New Series of Pyrazoles and Imidazo-Pyrazoles Targeting Different Cancer and Inflammation Pathways

(1) Background: different previously synthesized pyrazoles and imidazo-pyrazoles showed interesting anti-angiogenic action, being able to interfere with ERK1/2, AKT and p38MAPK phosphorylation in different manners and with different potency; (2) Methods: here, a new small compound library, endowed with the same differently decorated chemical scaffolds, has been synthetized to obtain new agents able to inhibit different pathways involved in inflammation, cancer and human platelet aggregation. (3) Results: most of the new synthesized derivatives resulted able to block ROS production, platelet aggregation and p38MAPK phosphorylation both in platelets and Human Umbilical Vein Endothelial cells (HUVEC). This paves the way for the development of new agents with anti-angiogenic activity.

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Inhibitory Effect of Staphylokinase on Platelet Aggregation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649679 ◽

1993 ◽

Vol 70 (05) ◽

pp. 834-837 ◽

Cited By ~ 6

Author(s):

Akira Suehiro ◽

Yoshio Oura ◽

Motoo Ueda ◽

Eizo Kakishita

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Degradation Products ◽

Platelet Rich Plasma ◽

Inhibitory Effect ◽

Effective Concentration ◽

Inhibit Platelet Aggregation ◽

Platelet Suspension ◽

Washed Platelet ◽

Human Platelet Aggregation

SummaryWe investigated the effect of staphylokinase (SAK), which has specific thrombolytic properties, on human platelet aggregation. Platelet aggregation induced with collagen was observed following preincubation of platelets in platelet-rich plasma (PRP) or washed platelet suspension (WP) with SAK at 37° C for 30 min. SAK inhibited platelet aggregation in PRP only at the highest examined concentration (1 x 10-4 g/ml). Although SAK did not inhibit platelet aggregation in WP which contained fibrinogen, it did when the platelets had been preincubated with SAK and plasminogen. The most effective concentration in WP was 1 x 10-6 g/ml. The effect could be inhibited by adding aprotinin or α2-antiplasmin. The highest generation of plasmin in the same preincubation fluid was detected at 1 x 10-6 g/ml SAK. We concluded that SAK can inhibit platelet aggregation in WP by generating plasmin and/or fibrinogen degradation products, but is only partially effective in PRP because of the existence of α2-antiplasmin.

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Differential Ability of Agonists to Express Distinct Pools of Fibrinogen (Gpllb/llla) Receptors which Can Mediate the Aggregation of Human Platelets

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651035 ◽

1989 ◽

Vol 62 (03) ◽

pp. 955-961 ◽

Cited By ~ 4

Author(s):

Ian S Watts ◽

Rebecca J Keery ◽

Philip Lumley

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Surface Membrane ◽

Blood Platelet ◽

Human Platelets ◽

Membrane Glycoprotein ◽

Platelet Surface ◽

Human Platelet Aggregation ◽

Differential Ability ◽

Blood Platelet Aggregation

SummaryWe have investigated the effect of two procedures that modify human platelet surface membrane glycoprotein (Gp) IIb and IIIa complexes upon whole blood platelet aggregation to a range of agonists. (A) Irreversible disruption of complexes by temporary (30 min) Ca2+-deprivation with EGTA at 37° C. (B) Binding of a monoclonal antibody M148 to the complex. EGTA exposure abolished aggregation to ADP, adrenaline and PAF. In contrast, full aggregation curves to collagen and U-46619 could still be established. EGTA exposure reduced M148 binding to platelets by 80%. Excess M148 abolished aggregation to ADP, PAF, collagen and U-46619. However, upon removal of unbound antibody from platelets full aggregation curves to collagen and U-46619 but not to ADP and PAF could be re-established. Thus human platelet aggregation to ADP, PAF and adrenaline appears absolutely dependent upon surface membrane GpIIb/IIIa complexes. In contrast, collagen and U-46619 cause expression of an additional distinct pool of Gp complexes inaccessible to EGTA and M148 in unstimulated platelets which is intimately involved in aggregation to these agonists.

