HUMAN FIBRINOLYSIN WITH AND WITHOUT UROKINASE: ITS EFFECT ON EXPERIMENTAL ARTERIAL THROMBI IN DOGS

1962 ◽  
Vol 40 (1) ◽  
pp. 1819-1838 ◽  
Author(s):  
Walter H. E. Roschlau ◽  
Robert H. Painter
Keyword(s):  
Body Weight ◽  
Therapeutic Dose ◽  
Traditional Method ◽  
Fibrinolytic Activity ◽  
Single Injection ◽  
Clot Lysis ◽  
Undesirable Side Effect ◽  
Department Of Health ◽  
Heat Treated

The lytic effects of heat-treated, sterile solutions of spontaneously activated and urokinase-activated fibrinolysin on occlusive experimental arterial clots have been studied. For this purpose methods for the preparation of urokinase and activation of profibrinolysin, the production of traumatic arterial thrombi in dogs, and the recording of clot lysis are described. Single injection as a means of administration was compared with the traditional method of infusion. When used in conjunction with a prompt assay of the in vivo fibrinolytic activity, which was developed for this purpose, the injection method was preferred. The results indicated that spontaneous fibrinolysin, given by single injection, was as effective in lysing clots as were preparations of fibrinolysin that contained activator. The approximate therapeutic dose for both types of fibrinolysin under the conditions described was found to be 225–325 Michigan Department of Health caseinolytic units per kg body weight. Lysis of occluding arterial thrombi was achieved within a few hours after administration of fibrinolysin by injection, and arteries remained patent during the week of posttreatment observation. No toxic effects due to the fibrinolysin or the glycerol present as stabilizer could be demonstrated after the therapeutic dose. The only undesirable side effect of overdose of fibrinolysin was a transient incoagulability of the blood.

HUMAN FIBRINOLYSIN WITH AND WITHOUT UROKINASE: ITS EFFECT ON EXPERIMENTAL ARTERIAL THROMBI IN DOGS

1962 ◽  
Vol 40 (12) ◽  
pp. 1819-1838 ◽  
Author(s):  
Walter H. E. Roschlau ◽  
Robert H. Painter
Keyword(s):  
Body Weight ◽  
Therapeutic Dose ◽  
Traditional Method ◽  
Fibrinolytic Activity ◽  
Single Injection ◽  
Clot Lysis ◽  
Undesirable Side Effect ◽  
Department Of Health ◽  
Heat Treated

The lytic effects of heat-treated, sterile solutions of spontaneously activated and urokinase-activated fibrinolysin on occlusive experimental arterial clots have been studied. For this purpose methods for the preparation of urokinase and activation of profibrinolysin, the production of traumatic arterial thrombi in dogs, and the recording of clot lysis are described. Single injection as a means of administration was compared with the traditional method of infusion. When used in conjunction with a prompt assay of the in vivo fibrinolytic activity, which was developed for this purpose, the injection method was preferred. The results indicated that spontaneous fibrinolysin, given by single injection, was as effective in lysing clots as were preparations of fibrinolysin that contained activator. The approximate therapeutic dose for both types of fibrinolysin under the conditions described was found to be 225–325 Michigan Department of Health caseinolytic units per kg body weight. Lysis of occluding arterial thrombi was achieved within a few hours after administration of fibrinolysin by injection, and arteries remained patent during the week of posttreatment observation. No toxic effects due to the fibrinolysin or the glycerol present as stabilizer could be demonstrated after the therapeutic dose. The only undesirable side effect of overdose of fibrinolysin was a transient incoagulability of the blood.

In Vivo Effect of Heparin on Acid and Alkaline Ribonuclease Activities of Mouse Liver

1956 ◽  
Vol 184 (2) ◽  
pp. 415-417 ◽  
Author(s):  
Gaston De Lamirande ◽  
George Weber ◽  
Antonio Cantero
Keyword(s):  
Tissue Culture ◽  
Body Weight ◽  
Single Dose ◽  
Ribonucleic Acid ◽  
Mouse Liver ◽  
Single Injection ◽  
Coagulation Time ◽  
Alkaline Ribonuclease ◽  
Blood Coagulability

A single dose of 30 µg/gm body weight of depo-heparin was injected subcutaneously into white Swiss mice. At 1, 3, 6 and 12 hours after the injection, the blood coagulation time was measured and the activity of acid and alkaline ribonuclease of liver was determined. This single injection of depo-heparin significantly inhibited the acid and alkaline ribonucleases of liver 1 hour after injection. The enzymatic activities significantly increased after the blood coagulability was restored. The in vivo inhibition of acid and alkaline ribonuclease activity supports the explanation that the accumulation of ribonucleic acid in cells of tissue culture in the presence of heparin might be due to the inhibition of ribonuclease.

