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Biomedical subjects

W Terres

Publications and source records attributed to W Terres.

54 records · Page 3Linked to original sources
PubMed1992

Prevalence and mechanism of streptokinase-induced platelet stimulation. Effect of acetylsalicylic acid.

It was recently shown that streptokinase may induce clot formation in vivo by immunoglobulin G mediated platelet stimulation. We evaluated the in vitro effect of streptokinase on platelet function in 103 subjects, of whom 52 were < or = 30 years and 51 were > or = 50 years old. Although streptokinase inhibited platelet aggregation in the majority of cases, in nine the threshold concentration of ADP required to induce irreversible aggregation decreased with streptokinase (1 million Units. l-1) by 30% or more. This observation was confirmed in five of the nine by repeated measurements indicating reproducible streptokinase-induced platelet stimulation. Among the five, two were < or = 30, and three were > or = 50 years old. In none of the five subjects did the radio allergo sorbent test detect type E immunoglobulins directed against streptokinase in the serum. In contrast, in four of the five subjects, streptokinase-induced platelet hyperaggregability was suppressed by addition of goat antibodies against human immunoglobulin G, or F(ab')2-fragments of such antibodies. Acetylsalicylic acid did not prevent streptokinase-induced platelet stimulation, but in three of five cases, led to an increase in the control threshold concentration for ADP, so that after the decrease induced by streptokinase the threshold concentration for ADP was in the same range as before acetylsalicylic acid and streptokinase administration. Thus, streptokinase led to an inhibition of platelet aggregation in the majority of subjects evaluated. In a minority of five out of 103, however, streptokinase reproducibly caused platelet stimulation, presumably mediated by immunoglobulin G.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Residual platelet function under acetylsalicylic acid and the risk of restenosis after coronary angioplasty.

Restenosis after percutaneous transluminal coronary angioplasty (PTCA) was shown not to be preventable by antiplatelet therapy; residual platelet function under treatment with platelet inhibitors could be one cause of this. Therefore, in a prospective investigation, residual platelet function was assessed in 98 patients treated with acetylsalicylic acid (ASA) on three occasions during the first 3 months after successful PTCA. Control cardiac catheterization was obtained in 75 of these patients (77%) with 82 dilated stenoses 173 +/- 117 days after PTCA. Restenosis, defined as diameter stenosis greater than or equal to 50% at control angiography, occurred in 41% of the dilated vessels, and 43% of patients experienced restenosis in at least one vessel. The in vitro platelet aggregatory response to either ADP (0.5, 1, and 10 microM) or collagen (1 and 5 mg/L) as aggregating agents did not differ between patients with and without restenosis. In addition, neither the collagen-stimulated in vitro synthesis of thromboxane nor the basal or prostaglandin E1-stimulated concentrations of cyclic AMP in platelet-rich plasma (PRP) was different in the two groups. There was no significant correlation between any of the parameters of platelet function assessed and the change in coronary luminal diameter observed between immediately after PTCA and control coronary angiography. The mean dose of ASA ingested during follow-up was also not a determinant of the occurrence of restenosis. Thus, residual platelet function under treatment with ASA as measured in vitro in this study, did not influence the occurrence of restenosis after successful PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1992

[Cardiovascular risk factors and restenosis after PTCA].

We prospectively investigated the influence of the cardiovascular risk factors hypercholesterolemia, smoking, diabetes mellitus, and arterial hypertension on the occurrence and extent of restenosis after successful coronary dilatation (PTCA). Of the 103 patients included in the study, control coronary angiography was obtained in 75 (73%) after 173 +/- 117 days. The restenosis rate (82 stenoses), defined as greater than or equal to 50% loss of initial gain in percent diameter stenosis, was 37%. Older age, male gender, and a history of diabetes mellitus were associated with a significantly increased mean extent of restenosis (p less than 0.05). In patients with hypertension, the initial success of dilatation was less than in controls without hypertension (p less than 0.05), and restenosis tended to be enhanced (p = 0.06). The risk of restenosis was unaffected by smoking and the presence of hypercholesterolemia. In spite of the mostly insignificant influence of single cardiovascular risk factors, the extent of restenosis clearly increased with the number of risk factors.

