Plasma metabonomics and proteomics studies on the anti-thrombosis mechanism of aspirin eugenol ester in rat tail thrombosis model

SummaryAdhesion of rat blood platelets to native rat tail collagen fibrils was studied in the electron microscope under conditions that preserved collagen-associated proteoglycans (CAPG). The CAPG molecules were aligned in chain-like configurations that encircled the fibrils with a 65 nm period; they appeared to coat the fibrils completely and extended 60-100 nm away from the fibril. The initial platelet-fibril contact occurred between the platelet glycocalyx and the CAPG of the fibrils i.e. between two surfaces with net-negative charges. When close contact was established between the fibril surface proper and the platelet membrane, CAPG were not identified in the area of contact, and the collagen-platelet distance was reduced to a ~10-12 nm wide gap traversed by delicate links in register with fibril periodicities.

Download Full-text

Comparison of the Anticoagulant and Antithrombotic Effects of Synthetic Thrombin and Factor Xa Inhibitors

Thrombosis and Haemostasis ◽

10.1055/s-0038-1645198 ◽

1990 ◽

Vol 63 (02) ◽

pp. 220-223 ◽

Cited By ~ 19

Author(s):

J Hauptmann ◽

B Kaiser ◽

G Nowak ◽

J Stürzebecher ◽

F Markwardt

Keyword(s):

Factor Xa ◽

Thrombin Inhibitors ◽

Factor Xa Inhibitors ◽

Venous Stasis ◽

Clotting Time ◽

Thrombosis Model ◽

Activity Factor ◽

Antithrombotic Effects

SummaryThe anticoagulant effect of selected synthetic inhibitors of thrombin and factor Xa was studied in vitro in commonly used clotting assays. The concentrations of the compounds doubling the clotting time in the various assays were mainly dependent on their thrombin inhibitory activity. Factor Xa inhibitors were somewhat more effective in prolonging the prothrombin time compared to the activated partial thromboplastin time, whereas the opposite was true of thrombin inhibitors.In vivo, in a venous stasis thrombosis model and a thromboplastin-induced microthrombosis model in rats the thrombin inhibitors were effective antithrombotically whereas factor Xa inhibitors of numerically similar IQ value for the respective enzyme were not effective at equimolar dosageThe results are discussed in the light of the different prelequisiles and conditions for inhibition of thrombin and factor Xa in the course of blood clotting.

Download Full-text

Thrombolytic Treatment with Tissue-type Plasminogen Activator (t-PA) Containing Liposomes in Rabbits: a Comparison with Free t-PA

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653802 ◽

1995 ◽

Vol 73 (03) ◽

pp. 488-494 ◽

Cited By ~ 62

Author(s):

J L M Heeremans ◽

R Prevost ◽

M E A Bekkers ◽

P Los ◽

J J Emeis ◽

...

Keyword(s):

Plasminogen Activator ◽

Therapeutic Index ◽

Tissue Type ◽

Jugular Vein Thrombosis ◽

Thrombolytic Activity ◽

Tissue Type Plasminogen Activator ◽

Liposome Encapsulation ◽

Thrombosis Model ◽

Lysis Activity ◽

Type Plasminogen Activator

SummaryIn this study, we aimed at improving the therapeutic index of tissue- type Plasminogen Activator (t-PA) as thrombolytic agent in the treatment of myocardial infarction. Liposome-encapsulated t-PA was tested in a rabbit jugular vein thrombosis model: administration of free t-PA (t-PA) as a bolus injection in the ear vein was compared to a similar administration of liposomal t-PA (t-PA-lip), liposomal t-PA in plasminogen-coated liposomes (Plg-t-PA-lip), a mixture of free t-PA and empty liposomes (t-PA+empty lip) and a saline-blank (blank) in terms of thrombolytic activity and side effects.Liposomal t-PA (t-PA-lip/Plg-t-PA-lip) showed a significantly better thrombolysis efficiency than equimolar doses of free t-PA (t-PA/ t-PA+ empty lip): about 0.24 mg/kg of liposomal t-PA practically equalled the lysis-activity of a dose of free t-PA of 1.0 mg/kg (t-PAlmg/kg). On the other hand, liposome encapsulation did not affect the systemic activation of alpha2-antiplasmin and plasminogen by t-PA.We conclude that for this model an improvement in thrombolytic efficacy of t-PA is achieved by liposome encapsulation of t-PA. As t-PA-lip and Plg-t-PA-lip -treatment induced similar results, targeting of liposomal t-PA by coupled glu-Plg remains a topic to be optimized in future studies.

