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Biomedical subjects

J Vermylen

Publications and source records attributed to J Vermylen.

At least 271 records · Page 15Linked to original sources
PubMed1981

The effect of clinical prostacyclin infusions in advanced arterial disease on platelet function and plasma 6-keto PGF1 alpha levels.

We have infused synthetic prostacyclin (PGI2) continuously for approximately 72 h at the maximum tolerated dose (ranging from 5 to 60 ng/kg/min) into nine patients with advanced arterial disease. Prior to the infusion seven out of nine patients had spontaneous platelet aggregation and five out of six patients tested had an abnormal circulating platelet aggregate ratio. During the infusion only one patient still had spontaneous aggregation and all the abnormal circulating platelet aggregate ratios returned to the normal range. However, none of the patients showed any suppression of ADP induced aggregation. The level of exogenous PGI2 required in vitro prior to the infusion to completely inhibit ADP induced aggregation was 5-10 ng/ml in three of the four patients tested. Ten healthy adults showed complete inhibition with 1 ng/ml of PGI2. It appears that the platelets of some patients with arterial disease are more resistant to the anti-aggregating properties of PGI2. Plasma 6-keto PGF1 alpha levels, measured by radioimmunoassay, were within the normal range (100-381 pg/ml) in all but one of the patients prior to the infusion. During the infusion plasma 6-keto PGF1 alpha levels rose proportionally to the infusion dose. After stopping the infusion 6-keto PGF1 alpha levels declined according to an exponential process with a half life of 18-29 min, prolonged to 47 min in one patient who was anuric. The linear increase in 6-keto PGF1 alpha levels suggests this as a useful indicator of increased circulating PGI2.

Adult↗
PubMed1981

Familial bleeding tendency with partial platelet thromboxane synthetase deficiency: reorientation of cyclic endoperoxide metabolism.

Three family members from three successive generations presented with a moderate bleeding tendency and a functional platelet defect. They had absent aggregation with arachidonic acid (0.6--3 microM), reversible aggregation with ADP (4 microgram) and cyclic endoperoxide analogues, single wave aggregation only with adrenaline (5.4 microgram) and a prolonged template bleeding time (> min). Malondialdehyde formation was reduced after N-ethylmaleimide stimulation (2--6 nmol/10(9) platelets; control values 8--12 nmol) and serum thromboxane B2 values were reduced (33--101 ng/ml; control values 200--700 ng/ml). When the platelets were incubated with [3H]arachidonic acid the final metabolite of the lipoxygenase pathway (HETE) was produced in normal amounts but the production of thromboxane B2 and HHT was decreased whereas prostaglandin F2a, and E2 and probably D2 were increased. Evidence for enhanced production of prostaglandin D2 was also provided by the rise in the patient's platelet cyclic AMP levels following stimulation with arachidonic acid. The patient's washed platelets stimulated the production of 6-keto PGF 1a by aspirin-pretreated cultured bovine endothelial cells. The plasma levels of 6-keto PGF1a (439--703 pg/ml; normal 181 +/- 46 pg/ml) were raised. The decreased production of thromboxane B2, HHT and malondialdehyde and increased formation of prostaglandin F2a, E2, D2 and of 6-keto PGF1a are compatible with a partial platelet thromboxane synthetase deficiency and reorientation of cyclic endoperoxide metabolism. The markedly prolonged bleeding time would result not only from reduced formation of thromboxane A2 but also from increased production of the aggregation inhibiting prostaglandins PGI2 and PGD2.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1981

Clotting and fibrinolytic activities in peritoneal fluid.

Peritoneal fluid does not clot spontaneously on collection, due to a lack of prothrombin activation, consequent upon a virtual absence of factors V and VIII. Factor VIII related antigen is present in peritoneal fluid in only very small amounts, suggesting that this factor is excluded from the peritoneal cavity, probably by virtue of its size. Slight thrombin activity is demonstrated by the presence of fibrin monomers in the fluid. That peritoneal fluid also contains fibrinolytic activity is shown by high levels of plasminogen and plasmin-antiplasmin complexes, though no plasminogen activator could be detected. No differences were found in clotting and fibrinolytic activities, between fluid taken from these patients with, and those without, laparoscopic evidence of pelvic endometriosis.

Ascitic Fluid↗
PubMed1981

"Lupus" anticoagulant and inhibition of prostacyclin formation in patients with repeated abortion, intrauterine growth retardation and intrauterine death.

We discovered a "lupus' anticoagulant in 2 out of 42 women with a history of repeated abortions, intrauterine growth retardation and intrauterine death of unknown origin. The "lupus' anticoagulant was detected by an abnormal dilute tissue thromboplastin assay(prothrombin time performed with dilute thromboplastin). The production of prostacyclin by fresh or exhausted rings of rat aorta was decreased by the plasma of one of these two patients with a "lupus' anticoagulant. In view of the increasing evidence for a physiological role of prostacyclin in pregnancy and fetal life, we suggest that an inhibition of prostacyclin production could compromise fetal outcome.

Abortion, Habitual↗
PubMed1981

Increased release of vascular prostacyclin-like activity after long-term treatment of diabetic rats with Bay g 6575.

