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Biomedical subjects

J Vermylen

Publications and source records attributed to J Vermylen.

At least 199 records · Page 11Linked to original sources
PubMed1987

Continuous inhibition of serotonin-induced platelet aggregation during chronic ketanserin administration to man can be detected after plasma pH control.

Ketanserin is a well-known serotonin S2 receptor antagonist but its capacity to inhibit serotonin-induced aggregation ex vivo during chronic administration has been a matter of debate. In vitro evidence is presented that the inhibitory capacity of ketanserin is lowered by increasing plasma pH. Since the pH of plasma kept at the open air increases with time, we studied the effect of chronic administered ketanserin on serotonin-induced platelet aggregation in plasma kept at a lowered pH of 7.70, by replacing the air with 95% O2-5% CO2. Using this slightly modified technique, we could, in contrast to our previous studies, observe a complete inhibition of the serotonin-induced aggregation throughout the ketanserin treatment period.

Humans↗
PubMed1987

Role of proaggregatory and antiaggregatory prostaglandins in hemostasis. Studies with combined thromboxane synthase inhibition and thromboxane receptor antagonism.

Thromboxane synthase inhibition can lead to two opposing effects: accumulation of proaggregatory cyclic endoperoxides and increased formation of antiaggregatory PGI2 and PGD2. The elimination of the effects of the cyclic endoperoxides by an endoperoxide-thromboxane A2 receptor antagonist should enhance the inhibition of hemostasis by thromboxane synthase blockers. We have carried out a series of double-blind, placebo-controlled, crossover studies in healthy volunteers to check if this hypothesis may be operative in vivo in man. In a first study, in 10 healthy male volunteers, the combined administration of the thromboxane receptor antagonist BM 13.177 and the thromboxane synthase inhibitor dazoxiben gave stronger inhibition of platelet aggregation and prolonged the bleeding time more than either drug alone. In a second study, in 10 different healthy male volunteers, complete inhibition of cyclooxygenase with indomethacin reduced the prolongation of the bleeding time by the combination BM 13.177 plus dazoxiben. In a third study, in five volunteers, selective cumulative inhibition of platelet TXA2 synthesis by low-dose aspirin inhibited platelet aggregation and prolonged the bleeding time less than the combination BM 13.177 plus dazoxiben. In vitro, in human platelet-rich plasma stimulated with arachidonic acid, the combination of BM 13.177 and dazoxiben increased intraplatelet cAMP while the single drugs did not affect it. Our results indicate that prostaglandin endoperoxides can partly substitute for the activity of TXA2 in vivo in man and that an increased formation of endogenous antiaggregatory and vasodilatory prostaglandins, as obtained with selective thromboxane synthase inhibitors, may contribute to the impairment of hemostasis.

Adult↗
PubMed1987

Sodium fluoride mimics effects of both agonists and antagonists on intact human platelets by simultaneous modulation of phospholipase C and adenylate cyclase activity.

Using intact human platelets, we studied the effect of sodium fluoride (NaF) on platelet aggregation and release reaction and correlated the functional changes to intracellular events specific for either agonist-induced or antagonist-induced platelet responses. At lower concentrations, with a peak activity between 30 and 40 mmol/L, NaF induced aggregation and release of adenosine 5'-triphosphate (ATP) that was associated with increased formation of inositol phosphates, a rise in cytosolic free Ca2+, and phosphorylation of 20-kd and 40-kd proteins. At NaF concentrations greater than 40 mmol/L, aggregation and ATP release decreased dose-dependently in parallel with a decrease in Ca2+ mobilization, whereas neither inositol phosphate formation nor 40-kd protein phosphorylation was reduced. At these concentrations, NaF caused a dose-dependent transient rise in platelet cyclic adenosine 3',5'-monophosphate (cAMP) levels that was sufficient to account for the observed reduction in Ca2+ mobilization, aggregation, and ATP release. Stimulated cAMP levels started declining rapidly within 30 seconds of addition of NaF, however. Similarly, prostacyclin (PGI2)-induced cAMP accumulation was temporarily enhanced but subsequently suppressed by NaF, suggesting either stimulation of a cAMP phosphodiesterase or delayed inhibition of adenylate cyclase. Evidence for the latter was provided by the finding that NaF pretreatment of platelets resulted in partial inhibition of PGI2-stimulated cAMP formation in the presence of the cAMP phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (MIX). We conclude that NaF exerts a dual (stimulatory and inhibitory) effect on adenylate cyclase in intact platelets that is accompanied by simultaneous activation of a phosphoinositide-specific phospholipase C; in addition, a cAMP phosphodiesterase may be activated.

Adenosine Triphosphate↗
PubMed1987

[Molecular defects of coagulation factors and of the fibrinolytic system associated with thromboembolism].

