Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington's disease mice

Brain cholesterol biosynthesis and cholesterol levels are reduced in mouse models of Huntington's disease (HD), suggesting that locally synthesized, newly formed cholesterol is less available to neurons. This may be detrimental for neuronal function, especially given that locally synthesized cholesterol is implicated in synapse integrity and remodeling. Here, we used biodegradable and biocompatible polymeric nanoparticles (NPs) modified with glycopeptides (g7) and loaded with cholesterol (g7-NPs-Chol), which per se is not blood-brain barrier (BBB) permeable, to obtain high-rate cholesterol delivery into the brain after intraperitoneal injection in HD mice. We report that g7-NPs, in contrast to unmodified NPs, efficiently crossed the BBB and localized in glial and neuronal cells in different brain regions. We also found that repeated systemic delivery of g7-NPs-Chol rescued synaptic and cognitive dysfunction and partially improved global activity in HD mice. These results demonstrate that cholesterol supplementation to the HD brain reverses functional alterations associated with HD and highlight the potential of this new drug-administration route to the diseased brain

Prevalence of Rheumatic Heart Disease in North Madagascar: An echocardiographic screening in young and adult populations

BackgroundRheumatic Heart Disease (RHD) prevalence in Madagascar is poorly known. Echocardiographic screening detects a higher prevalence of RHD than clinical examination.AimsWe aimed to describe RHD prevalence in children and adults in North Madagascar using the most updated World Heart Federation (WHF) criteria for RHD echocardiographic diagnosis.Methods Children aged 5–19 years (Group One) and adults aged more than 20 years (Group Two) underwent a four-steps visit: clinical questionnaire, physical examination, laboratory test - oropharyngeal swab for Group One and Anti-streptolysin O (ASO) titre for Group Two - and echocardiogram using a portable machine..Results Among 859 people (522 in Group One, 337 in Group Two) RHD prevalence was 2.1 per cent. Group Two had a higher risk of having RHD than Group One (OR 4.39, CI 1.39–13.9, p=0.004), while clinical findings were more frequent in Group One (children had a higher risk of heart murmur (O.R. 3.85 C.I. 1.08–13.72; p=0.029)). RHD prevalence was 1.34 per cent in children. Those positive to oropharyngeal swab had a higher risk of RHD (OR 14.5, CI 3.04–69.44, p=0.0024); children with history of fever and sore-throat had a higher risk of positive oropharyngeal swab (OR 15.97, CI 3.14–81.19, p=0.002). RHD prevalence was 3.3 per cent in adults. None of those had history of fever and throat-pain, positive ASO titre and cardiac murmur simultaneously. ConclusionThis is the first study describing prevalence of RHD in Madagascar. Our results, although preliminary, are important to enhance prevention programs in this country

Rac1 pharmacological inhibition rescues human endothelial dysfunction

Background-Endothelial dysfunction contributes significantly to the development of vascular diseases. However, a therapy able to reduce this derangement still needs to be identified. We evaluated the effects of pharmacological inhibition of Rac1, a small GTPase protein promoting oxidative stress, in human endothelial dysfunction. Methods and Results-We performed vascular reactivity studies to test the effects of NSC23766, a Rac1 inhibitor, on endothelium-dependent vasorelaxation of saphenous vein segments collected from 85 subjects who had undergone surgery for venous insufficiency and from 11 patients who had undergone peripheral vascular surgery. The endothelium-dependent vasorelaxation of the varicose segments of saphenous veins collected from patients with venous insufficiency was markedly impaired and was also significantly lower than that observed in control nonvaricose vein tracts from the same veins. Rac1 activity, reactive oxygen species levels, and reduced nicotine adenine dinucleotide phosphate (NADPH) oxidase activity were significantly increased in varicose veins, and NSC23766 was able to significantly improve endothelium-dependent vasorelaxation of dysfunctional saphenous vein portions in a nitric oxide-dependent manner. These effects were paralleled by a significant reduction of NADPH oxidase activity and activation of endothelial nitric oxide synthase. Finally, we further corroborated this data by demonstrating that Rac1 inhibition significantly improves venous endothelial function and reduces NADPH oxidase activity in saphenous vein grafts harvested from patients with vascular diseases undergoing peripheral bypass surgery. Conclusions-Rac1 pharmacological inhibition rescues endothelial function and reduces oxidative stress in dysfunctional veins. Rac1 inhibition may represent a potential therapeutic intervention to reduce human endothelial dysfunction and subsequently vascular diseases in various clinical settings

The integrated Marine Hazard {webGIS} platform for management of open and coastal ocean in Sicily

This paper describes an integrated webGIS system dedicated to the central Mediterranean region surrounding Sicily, contributing to the Marine Hazard Project. The webGIS system aims at integrating information from in situ and remote sensing measurements made at the Observatories at Lampedusa and Capo Granitola, in Sicily, and from satellite products distributed by the Copernicus Marine Environment Monitoring Service. The background structure of the webGIS system, the contributing datasets, and an example case study are described in this wor

Physiologic Range of Myocardial Mechano-Energetic Efficiency among Healthy Subjects: Impact of Gender and Age

Myocardial mechano-energetic efficiency (MEE) is the capability of the left ventricle (LV) to convert the chemical energy obtained from the cardiac oxidative metabolism into mechanical work. The aim of present study was to establish normal non-invasive MEE and MEEi reference values