Aged↗
PubMed1991

Age, cardiovascular risk factors and coronary heart disease as determinants of platelet function in men. A multivariate approach.

Older age, the cardiovascular risk factors and arteriosclerosis have been reported to be associated with stimulated platelet function. To evaluate the relative importance of these factors in determining platelet function, a cross-sectional multivariate study in 191 men, 113 healthy subjects and 78 patients with angiographically documented coronary heart disease, was performed. In healthy subjects, stepwise multiple linear regression identified age to be a major determinant of platelet aggregability. After induction with both ADP and collagen the platelet aggregatory response markedly increased with age. In the patients, platelet function was not age dependent. In multivariate analysis of variance, neither smoking status nor hypercholesterolemia (greater than or equal to 240 mg/dl) were determinants of platelet function in either group. An increase in systolic blood pressure was associated with slightly more inhibited ADP induced aggregation in both healthy subjects and patients with coronary heart disease. In patients compared to healthy subjects, aggregation after induction with ADP and collagen was markedly enhanced and the in vitro formation of thromboxane after collagen stimulation increased. Thus, by multivariate analysis, age and the presence or absence of coronary heart disease were found to be major determinants of platelet function. In contrast, the cardiovascular risk factors smoking, hypercholesterolemia and hypertension were associated with only minor or no alterations of platelet function.

Adult↗
PubMed1991

[Low-dose fish oil in primary hypertriglyceridemia. A randomized placebo-controlled study].

In a double-blind, randomized, placebo-controlled trial, we prospectively investigated the effects of two low doses of fish oil (10.5 and 5.25 g daily) in capsule form in patients with primary hypertriglyceridemia. During a 6 weeks' therapy with 10.5 g fish oil, serum triglycerides decreased by a mean of 38% from 578 +/- 167 to 358 +/- 66 mg/dl (p less than 0.05). With 5.25 g daily, triglyceride levels fell by 20% from 538 +/- 100 to 431 +/- 64 mg/dl (n.s.). With placebo, triglycerides increased by 8% from 835 +/- 176 to 900 +/- 228 mg/dl (n.s.). Total and HLD-cholesterol levels remained uninfluenced in all groups. Serum alkaline phosphatase decreased by a mean of 12% from 86 +/- 7 to 76 +/- 6 units/l in the patients treated with 10.5 g fish oil (p less than 0.01). Platelet aggregation after induction with collagen was slightly, but significantly inhibited in the patients treated with the higher dose of fish oil. Thus, in patients with primary hypertriglyceridemia, fish oil at a daily dose of 10.5, but not at 5.25 g, led to a significant reduction of serum triglyceride levels and to an inhibition of platelet aggregation.

Cholesterol↗
PubMed1990

Effects of streptokinase, urokinase, and recombinant tissue plasminogen activator on platelet aggregability and stability of platelet aggregates.

STUDY OBJECTIVE: The aim of the study was to evaluate the effects of streptokinase, urokinase and recombinant tissue plasminogen activator (TPA) on platelet aggregability and metabolism and the stability of preformed platelet aggregates. DESIGN: The experiments (n = 15 for each condition) were performed on citrated plasma or on platelet suspensions in phosphate buffered saline, both with a standardised platelet count of 250 x 10(9).litre-1. SUBJECTS: were healthy volunteers. MEASUREMENTS AND MAIN RESULTS: With both ADP (1 mumol.litre-1) and collagen (1 mg.litre-1) as aggregating agents, streptokinase at greater than or equal to 10(5) units.litre-1 led to reduction in the rate of platelet aggregation. With collagen and in most instances with ADP, this was associated with a decreased extent of aggregation, though in five out of 30 cases with ADP as aggregating agent, a conversion from reversible to irreversible aggregation occurred with streptokinase. Urokinase inhibited platelet aggregation at greater than or equal to 3 x 10(5) units.litre-1 with both aggregating agents. TPA inhibited aggregation at greater than or equal to 1 mg.litre-1 with ADP and at greater than or equal to 3.3 mg.litre-1 with collagen as aggregating agent. The inhibitory effect was still present when the platelets were suspended in saline. Platelet synthesis of thromboxane on stimulation with collagen, and of c-AMP on stimulation with prostaglandin E1, was markedly reduced by either agent. The stability of platelet aggregates, as assessed photometrically during a 90 min exposure to stirring stress, increased when streptokinase or urokinase was added to platelet rich plasma, but remained uninfluenced with TPA. CONCLUSIONS: Urokinase and TPA inhibited platelet aggregability uniformly and in a dose dependent manner. Streptokinase inhibited platelet aggregation in most instances, but led to a stimulation of aggregation in a minority of cases. These effects of the thrombolytic agents on platelets might have an influence on the occurrence of bleeding and of reocclusion after thrombolytic therapy.

