scholarly journals Inhibitory Effects of Dimeric Copper(II) bis(o-acetoxybenzoate) on Platelet-neutrophil adhesion and Thrombosis

2001 ◽  
Vol 8 (2) ◽  
pp. 103-105
Author(s):  
Zhiqiang Shen ◽  
Lanou Wu ◽  
Weiping Liu ◽  
Jikai Liu ◽  
Zhihhe Chen
Keyword(s):  
Arachidonic Acid ◽  
Venous Thrombosis ◽  
Neutrophil Adhesion ◽  
Inhibitory Effects ◽  
Antithrombotic Effect ◽  
Antithrombotic Activity ◽  
Activated Platelets ◽  
Copper Aspirinate

Antithrombotic effect of the copper-aspirin complex (dimeric copper(II) bis(o-acetoxybenzoate) was evaluated in the model of venous thrombosis; its effects on platelet-neutrophil adhesion were investigated by use of rosette assay. The results showed that the intragastrically administered copper-aspirin complex (5, 7, and 10 mg kg−1) dose-dependently lowered the wet and dry thrombus weight; it significantly decreased the binding of arachidonic acid-activated platelets to neutrophils with an IC50 value of 41.5 μmol L-1. The results suggested that copper aspirinate inhibited platelet-neutrophil adhesion and resulted in a more potent antithrombotic activity.

Pharmacological Properties of CY 216 and of Its ACLM and BCLM Components in the Rabbit

1994 ◽  
Vol 72 (02) ◽  
pp. 268-274 ◽  
Author(s):  
V Peyrou ◽  
J C Lormeau ◽  
C Caranobe ◽  
A M Gabaig ◽  
B Crepon ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thrombosis ◽  
Unfractionated Heparin ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
Factor Xa ◽  
Pharmacological Properties ◽  
Antithrombotic Effect ◽  
Antithrombotic Activity ◽  
Thrombin Activity

SummaryThis study compares some in vivo pharmacological properties of CY 216 and of its ACLM and BCLM components having a molecular weight above and below 5.4 kDa respectively. The anti-factor Xa/anti-thrombin ratio of these compounds determined in a rabbit plasma system were 2.5 and 1.2 for CY 216 and ACLM respectively while BCLM was devoid of anti-thrombin effect. After bolus intravenous injection, continuous infusion and subcutaneous administration, the clearances of anti-factor Xa activity generated by ACLM were, on the average, 2 and 1.5 times higher than those generated by BCLM and CY 216 respectively. The clearances of the anti-thrombin activity were comparable for CY 216 and ACLM, and higher than those of the antifactor Xa activity. The duration of the antithrombotic effect was investigated in the Wessler model after a single subcutaneous injection of 1000 anti-factor Xa units of one of the compounds. Using thromboplastin as thrombogenic stimulus, the most efficient agent was ACLM and the antithrombotic activity was essentially correlated to the circulating anti-thrombin activity. Using human serum as thrombogenic stimulus, ACLM and BCLM were more efficient than CY 216 and the antithrombotic activity was mainly correlated to the anti-factor Xa activity. The ability of the 3 compounds to inhibit venous thrombosis growth was compared: they were found equipotent and the antithrombotic effect was independent of the anti-thrombin activity. The pro-haemorrhagic properties were compared in the rabbit ear model. The activity of the 3 compounds were comparable and significantly less prohaemorrhagic than unfractionated heparin. These results suggest that the haemorrhagic potential of unfractionated heparin and of LMWH is independent of the anti-thrombin and anticoagulant activity, but related to the molecular weight. These observations indicate that factor Xa inhibition is a valuable target to prevent and to treat venous thrombosis and that the anti-factor Xa activity of a low molecular weight heparin (LMWH) largely contributes to its antithrombotic effect.

