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Biomedical subjects

M Verstraete

Publications and source records attributed to M Verstraete.

At least 145 records · Page 8Linked to original sources
PubMed1984

Biological and thrombolytic properties of proenzyme and active forms of human urokinase--III. Thrombolytic properties of natural and recombinant urokinase in rabbits with experimental jugular vein thrombosis.

The thrombolytic properties of recombinant pro-urokinase (Rec-pro-UK), recombinant active urokinase (Rec-UK) and natural urinary urokinase (Nat-UK) were compared with those of tissue-type plasminogen activator (t-PA) in rabbits with a radiolabeled thrombus in the jugular vein. The thrombolytic agents were infused intravenously over a time period of 4 hr and the extent of thrombolysis measured two hours later. In control animals the extent of thrombolysis was 11 +/- 2% (n = 8) after 6 hr. Nat-UK and Rec-UK had very similar thrombolytic properties. Significant thrombolysis was only obtained with infusion of 240,000 IU per kg (41 +/- 2%, n = 4 for Nat-UK and 37 +/- 4%, n = 4 for Rec-UK) and this was associated with a marked systemic activation of the fibrinolytic system, as evidenced by consumption of plasminogen and alpha 2-antiplasmin and fibrinogen breakdown. Infusion of Rec-pro-UK induced thrombolysis at a dose of 60,000 IU per kg (44 +/- 8%, n = 3) but without associated systemic activation of the fibrinolytic system. In this respect the properties of Rec-pro-UK were similar to those of t-PA, which, however, had a 2- to 4-fold higher specific thrombolytic activity (30,000 IU/kg yielding 48 +/- 1% lysis, n = 4). It is concluded that Rec-UK has very similar thrombolytic properties as Nat-UK and that Rec-pro-UK has a better thrombus-selectivity and less systemic side effects than the active enzymes.

Animals↗
PubMed1984

Blood changes and enhanced thromboxane and 6-keto prostaglandin F1 alpha production in experimental acute Plasmodium bergei infection in hamsters.

Golden hamsters inoculated intraperitoneally with Plasmodium bergei infected mouse blood regularly developed P. bergei parasitaemia. This was associated with progressive thrombocytopenia and leucocytosis as the degree of parasitaemia increased with time. When infected whole blood was stimulated with collagen, significantly enhanced thromboxane B2 (TXB2) production per platelet was seen. 6-keto prostaglandin (PG) F1 alpha formation in the same system increased from the sixth infection day onwards and correlated with the relative leukocytosis. The production of 6-keto PGF1 alpha by aorta rings was significantly higher during the 4-7th days postinoculation. The increase in thromboxane production however was much more important than that of 6-keto PGF1 alpha and it therefore is concluded that P. bergei parasitaemia in hamsters tilts the haemostatic balance towards the platelet hyperaggregability that has also been described in P. falciparum infection in man.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Immunological alterations in haemophiliacs treated with lyophilized Factor VIII cryoprecipitate from volunteer donors.

We studied immune function in Belgian haemophiliacs treated with Factor VIII from volunteer donors. No patient had clinical evidence of immune deficiency. We found a decrease in T-helper cells (p less than 0.0005), in the ratio of T-helper over T-cytotoxic/suppressor cells (1.72 +/- 0.47 versus 2.24 +/- 0.82 in controls, p less than 0.005) and in lymphocyte responsiveness to mitogens (p less than 0.05). These findings could not be linked to the amount of F VIII received over the last year, the time since last F VIII administration, circulating immune complexes (54% positive patients, 7% positive controls, p less than 0.005), increased ALT levels, antibodies to cytomegalo -virus (85% of the patients, 45% of the controls, p less than 0.005), antibodies to Epstein-Barr virus, nor to the presence of HLA-DR 5 which was found in 56% of the haemophiliacs (20% of the overall Belgian population, p less than 0.005). Either F VIII induces long lasting immunological alterations unrelated to AIDS, or haemophilia is itself associated with such changes.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Coronary thrombolysis with tissue-type plasminogen activator in patients with evolving myocardial infarction.

