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Biomedical subjects

I Catalano

Publications and source records attributed to I Catalano.

At least 19 recordsLinked to original sources
PubMed1996

Influence of metabolic control on thromboxane biosynthesis and plasma plasminogen activator inhibitor type-1 in non-insulin-dependent diabetes mellitus.

We have previously shown that tight metabolic control by insulin therapy reduced thromboxane-dependent platelet activation in non-insulin-dependent diabetes mellitus (NIDDM) patients. The present study was undertaken to determine whether a similar effect could be obtained without switching diabetics in secondary failure to insulin treatment. For this purpose, we gave strict diet and exercise advise program and adjusted on a weekly basis the oral antidiabetic therapy (glipizide) that 26 patients with NIDDM had been given over the previous months. Basal measurements of urinary 11-dehydro-TXB2 and PAI-1 confirmed previous findings of enhanced levels of these parameters in NIDDM patients with macrovascular disease in comparison to age- and sex-matched controls. After 2-6 weeks, 16 patients achieved tight metabolic control associated with significant reduction of both thromboxane biosynthesis and PAI-1 levels; 10 patients remained in poor control and no significant decrease of both parameters was observed. We conclude that reduction of in-vivo platelet activation and PAI-1 antigen levels after metabolic improvement obtained by frequent reassessment of sulphonylurea therapy together with strict diet and exercise programs may have beneficial effects on the progression of diabetic micro- and macrovascular disease.

Adult↗
PubMed1995

Prolonged inhibition of platelet aggregation after n-3 fatty acid ethyl ester ingestion by healthy volunteers.

This study addressed two questions: 1) whether a relatively low dose of n-3 fatty acid ethyl esters (n-3 FAs) administered to healthy volunteers for a prolonged period of time would exert beneficial effects on plasma lipids, platelet function, and thromboxane biosynthesis; and 2) whether a short-term loading treatment (6 wk) with 6 g n-3 FAs/d followed by 12 wk with 3 g/d results in more pronounced effects. After 6 wk treatment a reduction of plasma triglyceride concentration and an accumulation of EPA and DHA in plasma were observed. A longer period of treatment with n-3 FAs was necessary to affect platelet aggregation and thromboxane A2 biosynthesis. At 12 and 18 wk, platelet aggregation, thromboxane A2 formation, and the excretion of thromboxane metabolites in urine were reduced, particularly in subjects who received 6 g n-3 FAs/d during the initial 6 wk. After treatment ended, triglyceride and thromboxane A2 biosynthesis returned to baseline values within 4 wk, whereas platelet aggregation remained impaired for > or = 14 wk. The longlasting impairment in platelet aggregation was accompanied by the retention of n-3 FAs in platelet phospholipids.

Administration, Oral↗
PubMed1995

Thromboxane biosynthesis, neutrophil and coagulative activation in type IIa hypercholesterolemia.

Thromboxane (Tx) A2 biosynthesis is enhanced in the majority of patients with type IIa hypercholesterolemia. Because blood clotting activation is an important component of the inflammatory response, involved in the initiation and progression of atherosclerotic plaques, we have investigated TxA2 biosynthesis, neutrophil activation and thrombin generation in 24 patients with type IIa hypercholesterolemia. Urinary 11-dehydro-TxB2, was significantly higher (p = 0.0001) in patients than in 24 sex- and age matched healthy subjects. Similarly, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complexes and plasma elastase were significantly higher in patients than in controls. Urinary 11-dehydro-TxB2 excretion was correlated with plasma elastase (r = 0.758; p = 0.0001), and prothrombin fragment 1 + 2 (r = 0.804; p = 0.001). The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (20 mg/day for 2 months) significantly reduced cholesterol levels, urinary 11-dehydro-TxB2 excretion, plasma elastase and plasma F1 + 2 in 8 patients. We conclude that type IIa hypercholesterolemia is associated with biochemical evidence of platelet, neutrophil and blood clotting activation. The relationship between these events remains to be investigated.

Adult↗
PubMed1994

Platelet aggregation, ATP release and cytoplasmic Ca2+ movement: the effects of cloricromene.