Enhancement of Spontaneous Fibrinolytic Activity in Diabetic Retinopathy

1992 ◽  
Vol 68 (04) ◽  
pp. 400-403 ◽  
Author(s):  
Helmut Ostermann ◽  
Diethelm Tschöpe ◽  
Wolfgang Greber ◽  
Hans-Werner Meyer-Rüsenberg ◽  
Jürgen van de Loo
Keyword(s):  
Fibrinolytic Activity ◽  
Type I Diabetes ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Fibrinolytic System ◽  
Clot Lysis ◽  
Diabetic Patients ◽  
Type I ◽  
Activated State

SummaryThe fibrinolytic system was studied in 96 patients with type I diabetes mellitus. Patients were grouped according to their degree of retinopathy; 38 patients with no evidence of retinopathy, 28 patients with background retinopathy and 30 patients with proliferative retinopathy. Thirty healthy individuals served as controls. The basal fibrinolytic activity as measured by clot lysis time and t-PA activity was increased in diabetic patients. This was associated with low levels of plasminogen activator inhibitor. Increased levels of D-dimer in diabetic patients further indicate enhanced in vivo fibrinolysis. The increase in fibrinolytic activity was highest in diabetics without retinopathy, and decreased with increasing retinopathy. Endothelial release of t-PA after venous occlusion was not different between controls and all diabetic groups. These findings suggest that in type I diabetics the fibrinolytic system is in an activated state. With worsening of retinopathy this increase in fibrinolytic activity diminishes.

Retinoic Acid Enhances Fibrinolytic Activity In-Vivo by Enhancing Tissue Type Plasminogen Activator (t-PA) Activity and Inhibits Venous Thrombosis

1993 ◽  
Vol 69 (04) ◽  
pp. 381-386 ◽  
Author(s):  
J J J van Giezen ◽  
G d I A Boon ◽  
J W C M Jansen ◽  
B N Bouma
Keyword(s):  
Retinoic Acid ◽  
Platelet Aggregation ◽  
Venous Thrombosis ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Tissue Type ◽  
Clot Lysis ◽  
Thrombin Time ◽  
Tissue Extracts

SummaryWe studied the profibrinolytic effect and the anti-thrombotic potential of retinoic acid in-vivo. Male Wistar rats were treated with retinoic acid either acutely or twice daily for a period of 5 consecutive days in a dose range of 0.01 to 3.0 mg/kg. Fibrinolytic activity was measured ex-vivo using the diluted blood clot lysis test and net t-PA activity in tissue extracts was measured in a spectrophotometric rate assay. Clot lysis was dose dependently increased by retinoic acid up to about 170% (relative to vehicle treated rats) at a dose of 3 mg/kg. No tachyphylaxis could be detected. Ex-vivo measured fibrinolytic activity after single administration of 1 mg/kg of retinoic acid peaked at 3 h after ingestion. Even after 18 h a significantly higher clot lysis rate was measured. Lysis of blood clots from vehicle and retinoic acid treated rats could be completely blocked by addition of tranexamic acid or antibodies against rat t-PA before clot formation. t-PA activity in plasma was slightly increased after retinoic acid treatment; no effects were measured on plasma PAI-1, u-PA, plasminogen, and α2-antiplasmin levels. t-PA activity in lung and kidney was marginally enhanced by retinoic acid but in heart and aortic tissue extracts t-PA activity was increased by about 50%. We confirmed this potential anti-thrombotic property in an in-vivo venous thrombosis model. A reduced clot size was observed after retinoic acid administration (35% reduction at a dose of 1 mg/kg). We could not detect any effect on ex-vivo measured platelet aggregation, bleeding time, prothrombin time, thrombin time, partial thromboplastin time or plasma fibrinogen level, indicating that there were no effects on platelet aggregation or blood coagulation. We conclude that retinoic acid enhanced fibrinolytic activity in-vivo by selectively enhancing t-PA activity and that retinoic acid is a potential anti-thrombotic agent in-vivo.

