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)

Fibrinolytic activities on cases with chronic renal failure, 13 cases at pre and post introduction of hemodialysis and 40 cases at pre and post hemodialysis of maintenance hemodialysis with 38 normal controls were investigated. The plasminogen activator of untreated chronic renal failure was lower than controls, yet increased with the introduction of hemodialysis. On the other hand the antiplasmin was lowered with the introduction. In cases with maintenance hemodialysis, the plasminogen activator was lower than controls, but was elevated with hemodialysis. The level of antiactivator was higher in uremia of either pre or post hemodialysis than controls. The levels of alpha 2-macroglobulin and alpha 1-antitrypsin were reduced at prehemodialysis state comparing to controls, and yet, increased with hemodialysis, respectively. The low molecular weight antiplasmin and antiactivator, molecular weight below 30,000 were separated with Sephadex G-50 gel filtration of plasma. The low molecular weight fibrinolysis inhibitors of plasma with untreated uremia were elevated comparing to controls, but decreased with the hemodialysis. The removable fibrinolytic inhibitors were indicated, however, the ratio of the low molecular weight fibrinolytic inhibitors to the total fibrinolytic inhibitors were little.
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PMID:Studies of fibrinolytic activity of uremic and longterm hemodialytic patients with special reference to fibrinolytic inhibitor. 12 65

To determine the possible role of vascular factors in the bleeding tendency of uraemic patients, three major factors of the haemostatic system normally present in vascular tissues were studied. Factor VIII-related protein (F VIII) was detected on the vascular intima of 13 patients and 10 normal subjects. Comparable values of plasminogen activator (PA) were found in tissue slices from 7 patients and 7 controls. In contrast, prostacyclin like (PGI2) activity, measured as platelet aggregation inhibitory potency, was significantly higher in specimens from 15 patients with either acute or chronic uraemia than in 10 controls. The latter abnormality, leading to impaired platelet-vessel wall interaction, might contribute to the disturbed haemostasis of uraemic patients.
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PMID:Vascular factors in the pathogenesis of uraemic bleeding. 36 87

In several experimental and clinical conditions associated with thrombotic tendency, or complicated by thrombotic episodes, either prostacyclin (which inhibits platelet aggregation) or plasminogen activator (which promotes fibrinolysis), or both, appear to be decreased in the vessel wall. In other conditions, however, either activity may not change or even be increased. Possibly, vascular damage is followed by an early stimulation of both activities (a defence mechanism?) which may be subsequently reduced or exhausted. While the role of vascular plasminogen activator in haemorrhagic conditions is apparently unknown, prostacyclin activity appears to be markedly enhanced both in experimental animals and in patients with uraemia and bleeding complications. There is a suggestive evidence that uraemic plasma powerfully stimulates vascular prostacyclin generation.
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PMID:Vascular prostacyclin and plasminogen activator activity in experimental and clinical conditions of disturbed haemostasis or thrombosis. 38 60

Recombinant human erythropoietin (rh-EPO) has been shown to be effective in the treatment of renal anemia. Additionally, rh-EPO improves the hemostatic defect of uremia. On the other hand, a hypertensinogen effect and an increased risk for thrombosis have been reported in hemodialysis (HD) patients with rh-EPO. 20 HD patients in Homburg were recruited for a multicenter, placebo-controlled study (MF 3981), aiming to assess the risk of rh-EPO. Initially, 10 patients received rh-EPO at a dose of 3 x 80 U/kg body weight and week which was subsequently adjusted according to the hematocrit. After 6 months, the patients receiving placebo were changed to rh-EPO therapy. Clinical and laboratory data were obtained before, as well as 1, 3, 6 and 12 months after beginning of the study. Erythrocyte counts increased significantly in the rh-EPO group. Also, an increase of platelet count, fibrinogen and plasma viscosity was observed during rh-EPO. Tissue type plasminogen activator and plasminogen activator inhibitor as well as von-Willebrand-factor remained unchanged, although a shortening of the bleeding time was observed. Blood pressure and arterial blood flow were not influenced by rh-EPO.
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PMID:[Recombinant human erythropoietin (rh-EPO) in chronic, dialysis-dependent renal failure: effects on macro- and microcirculation and hematologic parameters]. 170 9

Accelerated atherosclerosis is a serious complication of chronic renal failure (CRF) treated by peritoneal dialysis. In order to study the pathological mechanisms underlying its development we are using an animal model, namely the C57BL/6J mouse, which develops foam cell-type atherosclerotic lesions after surgical induction of CRF. During atherogenesis, monocyte/macrophages move from the circulation to the blood vessel wall, migrate through the endothelium, imbibe lipid and transform into foam cells. Migration through the endothelium involves proteolysis by plasminogen activator (PA) and uptake of lipids involves hydrolysis of lipoproteins by lipoprotein lipase (LPL). Both of these enzymes are secreted by macrophages. In this paper we report the results of studies on the effect of uremia on the secretion of PA and LPL by macrophages from C57BL/6J mice. The secretion of PA and LPL by macrophages from uremic mice (as defined by BUN levels) was higher than that by cells from control animals. Furthermore, whereas macrophage secretion of PA and LPL was significantly less in normal mice fed a high fat diet than in mice fed rodent chow, it was increased above control levels in uremic animals fed the atherogenic diet. We conclude that increased secretion of PA and LPL by macrophages may contribute to atherogenesis in uremic C57BL/6J mice.
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PMID:Macrophage secretory activity and atherosclerosis during chronic renal failure. 198 12

