Vitamin C inhibits platelet expression of CD40 ligand

Upon stimulation with agonists, platelets express CD40 ligand (CD40L), a transmembrane protein implicated in the initiation and progression of atherosclerotic disease. We have recently discovered that oxidative stress plays a major role in platelet CD40L expression. In this study, we sought to determine whether vitamin C, a known antioxidant, is able to influence platelet CD40L expression. In vitro experiments were done by stimulating platelets with collagen in the presence or absence of vitamin C (50-100 mu M) or vehicle as control. An in vivo study was done in 10 healthy subjects who were randomized to intravenous infusion of placebo or 1 g vitamin C for 45 min in a crossover design. At the end of infusion platelet CD40L and O2- were measured. The in vitro study demonstrated that vitamin C dose dependently inhibited platelet CD40L expression without affecting agonist-induced platelet aggregation. In subjects treated with placebo no changes of platelet CD40L and O2- were observed; conversely, vitamin C infusion caused a significant and parallel decrease of platelet O2- (-70%, P < 0.001) and CD40L (-68%, P < 0.001). Platelet aggregation was not modified by either treatment. This study suggests that water-soluble antioxidants, which scavenge superoxide radicals, may reduce platelet CD40L expression. (c) 2005 Elsevier Inc. All rights reserved

gp91phox-dependent expression of platelet CD40 ligand

Background-CD40 ligand (CD40L) expression on platelets is mediated by agonists, but the underlying mechanism is still unclear. Methods and Results-CD40L expression was measured in platelets from healthy subjects both with and without the addition of antioxidants or a phospholipase A2 (PLA2) inhibitor and in platelets from 2 patients with an inherited deficiency of gp91phox. Immunoprecipitation analysis was also performed to determine whether normal platelets showed gp91phox expression. Unlike catalase and mannitol, superoxide dismutase inhibited agonist-induced platelet CD40L expression in healthy subjects. Immunoprecipitation analysis also showed that platelets from healthy subjects expressed gp91phox. In 2 male patients with inherited gp91phox deficiency, collagen-, thrombin-, and arachidonic acid-stimulated platelets showed an almost complete absence of superoxide anion (O2-) and CD40L expression. Incubation of platelets from healthy subjects with a PLA2 inhibitor almost completely prevented agonist-induced O2- and CD40L expression. Conclusions-These data provide the first evidence that platelet CD40L expression occurs via arachidonic acid-mediated gp91phox activation

Effet de la pression interstitielle sur la réponse sismique des sols : modélisation numérique 1D-3 Composantes

International audienceDuring strong quakes, the propagation of seismic waves in soil layers involves nonlinearities changing with the excitation level. A nonlinear hysteretic law is necessary to describe the variations of the stiffness and the energy dissipation during the seismic shaking. Furthermore, the influence of the pore pressure (cyclic mobility and liquefaction) cannot be neglected for saturated soils under strong quakes. Starting from a FEM formulation describing 1D propagation and three-dimensional loading ("1D-3 components approach"), the influence of the water is accounted for through a relation between the pore pressure and the work of the shear stress initially proposed by Iai. This model describes the variations of the pore pressure from the three-dimensional stress state of the soil. It has been validated through comparisons to laboratory tests (cyclic triaxial tests on saturated sands) and an analysis under three-dimensional excitations (seismic loading polarized along the 3 directions of space). The results involving 3 simultaneous excitation components and a single component in 3 separated analyses show the influence of the loading path on the seismic response and the pore pressure build-up

Oxidative stress-mediated platelet CD40 ligand upregulation in patients with hypercholesterolemia: effect of atorvastatin

Objectives: We speculated that in patients with hypercholesterolemia CD40L overexpression could depend on low-density lipoprotein (LDL)-induced enhanced intraplatelet formation of O-2(.-) and statin could reduce platelet CD40L via interference with platelet O-2(.-) production. Background: CD40L is a protein with inflammatory and thrombotic properties. CD40L is upregulated in platelets from hypercholesterolemic (HC) patients but the underlying mechanism is unclear. Methods: Collagen-induced platelet CD40L and platelet O-2(.-) expression were investigated in 40 HC patients and 40 healthy subjects. HC patients were then randomized to either a diet (n = 20) (group A) or atorvastatin 10 mg day (n = 20) (group B); the above variables were measured at baseline and after 3 and 30 days of treatment. O-2(.-) and CD40L were also measured in vitro in LDL-treated platelets with or without nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor or atorvastatin added. Results: Compared with controls, HC patients showed higher values of platelet CD40L (P < 0.001) and O-2(.-) (P < 0.001). Platelet CD40L was significantly correlated with O-2(.-) (P < 0.001). The interventional trial showed no changes in group A and a significant and parallel decrease in platelet CD40L (P < 0.001) and O-2(.-) (P < 0.001) in group B. In vitro studies demonstrated that LDL-induced platelet CD40L and GP IIb/IIIa (PAC1 binding) activation via the NADPH oxidase pathway. CD40L upregulation was counteracted by atorvastatin in a dose-dependent fashion. Conclusions: This study suggests that in patients with hypercholesterolemia platelet CD40L is upregulated via NADPH oxidase-dependent O-2(.-) generation. Atorvastatin downregulated CD40L with an oxidative stress-mediated mechanism likely involving platelet NADPH oxidase, an effect that seemed to be independent of its cholesterol-lowering action

