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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0016018,
umls-concept:C0018557,
umls-concept:C0026336,
umls-concept:C0032143,
umls-concept:C0034065,
umls-concept:C0086418,
umls-concept:C0201734,
umls-concept:C0205245,
umls-concept:C0205419,
umls-concept:C0332597,
umls-concept:C0678594,
umls-concept:C0871161,
umls-concept:C1301820,
umls-concept:C1442161,
umls-concept:C1514562,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
|
| pubmed:issue |
2
|
| pubmed:dateCreated |
1991-7-24
|
| pubmed:abstractText |
A pulmonary embolism model in hamsters was used for the quantitative evaluation of the thrombolytic and pharmacokinetic properties of variants of tissue-type plasminogen activator (t-PA). A 25 microliters 125I-fibrin labeled human plasma clot was made in vitro and injected into the jugular vein of heparinized hamsters. The extent of thrombolysis within 90 min was determined as the difference between the radioactivity injected in the jugular vein and that recovered in the heart and lungs. Recombinant t-PA (home-made rt-PA or Activase) infused intravenously over 60 min caused dose-dependent progressive thrombolysis. The results of thrombolytic potency (clot lysis in percent versus dose administered in mg/kg) and of specific thrombolytic activity (clot lysis in percent versus steady state plasma level in microgram/ml) were fitted with an exponentially transformed sigmoidal function y = 100 c/(1 + e-a(ax-eh] and the maximal percent lysis (c), the dose or plasma level at which maximal rate of lysis is achieved (b) and the maximal rate of lysis (z = 1/4 ac.eb) were determined. With rt-PA, these parameters were c = 72 +/- 6% (mean +/- SEM), b = 0.19 +/- 0.08 mg/kg, z = 68 +/- 25% lysis per mg/kg, with corresponding values of 87 +/- 5%, 0.07 +/- 0.03 mg/kg and 150 +/- 38% lysis per mg/kg for Activase (p = NS). Deletion of the finger and growth factor domains in rt-PA (rt-PA-delta FE) was not associated with marked alteration of the thrombolytic potency (c = 90 +/- 30%, b = 0.34 +/- 0.35 mg/kg, and z = 54 +/- 14% per mg/kg), but was associated with a significant reduction of the specific thrombolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0340-6245
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
12
|
| pubmed:volume |
65
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
174-80
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:1905070-Animals,
pubmed-meshheading:1905070-Chromosome Deletion,
pubmed-meshheading:1905070-Cricetinae,
pubmed-meshheading:1905070-Disease Models, Animal,
pubmed-meshheading:1905070-Humans,
pubmed-meshheading:1905070-Multigene Family,
pubmed-meshheading:1905070-Mutation,
pubmed-meshheading:1905070-Pulmonary Embolism,
pubmed-meshheading:1905070-Structure-Activity Relationship,
pubmed-meshheading:1905070-Tissue Plasminogen Activator
|
| pubmed:year |
1991
|
| pubmed:articleTitle |
Thrombolytic and pharmacokinetic properties of human tissue-type plasminogen activator variants, obtained by deletion and/or duplication of structural/functional domains, in a hamster pulmonary embolism model.
|
| pubmed:affiliation |
Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
|
| pubmed:publicationType |
Journal Article,
Comparative Study
|