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F Violi

Publications and source records attributed to F Violi.

At least 73 records · Page 4Linked to original sources
PubMed1998

Hydrogen peroxide is involved in collagen-induced platelet activation.

In this study, we investigated whether (1) collagen-induced platelet aggregation is associated with a burst of H2O2, (2) this oxidant species is involved in the activation of platelets, and (3) the pathways of platelet activation are stimulated by H2O2. Collagen-induced platelet aggregation was associated with production of H2O2, which was abolished by catalase, an enzyme that destroys H2O2. H2O2 production was not observed when ADP or thrombin were used as agonists. Catalase inhibited dose-dependently thromboxane A2 production, release of arachidonic acid from platelet membrane, and Inositol 1,4,5P3 (IP3) formation. In aspirin-treated platelets stimulated with high concentrations of collagen, catalase inhibited platelet aggregation, calcium mobilization, and IP3 production. This study suggests that collagen-induced platelet aggregation is associated with a burst of H2O2 that acts as a second messenger by stimulating the arachidonic acid metabolism and phospholipase C pathway.

Blood Platelets↗
PubMed1998

Enhanced expression of monocyte tissue factor in patients with liver cirrhosis.

BACKGROUND: Previous studies have shown that cirrhotic patients produce increased amounts of thrombin but the underlying mechanism is still unknown. AIMS: To analyse the relation between the rate of thrombin generation and monocyte expression of tissue factor (TF) in cirrhosis. PATIENTS: Thirty three cirrhotic patients classified as having low (n = 7), moderate (n = 17), or severe (n = 9) liver failure according to Child-Pugh criteria. METHODS: Prothrombin fragment F1 + 2, monocyte TF activity and antigen, and endotoxaemia were measured in all patients. Polymerase chain reaction (PCR) analysis of TF mRNA was performed in monocytes of five cirrhotic patients. RESULTS: Prothrombin fragment F1 + 2 was higher in cirrhotic patients than in controls (p < 0.0001). Monocytes from cirrhotic patients had higher TF activity and antigen than those from controls (p < 0.001) with a progressive increase from low to severe liver failure. Monocyte expression of TF was significantly correlated with plasma levels of F1 + 2 (TF activity: r = 0.98, p < 0.0001; TF antigen: r = 0.95, p < 0.0001) and with endotoxaemia (TF activity: r = 0.94, p < 0.0001; TF antigen: r = 0.91, p < 0.0001). PCR analysis of TF mRNA showed TF expression only in three patients with endotoxaemia (more than 15 pg/ml). CONCLUSIONS: Cirrhotic patients have enhanced expression of TF which could be responsible for clotting activation, suggesting that endotoxaemia might play a pivotal role.

Adult↗
PubMed1998

Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2alpha-III, an index of oxidant stress.

Oxidative stress has been suggested as a potential mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). It has been difficult to address this hypothesis because of the limitations of conventional indices of lipid peroxidation in vivo. F2-isoprostanes (iPs) are prostaglandin isomers formed by free radical dependent peroxidation of arachidonic acid. Urinary iPF2alpha-III is a relatively abundant iPs produced in humans. In the present study, we investigated whether COPD is associated with enhanced oxidative stress by measuring urinary levels of this compound. Urinary excretion of iPF2alpha-III was determined in 38 patients with COPD and 30 sex- and age-matched healthy control subjects. Levels of iPF2alpha-III were significantly higher in patients with COPD (median, 84 pmol/ mmol creatinine; range, 38 to 321) than in healthy controls (median, 35.5 pmol/mmol creatinine; range, 15 to 65) (p < 0.0001). This elevation was independent of age, sex, smoking history, or duration of the disease. An inverse relationship was observed with the level of PaO2 (r = -0.38, p = 0. 019). Aspirin treatment failed to decrease urinary levels of iPF2alpha-III (102 +/- 8 versus 99.2 +/- 7.3 pmol/ mmol creatinine), whereas 11-dehydro TxB2 was significantly reduced (695 +/- 74 versus 95 +/- 10 pmol/mmol creatinine) (p < 0.0001). Elevated levels of iPF2alpha-III (median, 125 pmol/mmol creatinine; range, 110 to 170) in five patients with COPD declined (median, 90 pmol/mmol creatinine; range, 70 to 110) (p < 0.001) as an acute exacerbation in their clinical condition resolved. Increased urinary iPF2alpha-III is consistent with the hypothesis that oxidative stress occurs in COPD. This provides a basis for dose finding and evaluation of antioxidant therapy in the treatment of this disease.