Ecarin Clotting Time: a Predictive Coagulation Assay for the Antithrombotic Activity of Argatroban in the Rat

1998 ◽  
Vol 79 (01) ◽  
pp. 228-233 ◽  
Author(s):  
Catherine Lunven ◽  
Christine Girardot ◽  
Irène Lechaire ◽  
Denise Girard ◽  
Marie-Christine Charles ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Predictive Marker ◽  
Clotting Time ◽  
Antithrombotic Effect ◽  
Antithrombotic Activity ◽  
Thrombosis Model ◽  
Antithrombotic Effects ◽  
Ecarin Clotting Time ◽  
Predictive Assay

SummaryWe studied the use of the Ecarin Clotting Time (ECT) as a predictive assay of the antithrombotic effects of argatroban in a new tissue factor-dependent model of venous thrombosis and a model of arterial thrombosis in the rat. Heparin was used as a reference anticoagulant.Infusions of argatroban dose-dependently increased the ECT across the range of doses required for antithrombotic activity in models of venous and arterial thrombosis (1.25-40 μg/kg/min). The TT was only useful as a marker in the case of venous thrombosis, since, in the arterial thrombosis model, the clotting times were >200 s in the majority of animals receiving antithrombotic doses. The aPTT is not sufficiently sensitive to be predictive of an antithrombotic effect in the venous model, and shows only modest increases in the arterial thrombosis model. Heparin did not significantly increase the ECT at antithrombotic doses in the venous thrombosis model, and only increased the ECT by 53% at 40 μg/kg/min in the arterial model, despite a marked antithrombotic effect. Both the TT and aPTT were dose-dependently increased by heparin at doses active in the venous model, whereas both parameters were >200 s at doses active in the arterial thrombosis model.Thus, the ECT provides a predictive marker for the antithrombotic activity of argatroban in both venous and arterial thrombosis, at least in the rat.

scholarly journals Activated platelets induce MLKL-driven neutrophil necroptosis and release of neutrophil extracellular traps in venous thrombosis

2018 ◽  
Vol 4 (1) ◽  
Author(s):  
Daigo Nakazawa ◽  
Jyaysi Desai ◽  
Stefanie Steiger ◽  
Susanne Müller ◽  
Satish Kumar Devarapu ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps ◽  
Activated Platelets

scholarly journals Are all wines made from various grape varieties beneficial in the prevention of myocardial infarction and stroke?

2021 ◽  
Vol 7 (2) ◽  
pp. FSO649
Author(s):  
Masahiro Iwasaki ◽  
Masahiro Murakami ◽  
Yoshinobu Ijiri ◽  
Muneshige Shimizu ◽  
Junichiro Yamamoto
Keyword(s):  
Fruits And Vegetables ◽  
Red Wine ◽  
Animal Experiments ◽  
Epidemiologic Studies ◽  
Antithrombotic Effect ◽  
Antithrombotic Activity ◽  
Cast Doubt ◽  
Red Grape ◽  
Grape Varieties ◽  
French Paradox

Aim: Epidemiologic studies support the assumption (French paradox hypothesis) that drinking red wine is beneficial in the prevention of cardiovascular diseases. Our recent works however cast doubt on such claim. Earlier we have shown that the antithrombotic activity of various fruits and vegetables mainly depends on their varieties. For this reason, several varieties of red and white grapes were tested for antithrombotic effect in animal experiments. Results: Antithrombotic effect of 45 red and white grape varieties were assessed in the present study. Out of the 45, one red grape variety showed antithrombotic effect, while the majority of red and white grape varieties enhanced thrombosis. Conclusion: Most red and white grape varieties enhanced thrombotic activity of blood.

Tissue distribution and antithrombotic activity of unlabeled or 14C-labeled porcine intestinal mucosal heparin following administration to rats by the oral route

2000 ◽  
Vol 78 (4) ◽  
pp. 307-320 ◽  
Author(s):  
Linda M Hiebert ◽  
Sandra M Wice ◽  
Tilly Ping ◽  
Ronald E Hileman ◽  
Ishan Capila ◽  
...  
Keyword(s):  
Gel Electrophoresis ◽  
Wistar Rats ◽  
Jugular Vein ◽  
Oral Route ◽  
Gut Contents ◽  
Agarose Gel Electrophoresis ◽  
Antithrombotic Effect ◽  
Stomach Tube ◽  
Antithrombotic Activity ◽  
Male Wistar Rats

