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

Alteplase and saruplase are more fibrin-specific thrombolytic drugs than anistreplase. These and the thrombolytic drugs of the first generation (streptokinase and urokinase) have shortcomings and limitations. The prolonged intravenous maintenance infusions have been replaced by a bolus injection, accelerated infusions, or the combined intravenous administration of thrombolytic agents. Numerous truncated alteplase or saruplase molecules have been constructed by deletion and domain substitution or hybrids made of the two molecules without gaining in thrombolytic potency. Recombinant staphylokinase and plasminogen activator from bat saliva have some interesting properties and are being investigated. Thrombus-targeted thrombolytic drugs were constructed using monoclonal antibodies against fibrin fragments or against epitopes of activated platelets. Fibrin-specific thrombolytic drugs require the concomitant use of a potent antithrombotic drug to prevent reocclusion. Whether hirudin or synthetic thrombin inhibitors are superior to heparin and whether novel antiplatelet agents, including monoclonal antibodies to platelet receptors and disintegrins, are more effective than aspirin is under clinical investigation. The place of stable analogues of prostacyclin during thrombolytic treatment is still unsettled.
 ...
PMID:Advances in thrombolytic therapy. 139 Mar 21

An intravenous infusion of Fluosol enhanced significantly the t-PA thrombolysis of the arterio-venous shunt made by insertion of 125I-fibrin clot in rabbits. The plasma radioactivity released through thrombolysis increased in both time and dose-dependent manner after the administration of t-PA. Fluosol in combination with t-PA increased the plasma radioactivity, compared with the t-PA treatment alone at the corresponding dosage. The coronary blood flow was markedly reduced to almost zero after the thrombin injection into narrowed LCX with a clamp in open-chest dogs. An intravenous infusion of Fluosol or Pluronic F-68 solution at a dose of 15 ml/kg significantly shortened the thrombolysis time by intracoronary infusion of urokinase alone. While, little change in the QTc interval of ECG and the plasma CPK-MB activity was observed in the Fluosol group in combination with urokinase, suggesting a myocardial protective action of Fluosol possibly due to its oxygen carrying effect.
 ...
PMID:Extended use of Fluosol emulsion in acute myocardial ischemia treatment. 139 38

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.
 ...
PMID:The hemostatic effect of deacetylated chitin membrane on peritoneal injury in rabbit model. 139 45

A recombinant chimeric plasminogen activator consisting of a humanized monoclonal antibody specific for cross-linked human fibrin (MA-15C5Hu) and a 32 kDa single-chain urokinase-type plasminogen activator (scu-PA-32k) comprising amino acids Leu144-Leu411, MA-15C5Hu/scu-PA-32k, was previously found to have a 12-fold higher fibrinolytic potency than recombinant scu-PA-32k towards a human plasma clot in a human plasma milieu in vitro (Vandamme et al., Eur J Biochem 1992; 205: 139-46). Therefore, the thrombolytic and pharmacokinetic properties of MA-15C5Hu/scu-PA-32k were compared with those of recombinant single-chain urokinase-type plasminogen activator (scu-PA) in 3 different venous thrombosis models in vivo. In hamsters with a pulmonary embolus consisting of a human plasma clot, the thrombolytic potency (% lysis per dose in mg/kg administered) of MA-15C5Hu/scu-PA-32k was 23-fold higher than that of scu-PA (p less than 0.0005). In rabbits with a jugular vein clot prepared from human plasma, the thrombolytic potency of MA-15C5Hu/scu-PA-32k was 11-fold higher than that of scu-PA (p = 0.012). In baboons with an autologous whole blood clot in the femoral vein, the chimera had a 5-fold higher thrombolytic potency than scu-PA. In all three animal species, the clearance of the chimera was 10- to 27-fold reduced as compared to scu-PA. The specific thrombolytic activity (% lysis per micrograms/ml steady-state plasma u-PA antigen) was increased up to 7-fold with MA-15C5Hu/scu-PA-32k as compared with scu-PA, which is indicative of targeting of the chimera to the clot. No fibrinogen breakdown or alpha 2-antiplasmin depletion was observed during thrombolysis with the chimera. Thus, MA-15C5Hu/scu-PA-32k constitutes a recombinant chimeric plasminogen activator with a significantly enhanced thrombolytic potency in 3 different animal models of venous thrombosis.
 ...
PMID:Thrombolytic and pharmacokinetic properties of a recombinant chimeric plasminogen activator consisting of a fibrin fragment D-dimer specific humanized monoclonal antibody and a truncated single-chain urokinase. 141 63

