Effects of increased liver blood flow on the kinetics and dynamics of recombinant tissue-type plasminogen activator.

OBJECTIVE: To investigate the influence of increased liver blood flow on the pharmacokinetics and pharmacodynamics of recombinant tissue-type plasminogen activator (rt-PA) and to study the changes in endogenous urokinase-type plasminogen activator (u-PA). METHODS: This open, randomized, crossover trial was carried out in a clinical research unit. Eight healthy, nonsmoking volunteers received linear infusions of 24 mg rt-PA and 92 mg indocyanine green over 160 minutes. Sixty minutes after the infusions were started, the subjects consumed a standardized meal to increase liver blood flow on one occasion and abstained from taking food on the other occasion. Plasma concentrations of indocyanine green, tissue-type plasminogen activator (t-PA) antigen, t-PA activity, total u-PA antigen, plasmin-activatable single-chain u-PA (scu-PA), active two-chain u-PA (tcu-PA), fibrinogen, total fibrin, and fibrinogen/fibrin degradation products (TDP), and alpha 2-antiplasmin were measured. RESULTS: After the consumption of the meal, the area under the curve (AUC) was 35% (95% confidence interval [CI]: 25%, 43%) lower for indocyanine green, 15% (CI: 6%, 24%) lower for t-PA antigen, and 11% (CI: 2%, 19%) lower for t-PA activity compared to the AUC after subjects abstained from food. No changes were observed in fibrinogen, TDP, or alpha 2-antiplasmin concentrations that were attributable to the intake of food. The infusion of rt-PA caused a fivefold increase in the concentration of active tcu-PA and a concomitant decrease in scu-PA concentrations by more than 50%. CONCLUSIONS: Increased liver blood flow results in an increase in t-PA clearance. The conversion of the inactive zymogen scu-PA to the active tcu-PA is increased by an infusion of rt-PA, but total u-PA antigen concentrations remain unchanged.

Bovine immunodeficiency virus: immunochemical characterization and serological survey.

Bovine immunodeficiency virus (BIV) was purified by isodensity centrifugation; viral activities were monitored in gradient fractions using the reverse transcriptase assay and a p26-specific monoclonal antibody ELISA. In the coincident peak fractions (density about 1.17 g/ml) proteins with Mr values of 26K, 17K, 53K, 14K and 100K (with decreasing intensity) were detected by Western blotting using serum of a calf after experimental BIV infection. When 957 randomly collected cattle sera from The Netherlands were tested by indirect immunofluorescence and confirmed using Western blot and/or radioimmunoprecipitation, 1.4% appeared seropositive. Thus BIV infection is not uncommon in one European cattle population.