Mechanisms underlying production of vascular free radicals are unclear. We hypothesized that changes in blood flow might serve as a physiological stimulus for endothelial free radical release. Intact isolated aortas from 45 rabbits were perfused with the spin trap a-phenyl-N-tertbutylnitrone (PBN, 20 mmol/L) and formed radical adducts detected by electron paramagnetic resonance spectroscopy (EPR). Sequential perfusion at 2, 7.5, and 12 mL/min changed cumulative vascular PBN radical adduct yields, respectively, from 3.2+0.9 to 4.1±0.7 (P<.05) and 7.0±1.5 (P<.005) pmol/mg with endothelium and from 3.6±1.6 to 3.8±1.4 and 2.2±0.8 pmol/mg without endothelium (P=NS). In endothelialized aortas, superoxide dismutase (SOD) completely blocked flow-induced free radical production, whereas inactivated SOD, indomethacin, and the nitric oxide synthetase antagonist nitro-L-arginine methyl ester (L-NAME) had no effect; relaxations to acetylcholine remained unchanged with higher flows. To assess the role of flow on in vivo radical production, femoral arterial plasma levels of the ascorbyl radical, a stable ascorbate oxidation product, were measured by direct EPR in 56 other rabbits. Ascorbyl levels were assessed at baseline (30.2±0.7 nmol/L) and at peak-induced iliac flow changes. Flow increases from 25% to 100% due to saline injections through an extracorporeal aortic loop induced significant dose-dependent increases in ascorbyl levels (n=5). In addition, after papaverine bolus injections, flow increased by 114±8% versus baseline, and ascorbyl levels increased by 5.4±0.7 nmol/L (n=31, P<.001); similar results occurred with adenosine, isoproterenol, or hyperemia after 30-second occlusions (P<.05, n=4 or 5 in each group). Active SOD completely blocked papaverine-induced ascorbyl radical increase, despite preserved flow response (Aascorbyl=0.02±1.6 nmol/L, P=NS); inactivated SOD, catalase, indomethacin, and L-NAME had no effect. Blood flow decreases of 65% to 100% due to phenylephrine or 60-second balloon occlusions were accompanied by an average decrease of 4.4 nmol/L (P<.05) in ascorbyl levels. No change in ascorbyl signal was observed when rabbit blood alone was submitted to in vitro flow increases through a tubing circuit. Thus, increases in blood flow trigger vascular free radical generation; such a response seems to involve endothelium-derived superoxide radicals unrelated to cyclooxygenase or nitric oxide synthetase activities. This mechanism may contribute to explain vascular free radical generation in physiological or pathological circumstances. (Circ Res. 1994;74:700-709.) Key Words * ascorbyl radical * superoxide dismutase * nitric oxide * endothelium * oxidative stress T he identification of the gaseous free radical nitric oxide (QN=O) as a major signal transducer molecule and endothelium-derived vascular relaxing factor1 suggests that oxyreduction reactions are important effector steps for autocrine or paracrine regulation of vessel tone, permeability, and structure in physiological or pathological conditio...

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1) Various inflammatory markers were elevated in the studied population, although not necessarily exceeding the normal range; 2) Significant reduction could be demonstrated; 3) Some persistent effects of flaxseed supplement 2 weeks after discontinuation were observed.

BackgroundPlatelet activation and consumption are common in critically ill patients and are associated with poorer prognosis. Mean platelet volume is a simple surrogate for platelet activation, with higher MPV being associated with worse clinical condition on a large array of clinical diagnoses. We therefore aimed to investigate associations between changes in platelet count and mean platelet volume (MPV) with prognosis and inflammatory cytokine values in critically ill patients.MethodsThis study prospectively included 84 critically ill patients. Patients were stratified into four groups according to proportional changes in MPV (ΔMPV24h) and platelet count (ΔPlat24h) in the first 24 hours after admission. Mortality between groups was compared using the χ2 test. Logistic regression was performed using hospital mortality as outcome and Simplified Acute Physiology Score (SAPS 3), ΔPlat24h and ΔMPV24h as covariates. Concentrations of the following inflammatory mediators were measured using Miliplex® technology: IL1β, IL6, IL8, IL10, epidermal growth factor, vascular endothelial growth factor, TNFα and IFNα. Cytokine concentrations were compared between groups using the Kruskal-Wallis test with Bonferroni correction.ResultsPatients in whom MPV increased and platelet count decreased had higher mortality rates (46%). According to logistic regression, ΔMPV24h was independently associated with increased mortality (OR 1.28 per 1% increase; 95% CI 1.08 to 1.48). No strong associations between inflammatory mediators and changes in MPV and platelet count were found.ConclusionAn increase in MPV after admission to an ICU is independently associated with higher hospital mortality.

The role of hepatitis C virus (HCV) in the pathogenesis of atherosclerosis and cardiovascular events is unclear. The aim of this study was to evaluate the direct effect of HCV on cardiovascular risk and correlate it with pro and anti-inflammatory cytokines in patients with HCV. HCV monoinfected patients, genotype 1, naive, non-obese (BMI<30) and non-diabetics were included and compared to controls (blood donors). Patients with prior diagnosis of cardiovascular diseases, hypertension, chronic renal failure, cancer and chronic use of lipid-lowering drugs or immunosuppressants were excluded. Age, BMI, systolic blood pressure (SBP) and diastolic (DBP), fasting glucose and lipid levels were determined. Serum cytokines (IL-6, IL-10 and TNF-α) and Framingham score were also evaluated. 62 HCV patients, 34 (54.8%) were males and none of them was smoking. The Framingham scores (median and 25th and 75th percentiles) were 12% (6.5-14%), showing an intermediate cardiovascular risk in patients with HCV. There was significant direct correlation between Framingham and total cholesterol (p=0.043) and DBP (p=0.007). HDL-C (p=0.002) was inversely correlated with the Framingham score. HCV patients had higher levels of proinflammatory cytokines (IL-6 and TNF-α) compared to controls (p<0.0001) and the relation of proinflammatory/anti-inflammatory TNF-α/IL10 and IL-6/IL10 were higher in HCV patients (p<0.01). The Framingham score was directly correlated to IL-6 and TNF-α, but differences were not statistically significant. Patients with HCV monoinfected, nonobese, naïve and non diabetic have an intermediate cardiovascular risk, as measured by the Framingham score and high levels of proinflammatory cytokines (IL-6 and TNF).

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1) Frequent colonization of both gastric chambers was detected; 2) Aerobes, anaerobes and fungi were represented in both situations; 3) Gastric pH as well as bacterial count was higher in the functioning proximal stomach; 4) Breath test was positive in 40.5% of the subjects; 5) Clinical manifestation such as diarrhea, malabsorption or pneumonia were not demonstrated; 6) Further histologic and microbiologic studies of both the stomach and the small bowel are recommended.