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 formation of fibrin on peritoneal surface has been related to the appearance of adhesions both, in surgical and CAPD patients. It is known that mesothelial cells have fibrinolytic activity related with t-PA production. We studied plasma and overnight peritoneal effluent (OPE) from 20 CAPD stable patients. Antigenic PAI and t-PA were determined. These values and its correspondent peritoneal saturation indexes were compared to urea and creatinine MTCs, peritonitis incidence, UF capacity, protein losses, Pi, Ca, Na, CO2t, urea and creatinine OPE levels. Plasma t-PA 6.64 +/- 4.68 (2.4-20); Plasma PAI-I 24.8 +/- 17.1 (p < 0.001 in respect to controls) (4-62); OPEt-PA 1.46 +/- 0.95 (0.4-4.6); OPE PAI-I 7.3 +/- 5.6 (0-20.4). Peritoneal saturation ratios were for t-PA 29.6 +/- 21% (6-65) and for PAI-I 34 +/- 32% (7-132). In conclusion our data do not support strong relationship between peritoneal t-PA/PAI system and the functional characteristics of the peritoneal membrane although plasma PAI-I, after an increase in patients at early stages on CAPD, shows a tendency to decrease over time and frequent peritonitis. The values of peritoneal saturation ratios for t-PA/PAI are higher than expected for their molecular weight, which suggests local production. An elevated plasma t-PA levels has been found in older patients.
Adv Perit Dial 1992
PMID:Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-I (PAI-I) levels in plasma and peritoneal effluent in patients on CAPD. 136 77

Haemodialysis (HD) is associated with stimulation of the fibrinolytic system. The increase of fibrinolytic activity seems to be primarily due to tissue-type plasminogen activator (t-PA) released from the vessel wall. The aim of our study was to determine whether the t-PA release is the consequence of uraemic intoxication adjustment, extracorporeal circulation effect, heparin administration, or whether a mere reflection of the circadian rhythm of fibrinolysis is involved. To identify the factor, fibrinolytic system parameters were determined during HD, sham HD (SD), after the administration of heparin alone outside HD, and during a control period (CP). The plasma concentrations of t-PA antigen indicate that HD is associated with the release of t-PA from the vessel wall; 3.70 ng/ml before HD, 4.35 (NS) at the 15th min, 4.88 (P less than 0.05) at the 20th min, and 5.09 (P less than 0.05) after HD (medians). The respective values for a CP are 4.05, 4.37 (NS), 4.40 (NS), and 4.22 (NS). The effect of heparin alone and SD was evaluated for 120 min only, with the following t-PA concentrations determined after heparin: 5.10, 6.22 (NS), 4.72 (NS), 4.72 (NS); during SD and 4.50, 5.14 (NS), 5.20 (P less than 0.05). We conclude that t-PA is released from the vessel wall during HD. A factor contributing to its release is the extracorporeal circulation system.
Nephrol Dial Transplant 1991
PMID:What are the factors contributing to the changes in tissue-type plasminogen activator during haemodialysis? 177 62

This study was designed to evaluate platelet activation, enhancement of coagulation and fibrinolysis in patients with chronic renal failure on long-term haemodialysis. Beta thromboglobulin (BTG), platelet factor 4 (PF4), fibrinopeptide A, tissue plasminogen activator (t-PA) activity and antigen, tissue plasminogen activator inhibitor (PAI), fibrin, and fibrinogen degradation products were studied during dialysis. The influence of two types of membrane on these parameters was also evaluated. The patients comprised 24 individuals on long-term haemodialysis on either cuprophan membrane (CUP) (12 patients) or polyacrylonitrile membrane (AN 69) (12 patients). Blood samples were collected before, at 15 min, and at the end of dialysis. The results demonstrated that platelet activation was permanent and increased during haemodialysis. However, no difference could be demonstrated between patients treated on CUP and patients treated on AN 69. Coagulation was also enhanced permanently but did not show modification during haemodialysis. Fibrinolysis was activated at the end of haemodialysis in half the patients, but again no difference could be demonstrated between patients treated on AN 69 and CUP membranes. It was concluded that the process of haemodialysis itself enhanced platelet activation, coagulation, and fibrinolysis but that both membranes were of equal effect.
Nephrol Dial Transplant 1990
PMID:Activation of platelets, coagulation and fibrinolysis in patients on long-term haemodialysis: influence of cuprophan and polyacrylonitrile membranes. 214 56