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Synergism Between Prostacyclin (PGI2) and Prazosin on Human Platelet Aggregation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657131 ◽

1982 ◽

Vol 47 (01) ◽

pp. 76-76 ◽

Cited By ~ 1

Author(s):

P K Moore

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Human Platelet Aggregation

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Heparin Counteracts the Antiaggregating Effect of Prostacyclin by Potentiating Platelet Aggregation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657326 ◽

1983 ◽

Vol 49 (02) ◽

pp. 081-083 ◽

Cited By ~ 13

Author(s):

Vittorio Bertelé ◽

Maria Carla Roncaglioni ◽

Maria Benedetta Donati ◽

Giovanni de Gaetano

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Specific Interaction ◽

Inhibitory Effect ◽

Effective Inhibitor ◽

Inhibitory Potency ◽

Human Platelet Aggregation

SummaryIt has recently been reported that heparin neutralizes the inhibitory effect of prostacyclin (PGI2) on human platelet aggregation. The mechanism of this interaction has not yet been unequivocally established. We present here evidence that heparin (Liquemin Roche) does not react directly with PGI2 but counteracts its inhibitory effect by potentiating platelet aggregation. In the absence of heparin, PGI2 was a less effective inhibitor of platelet aggregation induced by the combination of ADP and serotonin than by ADP alone. Moreover, the inhibitory effect of PGI2 was similarly reduced when increasing the concentrations of ADP (in the absence of heparin). The lack of a specific interaction between heparin and PGI2 is supported by the observation that, in the presence of heparin, other prostaglandins such as PGD2 and PGE1, and a non-prostanoid compound such as adenosine also appeared to lose their inhibitory potency. It is concluded that heparin opposes platelet aggregation inhibitory effect of PGI2 by enhancement of platelet aggregation.

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Inhibition of Arachidonate-Induced Human Platelet Aggregation by a Single Low Oral Dose of Aspirin in Combination with a Thromboxane Synthase Inhibitor

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661177 ◽

1984 ◽

Vol 52 (02) ◽

pp. 215-215 ◽

Cited By ~ 3

Author(s):

Chiara Cerletti ◽

Grazyna Rajtar ◽

Vittorio Bertelé ◽

Giovanni de Gaetano

Keyword(s):

Platelet Aggregation ◽

Oral Dose ◽

Human Platelet ◽

Thromboxane Synthase ◽

Human Platelet Aggregation ◽

Thromboxane Synthase Inhibitor ◽

Synthase Inhibitor

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Anti-Platelet Properties of Apple Must/Skin Yeasts and of Their Fermented Apple Cider Products

Beverages ◽

10.3390/beverages7030054 ◽

2021 ◽

Vol 7 (3) ◽

pp. 54

Author(s):

Donal Moran ◽

Mary Fleming ◽

Eimear Daly ◽

Natasha Gaughan ◽

Ioannis Zabetakis ◽

...

Keyword(s):

Fatty Acids ◽

Platelet Aggregation ◽

Functional Properties ◽

Human Platelet ◽

Omega 3 ◽

Apple Cider ◽

Human Platelet Aggregation ◽

Yeast Strains ◽

Omega 6 ◽

Anti Inflammatory

Alcoholic beverages like apple cider are considered functional beverages with several health benefits, when consumed in moderation, which are mainly attributed to their microbiota and the plethora of their bioactive compounds. Among them, bio-functional polar lipids (PL) have recently been found in apple cider, which despite low quantities, have exhibited strong anti-inflammatory and anti-platelet properties, while fermentation seems to affect the functionality of apple cider’s PL bioactives. The aim of the present study was to elaborate yeast strains isolated from the complex mixtures of apple surface and must yeasts for evaluating their effects on the anti-platelet functional properties of PL bioactives from their final fermented apple cider products. First, bio-functional PL were extracted and separated from the biomass of the different isolated apple surface/must yeast strains, and were further assessed for their anti-platelet potency against human platelet aggregation induced by the potent inflammatory and thrombotic mediator platelet-activating factor (PAF), or by a classic platelet agonist like adenosine diphopshate (ADP). Novel functional apple ciders were then produced from the fermentation of apple juice by elaborating the most bioactive and resilient yeast strains isolated from the apple must with optimum fermentation properties. PL bioactives extracted from these novel apple cider products were also further assessed for their anti-platelet properties against both the PAF and ADP pathways of human platelet aggregation. These novel cider products were found to contain PL bioactives with lower IC50 values (~40 μg) and thus increased anti-platelet potency against platelet aggregation induced by PAF and ADP. GC-MS analysis of the PL bioactives extracted from these novel apple ciders showed that apple cider PL bioactives are rich in monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), such as the omega-6 linoleic acid (LA) and the omega-3 alpha linolenic acid (ALA), with favorably lower levels for their omega-6/omega-3 PUFA ratio, which further support the observed strong anti-platelet properties putative anti-inflammatory potency for the apple cider PL bioactives. However, further studies are needed in order to elucidate and fully characterize the apple yeast strains that can be utilized for increasing the anti-inflammatory, anti-platelet and cardioprotective functional properties of their fermented apple cider products.

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