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 a prospective randomized study heptest, thrombin-antithrombin complexes (TAT), D-dimer, and t-PA:ag were analysed pre- and postoperatively in 206 consecutive patients undergoing hip arthroplasty during thromboprophylaxis with either a LMW heparin (Enoxaparin) or Dextran 70. Deep vein thrombosis (DVT) developed in 6 of 102 (6%) Enoxaparin and in 21 of 104 (20%) Dextran patients diagnosed by bilateral phelobography. In the Enoxaparin group heptest showed a significant increase from the pre- to the postoperative level opposed to a significant decrease in the Dextran group. Postoperative levels of TAT, D-dimer, and t-PA:ag were significantly increased in both groups, however, TAT was significantly higher in patients in the Dextran group than in the Enoxaparin patients. D-dimer was significantly higher in Dextran patients with DVT postoperatively compared with patients without DVT. No differences concerning TAT or t-PA:ag were observed between patients with and without DVT in any of the groups.
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PMID:Components of coagulation and fibrinolysis during thrombosis prophylaxis with a low molecular weight heparin (Enoxaparin) versus Dextran 70 in hip arthroplasty. 171 55

To investigate short-term activation and inhibition of fibrinolysis during shock, we studied plasma levels of tissue-type plasminogen activator (t-PA) and t-PA inhibition capacity (PAI) in anaesthetized pigs. t-PA in euglobulin fractions of plasma was measured by the conversion of plasminogen to plasmin in the presence of fibrin split products. Plasmin thus generated was measured in a chromogenic substrate assay. PAI was measured as plasma inhibition capacity for human melanoma t-PA. Controls (n = 8) had constant t-PA and PAI for 6 h. Lipopolysaccharide from Salmonella abortus equi in four different doses (n = 9 - 11), or live Escherichia coli (n = 3) induced a transient t-PA increase with peak values at 2 h. PAI decreased to 50% at 2 h and increased to 250% at 6 h. Phorbol myristate acetate (n = 7) induced no change of t-PA or PAI. Dextran sulphate (n = 4) produced a t-PA rise at 30 min, followed by a rapid decline. Endotoxin was an appropriate stimulus for activation and inhibition of fibrinolysis whereas phorbol ester failed to elicit this response.
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PMID:Time dependent release of tissue-type plasminogen activator and plasminogen activator inhibitor into the circulation of pigs during shock. 183 37

Low Mr dextran has been utilized as a prophylactic therapy in treatment of coagulopathy. There is evidence that monocyte dysfunctions are important contributors to hypercoagulability episodes, as well as to immunoincompetence post-trauma. Dextran is a known monocyte modulator. Consequently, we evaluated the efficacy of dextran infusion in moderating immune dysfunction, monocyte aberrations, and hypercoagulability episodes. Twenty-eight trauma patients were randomly divided into two groups. One group of 15 received dextran at 1 g/kg wt/24 hr for 5 days in addition to standard resuscitation and treatment. The control or nontreated patient group received only standard treatment. Trauma patients in the two groups were retrospectively matched by injury severity score (ISS) to ensure comparability. Blood samples were collected daily for some studies and at 3-day intervals for other assays. In vivo coagulation status was evaluated by assessing the changes in intravascular fibrinopeptide A (FPA). Immune reactivity to the mitogen phytohemagglutinin (PHA) was also evaluated. Both monocyte production of plasminogen activator (PA) and monocyte production of procoagulant activity (PCA) have been shown to correspond to and be augmented by monocyte-T lymphocyte interactions. Consequently, monocyte production of plasminogen activator and procoagulant activity were assessed as measures of monocyte immune activity as well as indicators of monocyte function in controlling the balance between fibrinolysis and coagulation. Only patients with ISS of greater than 25 experienced significant immune, coagulation, or monocyte aberrations. Of those having an injury severity score (ISS) score of 25-35, all of the control and two of the dextran patients had significant perturbations in their immune and monocyte functions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dextran as a modulator of immune and coagulation activities in trauma patients. 241 2

Blood pressure (BP), plasma prekallikrein (PK), and the extent of activation of factor XII (XII-ACT) were studied after the intravenous injection into rats of dextran (Macrodex), the ionic radiographic contrast substance iodipamide (Biligrafin), or the non-ionic contrast substance iohexol (Omnipaque). After acetone activation plasma kallikrein was assayed as plasminogen activator, BAEe esterase or S-2302 amidase, and factor XIIa was assayed as kaolin-activated prekallikrein activator. Dextran induced a strong and lasting hypotension, preceded by significant lowerings in PK and XII-ACT. Iodipamide induced a rapid and dose dependent BP fall, no change in plasma PK, but a slightly reduced XII-ACT. Iohexol induced no significant alterations, neither in BP, nor in plasma parameters. Pretreatments of the rats with iodipamide abolished the dextran-induced reductions in PK and XII-ACT, and almost blocked the fall in BP. We conclude that the ionic contrast substance iodipamide is capable of blocking dextran shock in the rat by preventing an activation of the contact activating system in plasma.
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PMID:Effects of intravenous radiographic contrast media on the blood pressure and on factors of the contact activation system in the rat. 243 54

