Endothelial nitric oxide pathways in the pathophysiology of dengue: a prospective observational study.

Background: Dengue can cause increased vascular permeability that may lead to hypovolemic shock. Endothelial dysfunction may underlie this; however the association of endothelial nitric oxide pathways with disease severity is unknown. Methods: We performed a prospective observational study in two Vietnamese hospitals, assessing patients presenting early (<72 hours fever) and patients hospitalized with warning signs or severe dengue. The reactive hyperaemic index (RHI), which measures endothelium-dependent vasodilation and is a surrogate marker of endothelial function and NO bioavailability was evaluated using peripheral artery tonometry (EndoPAT) and plasma levels of L-arginine, Arginase-1 and ADMA were measured at serial time-points. The main outcome of interest was plasma leakage severity. Results: 314 patients were enrolled, median age of the participants was 21 (IQR 13-30) years. No difference was found in the endothelial parameters between dengue and other febrile illness (OFI). Considering dengue patients, the RHI was significantly lower for patients with severe plasma leakage compared to those with no leakage (1.46 vs. 2.00, P<0.001), over acute time-points, apparent already in the early febrile phase (1.29 vs. 1.75, P=0.012). RHI correlated negatively with arginase-1, and positively with L-arginine (P=0.001). Endothelial dysfunction/NO bioavailability is associated with worse plasma leakage, occurs early in dengue illness and correlates with hypoargininaemia and high arginase-1 levels

Butyrate Transcriptionally Enhances Peptide Transporter PepT1 Expression and Activity

Background: PepT1, an intestinal epithelial apical di/tripeptide transporter, is normally expressed in the small intestine and induced in colon during chronic inflammation. This study aimed at investigating PepT1 regulation by butyrate, a short-chain fatty acid produced by commensal bacteria and accumulated inside inflamed colonocyte. Results: We found that butyrate treatment of human intestinal epithelial Caco2-BBE cells increased human PepT1 (hPepT1) promoter activity in a dose- and time-dependent manner, with maximal activity observed in cells treated with 5 mM butyrate for 24 h. Under this condition, hPepT1 promoter activity, mRNA and protein expression levels were increased as assessed by luciferase assay, real-time RT-PCR and Western blot, respectively. hPepT1 transport activity was accordingly increased by,2.5-fold. Butyrate did not alter hPepT1 mRNA half-life indicating that butyrate acts at the transcriptional level. Molecular analyses revealed that Cdx2 is the most important transcription factor for butyrate-induced increase of hPepT1 expression and activity in Caco2-BBE cells. Butyrate-activated Cdx2 binding to hPepT1 promoter was confirmed by gel shift and chromatin immunoprecipitation. Moreover, Caco2-BBE cells overexpressing Cdx2 exhibited greater hPepT1 expression level than wild-type cells. Finally, treatment of mice with 5 mM butyrate added to drinking water for 24 h increased colonic PepT1 mRNA and protein expression levels, as well as enhanced PepT1 transport activity in colonic apical membranes vesicles

Carvedilol improves glucose tolerance and insulin sensitivity in treatment of adrenergic overdrive in high fat diet-induced obesity in mice.

Catecholamine excess reflecting an adrenergic overdrive of the sympathetic nervous system (SNS) has been proposed to link to hyperleptinemia in obesity and may contribute to the development of metabolic disorders. However, relationship between the catecholamine level and plasma leptin in obesity has not yet been investigated. Moreover, whether pharmacological blockade of the adrenergic overdrive in obesity by the third-generation beta-blocker agents such as carvedilol could help to prevent metabolic disorders is controversial and remains to be determined. Using the high fat diet (HFD)-induced obese mouse model, we found that basal plasma norepinephrine, the principal catecholamine as an index of SNS activity, was persistently elevated and highly correlated with plasma leptin concentration during obesity development. Targeting the adrenergic overdrive from this chronic norepinephrine excess in HFD-induced obesity with carvedilol, a third-generation beta-blocker with vasodilating action, blunted the HFD-induced hepatic glucose over-production by suppressing the induction of gluconeogenic enzymes, and enhanced the muscular insulin signaling pathway. Furthermore, carvedilol treatment in HFD-induced obese mice decreased the enlargement of white adipose tissue and improved the glucose tolerance and insulin sensitivity without affecting body weight and blood glucose levels. Our results suggested that catecholamine excess in obesity might directly link to the hyperleptinemic condition and the therapeutic targeting of chronic adrenergic overdrive in obesity with carvedilol might be helpful to attenuate obesity-related metabolic disorders

Expert voices and equal partnerships: Establishing Controlled Human Infection Models (CHIMs) in Vietnam

The number of controlled human infection models (CHIMs) conducted worldwide has increased considerably in recent years, although few have been conducted in low and middle-income countries (LMICs), where infectious diseases have the greatest burden. Recently Oxford University Clinical Research Unit (OUCRU) in Ho Chi Minh City (HCMC) started developing CHIM research proposals motivated by the need to develop a clearer and more grounded understanding of the issues surrounding the conduct of CHIMs in LMICs. To explore initial perceptions and barriers to conducting CHIMs in Vietnam, OUCRU researchers conducted a set of key stakeholder interviews early in 2018 and held a CHIM workshop in HCMC in March 2018. This paper summarizes the discussions from the workshop and outlines a way forward for conducting CHIMs in Vietnam

Effect of carbonaceous support between graphite oxide and reduced graphene oxide with anchored Co3O4 microspheres as electrode-active materials in a solid-state electrochemical capacitor

Hydrothermally synthesized CoO microspheres were anchored to graphite oxide (GO) and thermally reduced graphene oxide (rGO) composites at different cobalt weight percentages (1, 10, and 100 wt%). The composite materials served as the active materials in bulk electrodes for two-electrode cell electrochemical capacitors (ECCs). GO/CoO–1 exhibited a high energy density of 35 W kg with a specific capacitance (C) of 196 F g at a maximum charge density of 1 A g. rGO/CoO-100 presented high specific power output values of up to 23.41 kW h kg with linear energy density behavior for the charge densities applied between 0.03 and 1 A g. The composite materials showed Coulombic efficiencies of 96 and 93 % for GO/CoO–1 and rGO/CoO–100 respectively. The enhancement of capacitive performance is attributed to the oxygenated groups in the GO ECC and the specific area in the rGO ECC. These results offer an interesting insight into the type of carbonaceous support used for graphene derivative electrode materials in ECCs together with CoO loading to improve capacitance performance in terms of specific energy density and specific power. [Figure not available: see fulltext.]This work was supported by the Consejo Nacional de Ciencia y Tecnología (Mexico) CB 2011-166356 project fund. The authors would like to thank PRODEP for the support provided throughout the UQROO/DGIP/003/16 project; Consejo Nacional de Ciencia y Tecnología student grant (362308), and the CICY student exchange program. V.P., also acknowledges the technical support for characterization from M. Bass- López (CICY), I. Muñoz, J. Gómez, P. González, and E. Benito (ICTP).Peer Reviewe