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S Basili

Publications and source records attributed to S Basili.

At least 37 records · Page 2Linked to original sources
PubMed1999

Soluble P-selectin and proinflammatory cytokines in patients with polygenic type IIa hypercholesterolemia.

Plasma soluble P-selectin (sP-selectin), beta-thromboglobulin (beta-TG), von Willebrand Factor (vWF), prothrombin factor 1+2 (F1+2), IL-6 and IL-1beta levels were analyzed in 35 consecutive patients with polygenic type IIa hypercholesterolemia (HC) and 35 age- and sex-matched healthy subjects. sP-selectin (p < 0.005), beta-TG (p < 0.05) and IL-1beta (p < 0.02) levels were higher in HC patients than healthy subjects whereas no significant difference was observed for vWF. sP-selectin directly correlated with beta-TG (p < 0.05) and IL-1beta levels (p < 0.005), but not with the other variables analyzed. A direct correlation was observed between F1+2 and IL-6 (p < 0.05), total cholesterol (p < 0.05) or LDL cholesterol (p < 0.05). We conclude that HC is associated with an increase of plasma sP-selectin levels, and that sP-selectin may be considered as a marker of in vivo platelet activation in type IIa polygenic HC. The correlations observed among the variables analyzed in the study suggest that proinflammatory cytokines might play a role in the prothrombotic state often associated with HC.

Adult↗
PubMed1999

Clotting activation after transjugular intrahepatic portosystemic stent shunt.

BACKGROUND AND AIM: Aim of the study was to investigate the behaviour of clotting system in peripheral circulation of cirrhotic patients undergoing transjugular intrahepatic portosystemic stent shunt (TIPS). METHODS: Clotting variables and endotoxemia were measured 48 h and 30 days after TIPS in patients randomised to receive heparin or not. RESULTS: Forty-eight hours after TIPS, a significant increase of prothrombin fragment F1+2 was observed; such increase was less evident in patients given heparin. Similar findings were observed for endotoxemia, which, however, was not affected by heparin treatment. Thirty days after TIPS procedure prothrombin fragment F1+2 and endotoxemia returned to baseline values independently of the treatment given. CONCLUSION: This study shows that TIPS is associated with an increase of clotting activation which might contribute to acute thrombosis observed after this procedure.

Adult↗
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↗
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

Lipoprotein (a) serum levels in patients with hepatocarcinoma.

Lipoprotein (a) [Lp(a)] is synthesised by liver cells, and patients with liver cirrhosis (LC) show low serum levels of Lp(a) associated with the degree of liver failure. On the contrary, increased serum levels of Lp(a) have been reported in patients with cancer. In this report, the behaviour of Lp(a) serum levels in patients with hepatocarcinoma (HC), a complication of LC, has been evaluated with the aim to study whether HC cells were able to cause an increase of serum concentrations of this lipoprotein when impaired liver protein synthesis is present. We selected eighteen patients affected by LC + HC, eighteen patients matched for sex, age and degree of liver failure with LC only, and eighteen patients with other cancer types. A significant increase of serum levels of Lp(a) was observed in patients affected by LC + HC or other cancer types compared with healthy subjects. Forty-four percent of LC + HC patients showed Lp(a) values more than 70.4 Units/dl, i.e., the upper limit of values observed in patients with LC only. Lp(a) serum concentrations were significantly associated with serum albumin both in LC and in LC + HC but not in other cancer-type patients. Thus, comparing patients with similar serum albumin concentrations, Lp(a) serum levels were significantly higher in patients with LC + HC than in patients with only LC and quite similar to those observed in patients with other cancer types. In conclusion, HC cells, in vivo, seem able to produce a greater amount of Lp(a) despite the reduced liver protein synthesis typical of LC.

Aged↗
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

Polyol pathway activation and glutathione redox status in non-insulin-dependent diabetic patients.