Some molecular defects of components of the coagulation or fibrinolytic system are associated with thromboembolism. One possibility is that physiologic inhibitors of the coagulation system have an abnormal function e.g. protein C, protein S, antithrombin III and cofactor II of heparin. Also a hindered activation of the fibrinolytic system may predispose to thrombosis; the impaired activation may be due to deficient synthesis and/or release of tissue-plasminogen activator, an increased level of its inhibitor or a functional defect of the plasminogen molecule. A few cases of congenital dysfibrinogenemia have been described in which the functional defects of the molecule are held responsible for recurrent thrombosis. An acquired thrombotic disorder is due to the presence of immunoglobulins which prolongs phospholipid-dependent coagulation by binding to epitopes of some phospholipids. This so-called lupus anticoagulant was originally described in patients with systemic lupus erythematosus but is a misnomer as it is more frequently encountered in patients without lupus.

Blood Coagulation Disorders↗
PubMed1987

Comparison of quantification methods of 111In-labelled platelet deposition in peripheral bypass grafts.

The action of antithrombotic drugs can be evaluated by measuring the deposition of 111In-labelled platelets on peripheral bypass grafts several days after injection. This evaluation can be performed qualitatively (visual interpretation on the daily images) or quantitatively. Four different methods which calculate the ratio of platelet uptake with a reference region are compared: two methods use a gamma camera and two a detector. A blood sample or the region under the sternal angle are used as reference. The daily ratio of the counts, recorded by a gamma camera in a region of interest covering the graft, and the blood radioactivity interpolated from a platelet survival curve appears to be the most reliable method. The information of all the ratios can be combined in a single thrombogenicity index which reflects the daily rise of a linear or exponential regression versus time.

Aged↗
PubMed1987

Intraarterial low-dose streptokinase infusion in the treatment of acute renal thromboembolism.

A case of acute renal thromboembolism treated by intraarterial low dose streptokinase infusion is reported. The treatment appears effective, safe and less-invasive then surgery, with quick relief of pain and normalisation of blood pressure and renal function. It is concluded that intraarterial infusion of thrombolytic agents should be attempted first in the treatment of renal arterial thrombo-embolism.

Female↗
PubMed1986

Leukotriene B4 production by stimulated whole blood: comparative studies with isolated polymorphonuclear cells.

A new method was developed to study leukotriene B4 (LTB4) production by stimulated whole blood. The calcium ionophore A23187 and serum-treated zymosan induced LTB4 production, measured by radioimmunoassay, in a dose- and time-dependent manner. The pattern of LTB4 production by whole blood differed markedly from that observed with isolated, purified polymorphonuclear leukocytes. Higher levels of LTB4 were reached and maintained in whole blood. The system allowed to detect drug effects on LTB4 synthesis in vitro. This new method to study the synthesis of LTB4 takes into account the complex interactions between different cell types which can modulate LTB4 metabolism.

Calcimycin↗
PubMed1986

Heparin-induced thrombocytopenia platelet aggregation studies in the presence of heparin fractions or semi-synthetic analogues of various molecular weights and anticoagulant activities.

One case of heparin-induced thrombocytopenia is reported. Aggregation was observed in the platelet-rich plasma of this patient in the presence of two commercial standard heparin preparations (from a final concentration of 0.025 IU/ml upwards), of two semi-synthetic heparin analogues (0.1 APTT U/ml) and of three low-molecular weight heparin (LMWH) fractions (0.1 anti-Xa U/ml) but not in the presence of five other LMWH fractions. The patient's isolated platelets no longer aggregated in the The patient's isolated platelets no longer aggregated in the presence of heparin but the phenomenon recurred after addition of the patient's platelet poor plasma (PPP). Furthermore, addition of patient's PPP to control platelets led to heparin-induced aggregation. The phenomenon was associated with thromboxane generation and could be blocked by in vitro addition of aspirin, PGI2, and PGD2 whereas the lag phase was dose-dependently prolonged by adenosine. It is concluded that platelet aggregation may be induced in some patients by standard heparin and by certain LMWH fractions or semi-synthetic analogues, independently of their molecular weight and anticoagulant activity.

Adenosine↗
PubMed1986

Mechanism of the antiplatelet action of dipyridamole in whole blood: modulation of adenosine concentration and activity.