Activity of peritoneal plasminogen activator and its regulation by dextran and other macromolecules that clinically suppress postoperative adhesions was studied. Plasminogen activator activity was assayed by a two-stage globinolytic assay that monitors formation of plasmin, as well as by cleavage of a chromogenic peptide substrate (S-2444) in the presence of aprotinin (Trasylol). Plasminogen activator activity was located on the outer surface of human peritoneum. Incubation of peritoneal tissue with buffer in vitro (conditioning) prompted release of plasminogen activator into the conditioning medium. The released plasminogen activator formed a single band on sodium dodecyl sulfate-gel electrophoresis at an apparent molecular weight of 174,000 and was markedly suppressed by antiserum raised against human melanoma tissue-type plasminogen activator. Nonspecific proteolytic activity did not accumulate in the medium during conditioning. The presence of dextran 80 during conditioning of peritoneum reversibly suppressed tissue-bound plasminogen activator activity and reduced plasminogen activator activity in the spent medium. A similar inhibition of peritoneal plasminogen activator was induced by dextran 500, methyl cellulose, and polyvinylpyrrolidone. Dextran, when added to the medium after conditioning, had no direct inhibitory effect on plasminogen activator activity. Dextran did not induce peritoneal production of inhibitor(s) of trypsin, chymotrypsin, or urokinase. On the basis of these findings, two possible mechanisms for the effect of viscous polymers in the reduction of adhesion formation are proposed. These mechanisms consider the importance of peritoneal tissue-type plasminogen activator for removal of fibrin clots and suggest that polymer coating either prevents the shedding of plasminogen activator into the abdominal cavity or reduces the access of fibrin clots to the serosal surfaces.
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PMID:Effect of viscous macromolecules on peritoneal plasminogen activator activity: a potential mechanism for their ability to reduce postoperative adhesion formation. 245 68

Postoperative abdominal adhesion formation can undo the reconstructive work of the infertility surgeon. Adhesions can form in as little as three hours after surgery. Most adhesions are transient and lyse spontaneously within 72 hours of surgery. Such factors as tissue trauma, anoxia and ischemia cause a reduction in plasminogen activator activity that is strongly correlated with the persistence and progression of postoperative adhesions. Adhesions can be prevented by a proper and meticulous surgical technique emphasizing preservation of tissue without abrasion, anoxia or ischemia. Dextran, antiprostaglandins, antibiotics, steroids, antihistamines, anticoagulants and enzymes have various roles. Our current regimen involves Hyskon, Motrin and deoxycycline.
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PMID:Formation and prevention of postoperative abdominal adhesions. 672 92

Dextran is known to increase the plasminogen activation rate in vitro and to decrease the alpha2-antiplasmin activity. We decided to explore the effect of dextran on plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) during surgical trauma. Thirty-one patients undergoing elective surgery were given 500 ml of 6% dextran 70. Another nine patients serving as controls were given 500 ml of a glucose-electrolyte solution. The activities of t-PA and PAI-1 during surgery were determined, as was the concentration of t-PA antigen. PAI-1 activity was decreased by 19% after infusion of 250 ml of dextran. After 500 ml, the activity was reduced by 22% (both P < 0.05). The activity of t-PA was increased by 43% and 29% (both P < 0.05) and the antigenic amount of t-PA was increased by 18% and 15% (both P < 0.05) after infusion of 250 ml and 500 ml of dextran, respectively. No changes in these variables were observed in the control patients. It is concluded that infusion of dextran promotes fibrinolysis by enhancing plasminogen activation in patients subjected to trauma. Since elevated levels of PAI-1 prior to surgery are known to predispose to deep vein thrombosis, which may form already during the operation, the effect of dextran on PAI-1 described here may explain its clot preventing properties.
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PMID:Effect of dextran on plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) during surgery. 754 Jul 88

