Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we determined the effect of 80% deacetylated chitin (DAC-80) membrane on postsurgical bleeding after visceral and parietal peritoneal abrasion. Japanese white rabbits underwent a midline laparotomy followed either by a bilateral peritoneal sidewall abrasion (4 x 4 cm) or an abrasion of liver surface (3 x 2 cm). The injured surface was then covered with a 0.2 mm thick DAC-80 membrane. On postsurgical day 2, the rabbits were sacrificed and the amounts of postsurgical bleeding was determined by quantitating the number of red blood cells recovered in 50 ml peritoneal lavage fluid. The DAC-80 membrane was found to reduce postsurgical bleeding after the abrasion of liver surface (treated with DAC-80 membrane: 2.9 +/- 0.8; control: 24.6 +/- 5.9 x 10(8) cells/peritoneal cavity, P less than 0.005). This same hemostatic activity was not observed after application in the peritoneal sidewall abrasion model. We also measured plasminogen activator activity (PA) and urokinase inhibitory (PAI) activity in the spent culture media of macrophages recovered from the postsurgical peritoneal exudate. The DAC-80 membrane reduced the PA secretion from postsurgical macrophages after liver surface abrasion (treated with DAC-80: 2.8 +/- 0.7; control: 3.9 +/- 0.9 mPU/ml). The DAC-80 membrane also showed similar effects on PA secretion after peritoneal sidewall abrasion. No significant effects were found in the secretion of PAI by postsurgical macrophages in both surgical models. These findings suggest that the DAC-80 membrane may have hemostatic activity through the modulation of fibrinolytic activity of peritoneal exudative macrophages.
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PMID:The hemostatic effect of deacetylated chitin membrane on peritoneal injury in rabbit model. 139 45

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

Severe microangiopathy resembling thrombotic thrombocytopenic purpura (TTP) has been reported as a complication of acute graft-versus-host disease (aGvHD) in patients receiving cyclosporin (CsA) prophylaxis following allogeneic BMT. In order to analyze the pathophysiological events involved in microangiopathy, a prospective study comparing release of von Willebrand Factor (vWF), t-PA and PAI, as well as TNF alpha and further coagulation parameters was performed in 32 patients. Endothelial damage as the central lesion was confirmed by the close association of vWF and t-PA:Antigen with severity of microangiopathy. t-PA activity, however, was neutralized by a simultaneous rise in PAI. Activation of coagulation in the course of microangiopathy was further confirmed by increased levels of DDimer (DDi), fibrinopeptide A (FPA), beta-thromboglobulin (beta TG) and platelet factor 4 (PF4). As clinical grades of microangiopathy, as well as the release of t-PA:Ag and PAI were correlated with systemic release of TNF alpha our data further support our hypothesis of cytokine induced endothelial damage in clinical complications following allogeneic BMT.
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PMID:Increased levels of tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor (PAI) correlate with tumor necrosis factor alpha (TNF alpha)-release in patients suffering from microangiopathy following allogeneic bone marrow transplantation (BMT). 141 3

Data from a number of laboratories indicate that human platelets contain type I plasminogen activator inhibitor (PAI-1) primarily in a latent form; however, one report (Biochemistry 28:5773, 1989) indicated that it is predominantly the active form of PAI-1 that is present in and can be purified from an ammonium sulfate precipitate of porcine platelets. To clarify this situation, we investigated and compared the status of PAI-1 in porcine and human platelets. Immunologic analysis of the ability of PAI-1 to form complexes with immobilized t-PA indicated that porcine and human platelets contained 3.7 +/- 0.4 and 1.7 +/- 0.3 U of PAI activity per 10(8) platelets (n = 6; +/- SD), respectively; sodium dodecyl sulfate (SDS)-activation of the lysates increased PAI-1 activity to 10.8 +/- 3.0 and 3.8 +/- 0.5 U per 10(8) platelets. Platelet lysates were also treated with an excess of soluble t-PA, which formed complexes with active PAI-1, whereas the latent form was detected by SDS-polyacrylamide gel electrophoresis and reverse fibrin autography. Furthermore, immobilized t-PA was able to deplete active PAI-1 from the platelet extracts, and the latent form remaining in the absorbed extract could be quantitated by activation with 4 mol/L guanidine. To investigate the differences between our observations and the published data, porcine platelets were extracted, and PAI-1 was partially purified as described in the literature. For quantitative analysis, porcine platelet PAI-1 was also purified to homogeneity using standard chromatographic procedures optimized in our laboratory for endothelial PAI-1, and the purified protein was used to develop an enzyme-linked immunoabsorbent assay for porcine PAI-1 antigen. Our results indicate that: (1) latent PAI-1 in concentrated ammonium sulfate precipitates of porcine platelet lysates cannot be detected unless the precipitates are diluted before treatment with denaturants; and (2) active and latent porcine platelet PAI-1 can be separated by gel filtration over molecular sieving columns. In summary, this report documents that PAI-1 in porcine platelets is present in both an active and a latent form.
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PMID:Presence of active and latent type 1 plasminogen activator inhibitor associated with porcine platelets. 142 97

