Vitamin E supplementation and atherosclerosis : epidemiological studies in elderly and smokers

The antioxidant vitamin E may have beneficial effects on several indicators of human health. We studied the impact on atherosclerosis, immune response and total mortality in smokers and elderly people, who are at risk for increased oxidative stress. Vitamin E may exert its effect on atherosclerosis by protecting low density lipoprotein (LDL) against lipid peroxidation. Moreover, lipid peroxidation may also negatively influence the immune response. In addition to its antioxidant function, vitamin E may be beneficial through effects on cellular function, e.g., by preserving endothelium-dependent vaso-relaxation or decreasing cytokine production.Observational studies . In a cross-sectional study among 158 male lifelong smokers aged 50 to 75 years, adjusted vitamin E intake and plasma levels were not associated with intima media wall thickness (IMT) of the common carotid artery. IMT ,which is a marker for atherosclerosis, was measured non-invasively by using the B-mode ultrasound technique. In a prospective study among 638 independently living elderly aged 65 to 85, no significant association was observed between cholesterol adjusted serum levels of vitamin E and 7.2 years total mortality. (Hazard ratio for lowest tertile vs. highest of 1.11, 95% confidence interval 0.74 to 1.65).Intervention trials. In a randomized placebo-controlled double-blind trial among 218 lifelong male smokers, 400 IU (364 mg) vitamin E was administered daily for two years. A non significant (p=0.34) reduced progression of carotid IMT by 47% was observed compared to a significant spontaneous progression in the placebo group of 0.030 mm (p=0.006). Results were adjusted for initial IMT values and traditional CVD risk factors. Vitamin E significantly reduced the in vitro susceptibility of LDL to oxidation, which was not related to progression.In this trial results were stratified by genetic predisposition. Smokers lacking the detoxifying enzyme activity of glutathion S -transferase µ (genotype GSTM1- 0 ) were compared with those with the positive genotype (GSTM1- 1 ). In the GSTM1- 0 group vitamin E reduced the proportion of smokers with increased carotid IMT by 62% (p=0.06) for the left posterior and by 73% (p=0.01) for the left anterior wall. No effects were observed for the IMT at the right side.In a 3-month randomized double-blind placebo-controlled trial among 83 apparently healthy elderly, aged 67-87 years, 100 mg vitamin E supplementation significantly decreased the percentage of oxidized linoleic acid in LDL (10.4%) compared to the placebo group (4.6%). In this trial vitamin E supplementation did not affect the cellular and humoral immune response.In conclusion , no supportive evidence is provided that vitamin E supplementation has beneficial effects on atherosclerosis and immune response among smokers and elderly. The observations for GSTM1- 0 genotype needs further confirmation. The protective effect of vitamin E on LDL oxidation in vitro lacks validation in vivo. Research on biomarkers of lipid oxidation and arterial damage needs priority to more adequately assess the clinical relevance and optimal intake of vitamin E.</p

TripleSent: a triple store of events associated with their prototypical sentiment

The current generation of sentiment analysis systems is limited in their real-world applicability because they cannot detect utterances that implicitly carry positive or negative sentiment. We present early stage research ideas to address this inability with the development of a dynamic triple store of events associated with their prototypical sentiment

Interaction of prothrombin with factor Va-phospholipid complexes

The effects of factor Va and the phospholipid-binding fragment of factor Va [factor Va light chain (LC), Mr 80000] on the binding of prothrombin, factor X, and factor Xa to phospholipid vesicles are reported. Equilibrium binding experiments were performed that utilized large-volume vesicles, which can be removed from the bulk solution by centrifugation. Factor Va decreased the dissociation constant of the prothrombin-phospholipid complex 50-fold, from 2.0 X 10(-7) M to 4.0 X 10(-9) M. For the factor X-phospholipid complex the decrease was 60-fold (1.8 X 10(-7) M to 3.0 X 10(-9) M) and for factor Xa, 160-fold (1.6 X 10(-7) M to 1.0 X 10(-9) M). The ratios of moles of protein bound to moles of total added factor Va at saturation of phospholipid-bound factor Va indicate an 1:1 stoichiometric complex of either factor Xa, factor X, or prothrombin and phospholipid-bound factor Va. In the presence of factor Va LC, the dissociation constants of factor Xa- and prothrombin-phospholipid complexes were increased, while the maximal protein-binding capacities of the vesicles were not affected by factor Va LC. The data suggest a competitive interaction between factor Xa and factor Va LC binding as well as between prothrombin and factor Va LC binding at the phospholipid surface. From this, it is concluded that the phospholipid-binding fragment of factor Va alone does not serve as the binding site for interactions of factor Xa and prothrombin with factor Va

Tactility Trialing: Exploring Materials to Inform Tactile Experience Design

Although materials of tangible interaction designs largely determine their user experience, material choices are often steered by practical motives. This paper presents ‘tactility trialing’, an approach to explore tactile experiences of materials to inform the design of tangible artifacts. Through experience formulation, material selection, artifact creation and short user studies, designers and design-researchers are enabled to make informed decisions on the materials to be used in order to evoke the intended experience. The approach is illustrated through two case studies of student work. Tactility trialing helped them in getting acquainted with tactile material qualities in practice, and with the applicability of material characteristics such as resilience and hardness in design

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Medicolegal storm threatening maternal and child healthcare service

Interaction of bovine blood clotting factor Va and its subunits with phosolipid vesicles

Thrombin-activated factor Va and factor Va subunit binding to large-volume vesicles was investigated by a technique based on the separation by centrifugation of phospholipid-bound protein from the bulk solution. This technique allows the direct measurement of free-protein concentration. It is concluded that the phospholipid binding site on factor Va is located on a basic factor Va subunit with Mr 80 000 (factor Va-LC). The effects of phospholipid vesicle composition, calcium concentration, pH, and ionic strength on the equilibrium constants of factor Va- and factor Va-LC-phospholipid interaction were studied. Factor Va and factor Va-LC binding to phospholipid requires the presence of negatively charged phospholipids. It is further demonstrated that the following occur: (a) Calcium ions compete with factor Va and factor Va-LC for phospholipid-binding sites. (b) The dissociation constant of protein-phospholipid interaction increases with the ionic strength, whereas the maximum protein-binding capacity of the phospholipid vesicle was not affected by ionic strength. (c) The dissociation constant for factor Va-phospholipid interaction depends on pH when the vesicle consists of phosphatidic acid. It is concluded that factor Va-phospholipid interaction is primarily electrostatic in nature, where positively charged groups on the protein directly interact with the phosphate group of net negatively charged phospholipids. The results suggest that factor Va, like factor Xa and prothrombin, has the characteristics of an extrinsic membrane protein