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)

Infusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established. A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor alpha 2-antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated alpha 2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system. Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex. We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.
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PMID:Plasminogen activation in vivo upon intravenous infusion of DDAVP. Quantitative assessment of plasmin-alpha 2-antiplasmin complex with a novel monoclonal antibody based radioimmunoassay. 137 12

In congenital nephrogenic diabetes insipidus (NDI) blunted responses of plasma factor VIII, von Willebrand factor, and plasminogen activator to the synthetic V2 analogue 1-desamino-8-D-arginine vasopressin (DDAVP) have been reported. In addition, vasodilatory responses to DDAVP appear to be absent in NDI. We describe a boy, who presented shortly after birth with the typical features of NDI, but who showed normal coagulation, fibrinolytic and vasodilatory responses to DDAVP. We conclude that in this patient the defect is confined to the kidney, while in other NDI patients there may be a general V2 receptor abnormality. These findings point to heterogeneity in NDI.
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PMID:A variant of nephrogenic diabetes insipidus: V2 receptor abnormality restricted to the kidney. 182 22

In this study the contribution of activation of the contact system to activation of the fibrinolytic system in vivo was investigated in healthy volunteers and in factor XII deficient patients. The plasminogen activating activity in plasma from healthy volunteers after infusion of desamino D-arginine vasopressin (DDAVP) was only partially blocked (for 77%) with specific antibodies to tissue-type plasminogen activator and urokinase type plasminogen activator. The residual activity could be quenched by a monoclonal antibody that inhibits factor XII activity and was not present in patients with a factor XII deficiency. The formation of plasmin upon the DDAVP stimulus as reflected by circulating plasmin-alpha 2-antiplasmin complexes was lower in factor XII deficient patients than in healthy volunteers. Activation of the contact system occurred after DDAVP infusion in healthy volunteers and was absent in factor XII deficient patients. These results indicate that DDAVP induces a plasminogen activating activity that is partially dependent on activation of the contact system and that contributes to the overall fibrinolytic activity as indicated by the formation of plasmin-alpha 2-antiplasmin complexes. This fibrinolytic activity is impaired in factor XII deficient patients which may explain the occurrence of thromboembolic complications in these patients.
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PMID:Reduction of contact activation related fibrinolytic activity in factor XII deficient patients. Further evidence for the role of the contact system in fibrinolysis in vivo. 183 21

The mechanism of tissue plasminogen activator (t-PA) release during arm and leg venous occlusions and DDAVP (1-desamino-8-D-arginine vasopressin) infusion was studied in 10 healthy males. The following determinations were carried out on venous blood: t-PA antigen (ELISA), t-PA activity, and t-PA inhibitor (PAI) activity (amidolytic assays). Before DDAVP, there was a 270% t-PA antigen increase in the arm at the end of occlusion as opposed to only a 40% increase in the leg. After DDAVP, t-PA antigen at the end of arm and leg occlusion reached an equal level which was significantly higher than in the arm before DDAVP. The study produced no evidence of PAI release during venous occlusion of a limb. It is concluded that DDAVP is able to elicit t-PA release from arm as well as from leg vessels. The poor fibrinolytic response of leg vessels to venous occlusion is not due to a high PAI release or t-PA stores depletion in leg vessels, but rather to low basal t-PA release in leg vessels.
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PMID:Different tissue plasminogen activator release in the arm and leg during venous occlusion is equalized after DDAVP infusion. 211 Oct 49

In this paper we report the case of a new Italian family with severe cross-reacting material prekallikrein deficiency (CRM-). The proposita is a 22-year-old woman referred for evaluating an extremely prolonged activated partial thromboplastin time (APTT) detected during a routine screening. No clearcut bleeding history was reported. Prekallikrein antigen and activity were not measurable. The other contact-phase factors were within the normal range. Using an electromechanical coagulometer, six different commercial reagents yielded a markedly prolonged APTT (ratio greater than 2). By prolonging the incubation time up to 10 min, APTT was normalized only with reagents employing ellagic acid as activator. On the contrary, APTT remained markedly prolonged using particulate activators (i.e. micronized silica and celite). No differences were observed using either rabbit or bovine brain cephalin. APTT was also performed on a laser automated ACL instrument; in this case reagents using ellagic acid yielded only moderately prolonged APTT values (ratio 1.3 vs 1.4). The intrinsic fibrinolytic activity, as assessed by blood activator inventory test, was found to be moderately reduced (about 50% of normal) in the proposita, whereas normal values were measured in the heterozygous relatives. After infusion of 0.3 micrograms/kg 1-desamino-8-D-arginine vasopressin (DDAVP), kallikrein levels did not change in the proposita and her heterozygous relatives. A normal release of tissue-plasminogen activator, as assessed by fibrin-plate assay, was observed in all family members including the proposita.
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PMID:A new Italian family with severe prekallikrein deficiency. Desmopressin-induced fibrinolysis and coagulation changes in homozygous and heterozygous members. 212 71