Tissue-type plasminogen activator is a naturally occurring, clot-selective activator of fibrinolysis. We recently reported that human tissue-type plasminogen activator isolated from a Bowes-melanoma-tissue-culture supernate lysed coronary thrombi in dogs without depleting circulating fibrinogen or alpha 2-antiplasmin, in contrast to the case with streptokinase and urokinase. In the present study coronary thrombolysis, confirmed angiographically, was induced within 19 to 50 minutes with intravenous or intracoronary tissue-type plasminogen activator in six of seven patients with evolving myocardial infarction. Circulating fibrinogen, plasminogen, and alpha 2-antiplasmin were not depleted by this agent, in contrast to the case in the two patients subsequently given streptokinase. In the one patient in whom lysis was not inducible with tissue-type plasminogen activator, it was also not inducible with streptokinase. These observations indicate that clot-selective coronary thrombolysis can be induced in patients with evolving myocardial infarction by means of tissue-type plasminogen activator, without concomitant induction of a systemic lytic state. Definition of its therapeutic benefit must await greater availability of the agent and the performance of appropriate clinical trials.

Aged↗
PubMed1984

Precapillary vessels and peripheral vascular ischemic disease.

The vast majority of patients with peripheral arterial insufficiency have degenerative lesions in large arteries; however, collateral circulation develops in smaller arteries and arterioles. Vascular disorders affecting arterioles are idiopathic Raynaud's disease and systemic sclerosis. The pathogenesis of Raynaud's phenomenon is still poorly understood. There is some evidence that systemic sclerosis is a primary disorder of small arterioles.

Animals↗
PubMed1983

Dipyridamole inhibits platelet aggregation in whole blood.

Dipyridamole possesses antithrombotic properties in the animal and in man but it does not inhibit platelet aggregation in plasma. We evaluated the effect of dipyridamole ex vivo and in vitro on platelet aggregation induced by collagen and adenosine-5'-diphosphate (ADP) in human whole blood with an impedance aggregometer. Two hundred mg dipyridamole induced a significant inhibition of both ADP- and collagen-induced aggregation in human blood samples taken 2 hr after oral drug intake. Administration of the drug for four days, 400 mg/day, further increased the antiplatelet effect. A significant negative correlation was found between collagen-induced platelet aggregation in whole blood and dipyridamole levels in plasma (p less than 0.001). A statistically significant inhibition of both collagen (p less than 0.0025) and ADP-induced (p less than 0.005) platelet aggregation was also obtained by incubating whole blood in vitro for 2 min at 37 degrees C with dipyridamole (3.9 microM). No such effects were seen in platelet-rich plasma, even after enrichment with leukocytes. Low-dose adenosine enhanced in vitro inhibition in whole blood. Our results demonstrate that dipyridamole impedes platelet aggregation in whole blood by an interaction with red blood cells, probably involving adenosine.

Adenosine↗
PubMed1983

Manipulation of the local thromboxane and prostacyclin balance in vivo by the antithrombotic compounds dazoxiben, acetylsalicylic acid and nafazatrom.

We have developed an experimental model for the study of local prostaglandin production by platelets and the vessel wall following stimulation 'in vivo'. A nylon thread was inserted into the external jugular vein of rabbits; its presence did not induce an occluding thrombus. Thromboxane (TXB2) values in the blood, sampled through the facial vein, immediately distal to the stimulus, rose and remained high for at least 4 hr, while 6-keto prostaglandin (PG) F1 alpha levels, after a first increase, gradually returned to normal ('exhaustion' of the endothelial cells?). No changes were observed in the contralateral jugular vein without thread. After infusion via the femoral vein of 10 mg/kg dazoxiben, a thromboxane synthetase inhibitor, local TXB2 production was completely abolished, whereas 6-keto PGF1 alpha formation no longer returned to basal values, but tended to increase. This leads to the conclusion that upon inhibition of TXB2 formation endoperoxide metabolism is reoriented 'in vivo' towards prostacyclin, and this mainly at the site where platelets are activated. Injection of 100 mg/kg lysine acetylsalicylic acid resulted in complete inhibition of TXB2 and 6-keto PGF1 alpha formation, the latter, however, slowly recovering with time. The administration of nafazatrom to the animals did not influence the local TXB2 changes, but partially prevented the decline of 6-keto PGF1 alpha with time. The antithrombotic properties of this drug thus could be related to protection of the endothelial cells from 'exhaustion'.