Study of a New Trigger on Multiplicity and Primary Interaction Vertex using the ALICE Silicon Pixel Detector

New trigger inputs for the ALICE Central Trigger Processor (CTP) are proposed. They are based on the use of Fast Multiplicity (FM) output signals generated by the ALICE Silicon Pixel Detector (SPD). These can be used for a multiplicity based centrality trigger and for a fast on-line computation of the primary vertex. A simple algorithm for primary vertex location at the trigger level is proposed. The precision that can be achieved with this method on centrality selection and primary vertex location, is discussed for interactions with different pseudo-rapidity density level. The feasibility of background rejection is also considered

Fast front-end L0 trigger electronics for ALICE FMD-MCP tests and performance

We present design details and new measurements of the performance of fast electronics for the Forward Multiplicity Detector for ALICE. These detectors based on sector type Microchannel Plates (MCP) forming several disks gave the very first trigger decision in the experiment (L0). Fast passive summators integrated with the detectors are used for linear summation of up to eight isochronous signal channels from MCP pads belonging to one sector. Two types of microelectronics design thin film summators were produced. We present test results for these summators, working in the frequency range up to 1 Ghz. New low noise preamplifiers have been built to work with these summators. The new design shows a good performance with the usable frequency range extended up to 1 Ghz. An upgrade of the functional scheme for the L0 ALICE pre-trigger design is also presented.Abstract:List of figures Figure 1: ALICE L0 Trigger Front-End Electronics Functional Scheme. Figure 2: UHF design for a fast passive summator based on directional couplers. Figure 3: Photo of an industrially produced passive summator based on circular bridges. Figure 4: Oscillogram of the fast 4 signals separated by different delays shown at the fast output of the passive summator. Figure 5: The same as in Figure 4, but with the delays removed. Figure 6: Fast preamplifier layout. Figure 7: Gain versus Frequency Response for fast preamplifier. Figure 8: Transition response of the preamplifier for a 100 psec rise time step function. Figure 9: The shape of the MCP signal measured after the summator and fast preamplifier. </A

Fast Pre-Trigger Electronics of T0/Centrality MCP-Based Start Detector for ALICE

This work describes an alternative to the current ALICE baseline solution for a TO detector, still under development. The proposed system consists of two MCP-based T0/Centrality Start Detectors (backward-forward isochronous disks) equipped with programmable, TTC synchronized front-end electronic cards (FEECs) which would be positioned along the LHC colliding beam line on both sides of the ALICE interaction region. The purpose of this arrangement, providing both precise timing and fast multiplicity selection, is to give a pre-trigger signal at the earliest possible time after a central event. This pre-trigger can be produced within 25 ns. It can be delivered within 100 ns directly to the Transition Radiation Detector and would be the earliest L0 input coming to the ALICE Central Trigger Processor. A noise-free passive multichannel summator of 2ns signals is used to provide a determination of the collision time with a potential accuracy better than 10 ps in the case of Pb-Pb collisions, the limit coming from the electronics. Results from in-beam tests confirm the functionality of the main elements. Further development plans are presented

Performance of ALICE pixel prototypes in high energy beams

The two innermost layers of the ALICE inner tracking system are instrumented with silicon pixel detectors. Single chip assembly prototypes of the ALICE pixels have been tested in high energy particle beams at the CERN SPS. Detection efficiency and spatial precision have been studied as a function of the threshold and the track incidence angle. The experimental method, data analysis and main results are presented.Comment: 10 pages, 9 figures, contribution to PIX2005 Workshop, Bonn (Germany), 5-8 September 200

Inherited human gp91phox deficiency is associated with impaired isoprostane formation and platelet dysfunction

Platelet isoprostane 8-ISO-prostaglandin F2α (8-iso-PGF2α), a proaggregating molecule, is believed to derive from nonenzymatic oxidation of arachidonic acid. We hypothesized that NADPH is implicated in isoprostane formation and platelet activation

Beam Test Performance and Simulation of Prototypes for the ALICE Silicon Pixel Detector

The silicon pixel detector (SPD) of the ALICE experiment in preparation at the Large Hadron Collider (LHC) at CERN is designed to provide the precise vertex reconstruction needed for measuring heavy flavor production in heavy ion collisions at very high energies and high multiplicity. The SPD forms the innermost part of the Inner Tracking System (ITS) which also includes silicon drift and silicon strip detectors. Single assembly prototypes of the ALICE SPD have been tested at the CERN SPS using high energy proton/pion beams in 2002 and 2003. We report on the experimental determination of the spatial precision. We also report on the first combined beam test with prototypes of the other ITS silicon detector technologies at the CERN SPS in November 2004. The issue of SPD simulation is briefly discussed.Comment: 4 pages, 5 figures, prepared for proceedings of 7th International Position Sensitive Detectors Conference, Liverpool, Sept. 200