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At least 1,207 records · Page 67Linked to original sources
PubMed1997

Effects of the co-polymer surfactant, Pluronic F-68, on platelet aggregation in human whole blood.

The effects have been studied of Pluronic F-68 on platelet aggregation in human whole blood. The median spontaneous platelet aggregation in normal blood (n = 15) was 18.4% [interquartile range (IQ) = 10.5-24.2%]. Commercial grade Pluronic F-68 significantly (P < 0.05) reduced platelet aggregation at 7.3 microM (median = 8.4%, IQ = 3.9-13.4; n = 12) and almost eliminated aggregation at concentrations of > 58 microM (median = 2.0%, IQ = 0.0-3.5). Similar results were obtained with a silica gelpurified Pluronic F-68 fraction (n = 3). Pluronic F-68 also accelerated the rate of platelet dis-aggregation in blood treated with 0.3, 1.0 or 3.0 mM adenosine di-phosphate. These results suggest that the therapeutic effects of Pluronic F-68 in ischaemic injury may be due, in part, to inhibition of platelet aggregation in the microcirculation. The beneficial effects of tissue perfusion with oxygen-carrying perfluorochemical emulsions, containing Pluronic F-68, may also involve direct effects of the surfactant on platelets.

Adenosine Diphosphate↗
PubMed1989

PAF-induced platelet aggregation ex vivo as a method for monitoring pharmacological activity in healthy volunteers.

Platelet aggregation induced ex vivo by aggregating factors such as adrenaline, ADP, collagen or PAF may be useful as a model for describing drug effects in humans. In the two studies reported here, PAF-induced platelet aggregation ex vivo was used as an indicator of the pharmacological activity in healthy volunteers of the newly developed specific PAF-antagonist WEB 2086. In intravenous and inhalative single rising dose tolerance trials this method proved useful for monitoring the pharmacological action of the compound tested. After administration of placebo no relevant pharmacological activity was observed. In both studies increasing dosages of the test substance showed clear, dose-related inhibition of PAF-induced platelet aggregation. Ex vivo PAF-induced platelet aggregation thus provides a simple and rapid means of assessing functional PAF antagonism during trials of PAF-antagonists in human volunteers.

Adult↗
PubMed2000

Bioactive amide of prostaglandin E1 and ethanolamine plasmalogen analog of platelet-activating factor inhibits several pathways of human platelet aggregation.

The influence of an amide of prostaglandin E1 and ethanolamine plasmalogen platelet-activating factor analog 1-O-alk-1;-enyl-2-acetyl-sn-glycero-3-phospho-(N-11alpha, 15alpha-dioxy-9-keto-13-prostenoyl)ethanolamine (PGE1-PPAF) on platelet-activating factor (PAF)-, ADP-, and thrombin-induced human platelet aggregation has been studied. It was found that PGE1-PPAF inhibits the PAF-, ADP-, and thrombin-induced platelet aggregation in platelet-rich plasma. 1-O-alk-1;-enyl-2-acetyl-sn-glycero-3-phosphoethanolamine inhibited PAF-induced aggregation up to 50% but had no influence on platelet aggregation induced by ADP or thrombin. The ethanolamine plasmalogen analog of PAF 1-O-alk-1;-enyl-2-acetyl-sn-glycero-3-phospho-(N-palmitoyl)ethanolami ne, having a palmitoyl residue instead of PGE1, did not inhibit platelet aggregation induced by PAF, ADP, or thrombin. We propose that inhibition of human platelet aggregation by PGE1-PPAF is mediated by its action on platelet PAF-receptors and the adenylate cyclase system.

Alprostadil↗
PubMed1985

Effect of cetiedil on platelet aggregation and thromboxane synthesis.

Cetiedil was found to inhibit platelet aggregation and thromboxane synthesis induced by thrombin and arachidonic acid. When platelets were activated by thrombin, half maximal inhibition (ED50 effective dose of cetiedil necessary for 50% inhibition) for platelet aggregation was 100 microM while that for thromboxane B2 (TXB2) production was 50 microM. When arachidonic acid was used, the ED50 for platelet aggregation was 100 microM while that for TXB2 production was 150 microM. The presence of calcium ions did not affect on the inhibitory effects of cetiedil. The cAMP level in platelets did not increase after incubation with cetiedil. Cetiedil appears to inhibit the activation of platelets related to thromboxane synthesis.

Antisickling Agents↗
PubMed1998

Distinct sequences of the glycoprotein Ib-binding domain of von Willebrand factor involved in shear induced platelet aggregation.

