Procalcitonin and C-reactive protein in pericardial fluid for postmortem diagnosis of sepsis.

The aim of this study was to investigate the presence and concentrations of procalcitonin and C-reactive protein in pericardial fluid and compare these levels to those found in the postmortem serum obtained from the femoral blood. Two groups were formed, a sepsis-related fatalities group and a control group. Postmortem native CT scans, autopsies, histology, neuropathology and toxicology as well as other postmortem biochemistry investigations were performed in all cases. Pericardial fluid procalcitonin levels were significantly different between the cases of sepsis-related fatalities and those of the control group. Postmortem serum procalcitonin levels below the detection limit were also reflected in undetectable pericardial fluid levels. Similarly, a large increase in postmortem serum procalcitonin levels was reflected in a large increase of procalcitonin pericardial fluid levels. Based on these findings, pericardial fluid could be an alternative to postmortem serum for the determination of procalcitonin levels in cases where postmortem serum is not available and measurements of procalcitonin are required to circumstantiate the pathogenesis of death.

Reactive electrophile species activate defense gene expression in Arabidopsis.

Compounds containing alpha,beta-unsaturated carbonyl groups are increasingly implicated as potent regulators of gene expression; some are powerful cytotoxins known to accumulate at the site of lesion formation in host-pathogen interactions. We used a robust measurement of photosynthetic efficiency to quantify the toxicity of a variety of lipid derivatives in Arabidopsis leaves. Small alpha,beta-unsaturated carbonyl compounds (e.g. acrolein and methyl vinyl ketone) were highly active and proved to be potent stimulators of expression of the pathogenesis-related gene HEL (PR4). These small volatile electrophiles were far more active than larger alkenal homologs like 2(E)-hexenal, and activated HEL expression in a manner independent of salicylate, ethylene, and jasmonate production/perception. Electrophile treatment massively increased the levels of unesterified cyclopentenone jasmonates, which themselves are electrophiles. Patterns of gene expression in response to electrophile treatment and in response to avirulent bacteria were compared, which revealed strikingly similar transcript profiles. The results broaden the range of known biologic effects of reactive electrophile species to include the activation of a pathogenesis-related gene (HEL) and genes involved in metabolism. Electrophiles can act as mediators of both genetic and biochemical effects on core defense signal transduction.

Inertial effects on reactive particles advected by turbulence

We study the problem of the advection of passive particles with inertia in a two-dimensional, synthetic, and stationary turbulent flow. The asymptotic analytical result and numerical simulations show the importance of inertial bias in collecting the particles preferentially in certain regions of the flow, depending on their density relative to that of the flow. We also study how these aggregates are affected when a simple chemical reaction mechanism is introduced through a Eulerian scheme. We find that inertia can be responsible for maintaining a stationary concentration pattern even under nonfavorable reactive conditions or destroying it under favorable ones.

Nonequilibrium patterns and shape fluctuations in reactive membranes

A simple kinetic model of a two-component deformable and reactive bilayer is presented. The two differently shaped components are interconverted by a nonequilibrium reaction, and a phenomenological coupling between local composition and curvature is proposed. When the two components are not miscible, linear stability analysis predicts, and numerical simulations show, the formation of stationary nonequilibrium composition/curvature patterns whose typical size is determined by the reactive process. For miscible components, a linearization of the dynamic equations is performed in order to evaluate the correlation function for shape fluctuations from which the behavior of these systems in micropipet aspiration experiments can be predicted.

Generation of dynamic structures in nonequilibrium reactive membranes

We present a nonequlibrium approach for the study of a flexible bilayer whose two components induce distinct curvatures. In turn, the two components are interconverted by an externally promoted reaction. Phase separation of the two species in the surface results in the growth of domains characterized by different local composition and curvature modulations. This domain growth is limited by the effective mixing due to the interconversion reaction, leading to a finite characteristic domain size. In addition to these effects, first introduced in our earlier work [ Phys. Rev. E 71 051906 (2005)], the important new feature is the assumption that the reactive process actively affects the local curvature of the bilayer. Specifically, we suggest that a force energetically activated by external sources causes a modification of the shape of the membrane at the reaction site. Our results show the appearance of a rich and robust dynamical phenomenology that includes the generation of traveling and/or oscillatory patterns. Linear stability analysis, amplitude equations, and numerical simulations of the model kinetic equations confirm the occurrence of these spatiotemporal behaviors in nonequilibrium reactive bilayers.

Traveling waves and nonequilibrium stationary patterns in two-component reactive Langmuir monolayers

A simple kinetic model of a two-component phase-separating Langmuir monolayer with a chemical reaction is proposed. Its analysis and numerical simulations show that nonequilibrium periodic stationary structures and patterns of traveling stripes can spontaneously develop. The nonequilibrium phase diagram of this system is constructed and the properties of the patterns are discussed.

Comparative localization of glioma-reactive monoclonal antibodies in vivo in an athymic mouse human glioma xenograft model.