Adenosine Diphosphate↗
PubMed1989

[Effects of low-dose acetylsalicylic acid on thrombocytes in health subjects and in patients with coronary heart disease].

The effects on platelet function of a four-week administration of aspirin at a low dosage (100 mg daily) were compared in two groups, 14 healthy young volunteers and 14 patients with coronary heart disease. In both groups there occurred a clear inhibition of platelet aggregation with collagen (1 and 5 micrograms/l) and arachidonic acid (1 mmol/l) during the aspirin period. The inhibitory effect reached its maximum after three days, remaining at maximum for the remainder of the four weeks. Platelet functions returned to normal within eight days of discontinuing aspirin. The inhibitory effects went together with a definite in-vitro decrease in thromboxane synthesis. In both groups there was no change in aggregation velocity with adenosine diphosphate (ADP) as aggregation-inducing substance, while the frequency of irreversible aggregation decreased with submaximal concentrations of ADP (0.5 and 1.0 mumol/l). The results indicate that low-dose aspirin causes a definite inhibition of platelet function, in a similar manner, in both healthy subjects and patients with coronary heart disease.

Adenosine Diphosphate↗
PubMed1989

Effects of chronic treatment with adrenaline or propranolol on platelet function and c-AMP levels in the rat.

Most of our knowledge about the modulation of platelet function by catecholamines is based on observations of acute in vitro actions. Little is known about the effects of chronically elevated or reduced adrenergic stimulation of the platelets. We therefore treated rats for 8 weeks with either adrenaline or the beta-blocker propranolol. Adrenaline (0.5 mg.kg-1.d-1) continuously administered from subcutaneously implanted osmotic mini pumps caused an increase in the sensitivity of the platelets towards ADP as stimulating agent. In contrast, chronic application of propranolol (10 mg.kg-1.d-1) via the drinking water led to a reduction in platelet aggregability. For animals treated with adrenaline, in accordance with the results of the aggregation experiments, the levels of c-AMP found in platelet rich plasma were reduced, both basally (by 33%) and after stimulation of platelet adenylate cyclase with prostaglandin E1 (by 39%). For the propranolol treated animals, the basal c-AMP concentrations remained unchanged. The levels of c-AMP attained after stimulation with prostaglandin E1 were diminished to a similar extent as for the adrenaline treated animals (by 38%). Although the in vitro addition of adrenaline to platelet rich plasma causes a beta-adrenoceptor mediated inhibition of platelet aggregation in the rat, the simulation seen after chronic adrenaline exposure in vivo, which is associated with decreases in both basal and stimulated c-AMP levels, suggests a functional preponderance of alpha-adrenoceptors over beta-adrenoceptors on the rat platelets. Although intraplatelet metabolic changes (blockade of stimulated c-AMP formation) after chronic application of propranolol should have resulted in enhancement of platelet aggregability, an inhibition of aggregation was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1989

Inhibition of platelet aggregation following chronic in vivo treatment of rats with nicotine: prevention by simultaneous application of propranolol.

