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Biomedical subjects

M A Barradas

Publications and source records attributed to M A Barradas.

At least 91 records · Page 5Linked to original sources
PubMed1985

Heparin-induced platelet aggregation in anorexia nervosa and in severe peripheral vascular disease.

We have previously demonstrated that platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease are hyperaggregable. Since conventional heparins are known to activate platelets in vitro and occasionally induce thrombosis and consumptive thrombocytopenia in vivo, we have investigated the direct effect of a conventional heparin on platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease. Heparin at therapeutic concentrations was found to induce platelet aggregation of such platelets in vitro. In contrast, a recently developed low molecular weight heparinoid (Org 10172), at therapeutic concentrations, had no effect on these hyperaggregable platelets. We conclude that: heparin may be potentially harmful to patients with hyperaggregable platelets; thrombocytopenia and thrombosis associated with heparin therapy may be mediated through a direct effect of heparin on platelets; it is unlikely that heparin induced thrombocytopenia is always mediated by classical immunological mechanisms, especially in patients with hyperaggregable platelets; and low molecular weight heparinoids may be safer anticoagulants in patients with platelet hyperaggregability.

Adolescent↗
PubMed1985

Fibrinogen mediated activation of platelet aggregation and thromboxane A2 release: pathological implications in vascular disease.

The effect of a human fibrinogen preparation on in vitro platelet aggregation was assessed. Platelets were obtained from healthy volunteers. Human fibrinogen induced platelet aggregation in 65% of platelet rich plasma samples and enhanced submaximal platelet aggregation induced by heparin or by several conventional agonists in all samples. Aggregation induced by fibrinogen alone was reversed by the in vitro addition of human albumin. Fibrinogen induced aggregation was associated with the release of the vasoconstrictor, thromboxane A2. Preincubation with indomethacin inhibited both the aggregation and the release of thromboxane A2. Fibrinogen had no effect on in vitro vascular prostaglandin I2 synthesis (rat aortic rings) during a 60 minute incubation. The observed effects of fibrinogen on platelet function may be relevant to clinical conditions in which hyperaggregability of platelets is associated with hyperfibrinogenemia and thrombosis.

Animals↗
PubMed1985

Thrombocytopenia and lupus-like anticoagulant in a patient with peripheral vascular disease: response to infusion of prostacyclin.

A 46 year old man with intermittent claudication due to severe peripheral vascular disease had a circulating lupus like anticoagulant (LLAC), thrombocytopenia (79 X 109/1), markedly reduced platelet survival and a normal bone marrow. He was treated with intravenous prostacyclin (PGI2) infusions which resulted in improvement of the patient's exercise tolerance and normalisation of his platelet count (300 X 109/1) and platelet aggregation could then be assessed. The platelets were markedly hyperaggregable and generated supranormal quantities of thromboxane A2. A diagnosis of consumptive thrombocytopenia secondary to peripheral vascular disease and platelet hyperaggregability was made. Despite therapy with aspirin and dipyridamole, gradual and progressive reduction in platelet count followed and his exercise tolerance declined over the next three months. Immunoglobulin prepared from the patient's serum did not inhibit vascular PGI2 synthesis in vitro. To our knowledge this is the first reported case of consumptive thrombocytopenia due to severe peripheral vascular disease and platelet hyperaggregability. PGI2 administration caused a transient resolution of these features which was not sustained by aspirin and dipyridamole.

Arteriosclerosis Obliterans↗
PubMed1985

The effect of non-specific beta-blockade on metabolic and haemostatic variables during hypoglycaemia.

Several haemostatic and metabolic variables were monitored during insulin stress tests (ISTs), which were preceded by placebo, nadolol or propranolol ingestion for 10 days. Nadolol administration blocked the rise in plasma factor VIII: RAg concentrations, but no significant changes were observed in platelet aggregation/thromboxane A2 release. Propranolol administration reduced the significance, but not the magnitude, of the plasma factor VIII:Rag rise and also marginally inhibited platelet aggregation/TXA2 release. Both nadolol and propranolol inhibited the hypokalaemia of hypoglycaemia and retarded the recovery of plasma glucose concentrations, probably by inhibiting lipolysis (as indicated by serum nonesterified fatty acid concentrations). Both nadolol and propranolol often masked and delayed the onset of the symptoms of hypoglycaemia. Beta-blockers may exert beneficial effects by modifying haemostatic variables and by preventing hypokalaemia during stressful situations, such as hypoglycaemia or myocardial infarction, both in diabetics and in non-diabetics. However, any benefit must be balanced against the risk of masking, and possibly increasing the incidence of, hypoglycaemia in diabetics.

