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Titolo:
IN-VITRO STABILITY OF A TISSUE-TYPE PLASMINOGEN-ACTIVATOR MUTANT, BM-06.022, IN HUMAN PLASMA
Autore:
RIJKEN DC; GROENEVELD E; BARRETTBERGSHOEFF MM;
Indirizzi:
TNO,PG,GAUBIUS LAB,POB 430 2300 AK LEIDEN NETHERLANDS
Titolo Testata:
Thrombosis and haemostasis
fascicolo: 6, volume: 72, anno: 1994,
pagine: 906 - 911
SICI:
0340-6245(1994)72:6<906:ISOATP>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY THROMBOSIS; CANINE MODEL; T-PA; ESCHERICHIA-COLI; PHARMACOKINETIC PROPERTIES; FIBRINOLYTIC PROPERTIES; THROMBOLYTIC AGENTS; INHIBITOR COMPLEXES; DOUBLE BOLUS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
53
Recensione:
Indirizzi per estratti:
Citazione:
D.C. Rijken et al., "IN-VITRO STABILITY OF A TISSUE-TYPE PLASMINOGEN-ACTIVATOR MUTANT, BM-06.022, IN HUMAN PLASMA", Thrombosis and haemostasis, 72(6), 1994, pp. 906-911

Abstract

BM 06.022 is a non-glycosylated mutant of human tissue-type plasminogen activator (t-PA) comprising only the kringle-2 and proteinase domains. The in vivo half-life of BM 06.022 antigen is 4- to 5-fold longer than that of t-PA antigen. The in vitro half-life of the activity of BM 06.022 at therapeutic concentrations in plasma is shorter than that of t-PA. In this study the inactivation of BM 06.022 in plasma was further investigated. Varying concentrations of BM 06.022 were incubated in plasma for 0-150 min. Activity assays on serial samples showed a dose-dependent decline of BM 06.022 activity with a half-life from 72 min at 0.3 mu g/ml to 38 min at 10 mu g/ml. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) followed by fibrin autography showed the generation of several BM 06.022-complexes. These complexes could be completely precipitated with antibodies against C1-inactivator, alpha(2)-antiplasmin and alpha(1)-antitrypsin. During the incubation of BM 06.022 in plasma, plasmin was generated dose-dependently as revealed by varying degrees of alpha(2)-antiplasmin consumption and fibrinogen degradation. SDS-PAGE and immunoblotting showed that single-chain BM 06.022 was rapidly (i.e, within 45 min) converted into its two-chain form at concentrations of 5 mu g/ml BM 06.022 and higher. In conclusion, BM 06.022 at therapeutic concentrations in plasma was inactivated by C1-inactivator, alpha(2)-antiplasmin and alpha(1)-antitrypsin. The half-life of the activity decreased at increasing BM 06.022 concentrations, probablyas a result of the generation of two-chain BM 06.022 which may be inactivated faster than the single-chain form.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 09:46:30