The current study aimed to evaluate whether nicotinamide adenine dinucleotide phosphate (NADPH) alteration in erythrocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM) is responsible for the impaired glutathione (GSH) redox status, and to assess if short-term inhibition of the polyol pathway normalizes NADPH levels and GSH redox status via an amelioration of the NADPH/total NADP (tNADP) ratio. For this purpose, erythrocyte NADPH and GSH levels were measured in 18 NIDDM patients at baseline and then after 1 week of random double-blind assignment to treatment with either tolrestat (an aldose reductase inhibitor, 200 mg daily) (n = 12) or placebo (n = 6). A group of 16 healthy volunteers served as the control. In the basal condition, mean GSH (P < .0001) and NADPH (P < .0001) levels and NADPH/tNADP (P < .0001) and GSH/ glutathione disulfide (GSSG) (P < .005) ratios were lower in NIDDM patients than in control subjects. Tolrestat treatment increased GSH levels (P < .05 v placebo and baseline) and the NADPH/tNADP ratio (P < .05 v placebo and baseline). Interestingly, tolrestat-induced changes in GSH and NADPH levels and in GSH/GSSG and NADPH/tNADP ratios were significant only in patients who showed a decreased NADPH/tNADP ratio at baseline (n = 8). In these latter patients, we also found a direct correlation between percentage increments in GSH levels and NADPH/tNADP ratios after tolrestat treatment (r = .71, P < .05). In conclusion, our findings support the hypothesis that polyol pathway activation decreases NADPH and GSH levels. Accordingly, short-term inhibition of this enzymatic route increased both the GSH level and the NADPH/tNADP ratio. These changes were observable only in the subgroup of patients with an abnormal NADPH/tNADP ratio at baseline. Polyol pathway inhibition could be useful for decreasing oxidative stress in NIDDM.

Adult↗
PubMed1997

Proinflammatory cytokines and hemostatic system in patients with chronic obstructive pulmonary disease.

The prothrombotic state frequently observed in patients with chronic obstructive pulmonary disease (COPD) may be related to a systemic inflammatory response. In the present study plasma interleukin-6 (IL-6), IL-2 and IL-1beta levels have been investigated in 33 patients with COPD. In vitro platelet activity, plasma C-reactive protein (CRP) and fibrinogen levels were also determined in all patients. The results obtained demonstrated that plasma IL-6 levels were significantly higher in the patient group compared with a control population age and sex-matched ( P < 0.02), while plasma IL-2 and IL-1beta levels were not significantly modified. An overall condition of platelet hyperactivity in COPD patients was also observed. A comparative analysis of platelet activity and blood gas levels demonstrated a correlation between platelet hyperactivity and a severe impairment of oxygen ( P < 0.001) and carbon dioxide tensions ( P < 0.01). Finally, a statistical analysis of the population under study showed the presence of a significant correlation between elevated plasma IL-6 ( P < 0.001) and IL-1beta levels ( P < 0.007), and an increased sensitivity of platelets to arachidonic acid, suggesting a possible correlation between the inflammatory response and the prothrombotic state observed in patients with COPD.

Journal Article↗
PubMed1997

Enhanced thromboxane biosynthesis in patients with chronic obstructive pulmonary disease. The Chronic Obstructive Bronchitis and Haemostasis Study Group.

Thrombotic complications of pulmonary circulation occur in patients with chronic obstructive pulmonary disease (COPD). In the present study, we sought to evaluate in vivo platelet activation through the measurement of 11/dehydro-thromboxane (Tx) B2 TxA2 major metabolite in the urine, in 29 patients with COPD, compared with 29 sex- and age-matched healthy subjects. The urinary excretion of 11-dehydro-TxB2 was significantly higher in patients with COPD than in control subjects: median (range), 753 (277-4,409) and 275 (129-612) pg/mg creatinine, respectively; p < 0.0001). Moreover, 11-dehydro-TxB2 excretion was inversely related with arterial oxygen tension (rho = -0.46; p = 0.0145). In five of the 29 patients a short-term therapeutic course with oxygen supplementation induced a significant decrease of urinary 11-dehydro-TxB2 excretion: median range, 941 (452-2,640) to 445 (166-1,560) pg/mg creatinine. Moreover, selective inhibition of platelet cyclooxygenase activity by low-dose aspirin was associated with more than 90% inhibition of thromboxane metabolite excretion, demonstrating its being of platelet origin. Plasma levels of prothrombin fragment F1 + 2 were higher in patients than in control subjects (2.6 +/- 1.5 versus 0.9 +/- 0.4 nM, p = 0.0001). No relation between 11-dehydro-TxB2 excretion and plasma F1 + 2 levels was found. We conclude that platelet TxA2 biosynthesis is enhanced in patients with COPD and may be influenced by arterial oxygen tension changes.