A more concentrated desmopressin (DDAVP) preparation (40 micrograms/ml), which required small injection volumes (less than 1 ml), was studied in a double-blind trial in 10 healthy volunteers, 12 patients with haemophilia A, and 8 patients with uraemic bleeding. DDAVP was administered by subcutaneous injection at a dose of 0.4 micrograms/kg body weight. In healthy subjects, peak levels of DDAVP ranging from 480 to 638 pg/ml were reached 1 h after the subcutaneous injection and DDAVP was eliminated with a mean half-life of 3.1 h. DDAVP produced a 2.5-fold (3.0-fold) increase of factor VIII:C (factor VIII:Ag) and a 1.9-fold (2.2-fold) increase of von Willebrand factor:Ag (ristocetin cofactor) over baseline levels. Additionally, a 2.1-fold increase of tissue-type plasminogen activator antigen was observed. Factor VIII and von Willebrand factor were rapidly eliminated with a half-life ranging from 1.3 to 5.7 h and from 1.1 to 11.4 h, respectively. In haemophilia A patients, DDAVP produced a 2.3-fold increase of factor VIII:C 1 h after the injection. DDAVP was given on 8 occasions for management of bleeding, and only in 1 patient did a wound haematoma (after herniotomia) occur. In 7 of the 8 patients with uraemia the bleeding time shortened, and in all patients an increase of platelet retention and a decrease of platelet count was observed (p less than 0.05). No serious local or systemic untoward side effects were observed.
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PMID:Subcutaneous injection of desmopressin (DDAVP): evaluation of a new, more concentrated preparation. 249 11

Biopsy specimens were obtained from 138 arteries and concomitant veins in different anatomic regions of both healthy subjects and patients undergoing surgery of various kinds. A fibrin slide technique was used to determine plasminogen activator (PA) activity, no significant difference being found between activity in arteries and that in veins, other than in epigastric veins where it was significantly greater. Arterial PA activity was similar in both healthy and uraemic subjects, and was unaffected by uraemia due to diabetes or other renal disorder, and by such factors as age and sex. Correlation between arterial activity and that in concomitant veins was found for all the anatomic regions studied.
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PMID:Comparison of plasminogen activator activity in human arteries and veins. 668 29

Due to the incidence of symptomatic atherosclerosis in uremic patients, hemostasis-derived cardiovascular risk factors, basal plasma concentrations of some endothelial-derived glycoproteins and desmopressin-induced variations of endothelial-derived proteins were studied in 22 uremic patients on prolonged maintenance hemodialysis with no cardiovascular antecedent. Compared to control subjects, patients had increased predialysis hemostasis-related cardiovascular risk factors: high fibrinogen, proconvertin, and type 1 plasminogen activator inhibitor plasma concentrations; low albumin values; generally low antithrombin III values but sometimes high. They had high predialysis plasma concentrations of endothelium-derived glycoproteins: von Willebrand factor, tissue-type plasminogen activator and urokinase-type plasminogen activator, which are secreted by endothelial cells, but also soluble thrombomodulin, a marker of endothelial cell injury. The desmopressin-induced release of tissue-type plasminogen activator and of von Willebrand factor were lower than in controls. High fibrinogen, type 1 plasminogen activator inhibitor and low albumin plasma concentrations may be linked to repeated acute phase reactions associated with hemodialysis. Data concerning endothelium-related proteins are concordant with the co-existence of a chronic in vivo endothelial activation and endothelial injury in uremia. This could be linked to the initiation and progression of atherosclerosis.
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PMID:Increased cardiovascular risk factors and features of endothelial activation and dysfunction in dialyzed uremic patients. 799 2

We measured plasma parameters of the prothrombotic state, namely thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA). D-dimer (DD), von Willebrand factor (vWF), tissue-type plasminogen activator (tPA), beta-thromboglobulin (beta TG), platelet factor 4 (PF4) and serotonin (5HT) in a series of 51 adult patients with chronic uremia: 22 were on maintenance hemodialysis (MHD) and 29 on conservative dietary treatment. Serum tumor necrosis factor alpha (TNF) was determined as well. Uremics presented significantly higher levels of TAT, FPA, DD, vWF, TNF, beta TG and 5HT than normal controls. Patients on conservative treatment showed lower levels of TAT, DD, TNF and beta TG than patients on MHD. Our results provide evidence that a prothrombotic state exists in chronic uremia and that MHD patients have a higher degree of hypercoagulation. Both hemodialysis procedure and uremia-related factors are likely to contribute to the hemostatic derangement.
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PMID:Plasma parameters of the prothrombotic state in chronic uremia. 844 63

The overall fibrinolytic activity is depressed in patients with chronic renal failure where a prothrombotic state is described, thereby enhancing the risk of vascular occlusive events. The mechanism responsible for fibrinolysis derangement has not yet been elucidated. To evaluate the effect of the uremic environment on the fibrinolytic activity of endothelial cells, we studied plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) production by human umbilical vein endothelial cells (HUVEC) in culture, exposed either to uremic or normal sera, before and after cytokine stimulation. Twenty uremics were studied: 11 were on conservative dietary treatment and nine were on maintenance hemodialysis. Eight healthy subjects served as controls. Before cytokine stimulation, no difference in the HUVEC supernatant concentration of t-PA and PAI-1 was found among the groups studied. After stimulation with interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, the HUVEC supernatant levels of PAI-1 in the uremics were higher than in the controls, whereas the supernatant levels of t-PA did not differ. Our data provide evidence that uremic serum, in concert with IL-1 or TNF-alpha, can enhance PAI-1 secretion by endothelial cells, thereby depressing the fibrinolytic system. This impaired endothelial fibrinolytic response to hypercoagulation could favor vascular events, which are the major cause of morbidity and mortality in patients with chronic uremia.
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PMID:Uremic medium increases cytokine-induced PAI-1 secretion by cultured endothelial cells. 980 72


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