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Biomedical subjects

U Till

Publications and source records attributed to U Till.

At least 55 records · Page 3Linked to original sources
PubMed1988

Substances that polymerize or depolymerize cytoskeletal proteins affect platelet spreading and thrombus-formation on surfaces coated with human collagen isotypes I, IV, and V.

The effect of substances that affect platelet cytoskeleton on the interaction of gel-filtered platelets with surfaces coated with human monomeric type I, IV, and V collagen was studied. The sulfhydryl group oxidizing agent azodicarboxylic acid-bis-dimethylamide (diamide) which causes disulfide-linked polymer formation of certain cytoskeletal proteins, the actin-polymerization inhibitor, cytochalasin B, and 2-mercaptopropionylglycine (2-MPG), a cell-permeable SH-reagent, completely abolish adhesion-induced platelet spreading and mural platelet aggregate formation on collagen-coated surfaces. Extrusion of pseudopods was inhibited by cytochalasin B and 2-MPG as well as by diamide, but only the latter caused spherulation of platelets, whereas cytochalasin B and 2-MPG left the discoid shape of resting platelets intact. These effects are dose-dependent and are not accounted for by a chemical modification of the collagenous substrates by the cytoskeletal perturbing substances. The present data indicate that (i) cytoskeletal rearrangements are essential in adhesion-induced platelet spreading and aggregate formation on surfaces coated with collagen, but not in supporting the initial attachment of native platelets to the substrate; (ii) both, polymerization and depolymerization of actin filaments affect platelet activation; (iii) the sulfhydryl-disulfide status of the platelet seems to be a possible target for anti-platelet drugs, since chemical modification of platelets by the GSH-GSSG-active substances, diamide and 2-MPG, leads to a reversible inhibition of adhesion-induced platelet activation.

Chromatography, Gel↗
PubMed1988

Regulation of arachidonic acid-dependent Ca++ influx in human platelets.

Quin2 was used to study the rise in cytoplasmic free calcium ([Ca++]i) and the role of prostaglandin (PG) endoperoxides/thromboxane A2 (TxA2), reduced glutathione (GSH), ADP and the glycoprotein (GP) IIb-IIIa complex in mediating [Ca++]i rise during arachidonic acid (AA)-induced platelet aggregation. Ca++ mobilization, mostly due to an influx across the plasma membrane, is completely inhibited by aspirin and persists after selective blockade of TxA2 synthase by dazoxiben. GSH total depletion causes a complete aggregation block and 90% inhibition of the transient: U-46619, a stable analog of cyclic endoperoxide PGH2, stimulates [Ca++]i transient in aspirin-treated or in GSH-depleted platelets. ADP-scavengers, ATP (which competes for the ADP receptor), and monoclonal antibodies against the GP IIb-IIIa complex reduce AA-induced Ca++ influx. Therefore, PG endoperoxides alone or a PGH2/TxA2 mimetic stimulate Ca++ influx. Synthesis of PGH2 and TxA2 depends on the availability of GSH, which acts as the reducing cofactor for the PG-peroxidase activity. ADP and GP IIb-IIIa are regulating factors of AA-mediated Ca++ influx during platelet activation.

Adenosine Diphosphate↗
PubMed1988

Proaggregatory and inhibitory effects of 2-O-ethyl analogues of platelet-activating factor (PAF) on human and rabbit platelets.

A series of 8 analogues of platelet-activating factor (PAF) in which both the acetyl group and the polar head are changed, were tested for biological activities on human and rabbit platelets in plasma. Two of these compounds, 1-O-hexadecyl-2-O-ethyl-rac-glycero-3-phosphoric acid-5'-trimethylammoniumpentyl ester and 1-O-hexadecyl-2-O-ethyl-rac-glycero-3-phosphoric acid-6'-trimethylammoniumhexyl ester inhibit selectively the PAF-induced aggregation response without showing any agonistic activity. Schild analysis revealed a competitive antagonism and KB values of 4.4 and 10.5 mumol/l, respectively. These results point to a crucial role of the distance between the phosphoryl group and the polar head for expression of PAF-antagonistic properties. Moreover, the substituent at the 2-position was found to influence predominantly the agonistic behaviour.

