We tested the hypothesis that levels of pentraxin high sensitivity C-reactive protein and pentraxin 3 might be correlated with cardiovascular complications in patients with essential thrombocythemia ...and polycythemia vera. High sensitivity C-reactive protein and pentraxin 3 were measured in 244 consecutive essential thrombocythemia and polycythemia vera patients in whom, after a median follow up of 5.3 years (range 0-24), 68 cardiovascular events were diagnosed. The highest C-reactive protein tertile was compared with the lowest (>3 vs. <1 mg/L) and correlated with age (P=0.001), phenotype (polycythemia vera vs. essential thrombocythemia, P=0.006), cardiovascular risk factors (P=0.012) and JAK2V617F allele burden greater than 50% (P=0.003). Major thrombosis rate was higher in the highest C-reactive protein tertile (P=0.01) and lower at the highest pentraxin 3 levels (P=0.045). These associations remained significant in multivariate analyses and indicate that blood levels of high sensitivity C-reactive protein and petraxin 3 independently and in opposite ways modulate the intrinsic risk of cardiovascular events in patients with myeloproliferative disorders.
Diabetes and oxidative stress concur to cardiac myocyte death in various experimental settings. We assessed whether
N-acetyl-
l-cysteine (NAC), an antioxidant and glutathione precursor, has a ...protective role in a rat model of streptozotocin (STZ)-induced diabetes and in isolated myocytes exposed to high glucose (HG). Diabetic rats were treated with NAC (0.5 g/kg per day) or vehicle for 3 months. At sacrifice left ventricle (LV) myocyte number and size, collagen deposition and reactive oxygen species (ROS) were measured by quantitative histological methods. Diabetes reduced LV myocyte number by 29% and increased myocyte volume by 20% compared to non-diabetic controls. NAC protected from myocyte loss (+25% vs. untreated diabetics,
P < 0.05) and reduced reactive hypertrophy (–16% vs. untreated diabetics,
P < 0.05). Perivascular fibrosis was high in diabetic rats (+88% vs. control,
P < 0.001) but prevented by NAC. ROS production and fraction of ROS-positive cardiomyocyte nuclei were drastically raised in diabetic rats (2.4- and 5.1-fold vs. control,
P < 0.001) and normalized by NAC. In separate experiments, isolated adult rat ventricular myocytes were incubated in a medium containing high concentrations of glucose (HG, 25 mM) ± 0.01 mM NAC; myocyte survival (Trypan blue exclusion and apoptosis by TUNEL) and glutathione content were evaluated. The number of dead and apoptotic myocytes increased five and 6.7-fold in HG and glutathione decreased by 48% (
P < 0.05). NAC normalized cell death and apoptosis and prevented glutathione loss. NAC effectively protects from hyperglycemia-induced myocyte cell death and compensatory hypertrophy through direct scavenging of ROS and replenishment of the intracellular glutathione content.
Different cardiac stem/progenitor cells have been recently identified in the post-natal heart. We describe here the identification, clonal expansion and characterization of self-renewing progenitors ...that differ from those previously described for high spontaneous cardiac differentiation. Unique coexpression of endothelial and pericyte markers identify these cells as cardiac mesoangioblasts and allow prospective isolation and clonal expansion from the juvenile mouse ventricle. Cardiac mesoangioblasts express many cardiac transcription factors and spontaneously differentiate into beating cardiomyocytes that assemble mature sarcomeres and express typical cardiac ion channels. Cells similarly isolated from the atrium do not spontaneously differentiate. When injected into the ventricle after coronary artery ligation, cardiac mesoangioblasts efficiently generate new myocardium in the peripheral area of the necrotic zone, as they do when grafted in the embryonic chick heart. These data identify cardiac mesoangioblasts as committed progenitors, downstream of earlier stem/progenitor cells and suitable for the cell therapy of a subset of juvenile cardiac diseases.
Abstract Background and aim Pentraxin 3 (PTX3) is an essential component of the humoral arm of innate immunity and, like C-reactive protein, is independently associated with the risk of developing ...vascular events. Aim of this study was to investigate, in two large population-based surveys, the Bruneck Study and the PLIC Study, whether PTX3 plasma levels predict the progression of common carotid artery intima–media thickness (CCA-IMT), a surrogate marker of atherosclerosis, in the general population during 5 or 6 years of follow-up. Results In the Bruneck Study, PTX3 plasma levels did not predict a faster progression of CCA-IMT either in the carotid artery or in the femoral artery. This finding was confirmed in the PLIC Study where subjects within the highest tertile of PTX3 did not show an increased progression of CCA-IMT. PTX3 plasma levels were also not associated with the fastest maximum IMT progression. In summary, in more than 2400 subjects from the general population, PTX3 plasma level is neither an independent predictor of progression of subclinical atherosclerosis in different arterial territories, including carotid and femoral arteries nor of incident cardiovascular events. Conclusion These findings support the relevance of investigating the predictive value of PTX3 plasma levels only in specific settings, like overt CVD, heart failure or acute myocardial infarction.
Aims
Pentraxin‐3 (PTX3) is a component of the humoral arm of innate immunity which can regulate inflammatory processes. Since the role of inflammation in the progression of chronic heart failure (HF) ...is debated, we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF.