Inflammatory processes are accompanied by extravascular deposition and breakdown of fibrin. We measured fibrinolytic parameters in synovial fluid (SF) and in plasma of 36 patients with rheumatoid arthritis (RA). As a control, SF of 13 patients with blunt knee trauma, and plasma of 17 healthy volunteers were studied. In RA patients, extravascular t-PA mediated plasminogen activation was depressed: mean SF tissue-type plasminogen activator (t-PA:Ag) concentration (2.1 +/- 1.6 ng/ml) was four-fold lower, and plasminogen activator inhibitor (PAI) activity (284 +/- 212%) four-fold higher than the plasma values of the same patients or of healthy donors. In contrast, u-PA related plasminogen activation was strongly enhanced: urokinase-type plasminogen activator (u-PA) antigen (23.1 +/- 12.4 ng/ml) was more than four-fold higher, single-chain u-PA (scu-PA) (5.3 +/- 1.9 ng/ml) three-fold higher than in plasma of the same patients or of healthy donors, and active two-chain u-PA (tcu-PA) was detected in 14 of the 36 SF samples of RA patients. All of these changes in extravascular fibrinolytic parameters correspond with those induced by inflammatory mediators in cell cultures. In joint effusions of patients with a blunt knee trauma, the effects were intermediate: u-PA related parameters showed moderate changes in the same direction as in arthritis; t-PA antigen was also decreased. The only exception was that PAI was not increased. We conclude that the findings in traumatic effusions reflect transient effects as a reaction to trauma. In joint inflammation, the depressed t-PA mediated plasminogen activation, although more than compensated by the enhanced u-PA mediated plasminogen activation, results in protraction of fibrin removal. Besides, the enhanced u-PA activation might lead to proteolytic damage of the cartilage.
 ...
PMID:Depression of tissue-type plasminogen activator and enhancement of urokinase-type plasminogen activator as an expression of local inflammation. 141 64

Women suffering of infectious-dependent bronchial asthma show at the second half of pregnancy a sharp reduction of the fibrinolytic potential that is manifested in a decrease of plasminogen activator and urokinase activity of the urine, in an elevation of the antiactivator and antiplasmin activity, growth of the concentration of alpha2-macroglobulins. At the same time high levels of fibrinogen are noted and low levels of fibrin degradation.
 ...
PMID:[The fibrinolytic system of bronchial asthma patients in the late terms of pregnancy]. 141 96

An exaggerated hemorrhagic syndrome is a characteristic in acute non-lymphoblastic leukemia (ANLL) and it determines the patient's outcome. Disseminated intravascular coagulation as a result of a procoagulant factor release and primary hyperfibrinolysis due to plasminogen activators also released by leukemic cells have been implicated in the development of this syndrome. The aim of this work was to evaluate urokinase-type plasminogen activator (u-PA) and related parameters of the fibrinolytic system in 14 ANLL patients. Our results showed an increased u-PA concentration in ANLL patients compared to controls [2.63 (1.61-4.62) vs. 0.95 (0.77-1.48) ng/ml, p < 0.01]. u-PA levels correlated positively with tissue-type plasminogen activator. The relevance of the enhancement of u-PA in this clinical setting was supported by the fact that it was the only analytical parameter positively correlated with patient mortality (p < 0.05). Though u-PA levels do not seem to be the determining factor in the development of the hemorrhagic syndrome of ANLL patients, a contributory role of this plasminogen activator is suggested from our results.
 ...
PMID:High plasma urokinase-type plasminogen activator levels are present in patients with acute nonlymphoblastic leukemia. 141 64

