Elisabetta Rossi

Platelet activation is associated with myocardial infarction in patients with pneumonia

BACKGROUNDnTroponins may be elevated in patients with pneumonia, but associations with myocardial infarction (MI) and with platelet activation are still undefined.nnnOBJECTIVESnThe aim of this study was to investigate the relationship between troponin elevation and inxa0vivo markers of platelet activation in the early phase of hospitalization of patients affected by community-acquired pneumonia.nnnMETHODSnA total of 278 consecutive patients hospitalized for community-acquired pneumonia, who were followed up until discharge, were included. At admission, platelet activation markers such as plasma soluble P-selectin, soluble CD40xa0ligand, and serum thromboxane B2 (TxB2) were measured. Serum high-sensitivity cardiac troponin T levels and electrocardiograms were obtained every 12 and 24 h, respectively.nnnRESULTSnAmong 144 patients with elevated high-sensitivity cardiac troponin T, 31 had signs of MI and 113 did not. Baseline plasma levels of soluble P-selectin and soluble CD40 ligand and serum TxB2 were significantly higher in patients who developed signs of MI. Logistic regression analysis showed plasma soluble CD40 ligand (pxa0< 0.001) and soluble P-selectin (pxa0< 0.001), serum TxB2 (pxa0= 0.030), mean platelet volume (pxa0= 0.037), Pneumonia Severity Index score (pxa0=xa00.030), and ejection fraction (pxa0= 0.001) to be independent predictors of MI. There were no significant differences in MI rate between the 123 patients (45%) taking aspirin (100 mg/day) and those who were not aspirin treated (12%xa0vs.xa010%; pxa0= 0.649). Aspirin-treated patients with MIs had higher serum TxB2 compared with those without MIsxa0(pxa0= 0.005).nnnCONCLUSIONSnMI is an early complication of pneumonia and is associated with inxa0vivo platelet activation and serum TxB2 overproduction; aspirin 100 mg/day seems insufficient to inhibit thromboxane biosynthesis. (MACCE in Hospitalized Patients With Community-acquired Pneumonia; NCT01773863).

Low-grade endotoxemia, gut permeability and platelet activation in community-acquired pneumonia

OBJECTIVESnPlatelet activation seems to be implicated in the cardiovascular events occurring in patients with community-acquired pneumonia (CAP) but the underlying mechanism is still unclear. Aim of the study was to assess the mechanism involved in platelet activation in CAP patients.nnnMETHODSnTwo-hundred-seventy-eight consecutive patients hospitalized for CAP were recruited and followed-up until discharge. Hospitalized patients matched for sex, age and comorbidities but without acute infectious diseases were used as controls.nnnRESULTSnAt hospital admission patients disclosed enhanced plasma levels of sP-selectin, a maker of in-vivo platelet activation, serum sNOX2-dp, a marker of NADPH-oxidase activation, serum Lipopolysaccharide (LPS) and serum zonulin, a marker of gut permeability, compared to controls (pxa0<xa00.001). Baseline sP-selectin was independently associated to serum LPS, sNOX2-sp and Pneumonia Severity Index score (pxa0<xa00.001). Plasma sP-selectin, serum sNOX2-dp, LPS and zonulin coincidentally decreased at hospital discharge (pxa0<xa00.001). An in vitro study showed that LPS, at concentration similar to that found in CAP patients, induced sP-selectin release by agonist-activated platelets, a phenomenon that was counteract by treating cells with gp91ds-tat, a specific inhibitor of NOX2.nnnCONCLUSIONSnCAP patients display enhanced platelet activation, which is related to LPS-mediated NOX2 activation. Enhanced gut permeability seems be implicated in enhancing circulating levels of LPS.

