scholarly journals Thromboxane Production

2020 ◽  
Author(s):  
Keyword(s):  
Thromboxane Production

Potentiation by Adrenaline of Ca2+ Influx and Mobilization in Stimulated Human Platelets: Dissociation from Thromboxane Generation and Aggregation

1988 ◽  
Vol 59 (02) ◽  
pp. 212-215 ◽  
Author(s):  
M J Powling ◽  
R M Hardisty
Keyword(s):  
Human Platelets ◽  
The Other ◽  
Fibrinogen Binding ◽  
Thromboxane Production

SummaryIn a medium containing 1 mM extracellular Ca2+ (Ca2+o), the prior addition of 0.5 pM adrenaline to quin 2-loaded human platelets increased both the rate and amplitude of the rise in cytosolic free Ca2+ (Ca2+i) in response to sub-threshold concentrations of thrombin and PAF and these effects were not prevented by blocking either fibrinogen binding and aggregation or cyclo-oxygenase. In the presence of 2 mM EGTA ([Ca2+o] >100 nM), the rate, but not the extent of rise of [Ca2+i] was enhanced by adrenaline, and this was also unaffected by blockade of cyclo-oxygenase. Addition of adrenaline 1 min after the other agonist in the presence of 1 mM Ca2+o resulted in aggregation without further elevation of [Ca2+i]. Adrenaline thus enhances both influx and intracellular mobilization of Ca2+ by a mechanism independent of both fibrinogen binding and thromboxane production, but these effects do not fully explain its potentiation of aggregation by other agonists

Platelet Function and the Bleeding Time in Progressive Renal Failure

1988 ◽  
Vol 60 (01) ◽  
pp. 083-087 ◽  
Author(s):  
M P Gordge ◽  
R W Faint ◽  
P B Rylance ◽  
G H Neild
Keyword(s):  
Renal Failure ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Bleeding Time ◽  
C Reactive Protein ◽  
Severe Renal Failure ◽  
Reactive Protein ◽  
Thromboxane Production ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryBleeding time and platelet function tests were performed on 31 patients with progressive chronic renal failure (CRF) due to non-immunological (urological) causes, and compared with 22 healthy controls. Patients were classified as mild (plasma creatinine <300 μmol/l), moderate (300-600 μmol/l) or severe renal failure (>600 μmol/l). Bleeding time was rarely prolonged in mild and moderate CRF and mean bleeding time significantly elevated only in severe CRF (p <0.005). Haematocrit was the only index which correlated with bleeding time (r = -0.40). Platelet counts, collagen stimulated thromboxane generation, and platelet aggregation responses to ADP, collagen and ristocetin were all either normal or increased in all three CRF groups, but thromboxane production in clotting blood was reduced. Plasma fibrinogen, C reactive protein and von Willebrand factor (vWF) were elevated in proportion to CRF. We found no evidence that defects in platelet aggregation or platelet interaction with vWF prolong the bleeding time in patients with progressive CRF.

The Interrelationship between Thromboxane Biosynthesis, Aggregation and 5-Hydroxytryptamine Secretion in Human Platelets in Vitro

1980 ◽  
Vol 43 (01) ◽  
pp. 038-040 ◽  
Author(s):  
L C Best ◽  
T K Holland ◽  
P B B Jones ◽  
R G G Russell
Keyword(s):  
Human Platelet ◽  
Human Platelets ◽  
Dense Granule ◽  
Thromboxane B2 ◽  
Essential Requirement ◽  
Direct Mechanism ◽  
Thromboxane Synthetase ◽  
Thromboxane Production ◽  
Higher Doses

SummaryPlatelet aggregation, secretion of 5-hydroxy tryptamine and production of thromboxane B2 were monitored simultaneously in human platelet suspensions in the absence and presence of cyclooxygenase or thromboxane synthetase inhibitors. Aggregation, secretion and thromboxane B2 formation in response to either sodium arachidonate or epinephrine were blocked by aspirin or by 1-N-butyl imidazole suggesting that thromboxane biosynthesis was an essential requirement for platelet activation by these agents. In contrast, thrombin and collagen could apparently induce aggregation and secretion via two pathways: at low doses involving thromboxane production, but at higher doses by a direct mechanism independent of thromboxane biosynthesis. In the case of ADP, inhibition of thromboxane production blocked secretion but had little effect on aggregation, indicating that secretion was probably dependent on thromboxane biosynthesis which probably occurred as a result of aggregation. Thus it appears that although the processes of thromboxane production, release of dense granule constituents and aggregation may often be intimately linked, each process can occur independently of the other, depending upon the stimulus used.