Adenosine Diphosphate↗
PubMed1985

The effect of tiaprofenic acid and indomethacin on vascular prostacyclin and platelet thromboxane A2 production.

Two experimental models were used to compare tiaprofenic acid and indomethacin. The first model involved assessing their effect on in vitro prostacyclin synthesis by rat aortic rings and human umbilical endothelial cells. The results showed that the inhibitory effect of the two drugs was similar. The second model involved assessing the effect of these drugs on in vitro thromboxane A2 release by human platelets. Indomethacin was shown to be a more potent inhibitor of TXA2 release than tiaprofenic acid, but this difference was only significant at low concentrations of the drugs; at concentrations equivalent to those achieved during routine treatment, both produced near maximal inhibition of TXA2 release by platelets. It is concluded that the findings do not support the claim that tiaprofenic acid is more 'selective' in its actions on these aspects of prostaglandin synthesis than another non-steroidal anti-inflammatory drug, indomethacin.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

An investigation into the effects of nifedipine and nimodipine on platelet function and vascular prostacyclin synthesis.

The effect of two calcium-channel blockers (nifedipine; nimodipine) on in vitro platelet function and prostacyclin (PGI2) synthesis was investigated. Platelet aggregation and thromboxane A2 release in platelet-rich plasma were inhibited by both drugs, but the effective concentrations (20 mg/l) were considerably higher than the reported therapeutic levels of the drugs (60 micrograms/l). Platelet impedance aggregometry (PIA) in whole blood was a more sensitive (4-fold) index of the effect of nifedipine on platelets, but inhibitory concentrations of the drug were still considerably higher (5 mg/l) than therapeutic concentrations. Neither nifedipine nor nimodipine had any effect on PGI2 synthesis, which was assessed in terms of conversion of arachidonic acid to PGI2 (in rat aortic and human umbilical tissue) and spontaneous release of PGI2 from rat aortae following in vitro incubations or in vivo administration of nifedipine. The mechanism responsible for the reported inhibition of platelet function following administration of nifedipine remains unclear, but does not appear to involve acute direct effects on platelets or vascular PGI2 production. The authors' PIA findings also indicate that: (a) PIA may be a more sensitive method than conventional (PRP) aggregometry to demonstrate platelet antiaggregatory effects of drugs; and (b) erythrocytes and leucocytes may be involved in the mechanism underlying the antiaggregatory effect of nifedipine.

Animals↗
PubMed1985

The effect of diflunisal administration on platelet aggregation and cerebral blood flow.

The effect of a high dose of diflunisal (750 mg twice daily) on platelet aggregation and cerebral blood flow was investigated in 8 healthy volunteers. Diflunisal inhibited platelet aggregation consistently; this effect on platelets was reversed within 24 hours after the last dose of diflunisal. There was, however, no correlation between the anti-aggregatory effect of diflunisal and its plasma concentration. Diflunisal did not alter cerebral blood flow.

Adenosine Diphosphate↗
PubMed1984

Comparison of the effect of a conventional heparin and a low molecular weight heparinoid on platelet function.

In a study comparing the in vitro effects of heparin and a low molecular weight heparinoid (Organon 10172) on aggregation of platelets from normal subjects, we have demonstrated that whereas heparin markedly enhances platelet aggregation induced by other aggregators and inhibits the anti-aggregatory effect of epoprostenol (prostacyclin, PGI2), heparinoid does not produce such effects. The use of heparinoid may thus have a significant advantage over that of heparin in situations where enhanced platelet aggregation is the main factor leading to thrombosis or where heparin treatment is followed by thrombocytopaenia.

Drug Evaluation↗
PubMed1983

Effect of ethanol on vascular prostacyclin (prostaglandin I2) synthesis, platelet aggregation, and platelet thromboxane release.

A series of experiments with platelets from healthy volunteers showed a concentration related inhibitory effect of ethanol on platelet aggregation and release of thromboxane A2. This effect was observed at blood alcohol concentrations ranging between 66 and 132 mg/dl (14.3 and 28.6 mmol/l), which are commonly found in alcoholics. Investigations carried out by incubating ethanol with platelet rich plasma in vitro also showed an inverse linear correlation between ethanol concentration and platelet thromboxane synthesis. In contrast, the incubation of a wide range of concentrations of ethanol with human endothelial cells and rat aortic rings did not alter the ability of these systems to synthesise prostacyclin (prostaglandin I2). This finding of a selective inhibition of thromboxane A2 synthesis and platelet aggregation without an alteration of prostaglandin I2 synthesis may provide an explanation for the reported ethanol mediated protection against vascular disease. This effect of ethanol may also be relevant to the induction of acute gastrointestinal haemorrhage that occurs after bouts of excessive alcohol consumption.

Adenosine Diphosphate↗