Age Factors↗
PubMed1998

Enhanced lipid peroxidation in hepatic cirrhosis.

BACKGROUND: Lipid peroxidation is thought to play a role in the evolution of liver damage, based on evidence in experimental models. However, evidence that lipid peroxidation occurs in patients with liver disease remains to be provided. We addressed the hypothesis by measuring levels of 8-epi Prostaglandin F2 alpha a bioactive prostaglandin isomer produced by free radical catalyzed peroxidation of arachidonic acid, in patients with liver cirrhosis. METHODS: In 42 patients with hepatic cirrhosis 8-epi Prostaglandin F2 alpha, factor VII activity, endotoxemia, carotenoids and alpha-tocopherol were measured. In 10 patients 8-epi Prostaglandin F2 alpha was also measured before and 30 days after 300 mg b.i.d. vitamin E administration. RESULTS: Cirrhotic patients had significant higher 8-epi Prostaglandin F2 alpha, excretion than controls [median (range): 199.2 (60.0-812) vs 85.9 (55.6-160.0) pg/mg creatinine, p < 0.0001]. Patients with urinary 8-epi Prostaglandin F2 alpha above the range in controls were more likely to have moderate or severe than mild liver failure (p < 0.004). They also had lower factor VII activity (62 +/- 19 vs 74 +/- 15%, P < 0.02) than patients with normal levels of the isoprostane. Urinary excretion of 8-epi Prostaglandin F2 alpha correlated directly with endotoxemia (Rho = 0.56, p < 0.0002) and inversely with factor VII (Rho = -0.39, p < 0.02). Cirrhotic patients given vitamin E showed a significant decrease of urinary 8-epi Prostaglandin F 2 alpha [median (range): 342.5 (170 - 812) vs 292.5 (142-562) pg/mg creatinine, p < 0.04]. CONCLUSION: This study demonstrated that lipid peroxidation is increased in vivo in patients with cirrhosis and suggests that oxidant stress might contribute to the deterioration of liver disease.

Adult↗
PubMed1998

Increased thromboxane metabolites excretion in liver cirrhosis.

An augmented systemic production of thromboxane (TX) A2, as assessed by urinary excretion of the thromboxane metabolites, has been described in severe liver cirrhosis. However, the significance of this finding remains unclear since in liver cirrhosis a number of phenomena i.e. altered hepatic TXA2 metabolism, increased intrasplenic platelet destruction, may affect TXA2 entry into systemic circulation as well as its metabolism. In order to further clarify this, we measured both major enzymatic metabolites of TXB2 in the urine of 44 patients affected by liver cirrhosis, subdivided in three classes on the basis of Child-Pugh criteria. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were assayed with previously validated RIA techniques. The urinary excretion rate of 11-dehydro-TXB2 was significantly (p = 0.0001) increased in the cirrhotic patients (673.5 pg/mg cr, median) in comparison with the controls (275 pg/mg cr, median) but no significant difference could be demonstrated among the excretion rates of the three patient subgroups. The excretion rate of 2,3 dinor-TXB2 was also significantly (p = 0.0001) increased in the patients (824 pg/mg cr, median) in comparison with controls (175 pg/mg cr, median), with a significant (p < 0.05) increase from class A (381 pg/mg cr) to class C (1337 pg/mg cr). The sum of the two enzymatic metabolites was significantly (p = 0.0001 ) increased in the cirrhotic patients in comparison to controls, with a progressive increase from class A (1003 pg/mg cr, median) to class C (2240 pg/mg cr, median). The urinary excretion of 2,3 dinor-TXB2 was significantly (p = 0.008) related to plasma prothrombin fragment 1+2 (F1+2). This study provides further evidence of increased thromboxane biosynthesis in liver cirrhosis. Moreover, we demonstrate intraliver shift of thromboxane metabolic disposition, due to progressive liver decompensation, because only the fraction undergoing beta-oxidation to 2,3-dinor-TXB2 was progressively increased with the degree of liver failure. We, also, find a significant correlation between urinary excretion of 2,3-dinor-TXB2 and plasma F1+2, suggesting that clotting activation could partly account for in vivo platelet activation.

Adult↗
PubMed1998

Determinants of fibrinogen in an Italian population suffering from claudication. Lower fibrinogen in the south compared to middle and north of Italy. The ADEP Group.