Rapeseed Oil and Sunflower Oil Diets Enhance Platelet In Vitro Aggregation and Thromboxane Production in Healthy Men when Compared with Milk Fat or Habitual Diets

1992 ◽  
Vol 67 (03) ◽  
pp. 352-356 ◽  
Author(s):  
Marja Mutanen ◽  
Riitta Freese ◽  
Liisa M Valsta ◽  
Irma Ahola ◽  
Antti Ahlström
Keyword(s):  
Sunflower Oil ◽  
Milk Fat ◽  
Rapeseed Oil ◽  
Controlled Trial ◽  
Collagen Concentration ◽  
Aggregation Pattern ◽  
Thromboxane Production ◽  
Low Erucic Acid ◽  
Platelet Thromboxane

SummaryIn this highly controlled trial, 26 normolipidemic men (average age 28 years, range 18 to 60) were fed a baseline diet high in milk fat (MF) (fat 36% of energy, saturates 19%, monounsaturates 11%, polyunsaturates 4%), followed by a diet high in sunflower oil (SO) (fat 38% of energy, saturates 13%, monounsaturates 10%, polyunsaturates 13%) and another diet high in low erucic-acid rapeseed oil (RO) (fat 38% of energy, saturates 12%, monounsaturates 16%, polyunsaturates 8%). All diets were mixed natural diets with the same cholesterol contents. The baseline milk fat diet was given for 14 days and the oil diets for 24 days in a blind cross-over design. The platelet in vitro aggregation (slope %/min) induced by 1, 2 and 3 pM ADP and collagen (25 pg/ml PRP) was highly significantly (p <0.001) increased after both oil diets when compared with the results from the milk fat diet. The aggregation pattern determined by threshold collagen concentration confirmed increased collagen sensitivity of the platelets after the rapeseed oil diet (p <0.001). The enhancement of platelet aggregation was associated with increased in vitro platelet thromboxane production after the oil diets vs. the milk fat diet (p <0.05 after the sunflower oil diet and p <0.001 after the rapeseed oil diet).

THROMBOXANE-A2 MEDIATES THE ACTION OF INOSITOL (1.4.5) TRISPHOSPHATE (IP3) IN SAPONIN-PERMEABILISED PLATELETS

1987 ◽  
Author(s):  
K S Authi ◽  
B J Evenden ◽  
E J Hornby ◽  
N Crawford
Keyword(s):  
Phospholipase A2 ◽  
Shape Change ◽  
Thromboxane A2 ◽  
Thromboxane B2 ◽  
Cyclooxygenase Inhibitors ◽  
Storage Site ◽  
Platelet Surface ◽  
Surface Receptors ◽  
Thromboxane Receptor ◽  
Thromboxane Production

Inositol trisphosphate (IP3) has now been identified as an important intracellular second messenger that can initiate the release of Ca2+ from intracellular stores in a variety of cells, including platelets. We have studied the effects of IP3 on washed platelets permeabilised with saponin (12-14 μg/mi) which allows penetration into the cell of low M.Wt polar molecules. The permeabilised cells show normal responses to the agonists thrombin and collagen. The addition of IP (1-20 μM) after saponin treatment induces shape change, aggregation and secretion of preloaded [14C] 5HT. Concomitant with these responses, thromboxane is produced in a dose related manner. With 20 μM IP3 thromboxane B2 increases from basal levels of 5-4 ± 3-0 ng/ml to 140 ± 23 ng/ml. Both thromboxane production and the platelet responses induced by IP3 are inhibited by pretreatment with the cyclooxygenase inhibitors, indomethacin (EC50 50 μM) and aspirin (EC50 30 μM). Aggregation and secretion responses to IP3 are also inhibited by thromboxane B2 receptor agonists; EPO 92 (R. Jones, Edinburgh) and AH 23848 (Glaxo Ltd.). If Ca2+ EGTA buffers age used with permeabilised platelets to "lock" the cytosolic [Ca2+] at 0.1 μM, thromboxane production is reduced to the basal level. Intact platelets were labelled with Ca2+ (4h incubation) and after washing, resuspension and saponisation, IP3 induced the release of 20% of the cell associated Ca2+. The release was unaffected by pretreatment with antimycin and oligomycin indicating an gndoplasmic reticulum-lige storage site for the sequestered Ca2+. This IP3 -induced Ca2+ release was also not affected by pretreatment with either cyclooxygenase inhibitors or thromboxane receptor antagonists (EPO 92 and AH 23848). We believe these studies indicate that the action of IP3 in sagonised platelets involves release of intracellularly stored Ca2+, activation of phospholipase A2 and cyclooxygenase, and production of thromboxane A2. The release of thromboxane mediates and/or attenuates platelet responses by acting upon platelet surface receptors.

