Anthocyanin-rich extract decreases indices of lipid peroxidation and DNA damage in vitamin E-depleted rats

Anthocyanins are secondary plant metabolites responsible for the blue, purple, and red color of many plant tissues. The phenolic structure of anthocyanins conveys marked antioxidant activity in model systems via donation of electrons or hydrogen atoms from hydroxyl moieties to free radicals. Dietary intakes of anthocyanins may exceed 200 mg/day, however, little is known about their antioxidant potency in vivo. Consequently, the aim of this study was to establish whether anthocyanins could act as putative antioxidant micronutrients. Rats were maintained on vitamin E-deficient diets for 12 weeks in order to enhance susceptibility to oxidative damage and then repleted with rations containing a highly purified anthocyanin-rich extract at a concentration of 1 g/kg diet. The extract consisted of the 3-glucopyranoside forms of delphinidin, cyanidin, petunidin, peonidin, and malvidin. Consumption of the anthocyanin repleted diet significantly improved (p < 0.01) plasma antioxidant capacity and decreased (p < 0.001) the vitamin E deficiency-enhanced hydroperoxides and 8-Oxo-deoxyguanosine concentrations in liver. These compounds are indices of lipid peroxidation and DNA damage, respectively. Dietary consumption of anthocyanin-rich foods may contribute to overall antioxidant status, particularly in areas of habitually low vitamin E intake.Fundação para Ciência e Tecnologi

Linear Response, Validity of Semi-Classical Gravity, and the Stability of Flat Space

A quantitative test for the validity of the semi-classical approximation in gravity is given. The criterion proposed is that solutions to the semi-classical Einstein equations should be stable to linearized perturbations, in the sense that no gauge invariant perturbation should become unbounded in time. A self-consistent linear response analysis of these perturbations, based upon an invariant effective action principle, necessarily involves metric fluctuations about the mean semi-classical geometry, and brings in the two-point correlation function of the quantum energy-momentum tensor in a natural way. This linear response equation contains no state dependent divergences and requires no new renormalization counterterms beyond those required in the leading order semi-classical approximation. The general linear response criterion is applied to the specific example of a scalar field with arbitrary mass and curvature coupling in the vacuum state of Minkowski spacetime. The spectral representation of the vacuum polarization function is computed in n dimensional Minkowski spacetime, and used to show that the flat space solution to the semi-classical Einstein equations for n=4 is stable to all perturbations on distance scales much larger than the Planck length.Comment: 22 pages: This is a significantly expanded version of gr-qc/0204083, with two additional sections and two new appendices giving a complete, explicit example of the semi-classical stability criterion proposed in the previous pape

A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis

A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility

We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10−40, OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1∗04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10−43) and HLA-DQα1 47 (p = 4.02 × 10−46), 56, and 76 (both p = 1.84 × 10−45) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10−6, OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10−6, OR = 1.20), and REL (rs115674477, p = 1.10 × 10−5, OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Analytical methods for quantification of modified fatty acids and sterols formed as a result of processing

International audienceFats and oils are often submitted to technological treatments before being consumed. Some treatments like refining, hydrogenation, and frying often lead to the formation of modified fatty acids such as cyclic fatty acid monomers (CFAM), geometrical fatty acid isomers, and/or oxidized fatty acids and sterols (cholesterol and phytosterols). Both cholesterol oxidation products (COP) and phytosterol oxidation products (POP), may be present in foods. As some of the newly formed components may present some adverse effects upon consumption, methods have been developed to analyze these compounds in food products and biological samples. Gas liquid chromatography (GC) on long polar columns (100m) is a good choice to quantify trans mono- and poly-unsaturated fatty acids. In some cases a pre-fractionation step using silver nitrate thin layer chromatography (AgNO3-TLC) may be necessary to avoid GC overlapping of cis and trans isomers. Analysis of CFAM usually involves transformation of the sample in fatty acid methyl esters (FAME) which after addition of an internal standard (IS) are further hydrogenated. An enrichment step using reverse phase high performance liquid chromatography (RP-HPLC) permits to obtain a fraction which consists of a mixture of CFAM and the IS. This fraction is further analyzed by GC on a polar column. The analysis of oxidized triacylglycerol monomers (oxTG) as a group was feasible by a combination of adsorption and size-exclusion chromatography. Quantification in used frying fats and oils around the limit of rejection for human consumption (25% polar compounds) has shown that the amount of oxTG range 5.9–9.4% expressed on fat or oil weight. In foods and biological tissues, the level of oxidized sterols (SOP) is often a very small fraction of their unoxidized forms. Analysis of SOP involved extraction of lipids, saponification or transesterification, enrichment, and subsequent qualitative and quantitative determination by GC and GC-MS, or HPLC and HPLC-MS. In addition, enrichment of SOP requires complete separation from the unoxidized sterols in order to separate these compounds even by high resolution GC capillary columns