (SIT), 2) sitting with 3-min bouts of SRA every 30 min (SRA3), and 3) sitting with 6 min bouts of SRA every 60 min (SRA6). Femoral artery flow-mediated dilation (FMD), resting shear rate, blood flow, and endothelin-1 were measured at 0, 1, 3.5, 4.5, and 6.5-7 h. Mean femoral artery FMD over 7 h was significantly higher in SRA3 (4.1 ± 0.3%) compared with SIT (3.7 ± 0.3%, P = 0.04) but not in SRA6. Mean resting femoral shear rate over 7 h was increased siabetes.Hormonal contraceptives are one of the most widely used prescriptions for premenopausal women worldwide. Although the risk of venous and arterial cardiovascular events (e.g., deep vein thrombosis, arterial clotting) with hormonal contraceptives, specifically oral contraceptive pills, has been established, the literature on early risk indicators, such as peripheral vascular structure and function has yet to be consolidated. The purpose of this review is to summarize literature examining the impact of different hormonal contraceptives on vascular function and structure, including consideration of phasic differences within a contraceptive cycle, and to propose future directions for research. It is evident that hormonal contraceptive use appears to impact both macrovascular and microvascular endothelial function, with phasic differences in some contraceptive types dependent on progestin type, the ratio of ethinyl estradiol-to-progestin, and route of administration. However, hormonal contraceptives do not appear to impact smooth muscle function in the macrovasculature or microvasculature, arterial stiffness, or vascular structure. Underlying mechanisms for observed impacts and areas of future research are discussed. This review provides timely consolidation of research examining hormonal contraceptives and peripheral vascular function and structure and provides guidance on considerations for hormonal contraceptive use in study design.Although trehalose has recently gained interest because of its pharmaceutical potential, its clinical use is hampered due to its low bioavailability. Hence, hydrolysis-resistant trehalose analogues retaining biological activity could be of interest. In this study, 34 4- and 6-O-substituted trehalose derivatives were synthesised using an ether- or carbamate-type linkage. Their hydrolysis susceptibility and inhibitory properties were determined against two trehalases, i.e. porcine kidney and Mycobacterium smegmatis. With the exception of three weakly hydrolysable 6-O-alkyl derivatives, the compounds generally showed to be completely resistant. Moreover, a number of derivatives was shown to be an inhibitor of one or both of these trehalases. For the strongest inhibitors of porcine kidney trehalase IC50 values of around 10 mM could be determined, whereas several compounds displayed sub-mM IC50 against M. smegmatis trehalase. Dockings studies were performed to explain the observed influence of the substitution pattern on the inhibitory activity towards porcine kidney trehalase.
Website: https://www.selleckchem.com/products/MGCD0103(Mocetinostat).html
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