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 nine patients with non-malignant diseases undergoing major upper abdominal surgery, the mechanism of the postoperative fibrinolytic shut-down was investigated because of its potential significance for postoperative deep vein thrombosis by employing new and specific methods for assessing and stimulating the fibrinolytic system. The shut-down was found to result from an impairment of the balance between tissue-type plasminogen activator, t-PA, and its recently discovered fast-acting inhibitor. In this balance, the t-PA antigen concentrations both in resting conditions and after stimulation evoked by desamino-D-arginine vasopressin (DDAVP) were found to be unchanged by surgery. However, there was a significant postoperative increase in t-PA inhibitor levels. The release of t-PA under the stimulus of DDAVP infusion overcame the postoperative shut-down of t-PA activity. However, DDAVP infusion was associated with potentially unfavourable increases in the Factor VIII/von Willebrand factor complex. The discovery of increased t-PA inhibitor in the postoperative period opens new possibilities for a rational approach to reduce or abolish the postoperative fibrinolytic shut-down.
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PMID:Fibrinolytic shut-down after surgery: impairment of the balance between tissue-type plasminogen activator and its specific inhibitor. 393

The contribution of vascular plasminogen activator (v-PA) to the lysis of whole blood and plasma clots was investigated. v-PA released into the circulation after infusion of deamino-D-arginine vasopressin (DDAVP) was shown to bind quantitatively to plasma clots. Its apparent molecular weight, determined by the SDS-PAGE fibrin-agarose underlay method, was approximately 68,000 daltons, and its activity was quenched by antibodies against human tissue plasminogen activator (t-PA). Clots prepared from post-DDAVP plasma or post-DDAVP whole blood, rich in v-PA, did not lyse when incubated in imidazole buffer or normal plasma, as determined by the release of 125I from radiolabeled clots. However, clots made of v-PA-poor plasma or whole blood, incubated in v-PA-rich plasma, underwent substantial lysis. The concentration of PA in clots incubated in v-PA-rich plasma progressively increased in relation to the initial concentration of v-PA in the surrounding plasma. The results suggest that, at low concentrations of circulating v-PA, a hemostatic plug will lyse at a very low rate. However, when the v-PA concentration in the clot environment is increased, v-PA will accumulate progressively onto fibrin and induce thrombolysis.
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PMID:The mechanism of in vitro clot lysis induced by vascular plasminogen activator. 653 38

We have studied the possible role of the hypothalamic-pituitary system in the control of the release of plasminogen activator (PA) into peripheral blood of male rats. Plasminogen activator was measured by euglobulin lysis time. Desamino-D- arginine vasopressin (dDAVP) and adrenaline injected i.v. induced an increase in plasma PA as did electrical stimulation of the median eminence (ME), but dDAVP had no effect on plasma PA in hypophysectomized rats. The PA response to ME stimulation was similar in Brattleboro rats (deficient in vasopressin) and adrenalectomized Wistar rats compared with intact Wistar rats, but was abolished by section of the pituitary stalk and was negligible in hypophysectomized rats. The 41-residue corticotropin releasing factor (CRF) had no effect on PA release. Saline extracts of anterior pituitary gland from both normal Wistar and Brattleboro rats produced a dose-dependent increase in plasma PA when injected into normal Wistar rats. The activity of pituitary tissue was abolished by boiling, but not by di-isopropyl fluorophosphate which inactivates PA itself. Thus the anterior pituitary gland of the rat contains a heat-labile factor which stimulates the release of PA from peripheral stores into the circulation. This pituitary factor is released by a hypothalamic factor that is neither vasopressin nor CRF.
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PMID:A hypothalamic-pituitary system that stimulates the release of plasminogen activator in the rat. 653 43