A placebo-controlled, double-blind, randomized, cross-over study was performed in 24 healthy volunteers. 12 volunteers received Cloricromene (100mg gastroresistant capsules twice a day) for 7 days, the other volunteers received identical placebo capsules. Subsequently, after a 7-day wash-out period, at day 15, each subject received the other treatment. Blood samples were taken on days 1 and 15 (1st day of each treatment) as well as on days 7 and 21 (7th day of each treatment) before the morning drug administration and 2 and 4 hours later. Platelet aggregation and ATP secretion were studied in whole blood (WB) using ADP and collagen as stimulating agents. Ca2+ fluxes were studied in aequorin-loaded, washed platelets stimulated with ADP and collagen, while aggregation in platelet-rich plasma (PRP) was studied using PAF, ADP and adrenaline as agonists. Consistent inhibition of aggregation and release induced by both ADP and collagen was observed in WB after Cloricromene administration. Similarly, Ca2+ flux was also inhibited after drug administration. Platelet aggregation in PRP was inhibited only after 7 days of Cloricromene treatment with ADP and adrenaline as stimuli. We conclude that oral administration of Cloricromene leads to significant antiplatelet activity in healthy volunteers, in particular when platelets are studied in the presence of other blood elements.

Adenosine Diphosphate↗
PubMed1993

Inhibition of thromboxane biosynthesis and platelet function by indobufen in type II diabetes mellitus.

Indobufen is a reversible inhibitor of platelet prostaglandin G/H-synthase. To verify the dose dependence of the antiplatelet effect of indobufen on ex vivo and in vivo indexes of thromboxane (TX) biosynthesis and TXA2-dependent platelet function, we studied nine patients with non-insulin-dependent diabetes mellitus (NIDDM). This was a randomized, double-blind, crossover study in which each patient was treated with three different daily regimens (50 mg BID, 100 mg BID, and 200 mg BID) of indobufen for 1 week, with a 7-day washout period between treatments. Urinary 11-dehydro-TXB2 excretion averaged 58.2 +/- 21.8 ng/h at baseline. TX metabolite excretion was reduced dose dependently by indobufen: by 67% at 50 mg BID, 72% at 100 mg BID, and 81% at 200 mg BID. Platelet cyclooxygenase activity, ATP release, collagen-induced platelet aggregation, and bleeding time also were modified dose dependently by indobufen. Biochemical demonstration of suppressed platelet TXA2 in vivo was accompanied by evidence of inhibited platelet function as assessed ex vivo. Under pathophysiological conditions, such as NIDDM, which are associated with enhanced TXA2 synthesis, more than 95% suppression of platelet cyclooxygenase activity may be necessary to produce virtually maximal inhibition of platelet TXA2 biosynthesis in vivo.

Aged↗
PubMed1993

Abnormally high thromboxane biosynthesis in homozygous homocystinuria. Evidence for platelet involvement and probucol-sensitive mechanism.

Homocystinuria due to homozygous cystathionine beta-synthase deficiency is an inborn error of metabolism characterized by a high incidence of thrombosis and premature atherosclerosis. We evaluated TXA2 biosynthesis in vivo and several in vitro tests of platelet function in 11 homocystinuric patients and 12 healthy controls. In vitro, patients' platelet aggregation was within control values as were TXB2 formation, fibrinogen binding, and ATP secretion in response to thrombin. In contrast, the urinary excretion of 11-dehydro-TXB2, a major enzymatic derivative of TXA2, was > 2 SD of controls in all patients (1,724 +/- 828 pg/mg creatinine, mean +/- SD, in patients vs. 345 +/- 136 in controls, P < 0.001). The administration to four patients of low-dose aspirin (50 mg/d for 1 wk) reduced metabolite excretion by > 80%. The recovery of 11-dehydro-TXB2 excretion over the 10 d that followed aspirin cessation occurred with a pattern consistent with the entry into the circulation of platelets with intact cyclooxygenase activity. Prolonged partial reduction in the abnormally high excretion of both 11-dehydro-TXB2 and 2,3-dinor-TXB2, was also observed in seven patients who ingested 500 mg daily for 3 wk of the antioxidant drug probucol. These results provide evidence for enhanced thromboxane biosynthesis in homocystinuria and for its partial dependence on probucol-sensitive mechanisms. Furthermore, the elevated TXA2 formation in homocystinuria is likely to reflect, at least in part, in vivo platelet activation.

