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Biomedical subjects

Francesco Violi

Publications and source records attributed to Francesco Violi.

33 records · Page 2Linked to original sources
PubMed2004

Inhibition of platelet aggregation by aspirin progressively decreases in long-term treated patients.

OBJECTIVES: We sought to investigate, during a two-year follow-up period, the effects of aspirin on platelet aggregation. BACKGROUND: The platelets of patients given aspirin may be less sensitive to antiplatelet treatment, although the extent of such phenomenon over long-term follow-up is unclear. METHODS: Adenosine diphosphate (ADP) and collagen-induced platelet aggregation was periodically monitored before and after 2, 6, 12, and 24 months of treatment with aspirin (n = 150) or ticlopidine (n = 80) in patients matched for gender, age, and risk factors for atherothrombosis. RESULTS: Compared with baseline values, two months of aspirin treatment significantly inhibited platelet aggregation; thereafter, this inhibitory effect progressively decreased. At 24-month follow-up, collagen-induced platelet aggregation was significantly higher than that observed at two months (p < 0.05); a more pronounced difference was observed when collagen-induced lag phase was considered (p < 0.01). Restoration of platelet aggregation was less evident when ADP was used as an agonist. Conversely, the inhibition induced by ticlopidine was constant throughout follow-up with both agonists. CONCLUSIONS: The study demonstrates that a long-term treatment with aspirin is associated with a progressive reduction in platelet sensitivity to this drug.

Adenosine Diphosphate↗
PubMed2004

Picotamide, a combined inhibitor of thromboxane A2 synthase and receptor, reduces 2-year mortality in diabetics with peripheral arterial disease: the DAVID study.

AIMS: Patients with diabetes are at excessive risk of mortality and cardiovascular morbidity. Previous studies suggest that aspirin may be less effective in diabetic patients. In this multi-centre, randomized, double blind trial picotamide, a dual inhibitor of thromboxane A2 synthase and receptor, was compared with aspirin for the prevention of mortality and major cardiovascular events in diabetics with peripheral arterial disease (PAD). METHODS AND RESULTS: A total of 1209 adults aged 40-75 years with type 2 diabetes and PAD were randomized to receive picotamide (600 mg bid) or aspirin (320 mg od) for 24 months. The cumulative incidence of the 2 years overall mortality was significantly lower amongst patients who received picotamide (3.0%) than in those who received aspirin (5.5%) with a relative risk ratio for picotamide versus aspirin of 0.55 (95% CI: 0.31-0.98%). Events were reported in 43 patients (7.1%) on picotamide and 53 (8.7%) on aspirin. The combined endpoint of mortality and morbidity had a slightly lower incidence in the picotamide group but this difference did not reach statistical significance. CONCLUSION: Picotamide is significantly more effective than aspirin in reducing overall mortality in type 2 diabetic patients with associated PAD.

Adult↗
PubMed2004

Enhanced platelet release of superoxide anion in systemic hypertension: role of AT1 receptors.

BACKGROUND: Enhanced oxidative stress has been observed in hypertension, but the underlying mechanism has not been fully clarified. OBJECTIVE: To study the relationship between oxygen free radicals and hypertension, using platelets as a tool to measure the cellular production of superoxide anion (O2). DESIGN: Forty patients with hypertension were allocated randomly to groups to receive either irbesartan, an inhibitor of angiotensin II type 1 (AT1) receptors (n = 20), or a diuretic (hydrochlorothiazide) (n = 20). In each patient, collagen-induced production of O2 by platelets was studied before and after 4 weeks of treatment. Forty sex- and age-matched healthy individuals were studied as controls. METHODS: Platelet-produced O2 was measured using lucigenin chemiluminescence and hydroethidine cytofluorimetric analysis. RESULTS: Compared with healthy individuals, patients with hypertension showed a greater production of O2 by platelets (P < 0.001); there was no correlation between blood pressure and platelet O2 production. After treatment, no changes in platelet O2 formation were observed in patients receiving hydrochlorothiazide; conversely, those treated with irbesartan showed a significant (P < 0.001) decrease in platelet O2 production. At the end of the treatment, no differences in blood pressures were observed between the two groups. In-vitro incubation of platelets with angiotensin II elicited a significant increase in O2 (P < 0.001) that was dose-dependently inhibited by irbesartan and diphenylene iodonium, an inhibitor of NADPH oxidase. CONCLUSION: Patients with hypertension showed an enhanced formation of O2 in platelets that was not dependent on blood pressure but could be mediated by AT1 receptors via NADPH oxidase activation.

Adult↗
PubMed2004

Vitamin E for the treatment of cardiovascular disease: is there a future?

Oxidative stress seems to play a key role in the pathogenesis of atherosclerosis. Agents that protect low-density lipoprotein from oxidation have been shown in a range of in vitro and animal models to reduce the development and progression of atherosclerosis. These agents include antioxidant micronutrients such as vitamin E. They have gained wide interest because of the potential for prevention of atherosclerotic vascular disease in humans. In the last decade, many trials with antioxidants have been carried out in patients with cardiovascular disease, but the results are equivocal. The reason for the disappointing findings is unclear, but one possible explanation is the lack of identification criteria of patients who are potential candidates for antioxidant treatment. This review analyses the data reported so far to determine whether they clearly support the premise that patients at risk of cardiovascular disease may be candidates for antioxidant treatment.

Animals↗
PubMed2003

Enhanced TNF alpha and oxidative stress in patients with heart failure: effect of TNF alpha on platelet O2- production.

