Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of physical conditioning on plasma fibrinolytic activity were studied in two groups of subjects. Volunteers not engaged in any sport were compared with individuals having been subjected to aerobic conditioning (middle-distance runners, defined as men running more than 80 km per week). Plasma concentrations of the different components of the fibrinolytic system were evaluated before and immediately after a maximal effort treadmill protocol. Comparison of the resting parameters revealed that under basal conditions for plasma concentrations of plasminogen, fibrinogen, alpha 2-antiplasmin, protein C and protein S there were no differences between the two groups. Concentrations of the fibrin degradation products (FbDP) and fibrinogen degradation products (FgDP) were significantly higher in the runners than in the control group, indicating an increased fibrinolytic potential that seemed to be a consequence of the reduced formation of tissue plasminogen activator-plasminogen activator inhibitor (t-PA-PAI) complexes. Acute maximal exercise resulted in pronounced fibrinolysis, evidenced by the elevation of FbDP and FgDP concentrations, in both groups of subjects. The acceleration of the fibrinolytic activity was larger in conditioned individuals, which could be accounted for by a higher t-PA release and reduced formation of t-PA-PAI complexes when compared to the untrained subjects.
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PMID:Changes in the fibrinolytic system associated with physical conditioning. 142 41

A major adverse effect of recombinant human erythropoietin (r-HuEPO) in hemodialyzed patients are thrombotic events. Several reports on platelet function during r-HuEPO treatment have been published but less is known about fibrinolysis. In the present study, the fibrinolytic capacity was studied in 20 patients on maintenance hemodialysis and treated with r-HuEPO. The patients were randomized into two groups and investigated in a crossover design. r-HuEPO was administered intravenously and subcutaneously in each group and was given for 3 months, respectively. Plasma tissue plasminogen activator (t-PA) and released t-PA remained unaffected by r-HuEPO in both groups throughout the study. Tissue plasminogen activator inhibitor (PAI) increased in a cyclic way reaching peak values 4-6 weeks after the start of investigation and again 4-6 weeks after changing therapy. The increase in PAI was significant in the two groups (0.025 > p > 0.01). Tissue plasminogen antigen was low in the uremic patients. The influence of r-HuEPO on this parameter was not investigated. Compensatory changes in plasma levels of factor XII procoagulant activity, activated protein C and of alpha 2-antiplasmin were not observed. Thrombotic events occurred in 4 patients at peak values of PAI. Six patients required an increase in heparin dose simultaneously with the increase in PAI. Thus, r-HuEPO seemed to affect the fibrinolytic capacity of uremic patients.
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PMID:Fibrinolytic capacity in hemodialysis patients treated with recombinant human erythropoietin. 143 39

Although thrombolytic drugs have been extensively used in adults, there is sparse information on their effectiveness in newborns whose fibrinolytic system differs significantly from adults. The purpose of this study was to determine if low plasma levels of plasminogen in cord plasma limited the therapeutic effectiveness of thrombolytic agents. Urokinase (UK), streptokinase (SK) and tissue plasminogen activator (TPA) were compared for their ability to lyse washed 125I-labelled adult or cord fibrin clots suspended in cord or adult plasma. 125I-labelled fibrin clots were prepared by recalcifying cord or adult plasma spiked with labelled fibrinogen and then placed into cord or adult plasma which contained either saline or differing amounts of a specific thrombolytic agent. After a 60 min incubation, the remaining 125I-fibrin in clots released 125I-fibrin fragments, and concentrations of fibrinogen, alpha 2-antiplasmin, and plasminogen in the bathing plasma were measured and compared to starting values. Cord fibrin clots were more resistant than adult fibrin clots to all thrombolytic drugs tested (p less than 0.001). On average, the cord system retained 27% more 125I-fibrin in clots, and released 32% less 125I-fibrin fragments into plasma. Fibrinogenolysis was also decreased in cord plasmas compared to adult plasmas. The degree of fibrinolysis and fibrinogenolysis in cord plasma increased to adult values when plasminogen concentrations were increased in the bathing plasma. Thus, cord fibrin clots have an impaired response to thrombolytic agents secondary to low levels of plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration. 144 Apr 99