Fibrinolytic Properties Of Microbial Proteases

1981 ◽  
Author(s):  
N S Egorov ◽  
N S Landau ◽  
G V Andreenko ◽  
V G Kreyer ◽  
S S Pokrovskaya ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Intravenous Injection ◽  
Fibrinolytic Activity ◽  
Clot Lysis ◽  
Albino Rats ◽  
Ecological Groups ◽  
Fibrinolytic Enzymes ◽  
Thrombolytic Effect

Our study of 820 microorganisms from various systematic and ecological groups revealed that 72% of the cultures contained enzymes caoable to dissolve human fibrin clots in vitro. Fibrinolytic enzymes are formed during growth of producers on strictly specific media. Changes in the composition of media and conditions of enzymatic synthesis were found to increase the specificity of microbial proteases to fibrin and to decrease their sensitivity to fibrinolytic enzymes inhibitors. A thrombolytic enzyme (TE) has been isolated and purified from the cultural fluid of actinomycetes. An intravenous injection of TE to albino rats results in an increase of fibrinolytic activity of the blood plasma euglobulin fraction. Time of euglobulin clot lysis is thereby decreased by 32%. The fibrinolytic activity measured from euglobulin precipitate on un-heated fibrin plates is increased 2.3-fold. However, the fibrinolytic activity of non-diluted blood plasma remains unchanged probably due to a sharp rise in antiplasmin content following TE injection. TE exerts marked thrombolytic effect in vivo. After intravenous injection of TE to animals with artificial clots in a v.jugularis segment a rapid clot lysis and reconstitution of blood flow are observed.

Quantifying in vivo dopaminergic D2-receptors Bmax and KdVr with microPET® focus after a single injection of [11C]raclopride

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S649-S649
Author(s):  
Laurent Besret ◽  
Jean-Dominique Gallezot ◽  
Frédéric Dollé ◽  
Philippe Hantraye ◽  
Marie-Claude Grégoire
Keyword(s):  
Single Injection ◽  
D2 Receptors ◽  
Quantifying In

Influence of Moderate and Strenuous Daily Physical Activity on Fibrinolytic Activity of Blood: Possibility of Plasminogen Activator Stores Depletion

1979 ◽  
Vol 41 (04) ◽  
pp. 745-755 ◽  
Author(s):  
Dušan Keber ◽  
Mojca Stegnar ◽  
Irena Keber ◽  
Bojan Accetto
Keyword(s):  
Physical Activity ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Regular Physical Activity ◽  
Clot Lysis ◽  
Moderate Activity ◽  
Lysis Time ◽  
Strenuous Activity ◽  
Activity Measurements ◽  
Clot Lysis Time

SummaryFibrinolysis was studied in 10 alpinists during regular physical activity of different intensity. Blood was sampled at rest and after exposure to submaximal workload on the treadmill on three occasions: before and after 6 months physical conditioning (moderate physical activity), and after 6 weeks of an alpinistic expedition (strenuous physical activity). Measurements included submaximal working capacity, fibrinogen, euglobulin clot lysis time (ELT), whole plasma clot lysis time, and estimations derived from ELT - percent increase in fibrinolytic activity after exercise (RFS), and absolute increase in fibrinolytic activity after exercise (PAR).Regular moderate activity increased the resting level of ELT, but strenuous activity decreased is. After each treadmill testing, a marked increase in fibrinolytic activity was observed. RFS was unaltered at all three testings. PAR increased after moderate activity, but decreased after strenuous activity.The results indicate that regular physical activity can lead from enhanced to decreased resting activity of plasminogen activator in blood. It is presumed that increased release of activator during prolonged stress causes partial depletion of endothelial stores with the consequence of decreased activator activity in the blood.