Animals↗
PubMed1988

Effects of an extract of feverfew on endothelial cell integrity and on cAMP in rabbit perfused aorta.

Extracts of feverfew inhibit platelet aggregation and secretion of granular contents from platelets and other cells. They also modify the interaction of platelets with collagen substrates: feverfew extracts inhibit both platelet spreading and formation of thrombus-like platelet aggregates on the collagen surface. We have now investigated the effect of an extract of feverfew on the vessel wall using rabbit aortas that were perfused with a physiological salt solution in-situ. Addition of feverfew extract to the perfusion medium protected the endothelial cell monolayer from perfusion-induced injury and led to a reversible increase in the cAMP content of aorta segments. The results indicate that feverfew may have a vasoprotective effect in addition to its effects on platelets.

Animals↗
PubMed1988

Inhibition of platelet activation by 2-mercaptopropionylglycin in vitro and in vivo.

2-mercaptopropionylglycin (2-MPG), a cell membrane penetrating thiol, was evaluated for its antithrombotic potential using in vitro and in vivo tests. 2-MPG was found to inhibit agonist-induced platelet aggregation and serotonin release as well as prostaglandin/thromboxane synthesis in platelet-rich plasma. Administration of 2-MPG to rats resulted in an inhibition of laser-induced thrombus formation in mesenteric vessels. When plasma was incubated with 2-MPG and then used for determination of various standard coagulation parameters, significant prolongation of the clotting times were observed.

Animals↗
PubMed1988

The role of the actin status in platelet behaviour.

The status of platelet actin has been studied analytically by the DNase-I inhibition assay. Exposure of platelets to diamide, which oxidizes sulphydryl groups, results in an increase of filamentous actin. Neutralization of the effect of diamide by addition of 2-mercaptopropionylglycine (2-MPG) or washing out the excess of diamide is associated with a normalization of the cellular actin status. These findings strongly suggest that the redox state of platelets is somehow involved in the process of actin polymerization. Alterations of the redox state in metabolically altered platelets could therefore account for changes in the G- to F-actin equilibrium. In the thrombin-induced actin polymerization the redox state of the cell seems to be not involved, since 2-MPG preincubation of platelets (1.25 mM, 30 min) does not inhibit the filament assembly.

Actins↗
PubMed1988

The use of N-(2-mercaptopropionyl)-glycine (MPG) for preparation and storage of platelets.

The SH group containing drug MPG which inhibits platelet aggregation in a reversible manner was used as a cytoprotective substance in some experiments on preparation and storage of human platelets for transfusion. In vitro (n = 6): concentration, morphology score, HSR and aggregation of stored platelets were measured after simulating in vitro the post transfusional conditions by resuspension of stored platelets in fresh drawn plasma (pH 7.4, 37 degrees C). In vivo (n = 2): Autologous platelets stored for 48 h at 22 degrees C were labelled with 111In and retransfused. The results obtained from platelets prepared and stored in plasma containing MPG were compared with those obtained from control platelets without MPG.

Blood Platelets↗
PubMed1988

Blood platelet calcium content and aggregation behaviour in myeloproliferative disorders and secondary thrombocytosis.

In 19 patients affected by various kinds of myeloproliferative disorders (MPD) and in 15 patients with secondary thrombocytosis (ST) due to a variety of aetiologies some tests of platelet function and chemistry were performed. The MPD patients showed slightly to excessively elevated platelet counts at the time of investigation and a great deal of them had a history of thrombotic and/or haemorrhagic events. The total calcium content of platelets was significantly lower (2P less than 0.001) in both groups of patients as compared to controls. In 14 of 19 patients with MPD platelet rich plasma did not respond to epinephrine (15 mumol/l), a concentration which induced at least weak aggregation in all patients with ST but one and also in healthy subjects. In patients with MPD the mean extent of all kinds of induced aggregation was significantly lower (2P less than 0.002) as compared to controls whereas in patients with ST in most cases this parameter did not differ significantly from that of controls. The results as a whole confirm the concept of an acquired storage pool deficiency in patients with MPD.

Adult↗
PubMed1988

[In vitro study of platelet concentrate preparations from whole blood using N-(2-mercaptopropionyl)-glycine].

