Evidence for the Progressive Uptake of Anisoylated Plasminogen Streptokinase Activator Complex by Clots in Human Plasma in Vitro

Drugs ◽  
1987 ◽  
Vol 33 (Supplement 3) ◽  
pp. 51-56 ◽  
Author(s):  
R. Fears ◽  
H. Ferres ◽  
R. Standring
Keyword(s):  
Human Plasma ◽  
Activator Complex

THE PROTECTIVE EFFECT OF ACYLATI0N ON THE STABILITY OF EMINASE (APSAC) IN HUMAN PLASMA

1987 ◽  
Author(s):  
R Fears ◽  
H Ferres ◽  
R Standring
Keyword(s):  
Protective Effect ◽  
Human Plasma ◽  
Fibrinolytic Activity ◽  
Animal Studies ◽  
Active Form ◽  
Α2 Macroglobulin ◽  
The Stability ◽  
High Level ◽  
Activator Complex

Clinical and animal studies indicate that APSAC (anisoylated plasminogen.streptokinase activator complex, Eminase) circulates longer in the bloodstream in an active form than the other thrombolytics. In the present studies in vitro u/e have found that functional activity of APSAC is maintained in human plasma longer than that of SK.plasmin(ogen): the relative stability half-lives are similar to the plasma clearance haif-lives in patients. Some of the loss of activity of SK at early times can be attributed to neutralisation by inhibitors. Thus, the survival of fibrinolytically-active SK was promoted in plasma depleted in α2-antiplasmin (α2AP) and α2AP-SK.plasmin complexes (detected by immunoblotting) formed rapidly in normal plasma. Corresponding studies with α2 macroglobulin-depleted plasma suggested a slight, late influence on SK activity but the inhibitor complex has not been detected unequivocally. In addition, loss of SK activity can be attributed, in part, to. rapid degradation to low molecular products. The degradation of SK in APSAC was much slower. In other comparative studies, the stability of APSAC was found to be similar to the stability of prourokinase and much superior to that of SK which is similar to UK; t-PA is intermediate in stability.Maintenance of fibrinolytic activity vivo depends on the stability of the thrombolytic, its rate of clearance and mode of administration. The protective effect of acylation, demonstrated in these experiments, explains why the objective of maintaining a high level of fibrinolytic activity after intravenous bolus injection of APSAC is less compromised by opposing inactivation processes.

In Vitro Effects of the Acylated StreptokinasePlasminogen Activator Complex BRL 33 575 Incubated with Normal Human Plasma

1984 ◽  
Vol 51 (03) ◽  
pp. 403-405 ◽  
Author(s):  
B Lämmle ◽  
G Noll ◽  
T H Tran ◽  
A Lohri ◽  
F Duckert
Keyword(s):  
Human Plasma ◽  
Clinical Studies ◽  
Systemic Effects ◽  
In Vitro Experiments ◽  
Normal Human Plasma ◽  
Normal Human ◽  
Repeated Doses ◽  
In Vitro Effects ◽  
Activator Complex

SummaryThrombolysis with acylated streptokinase-plasminogen complexes is aimed to achieve fibrinolysis without systemic fibrinogenolysis. The p-aminobenzoyl-streptokinase-(Lys)-plasminogen-complex (BRL 33 575) should be particularly useful due to its slow deacylation rate. Unexpectedly, repeated doses of 10 mg of BRL 33 575 (corresponding to 310'000 streptokinase equivalent units) induced systemic effects in patients though less than streptokinase alone. In vitro incubation of normal human plasma with BRL 33 575 at concentrations used in patients resulted in nearly complete consumption of α2-antiplasmin and plasminogen and significant fibrinogenolysis within 3 hr. This demonstrates that - despite of slow deacylation of BRL 33 575 - the small amounts of activator generated are highly efficacious in activating plasma plasminogen under conditions in which no physiological clearance of the free activator takes place. Simulating the calculated activator release from BRL 33 575 by infusing equivalent amounts of streptokinase into plasma resulted in less pronounced effects. This is probably explained by anti-streptokinase antibodies which will neutralize the initially infused streptokinase but will be bound by BRL 33 575.Our in vitro experiments indicate that further clinical studies should be done with lower doses of BRL 33 575 or prolonged dosage intervals.

