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)

Studies on the effect of DDAVP both in vitro and in vivo are reported. In order to define the extent of the DDAVP induced rise of circulating endothelial cell proteins in normal individuals and the endothelial cell defect in von Willebrand's disease (vWd) we have measured the effect of intravenous DDAVP on a range of possible endothelial cell markers in normal subjects and in patients with mild haemophilia and vWd. In a series of double blind cross over studies on normal volunteers we have tested the effect of naloxone, DDAVP or saline on circulating levels of factor VIII related activities (VIIIR) and plasminogen activator (PA). The results confirmed the effect of DDAVP on circulating levels of VIIIR and PA but showed that it did not induce release of these activities from cultured endothelial cells in vitro nor did it influence circulating levels of other endothelial cell markers including fibronectin, antithrombin III and platelet factor 4. Infusion of nalaxone did not significantly alter circulating levels of VIIIR or PA nor the response of these to DDAVP suggesting that normally these activities are not subjected to a vasopressin drive.
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PMID:The effect of desamino-D-arginine vasopressin (DDAVP) and naloxone infusions on factor VIII and possible endothelial cell (EC) related activities. 643 Mar 37

Patients with hyperlipoproteinaemia or spontaneous thromboembolism, known to be poor responders to DDAVP or to venous occlusion with regard to the rise in fibrinolytic activity of the blood, appeared to show a normal increase in t-PA-antigen after the same procedure. In their plasma a higher than normal level of free, fast-acting t-PA-inhibitor was found as measured by titration with purified t-PA. This free t-PA-inhibitor level only decreased after the test, in contrast to its complete disappearance in normal responders. The same happened in a healthy volunteer who failed to exhibit a rise in fibrinolytic activity after exhaustive exercise. We suppose that the lack of response of the fibrinolytic activity in these cases is due to a high inhibitor level and not to impaired release of t-PA into the blood. In contrast, patients with terminal renal insufficiency showed only a slight increase in t-PA-antigen after DDAVP. The level of free fast-acting inhibitor was normal in most cases and did not change appreciably during DDAVP-infusion. In these patients, a true impairment of the release of t-PA appears to exist.
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PMID:Masking of fibrinolytic response to stimulation by an inhibitor of tissue-type plasminogen activator in plasma. 644 2

A two-site immunoradiometric assay for human extrinsic (tissue-type) plasminogen activator was developed by using rabbit antibodies raised against plasminogen activator purified from human melanoma cell culture fluid. Samples of 100 microliters containing 1 to 100 ng/ml plasminogen activator were incubated in the wells of polyvinyl chloride microtiter plates coated with antibody. The amount of bound extrinsic plasminogen activator was quantitated by the subsequent binding of 125I-labeled affinospecific antibody. The mean level of plasma samples taken at rest was 6.6 +/- 2.9 ng/ml (n = 54). This level increased approximately threefold by exhaustive physical exercise, venous occlusion, or infusion of DDAVP. Extrinsic plasminogen activator in plasma is composed of a fibrin-adsorbable and active component (1.9 +/- 1.1 ng/ml, n = 54, in resting conditions) and an inactive component that does not bind to a fibrin clot (probably extrinsic plasminogen activator-proteinase inhibitor complexes). The fibrin-adsorbable fraction increased approximately fivefold to eightfold after physical exercise, venous occlusion, or DDAVP injections. Potential applications of the immunoradiometric assay are illustrated by the measurement of extrinsic plasminogen activator in different tissue extracts, body fluids, and cell culture fluids and in oocyte translation products after injection with mRNA for plasminogen activator.
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PMID:Measurement of human tissue-type plasminogen activator by a two-site immunoradiometric assay. 668 23

Impairment of fibrinolysis is supposed to contribute to CVD. In 38 hyperlipoproteinemic patients, known to be at risk for early CVD, fibrinolytic activity was measured before and after stimulation with DDAVP. A negative correlation was found between serum triglyceride levels and fibrinolytic activity, both before and after DDAVP. A subnormal activity was invariably found when serum triglyceride concentration was above 8 mmol/L. The defect can be attributed to low levels of extrinsic plasminogen activator. High cholesterol levels were not associated with impairment of fibrinolysis. Fibrinolytic activity and response to DDAVP were lowest in those patients with hypertriglyceridemia who also had a tendency to develop hyperchylomicronemia. (type V/IV). The low fibrinolytic activity in this type of hyperlipoproteinemia cannot be explained by obesity. Factor VIII was higher than normal in most patients with hyperlipoproteinemia; the level increased after stimulation with DDAVP in every patient. This imbalance between coagulation and fibrinolysis might increase the risk of CVD.
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PMID:Response to fibrinolytic activity and factor VIII-related antigen to stimulation with desmopressin in hyperlipoproteinemia. 680 18