Distribution and antithrombotic activity of orally administered unfractionated porcine heparin were studied. [14C]Heparin was prepared by de-N-acetylation of porcine mucosal heparin followed by re-N-acetylation, using [14C]acetic anhydride. [14C]Heparin and (or) cold heparin (60 mg/kg) were administered by stomach tube to male Wistar rats. Blood, all levels of gut and gut contents, liver, lung, spleen, kidney, and aortic and vena caval endothelium were collected under deep anesthesia at 3, 6, 15, 30, and 60 min and 4 and 24 h (6 rats/group) after administration. Urine and feces were collected at 24 h, using metabolic cages. In three additional rats, drugs were administered in gelatin capsules. Tissues listed above and tongue, esophagus, trachea, brain, heart, thymus, bile ducts, vena caval and aortic walls, ureters, bladder, samples of muscle, skin, hair, and bone marrow were collected at 24 h. Radioactivity and chemical heparin, measured by agarose gel electrophoresis, were observed in all tissues examined as well as gut washes, plasma, urine, and feces. Radiolabel recovered was confirmed to be heparin by autoradiograms of gradient polyacrylamide electrophoretic gels. [14C]Heparin and chemical heparin in gut tissue suggest a transit time of 4 h. Porcine or bovine heparin (7.5 mg/kg), administered by stomach tube, decreased the incidence of thrombosis induced by applying 10% formalin in 65% methanol to the exposed jugular vein of rats. Heparin isolation from non-gut tissue, endothelium, urine, and plasma and the observed antithrombotic effect are consistent with oral bioavailability.Key words: heparin, [14C]heparin, oral administration, distribution, radiolabel, thrombosis.

EXPERIMENTAL THROMBUS FORMATION AND HAEMOSTASIS OF DIFFERENT LOW MOLECULAR WEIGHT HEPARINS AND DOSAGES

1987 ◽  
Author(s):  
R A Zimmerman ◽  
C T Rieger ◽  
K Hübner ◽  
C W Harenber ◽  
W Kübler
Keyword(s):  
Molecular Weight ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Bleeding Complications ◽  
Maximum Effect ◽  
Low Molecular Weight ◽  
Antithrombotic Effect ◽  
Low Molecular Weight Heparins ◽  
Antithrombotic Activity ◽  
Thrombosis Model

Low molecular weight heparin induces a higher anti factor Xa (a-Xa) and a lower antithrombin activity in plasma in comparison to conventional heparin. From this constellation a more pronounced antithrombotic effect and a minor incidence of bleeding Complications has been suggested.Therefore the antithrombotic activity of heparins was studied in a standardized experimental thrombosis model in rabbits. Three low molecular weight heparins with a mean molecular weight of 4.200 (heparin I),4.000 (heparin II),4.600 Dalton (heparin III) and standard heparin were tested at different dosages in 120 experiments. In the first series the dose of 60 anti Xa units (a-Xa U) given initially and 60 a-Xa U/kg/h induced a reduction of the thrombus size by 40 % (heparin I),37 % (heparin II) and 53 % (heparin III) and a prolongation of the aPTT to 45 (heparin I),66 (heparin II) and 79 sec (heparin III). The a-Xa activity was minor than 0.1 U/ml. In the second series heparins were given to aim at an a-Xa activity of 0.2-0.3 U/ml. Thereby the thrombus formation could be reduced by 84 % (heparin I), 62 % (heparin II) and 39 % (heparin III). aPTT and a-Xa activity were measured at 65.5 sec and 0.22 a-Xa U/ml (heparin I),67.3 sec and 0.3 a-Xa U/ml (heparin II) and 67.5 and 0.31 a-Xa U/ml (heparin III),respectively. In the third series the increase of the a-Xa activity to more than 0.3 U/ml showed no further reduction of the thrombus formation by heparin I, while heparins II and III already at this level reachedthe antithrombotic activity of heparin I.Our data on three different low molecular weight heparins demonstrate that already a heparin level ranging at a minimal a-Xa activity induces a clear and statistically significant antithrombotic effect. A higher heparin dosage with higher a-Xa activity increases the antithrombitic effect. At a level of 0.2-0.3 a-Xa U/ml an obvious and maximum effect could be reached, but the further elevation of the a-Xa activity produced no further antithrombotic action.