Shear-induced platelet aggregation (SIPA) requires von Willebrand factor (vWF) binding to the platelet receptors GPIb and alphaIIbbeta3. In order to determine the vW F sequences involved in SIPA at 4000/s, we studied the llb 3 effect of three monoclonal antibodies (mabs) 724, 713 and 328 to the A1 domain of vWF. We found that mab 724 induced an enhanced SIPA via a Fc gamma-receptor independent mechanism. In contrast, mab 713 and mab 328 could inhibit SIPA by 52 and 91% , respectively. Based on distinct effects on SIPA, we can propose the following working model for the interaction between vWF and GPIb: mabs 713 and 328, which block SIPA, may recognize an epitope that is involved in binding to GPIb, whereas mab 724, which increases SIPA in the presence of vWF, may mimic the effect of botrocetin when binding to vWF, by inducing an active conformation of vWF, which may be more sensitive to high shear rate.

Journal Article↗
PubMed2000

Molecular cloning of glycoprotein Ib-binding protein, flavocetin-A, which inhibits platelet aggregation.

Flavocetin-A is a strong platelet aggregation inhibitor isolated from the venom of Trimeresurus flavoviridis. It binds specifically to platelet glycoprotein Ib with high affinity and inhibits von Willebrand factor-dependent platelet aggregation. The apparent molecular weight of flavocetin-A is 149 kDa. It consists of two subunits, alpha (17 kDa) and beta (14 kDa). The amino acid sequences of the alpha and beta subunits were determined from cloned cDNAs. Deduced amino acid sequences showed signal peptide-sequences of 23 amino acids for both alpha and beta subunits, mature peptide sequences of 135 amino acids for the alpha subunit, and 125 amino acids for the beta subunit. The amino acid sequences of alpha and beta subunits show high degrees of homology to those of C-type lectin-like venom proteins such as habu coagulation factors IX/X-binding protein (IX/X-bp), botrocetin, and alboaggregin-B. The cysteinyl residues of flavocetin-A, IX/X-bp, and botrocetin are conserved, except that flavocetin-A contains Cys 135 in the alpha subunit and Cys 3 in the beta subunit. We assumed that the arrangements of disulfide bridges in flavocetin-A are similar to those of IX/X-bp and botrocetin, and the additional Cys 135 of the alpha subunit and Cys 3 of the beta subunit are involved in novel disulfide bridges. These findings suggested that the additional disulfide bridges formed with Cys 135 of the alpha subunit and Cys 3 of the beta subunit cause polymerization of C-type lectin-like heterodimers.

Amino Acid Sequence↗
PubMed2000

Inhibiting and disaggregating effect of gel-filtered Galega officinalis L. herbal extract on platelet aggregation.

The in vitro inhibiting and disaggregating effect on platelet aggregation of a gel-fractionated herbal extract from Galega officinalis L. is examined. The obtained Sephadex G-25 filtered fraction was 35-36 times more active than the crude extract. The threshold concentration at which this fraction inhibits platelet aggregation (5-10% inhibition) by 50 microM adenosine 5'-diphosphate (ADP) is 4.5-5 microg per 1 ml platelet-rich plasma (PRP). At a concentration of 35 microg/ml PRP the fraction inhibits 50% of aggregation by ADP and at a concentration of 125 microg/ml PRP fully inhibits the aggregation of PRP by ADP. At a concentration of 40 microg/ml PRP the fraction inhibits initiation of platelet aggregation by 0.18 mg/ml collagen and at 50 microg/ml PRP inhibits the initiation of aggregation by 0.7 units/ml thrombin. The G-25 filtered fraction shows a strong disaggregating effect on aggregated PRP. At a concentration of 65-75 microg/ml PRP, the fraction is able to disaggregate the 50-53% of aggregated platelet-rich plasma by 50 microM ADP, and 25% of aggregated PRP by 0.18 mg/ml collagen.

Chromatography, Gel↗
PubMed1980

Effect of prenatal drug administration on maternal and neonatal platelet aggregation and PF4 release.

Release of platelet antiheparin activity (platelet factor 4, PF4) induced by collagen and l-epinephrine, is normal in newborn infants without antenatal drug exposure. In contrast, PF4 release in platelets of infants of mothers with membrane-stabilizing drug ingestion is decreased to a greater extent than in their respective mothers. Platelet aggregation gives a qualitative indication of response. Platelets of mothers with antenatal drug exposure and those of their infants showed only a one-wave response to adenosine diphosphate, while platelets of these same mothers still showed a two-wave aggregation response to l-epinephrine. In contrast, platelets of all neonates lacked epinephrine-induced aggregation response, even when washed and resuspended in adult plasma. Our studies show that prenatal drugs have an effect on the platelet release mechanism in both mothers and their exposed infants; but the effect on the epinephrine-induced platelet response is less in mothers. Newborn infants have different aggregation and platelet release response to epinephrine which suggests that platelet aggregation and the release reaction can occur independently of each other.