Adolescent↗
PubMed1992

Effects of defibrotide on fibrinolytic activity in diabetic patients with stable angina pectoris.

18 type II diabetes mellitus patients with coronary artery disease (CAD) have been studied. Tissue plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) antigen and activity, thrombin-antithrombin III (TAT) complexes were determined in blood samples. Diabetic CAD patients showed higher TAT levels with clearly increased PAI levels whereas t-PA levels levels were similar in patients and controls. Long term defibrotide treatment induced marked changes in fibrinolytic parameters of these diabetic patients with CAD with increased t-PA activity, that could be related to an evident reduction of PAI antigen and activity. Drugs able to modulate PAI activity may be useful in clinical conditions at high risk of thrombotic vascular complications like diabetics with stable angina.

Aged↗
PubMed1992

Increased thromboxane biosynthesis in type IIa hypercholesterolemia.

BACKGROUND: Increased platelet thromboxane (TX)A2 production has been described in type IIa hypercholesterolemia. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo, we studied the urinary excretion of its major enzymatic metabolites in 46 patients with type IIa hypercholesterolemia and 20 age-matched controls. METHODS AND RESULTS: Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. The excretion rate of 11-dehydro-TXB2 was significantly (p less than 0.001) higher in patients (68.7 +/- 35.1 ng/hr, mean +/- SD) than in controls (22.4 +/- 9.4 ng/hr), with metabolite excretion greater than 2 SD of the normal mean in 74% of the patients. Urinary 11-dehydro-TXB2 was significantly (p less than 0.01) correlated with the threshold aggregating concentration of collagen (r = -0.641) and arachidonate (r = -0.734) and with agonist-induced platelet TXB2 production in vitro (r = 0.647 and 0.748, respectively). Moreover, a statistically significant correlation (r = 0.673, p less than 0.001, n = 66) was found between 11-dehydro-TXB2 excretion and total plasma cholesterol. The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (20 mg/day for 6 months) significantly reduced cholesterol levels by 22-28% and urinary 11-dehydro-TXB2 excretion by 32-42% in 10 patients. However, the reduction in the latter did not correlate with the reduction in the former and may have resulted from a nonspecific effect of simvastatin. Moreover, selective inhibition of platelet cyclooxygenase activity by low-dose aspirin (50 mg/day for 7 days) was associated with cumulative inhibition of 11-dehydro-TXB2 excretion by approximately 70% in six patients. CONCLUSIONS: TXA2 biosynthesis is enhanced in the majority of patients with type IIa hypercholesterolemia; this is, at least in part, a consequence of abnormal cholesterol levels, as suggested by the correlation between the two. Low-dose aspirin can largely suppress increased metabolite excretion, thus suggesting that it reflects TXA2-dependent platelet activation in vivo.

Adult↗
PubMed1991

Increased plasminogen activator inhibitor antigen levels in diabetic patients with stable angina.

PAI-1 antigen, tPA antigen and thrombin - antithrombin III complexes (TAT) levels were measured in 10 males with stable angina and type-II diabetes mellitus and in 16 males with stable angina without diabetes or other risk factors (hyperfibrinogenaemia, hyperlipidaemia, diabetes, hypertension, smoking and obesity) known to increase PAI levels. Ten healthy men of equivalent age served as controls. Because only diabetics with coronary artery disease (CAD) showed a decreased fibrinolytic capacity, a second study was performed on the 16 non-diabetic CAD patients to determine whether submaximal workload induces significant changes of tPA and PAI levels. TAT levels were increased in CAD, and significantly so in the diabetic group. tPA levels were increased only in the CAD patients without diabetes. PAI levels were significantly increased in diabetic CAD patients (5.26 +/- 1.96 ng/ml) but not in the stable angina patients without diabetes (2.97 +/- 1.44 ng/ml). Immunologically-reactive tPA released after exercise was higher in the 16 CAD patients without diabetes than in controls. Our data could indicate that in stable angina without diabetes there is no chronic latent activation of the clotting system, with no impairment of fibrinolytic activity. On the other hand, the presence of diabetes mellitus seems to influence the fibrinolytic capacity in CAD, particularly increasing PAI levels.

Adult↗
PubMed1990

Thromboxane biosynthesis and platelet function in type II diabetes mellitus.