We compared peritoneal dialysis effluents from 18 CAPD patients who had not suffered from peritonitis during the last 6 months (group 1) with the effluents from five patients with acute peritonitis (group 2), measuring activation markers of coagulation and fibrinolysis. These markers included prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin monomer (FM), and fibrin degradation products (FbDP). In the dialysate of group 1 we found remarkably high levels of F1 + 2, TAT and FM concomitant with a high concentration of FbDP, indicating a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin was disturbed in untreated patients of group 2, who had significantly higher levels of coagulation markers and a higher ratio between FM and FbDP. Seven days after treatment with intraperitoneal administration of antibiotics and heparin, F1 + 2, TAT, FM and FbDP decreased significantly. To evaluate the role of mesothelial cells (MC) in the high peritoneal fibrin turnover we investigated the expression of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type-1 (PAI-1), and tissue factor in cultured human peritoneal MC under basal conditions and after exposure to tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), or bacterial lipopolysaccharide (LPS). The exposure of MC to TNF alpha or to a lesser extent IL-1 alpha or LPS reduced their fibrinolytic activity by decreasing t-PA production and increasing PAI-1 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1995
PMID:Imbalance between intraperitoneal coagulation and fibrinolysis during peritonitis of CAPD patients: the role of mesothelial cells. 756 82

Elevated plasma levels of fibrinogen, factor VII coagulant activity (F VIIc), and plasminogen activator inhibitor (PAI-1) have been reported to be strictly associated with thrombotic events and are considered to be important risk markers of atherothrombotic cardiovascular disease. Therefore, we evaluated in 15 patients on continuous ambulatory peritoneal dialysis (CAPD) the plasma levels of these coagulation factors, basal insulin values, and the lipid pattern in comparison with 33 hemodialysis (HD) patients and 59 healthy subjects. In CAPD the total cholesterol and triglyceride results were significantly increased, but no difference was found in HDL cholesterol. Fibrinogen and F VIIc results were significantly higher in CAPD and HD than in the control group, probably due to an increased hepatic synthesis as a nonspecific response to the peritoneal protein loss. Elevated F VIIc activity may be caused by the presence of large negatively charged lipoproteins, in vivo thrombin formation, or reduced hepatic clearance. Both PAI 1 and t-PA results were higher in CAPD, probably due to an increased synthesis by endothelial cells activated by glucose peritoneal absorption and hypertonic dialysis solutions. The contemporary elevation of fibrinogen, F VIIc, PAI-1, and t-PA suggests that CAPD patients present a hypercoagulability and hypofibrinolysis condition, which may promote the development of atherothrombotic events.
Perit Dial Int 1993
PMID:Risk factors of ischemic cardiac disease in patients on continuous ambulatory peritoneal dialysis. 839 23

The authors tested in vitro the effect of glucose-based and amino acid-based dialysate effluent on the function of human peritoneal mesothelial cells. After 9 days of exposure to the tested effluents with medium (1:1 v/v) or to a medium supplemented with 10% fetal calf serum (FCS) (control), several functional properties of the cells were studied. The synthesis of DNA measured by incorporation of 3H-methyl-thymidine was higher in mesothelial-cell monolayers exposed to the dialysates than in the controls. Synthesis of hyaluronic acid was similar in all three groups, but after stimulation with Il-1 the cells exposed to the dialysates produced more hyaluronic acid. Synthesis of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) was higher in the control cells. However, after stimulation with IL-1, the cells exposed to the dialysate showed greater synthesis of PAI-1 than of t-PA. Also, procoagulant activity of the control cells was higher than that of the cells exposed to the dialysates. We have concluded that the functional properties of the mesothelial cells may be altered in vitro during prolonged exposure to the dialysate, something that may also occur in vivo.
Adv Perit Dial 1995
PMID:Functional properties of mesothelial cells after prolonged exposure to dialysate effluent. 853 91

Atherosclerosis and thrombosis, two major causes of morbidity and mortality in renal transplant recipients, share the same clinical risk factors including decreased fibrinolysis and lipid disturbances. In a cross-sectional study we have determined parameters of fibrinolysis in control subjects (n = 23) and stable renal allograft recipients without cyclosporin (CsA) (n = 10) and with CsA (n = 87) in their immunosuppressive treatment. In CsA-treated patients, tissue-type plasminogen activator was moderately increased compared to patients without CsA (8.4+/-3.3 vs 5.5+/-2.8 ng/ml). The plasminogen activator inhibitor (PAI) activity in plasma was clearly increased in CsA-treated patients: 14.5+/-8.8 vs 7.2+/-3.2 in normal controls and 8.5+/-2.4 AU/ml in patients without CsA. Total cholesterol and LDL cholesterol levels were higher in CsA-treated patients (256+/-62 and 169+/-60 mg/dl) than in patients without CsA (209+/-45 and 136+/-44 mg/dl). The two groups did not differ in HDL cholesterol, triglycerides, and lipoprotein(a). Hypercholesterolaemia, obesity, and steroid-induced diabetes could be identified as risk factors for elevated plasma PAI activity in CsA-treated patients. Hypofibrinolysis induced by elevated PAI levels and increased LDL cholesterol may contribute to the increased thrombogenicity and accelerated atherosclerosis observed in cyclosporin-treated patients.
Nephrol Dial Transplant 1996 Feb
PMID:Elevated plasminogen activator inhibitor levels in cyclosporin-treated renal allograft recipients. 867 91

