Aceite de oliva y la hemostasia

Olive oil is a key component of the traditional Mediterranean diet; a diet that may explain the low rate of cardiovascular disease (CVD) in Southern European. (Extra virgin) Olive oil is a good source of monounsaturated fatty acids (MUFA) and phenolic compounds, both of which have been investigated for their effects on plasma lipids and lipoproteins, measures of oxidation and factors related to thrombosis. This issue aims to summarise the current understanding of the effects of such dietary components on the haemostatic system and subsequent risk of CVD. To date, evidence suggests that diets rich in MUFA and thus in olive oil attenuate the thrombotic response via a reduction in platelet aggregation and in postprandial FVII levels. Thrombosis is a key event in causing heart attacks and strokes, which if modulated by diet could pose a cost-effective way of reducing CVD incidence in populations that adhere to MUFA/olive oil-rich diets long-term.El aceite de oliva es un componente esencial de la dieta Mediterránea que puede explicar el bajo índice de enfermedad cardiovascular (CVD) en los países del sur de Europa. El aceite de oliva (extra virgen) es una fuente de ácidos grasos monoinsaturados (MUFA) y de compuestos fenólicos, de gran interés por sus efectos, entre otros, sobre las lipoproteínas y los lípidos plasmáticos, su capacidad antioxidante y su papel en la expresión de factores relacionados con la trombosis. En este capítulo se presenta un resumen del conocimiento actual sobre la influencia derivada del consumo de aceite de oliva (extra virgen) en el sistema hemostático y el riesgo de CVD. Por ahora se sabe que dietas ricas en MUFA (aceite de oliva) pueden atenuar la respuesta trombótica mediante la reducción de la agregación plaquetaria y de las concentraciones postprandiales del factor VII de coagulación (FVII). La trombosis es un evento relevante en los ataques al corazón y el ictus, de manera que su modulación con la dieta puede constituir una forma rentable para la disminución de la incidencia de CVD en poblaciones que consumen dietas enriquecidas en MUFA/aceite de oliva durante largo tiempo

Homogeneous nucleation of a non-critical phase near a continuous phase transition

Homogeneous nucleation of a new phase near a second, continuous, transition, is considered. The continuous transition is in the metastable region associated with the first-order phase transition, one of whose coexisting phases is nucleating. Mean-field calculations show that as the continuous transition is approached, the size of the nucleus varies as the response function of the order parameter of the continuous transition. This response function diverges at the continuous transition, as does the temperature derivative of the free energy barrier to nucleation. This rapid drop of the barrier as the continuous transition is approached means that the continuous transition acts to reduce the barrier to nucleation at the first-order transition. This may be useful in the crystallisation of globular proteins.Comment: 6 pages, 1 figur

Functional polymorphism in ABCA1 influences age of symptom onset in coronary artery disease patients

ATP-binding-cassette-transporter-A1 (ABCA1) plays a pivotal role in intracellular cholesterol removal, exerting a protective effect against atherosclerosis. ABCA1 gene severe mutations underlie Tangier disease, a rare Mendelian disorder that can lead to premature coronary artery disease (CAD), with age of CAD onset being two decades earlier in mutant homozygotes and one decade earlier in heterozygotes than in mutation non-carriers. It is unknown whether common polymorphisms in ABCA1 could influence age of symptom onset of CAD in the general population. We examined common promoter and non-synonymous coding polymorphisms in relation to age of symptom onset in a group of CAD patients (n = 1164), and also carried out in vitro assays to test effects of the promoter variations on ABCA1 promoter transcriptional activity and effects of the coding variations on ABCA1 function in mediating cellular cholesterol efflux. Age of symptom onset was found to be associated with the promoter − 407G > C polymorphism, being 2.82 years higher in C allele homozygotes than in G allele homozygotes and intermediate in heterozygotes (61.54, 59.79 and 58.72 years, respectively; P = 0.002). In agreement, patients carrying ABCA1 haplotypes containing the −407C allele had higher age of symptom onset. Patients of the G/G or G/C genotype of the −407G > C polymorphism had significant coronary artery stenosis (>75%) at a younger age than those of the C/C genotype (P = 0.003). Reporter gene assays showed that ABCA1 haplotypes bearing the −407C allele had higher promoter activity than haplotypes with the −407G allele. Functional analyses of the coding polymorphisms showed an effect of the V825I substitution on ABCA1 function, with the 825I variant having higher activity in mediating cholesterol efflux than the wild-type (825V). A trend towards higher symptom onset age in 825I allele carriers was observed. The data indicate an influence of common ABCA1 functional polymorphisms on age of symptom onset in CAD patient