The activity of plasminogen activators and inhibitors in the synovial fluid and plasma of patients with various forms of chronic arthritis was characterised. Tissue-type plasminogen activator antigen (t-PA:Ag), urokinase-type plasminogen activator antigen (u-PA:Ag), the proenzyme single chain u-PA (scu-PA), and plasminogen activator inhibitor (PAI) were measured in the synovial fluid and plasma of 22 patients with seropositive rheumatoid arthritis (RA), 13 with seronegative RA, and 23 patients with various forms of arthritis. In all patient groups the levels of t-PA:Ag in synovial fluid were lower and the levels of u-PA:Ag and PAI higher than plasma levels. Synovial fluid u-PA was more activated than plasma u-PA. Comparison of the patient groups showed that the largest differences between fibrinolytic parameters in synovial fluid and plasma were present in patients with seropositive RA followed by patients with seronegative RA and patients with various forms of arthritis. This order paralleled the functional and radiological scores of joint destruction in the patient groups studied. The results of this study indicate that suppression of t-PA production and enhancement of u-PA synthesis and activation in arthritic joints are associated with the clinical severity of arthritis.
 ...
PMID:Plasminogen activators in synovial fluid and plasma from patients with arthritis. 141 21

Urokinase-type (uPA) and tissue-type (tPA) plasminogen activators were identified by fibrinolytic autography in the sulcus epithelium of human gingival mucosa but not in the orthokeratinized gingival epithelium. Fibrinolytic activity was present only over blood vessels in frozen sections of oral squamous cell carcinomas, the malignant epithelial cells showing no plasminogen activator activity. Plasminogen activators could not be demonstrated in either the sulcus or gingival epithelium by immunofluorescence, but both uPA and tPA were found in occasional squamous carcinoma cells. Fibrinolytic activity of culture fluids from epithelial explants grown in vitro from human gingival mucosa showed marked variation, but activity was much higher in the culture supernatants than in the cell lysates. Fibrinolytic activity of culture fluids from epithelial explants of squamous cell carcinomas was low both in supernatants and lysates. Zymogram overlays of sodium dodecyl sulphate-polyacrylamide electrophoretic gels from culture supernatants showed that the low fibrinolytic activity of culture supernatants of oral squamous cell carcinomas was due to the associated presence of plasminogen activator inhibitors. The fibrinolytic activity in the zymogram was due predominantly to uPA but some lysis was due also to tPA.
 ...
PMID:Plasminogen activators in normal and malignant oral epithelium in vivo and in vitro. 141 24

The generation of the proteolytic enzyme plasmin from its inactive precursor plasminogen, mediated by so called plasminogen activators, is the essential step in thrombolytic therapy. Plasmin is responsible for the degradation of the insoluble fibrin, the major component of a thrombus, to soluble fibrin degradation products. So far, the use of the more recently developed thrombolytic agents single-chain urokinase-type plasminogen activator (scu-PA) and tissue-type plasminogen activator (t-PA) were disappointing, mainly due to some of their negative properties in vivo, i.e., rapid inhibition and/or hepatic clearance. Besides some background information on the haemostatic balance; t-PA and scu-PA structure; and mechanisms of action, we here review some reported attempts to improve on these agents for thrombolytic therapy following various strategies. One of the more potential strategies, antibody-targeted thrombolytic therapy using bispecific monoclonal antibodies, is discussed somewhat more extensively, as are the several procedures that can be followed for bispecific antibody preparation.
 ...
PMID:The potential improvement of thrombolytic therapy by targeting with bispecific monoclonal antibodies: why they are used and how they are made. 141 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>