Intravenous infusion of desmopressin (DDAVP, 0.4 micrograms/kg b.w. in 12') causes an increase in the level of extrinsic plasminogen activator, measured in plasma euglobulin fractions with added C1-inactivator on fibrin plates. A poor response or no response at all was elicited in two out of 21 patients with spontaneous thrombosis, 18/38 with hyperlipoproteinaemia and 10/14 with terminal renal insufficiency requiring haemodialysis. Haemodilution during the first 30' after starting the DDAVP-infusion occurred both in responders and in non-responders; so did haemodynamic reactions: increase in heart rate, drop in diastolic blood pressure, facial flushing. The rise of fibrinolytic activity was shown not to be associated with decreased hepatic blood flow. Normal factor VIII-rises in "non-responders" indicate the responsiveness of the receptive organs, including the hypothalamus, to DDAVP. Despite a normal baseline level of fibrinolytic activity in the blood, as occurs for instance in terminal renal insufficiency, the vascular endothelium may be refractory to stimulation. In some patients especially in type IV hyperlipoproteinaemia, a selective defect of the release of plasminogen activator is postulated. In subjects with low fibrinolytic activity at rest, as observed in spontaneous thromboembolism and in hypertriglyceridaemia, the failure to release plasminogen activator upon stimulation with DDAVP might be a consequence of an impairment of synthesis as well.
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PMID:The use of desmopressin acetate (DDAVP) as a test of the fibrinolytic capacity of patients--analysis of responders and non-responders. 681 44

The aim of the present study was to find out whether plasminogen activator inhibitor type-1 (PAI-1) controls the formation of plasmin in patients with ischaemic heart disease. We examined PAI activity, PAI-1 antigen, tissue type plasminogen activator (t-PA) activity, t-PA antigen, plasmin-alpha2-antiplasmin complex (PAP-complex) and fibrin degradation products D-dimer in 62 patients before (unstimulated) and after infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; stimulated). DDAVP was used in a standardized dose to trigger the release of t-PA from the vascular endothelium. We observed that under basal conditions (unstimulated) median plasma t-PA activity for the whole group of patients was 86.5 mIU/ml (0-900), and after stimulation 2550 mIU/ml (0-6800), P < 0.0001; median plasma concentration of t-PA antigen was 14.7 ng/ml (7.0-115.5) under basal conditions, and after stimulation 34.1 ng/ml (15.8-58.6), P < 0.0001; median plasma PAI activity was 16.9 IU/ml (1.5-144.8) under basal conditions, and after stimulation 3.1 IU/ml (0-118.5), P < 0.0001; median plasma concentration of PAI-1 antigen was 21.5 ng/ml (8.1-132.2) under basal conditions, and after stimulation 14.9 ng/ml (4.8-149.0), P < 0.0001; the median plasma concentration of PAP-complex was 469.5 ng/ml (185.0-1802.0) under basal conditions, and after stimulation 695.5 (243.0-2292.0), P < 0.0001; median plasma concentration of D-dimer was 298.0 ng/ml (103.0-948.0) under basal conditions, and after stimulation 296.5 ng/ml (97.0-917.0), P < 0.0008.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasminogen activator inhibitor type-1 determines plasmin formation in patients with ischaemic heart disease. 748 12

The acute simultaneous release of tissue plasminogen activator (t-PA) and von Willebrand factor (vWF) from endothelial cells in response to a variety of agonists including thrombin, DDAVP, histamine and adrenalin has been described. In the present study we investigated the effect of venous occlusion on the circulating levels of t-PA and vWF, as well as the molecular organization of vWF in 20 normal subjects. After occlusion a significant increase in plasma t-PA levels was observed even after the values were corrected for haemoconcentration. Venous occlusion also enhanced plasma vWF values, but the increase was abolished when the correction for haemoconcentration was introduced. Following venous occlusion, no circulating abnormally large vWF multimers were detected in the subjects studied. These forms are normally not present in the circulation and are released from endothelial cells through the regulated vWF pathway; their absence therefore seems to demonstrate that this pathway is not activated after venous occlusion. Since occlusion does not enhance vWF synthesis, the increase in vWF observed in the subjects investigated may be fully attributed to haemoconcentration.
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PMID:Demonstration that venous occlusion fails to release von Willebrand factor multimers. 757 1