The aim of this study was to evaluate the thrombolytic activity of two hybrid plasminogen activators (HPAs) in a rabbit jugular vein thrombosis model. In the two HPAs the kringle-2 domain (K2tu-PA) or the finger and the kringle-2 domains (FK2tu-PA) of tissue-type plasminogen activator (t-PA) are linked to the catalytic protease domain of single chain urokinase type plasminogen activator (scu-PA). The two HPAs were compared with rt-PA and scu-PA on a weight/weight basis. K2tu-PA, FK2tu-PA, rt-PA and scu-PA were infused at doses of 0.4, 0.8 and 1.2 mg/kg over 3 h. Saline served as control. Saline produced 11 +/- 2% thrombolysis. The three doses of K2tu-PA led to 38 +/- 4%, 66 +/- 5% and 89 +/- 7% thrombolysis, respectively; the three doses of FK2tu-PA: 18 +/- 3%, 29 +/- 5% and 33 +/- 6%, respectively; the three doses of rt-PA 32 +/- 2%, 49 +/- 3% and 68 +/- 6%, respectively; the three doses of scu-PA 16 +/- 2%, 24 +/- 3% and 32 +/- 4%, respectively. K2tu-PA and rt-PA showed a statistically significant higher thrombolytic activity than FK2tu-PA and scu-PA at the three tested doses (p less than 0.01). The thrombolytic activity of K2tu-PA was significantly higher than rt-PA at the two higher doses (p less than 0.01). Both K2tu-PA and rt-PA produced a statistically significant reduction of fibrinogen, alpha 2-antiplasmin and plasminogen 3 h after the start of the infusions of the two higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolytic activity of two chimeric recombinant plasminogen activators (FK2tu-PA and K2tu-PA) in rabbits. 144 May

The effect of trans-5-prostaglandin E2 (trans-PGE2) on fibrinolysis was examined in vitro using synthetic chromogenic substrate S-2251. trans-PGE2 was found to enhance plasminogen (PLG) activation mediated by tissue-type plasminogen activator (tPA). The enhancing effect was dependent on the concentration of trans-PGE2. cis-PGE2 and the other PGs (PGE1 and PGI2) did not show such an effect as trans-PGE2, despite to the fact that their structures are similar to that of trans-PGE2. trans-Configuration around the double bond at the 5-position seems to be important in the enhancement of the fibrinolytic activity.
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PMID:trans-5-prostaglandin E2 stimulates plasminogen activation by tissue-type plasminogen activator. 144 33

Semen specimens from four groups of patients were evaluated for coagulation and fibrinolysis factors: a group of patients with infertile semen and involuntary childlessness (n = 35), a group with fertile semen and involuntary childlessness (n = 39), a group with fertile semen and proven fertility before vasectomy (n = 34) and a group with infertile semen after vasectomy (n = 147). The third patient group with proven fertility before vasectomy was considered as a control group. Only small amounts of fibrinogen, factor VIII:c, plasminogen, antithrombin III, fibrin monomers and plasminogen activator inhibitor-1 were detected in seminal plasma. The thrombin-antithrombin III, D-dimer and tissue plasminogen activator regular concentrations were measured and the D-dimer/thrombin-antithrombin III ratios calculated. The reference ranges were assessed and the quantities were compared in the different patient groups. Significant differences were demonstrated between the prevasectomy group (= control group) and both the postvasectomy and the infertility groups with respect to D-dimer and D-dimer/thrombin-antithrombin III ratio. We conclude that both coagulation and fibrinolysis play a part in coagulum formation and liquefaction of seminal plasma. The balance between coagulation and fibrinolysis (expressed as D-dimer/thrombin-antithrombin III ratio) was significantly different between the control group and the three patient groups. The coagulation/fibrinolysis balance was impaired in the semen from post vasectomy patients and from those with involuntary childlessness and the D-dimer/thrombin-antithrombin III ratios in both these patient groups were very similar.
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PMID:Coagulation and fibrinolysis markers in seminal plasma of patients under evaluation for involuntary childlessness. 144 60