Radioiodinated murine monoclonal antibodies (Mabs) 81C6, Me 1-14, C12, D12, and E9, made against or reactive with human gliomas but not normal brain, and Mab UJ13A, a pan-neuroectodermal Mab reactive with normal human glial and neural cells, were evaluated in paired label studies in the D-54 MG subcutaneous human glioma xenograft model system in nude mice. Following intravenous injection in the tail vein of mice bearing 200-400 mm3 tumors, specific localization of Mabs to tumor over time (6 h-9 days) was evaluated by tissue counting; each Mab demonstrated a unique localization profile. The comparison of localization indices (LI), determined as a ratio of tissue level of Mab to control immunoglobulin with simultaneous correction for blood levels of each, showed Mabs 81C6 and Me 1-14 to steadily accumulate in glioma xenografts, maintaining LI from 5-20 at 7-9 days after Mab injection. Mab UJ13A peaked at day 1, maintaining this level through day 2, and declining thereafter. Mabs D12 and C12 peaked at days 3 and 4, respectively, and E9 maintained an LI of greater than 3 from days 3-9. Percent injected dose localized/g of tumor varied from a peak high of 16% (81C6) to a low of 5% (Me 1-14 and UJ13A). Immunoperoxidase histochemistry, performed with each Mab on a battery of primary human brain neoplasms, revealed that Mabs 81C6 and E9, which demonstrated the highest levels of percent injected dose localized/g of tumor over time, reacted with antigens expressed in the extracellular matrix. This finding suggests that extracellular matrix localization of antigen represents a biologically significant factor affecting localization and/or binding in the xenograft model used. The demonstration of significant localization, varied kinetics and patterns of localization of this localizing Mab panel warrants their continued investigation as potential imaging and therapeutic agents for human trials.

Melt variability in percolated peridotite: an experimental study applied to reactive migration of tholeiitic basalt in the upper mantle

Melt-rock reaction in the upper mantle is recorded in a variety of ultramafic rocks and is an important process in modifying melt composition on its way from the source region towards the surface. This experimental study evaluates the compositional variability of tholeiitic basalts upon reaction with depleted peridotite at uppermost-mantle conditions. Infiltration-reaction processes are simulated by employing a three-layered set-up: primitive basaltic powder ('melt layer') is overlain by a 'peridotite layer' and a layer of vitreous carbon spheres ('melt trap'). Melt from the melt layer is forced to move through the peridotite layer into the melt trap. Experiments were conducted at 0.65 and 0.8 GPa in the temperature range 1,170-1,290 degrees C. In this P-T range, representing conditions encountered in the transition zone (thermal boundary layer) between the asthenosphere and the lithosphere underneath oceanic spreading centres, the melt is subjected to fractionation, and the peridotite is partially melting (T (s) similar to 1,260 degrees C). The effect of reaction between melt and peridotite on the melt composition was investigated across each experimental charge. Quenched melts in the peridotite layers display larger compositional variations than melt layer glasses. A difference between glasses in the melt and peridotite layer becomes more important at decreasing temperature through a combination of enrichment in incompatible elements in the melt layer and less efficient diffusive equilibration in the melt phase. At 1,290A degrees C, preferential dissolution of pyroxenes enriches the melt in silica and dilutes it in incompatible elements. Moreover, liquids become increasingly enriched in Cr(2)O(3) at higher temperatures due to the dissolution of spinel. Silica contents of liquids decrease at 1,260 degrees C, whereas incompatible elements start to concentrate in the melt due to increasing levels of crystallization. At the lowest temperatures investigated, increasing alkali contents cause silica to increase as a consequence of reactive fractionation. Pervasive percolation of tholeiitic basalt through an upper-mantle thermal boundary layer can thus impose a high-Si 'low-pressure' signature on MORB. This could explain opx + plag enrichment in shallow plagioclase peridotites and prolonged formation of olivine gabbros.

Edelfosine-induced metabolic changes in cancer cells that precede the overproduction of reactive oxygen species and apoptosis

Background: Metabolic flux profiling based on the analysis of distribution of stable isotope tracer in metabolites is an important method widely used in cancer research to understand the regulation of cell metabolism and elaborate new therapeutic strategies. Recently, we developed software Isodyn, which extends the methodology of kinetic modeling to the analysis of isotopic isomer distribution for the evaluation of cellular metabolic flux profile under relevant conditions. This tool can be applied to reveal the metabolic effect of proapoptotic drug edelfosine in leukemia Jurkat cell line, uncovering the mechanisms of induction of apoptosis in cancer cells. Results: The study of 13C distribution of Jukat cells exposed to low edelfosine concentration, which induces apoptosis in ¿5% of cells, revealed metabolic changes previous to the development of apoptotic program. Specifically, it was found that low dose of edelfosine stimulates the TCA cycle. These metabolic perturbations were coupled with an increase of nucleic acid synthesis de novo, which indicates acceleration of biosynthetic and reparative processes. The further increase of the TCA cycle fluxes, when higher doses of drug applied, eventually enhance reactive oxygen species (ROS) production and trigger apoptotic program. Conclusion: The application of Isodyn to the analysis of mechanism of edelfosine-induced apoptosis revealed primary drug-induced metabolic changes, which are important for the subsequent initiation of apoptotic program. Initiation of such metabolic changes could be exploited in anticancer therapy.