Potentially Thrombogenic Materials in Factor IX Concentrates

1975 ◽  
Vol 33 (03) ◽  
pp. 617-631 ◽  
Author(s):  
H. S Kingdon ◽  
R. L Lundblad ◽  
J. J Veltkamp ◽  
D. L Aronson
Keyword(s):  
Human Plasma ◽  
Antithrombin Iii ◽  
Factor Ix ◽  
In Vitro Assays ◽  
Substantial Agreement ◽  
Coefficient Of Correlation

SummaryFactor IX concentrates manufactured from human plasma and intended for therapeutic infusion in man have been suspected for some time of being potentially thrombogenic. In the current studies, assays were carried out in vitro and in vivo for potentially thrombogenic materials. It was possible to rank the various materials tested according to the amount of thrombogenic material detected. For concentrates not containing heparin, there was substantial agreement between the in vivo and in vitro assays, with a coefficient of correlation of 0.77. There was no correlation between the assays for thrombogenicity and the antithrombin III content. We conclude that many presently available concentrates of Factor IX contain substantial amounts of potentially thrombogenic enzymes, and that this fact must be considered in arriving at the decision whether or not to use them therapeutically.

Presence and Possible Origin of ɛ(γ-Glutamyl)Lysine Isodipeptide in Human Plasma

1992 ◽  
Vol 67 (01) ◽  
pp. 060-062 ◽  
Author(s):  
J Harsfalvi ◽  
E Tarcsa ◽  
M Udvardy ◽  
G Zajka ◽  
T Szarvas ◽  
...  
Keyword(s):  
Human Plasma ◽  
Fibrinolytic Therapy ◽  
Normal Human Plasma ◽  
Normal Human ◽  
Hplc Technique ◽  
Significant Change

Summaryɛ(γ-glutamyl)lysine isodipeptide has been detected in normal human plasma by a sensitive HPLC technique in a concentration of 1.9-3.6 μmol/1. Incubation of in vitro clotted plasma at 37° C for 12 h resulted in an increased amount of isodipeptide, and there was no further significant change when streptokinase was also present. Increased in vivo isodipeptide concentrations were also observed in hypercoagulable states and during fibrinolytic therapy.

Observations on the in vitro Effects of Chylomicra, Low-Density Lipoproteins and Phospholipids on Human Plasma Euglobulin Lysis

1963 ◽  
Vol 09 (01) ◽  
pp. 164-174 ◽  
Author(s):  
Albert R Pappenhagen ◽  
J. L Koppel ◽  
John H Olwin
Keyword(s):  
Human Plasma ◽  
Phosphatidyl Ethanolamine ◽  
Phosphatidyl Inositol ◽  
Plasma Lipoproteins ◽  
Low Density ◽  
Inhibitory Effects ◽  
Soybean Phospholipids ◽  
In Vitro Effects ◽  
Complete Precipitation

SummaryData have been presented on the in vitro effects of human chylomicra, low-density human plasma lipoproteins, and partially purified preparations of various phospholipids on human plasma euglobulin lysis. Euglobulin lysis was found to be accelerated by preparations of mixed soybean phospholipids (aso-lectin), cephalin, phosphatidyl inositol, phophatidyl serine and phosphatidyl ethanolamine. In contrast, it was found to be inhibited by preparations of human chylomicra, low-density human plasma liproproteins and lecithin. Inhibition of euglobulin lysis produced by any of these three agents could be diminished or completely overcome by the simultaneous presence of suitable levels of any one of the accelerating agents. In all cases studied, both inhibitory and accelerating effects were observed to be concentration-dependent. Evidence has been obtained to suggest that in the case of the accelerating agents the observed increased rate of euglobulin lysis is not a direct effect on lysis itself, but rather is due to more complete precipitation of plasminogen in the presence of these substances. On the other hand, it appears that the inhibitory effects observed are not related to the extent of plasminogen precipitation, but are actually true inhibitions of euglobulin lysis. The possible clinical significance of some of these observations has been briefly discussed.