It has been suggested that platelet hyperreactivity in patients with diabetes mellitus is associated with increased platelet production of thromboxane. We therefore compared the excretion of a thromboxane metabolite and platelet function in 50 patients with Type II diabetes mellitus who had normal renal function and clinical evidence of macrovascular disease and in 32 healthy controls. The mean (+/- SD) excretion rate of urinary 11-dehydro-thromboxane B2 was significantly higher in the patients than in the controls (5.94 +/- 3.68 vs. 1.50 +/- 0.79 nmol per day; P less than 0.001), irrespective of the type of macrovascular complication. Tight metabolic control achieved with insulin therapy reduced the levels of 11-dehydro-thromboxane B2 by approximately 50 percent. The fractional conversion of exogenous thromboxane B2 (infused at a rate of 4.5, 45.3, or 226.4 fmol per kilogram of body weight per second) to urinary 11-dehydro-thromboxane B2 was assessed in four patients, in whom it averaged 5.4 +/- 0.1 percent; this value did not differ from that measured in healthy subjects. Aspirin in low doses (50 mg per day for seven days) reduced urinary excretion of the metabolite by approximately 80 percent in four patients. The fact that thromboxane biosynthesis recovered over the following 10 days was consistent with a platelet origin of the urinary metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Platelet function in hypo- and hyperthyroidism.

Alterations in cardiovascular hemodynamics are found in patients with hypofunction of the thyroid. Frank hypothyroidism favours the development of coronary heart disease. Platelets are thought to be important in atherosclerotic lesions initiation and progression. We studied platelet sensitivity to several agonists and to a physiological antagonist, prostacyclin, and thromboxane production in patients with hyperthyroidism and hypothyroidism. No statistically significant differences were found between platelets activities in patients and control subjects. We conclude that increased platelet function is not a direct indicator of susceptibility to cardiovascular diseases in patients with hypothyroidism whereas the hyperdynamic state, cardinal manifestation of thyrotoxicosis, is not associated with platelet activation.

Adult↗
PubMed1989

Platelet function in patients with type 2 diabetes mellitus: the effect of glycaemic control.

In the present study the effects of a short term intensive glycaemic control obtained with subcutaneous insulin therapy on lipids and apoprotein levels, platelet aggregation, platelet sensitivity to prostacyclin and platelet thromboxane production were investigated in 20 patients with type 2 diabetes and vascular disease. In 11 out of the 20 patients there was a significant improvement of glycaemic control (fructosamine reduction). Only with tight improvement of glycaemic control there was significant change in the concentration of ADP and collagen required to produce 50% of the maximum aggregation wave response, in the responsiveness of platelet to PGI2 and in the TxB2 synthesis. Lower Apo B levels were also shown in the tight control group suggesting that Apo B changes may have influenced platelet aggregation and thromboxane synthesis.

Adult↗
PubMed1989

[Antiplatelet effects of combined therapy with ticlopidine and low doses of aspirin on patients with ischemic cardiopathy].

The aim of study was to evaluate the effects on platelet function, in 8 patients with ischemic heart disease, of the following treatments administered consecutively: ticlopidine in a daily dose of 500 mg (10 days); aspirin in a daily dose of 50 mg (10 days); ticlopidine plus ASA, at the same dosages, for the last 10 days. Only ticlopidine plus ASA significantly inhibited EC 50 of ADP, collagen and arachidonate. Platelet activation and platelet sensitivity to prostacyclin was affected by ticlopidine and ticlopidine plus ASA but not by ASA alone. We conclude that in our ischemic heart disease patients the association of ticlopidine and low dose aspirin seems superior to each drug alone in inhibiting platelet activity.

Aged↗
PubMed1988

In vitro effects of gallopamil on platelet aggregation and thromboxane generation.

The in vitro effects of gallopamil, a highly specific calcium-channel blocker, on platelet function were investigated. Gallopamil caused a dose-dependent inhibition of platelet aggregation. In fact, the drug in concentrations as low as 0.5 microgram/ml inhibited platelet activating factor and epinephrine-induced platelet aggregation. Similarly, the inhibition of adenosine diphosphate and epinephrine-induced thromboxane generation was demonstrated. Since platelet activation and thromboxane release may be related to myocardial ischemia, it is conceivable that some of the antianginal effects of gallopamil may in part be due to platelet inhibitory effects.

Blood Platelets↗