Combinatorial peptide library-based identification of peptide ligands for tumor-reactive cytolytic T lymphocytes of unknown specificity.

A novel approach for the identification of tumor antigen-derived sequences recognized by CD8(+) cytolytic T lymphocytes (CTL) consists in using synthetic combinatorial peptide libraries. Here we have screened a library composed of 3.1 x 10(11) nonapeptides arranged in a positional scanning format, in a cytotoxicity assay, to search the antigen recognized by melanoma-reactive CTL of unknown specificity. The results of this analysis enabled the identification of several optimal peptide ligands, as most of the individual nonapeptides deduced from the primary screening were efficiently recognized by the CTL. The results of the library screening were also analyzed with a mathematical approach based on a model of independent and additive contribution of individual amino acids to antigen recognition. This biometrical data analysis enabled the retrieval, in public databases, of the native antigenic peptide SSX-2(41-49), whose sequence is highly homologous to the ones deduced from the library screening, among the ones with the highest stimulatory score. These results underline the high predictive value of positional scanning synthetic combinatorial peptide library analysis and encourage its use for the identification of CTL ligands.

No implication of thromboxane-prostanoid receptors in reactive hyperemia of skin skeletal muscle in human forearm

L'hyperhémie réactive, définie comme l'augmentation transitoire du flux sanguin après une courte période d'ischémie, pourrait être influencée par des vasoconstricteurs de la famille des prostanoïdes, telle que la thromboxane. Le terutroban (S18886) est un antagoniste spécifique des récepteurs à la thromboxane. L'étude présentée a cherché à déterminer l'effet du terutroban sur l'hyperhémie réactive dans la peau et le muscle squelettique de l'avant-bras de volontaires sains. Vingt volontaires sains ont été randomisés en aveugle pour recevoir oralement 30mg/j de terutroban ou un placebo pendant 5 jours puis réciproquement pendant une deuxième période de 5 jours, selon un schéma cross-over. L'ischémie transitoire a été provoquée par l'occlusion de l'artère brachiale par une manchette gonflée au dessus de la pression systolique. L'hyperhémie réactive était évaluée dans les tissus de l'avant- bras, en mesurant le flux sanguin, pour la peau par une méthode laser Doppler, et pour le muscle au moyen d'une pléthysmographie par jauge de contrainte durant une occlusion veineuse. Au premier et au dernier jour de chaque période de traitement, l'hyperhémie réactive était mesurée avant et 2 heures après l'ingestion du comprimé. Que ce soit dans la peau ou le muscle, le terutroban n'a pas montré d'effet sur le flux de pic post-occlusion ni sur la réponse globale d'hyperhémie, exprimée en aire sous la courbe. En conclusion, dans la peau et le muscle de sujets sains, l'hypérémie réactive n'est pas influencée par les récepteurs spécifiques à la thromboxane.

Rapid IL-4 production by Leishmania homolog of mammalian RACK1-reactive CD4(+) T cells in resistant mice treated once with anti-IL-12 or -IFN-gamma antibodies at the onset of infection with Leishmania major instructs Th2 cell development, resulting in nonhealing lesions.

Rapid production of IL-4 by Leishmania homolog of mammalian RACK1 (LACK)-reactive CD4(+) T cells expressing the V beta 4-V alpha 8 TCR chains has been shown to drive aberrant Th2 cell development and susceptibility to Leishmania major in BALB/c mice. In contrast, mice from resistant strains fail to express this early IL-4 response. However, administration of either anti-IL-12 or -IFN-gamma at the initiation of infection allows the expression of this early IL-4 response in resistant mice. In this work we show that Leishmania homolog of mammalian RACK1-reactive CD4(+) T cells also expressing the V beta 4-V alpha 8 TCR chains are the source of the early IL-4 response to L. major in resistant mice given anti-IL-12 or -IFN-gamma Abs only at the onset of infection. Strikingly, these cells were found to be required for the reversal of the natural resistance of C57BL/6 mice following a single administration of anti-IL-12 or -IFN-gamma Abs. Together these results suggest that a deficiency in mechanisms capable of down-regulating the early IL-4 response to L. major contributes to the exquisite susceptibility of BALB/c mice to L. major.

Utilité du dosage de la CRP dans le diagnostic, le pronostic et le suivi de la pneumonie acquise dans la communauté [Role of C-reactive protein in the diagnosis, prognosis and follow-up of community-acquired pneumonia].

Community-acquired pneumonia (CAP) is a major clinical problem in terms of morbidity, mortality, and use of hospital resources. It is well recognized that a delay in making the diagnosis and instituting appropriate antibiotic treatment is associated with an increased mortality. C-reactive protein may be helpful in the management of patients with CAP. CRP is widely used in the management of CAP, including diagnosis, prognosis and follow-up. But its usefulness is not known. The aim of this systematic review was to evaluate the usefulness of CRP in the diagnosis, prognosis and follow-up of CAP.