Platelet aggregability is known to be enhanced and platelet-survival time shortened in smokers when compared with nonsmokers. Up to now it is unknown which of the substances in tobacco smoke are responsible for these effects. To evaluate a possible role of nicotine, rats were chronically treated with the alkaloid (10 mg/kg/day), continuously released from subcutaneously implanted osmotic minipumps. Surprisingly, after 8 weeks, platelet sensitivity toward the aggregating stimulus adenosine 5'-diphosphate (ADP) was markedly reduced. The mean ADP concentration required to induce half the maximum rate of aggregation (EC50) was 0.88 mumol/L in nicotine-treated animals, as compared with 0.67 mumol/L in controls (p less than 0.002). Platelet aggregability remained normal when the rats were treated simultaneously with nicotine and the beta blocker propranolol (3.5 mg/kg/day); for these animals, the mean EC50 for ADP was 0.73 mumol/L. These results are suggestive of a catecholamine-mediated action of nicotine. However, neither the basal levels of cAMP in platelet-rich plasma, nor the cAMP levels attained after stimulation of platelet adenylate cyclase with prostaglandin E1 (PGE1), were affected by 8 weeks of treatment with nicotine or nicotine plus propranolol. No effect on platelet aggregation was observed when the rats were treated with nicotine for only 2 weeks, or when nicotine or nicotine plus cotinine were added to platelet-rich plasma in vitro in concentrations equal to those attained in vivo after 8 weeks. Thus, prolonged application of nicotine in vivo caused an inhibition of ADP-induced rat platelet aggregation presumably mediated by beta-catecholaminergic stimulation of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1989

Effects of aspirin and prostaglandin E1 on in vitro thrombolysis with urokinase. Evidence for a possible role of inhibiting platelet activity in thrombolysis.

The formation of thrombi in vivo includes the activation of both platelets and the coagulation cascade. Conventional thrombolytic therapy is primarily directed toward the dissolution of fibrin. To evaluate the possibility that platelet activity impairs the lysis of thrombi, we studied the effects of aspirin and platelet-deaggregating prostaglandin E1 on thrombolysis with urokinase. Combined platelet and fibrin thrombi were produced in vitro by adding CaCl2 and collagen (1 microgram/ml) to citrated platelet-rich plasma (250,000 platelets per microliters). Urokinase (500-10,000 units/ml) caused a dose-dependent weight loss of the thrombi that was maximal at 2,000 units/ml. The addition of aspirin (10-200 micrograms/ml) to platelet-rich plasma before thrombus formation markedly enhanced thrombolysis with urokinase. This effect was most pronounced at 20 micrograms/ml aspirin. However, when aspirin was added after completion of thrombus formation, no significant effect on thrombolysis was noted. Prostaglandin E1 (1-100 mumol/l) improved the lysis with urokinase of the combined platelet and fibrin thrombi. This effect was maximal at 20 mumol/l prostaglandin E1. When pure fibrin thrombi were produced in platelet-free plasma, prostaglandin E1 was without effect on lysis. Thus, in vitro lysis with urokinase of combined platelet and fibrin thrombi was enhanced by the addition of platelet-deaggregating prostaglandin E1 and by pretreatment with aspirin.

Adult↗
PubMed1989

[Lipid-lowering and anti-aggregating effect of low-dose therapy with fish oil].

Fifteen healthy volunteers were treated for 30 days with 5 g daily fish oil in capsule form (MaxEPA). After that time, serum triglycerides had decreased by a mean of 26% (p less than 0.05). This relative decrease in triglycerides was the larger the higher were the baseline levels before the start of therapy (p less than 0.01). Total cholesterol remained unchanged with fish oil. HDL-cholesterol showed a small mean increase by 12% (p less than 0.10). The rate of platelet aggregation after induction with collagen 1 microgram/ml was reduced after 30 days of therapy (p less than 0.05), while no effect on platelets was observed with collagen 5 micrograms/ml or ADP (0.5, 1 and 10 mumol/l) as aggregating agents. In vitro thromboxane synthesis after stimulation with collagen (1 microgram/ml) or arachidonic acid (1 mmol/l) was inhibited cumulatively by fish oil and, after 30 days, reached 56% (p less than 0.02) and 44% (p less than 0.05) of the initial values, respectively. Both the basal and prostaglandin E1 stimulated concentrations of c-AMP in platelet rich plasma remained uninfluenced. Thus, the ingestion of a low dose of fish oil by young and healthy subjects led to significant changes in serum triglycerides and platelet function.