Download Full-text

Acyl-Enzymes as Thrombolytic Agents in Dog Models of Venous Thrombosis and Pulmonary Embolism

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661069 ◽

1984 ◽

Vol 51 (02) ◽

pp. 248-253 ◽

Cited By ~ 22

Author(s):

R J Dupe ◽

P D English ◽

R A G Smith ◽

J Green

Keyword(s):

Pulmonary Embolism ◽

Side Effects ◽

Venous Thrombosis ◽

Active Site ◽

Acute Pulmonary Embolism ◽

Quantitative Model ◽

Beagle Dog ◽

Thrombosis Model ◽

Derivatives Of

SummaryA quantitative model of venous thrombosis in the beagle dog is described. The model was adapted to permit ageing of isolated experimental clots in vivo. A model of acute pulmonary embolism in this species is also described. In the venous thrombosis model, infusion of streptokinase (SK) or SK-activated human plasmin gave significant lysis but bolus doses of SK. plasmin complex were ineffective. Active site anisoylated derivatives of SK. plasminogen complex, SK-activated plasmin and activator-free plasmin were all active when given as bolus doses in both models. At lytic doses, the acyl-enzymes caused fewer side-effects attributable to plasminaemia than the corresponding unmodified enzymes.

Download Full-text

The Effect of Pentosan Polysulphate (SP54) on the Fibrinolytic Enzyme System - A Human Volunteer and Experimental Animal Study

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660143 ◽

1985 ◽

Vol 54 (04) ◽

pp. 833-837 ◽

Cited By ~ 7

Author(s):

N A Marsh ◽

P M Peyser ◽

L J Creighton ◽

M Mahmoud ◽

P J Gaffney

Keyword(s):

Plasminogen Activator ◽

Surface Effect ◽

Ex Vivo ◽

Vena Cava ◽

Tissue Type ◽

Similar Response ◽

Small Contribution ◽

Thrombosis Model ◽

Pentosan Polysulphate

SummaryPentosan polysulphate causes an increase in plasminogen activator activity in plasma both after oral ingestion and after subcutaneous injection. The effect is greatest after 3 h and has disappeared by 6 h. Repeat doses by mouth over 5 days elicit a similar response. The recorded increase in activity is due largely to the release of tissue-type plasminogen activator (tPA) from the endothelium according to the antigen assay although there could be a small contribution from Factor XH-related “intrinsic” fibrinolysis induced in vitro. SP54 enhances activity ex vivo by a non-specific surface effect, and this phenomenon may contribute the increased levels of activity seen in vitro. Administration of SP54 to animals elicits a similar increase in activator activity, the intramuscular route being slightly more effective. Results with an inferior vena cava thrombosis model in the rat suggest that pentosan polysulphate may induce a thrombolytic effect.

Download Full-text

Antithrombotic Effect of Two Low Molecular Weight Thrombin Inhibitors and a Low-Molecular Weight Heparin in a Caval Vein Thrombosis Model in the Rat

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665419 ◽

1997 ◽

Vol 78 (05) ◽

pp. 1404-1407 ◽

Cited By ~ 53

Author(s):

B I Eriksson ◽

S Carlsson ◽

M Halvarsson ◽

B Risberg ◽

C Mattsson

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Clinical Situation ◽

Thrombin Inhibitors ◽

Thrombin Inhibitor ◽

Low Molecular Weight ◽

Surgical Trauma ◽

Antithrombotic Effect ◽

Caval Vein ◽

Thrombosis Model

SummaryA sensitive thrombosis model with a high reproducibility was developed in the rat, utilizing stasis of the caval vein and a standardized surgical trauma as the only thrombogenic stimuli. Since no procoagulant substances were used, the results of the present study might be relevant in a clinical situation. The antithrombotic effect of two recently synthesized low-molecular-weight thrombin inhibitors have been compared to dalteparin, (Fragmin) a low-molecular-weight heparin fragment. Each compound was studied at 8 different doses with 10 rats in each group. On a gravimetric basis, the thrombin inhibitor melagatran was twice as potent as dalteparin (ED50 16 and 33 µ/kg per h, respectively). The second thrombin inhibitor, inogatran, had an intermediate effect, with an ED50 of 24 µLg/kg per h. No differences in antithrombotic effect were, however, found when the compounds were compared at anticoagulant equivalent doses (same APTT prolongation). A 50% reduction in the mean thrombus weight was obtained when APTT was prolonged to 1.2 to 1.3 times the pretreatment value.

Download Full-text