Gastric Fibrinolysis

1975 ◽  
Vol 34 (02) ◽  
pp. 409-418 ◽  
Author(s):  
I. M Nilsson ◽  
S.-E Bergentz ◽  
U Hedner ◽  
K Kullenberg
Keyword(s):  
Gastric Ulcer ◽  
Gastric Juice ◽  
High Activity ◽  
Fibrinolytic Activity ◽  
Duodenal Juice ◽  
Bleeding Tendency ◽  
Local Fibrinolysis ◽  
Heated Plates

SummaryGastric juice from 15 normals, 20 patients with gastric ulcer and 4 patients with erosive haemorrhagic gastroduodenitis was investigated in respect of its activity on unheated and heated fibrin plates and its content of FDP and plasminogen or plasmin with immunochemical methods. Gastric juice from normals showed no activity on unheated and heated fibrin plates, and no FDP or plasminogen could be demonstrated. In the patients with gastric ulcer the gastric juice showed little or no fibrinolytic activity on fibrin plates except in 2, who had regurgitation of duodenal juice and neutral pH of the juice. These patients had equally high activity on heated as on unheated plates and no plasmin could be demonstrated. It was shown that this activity was not due to fibrinolysis, but to non-specific proteolytic activity (probably trypsin). The patients with erosive haemorrhagic gastroduodenitis exhibited quite a different picture. The gastric juice from these patients showed extremely high activity on fibrin plates, the activity was higher on unheated than on heated plates. The activity was inhibited in vitro by addition of EACA and in vivo after administration of AMCA. The occurrence of plasmin could be demonstrated directly immunologically in the gastric juice. By comparison of plasmin and trypsin in various assays it could further be proved that the gastric juice in these cases contained plasminogen activator and plasmin. The patients with erosive haemorrhagic gastroduodenitis showed no increase in fibrinolysis in the blood, but low values for plasminogen and α2M, and the serum contained FDP. These findings in the blood and gastric juice were interpreted as signs of local fibrinolysis in the stomach and duodenum. There is reason to assume that this gastric fibrinolysis contributes substantially to the bleeding tendency. The effect of administration of AMCA on fibrinolytic activity and the haemorrhage lends support to the assumption of such a mechanism.

Anti-thrombotic Effect of a PAI-1 Inhibitor in Rats Given Endotoxin

1996 ◽  
Vol 75 (01) ◽  
pp. 118-126 ◽  
Author(s):  
T Abrahamsson ◽  
V Nerme ◽  
M Strömqvist ◽  
B Åkerblom ◽  
A Legnehed ◽  
...  
Keyword(s):  
Plasminogen Activator Inhibitor ◽  
Rat Plasma ◽  
Clot Lysis ◽  
Fibrin Deposition ◽  
Plasminogen Activator Inhibitor 1 ◽  
Fab Fragment ◽  
Dose Dependent Decrease ◽  
Pai 1

SummaryThe aim of this study was to investigate the anti-thrombotic effects of an inhibitor of the plasminogen activator inhibitor-1 (PAI-1) in rats given endotoxin. In studies in vitro, PRAP-1, a Fab-fragment of a polyclonal antibody against human PAI-1, was shown to inhibit PAI-1 activity in rat plasma as well as to stimulate clot-lysis of the euglobulin fraction derived from rat plasma. Endotoxin administered to anaesthetised rats produced a marked increase in plasma PAI-1 activity. To study fibrin formation and lysis in vivo after intravenous (i. v.) injection of the coagulant enzyme batroxobin, 125I-fibrinogen was administered to the animals. The thrombi formed by batroxobin were rapidly lysed in control animals, while the rate of lysis was markedly attenuated in rats given endotoxin. PRAP-1 was administered i.v. (bolus + infusion) to rats given endotoxin and batroxobin and the PAI-1 inhibitor caused a dose-dependent decrease in the 125I-fibrin deposition in the lungs. An immunohistochemical technique was used to confirm this decrease in density of fibrin clots in the tissue. Furthermore, PRAP-1 decreased plasma PAI-1 activity in the rats and this reduction was correlated to the decrease in lung 125I-fibrin deposition at the corresponding time point. It is concluded that in this experimental model the PAI-1 antibody PRAP-1 may indeed inhibit thrombosis in animals exposed to endotoxin.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

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