Aged↗
PubMed1997

Ongoing prothrombotic state in the portal circulation of cirrhotic patients.

Portal thrombosis may complicate the clinical course of cirrhosis, but the pathophysiologic mechanism is unclear. Aim of the study was to evaluate the behavior of clotting system and endotoxemia in portal vein and in peripheral circulation of 11 cirrhotic patients undergoing transjugular port-systemic shunt (TIPS). Portal blood showed higher values of F1 + 2 [Median (range): 2.5 (1.1-5.3) vs. 1.1 (0.6-2.1) nM, p < 0.01], D-dimer [765 (184-1713) vs. 192 (64-813) ng/ml, p < 0.01] and endotoxemia [31 (16-47.2) vs. 13.7 (7.5-23.5) pg/ml, p < 0.01] than peripheral circulation. In the portal vein, all but one sample had F1 + 2 > 1.2 nM (upper limit of control values), all but one had D-dimer > 216 mg/dl (mean + 2 SD of controls) and 100% had values of endotoxemia > 9.6 pg/ml (upper limit of control values). Fibrinogen was lower in the portal circulation compared to peripheral circulation but the difference was not significant [85 (58-195) vs. 134 (75-244) mg/dl, p > 0.05]. Endotoxemia was directly correlated with F1 + 2 (Rho = 0.92 p < 0.006) and D-dimer (Rho = 0.93, p < 0.005). This study shows that an ongoing prothrombotic state is present in the portal circulation of cirrhotic patients and may play a pivotal role in the thrombotic episodes occurring in this clinical setting.

Adult↗
PubMed1997

Systemic clotting activation by low-grade endotoxaemia in liver cirrhosis: a potential role for endothelial procoagulant activation.

BACKGROUND: The pathophysiologic mechanism underlying the association between endotoxaemia and clotting activation in liver cirrhosis is still to be explained. AIMS: To investigate the relationship between endotoxaemia, endothelial perturbation and clotting system activation in liver cirrhosis patients. PATIENTS: The study was carried out in 30 consecutive patients (17 males, 13 females, age range 42 to 71 years) with liver cirrhosis. METHODS: Prothrombin fragment F1 + 2, endotoxaemia, von Willebrand factor and ristocetin cofactor activity were studied in all patients. Von Willebrand factor antigen release and tissue factor expression were also evaluated in cultured endothelial cells incubated with low endotoxin concentrations (125-500 pg/ml). RESULTS: Thirteen (43%) out of 30 liver cirrhosis patients showing von Willebrand factor antigen levels > 157 IU/dl (mean +/- 2SD of controls) were considered to have signs of endothelial perturbation; they had more severe liver failure (p = 0.0001), higher ristocetin cofactor activity (p = 0.0001), endotoxin (p = 0.0001) and prothrombin fragment F1 + 2 (p = 0.0001) plasma values than liver cirrhosis with normal von Willebrand factor antigen. A strong correlation (r = 0.97; p = 0.0001) was found between prothrombin fragment F1 + 2 and von Willebrand factor antigen. In in vitro experiments endotoxin induced a concentration-dependent release of von Willebrand factor antigen (p = 0.0001) and expression of tissue factor activity (p = 0.0001) and antigen (p = 0.0001) from cultured endothelial cells. CONCLUSIONS: This study suggests that the endothelial procoagulant activation induced by low-grade endotoxaemia may represent a trigger for systemic clotting activation in liver cirrhosis patients.

Adult↗