The role of oxysterols in vascular aging.

The ageing endothelium progressively loses its remarkable and crucial ability to maintain homeostasis of the vasculature, as it acquires a proinflammatory phenotype. Cellular and structural changes gradually accumulate in the blood vessels, and markedly in artery walls. Most changes in aged arteries are comparable to those occurring during the atherogenic process, the latter being more marked: pro‐oxidant and proinflammatory molecules, mainly deriving from or triggered by oxidized low density lipoproteins (oxLDLs), are undoubtedly a major driving force of this process. Oxysterols, quantitatively relevant components of oxLDLs, are likely candidate molecules in the pathogenesis of vascular ageing, because of their marked pro‐oxidant, proinflammatory and proapoptotic properties. An increasing bulk of experimental data point to the contribution of a variety of oxysterols of pathophysiological interest, also in the age‐related genesis of endothelium dysfunction, intimal thickening due to lipid accumulation, and smooth muscle cell migration and arterial stiffness due to increasing collagen deposition and calcification. This review provides an updated analysis of the molecular mechanisms whereby oxysterols accumulating in the wall of ageing blood vessels may ‘activate’ endothelial and monocytic cells, through expression of an inflammatory phenotype, and ‘convince’ smooth muscle cells to proliferate, migrate and, above all, to act as fibroblast‐like cells. [Image: see text

Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease

Alzheimer’s disease (AD), the most common neurodegenerative disorder associated with dementia, is typified by the pathological accumulation of amyloid β peptides and neurofibrillary tangles within the brain. Considerable evidence indicates that many events contribute to AD progression, including oxidative stress, inflammation, and altered cholesterol metabolism.The brain’s high lipid content makes it particularly vulnerable to oxidative species, with the consequent enhancement of lipid peroxidation and cholesterol oxidation, and the subsequent formation of end products, mainly 4-hydroxynonenal and oxysterols, respectively from the two processes. The chronic inflammatory events observed in the AD brain include activation of microglia and astrocytes, together with enhancement of inflammatory molecule and free radical release. Along with glial cells, neurons themselves have been found to contribute to neuroinflammation in the AD brain, by serving as sources of inflammatory mediators. Oxidative stress is intimately associated with neuroinflammation, and a vicious circle has been found to connect oxidative stress and inflammation in AD. Alongside oxidative stress and inflammation, altered cholesterol metabolism and hypercholesterolemia also significantly contribute to neuronal damage and to progression of AD. Increasing evidence is now consolidating the hypothesis that oxidized cholesterol is the driving force behind the development of AD, and that oxysterols are the link connecting the disease to altered cholesterol metabolism in the brain and hypercholesterolemia; this is because of the ability of oxysterols, unlike cholesterol, to cross the blood brain barrier. The key role of oxysterols in AD pathogenesis has been strongly supported by research pointing to their involvement in modulating neuroinflammation, Aβ accumulation, and cell death.This review highlights the key role played by cholesterol and oxysterols in the brain in AD pathogenesis

AD HOC SURVEYS: HOW TO MEASURE AND REPORT QUALITY METHODS

Surveys need a clear report on adopted quality methods to support surveillance, research and to implement evidence-based health policies. Aim of this report is to provide a simple and practical tool to those interested in survey, like HIS or HES , suggesting the different aspects of the quality to be controlled. These are crucial to generate useful and reliable results that can help the monitoring of health policy in Europe. Starting from the wide literature available in the field, the various quality dimensions that should be documented in a quality report and support the published results are briefly presented. In this paper, the six dimensions of the quality are analysed, as well as the different steps necessary to implement a survey, with particular attention to the quality and taking account of the remarkable expertise in the field. Before starting the survey, as known, the planning of specific steps is required. Moreover, to improve quality, training and testing of personnel involved in the different sets (organization, data collection, data processing, and statistical analysis) are fundamental. The methods used and the results obtained need to be published