Age-associated decline in cardiovascular function is believed to occur from the deleterious effects of reactive oxygen species (ROS). However, failure of recent clinical trials using antioxidants in patients with cardiovascular disease, and the recent findings showing paradoxical role for NADPH oxidase-derived ROS in endothelial function challenge this long-held notion against ROS. Here, we examine the effects of endothelium-specific conditional increase in ROS on coronary endothelial function. We have generated a novel binary (Tet-ON/OFF) conditional transgenic mouse (Tet-Nox2:VE-Cad-tTA) that induces endothelial cell (EC)-specific overexpression of Nox2/gp91 (NADPH oxidase) and 1.8±0.42-fold increase in EC-ROS upon tetracycline withdrawal (Tet-OFF). We examined ROS effects on EC signaling and function. First, we demonstrate that endothelium-dependent coronary vasodilation was significantly improved in Tet-OFF Nox2 compared to Tet-ON (control) littermates. Using EC isolated from mouse heart, we show that endogenous ROS increased eNOS activation and nitric oxide (NO) synthesis through activation of the survival kinase AMPK. Coronary vasodilation in Tet-OFF Nox2 animals was CaMKKβ-AMPK-dependent. Finally, we demonstrate that AMPK activation induced autophagy and thus, protected ECs from oxidant-induced cell death. Together, these findings suggest that increased ROS levels, often associated with cardiovascular conditions in advanced age, play a protective role in endothelial homeostasis by inducing AMPK-eNOS axis.

Aim: To compare the body composition of overweight children and adolescents by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) before and after physical activity program. Methods: One hundred and eleven patients with mean age (SD) of 12 (1.9) participated in the study. We assessed the weight, height, waist circumference (WC), and body composition by DXA and BIA. Patients underwent a program of diet and physical activity (1 h 30 min/day, 3 times a week for 3 months) and were evaluated before and after this period. Results: Mean initial zBMI were 2.3 (0.5) and waist SDS 5.9 (1.8). Significant differences were observed when we compared the measurements taken by DXA and BIA, respectively: total body fat percentage (40 and 31.5) and fat-free mass (43.1 and 50.6 kg). Regarding the trunk fat by DXA, there was a positive correlation with the WC/height ratio (r = 0.65; p < 0.01). After the intervention period, we observed a reduction in the zBMI, waist SDS, and total body fat and increase of fat-free mass by DXA. BIA only detected reduction in fat. Conclusion: BIA underestimates the percentage of fat and overestimates fat-free mass in relation to DXA. There is positive correlation between trunk fat and the ratio WC/height. In addition, DXA detected changes in body composition induced by a short period of physical training, unlike BIA. © 2014 S. Karger AG, Basel

Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes occurring mainly in the first 6 months of life. Approximately 30% of transient NDM (TNDM) cases will have an activating mutation in the K ATP channel genes ABCC8 and KCNJ11. The majority of the patients with KCNJ11 mutations who are receiving insulin treatment can be transferred to treatment with sulfonylurea (SU), with an improvement in metabolic control and quality of life. Intermittent continuous glucose monitoring (iCGM) is used to assess the current and retrospective interstitial glucose, providing information such as hypo/hyperglycemia tendency and time on target. This case report describes the use of iCGM in the transition from insulin treatment to glibenclamide in a patient with TNDM caused by a pathogenic variant of KCNJ11. This is the first report of a successful outpatient transition from insulin to glibenclamide, in a Brazilian child with TNDM using iCGM (FreeStyle Libre@). The remote monitoring and online management allowed the patient to safely stay at home during the transition from insulin to SU, especially important in the context of the COVID-19 pandemic. We conclude that iCGM is a helpful tool in cases of NDM and should be used to increase safety and speed up dose adjustments in outpatient transition from insulin to glibenclamide.