Dipyridamole inhibits platelet aggregation in whole blood at lower concentrations than in plasma. The blood cells responsible for increased effectiveness in blood are the erythrocytes. Using the impedance aggregometer we have carried out a series of pharmacological studies in vitro to elucidate the mechanism of action of dipyridamole in whole blood. Adenosine deaminase, an enzyme breaking down adenosine, reverses the inhibitory action of dipyridamole. Two different adenosine receptor antagonists, 5'-deoxy-5'-methylthioadenosine and theophylline, also partially neutralize the activity of dipyridamole in blood. Enprofylline, a phosphodiesterase inhibitor with almost no adenosine receptor antagonistic properties, potentiates the inhibition of platelet aggregation by dipyridamole. An inhibitory effect similar to that of dipyridamole can be obtained combining a pure adenosine uptake inhibitor (RE 102 BS) with a pure phosphodiesterase inhibitor (MX-MB 82 or enprofylline). Mixing the blood during preincubation with dipyridamole increases the degree of inhibition. Lowering the haematocrit slightly reduces the effectiveness. Although we did not carry out direct measurements of adenosine levels, the results of our pharmacological studies clearly show that dipyridamole inhibits platelet aggregation in whole blood by blocking the reuptake of adenosine formed from precursors released by red blood cells following microtrauma. Its slight phosphodiesterase inhibitory action potentiates the effects of adenosine on platelets.

Adenosine↗
PubMed1986

'Lupus' anticoagulant and thrombosis of the hepatic veins (Budd-Chiari syndrome). Report of three patients and review of the literature.

Three patients with Budd-Chiari syndrome in association with the 'lupus' anticoagulant are described. This anticoagulant was looked for in our patients with an otherwise idiopathic hepatic venous thrombosis because of the presence of a pronounced thrombocytopenia, a prolonged activated partial thromboplastin time or a history of repeated abortions and deep leg vein thrombosis, respectively. An active search for the 'lupus' anticoagulant should be performed to lower the percentage of apparently idiopathic cases of Budd-Chiari syndrome.

Adult↗
PubMed1986

Role of platelet activation and fibrin formation in thrombogenesis.

Further progress in the search for more effective but safe antithrombotic agents is coupled to an improved understanding of the factors involved in arterial and venous thrombogenesis. Although arterial thrombosis is initiated by formation of a layer of platelets on modified endothelium or subendothelial constituents and subsequent recruitment of passing-by platelets, this phenomenon is not sufficient to lead to a full thrombus. Further growth of such a platelet mass depends, to a large extent, on the presence of free thrombin. Thrombin is mainly generated by activation of factor XI on the platelet contact with collagen. In addition, thrombin leads to formation of fibrin, which maintains the stability of the arterial platelet thrombus and is the main component of the venous thrombus. The search for agents that inhibit platelet activation and thrombin formation is, therefore, a logical endeavor.

Blood Coagulation↗
PubMed1986

Venous thromboses in particular organs.

Although venous thrombosis most often occurs in the return circulation of the legs and pelvis, it may also occur in the veins of several organs and compromise venous return. Thus, the clinician, in any field will regularly be confronted with manifestations of venous thrombosis in particular organs. This review summarizes the pathogenesis and the main clinical features of venous thrombosis in the central retinal vein, the cerebral veins and sinuses of the skull, the renal and the portal veins and the hepatic and mesenteric veins as well as priapism. The principles of treatment are outlined.

Budd-Chiari Syndrome↗
PubMed1986

Current issues in thrombosis prevention with antiplatelet drugs.

In this review, the major current problems related to the pharmacology and clinical use of antiplatelet drugs are discussed in relation to the physiopathology of the platelet-vessel wall interaction and arterial thrombus formation. Although platelet adhesion to injured vessels is a crucial step in thrombogenesis, none of the currently used antiaggregating drugs prevents this phenomenon. Why the normal endothelium does not react with platelets is not known. Thus we are unable to pharmacologically restore endothelial 'non-thrombogenicity' when lost by single or repeated injury. In contrast, more information is available on the mechanisms controlling and amplifying platelet activation by physiological stimuli (such as collagen and thrombin), and on their pharmacological modulation. The 3 main amplification loops involve arachidonic acid metabolism, ADP release and possibly the availability of a phospholipid platelet activating factor. These pathways are in turn activated by the phosphatidylinositol cycle. The most widely used antiaggregating drug is aspirin. It prevents the formation of arachidonic acid metabolites both in platelets and in vascular cells. The use of low-dose aspirin, thromboxane-synthase inhibitors, thromboxane receptor antagonists, epoprostenol (prostacyclin) and its stable analogues, and ticlopidine all appear to be promising pharmacological approaches, but none has so far been tested in clinical trials for thrombosis prevention. On the other hand, aspirin (in relatively large doses of 300 to 1500 mg daily), sulphinpyrazone and dipyridamole have been tested alone or in combination in the secondary prevention of thromboembolic complications. Aspirin has significantly reduced both the occurrence of myocardial infarction and mortality rate in patients with unstable angina and/or previous myocardial infarction; it has also proved beneficial in cerebrovascular disease. The beneficial effect of aspirin was dose-independent. In some of these trials aspirin was combined with either dipyridamole or sulphinpyrazone. When used alone, the latter compound has reduced sudden death or thromboembolic complications in patients with myocardial infarction. It remains to be established whether antiplatelet therapy may prevent or stop the progression of atherosclerosis.

Aspirin↗