Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that the fibrinolytic activity of peritoneum is depressed in local inflammation. We measured fibrinolytic parameters in peritoneal fluid and in plasma of 10 women with pelvic inflammatory disease (PID). Nine women, in whom laparoscopy for sterilisation was performed, served as a control group. In the peritoneal fluid of women with PID, PAI-Ag, t-PA-Ag and u-PA-Ag were many times higher than in the control group. In contrast to the antigens which may be present in inert complexes, the potentially active compounds, measured as t-PA activity and plasmin-activable scu-PA, were not significantly different in the two groups, and in none of the samples was the active enzyme tcu-PA detectable. Nevertheless, the mean peritoneal fluid TDP and FbDP concentrations were about twenty times higher in the PID group than in the control group. In plasma of PID patients, none of the parameters except u-PA-Ag differed from those in the control group. The difference between control and patient plasma u-PA-Ag was statistically significant, but too small to attach any relevance to the observation. Our data suggest that, in contrast to the classical concept of decreased fibrinolytic activity as a cause of adhesion formation, intraperitoneal fibrinolysis is enhanced in peritoneal inflammation through stimulation of the local production of t-PA and u-PA. Despite concomitant production of PAI, fibrinolysis occurs at a high rate, resulting in high levels of fibrin degradation products. Since this activated fibrinolysis does not meet the demand, therapeutic enhancement should be considered to prevent adhesions.
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PMID:Peritoneal fluid and plasma fibrinolytic activity in women with pelvic inflammatory disease. 141 51

We should distinguish fibrin degradation products (FbDP) from fibrinogen degradation products (FgDP) in order to analyze fibrinolysis in vivo. We analyzed some disorders associated with hyperfibrinolytic states using ELISA for FbDP, FgDP and total fibrin (ogen) degradation products (TDP) (ORGANON TEKNIKA). Each ELISA was useful in terms of reproducibility and dilution linearity of plasma samples. There was no cross-reaction between FbDP and FgDP. The FgDP/FbDP ratio in normal individuals was 1.65. In patients with DIC, it was 0.43, with FgDP level being increased. These results suggest that fibrinolysis is enhanced in patients with DIC, but it is accompanied by fibrinogenolysis. On the other hand, the FgDP/FbDP ratio in patients given urokinase (UK) was 2.88. This suggests that fibrinogenolysis is enhanced in them. In our study, the FgDP/FbDP ratio increased as DIC improved. Thus, we can regard this as an index of therapeutic effects in patients with DIC. We conclude that these three ELISA are useful in analyzing disorders associated with hyperfibrinolytic states.
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PMID:[Differentiation between fibrin degradation products and fibrinogen degradation products by using newly developed ELISAs]. 192 Aug 69

The PTCA procedure fails in 30-50% of patients due to late restinosis, meaning that this is a problem of 100,000-150,000 people per year in the USA alone. It has been found that heparin and low-molecular-weight heparin (LMWH) have an inhibitory effect on smooth muscle cell (SMC) proliferation and migration, the major causes of restinosis. However, little is known about the toxicity and side effects of these drugs when used for a long period as may be required for prophylaxis of PTCA restinosis. To investigate possible side effects, non-human primates received daily injections of 1 mg/kg s.c. LMWH (Mono-Embolex) over a 12-week period. The hemostatic system was monitored through measurement of ACT-celite, APTT, Heptest, TT(10U/mL), TFPI, Anti-IIa activity, Anti-Xa activity, ACA-Heparin, AT III, factor VIII R:Ag, fibrinogen, and thrombomodulin levels. Elisa tests for t-PA, PAI-1, u-PA, FgDP, TDP, and D-Di levels were used for measurements of fibrinolytic activity. Increased values of ACT, APTT, Heptest, TT, Anti-IIa, Anti-Xa, ACA-Heparin, and TFPI were observed four hours after LMWH injections. AT III, vWFAg, fibrinogen and thrombomodulin showed no change from the pre-study baseline. An accumulation effect was seen in the APTT and Heptest over the 12 weeks. After the first week the blood levels of Anti-IIa activity remained elevated at 20% inhibition rather than 0% 24 hrs after drug administration. This activity slowly decreased after discontinuation of drug. The Anti-Xa blood level activity remained elevated at 40% inhibition 24 hrs after drug administration 2 weeks into the study, and this activity was detectable even 2 weeks after cessation of drug administration. There was increasing activity of the fibrinolytic system with LMWH treatment. After two weeks t-PA increased two-fold to 6 ng/mL but returned to baseline at six weeks. There was a corresponding increase of the TDP but not a clear increase in D-Di and FgDP. The increase of u-PA was limited to the first days of LMWH treatment only. The PAI-1 activity increased gradually over the entire study period. No bleeding complications occurred throughout the study. The long-term administration of Mono-Embolex as projected for the use in the prophylaxis of restinosis following PTCA appears to be safe for patients.
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PMID:Evaluation of hemostatic and fibrinolytic alterations associated with daily administration of low-molecular-weight heparin for a 12-week period. 766 Jan 45