Fibrin structure contributes to the regulation of the fibrinolytic rate. As the fibrin fiber size is decreased, the fibrinolytic rate also decreases. Fibrin structure was altered by either changing the ratio of thrombin to fibrinogen, i.e. altering the assembly rate or by adding a fibrin assembly inhibitor, iopamidol. Changes in the fibrinolytic rate were followed by measuring the time dependence of the decrease in the fiber mass/length ratio during fibrinolysis. A measure of the overall fibrinolytic rate was determined from the decrease in the mass/length ratio versus time. An 8-fold reduction in the fibrinolytic rate was seen on decreasing the mass/length ratio from 2.7 x 10(12) daltons/cm to 0.5 x 10(12) daltons/cm. It is shown that thin fibrin fibers have a decreased rate of conversion of plasminogen to plasmin by tissue plasminogen activator and that thin fibrin fibers are lysed more slowly than thick fibrin fibers.
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PMID:The effect of fibrin structure on fibrinolysis. 144 76

This article has summarized known congenital and acquired alterations of hemostasis leading to thrombosis. Decreases in coagulation inhibitors, including antithrombin III, heparin cofactor II, and protein C and protein S, are of major importance in assessing patients with hypercoagulable states or patients with unexplained thrombosis. Newer assays for components of the fibrinolytic system, plasminogen, t-PA and t-PA inhibitor are also now readily available and are important for defining congenital or acquired fibrinolytic defects leading to hypercoagulability and thrombosis. By judicious use of these assays, combined with clinical evaluation, many patients with thrombosis will have an underlying etiologic blood protein defect defined. Delineating reasons for a thrombotic event is of obvious importance for planning long-term prophylactic therapy and for diagnosing and counseling afflicted family members. In this manner, newly found patients can be treated prophylactically before unalterable morbidity or mortality occurs.
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PMID:Hypercoagulability and thrombosis. 145 21

The contribution of activation of the contact system to activation of the fibrinolytic system in vivo was investigated in healthy volunteers and in factor XII deficient patients. The plasminogen activating activity in normal plasma was only partially blocked (for 77%) with specific antibodies to tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). The residual activity could be quenched by a monoclonal antibody that inhibits factor XII activity and was not present in patients with a factor XII deficiency. The formation of plasmin upon the DDAVP stimulus as reflected by circulating plasmin-alpha 2-antiplasmin (PAP) complexes was lower in factor XII deficient patients than in healthy volunteers. These results indicate that in vivo the plasminogen activating activity is partially dependent on activation of the contact system. This fibrinolytic activity is impaired in factor XII deficient patients which may explain the occurrence of thromboembolic complications in these patients.
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PMID:Contact system dependent fibrinolytic activity in vivo: observations in healthy subjects and factor XII deficient patients. 146 34

Oral contraceptives caused increased fibrinogen, FVII, FX, and fibrinolysis. The latter was associated with elevated FXII and PKK, while C1-INH was decreased, ATIII and alpha 2M were unchanged; it could not be accounted for by changes in t-PA, u-PA, PAI, plasminogen, alpha 2-AP, proteins C or S. HCII and alpha 1-PI were increased and may regulate the availability of thrombin and FXIa. The increased FXII/PKK dependent fibrinolytic potential and HCII may offset any increase in thrombin generation, while alpha 1-PI limits intrinsic coagulation.
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PMID:Procoagulant changes induced by oral contraceptives are balanced by an increased fibrinolytic tendency. 146 38


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