The sulfhydryl group containing drug N-(2-mercaptopropionyl)-glycine (MPG) which inhibits platelet aggregation in a reversible manner permits to prepare platelet concentrates in non-siliconized glass containers at pH 7.4. Resuspension of platelets is possible immediately after centrifugation. In vitro platelets tests were carried out after washing out the MPG in MPG-free plasma. Thereafter, no inhibitory effects on platelet functions were found. Platelets concentrated in presence of MPG were significantly better with respect to yield, maintenance of discoid shape, aggregability, and hypotonic shock response compared with control platelets concentrated in absence of MPG.

Blood↗
PubMed1988

Methylene blue inhibits the arachidonic acid metabolism in human blood platelets.

When human blood platelets are incubated with methylene blue (MB) that oxidizes cellular NADPH, a marked inhibition of platelet aggregation and of the metabolism of arachidonic acid (AA) in both the cyclooxygenase and lipoxygenase pathway is found. The inhibition of aggregation and AA metabolism is prevented, at least partially, by the thiol-oxidizing agent diamide. The results indicate an involvement of the reduced coenzymes NADPH and glutathione (GSH) in the regulation of cyclooxygenase and lipoxygenase activity in platelets.

Arachidonic Acids↗
PubMed1988

Evaluation of preoperative blood tests for predicting deep vein thrombosis after total hip replacement.

Determinations of the total calcium content and aggregability of the platelets as well as tests of coagulation and fibrinolysis were carried out on 93 patients before undergoing total hip replacement. All patients received low dose heparin, solely or combined with dihydroergotamine. Twenty-six patients developed deep vein thrombosis (DVT) detected by the labelled fibrinogen uptake test and confirmed by ascending phlebography. Only a few tests, among them the total calcium content of platelets, showed a statistical difference between the patients who subsequently developed DVT and those who did not. Combination of several tests by a multivariate statistical analysis programme proved to have more predictive value than the analysis of single tests.

Adult↗
PubMed1987

An extract of feverfew inhibits interactions of human platelets with collagen substrates.

The interaction of platelets with surfaces coated with collagens of type III (C III) or IV (C IV) has been studied by measuring the deposition of 51-Cr-labeled platelets and by scanning electron microscopy (SEM). Experiments were performed using platelet-rich plasma (PRP) and suspensions of gel-filtered platelets (GFP). Platelets were deposited on C III mainly as surface-bound aggregates. In contrast they were deposited on C IV mainly as spread forms of individual cells. Formation of aggregates on C III was more extensive for PRP than for GFP; in contrast platelet spreading on C IV was more extensive for GFP than for PRP. The effects of an extract of the plant feverfew on platelet-collagen interactions were determined. Feverfew extract inhibited the deposition of 51-Cr-labeled platelets on both C III and C IV in a dose-dependent way. Similar concentrations of extract were needed to inhibit the formation of surface-bound aggregates and to inhibit platelet spreading in both PRP and GFP.

Blood Platelets↗
PubMed1987

Plasma from atherosclerotic patients exerts an increased degradation of platelet-activating factor.

Platelet-activating factor (PAF) is a naturally occurring phospholipid that exerts diverse biological activities. In the present study the degradation of PAF as well as lipid concentrations were measured both in plasma from 28 patients suffering from peripheral vascular disease and 18 healthy volunteers of comparable age. Beside some changes of the lipoprotein pattern it was also found that the capacity to degrade PAF is significantly elevated in the patient group. In view of this finding the question arises whether there is any link between the degradation of PAF and the development of atherosclerosis.

Aged↗
PubMed1987

Modification of the polar head group of platelet-activating factor: influence on the biological activity.

Racemic analogues of platelet-activating factor and its lyso derivatives have been prepared in which one methyl of the trimethylammonium group has been replaced by ethyl, propyl, allyl, or carboxymethylene. The influence of chemical modification on the biological activity was assessed by measuring platelet aggregation and desensitization. The results point to a crucial role of a positively charged polar head group for the expression of biological activity of platelet-activating factor. There are also some indications of a more non-specific interaction of the polar head group of platelet-activating factor with its platelet binding sites.

Humans↗