BACKGROUND AND OBJECTIVE: Prospective studies have shown that high plasma levels of fibrinogen are independently associated with the risk of cardiovascular complications. In patients suffering from peripheral vascular disease (PVD) fibrinogen has been shown to be an independent predictor of cardiovascular disease but its determinants have never been examined in this clinical setting. DESIGN AND METHODS: Fibrinogen levels were related to clinical and laboratory variables in 2,111 patients suffering from PVD. We also analyzed whether there was a regional distribution of risk factors. RESULTS: The median values of fibrinogen was 312 mg/dL. The clinical variables examined did not differentiate patients with elevated or normal fibrinogen levels. In particular, patients with ankle/arm pressure ratio < 0.8 did not show a higher prevalence of fibrinogen > 312 mg/dL. Conversely, white blood cell (WBC) count and serum cholesterol levels were significantly associated with high fibrinogen levels (p < 0.0001). Multiple logistic regression analysis demonstrated that areas of Italy were differently associated with high plasma fibrinogen levels (p < 0.03): subjects in the north and middle of Italy having significantly higher values of fibrinogen than subjects in the south of Italy (p < 0.01). A similar regional distribution was observed for WBC count and serum cholesterol levels. INTERPRETATION AND CONCLUSIONS: The regional distribution of risk factors raises the question as to whether the already reported large variability of cardiovascular events so in PVD may be attributed to a non homogeneous distribution of risk factors.

Diabetes Mellitus↗
PubMed1998

The benefits of daily hemofiltration in the management of anuria in patients with severe heart failure (NYHA IV).

The aim of the study was to evaluate the daily use of hemofiltration in patients with anuria and heart failure IV NYHA, and not reacting to pharmacological therapy. Patients were submitted to daily hemofiltration therapy considering: the dry weight, BP, pO2, creatininemia, natriemia, kaliemia, and magnesiemia. Every month an echocardiogram and an ECG were done. Two patients passed from IV to III class NYHA, with a reduction in the telediastolic diameter and improvement in the ejection fraction and in the cardiothoracic index. In NYHA IV patients, it was possible to obtain a very good improvement in the clinical situation, echocardiographic parameters and survival with daily hemofiltration.

Aged↗
PubMed1998

Portal levels of the isoprostane F2 alpha-III, a marker of lipid peroxidation, do not correlate with increased portal pressure in cirrhotic patients.

BACKGROUND: Isoprostane F2 alpha-III (iPF2 alpha-III), a recently described member of a family of prostaglandin F2 alpha isomers and a biologically active end-product of lipid peroxidation, has been reported to increase portal pressure in cirrhotic rats. We found that its urinary levels were elevated in cirrhotic patients. METHODS: To investigate whether portal levels of iPF2 alpha-III were elevated in cirrhotic patients and whether there was a relationship between these levels and the portal pressure in the same patients, peripheral and portal plasma from cirrhotic patients (n = 18) undergoing elective transjugular intrahepatic portosystemic shunt and appropriate controls (n = 18) were assayed for iPF2 alpha-III levels by using a gas chromatography/mass spectrometry assay. Portal pressure was measured in all cirrhotic patients. RESULTS: Cirrhotic patients had higher peripheral plasma levels of iPF2 alpha-III [78 (27-150) pg/mL] than controls [18(10-30)pg/mL] (P < 0.001). Portal iPF2 alpha-III levels were higher than plasma peripheral levels [129(50-375) pg/mL; P < 0.0001]. No correlation was found between peripheral and portal levels of iPF2 alpha-III (Rho = 0.17, P = 0.5). Portal levels of iPF2 alpha-III and portal pressure did not correlate (Rho = 0.17, P = 0.49). CONCLUSIONS: This study shows that peripheral and portal levels of iPF2 alpha-III, marker of in vivo lipid peroxidation, are elevated in liver cirrhosis. There is no correlation between iPF2 alpha-III portal levels and the portal pressure observed in these patients. These findings suggest that this biologically active isoprostane does not directly contribute to the portal hypertension observed in hepatic cirrhosis.

Aged↗
PubMed1997

Enhanced lipid peroxidation in patients positive for antiphospholipid antibodies.