Des-amino-D-arginine vasopressin (DDAVP) stimulates the release of factor VIII and plasminogen activator from the vascular endothelium. An infusion of exogenous factor VIII given to haemophiliacs causes an increase in platelet activation. This activation does not occur after stimulating a rise in the patient's own factor VIII level caused by DDAVP infusion. We hypothesised therefore that DDAVP could also cause the endothelial release of prostacyclin (PGI2), a potent anti-platelet agent which would counteract the aggregating effect of factor VIII. To examine this possibility we studied the effect of DDAVP on prostacyclin release, as measured by its stable metabolite 6-oxo-PGF1 alpha, in vitro and in vivo. Rabbit aortic rings were incubated with different concentrations of DDAVP using saline as control. The supernatant was assayed for 6-oxo-PGF1 alpha by radioimmunoassay. All concentrations of DDAVP gave a significant release of 6-oxo-PGF1 alpha. Vasopressin was much less potent. When DDAVP was infused into haemophilic patients there was a significant increase in circulating 6-oxo-PGF1 alpha levels immediately after the infusion. The facial flushing observed as a side-effect of DDAVP could therefore be prostacyclin-mediated. We confirmed this by abolishing the DDAVP induced flushing seen in normal subjects by prior treatment with aspirin which inhibits PGI2 formation.
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PMID:DDAVP stimulates prostacyclin production. 680 93

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

Fibrinolytic parameters and von Willebrand factor (vWF) antigen were measured in the plasma of 10 patients with hemolytic uremic syndrome (HUS). Samples were taken at presentation and again 2 wk later, before and after infusion of 1-desamino-8-arginine vasopressin. Compared with the plasma values of healthy control children, levels of tissue-plasminogen activator (t-PA) antigen, plasminogen activator inhibitor type I (PAI-1) activity, and vWF as well as fibrin(ogen) degradation products were significantly elevated in the plasma of HUS patients on admission. No response of the fibrinolytic parameters and vWF were seen when 1-desamino-8-arginine vasopressin infusion was given on admission. After 2 wk, t-PA antigen and vWF had partially returned to basal values, and t-PA antigen increased rapidly again after 1-desamino-8-arginine vasopressin infusion. To investigate whether verocytotoxin contributes to the alteration of the fibrinolytic system found in HUS patients, purified verocytotoxin-1 (VT-1) was added to the media of cultured human endothelial cells. Addition of VT-1 alone did not change the production of t-PA, plasminogen activator inhibitor type I, and vWF antigen in these cells. However, when the endothelial cells were preincubated with tumor necrosis factor-alpha to increase the number of VT-1 receptors, VT-1 induced a marked decrease of the synthesis of t-PA, plasminogen activator inhibitor type I, and vWF. This was caused by a decrease in overall protein synthesis in the tumor necrosis factor-alpha- and VT-1-treated endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The fibrinolytic system in the hemolytic uremic syndrome: in vivo and in vitro studies. 797 Sep 42

Evaluation of fibrinolytic capacity is mostly done after stimulation by venous occlusion (VO) or 1-desamino-8-d-arginine vasopressin (DDAVP), either with global tests or with measurements of the specific fibrinolytic components. The serum D-dimer test has recently been described as a global fibrinolytic test in unstimulated individuals, and related to different levels of fibrinolytic activity. In the present study, we have compared the levels of serum D-dimer and t-PA before and after VO in order to see if the unstimulated values reflect the fibrinolytic capacity after stimulation. Twenty-eight healthy individuals and 126 patients with different metabolic disorders and/or coronary heart disease were included. Blood was drawn in a fasting state between 8 and 10 a.m. before and after VO for determinations of serum D-dimer after standardized coagulation, and of t-PA activity and antigen. There was a 7-fold increase in the median levels obtained after VO both for serum D-dimer and t-PA activity, whereas the increase in t-PA antigen was about 2.5 fold. The correlation coefficients between the levels of serum D-dimer, t-PA activity and t-PA antigen before and after VO were 0.63 (p < 0.001), 0.72 (p < 0.001) and 0.23 (p < 0.05), respectively. We conclude that the basal levels of t-PA and serum D-dimer to a certain degree reflect the fibrinolytic capacity after stimulation. Thus, the unstimulated serum D-dimer test, which reflects both t-PA and PAI-1, could be recommended as a global screening method for evaluation of the fibrinolytic potential.
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PMID:Global fibrinolytic capacity assessed by the serum D-dimer test. Correlation between basal and stimulated values. 797 89