Administration, Oral↗
PubMed1988

[Thrombocyte function in unstable angina pectoris].

In a prospective study, platelet aggregation in platelet-rich plasma after ADP stimulation (0.5, 1.0 and 10 mumol/l) and collagen (1 and 5 micrograms/ml) was measured in 36 patients with coronary heart disease, 18 with angina at rest during the eight hours preceding the time of blood sampling, and 18 patients with stable, exercise-dependent angina, matched for age and sex. In addition, c-AMP was determined, before and (as a measure of platelet adenylate cyclase activity) after stimulation of this enzyme by prostaglandin E1 (10 mumol/l for 30 sec). There were no differences between all the tested ADP and collagen concentrations with regard to platelet aggregation. c-AMP levels were also similar. Thus, in patients with unstable angina there was no evidence for generalized hyperaggregation of platelets in comparison with control subjects who had stable exercise-dependent angina.

Adenosine Diphosphate↗
PubMed1988

Blood platelet function after chronic treatment of rats and guinea pigs with nicotine.

To establish whether long-term application of nicotine can at all alter thrombocyte function, the alkaloid was administered to rats and guinea pigs for up to 8 weeks, using subcutaneously implanted ALZET minipumps. These two species were examined, since rat platelets are known to possess both alpha 2- and beta 2-adrenoceptors, whereas guinea pig platelets have practically none of either type. Platelet activity was assessed ex vivo by determining rates of ADP-induced aggregation and by applying a new in vitro technique giving a measure of primary hemostasis. Nicotine in doses of 2 mg/kg/day (rats) and 10 mg/kg/day (guinea pigs), continuously applied over 8 weeks, yielded alkaloid plasma levels in the respective species in the same range as found for smokers. This chronic in vivo pretreatment had no discernible effect on platelet function. However, platelets from rats having received the higher dose of 10 mg nicotine/kg/day for 8 weeks required a significantly higher concentration of ADP to induce the half-maximal rate of aggregation. Concomitantly, the in vitro determined bleeding time doubled. The nicotine-induced decrease in platelet sensitivity towards ADP could be prevented by simultaneously treating the rats with the beta-blocker propranolol. Adrenaline applied chronically to rats for 8 weeks stimulated platelet response instead of mimicking nicotine effects. The unexpected inhibition of rat platelet function at higher alkaloid-dosage thus seems to be an indirect nicotine action, mediated via platelet beta-adrenoceptors. Since chronic treatment with adrenaline did not exert such an effect, the action of nicotine may, rather, be attributed to increases in endogenous noradrenaline. These results could explain varying responses of human blood platelets in smokers.

Animals↗
PubMed1986

Increasing platelet aggregability after venepuncture is platelet, not plasma derived.

The time course of ADP induced aggregation of human platelets was determined in aliquots of stored platelet rich plasma 3.5, 10, 30 and 100 minutes after venepuncture. The maximal rate of aggregation was found to increase throughout this entire period, even though pH (7.4), CO2 (7 volume per cent) and temperature (35 degrees C) of the samples were kept constant. The mean acceleration (+/- SEM) between 3.5 and 100 minutes was 41.7 +/- 6.9 per cent (n = 67) at an ADP-concentration of 1 mumol/l and 18.3 +/- 6.2 per cent (n = 23) at 2 mumol/l ADP. The effect did not result from changes of any platelet regulatory factors putatively present alone in the plasma. Acceleration of aggregability was only found when the platelets themselves underwent storage, but not when freshly prepared plasma was given to prestored platelets. The change in aggregability was not diminished after inhibition of platelet cyclooxygenase by oral administration of acetylsalicylic acid.

Adenosine Diphosphate↗