The mechanism leading to the formation of antiphospholipid antibodies (aPL) is still unknown. Because an in vitro study suggested that aPL may derive from pro-oxidant conditions, we sought a relationship between aPL and isoprostanes, indices of lipid peroxidation in vivo. Thirty patients with systemic lupus erythematosus have been studied. Seventeen (56.6%) were positive for aPL because they had lupus anticoagulant and/or high titer of anticardiolipin antibodies (aCL). Plasma levels of tumor necrosis factor (TNF ) and urinary excretion of two isoprostanes, 8-epi-PGF2alpha and IPF2alpha -I, free radical catalyzed oxidation products of arachidonic acid, were measured. Patients with systemic lupus erythematosus had higher urinary excretion of 8-epi-PGF2alpha and IPF2alpha -I than controls; urinary excretion of the two isoprostanes was highly correlated (Rho = 0.74, P < .0001). Urinary 8-epi-PGF2alpha was highly correlated with both aCL titer (Rho = 0. 70, P < .0001) and TNF (Rho = 0.84, P < .0001), a measure of disease severity. Excretion of this isoprostane was also higher in those patients who exhibited aPL (P < .0001). Comparable correlations were observed with the isoprostane IPF2alpha -I. No difference of 8-epi-PGF2alpha was observed between patients with and without previous history of thrombosis. This study, showing the existence of a close association between aPL and increased in vivo lipid peroxidation, supports the hypothesis that these antibodies may result from pro-oxidative conditions and suggests that inflammation may play an important role.

Adolescent↗
PubMed1997

Localization of distinct F2-isoprostanes in human atherosclerotic lesions.

F2-Isoprostanes are prostaglandin (PG) isomers formed in situ in cell membranes by peroxidation of arachidonic acid. 8-epi PGF2alpha and IPF2alpha-I are F2-isoprostanes produced in humans which circulate in plasma and are excreted in urine. Measurement of F2-isoprostanes may offer a sensitive, specific, and noninvasive method for measuring oxidant stress in clinical settings where reactive oxygen species are putatively involved. We determined whether isoprostanes were present in human atherosclerotic lesions, where lipid peroxidation is thought to occur in vivo. 8-epi PGF2alpha ranged from 1.310-3.450 pmol/micromol phospholipid in atherectomy specimens compared with 0.045-0.115 pmol/micromol phospholipid (P < 0.001) in vascular tissue devoid of atherosclerosis. Corresponding values of IPF2alpha-I were 5.6-13.8 vs. 0.16-0.44 pmol/micromol phospholipid (P < 0.001). Levels of the two isoprostanes in vascular tissue were highly correlated (r = 0.80, P < 0.0001). Immunohistochemical studies confirmed that foam cells adjacent to the lipid necrotic core of the plaque were markedly positive for 8-epi PGF2alpha. These cells were also reactive with anti-CD68, an epitope specific for human monocyte/macrophages. 8-epi PGF2alpha immunoreactivity was also detected in cells positive for anti-alpha-smooth muscle actin antibody, which specifically recognizes vascular smooth muscle cells. Our results indicate that 8-epi PGF2alpha and IPF2alpha-I, two distinct F2-isoprostanes and markers of oxidative stress in vivo, are present in human atherosclerotic plaque. Quantitation of these chemically stable products of lipid peroxidation in target tissues, as well as in biological fluids, may aid in the rational development of antioxidant drugs in humans.

Adult↗
PubMed1997

Diabetes mellitus, hypercholesterolemia, and hypertension but not vascular disease per se are associated with persistent platelet activation in vivo. Evidence derived from the study of peripheral arterial disease.

BACKGROUND: Previous studies relating increased thromboxane (TX) biosynthesis to cardiovascular risk factors do not answer the question whether platelet activation is merely a consequence of more prevalent atherosclerotic lesions or reflects the influence of metabolic and hemodynamic disturbances on platelet biochemistry and function. METHODS AND RESULTS: We examined 64 patients with large-vessel peripheral arterial disease and 64 age- and sex-matched control subjects. TXA2 biosynthesis was investigated in relation to cardiovascular risk factors by repeated measurements of the urinary excretion of its major enzymatic metabolite, 11-dehydro-TXB2, by radioimmunoassay. Urinary 11-dehydro-TXB2 was significantly (P = .0001) higher in patients with peripheral arterial disease (57 +/- 26 ng/h) than in control subjects (26 +/- 7 ng/h). Seventy percent of patients had metabolite excretion > 2 SD above the normal mean. However, 11-dehydro-TXB2 excretion was enhanced only in association with cardiovascular risk factors. Multivariate analysis showed that diabetes, hypercholesterolemia, and hypertension were independently related to 11-dehydro-TXB2 excretion. During a median follow-up of 48 months, 8 patients experienced major vascular events. These patients had significantly (P = .001) higher 11-dehydro-TXB2 excretion at baseline than patients who remained event free. CONCLUSIONS: The occurrence of large-vessel peripheral arterial disease per se is not a trigger of platelet activation in vivo. Rather, the rate of TXA2 biosynthesis appears to reflect the influence of coexisting disorders such as diabetes mellitus, hypercholesterolemia, and hypertension on platelet biochemistry and function. Enhanced TXA2 biosynthesis may represent a common link between such diverse risk factors and the thrombotic complications of peripheral arterial disease.