Adenosine Diphosphate↗
PubMed1983

[Platelet aggregation inhibition with calcium dobesilate].

In 52 patients with pathologically increased platelet aggregation the effect of a 4-day oral treatment of 500 mg, 1000 mg and 1500 mg calcium dobesilate (Dexium 500) on spontaneous platelet aggregation was assessed using PAT III of Breddin. In comparison to placebo 1500 mg calcium dobesilate reduced platelet aggregation significantly, 1000 mg and 500 mg calcium dobesilate, however, didn't influence platelet aggregation.

Adult↗
PubMed1982

Mechanisms of abnormal platelet aggregation in systemic lupus erythematosus.

Platelet aggregation was measured in 14 patients with systemic lupus erythematosus (SLE) and 13 normal controls. Ten SLE patients (group I) showed decreased responsiveness to collagen, while aggregation was normal in 4 (group II). Group I patients also responded poorly to epinephrine. Platelets from SLE patients did not differ from controls in the production of malondialdehyde in response to N-ethylmaleimide, suggesting intact prostaglandin synthetic pathways. However, a significant decrease (P less than 0.005) in platelet levels of the dense granule constituent, serotonin, was noted in group I SLE patients. Treatment of SLE platelet-rich plasma with deoxyribonuclease (DNase) resulted in enhancement of collagen-induced aggregation in 4 group I SLE patients, but not in 1 group II or 8 normal individuals. These results suggest that defective aggregation in SLE platelets may be partially related to a storage pool deficiency state. However, the ability to restore aggregation to collagen by digestion of platelet-rich plasma with DNase indicates that the defect is reversible and that it is perhaps mediated by plasma or platelet-associated DNA.

Blood Platelet Disorders↗
PubMed2000

Inhibition of rabbit platelet aggregation by nucleoside 5'-alkylphosphates: correlation with inhibition of agonist-induced calcium influx.

We investigated the effects of uridine 5'-alkylphosphates on agonist-induced aggregation, increased intracellular calcium concentration [Ca(2+)](i), and Ca(2+) (Mn(2+)) influx in washed rabbit platelets. Uridine 5'-hexadecylphosphate (UMPC16) and uridine 5'-eicosylphosphate (UMPC20) at a concentration of 1 x 10(-5) M inhibited platelet aggregation induced by platelet-activating factor (PAF), thrombin, arachidonic acid, and ADP. UMPC16 did not cause significant interference in the binding of [(3)H-acetyl]PAF to platelets. The inhibition of PAF-induced platelet aggregation by UMPC16 was dependent upon the addition time; UMPC16 was ineffective at 60 sec when the extracellular calcium uptake reached the maximum level in PAF-stimulated platelets. Furthermore, UMPC16 inhibited guanosine 5'-O-(3-thiotriphosphate)-induced platelet aggregation but did not affect ionophore A23187- and calcium-independent agonist phorbol 12-myristate 13-acetate-induced platelet aggregation. UMPC16 markedly inhibited the Ca(2+) (Mn(2+)) influx induced by PAF and ADP, and partly inhibited the [Ca(2+)](i) increase induced by the receptor-mediated stimulation. On the other hand, UMPC16 did not affect the [Ca(2+)](i) increase and Ca(2+) (Mn(2+)) influx induced by ionomycin. These experiments suggest that inhibition of calcium influx associated with receptor-mediated platelet activation may be involved in the action of UMPC16.

Adenosine Diphosphate↗
PubMed1988

Platelet aggregation and thromboxane B2 release in patients with acute myocardial infarction--their relation to coronary patency.

Platelet function in the aortic blood in 39 patients who underwent intracoronary thrombolysis with urokinase was evaluated in the acute stage of myocardial infarction and after 4 weeks. The patients were classified into 2 groups according to the patency of the infarct vessel shown by coronary arteriography before urokinase administration. In the acute stage, 26 patients with completely occluded infarct vessel (group 1) showed a decreased level of platelet aggregation induced by adenosine diphosphate or arachidonic acid as compared with 13 patients with patent infarct vessel (group 2). The platelet aggregation in group 1 increased 4 weeks later and both groups showed similarly enhanced platelet aggregation levels as compared with normal controls. Like platelet aggregation, serum thromboxane B2 production in group 1 was lower than that in group 2 in the acute stage. Plasma thromboxane B2 levels in the aorta in both groups were significantly elevated in the acute stage, and were normalized after 4 weeks. This elevation of thromboxane B2 seems to be due to its washout from the infarct vessel, because plasma thromboxane B2 levels were significantly higher in the great cardiac vein than those in the aorta after successful reperfusion in group 1 or group 2. In conclusion, despite a significant elevation in plasma thromboxane B2 levels, platelet aggregation and serum thromboxane B2 production relatively decrease in patients with totally occluded infarct vessel. The patency of the infarct vessels should be taken into account when evaluating platelet function in acute myocardial infarction.