Absence of Synergism Between Tissue-Type Plasminogen Activator (t-PA), Single-Chain UrokinaseType Plasminogen Activator (scu-PA) and Urokinase on Clot Lysis in a Plasma Milieu In Vitro

1986 ◽  
Vol 56 (01) ◽  
pp. 035-039 ◽  
Author(s):  
D Collen ◽  
F De Cock ◽  
E Demarsin ◽  
H R Lijnen ◽  
D C Stump
Keyword(s):  
Human Plasma ◽  
Plasminogen Activator ◽  
Dose Response ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Clot Lysis ◽  
Single Chain ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

SummaryA potential synergic effect of tissue-type plasminogen activator (t-PA), single-chain urokinase-type plasminogen activator (scuPA) or urokinase on clot lysis was investigated in a whole human plasma system in vitro. The system consisted of a human plasma clot labeled with 125I-fibrinogen, immersed in titrated whole human plasma, to which the thrombolytic agents were added. Clot lysis was quantitated by measurement of released 125I, and activation of the fibrinolytic system in the surrounding plasma by measurements of fibrinogen and α2-antiplasmin.t-PA, scu-PA and urokinase induced a dose-dependent and time-dependent clot lysis; 50 percent lysis after 2 h was obtained with 5 nM t-PA, 20 nM scu-PA and 12 nM urokinase. At these concentrations no significant activation of the fibrinolytic system in the plasma was observed with t-PA and scu-PA, whereas urokinase caused significant α2-antiplasmin consumption and concomitant fibrinogen degradation. The shape of the dose-response curves was different; t-PA and urokinase showed a log linear dose-response whereas that of scu-PA was sigmoidal.

Total weak acid concentration and effective dissociation constant of nonvolatile buffers in human plasma

2001 ◽  
Vol 91 (3) ◽  
pp. 1364-1371 ◽  
Author(s):  
Peter D. Constable
Keyword(s):  
Dissociation Constant ◽  
Human Plasma ◽  
Total Concentration ◽  
Weak Acid ◽  
Strong Ion Difference ◽  
Acid Base ◽  
Horse Plasma ◽  
Using Data ◽  
Species Specific

The strong ion approach provides a quantitative physicochemical method for describing the mechanism for an acid-base disturbance. The approach requires species-specific values for the total concentration of plasma nonvolatile buffers (Atot) and the effective dissociation constant for plasma nonvolatile buffers ( K a), but these values have not been determined for human plasma. Accordingly, the purpose of this study was to calculate accurate Atot and K a values using data obtained from in vitro strong ion titration and CO2tonometry. The calculated values for Atot (24.1 mmol/l) and K a (1.05 × 10−7) were significantly ( P < 0.05) different from the experimentally determined values for horse plasma and differed from the empirically assumed values for human plasma (Atot = 19.0 meq/l and K a = 3.0 × 10−7). The derivatives of pH with respect to the three independent variables [strong ion difference (SID), Pco 2, and Atot] of the strong ion approach were calculated as follows: [Formula: see text] [Formula: see text], [Formula: see text]where S is solubility of CO2 in plasma. The derivatives provide a useful method for calculating the effect of independent changes in SID+, Pco 2, and Atot on plasma pH. The calculated values for Atot and K a should facilitate application of the strong ion approach to acid-base disturbances in humans.

scholarly journals Modulation of Oxidative Stress and Hemostasis by Flavonoids from Lentil Aerial Parts

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 497
Author(s):  
Jerzy Żuchowski ◽  
Agata Rolnik ◽  
Weronika Adach ◽  
Anna Stochmal ◽  
Beata Olas
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Human Plasma ◽  
Crude Extract ◽  
Lens Culinaris ◽  
Bioactive Substances ◽  
Phenolic Fraction ◽  
Aerial Parts ◽  
Scientific Attention

While specific metabolites of lentil (Lens culinaris L.) seeds and their biological activity have been well described, other organs of this plant have attracted little scientific attention. In recent years, green parts of lentils have been shown to contain diverse acylated flavonoids. This work presents the results of the research on the effect of the crude extract, the phenolic fraction, and seven flavonoids obtained from aerial parts of lentils on oxidative damage induced by H2O2/Fe to lipid and protein constituents of human plasma. Another goal was to determine their effect on hemostasis parameters of human plasma in vitro. Most of the purified lentil flavonoids had antioxidant and anticoagulant properties. The crude extract and the phenolic fraction of lentil aerial parts showed antioxidant activity, only at the highest tested concentration (50 μg/mL). Our results indicate that aerial parts of lentils may be recommended as a source of bioactive substances.

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