The aim of this study was to compare the secretory response of the vascular wall in vivo to DDAVP (i.v. 0.3 microgram/kg, 30 min) and to venous occlusion (VO, 20 min) in control healthy subjects, patients with von Willebrand's disease type I (vWd I) and patients with von Willebrand's disease type III (vWd III). In controls (n = 10) and vWd I (n = 12), DDAVP induced a 2 to 3-fold rise in plasma von Willebrand factor antigen (vWf: Ag), factor VIII coagulant activity (VIII: C) and tissue--type plasminogen activator antigen (t-PA:Ag). VO was less effective in increasing vWf: Ag and VIII:C but produced a greater rise in t-PA:Ag. Large increments (over 10-fold) were observed in plasmin-alpha 2-antiplasmin complexes following both stimuli. In vWd III (n = 10), DDAVP and VO failed to increase vWf:Ag, VIII:C and t-PA:Ag. No significant changes in plasmin-alpha 2-antiplasmin complexes were observed in this group. Moreover, the baseline t-PA:Ag values were significantly lower in vWd III (2.17 +/- 1.13 ng/ml) than in controls (4.84 +/- 1.97 ng/ml, p < 0.001). A significant increase in urokinase--type plasminogen activator antigen (u-PA:Ag) was found only in controls after VO. Neither controls nor patients with vWd showed any changes in plasma fibronectin levels following DDAVP. The low t-PA:Ag results and the abnormal fibrinolytic response to DDAVP and VO in patients with severe (type III) vWd indicate that their endothelial cell abnormality is more extensive than the defect in the synthesis or release of vWf.
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PMID:Secretory response of the vessel wall to DDAVP and venous occlusion in von Willebrand's disease. 799 99

Some well-described similarities exist between tissue plasminogen activator (t-PA) and von Willebrand factor (vWf) which may suggest a link in either the synthesis or release of both proteins from endothelial cells. To investigate this relationship further immunocytochemical localization of t-PA and vWf was performed in normal tissues and in skin obtained from patients with type I and type III von Willebrand's disease (vWd). Components of the fibrinolytic system were measured at baseline and after venous occlusion in healthy controls and patients with vWd. Patients with severe vWd received intravenous vWf concentrate, followed by desmopressin (DDAVP), to study the plasma response of vWf and t-PA. By immunocytochemical staining, t-PA was demonstrated in endothelial cells of normal skin, kidney and liver and also in the skin of patients with type I and type III vWd. vWf was localized in endothelial cells of all tissues except the specimens from an individual with severe vWd. Basal plasma levels of fibrinolytic components were normal in patients with vWd. Venous occlusion resulted in a rise of fibrinolytic activity in controls and patients with type I, but not type III, vWd. No rise in plasma t-PA was observed following DDAVP in severe vWd, even though near-normalization of plasma vWf levels had been obtained by prior infusion of vWf concentrate. It is concluded that the synthesis of t-PA and vWf is probably regulated by independent processes. Constitutive and regulated release of both proteins occur through different mechanisms and the basal secretion of t-PA is intact in severe vWd.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Study of endothelial t-PA and vWf in normal subjects and in von Willebrand's disease. 807 4

Fibrinolytic parameters and von Willebrand factor (VWF) antigen were measured in 22 patients with glomerulonephritis (GN) who underwent renal biopsy after desmopressin (DDAVP) infusion. Blood was collected immediately before and after DDAVP infusion, after one week, and 3-6 months later. The main abnormalities on admission were the following: the mean baseline levels of t-PA antigen and VWF were significantly higher in GN patients than in 22 healthy controls; the median t-PA activity and the mean scu-PA level were significantly lower than normal. The t-PA response to DDAVP was impaired in 7 patients (32%), the response of VWF in 9 patients (41%), and the u-PA:Ag response in 11 patients (50%). When the patients were stratified according to creatinine clearance rate, significant differences between the subgroups with severely and moderately impaired renal function were noted: the baseline levels of PAI activity and VWF were higher in patients with severe renal failure and the VWF response to DDAVP was significantly lower. The response of u-PA (not of t-PA or VWF) to DDAVP appeared to correlate with urine flow during the first 24 h, suggesting the dependence of u-PA release on intact nephrons. A series of 18 patients with adult-type polycystic kidney disease (APKD) with creatinine clearance rates in the same abnormal range as the GN patients, had lower mean PAI and a significantly higher mean scu-PA level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blood fibrinolysis and the response to desmopressin in glomerulonephritis. 816 42


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