Adult↗
PubMed1994

Comparison of the effects of two diets rich in monounsaturated fatty acids differing in their linoleic/alpha-linolenic acid ratio on platelet aggregation.

The effect of dietary linoleic/alpha-linolenic acid ratio on human platelet aggregation in vitro was investigated using low-erucic acid rapeseed oil and high-oleic acid sunflower oil as the major fat sources. In a cross-over study 20 healthy male subjects, average age 29 year (range 20-46 yr), followed experimental rapeseed oil (RO) and Trisun-sunflower oil (TSO) diets after their habitual diet for six weeks. Subjects were provided most of the fat containing foods but were allowed to eat other foods almost freely. Fatty acid compositions of the diets calculated from dietary records were as follows (saturated/monounsaturated/polyunsaturated fatty acids): RO diet 12.4/18.6/8.9% of total energy (en%) (linoleic/alpha-linolenic acid ratio 2.8) and TSO diet 11.8/17.8/8.3 en% (linoleic/alpha-linolenic acid ratio 28), respectively. Plasma cholesterol ester fatty acid composition proved compliance to the experimental diets. Platelet aggregations induced by ADP (1, 2 and 3 microM) or thrombin (0.12, 0.15 and 0.18 NIH/ml) were significantly enhanced and collagen-(1.5, 2.5 and 5.0 micrograms/ml) induced aggregation tended to be enhanced after the TSO diet compared with the RO diet. After the TSO diet platelet aggregation was enhanced from the level of the habitual diets by one thrombin (0.18 NIH/ml), one collagen (1.5 micrograms/ml) and all three ADP concentrations. The diets had no effect on antithrombin III activity. Results show that platelet aggregation in vitro decreases as the ratio of linoleic acid to alpha-linolenic acid decreases in diets rich in monounsaturated fatty acids.

Adenosine Diphosphate↗
PubMed1994

Human recombinant phospholipase A2 inhibits platelet aggregation in vitro and in vivo in rat and guinea pig.

Platelets contain a phospholipase A2 in their granules which can be released in response to various activating stimuli in vitro as well as in vivo. Human recombinant phospholipase A2 (1-10 micrograms/ml) had no direct effect on platelet aggregation in vitro using rabbit platelet rich plasma. In contrast human recombinant phospholipase A2 (1-20 micrograms/ml) was able to inhibit aggregation of washed rabbit platelet in vitro induced by collagen (0.250-2.0 micrograms/ml). When rabbit platelet rich plasma was recalcified with CaCl2 1 M in the presence of the thrombin inhibitor hirulog (10 micrograms/ml), human recombinant phospholipase A2 (10-40 micrograms/ml) was able to inhibit platelet aggregation. The anti-aggregatory effect was removed by incubation of platelet rich plasma with a monoclonal anti-human recombinant phospholipase A2 antibody. Human recombinant phospholipase A2 (1-10 micrograms) inhibited 111In-labelled platelet accumulation within the thoracic region of rats and guinea pigs induced by i.v. administration of submaximal doses of collagen or adenosine diphosphate. Phospholipase A2 (1-20 micrograms/ml) from Naja mocambique mocambique snake venom had no direct effect on platelet aggregation in vitro. However, Naja phospholipase A2 administered i.v. to rats or guinea pigs was able to induce a dose related accumulation of 111In-labelled platelet within the thoracic region. The inhibitory effect of exogenously added human recombinant phospholipase A2 on platelet aggregation in vivo suggests a possible pathophysiological role for the extracellular form of phospholipase A2 but this property is not a feature of all phospholipase A2 preparations.

6-Ketoprostaglandin F1 alpha↗
PubMed2005

The organomercurial 4-aminophenylmercuric acetate, independent of matrix metalloproteinases, induces dose-dependent activation/inhibition of platelet aggregation.