Clinical effects of recombinant human erythropoietin (rHuEPO) such as thrombosis, convulsions, hyperviscosity, hypertension, and angiogenic effect in culture cells have been described. We studied the rHuEPO effect on endothelial damage markers and endothelial function markers: tissue-type plasminogen activator (t-PA), nitrate (NO3), thrombomodulin (TM), and von Willebrand factor (vWF). Twenty-six peritoneal dialysis patients treated with rHuEPO and 19 controls were included. The study design for rHuEPO patients consisted of four periods: long-term treatment (rHuEPO-1); 2 months of withdrawal (rHuEPO-2); and 4 months on 5000 IU/week rHuEPO subcutaneously, with markers being measured after 2 months (rHuEPO-3) and after 4 months (rHuEPO-4). After 2 months of rHuEPO withdrawal, a decrease in hemoglobin level appeared (11+/-1.8 g/dL to 9.2+/-1.5 g/dL, p < 0.01). After rHuEPO reintroduction, this value reached 10.6+/-1.5 g/dL at two months, and 11.1+/-1.4 g/dL at four months. A significant increase in t-PA ratio was observed from two months without rHuEPO to two months on rHuEPO, returning to previous values after four months. Similarly, TM increased for patients with creatinine clearances (CrC) < 5 mL/min. No changes in the higher-than-normal plasma vWF levels were found during the various periods. A statistically significant lower value was found in controls compared with rHuEPO-4 patients. A statistically significant increase in NO3 levels was observed in the pre-venous occlusion (VO) test immediately after the re-introduction of rHuEPO. This increment returned to prior values four months after rHuEPO was reintroduced. Our results show that rHuEPO treatment causes an increase in some endothelial damage markers (TM, t-PA) and modifies endothelial function markers (t-PA ratio, NO3). These changes might favor thrombosis and atherosclerosis.
Perit Dial Int 1999
PMID:Effects of recombinant human erythropoietin on functional and injury endothelial markers in peritoneal dialysis patients. 1040 11

We studied tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) levels in plasma and peritoneal effluent in 10 children on continuous ambulatory peritoneal dialysis (CAPD) before, and 8 and 12 weeks after, treatment with recombinant human erythropoietin (rHuEPO). Plasma t-PA and PAI-1 levels were lower in patients than in controls during the study. The plasma t-PA levels were increased by rHuEPO treatment. Although PAI-1 levels showed a tendency to increase in the early phase of rHuEPO treatment, they later returned to near baseline levels. Peritoneal effluent t-PA levels were decreased at week 8 of treatment, but returned to baseline levels at week 12. Peritoneal effluent PAI-1 levels were not changed by the rHuEPO treatment. No correlation was observed between levels of t-PA and PAI-1 in plasma and in peritoneal effluent. No correlation was seen between plasma PAI-1 levels and duration of CAPD. A significant negative correlation was found between the plasma PAI-1 levels and hemoglobin levels at week 8 and week 12. These results suggest that plasma t-PA levels can be increased by rHuEPO treatment, while plasma PAI-1 levels are associated with hemoglobin levels.
Adv Perit Dial 1999
PMID:Effects of recombinant human erythropoietin on fibrinolytic system in children on continuous ambulatory peritoneal dialysis. 1068 18

Acute dialysis catheters are non-cuffed, non-tunnelled catheters used for immediate vascular access. They are primarily used for acute renal failure in bed-bound patients and for short-term use in patients with malfunction of permanent access. Long-term use of acute catheters is not recommended, but does occur with acceptable infection rates in dialysis centers where tunnelled, cuffed catheters are not available. Most acute catheters are made of polyurethane, but silicone catheters are now available with larger lumen sizes capable of delivering blood flow rates over 300 ml/min. Acute catheters should be inserted in the internal jugular or femoral vein under ultrasound guidance to minimize complications. Subclavian catheters cause stenosis, thrombosis, and perforation of vessels. Intermittent catheter malfunction still occurs, particularly for left-sided internal jugular catheters and catheters placed in women. Blood flow may improve with lumen reversal, intraluminal t-PA, or guidewire exchange. Limiting duration of use and dressing catheter exit sites with dry gauze and antiseptic ointments can prevent catheter-related infections.
Semin Dial
PMID:Acute dialysis catheters. 1185 28


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