scholarly journals SERUM AND URINARY FIBRINOLYTIC ACTIVITY RELATED TO THE HEMORRHAGIC DIATHESIS IN IRRADIATED DOGS

1952 ◽  
Vol 95 (6) ◽  
pp. 531-542 ◽  
Author(s):  
J. Colgan ◽  
E. Gates ◽  
L. L. Miller

The urine and serum fibrinolytic activity were measured in dogs following whole body radiation ranging from 450 to 800 r generated by 1,000 kv. and 250 kv. machines. The fibrinolytic activity of the urine showed a precipitate rise 4 to 5 days before death in all dogs with pulmonary hemorrhage as the main cause of death. The fibrinolytic activity of the serum showed a similar rise, which was most pronounced in the case of those animals which did not survive. The fibrinolytic activities of the urine and serum approached control levels at about the 24th day after irradiation in all the surviving dogs. The possible mode of activation of the fibrinolytic enzyme in vivo is discussed and approaches to prevention of the hemorrhagic syndrome are suggested.

1960 ◽  
Vol 04 (02) ◽  
pp. 149-166 ◽  
Author(s):  
Nils U. Bang ◽  
Eugene E. Cliffton

Summary1. The effect of a standard, potent fibrinolytic enzyme therapy has been compared in fasting and lipemic dogs.2. The standard fibrinolytic regimen resulted in the complete dissolution of all clots produced experimentally in the fasting state in 10 dogs.3. Clots formed during alimentary lipemia exhibited a markedly increased resistance to the standard fibrinolytic regimen in 6 dogs.4. An increase in anti plasmin fibrinolytic titer with concomitant decrease in spontaneous fibrinolytic activity was observed in 15 dogs following the administration of a fatty meal. No difference in fibrinolytic activity and APF titer was demonstrable in fasting and lipemic blood samples obtained during fibrinolytic enzyme treatment.5. The possibility of the presence of specific inhibitors against the fibrinolytic enzyme in clots formed during lipemia has been investigated and the evidence to support this theory is discussed.


1960 ◽  
Vol 199 (3) ◽  
pp. 491-494 ◽  
Author(s):  
Clara M. Ambrus ◽  
Gabor Markus

When streptokinase-activated, urokinase-activated, or spontaneously activated human plasmin is mixed with increasing amounts of human antiplasmin, caseinolytic effect decreases much more rapidly than fibrinolytic effect. At concentrations of antiplasmin at which caseinolytic effect completely disappears, considerable fibrinolytic activity persists. Authors suggest that fibrin can compete for plasmin with antiplasmin while other proteins may be less effective in this respect. This may explain the specificity of plasmin for fibrin in vivo, in the presence of the inhibitor. Antiplasmin may play an important physiological role in protecting normal plasma proteins while allowing lysis of fibrin clots by plasmin.


1975 ◽  
Vol 34 (02) ◽  
pp. 409-418 ◽  
Author(s):  
I. M Nilsson ◽  
S.-E Bergentz ◽  
U Hedner ◽  
K Kullenberg

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.


1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou

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.


1972 ◽  
Vol 28 (01) ◽  
pp. 031-048 ◽  
Author(s):  
W. H. E Roschlau ◽  
R Gage

SummaryInhibition of blood platelet aggregation by brinolase (fibrinolytic enzyme from Aspergillus oryzae) has been demonstrated with human platelets in vitro and with dog platelets in vivo and in vitro, using both ADP and collagen as aggregating stimuli. It is suggested that the optimal inhibitory effects of brinolase occur indirectly through the generation of plasma fibrinogen degradation products, without compromising platelet viability, rather than by direct proteolysis of platelet structures.


1973 ◽  
Vol 30 (01) ◽  
pp. 114-122
Author(s):  
C.R.M Prentice ◽  
K.M Rogers ◽  
G.P McNicol

SummaryThe pharmacological effect of a new preparation of urokinase (Leo) has been studied, both in vitro and in six patients suffering from thrombo-embolic disorders. It was a non-toxic, effective fibrinolytic agent if given in sufficient dosage. A regimen consisting of an initial dose of 7,200 ploug units per kg body weight, followed by hourly maintenance therapy with 3,600 ploug units per kg intravenously, gave satisfactory evidence of whole body fibrinolytic activity. The preparation had minor but insignificant thromboplastic activity both when assayed in the laboratory and when given to patients.


1972 ◽  
Vol 28 (03) ◽  
pp. 351-358
Author(s):  
A.J Baillie ◽  
A. K Sim

SummaryThe activity of several synthetic compounds, rated from good to poor (or inactive) fibrinolytic activators, has been assessed by two different commonly-used in vitro methods. Compounds shown to be active over a narrow concentration range in the hanging clot test were shown to be inhibitors of plasmin and trypsin in the casein-olytic test. The inhibitory activity of these compounds was shown to increase with increasing substrate concentration and apparent activity in the hanging clot test. Possible explanations and relevance of these observations are discussed.


1970 ◽  
Vol 23 (02) ◽  
pp. 202-210 ◽  
Author(s):  
R Bishop ◽  
H Ekert ◽  
G Gilchrist ◽  
E Shanbrom ◽  
L Fekete

SummaryA new fibrin plate technic for evaluating components of the fibrinolytic system has been developed. It provides quick, accurate, and easily interpreted results for the fibrinolytic profile. The standardized human plasminogen-free fibrin plates can be produced in bulk and stored for prolonged periods of time. A test specimen placed in a well punched in the buffered agarose gel diffuses into the agar and lyses the fibrin clot, forming a clear reaction zone. The zone diameter is directly proportional to the log of the percent concentration of available fibrinolytic enzyme in the specimen. The plates may be used to quantitate total plasminogen, and estimate available plasmin and active plasmin. A good correlation between results obtained using these fibrin plates and caseinolytic methods was found. Performance and interpretation of tests of fibrinolysis done on these new fibrin plates indicate that it may be the most sensitive technic available for clinical laboratory work.


1992 ◽  
Vol 68 (01) ◽  
pp. 069-073 ◽  
Author(s):  
J J J van Giezen ◽  
J W C M Jansen

SummaryDexamethasone decreases the fibrinolytic activity in cultured medium of several cell types by an induction of PAI-1 synthesis. As a result of this enhanced PAI-1 synthesis a prothrombotic state is expected in patients treated with dexamethasone. However, such a prothrombotic state is not reported as a major adverse effect. We have studied the effects of dexamethasone (dose range: 0.1–3.0 mg/kg) on the fibrinolytic system of rats after a 5 day pretreatment period. It appeared that dexamethasone dose dependently decreased the fibrinolytic activity (a dose of 1 mg/kg showed a reduction of about 40%). This reduced fibrinolytic activity could be functionally translated into an increased thrombus size as measured with a venous thrombosis model: thrombus size was increased by 50% with 1 mg/kg dexamethasone. No effects could be measured on the coagulation system, but it appeared that ex-vivo measured platelet aggregation was dose dependently inhibited by dexamethasone treatment. This effect resulted in-vivo in prolonged obstruction times as measured with a modified aorta-loop model. These results indicate that the expected prothrombotic state due to a diminished fibrinolytic activity caused by dexamethasone is counterbalanced by an inhibition of platelet aggregation.


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