Is NOX2 Upregulation Implicated in Myocardial Injury in Patients with Pneumonia

In the present study, we tested the hypothesis that oxidative stress could be implicated in myocardial damage during the acute phase of pneumonia. NOX2 activation, the catalytic subunit of NADPH oxidase, and high-sensitivity cardiac troponin T (hs-cTnT) elevation have been analyzed in two hundred forty-eight consecutive patients hospitalized for community-acquired pneumonia. Serum NOX2-derived peptide (sNOX2-dp), a marker of NOX2 activation, and 8-isoprostaglandin F2α (8-iso-PGF2α), a marker of oxidative stress, were measured upon admission; serum hs-cTnT and ECG were measured every 12 and 24 h, respectively. One hundred thirty-five patients (54%) showed elevated serum levels of hs-cTnT (>0.014 μg/L). A logistic regression analysis showed sNOX2-dp (p<0.001), Pneumonia Severity Index score (p<0.001), renal failure (p=0.024), and ejection fraction (p<0.001) as independent predictors of elevated serum levels of hs-cTnT. Serum sNOX2-dp was linearly correlated with hs-cTnT (Rs=0.538; p<0.001) and 8-iso-PGF2α (Rs=0.354; p<0.001). The study provides the first evidence of a significant association between serum cardiac Troponin T elevation and NOX2 upregulation in patients with pneumonia. This finding raises the hypothesis that NOX2-derived oxidative stress may be implicated in myocardial injury and that its inhibition could be a novel therapeutic strategy to limit it.

Impaired flow-mediated dilation in hospitalized patients with community-acquired pneumonia

BACKGROUNDnCommunity-acquired pneumonia (CAP) is complicated by cardiovascular events as myocardial infarction and stroke but the underlying mechanism is still unclear. We hypothesized that endothelial dysfunction may be implicated and that endotoxemia may have a role.nnnMETHODSnFifty patients with CAP and 50 controls were enrolled. At admission and at discharge, flow-mediated dilation (FMD), serum levels of endotoxins and oxidative stress, as assessed by serum levels of nitrite/nitrate (NOx) and isoprostanes, were studied.nnnRESULTSnAt admission, a significant difference between patients with CAP and controls was observed for FMD (2.1±0.3 vs 4.0±0.3%, p<0.001), serum endotoxins (157.8±7.6 vs 33.1±4.8pg/ml), serum isoprostanes (341±14 vs 286±10 pM, p=0.009) and NOx (24.3±1.1 vs 29.7±2.2μM). Simple linear correlation analysis showed that serum endotoxins significantly correlated with Pneumonia Severity Index score (Rs=0.386, p=0.006). Compared to baseline, at discharge CAP patients showed a significant increase of FMD and NOx (from 2.1±0.3 to 4.6±0.4%, p<0.001 and from 24.3±1.1 to 31.1±1.5μM, p<0.001, respectively) and a significant decrease of serum endotoxins and isoprostanes (from 157.8±7.6 to 55.5±2.3pg/ml, p<0.001, and from 341±14 to 312±14 pM, p<0.001, respectively). Conversely, no changes for FMD, NOx, serum endotoxins and isoprostanes were observed in controls between baseline and discharge. Changes of FMD significantly correlated with changes of serum endotoxins (Rs=-0.315; p=0.001).nnnCONCLUSIONSnThe study provides the first evidence that CAP is characterized by impaired FMD with a mechanism potentially involving endotoxin production and oxidative stress.

EDTA Chelating Process for Lead Removal: Evaluation of Approaches by Means of a Reactive Transport Model.

A 1D reactive model is developed to simulate the EDTA chelating process in a lead (Pb)-contaminated saturated soil. The model is implemented using a multistep numerical approach in order to avoid numerical diffusion assuring at the same time the algorithm stability. The model takes into account first-order reactions where the lead species are splitted into three fractions: C1 (easily mobilized lead), C2 (lead associated with iron and manganese oxides), and C3 (lead bound to organic matter and in the residual fraction). Two different mobilization kinetics (“slow” and “fast”) are considered for each fraction. The model was therefore calibrated and validated using laboratory experimental data. A sequential extraction procedure was conducted to evaluate the lead mobilization due to the EDTA flushing through the column and to take into account the different soil fraction at which the metal is bound. Several remediation scenarios are used to show the suitability of the model to provide information and knowledge of the best EDTA feed and flux conditions for the lead extraction from soil. The model can therefore be considered as a tool to know in advance the performances of a remediation treatment and to optimize the extraction process minimizing the chelating agent costs and its effects on the soil.