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

In order to study the effects of chronic venous hypertension due to heart failure on blood fibrinolytic activity, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) antigen, t-PA activity and PAI activity were measured before and after venous occlusion of the arm for 20 min in 15 patients with right-sided heart failure, 15 patients with left-sided heart failure, and 30 control healthy subjects. Central venous pressure, measured by observing the jugular veins, was above 15 cm of the blood column in all patients with right-sided heart failure, and normal (below 8 cm) in all patients with left-sided heart failure and control subjects. There was no difference in the basal concentrations of t-PA (11.0, 10.2 and 10.8 ng/ml; all values medians) and PAI-1 antigens and their activities between right and left-sided heart failure and the control subjects. After the occlusion, t-PA antigen increased significantly less in right-sided heart failure (28.6 ng/ml) than in left-sided heart failure and the control subjects (54.5 and 45.9 ng/ml, respectively). It was concluded that the poor increase in fibrinolytic activity that had already been reported in patients with heart failure, was due to low t-PA release during occlusion and not to a high basal PAI level. It was limited to the patients with right-sided heart failure and was probably the consequence of chronic systemic venous hypertension.
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PMID:Tissue plasminogen activator release in chronic venous hypertension due to heart failure. 144 Apr 98

The contribution of hemodynamic changes to the pathogenesis of accelerated fibrinolysis in liver disease was investigated in rats. In animals with hepatic lesions induced by a 7-week inhalation of carbon tetrachloride there was a significant increase in blood t-PA activity and PAI activity, with no significant change in portal pressure. Following a 10-min portal vein occlusion there was a marked increase in portal pressure and t-PA activity and a significant decrease in PAI activity. Following ligation of both portal vein and hepatic artery, t-PA activity increased to a higher extent and PAI activity was reduced to a lesser extent than changes found in portal-stenosed rats. Our data suggest that high t-PA circulating levels in liver disease could be related not only to the reduced t-PA clearance as a consequence of liver injury but also to hemodynamic changes.
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PMID:Changes of the fibrinolytic system in liver dysfunction: role of portal hypertension. 144 May 12

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

TGF-beta plays a pivotal role in the pathological accumulation of extracellular matrix in experimental glomerulonephritis. Increased TGF-beta expression leads to increased synthesis and deposition of extracellular matrix components while administration of anti-serum to TGF-beta suppresses the major manifestations of the disease. We hypothesized that TGF-beta might also enhance matrix accumulation by decreasing matrix turnover via effects on protease/protease inhibitor balance. Plasmin is a potent protease capable of degrading a variety of matrix molecules. Plasmin generation from plasminogen is regulated by plasminogen activator(s) (PA) and plasminogen activator inhibitor(s) (PAI). In this study PA activity was markedly reduced and PAI-1 synthesis dramatically increased when TGF-beta was added to normal glomeruli. Diseased glomeruli also showed decreased PA activity, increased PAI-1 synthesis and increased PAI-1 deposition into matrix. Administration of anti-TGF-beta serum to glomerulonephritic rats blocked the expected increase in glomerular PAI-1 deposition. Thus changes in the PA/PAI balance favoring accumulation of matrix are induced by TGF-beta in normal glomeruli and are present in nephritic glomeruli when endogenous TGF-beta production is high. Our findings implicate the plasmin protease system in tissue repair following acute glomerular injury and suggest another mechanism by which TGF-beta enhances the matrix accumulation characteristic of many glomerular diseases.
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PMID:Glomerular matrix accumulation is linked to inhibition of the plasmin protease system. 147 81

The aim of this study was to verify the effects of oral administration of a new enteric-coated formulation of sulodexide on blood viscosity and fibrinolysis. Six outpatients suffering from peripheral artery occlusive disease were administered orally two enteric-coated tablets containing 50 mg of sulodexide, twice daily for seven days. On the first and seventh administration days, the following parameters were evaluated: plasminogen activator inhibitor (PAI-1) activity, PAI-1 antigen, tissue plasminogen activator (t-PA) and whole blood, serum and plasma viscosity, before (0 time) and 2, 4 and 8 hours after ingestion of the drug. Following the first administration (50 mg), a slight reduction of PAI was registered; after 7 days' administration, a clear-cut lowering of functional and antigenic PAI was observed, together with an increase of t-PA. As to the drug's influence on blood viscosity, after 7 days the most evident reduction was that registered for plasma viscosity. No side effects were observed throughout the treatment period.
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PMID:Sulodexide oral administration influences blood viscosity and fibrinolysis. 149 Apr 34


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