Adult↗
PubMed1997

Coexistence of anti-phospholipid antibodies and endothelial perturbation in systemic lupus erythematosus patients with ongoing prothrombotic state.

BACKGROUND: Anti-phospholipid antibodies (aPLs) were associated with an ongoing prothrombotic state in patients with systemic lupus erythematosus (SLE). Because aPLs are able to shift endothelial function toward procoagulant activity in vitro, we investigated the relationship among aPLs, ongoing prothrombotic state, and endothelial perturbation in SLE patients. METHODS AND RESULTS: We measured aPLs, anti-EC antibodies, circulating levels of prothrombin fragment F1 + 2 (F1 + 2), tumor necrosis factor-alpha (TNF-alpha), tissue-type plasminogen activator (TPA), and von Willebrand factor (vWF) in 43 SLE patients and 25 healthy subjects. Patients positive for aPLs (n = 23) had a higher prevalence of anti-EC antibodies (P = .02) and higher levels of F1 + 2 (P = .003) than aPL(-) patients. Endothelial perturbation, defined by elevated plasma levels of both TPA and vWF, was significantly associated with aPL positivity (P = .001). F1 + 2 > 1 nmol/L (mean +/- 2 SD of controls) was detected in all but one patient in whom aPL positivity and endothelial perturbation coexisted and in no aPL(+) patient without endothelial perturbation (P = .0039). F1 + 2 was significantly correlated with vWF (rho = .6, P = .004) and TPA (114 = .70, P = .0006) only in aPL(+) patients. Endothelial perturbation was closely associated with high values of TNF-alpha (P = .0001), anti-phospholipid (P = .001), and anti-EC antibodies (P = .012). In 31 patients without a clinical history of thrombosis followed up for 3 years, aPL(+) patients with endothelial perturbation showed higher F1 + 2 and TNF-alpha values than aPL(+) patients without endothelial dysfunction. CONCLUSIONS: This study shows that in SLE patients, aPL positivity is associated with an ongoing prothrombotic state only in the presence of endothelial perturbation. Our findings also suggest that aPLs and TNF-alpha might cooperate in inducing endothelial perturbation.

Adult↗
PubMed1997

Platelet activation by superoxide anion and hydroxyl radicals intrinsically generated by platelets that had undergone anoxia and then reoxygenated.

BACKGROUND: Platelet activation has been demonstrated in experimental and clinical models of ischemia-reperfusion, but the underlying mechanism is still unclear. We mimicked the ischemia-reperfusion model in vitro by exposing platelets to anoxia-reoxygenation (A-R) and evaluated the role of oxygen free radicals (OFRs), which are usually produced during the reperfusion phase, in inducing platelet activation. METHODS AND RESULTS: Human platelets were exposed to 15 and 30 minutes of anoxia and then reoxygenated. Compared with control platelets kept in atmospheric conditions, platelets exposed to A-R showed spontaneous platelet aggregation (SPA), which was maximal after 30 minutes of anoxia. Superoxide dismutase (SOD) (-74%, P < .005), catalase (-67%. P < .005). SOD plus catalase (-82%, P < .005), and the hydroxyl radical (OH0) scavengers mannitol (-66%, P < .005) and deoxyribose (-55%, P < .005) inhibited SPA. Platelets that had undergone A-R released superoxide anion (0-2), as detected by lucigenin chemiluminescence. Also, platelets exposed to A-R and incubated with salicylic acid generated 2.3- and 2,5-dihydroxybenzoates, which derive from salicylic acid reaction with OH0. SPA was significantly inhibited by the cyclooxygenase enzyme inhibitors aspirin and indomethacin: by SQ29548, a thromboxane (Tx) A2 receptor antagonist; by diphenyliodonium an inhibitor of flavoprotein-dependent enzymes: and by arachidonyl trifluoromethyl ketone, a selective inhibitor of cytosolic phospholipase A2. Platelets exposed to A-R markedly generated inositol 1,3,4-trisphosphate and TxA2, which were inhibited by incubation of platelets with SOD plus catalase. CONCLUSIONS: This study shows that platelets exposed to A-R intrinsically generated 0-2 and OH0, which in turn activate arachidonic acid metabolism via phospholipases A2 and C, and provides further support for the use of antioxidant agents as inhibitors of platelet function in ischemia-reperfusion models.

Acridines↗
PubMed1997

CAPRIE trial.

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Aspirin↗