THE ROLE OF A 3-0 SULFO GROUP IN THE GLUCOSAMINE RESIDUE OF A SYNTHETIC OLIGOSACCHARIDE FOR THE DETERMINATION OF ANTITHROMBOTIC ACTIONS

1987 ◽  
Author(s):  
J M Walenga ◽  
J Fareed ◽  
M Petitou ◽  
J C Lormeau ◽  
M Samama ◽  
...  
Keyword(s):  
Sulfo Group ◽  
Factor Xa ◽  
Antithrombotic Effect ◽  
Antithrombotic Activity ◽  
Thrombosis Model ◽  
Factor Xa Inhibition

We have previously reported on the antithromboticaction of a chemically synthesized heparin pentasaccharide which exhibits high affinity to anti thrombinIII and sole anti-factor Xa activity. In order to investigate the relative importance of the 3-0 sulfo group of this pentasaccharide, we evaluated the in vitro and in vivo antithrombotic activity of a synthetic pentasccharide devoid of the sulfo group at the third position of the glucosamine residue. In amidolytic and clot-based assays the 3-0 de- sulfated pentasaccharide (3-0-DP) failed to exhibit any antifactor Xa actions at concentrations <100 ug/ml in humanor rabbit plasmas, whereas pentasaccharide showed strong factor Xa inhibition at 1.0 ug/ml IK-=3.2x10 M)and at 10.0 ug/ml in rabbit plasma (K.=9.0×10™7 M). Using a rabbit stasis thrombosis model in which thrombosis was induce by human serum or an activated pro-thrombin complex concentrate, 3-0-DP failed to produce any antithrombotic action in acute intravenous regimens at dosages up to 200 ug/kg. In these two models, pentasaccharide produced >80% inhibition of induced thrombosis. These studies demonstrate the critical importance of the 3-0 sulfo group in this heparin pentasaccharide for the determination of antithrombotic activity, and that in this type of oligosaccharide, anti-factor Xa activity is responsible for producing the antithrombotic effect.

scholarly journals Beneficial Influence of Platelets on Antibiotic Efficacy in an In Vitro Model of Staphylococcus aureus-Induced Endocarditis

2004 ◽  
Vol 48 (7) ◽  
pp. 2551-2557 ◽  
Author(s):  
Renee-Claude Mercier ◽  
Robert M. Dietz ◽  
Jory L. Mazzola ◽  
Arnold S. Bayer ◽  
Michael R. Yeaman
Keyword(s):  
Staphylococcus Aureus ◽  
In Vitro Model ◽  
Antimicrobial Effect ◽  
Human Platelets ◽  
Inhibitory Effects ◽  
Activated Platelets ◽  
Vitro Model ◽  
Antibiotic Efficacy ◽  
Chamber Fluid

ABSTRACT Platelets contribute to antimicrobial host defense against infective endocarditis (IE) by releasing platelet microbicidal proteins (PMPs). We investigated the influence of thrombin-stimulated human platelets on the evolution of simulated IE in the presence and absence of vancomycin or nafcillin. Staphylococcus aureus strains differing in intrinsic susceptibility to PMPs or antibiotics were studied: ISP479C (thrombin-induced PMP-1 [tPMP-1] susceptible; nafcillin and vancomycin susceptible), ISP479R (tPMP-1 resistant; nafcillin and vancomycin susceptible), and GISA-NJ (tPMP-1 intermediate-susceptible; vancomycin intermediate-susceptible). Platelets were introduced and thrombin activated within the in vitro IE model 30 min prior to inoculation with S. aureus. At 0 to 24 h postinoculation, bacterial densities in chamber fluid and simulated endocardial vegetations (SEVs) were quantified and compared among groups. Activated platelets alone, or in combination with antibiotics, inhibited the proliferation of ISP479C in chamber fluid or SEVs over the initial 4-h period (P < 0.05 versus controls). Moreover, nafcillin-containing regimens exerted inhibitory effects beyond 4 h against ISP479C in both model phases. By comparison, activated platelets inhibited GISA-NJ proliferation in SEVs but not in chamber fluid. The combination of platelets plus nafcillin or vancomycin significantly inhibited proliferation of the GISA-NJ strain in SEVs compared to the effect of platelets or antibiotics alone (P < 0.05). In contrast, platelets did not significantly alter the antistaphylococcal efficacies of nafcillin or vancomycin against ISP479R. These data support our hypothesis that a beneficial antimicrobial effect may result from the interaction among platelets, PMPs, and anti-infective agents against antibiotic-susceptible or -resistant staphylococci that exhibit a tPMP-1-susceptible or -intermediate-susceptible phenotype.

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