The purpose of this study was to investigate differences in fibrinolytic activity in peritoneal fluid and plasma of women in the first and second part of the menstrual cycle. Given the classic concept of decreased fibrinolytic activity as a cause of adhesion formation, and if such differences are found, the stage of women's menstrual cycle should be taken into consideration when scheduling a laparotomy. We measured fibrinolytic parameters in peritoneal fluid and plasma in eight women in the pre-ovulatory period and in eleven women in the post-ovulatory period of the menstrual cycle. There were no differences in t-PA-Ag, t-PA-Act, u-PA-Ag and scu-PA concentrations in peritoneal fluid between the pre- and post-ovulatory group. Nevertheless, PAI-1-Ag in peritoneal fluid was three-fold higher in the post-ovulatory phase (p < 0.02). In peritoneal fluid the concentrations of both TDP and FbDP were three-fold higher at the same phase (p < or = 0.05). Plasma u-PA-Ag and scu-PA concentrations were significantly lower (30%, p < 0.05) in the post-ovulatory phase and also lower than plasma u-PA-Ag and scu-PA (measured with the same assay) in a group of 50 healthy individuals. No differences in t-PA and PAI concentration were found. In conclusion, the intraperitoneal fibrinolytic capacity might be impaired in the second part of the menstrual cycle, regarding the elevated levels of PAI-1-Ag, leading to an increased risk for post-ovulatory adhesion formation. The low plasma u-PA-Ag and scu-PA levels post-ovulatory may have clinical relevance.
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PMID:Parameters of fibrinolysis in peritoneal fluid and plasma in different stages of the menstrual cycle. 812 49

Ancrod is a purified coagulant venom which renders blood incoagulable by cleaving fibrinopeptide A (FPA) from fibrinogen, but the mechanism involved in the clearance of fibrin from the circulation is unknown. To investigate the fibrinolytic response to ancrod, and to increase understanding of clearance mechanisms, six patients with peripheral vascular disease causing claudication were infused with ancrod at 2 u/kg over 6 h followed by 2 u/kg at 12 h intervals for 38 h. Venous blood samples were taken at time 0, 3, 6, 25 and 49 h for assay of fibrinogen (Fbg), fibrinopeptide A (FPA), total fibrin(ogen) degradation products (TDP), fibrin degradation products (FbDP), fibrinogen degradation products (FgDP), cross-linked fibrin degradation products (XL-FDP), tissue plasminogen activator (tPA), urinary type plasminogen activator (u-PA), plasminogen, alpha 2 antiplasmin (alpha 2 AP) and plasminogen activator inhibitor-1 (PAI-1). Fibrinogen (median and range) was 2.3 (1.4-3.90) g/l at time 0 and thereafter was undetectable. FPA rose from 2.5 (1.8-3.6) to 600 and 188 pmol/l at 3 h and 6 h and remained elevated. TDP, FbDP and FgDP increased greatly following ancrod while there was no evidence of XL-FDP. The surprising increase in FgDP during defibrination suggests either that fibrinogen is digested following its incorporation into circulating fibrin protofibrils or that some of the fibrin subunits in the photofibril retain one of the two fibrinopeptide A's. tPA and uPA remained unchanged. Plasminogen fell from 125 (100-155)% to 79 (40-118)% at 49 h and alpha 2 AP fell from 91 (75-107)% to 24 (10-35)% at 49 h. The level of PAI-1 was depressed during defibrination, with the exception of the 6 h data. The results demonstrate that ancrod removes FPA from fibrinogen to produce non-cross-linked (soluble) fibrin. This is cleared from the circulation without evidence of an increase in the circulating activities of the plasminogen activators, tPA or UK, but with evidence of plasminogen activation and consumption.
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PMID:The fibrinolytic response to ancrod therapy: characterization of fibrinogen and fibrin degradation products. 845 76