Methods and results
Plasma levels of PTX3 were measured at randomization and after 3 months in 1457 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and 1233 patients enrolled in the GISSI‐Heart Failure trial (GISSI‐HF). The relationships between baseline PTX3 levels or their changes over time and mortality were evaluated with multivariable Cox proportional hazard models including clinical factors, high sensitivity C‐reactive protein (hsCRP), and N‐terminal pro brain natriuretic peptide (NT‐proBNP). PTX3 concentration median (Q1–Q3) = 5.34 (3.55–7.64) ng/mL, n = 2690 was higher in females, in older patients, and those with lower body mass index. Baseline elevated PTX3 was associated with a higher risk of all‐cause mortality 759 events, hazard ratio (HR) for 1 SD increase 1.20, 95% confidence interval (CI) 1.12–1.30, P < 0.0001, cardiovascular mortality (587 events, HR 1.27, 95% CI 1.17–1.38, P < 0.0001), or hospitalization for worsening HF (720 events, HR 1.21, 95% CI 1.12–1.30, P < 0.0001), and marginally improved discrimination. Three‐month changes in PTX3 were associated with fatal events after adjustment for hsCRP or NT‐proBNP. Rosuvastatin lowered hsCRP levels but significantly raised PTX3.
Conclusion
In two independent clinical trials that enrolled patients with chronic HF, PTX3 was consistently associated with outcomes. The opposite effects of a statin on hsCRP and PTX3 call for further investigation.
Trial registration
NCT00336336 (GISSI‐HF), NCT00206310 (CORONA).
Inflammation may play a significant role in the pathogenesis of atrial fibrillation (AF).
To examine the roles of three systemic inflammatory markers in predicting recurrent AF.
The association ...between the plasma concentrations of high-sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6) and pentraxin-3 (PTX3) with echocardiographic parameters and with the time to first recurrence of AF was tested in 382 patients with a history of AF but in sinus rhythm at randomisation, enrolled in the GISSI-AF biohumoral study.
Baseline PTX3 was related to left atrial, but not to left ventricular chamber volume. During one year of follow-up, 204 patients (53.1%) had a recurrent AF. There were no significant differences in baseline median Q1-Q3 plasma concentrations of IL-6, hsCRP and PTX3 among patients with (2.11 1.47-3.74 pg/ml, 3.30 1.40-6.80 mg/l and 4.66 3.27-6.97 ng/ml, respectively) or without recurrent AF (2.09 1.37-2.90 pg/ml, p=0.182; 3.00 1.10-6.20 mg/l, p=0.333; 5.09 3.22-7.98 ng/ml, p=0.637). At 6 and 12 months follow-up, AF patients had significantly higher concentrations of IL-6 and PTX3 than those in sinus rhythm, and those with most recent episodes of AF had higher hsCRP. Baseline levels of IL-6, hsCRP or PTX3 were not significantly associated with a higher risk of recurrence of AF.
In patients with a history of AF, but without significant left ventricular dysfunction or heart failure, inflammatory biomarkers may be raised but are, at best, weak predictors of the risk for first recurrence of AF.
D-mannose is a monosaccharide approximately a hundred times less abundant than glucose in human blood. Previous studies demonstrated that supraphysiological levels of D-mannose inhibit tumour growth ...and stimulate regulatory T cell differentiation. It is not known whether D-mannose metabolism affects the function of non-proliferative cells, such as inflammatory macrophages. Here, we show that D-mannose suppresses LPS-induced macrophage activation by impairing IL-1β production. In vivo, mannose administration improves survival in a mouse model of LPS-induced endotoxemia as well as decreases progression in a mouse model of DSS-induced colitis. Phosphomannose isomerase controls response of LPS-activated macrophages to D-mannose, which impairs glucose metabolism by raising intracellular mannose-6-phosphate levels. Such alterations result in the suppression of succinate-mediated HIF-1α activation, imposing a consequent reduction of LPS-induced Il1b expression. Disclosing an unrecognized metabolic hijack of macrophage activation, our study points towards safe D-mannose utilization as an effective intervention against inflammatory conditions.
Fibre Bragg grating (FBG) strain sensors are not only a very well-established research field, but they are also acquiring a bigger market share due to their sensitivity and low costs. In this paper ...we review FBG strain sensors with high focus on the underlying physical principles, the interrogation, and the read-out techniques. Particular emphasis is given to recent advances in highly-performing, single head FBG, a category FBG strain sensors belong to. Different sensing schemes are described, including FBG strain sensors based on mode splitting. Their operation principle and performance are reported and compared with the conventional architectures. In conclusion, some advanced applications and key sectors the global fibre-optic strain sensors market are envisaged, as well as the main market players acting in this field.
This paper is an overview of current gyroscopes and their roles based on their applications. The considered gyroscopes include mechanical gyroscopes and optical gyroscopes at macro- and micro-scale. ...Particularly, gyroscope technologies commercially available, such as Mechanical Gyroscopes, silicon MEMS Gyroscopes, Ring Laser Gyroscopes (RLGs) and Fiber-Optic Gyroscopes (FOGs), are discussed. The main features of these gyroscopes and their technologies are linked to their performance.
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