In healthy subjects, intravenous infusion of the selective V2-vasopressin receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP, 400 ng/kg in 10 min) causes a marked increase in heart rate with a slight decrease in diastolic blood pressure. These haemodynamic responses are associated with increments in the plasma levels of renin, noradrenaline (NA), clotting factor VIII (FVIII:C), von Willebrand factor (vWF:ag), and tissue-type plasminogen activator (t-PA), and a fall in the plasma level of plasminogen activator inhibitor (PAI). None of these changes was observed in 3 patients with congenital nephrogenic diabetes insipidus (NDI), who had a genetic defect of the V2-receptor. Plasma AVP levels in these patients were normal or slightly elevated, which makes it unlikely that the lack of DDAVP responsiveness was caused by down-regulation of vasopressin V1-receptors. In one NDI patient, arginine vasopressin (AVP) was given in incremental doses (62.5-4000 pg/kg/min). The heart rate and blood pressure responses to AVP were normal, indicating the absence of a V1-receptor defect. The responses of vWF:ag and t-PA to venous occlusion in the patients with NDI were similar to those in 5 healthy volunteers, which indicates that in NDI the endothelial release of both vWF:ag and t-PA is normal. We conclude that DDAVP causes its effects on heart rate and blood pressure, and on the plasma levels of renin, noradrenaline, FVIII:C, vWF:ag, and t-PA through V2-receptor stimulation.
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PMID:1-Desamino-8-D-arginine vasopressin (DDAVP) in patients with congenital nephrogenic diabetes insipidus. 823 94

Although the vasopressin analogue desamino-d-arginine vasopressin (DDAVP) induces a very well characterized increase in factor VIII (FVIII), von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), the mechanism(s) by which DDAVP enhances the plasma levels of these proteins is poorly understood. Some clinical evidence suggests that certain patients repeatedly treated with DDAVP at closely spaced intervals become progressively unresponsive (tachyphylaxis). In order to investigate the effect of repeated DDAVP infusion on the behaviour of FVIII, vWF, t-PA and u-PA, we infused three different doses of DDAVP (0.3 microgram/Kg) to six healthy volunteers (19-26 years old, mean 22) at 12-hour intervals. Blood samples were collected immediately before and after DDAVP. The second and third infusion of DDAVP induced a low response of FVIII and vWF. In contrast, t-PA and u-PA exhibited a consistent response after each DDAVP infusion. If the progressive decrease of FVIII and vFW response observed in healthy subjects after repeated doses of DDAVP at 12-hour intervals is extended to haemophiliacs and von Willebrand's patients, the usefulness of desmopressin may be limited when these proteins must be raised therapeutically for a prolonged period of time. Finally, our results suggest that the mechanism for regulating the release of vWF and plasminogen activators in the conditions of our study are not dependent.
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PMID:Repeated infusions of DDAVP induce low response of FVIII and vWF but not of plasminogen activators. 832 82

Three patients with autosomal-recessive nephrogenic diabetes insipidus (NDI), homozygous for mutations in the aquaporin 2 gene (AQP2), were tested for their fibrinolytic and hemodynamic responses to intravenous administration of 1-desamino-8-D-arginine vasopressin (DDAVP). They all showed an increase of tissue-type plasminogen activator antigen, facial flushing, an increase of heart rate and a decrease of diastolic blood pressure. These results confirm the hypothesis that NDI patients with an AQP2 defect can be discriminated from NDI patients with a vasopressin type 2 receptor defect by their normal extrarenal responses to DDAVP.
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PMID:Normal fibrinolytic responses to 1-desamino-8-D-arginine vasopressin in patients with nephrogenic diabetes insipidus caused by mutations in the aquaporin 2 gene. 873 Apr 18


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