Matrix metalloproteinases (MMPs) play an important role in many biological and pathological processes including tissue remodeling, wound healing, inflammation, atherosclerosis, and cancer. Numerous publications have supported the concept that activated MMP-2 enhances agonist-induced platelet aggregation and activated MMP-9 inhibits platelet aggregation. In this study, we demonstrated that the organomercurial compound, 4-aminophenyl mercuric acetate (APMA), which is routinely employed to activate latent MMPs at a concentration of 1000 microM, induces platelet aggregation at low concentration (5 microM) and inhibits agonist-induced platelet aggregation at concentrations >or= 50 microM. Activated MMP-2, MMP-1, and MMP-9, following removal of APMA by ultrafiltration through an anisotropic membrane, exert no independent effect on platelet aggregation. Acetylsalicylic acid and BAPTA inhibited APMA-induced platelet aggregation indicating that the APMA mediated pathway of platelet activation is dependent upon thromboxane and calcium signaling. Zinc chelation with 1,10-phenanthroline, which inhibits zinc-dependent proteins including metalloproteinases, also abrogated platelet functional responses to APMA. Additional studies will be required to clarify the mechanism of the biphasic effect of APMA on platelet aggregation.

Calcium Signaling↗
PubMedDate not supplied

[Characterization of platelets aggregation inhibitor from Agkistrodon blomhoffii ussuriensis snake venom].

Platelet aggregation inhibitor--"Blomus-B" from Agkistrodon blomhoffii ussuriensis venom has been isolated by affinity and ion-exchange chromatography. The purified inhibitor is a novel non-enzymatic single-chain protein with molecular weigth of 13 kDa. "Blomus-B" causes a change of platelets shape and takes effect on ADP- and adrenalin-induced platelet aggregation.

Agkistrodon↗
PubMed1998

Differential effect of the antidiabetic thiazolidinediones troglitazone and pioglitazone on human platelet aggregation mechanism.

Troglitazone and pioglitazone, antidiabetic thiazolidinediones, are known to improve insulin resistance. However, the effect of these drugs on platelet aggregation remains unclear. The chemical structure of troglitazone contains vitamin E. Accordingly, we studied the effect of troglitazone, pioglitazone, and vitamin E on thrombin-induced platelet aggregation, metabolism of phosphoinositide, protein phosphorylation, protein kinase C (PKC)-alpha and -beta, and phosphatidylinositol (PI) 3-kinase activation in vitro in human platelets. Maximum platelet aggregation by ADP, collagen, and thrombin decreased in the presence of 0.1-1 micromol/l troglitazone and 500 nmol/l vitamin E for 60 min compared with controls. However, pioglitazone did not inhibit ADP-, collagen-, or thrombin-induced platelet aggregation. Pretreatment with troglitazone and vitamin E, but not with pioglitazone, resulted in decreases in thrombin-induced phosphatidic acid production, hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C, and 47-kDa protein phosphorylation. Thrombin-induced PKC-alpha and -beta activation in membrane fraction was suppressed by pretreatment with troglitazone and vitamin E, but not with pioglitazone. Separately, troglitazone and pioglitazone stimulated PI 3-kinase activity, but thrombin-induced PI 3-kinase activation was suppressed by pretreatment with troglitazone and pioglitazone for 60 min. These results suggest that troglitazone and vitamin E, but not pioglitazone, have a potent inhibitory effect on platelet aggregation via suppression of the thrombin-induced activation of phosphoinositide signaling in human platelets. Finally, the chemical structure of vitamin E may contribute to the inhibitory effect of troglitazone on platelet aggregation in human platelets.

Adenosine Diphosphate↗
PubMedDate not supplied

In vitro inhibitory effect of SR 27417, a potent platelet-activating factor (PAF) receptor antagonist, on the PAF-induced bovine platelet aggregation.

The in vitro inhibitory effect of SR 27417, an antagonist of the platelet-activating factor (PAF) receptor, on PAF-induced platelet aggregation was studied in blood collected from seven healthy Friesien calves. Inhibitory effects of SR 27417 were determined at thirteen different concentrations (0.1-400 nM) by using the dose-response curves of PAF on calf platelet aggregation. In the presence of SR 27417, the maximal slopes of aggregation (%/min) induced by low and high concentrations of PAF were significantly different from the control values obtained without an antagonist at p < or = 0.05 and p < or = 0.01 respectively. In vitro PAF-induced calf platelet aggregation was dose-dependently inhibited by SR 27417. The drug inhibited PAF-induced platelet aggregation in a competitive reversible manner (pA2 = 10.46 +/- 2.36 mol x L(-1)). In conclusion, the results of our study showed that addition of SR 27417 to bovine platelet in vitro inhibits PAF-induced platelet aggregation.

Animals↗