Animals↗
PubMed1983

Thrombolysis with human extrinsic (tissue-type) plasminogen activator in rabbits with experimental jugular vein thrombosis. Effect of molecular form and dose of activator, age of the thrombus, and route of administration.

A simple venous thrombosis model in rabbits was used for the quantitative evaluation of the thrombolytic effect of human extrinsic (tissue-type) plasminogen activator as compared with urokinase.A thrombus was formed in an isolated segment of the jugular vein from a mixture of (125)I-labeled fibrinogen, whole rabbit blood, and thrombin. In order to immobilize the thrombus during lysis, it was formed around a woolen thread introduced longitudinally in the lumen of the vein. Thrombotic extension of the clot was prevented by subcutaneous injection of heparin. The extent of thrombolysis was measured as the difference between the radioactivity introduced in the clot and that recovered in the vein segment at the end of the experiment. In control animals the extent of thrombolysis was 5.6+/-1.4% (n = 5) after 6 h, 14.5+/-1.7% (n = 10) after 30 h, 16.0+/-1.5% (n = 11) after 78 h, and 48.1+/-2.7% (n = 10) after 174 h (mean+/-SEM). Extrinsic (tissue-type) plasminogen activator, highly purified from the culture fluid of a human melanoma cell line, was administered systemically or locally over a time period of 4 h and the percent thrombolysis measured 2 h after the end of the infusion. One- and two-chain extrinsic plasminogen activator had very similar thrombolytic potency. Systemic infusion resulted in a dose-dependent degree of thrombolysis. The activator-induced thrombolysis, after infusion of 100,000 IU ( congruent with1 mg protein), was approximately 75% for fresh clots, 35% for 1-d-old clots, 30% for 3-d-old clots, and 50% for 7-d-old clots. The thrombolytic activity of urokinase was more than five times lower than that of extrinsic plasminogen activator: Infusion of 500,000 IU resulted in approximately 40% lysis of fresh clots and 25% of 1-3-d-old clots, while 7-d-old clots appeared to have become resistent to urokinase. Local infusion resulted in a 5-10 times higher thrombolytic effect of both extrinsic plasminogen activator and urokinase. Thrombolysis with extrinsic plasminogen activator was not associated with systemic activation of the fibrinolytic system as evidenced by unaltered plasma levels of fibrinogen, plasminogen, and alpha(2)-antiplasmin. Systemic infusion of urokinase resulted in significant thrombolysis only at doses that were associated with disseminated plasminogen activation. Local infusion of urokinase required a 5-10-fold higher dose than extrinsic plasminogen activator to obtain a similar degree of thrombolysis, which also occurred in the absence of systemic activation of the fibrinolytic system. It is concluded that the extent of thrombolysis by extrinsic plasminogen activator is mainly determined by the dose of activator and its delivery in the vicinity of the thrombus and much less by the age of the thrombus or the molecular form of the activator. Extrinsic plasminogen activator appears to be superior to urokinase because of its higher (5-10-fold) specific thrombolytic activity and the absence of systemic activation of the fibrinolytic system, which results in defibrinogenation and a bleeding tendency.

Animals↗
PubMed1983

Transluminal angioplasty: late results sustained by digital intravenous subtraction angiography.

Digital intravenous subtraction angiography (DIVSA) appears to be a technique of minimal invasiveness and high accuracy in the follow-up of patients after percutaneous angioplasty (PTA) allowing correct angiographic evaluation in more than 96% of the cases. Correlation between clinical and angiographic findings seems to be excellent. Of the controlled intravenous examinations performed in 54 successful PTA procedures 75% appeared patent after 10 to 30 months, constituting 52% of the original attempts.

Angiography↗