Experimental studies have suggested that TNF alpha, a pro-inflammatory cytokine, may contribute to the deterioration of cardiovascular function through various mechanisms, including the generation of reactive oxygen species. It has not yet been demonstrated whether TNF alpha has prooxidant activity in patients with heart failure, and what the mechanism eventually resulting in this effect are. We analyzed 42 patients (38 men and 4 women, aged 26 to 74 years) with heart failure, secondary to idiopathic dilated cardiomyopathy (n=21), coronary artery disease (n=15), and valve disease (n=6), and 20 controls (18 men and 2 women, aged 49 to 67 years). Ten patients were in class I, 9 in class II, 15 in class III and 8 in class IV according to NYHA Classification. Blood samples were obtained from each patient to evaluate basal and collagen-induced platelet O(2)(-) production, and plasma TNF alpha. In vivo results showed increased platelet O(2)(-) production and plasma TNF alpha levels in NYHA class III-IV compared with that in controls or in NYHA I-II (p<0,001); platelet O(2)(-) production correlated significantly (R=0,6; p<0,01) with TNF alpha plasma levels. In vitro studies showed TNF alpha dose-dependently (5-40 pg/ml) induced platelet O(2)(-) production, and that this effect was significantly inhibited by its specific inhibitor, WP9QY (1 microM); aspirin (100 microM), AACOCF(3), a specific PLA(2) inhibitor (14 microM), and DPI, an inhibitor of NADPH oxidase, significantly inhibited TNF alpha-mediated platelet O(2)(-) production. This study suggests that in patients with heart failure, enhanced platelet O(2)(-) production is mediated by TNF alpha via activation of arachidonic acid and NADPH oxidase pathways.

Adult↗
PubMed2002

Vitamin E potentiates the antiplatelet activity of aspirin in collagen-stimulated platelets.

BACKGROUND AND OBJECTIVES: The combination of vitamin E with aspirin is becoming an attractive therapeutic approach to prevent thrombotic vascular accidents. In this study we investigated the capacity of vitamin E (50 and 100 M) to enhance the antiplatelet effect of aspirin. DESIGN AND METHODS: The dose-response curves of platelet aggregation, dense body secretion, phospholipase C activation and calcium mobilization were measured in aspirin-treated platelets with and without added vitamin E (50 and 100 M). The role of vitamin E in reducing platelet adhesion to collagen was also studied. RESULTS: We demonstrated that, in platelets incubated with 100 M vitamin E, collagen-concentration ( g/mL) able to induce 50% of the maximal platelet aggregation and of the calcium mobilization was higher than in controls (11.6 versus 3.8 and 21.3 versus 9.8, respectively). Furthermore, 50 M vitamin E reduced platelet adhesion to collagen by about 80%. INTERPRETATION AND CONCLUSIONS: These data demonstrate that vitamin E can potentiate the antiplatelet activity of aspirin by inhibiting the early events of platelet activation pathways induced by collagen. This finding provides a rationale for combining aspirin and vitamin E to prevent thrombotic complications in atherosclerotic patients.

Aspirin↗
PubMed2002

Increased superoxide anion production by platelets in hypercholesterolemic patients.

OBJECTIVES: The purpose of this study was to investigate the relationship between hypercholesterolemia and superoxide anion production. BACKGROUND: Experimental studies demonstrated that hypercholesterolemia is associated with enhanced cellular superoxide anion (O2-) production. Aim of the study was to assess whether the same phenomenon occurs in humans. METHODS: Lipid profile and platelet O2- production were measured in 28 patients with hypercholesterolemia, compared with 25 age- and sex-matched healthy subjects, and in 21 out of the 28 patients after 8-week treatment with 10 mg/day atorvastatin (a HMGCoA reductase inhibitor). In order to assess the mechanism by which LDL cholesterol interferes with platelet production of O2-, human platelets were incubated with LDL cholesterol in the presence of either an inhibitor of the phospholipaseA2 enzyme, AACOCF3, or an inhibitor of NADH/NADPH oxidases, DPI. RESULTS: O2- platelet generation was significantly higher (p <0.001) and significantly related to LDL cholesterol (p <0.001 ) in patients as compared to controls. 8-week treatment with 10 mg/day atorvastatin significantly reduced both LDL cholesterol and O2- platelet production. This effect was partially related to the cholesterol-lowering, in that three days of treatment with atorvastatin significantly decreased platelet O2- production, while no significant change in LDL-cholesterol levels was observed. Platelets incubated with LDL cholesterol showed an increased O2- production, which was significantly inhibited by AACOCF3 (-78%) and DPI (-56%). CONCLUSIONS: LDL cholesterol increases platelet O2- production by activating PLA2 and NADH/NADPH enzymes. Inhibition of platelet O2- release by atorvastatin is partially related to cholesterol lowering effect, suggesting that other mechanisms could be responsible for the antioxidant activity of the drug.

Anticholesteremic Agents↗
PubMedDate not supplied

Red and white wine differently affect collagen-induced platelet aggregation.

Moderate consumption of wine is associated with reduced cardiovascular events, but the mechanism is not fully elucidated. Aim of the study was to seek if consumption of red or white wine, that are known to have different amount of polyphenols, differently influenced platelet aggregation. 20 healthy subjects were randomly allocated to consume for two weeks 300 ml of red or white wine; both wines had the same concentration of alcohol. At baseline and 12 hours after last drink collagen-induced platelet aggregation was performed. At baseline no difference of laboratory values was observed between the two groups. At the end of treatment subjects given red wine had lower response to platelet agonist than those given white wine (<0.005). No ethanol could be found in plasma 12 hours after last drink. This study shows that red and white wine have different effect on platelet activation likely because of the different content of polyphenols present in the two types of wine.

Adult↗