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Titolo:
Method to measure in vivo blood fibrinolytic activity with a I-125-fibrin coated aorta loop validated with agents which affect blood fibrinolytic activity
Autore:
Jansen, JWCM; van den Brink, H; Hoogenboom, PH;
Indirizzi:
Solvay Pharmaceut, NL-1380 DA Weesp, Netherlands Solvay Pharmaceut WeespNetherlands NL-1380 DA 380 DA Weesp, Netherlands
Titolo Testata:
THROMBOSIS RESEARCH
fascicolo: 3, volume: 104, anno: 2001,
pagine: 223 - 232
SICI:
0049-3848(20011101)104:3<223:MTMIVB>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMINOGEN-ACTIVATOR INHIBITOR-1; EXPERIMENTAL PULMONARY EMBOLUS; NECROSIS-FACTOR-ALPHA; T-PA; ENDOTHELIAL-CELLS; RETINOIC ACID; PLATELET-AGGREGATION; CLINICAL-APPLICATION; THROMBOLYTIC AGENTS; VENOUS THROMBOSIS;
Keywords:
fibrinolysis; aorta loop; tissue-type plasminogen activator; tissue-type plasminogen activator inhibitor-1; thrombolytics; endotoxin; tranexamic acid; dexamethasone; retinoic acid;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Jansen, JWCM Solvay Pharmaceut, POB 900, NL-1380 DA Weesp, Netherlands Solvay Pharmaceut POB 900 Weesp Netherlands NL-1380 DA lands
Citazione:
J.W.C.M. Jansen et al., "Method to measure in vivo blood fibrinolytic activity with a I-125-fibrin coated aorta loop validated with agents which affect blood fibrinolytic activity", THROMB RES, 104(3), 2001, pp. 223-232

Abstract

A functional animal model to measure in vivo the blood fibrinolytic activity and pharmacological-induced changes thereof are described. A I-125-fibrin coated plastic loop is inserted in the rat aorta; the rate of label disappearance (sigmoid curve) is directly registered outside the animal with a gamma scintillation probe. The time needed to let disappear 50% of the removable-labeled fibrin is used as measure for the blood fibrinolytic activity. The direct advantage of this model is the absence of a blood or plasma clot: a thin labeled fibrin layer attached to the inner wall of the loop is indirect contact with the blood and is therefore sensitive to increased or decreased blood fibrinolytic activity. The total experiment needs about 60 min. Experiments with nontreated rats showed that, after an initial lag phase of about 10 min, the labeled fibrin started to disappear from the loop. Asigmoid pattern was obtained showing that about 20-30% of the coated-labeled fibrin is resistant to removal. Registration of the total curve of a nontreated (control or placebo) rat required about 30-40 min. The clinically used thrombolytics (intravenously administered) urokinase and t-PA showed a dose-dependent fibrinolytic activity resulting in increased removal of the bound I-125-fibrin. Streptokinase was not active, which is in agreement with literature. Tranexamic acid, dexamethasone and endotoxin (inhibitors of fibrinolysis) showed dose-dependent inhibition of removal of the coated fibrin. Retinoic acid was tested as compound, which may enhance the blood fibrinolytic activity; retinoic acid was not found to be significantly active inthis model. The disappearance of labeled fibrin is not sensitive to inhibitors of coagulation or platelet aggregation. This technically simple and fast model can thus be used to measure in vivo quantitatively the effects of pharmacological active compounds, which increase or decrease the blood fibrinolytic activity. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 22:54:47