Novel indole-thiazolidinone conjugates: Design, synthesis and whole-cell phenotypic evaluation as a novel class of antimicrobial agents

In connection with our research program on the development of novel anti-tubercular candidates, herein we report the design and synthesis of two different sets of indole-thiazolidinone conjugates (8a,b; 11a-d) and (14a-k; 15a-h). The target compounds were evaluated for their in vitro antibacterial and antifungal activities against selected human pathogens viz. Staphylococcus aureus (Gram positiveve), Pseudomonas aeruginosa, Escherichia coli (Gram negative), Mycobacterium tuberculosis (Acid-fast bacteria), Aspergillus fumigates and Candida albicans (fungi). Moreover, eukaryotic cell-toxicity was tested via an integrated ex vivo drug screening model in order to evaluate the selective therapeutic index (SI) towards antimicrobial activity when microbes are growing inside primary immune cells. Also, the cytotoxicity towards a panel of cancer cell lines and human lung fibroblast normal cell line, WI-38 cells, was explored to assure their safety. Compound 15b emerged as a hit in this study with potent broad spectrum antibacterial (MIC: 0.39-0.98 µg/ml) and antifungal (MIC: 0.49-0.98 µg/ml) activities, in addition to its ability to kill mycobacteria M. aurum inside an infected macrophage model with good therapeutic window. Moreover, compound 15b displayed promising activity towards resistant bacteria strains MRSA and VRE with MIC values equal 3.90 and 7.81 µg/mL, respectively. These results suggest compound 15b as a new therapeutic lead with good selectivity for further optimization and development

Arrangement of Type IV Collagen and Laminin on Substrates with Controlled Density of ¿OH Groups

This is a copy of an article published in the Diabetes Technology and Therapeutics © 2011 [copyright Mary Ann Liebert, Inc.]; Diabetes Technology and Therapeutics is available online at: http://online.liebertpub.com.Collagen IV (Col IV) and laminin (Lam) are the main structural components of the basement membrane where they form two overlapping polymeric networks. We studied the adsorption pattern of these proteins on five model surfaces with tailored density of-OH groups obtained by copolymerization of different ratios ethyl acrylate (EA) and hydroxyl EA (HEA): X OH=0, X OH=0.3, X OH=0.5, X OH=0.7, and X OH=1 (where X refers the ratio of HEA). Atomic force microscopy revealed substratum-specific adsorption patterns of Col IV and Lam, ranging from single molecules deposition on more hydrophilic substrata to the formation of complex networks on hydrophobic ones. Human umbilical endothelial cells were used to study the biological performance of adsorbed proteins, following the overall cell morphology, the quantities for cell adhesion and spreading, and the development of focal adhesion complexes and actin cytoskeleton. Surprisingly, two optima in the cellular interaction were observed-one on the most hydrophilic X OH=1 and other on the relatively hydrophobic X OH=0.3 substrate-valid for both Col IV and Lam. When the proteins were adsorbed consecutively, a hydrophobic shift to X OH=0 substratum was obtained. Collectively, these data suggest that varying with the density of-OH groups one can tailor the conformation and the functional activity of adsorbed basement membrane proteins. © 2011, Mary Ann Liebert, Inc.AFM was performed under the technical guidance of the Microscopy Service at the Universidad Politecnica de Valencia, whose advice is greatly appreciated. The work was supported by the Spanish Ministry of Science and Innovation through project nos. MAT2009-14440-C02-0 and MAT2009-14440-C02-02.Coelho, NM.; González García, C.; Salmerón Sánchez, M.; Altankov, G. (2011). Arrangement of Type IV Collagen and Laminin on Substrates with Controlled Density of ¿OH Groups. Tissue Engineering Part A. 17:2245-2257. doi:10.1089/ten.tea.2010.0713S224522571

