Biomedical subjects

Orlando Pignalosa

Publications and source records attributed to Orlando Pignalosa.

5 recordsLinked to original sources

PubMed2006

Nitric oxide and atherosclerosis: an update.

Nitric oxide (NO) is a molecule that has gained recognition as a crucial modulator of vascular disease. NO has a number of intracellular effects that lead to vasorelaxation, endothelial regeneration, inhibition of leukocyte chemotaxis, and platelet adhesion. Endothelium damage induced by atherosclerosis leads to the reduction in bioactivity of endothelial NO synthase (eNOS) with subsequent impaired release of NO together with a local enhanced degradation of NO by increased generation of reactive oxygen species with subsequent cascade of oxidation-sensitive mechanisms in the arterial wall. Many commonly used vasculoprotective agents have their therapeutic actions through the production of NO. L-Arginine, the precursor of NO, has demonstrated beneficial effects in atherosclerosis and disturbed shear stress. Finally, eNOS gene polymorphism might be an additional risk factor that may contribute to predict cardiovascular events. However, further studies are needed to understand the possible clinical implications of these correlations.

Animals↗

PubMed2005

Phenotypic APC resistance as a marker of hypercoagulability in primitive cerebral lymphoma.

UNLABELLED: Thrombosis is the most frequent complication and the second cause of death in patients with malignant disease. Primary central nervous system non-Hodgkin's lymphoma represents a rare pathology. Resistance to APC is usually linked to a factor V (FV) gene mutation changing an Arg 506 to a Gln in the APC cleavage site. AIM: In our study, we aimed at investigating the presence of activated protein C resistance (APC-r) and other markers of hypercoagulability in 25 selected patients with a diagnosis of primitive cerebral lymphoma who had suffered from an ischemic episode of TIA and/or stroke. PATIENTS AND METHODS: 25 selected patients with a diagnosis of primitive cerebral lymphoma and 50 healthy subjects acted as control group, were tested. We measured APC-r, natural clotting inhibitors, F1 + 2, aPTT and PAI-1 according to international guidelines. Genomic DNA was extracted from peripheral white blood cells and in order to detect FV Leiden gene polymorphism. RESULTS: Our results showed that 11 out of 25 patients had a poor response to APC (< or = 0.70, which represents the cut-off point in our general population) without deficiencies in natural clotting inhibitors. All patients had high plasma levels of F1+2 and PAI-1 compared to those found in healthy subjects (2.65 +/- 0.75 nM/L vs 0.40 +/- 0.35 nM/L; 67.5 +/- 18.5 ng/mL vs 17 +/- 11.5 ng/mL, respectively). In 9 patients resistance to APC was not associated to a FV gene defect demonstrating that such phenomenon may occur also as an acquired condition. However, the patients with resistance to APC showed the highest plasma values in F1 + 2 and PAI-1. CONCLUSION: In cerebral lymphoma with hypercoagulability the resistance to APC is not caused by the FV Arg 506-->Gln mutation (82%). APC resistance not caused by this FV gene defect may be an additional risk factor for thrombophilia in this selected population.

Activated Protein C Resistance↗

PubMed2005

[Childhood infection and endothelial dysfunction: a potential synergistic link in atherosclerosis].

The prodromal stage of atherosclerotic lesions is already formed during human fetal development. The presence of infections during childhood may increase synergistically the progression of atherogenesis. After delivery, especially those children exposed to severe maternal hypercholesterolemia should be followed up for the onset and development of acute and chronic infections and be included in clinical and noninvasive examinations of vascular function.

Atherosclerosis↗

PubMed2004

Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice.

The pathogenic mechanisms by which physical exercise influences atherosclerotic lesion formation remain poorly understood. Because vigorous physical training increases oxidative stress, this study tested the hypothesis that graduated and moderate physical exercise together with metabolic intervention (l-arginine and antioxidants) may contribute to increased vascular protection. Exercise training in mice was induced by graduated swimming. In hypercholesterolemic male mice on an atherogenic high-cholesterol diet, graduated and moderate exercise lowered plasma cholesterol and decreased atherosclerotic lesions compared with sedentary control mice. Antioxidants (1.0% vitamin E added to the chow and 0.05% vitamin C added to the drinking water) and l-arginine (6% in drinking water) supplementation to exercising hypercholesterolemic mice further and synergistically reduced atherosclerosis compared with untreated exercised mice. Arterial oxidation-specific epitopes and systemic oxidative stress were reduced by metabolic intervention. Graduated chronic exercise elicited an increase in production of nitric oxide through increased endothelial nitric oxide synthase expression and ameliorated scavenger activities. Thus, metabolic intervention with l-arginine and antioxidants together with graduated and moderate exercise training reduce atherosclerotic lesion formation.

Animals↗

PubMed2004

The beneficial effects of antioxidant supplementation in enteral feeding in critically ill patients: a prospective, randomized, double-blind, placebo-controlled trial.

We investigated whether intervention with antioxidant vitamins C and E in enteral feeding influenced oxidative stress and clinical outcome in critically ill patients. Two-hundred-sixteen patients expected to require at least 10 days of enteral feeding completed the study. One-hundred-five patients received enteral feeding supplemented with antioxidants, and 111 control patients received an isocaloric formula. Plasma lipoperoxidation (by thiobarbituric acid reactive substances [TBARS] and prostaglandin F(2alpha) isoprostane levels), low-density lipoprotein (LDL) oxidizability, and LDL tocopherol content were determined at baseline and at the end of the 10-day period. The clinical 28-day outcome was also assessed. Plasma TBARS and isoprostanes were 5.33 +/- 1.26 nM/mL and 312 +/- 68 pg/mL, respectively, before treatment and 2.42 +/- 0.61 nM/mL and 198 +/- 42 pg/mL after intervention (P < 0.01 for both comparisons). Antioxidants improved LDL resistance to oxidative stress by approximately 30% (the lag time before treatment was 87 +/- 23 min and was 118 +/- 20 min after treatment; P < 0.04). There was a significantly reduced 28-day mortality after antioxidant intervention (45.7% in the antioxidant group and 67.5% in the regular-feeding group; P < 0.05). Isoprostanes may provide a sensitive biochemical marker for dose selection in studies involving antioxidants.

Adult↗