The C50T polymorphism of the cyclooxygenase-1 gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid

2008 ◽  
Vol 100 (07) ◽  
pp. 70-75 ◽  
Author(s):  
Martijn G. H. van Oijen ◽  
Santosh Sundaresan ◽  
Marc A. Brouwer ◽  
Rene H. M. te Morsche ◽  
Wessel Keuper ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Platelet Aggregation ◽  
Primary Endpoint ◽  
Low Dose ◽  
Cardiovascular Death ◽  
Hazard Ratio ◽  
Cyclooxygenase 1 ◽  
Thromboxane Production ◽  
The Common ◽  
Cox 1

SummaryAspirin prevents thrombotic events by inhibiting platelet cyclooxygenase-1 (COX-1), thus reducing thromboxane A2 formation and platelet aggregation. The C50T polymorphism of COX-1 is associated with an impaired inhibition of both thromboxane production and in-vitro platelet aggregation by aspirin. We studied whether this polymorphism is also associated with the risk of clinical thrombotic events in patients using aspirin. We included 496 patients admitted to our Coronary Care Unit for various indications treated with aspirin 80 mg daily. Genotyping for the C50T polymorphism demonstrated that 86.7% of the patients had the common genotype, and 13.3% had the variant (12.5% heterozygous, 0.8% homozygous). Baseline variables were well balanced, except that patients with the common genotype more frequently used aspirin prior to admission compared to those patients with the variant genotype. The composite primary endpoint of myocardial infarction, stroke, and/or cardiovascular death occurred in 98 patients (19.8%). Myocardial infarction occurred in 9.6% of patients, stroke in 1.6%, and cardiovascular death in 12.1%.The unadjusted hazard ratio (95% CI) for the primary endpoint for patients with the variant versus the common genotype was 1.07 (0.62–1.85), p=0.8.The adjusted hazard ratio was 0.86 (0.49–1.50), p=0.6. In prior laboratory studies the COX-1 C50T polymorphism was associated with an impaired inhibitory effect of aspirin on thromboxane production and platelet function. However, in this cohort of patients using low-dose aspirin for secondary prevention the polymorphism was not associated with a higher risk of atherothrombotic events.

Effect of selective inhibition of the p38 MAP kinase pathway on platelet aggregation

2004 ◽  
Vol 92 (12) ◽  
pp. 1387-1393 ◽  
Author(s):  
Athan Kuliopulos ◽  
Ramon Mohanlal ◽  
Lidija Covic
Keyword(s):  
Platelet Aggregation ◽  
P38 Mapk ◽  
Coronary Intervention ◽  
Selective Inhibition ◽  
P38 Map Kinase ◽  
Significant Inhibition ◽  
Mitogen Activated Protein Kinase ◽  
Thromboxane Production ◽  
Mapk Inhibitor

SummarySystemic inflammation has been shown to be a contributing factor to the instability of atherosclerotic plaques in patients with acute coronary syndromes (ACS). VX-702, a novel p38 mitogen-activated protein kinase (MAPK) inhibitor, is currently under investigation in ACS patients with unstable angina to evaluate its safety and efficacy during percutaneous coronary intervention (PCI).The role of p38 MAPK in platelet aggregation of normal individuals was examined using the selective second generation p38 MAPK inhibitor VX-702. Treatment of platelets with thrombin (activates PAR1 and PAR4 thrombin receptors), SFLLRN (PAR1), AYPGKF (PAR4), collagen (α2β1 and GPVI/FCγIIR receptors) and U46619 (TXA2) resulted in strong activation of p38 MAPK. Activation of the GPIb von Willebrand factor receptor with ristocetin did not stimulate p38 MAPK. Pre-treatment of platelets with 1 μM VX-702 completely inhibited activation of p38 MAPK by thrombin, SFLLRN, AYPGKF, U46619, and collagen. There was no effect of VX-702 on platelet aggregation induced by any of the agonists in the presence or absence of aspirin, heparin or apyrase. It has been postulated that a potential role of p38 MAPK is to activate phospholipase A2 (cPLA2) which catalyses formation of arachidonic acid leading to production of thromboxane. Interestingly, we show contrasting effects of p38 MAPK inhibition as compared to aspirin inhibition on platelet aggregation in response to collagen. Blockade of TXA2 production by aspirin results in significant inhibition of collagen activation. However, VX-702 has no effect on collagen-mediated platelet aggregation, suggesting that blocking p38 MAPK does not effect thromboxane production in human platelets. Therefore, unlike aspirin blockade of thromboxane production in platelets, p38 MAPK inhibitors such as VX-702 do not significantly affect platelet function and would not be expected to contribute to an elevated risk of bleeding side-effects in treated patients.

Platelet thromboxane production during endotoxin shock

1981 ◽  
Vol 11 (6-7) ◽  
pp. 648-650 ◽  
Author(s):  
Arthur Prancan ◽  
David Simon ◽  
Larry Pope
Keyword(s):  
Endotoxin Shock ◽  
Thromboxane Production ◽  
Platelet Thromboxane

Dietary fatty acids and platelet thromboxane production in puerperal women and their offspring

1986 ◽  
Vol 155 (1) ◽  
pp. 146-149 ◽  
Author(s):  
Pekka Kääpä ◽  
Matti Uhari ◽  
Tapio Nikkari ◽  
Lasse Viinikka ◽  
Olavi Ylikorkala
Keyword(s):  
Fatty Acids ◽  
Dietary Fatty Acids ◽  
Thromboxane Production ◽  
Platelet Thromboxane
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