We studied extrinsic and intrinsic fibrinolysis in 20 patients with cirrhosis (nine mild/moderate, group 1; 11 severe, group 2) and 19 normal controls to define the role of intrinsic (contact factor medaited) fibrinolysis in cirrhosis. Global plasma fibrinolytic activity (fibrin plate lysis) was similar in all groups. Dextran sulphate activated contact factor mediated fibrinolysis was decreased in group 2 (median 95.2%) compared with group 1 (121.0%) and controls (131.7%). Tissue plasminogen activator antigen (t-PA Ag) levels were increased in group 2 (28.2 ng/ml) compared both with group 1 (8.5 ng/ml) and controls (5.9 ng/ml). Plasma t-PA activity was raised in group 2 (5.50 IU/ml) and group 1 (5.25 IU/ml) versus controls (0.82 IU/ml). Plasminogen activator inhibitor-1 (PAI-1 Ag) levels were raised in group 2 (28.0 IU/ml) versus controls (8.5 IU/ml) but PAI activity was similar in all groups. Factor XII activity was decreased in group 2 (48.76 u/dl), but not group 1, versus controls (89.1 u/dl). Prekallikrein activity was decreased both in group 2 (27.27 u/dl) and group 1 (33.01 u/dl) versus controls (108.59 u/dl) and was lower in group 2 than group 1. C1-esterase inhibitor chromogenic activity was decreased in group 1 (102.30 u/dl) and group 2 (58.76 u/dl) versus controls (116.24 u/dl). The normal global fibrinolytic activity despite increased t-PA activity may be due to a concomitant increase in PAI. The decreased intrinsic fibrinolysis in severe cirrhosis, unaccompanied by a rise in C1-esterase inhibitor, may be explained by the decreased factor XII and prekallikrein activity. These changes are probably due to reduced liver cell mass.
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PMID:Decreased contact factor mediated fibrinolysis in cirrhosis. 813 76

Dextran is used during surgery as a prophylactic agent to prevent deep venous thrombosis. Recently it has been shown that dextran increases t-PA plasma concentrations in patients. As dextran is a potential ligand for the mannose receptor, we studied whether this glucose-polymer would be able to inhibit mannose receptor-mediated clearance of t-PA. In this report we show that dextran 40 and dextran 70 were able to inhibit t-PA binding to the isolated human mannose receptor (IC50 14 and 4 mg/ml, respectively). Both glucose-polymers inhibited mannose receptor-mediated t-PA degradation by human monocyte-derived macrophages in vitro (IC50 7 and 2 mg/ml, respectively). The alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP)-mediated t-PA degradation by the macrophages was not affected by dextran. During and after a 45 min infusion of dextran 70 (Macrodex) in rats, in plasma endogenous t-PA concentrations increased to 162 +/- 33% and 122 +/- 35% respectively. The plasma clearance of a bolus injection of exogenous t-PA was decreased by 33 +/- 9% in the same rats. We conclude that dextran inhibits mannose receptor-mediated t-PA clearance. The inhibition of t-PA clearance during dextran infusion results in increased endogenous t-PA plasma concentrations. Increased t-PA concentrations present during thrombus formation are known to increase thrombus lysability. Thus the inhibition of t-PA clearance can contribute to the antithrombotic effect of dextran.
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PMID:Inhibition of mannose receptor-mediated clearance of tissue-type plasminogen activator (t-PA) by dextran: a new explanation for its antithrombotic effect. 936 93

Activated factor XII (FXIIa), the initiator of the contact activation system, has been shown to activate plasminogen in a purified system. However, the quantitative role of FXIIa as a plasminogen activator in contact activation-dependent fibrinolysis in plasma is still unclear. In this study, the plasminogen activator (PA) activity of FXIIa was examined both in a purified system and in a dextran sulfate euglobulin fraction of plasma by measuring fibrinolysis in a fibrin microtiter plate assay. FXIIa was found to have low PA activity in a purified system. Dextran sulfate potentiated the PA activity of FXIIa about sixfold, but had no effect on the PA activity of smaller fragments of FXIIa, missing the binding domain for negatively charged surfaces. The addition of small amounts of factor XII (FXII) to FXII-deficient plasma induced a large increase in contact activation-dependent PA activity, as measured in a dextran sulfate euglobulin fraction, which may be ascribed to FXII-dependent activation of plasminogen activators like prekallikrein. When more FXII was added, PA activity continued to increase but to a lesser extent. In normal plasma, the addition of FXII also resulted in an increase of contact activation-dependent PA activity. These findings suggested a significant contribution of FXIIa as a direct plasminogen activator. Indeed, at least 20% of contact activation-dependent PA activity could be extracted from a dextran sulfate euglobulin fraction prepared from normal plasma by immunodepletion of FXIIa and therefore be ascribed to direct PA activity of FXIIa. PA activity of endogenous FXIIa immunoadsorped from plasma could only be detected in the presence of dextran sulfate. From these results it is concluded that FXIIa can contribute significantly to fibrinolysis as a plasminogen activator in the presence of a potentiating surface.
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PMID:Fibrinolytic properties of activated FXII. 1046 57


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