Genome-wide association study identifies nine novel loci for 2D:4D finger ratio, a putative retrospective biomarker of testosterone exposure in utero

The ratio of the length of the index finger to that of the ring finger (2D:4D) is sexually dimorphic and is commonly used as a non-invasive biomarker of prenatal androgen exposure. Most association studies of 2D:4D ratio with a diverse range of sexspecific traits have typically involved small sample sizes and have been difficult to replicate, raising questions around the utility and precise meaning of the measure. In the largest genome-wide association meta-analysis of 2D:4D ratio to date (N=15 661, with replication N=75 821), we identified 11 loci (9 novel) explaining 3.8% of the variance in mean 2D:4D ratio. We also found weak evidence for association (b=0.06; P=0.02) between 2D:4D ratio and sensitivity to testosterone [length of the CAG microsatellite repeat in the androgen receptor (AR) gene] in females only. Furthermore, genetic variants associated with (adult) testosterone levels and/or sex hormone-binding globulin were not associated with 2D:4D ratio in our sample. Although we were unable to find strong evidence from our genetic study to support the hypothesis that 2D:4D ratio is a direct biomarker of prenatal exposure to androgens in healthy individuals, our findings do not explicitly exclude this possibility, and pathways involving testosterone may become apparent as the size of the discovery sample increases further. Our findings provide new insight into the underlying biology shaping 2D:4D variation in the general population

Antidepressant and skeletal muscle relaxant effects of the aqueous extract of the Prosopis cineraria

The aqueous leaves extract of Prosopis cineraria (AEPC) is used traditionally for the treatment of various CNS disorder. The purpose of this study was to evaluate the extract for antidepressant and skeletal muscle relaxant activity. The antidepressant effect of the extract was evaluated using Forced swim test (FST). The immobility periods of control and treated mice were recorded. The antidepressant-like effect of tested compound was compared to that of imipramine (15 mg/kg. p.o). Muscle relaxant property was studied using rotarod apparatus and total fall off time for standard and control group was recorded. Phytochemical screening revealed the presence of saponins, flavonoids, alkaloids, glycosides, tannins and phenolic compounds. The leaf extract at doses of 200 mg/kg significantly decreased the duration of immobility time in FST. The efficacy of tested extract was found to be comparable to that of imipramine. Our results suggested that the aqueous extract of Prosopis cineraria leaves exerts antidepressant-like effect.O extrato aquoso de folhas de Prosopis cineraria (AEPC) é utilizado, tradicionalmente, para o tratamento de várias disfunções do SNC. O propósito desse estudo foi avaliar o extrato quanto às atividades antidepressiva e relaxante muscular esquelética. O efeito antidepressivo do extrato foi avaliado usando o teste do nado forçado (FST). Registraram-se os períodos de imobilidade dos camundongos controle e dos tratados. O efeito antidepressivo do composto testado foi comparado com a imipramina ((15 mg/kg. p.o). A propriedade relaxante muscular foi estudada usando o cilindro giratório e o tempo total de queda para os grupos padrão e controle foram registrados. A triagem fitoquímica revelou a presença de saponinas, flavonoides, alcaloides, glicosídeos, taninos e compostos fenólicos. O extrato da folha em doses de 200 mg/kg diminui significativamente a duração do tempo de imobilidade no FST. A eficácia do extrato testado foi comparável àquela da imipramina. Nossos resultados sugeriram que o extrato aquoso das folhas da Prosopis cineraria exerce efeito semelhante ao antidepressivo

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Phenotypic Dissection of Bone Mineral Density Reveals Skeletal Site Specificity and Facilitates the Identification of Novel Loci in the Genetic Regulation of Bone Mass Attainment

Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ~4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (re = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (re = 0.20-0.24). To explore the basis fo