10 male Wistar rats were made diabetic by an intravenous injection of streptozotocin. 10 sex and age-matched rats served as control animals. 5 of the diabetic and 5 of the control rats received Bay g 6575 (20 mg/kg orally) for 6 days each week throughout the whole study period (9-11 months). From these animals aorta was removed for prostacyclin bioassay based upon its platelet aggregation inhibitory effect. The diabetic rats treated with Bay g 6575 released significantly more prostacyclin than the controls (p less than 0.005). Our study suggests further experiments in other animal models more susceptible to diabetic vascular lesions than the rat model to evaluate the possible beneficial role of the treatment with Bay g 6575.

Adenoma↗
PubMed1979

Action of brinase on human fibrinogen and plasminogen.

Brinase added to human plasma in vitro caused a decrease in fibrinogen concentration, positive paracoagulation tests and formation of a friable clot in sequence. Agarose gel filtration of these samples revealed the presence of fibrinogen derivatives both larger and smaller than the parent molecule. Infusion of the enzyme in vivo resulted in a decreased fibrinogen level, a prolonged thrombin time and an increase in fibrinogen related antigen (FRA) in serum. The elution pattern of FRA in the plasma samples obtained after infusion of Brinase was similar to that of the in vitro samples. The plasma pool of fibrinogen was partially consumed by infusion of Brinase, but the turnover of plasminogen remained unaffected. Purified plasminogen was partially degraded by addition of the enzyme but this was accompanied by a generation of proteolytic activity. These findings confirm that Brinase induces a proteolytic degradation of fibrinogen in plasma without activation of the plasminogen-plasmin system. Exposure of polymerization site(s) in the fibrinogen molecule is probably responsible for the reported clot promoting effect of the enzyme.

Antigens↗
PubMed1979

Stimulation of prostacyclin release from vessel wall by Bay g 6575, an antithrombotic compound.

Ingestion of 1.2 g Bay g 6575 daily for 1 week by six healthy volunteers had no effect on blood-coagulation, fibrinolysis, or platelet aggregation in vitro, but it seemed to inhibit platelet aggregation in vivo (shown by a smaller reduction in the platelet aggregate ratio after venous occlusion). Plasma drawn from five volunteers after ingestion of a single dose of 1.2 g of the drug stimulated prostacyclin release from slices of rat aorta which had been washed until they stopped releasing anti-aggregating substances, whereas plasma from the same individuals before ingestion of the substance did not. Administration of either Bay g 6575 or dipyridamole alone had no effect on platelet aggregation in vitro, but combined administration resulted in a striking and prolonged inhibition of A.D.P.-induced platelet aggregation. It is proposed that the previously described antithrombotic properties of Bay g 6575 in animals are due to stimulation of prostacyclin release from the vessel wall, and that this effect is also demonstrable in man.

Adenosine Diphosphate↗
PubMed1979

Clinical trial of brinase and anticoagulants as a method of treatment for advanced limb ischemia.

A randomized, single-blind trial of repeated intravenous infusion of Brinase was carried out in 70 petients with severe chronic limb ischemia, who were candidates for lumbar sympathectomy or amputation. The enzyme caused s significant increase in calf and ankle pressure index. At six months follow-up, the clinical results were statistically significant in favour of Brinase when all patients were considered, but not if 10 patients with Buerger's disease were omitted from the analysis. Patients treated with a combination of Brinase and coumarins had a better clinical outcome than patients receiving either treatment on its own.

Aged↗
PubMed1978

Biochemical changes noted during intermittent administration of streptokinase.

An intermittent dosage scheme of streptokinase (standard initial dose 600,000 units SK infused over 30 min and repeated injections of 250,000 units SK at 24 hr intervals) was applied during 4 days in 9 patients with chronic obliterative arterial disease and in 8 patients with venous occlusion. Each dose of streptokinase produced an immediate fall in plasminogen to 17% (SEM 5.1) of the initial value, the level then rose to 50% (SEM 5.4) within 24 hr. Lowered levels of antiplasmin and fibrinogen (both less than 40% of the initial values) were maintained. This safe level of fibrinogen was maintained despite brief but high peaks of plasmin activity after each injection of SK. A parallel increase of the thrombin time and the fibrin (ogen) degradation products was obtained following each infusion. No bleeding was observed. The relative therapeutic effect of intermittent infusions of streptokinase has still to be compared with the continuous administration of streptokinase in controlled clinical trials.

Antibodies↗
PubMed1978

Evidence that endotoxins enhance the factor X activator activity of washed human platelets.

The in vitro effect of several bacterial endotoxins on human platelets was determined. Nine different endotoxins failed to induce aggregation in platelet-rich plasma (PRP) or of platelets washed by two different methods; four of them which we studied further failed to induce [14C]serotonin release in PRP. In contrast, using recently described test systems for platelet coagulant activity, all the endotoxins shortened the latent period occurring before aggregation of a mixture of washed platelets, normal serum, and CaCl2, and the clotting time of this mixture upon addition of fibrinogen. Washed platelets obtained from PRP preincubated with endotoxin had a higher platelet coagulant activity than platelets obtained from PRP preincubated with buffer. Washed platelets contribute to thrombin generation by providing factor V, a factor X activator and possibly phospholipid. Since the endotoxins did not influence the factor V activity of platelets or the platelet factor 3 activity, either in PRP or using platelets washed by albumin density gradient centrifugation, it is suggested that they enhance the factor-X activator activity of human platelets.

Blood Platelets↗