The desamino-d-arginine vasopressin (DDAVP) induced enhancement of endogenous fibrinolysis is generally attributed to the release of tissue-type plasminogen activator (t-PA) from the vessel wall. The observation of concurrent release of urokinase-type plasminogen activator (u-PA), which eventually might cooperate in the enhanced fibrinolytic activity, has not been reported thus far. In a preliminary study in two healthy human volunteers we found a 1.8-fold increase of urokinase-antigen (UK-antigen) and a 1.7-fold increase of plasmin-activatable pro-urokinase (pro-UK) activity to DDAVP intravenously. The plasma-peak levels coincided with the maximal t-PA level. These responses following infusion of DDAVP were subsequently confirmed in a randomized double blind cross-over study in six human volunteers. We conclude that u-PA is released by DDAVP concurrently with t-PA and that it is presumably from the same origin as t-PA i.e. endothelial cells. u-PA and t-PA may therefore cooperate in the enhanced fibrinolytic activity upon DDAVP infusion.
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PMID:DDAVP induces systemic release of urokinase-type plasminogen activator. 251 Mar 48

Desamino-D-arginine vasopressin (DDAVP) is known to stimulate factor VIII (FVIII) and plasminogen activator release from endothelial cells, and has been shown to stimulate prostacyclin (PGI2) production in normal and haemophilic subjects. In von Willebrand's disease (vWd) some patients have a dissociate response with regard to FVIII and plasminogen activator. The aim of our study was to compare the PGI2, FVIII and plasminogen activator response to DDAVP infusion in vWd with the response to DDAVP in normal and haemophilic subjects. PGI2 metabolites thromboxane B2 (TxB2), factor VIII coagulant activity, factor VIII-related antigen and plasminogen activator were measured before and after DDAVP infusion. There was a significant increase in PGI2 metabolites, factor VIII-related antigen and plasminogen activator in all groups following DDAVP, but no effect on TxB2 was found, and there was no evidence of any dissociate response to DDAVP in any of the groups. Basal levels of PGI2 metabolites, however, were significantly lower in vWd as compared to normal and haemophilic subjects. Post-DDAVP levels of PGI2 metabolites were also significantly lower in vWd as compared with normal subjects. This may be due to a reduced stimulus to PGI2 production in vWd secondary to defective platelet adhesion.
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PMID:Endothelial stimulation by DDAVP in von Willebrand's disease and haemophilia. 308 64

In systemic lupus erythematosus (SLE) the lupus anticoagulant is known to be associated with thrombosis. However, this anticoagulant only occurs in a small percentage of patients. Histopathological studies suggest a more generalized thrombotic tendency with platelets and fibrin within the microvasculature. Fibrinogen is elevated in SLE and this may lead to the fibrin deposition described. We wondered if decreased fibrinolysis contributed to this and we infused desamino D-arginine vasopressin (DDAVP) into ten patients with SLE and eight controls. DDAVP stimulates endothelial production of plasminogen activator (PA) and factor VIII. Baseline results showed a significant decrease in PA activity with a concomitant increase in fibrinogen in SLE. The t-PA and inhibitor levels were normal but factor VIII was increased. After infusion of DDAVP, results indicated that, despite baseline results, SLE patients were able to respond to stimulation and the increase in PA activity produced a decrease in plasma fibrinogen levels. These findings may have therapeutic implications.
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PMID:Fibrinolysis in systemic lupus erythematosus: effect of desamino D-arginine vasopressin infusion. 311 77

The pharmacokinetics and haematological effects of 1-deamino-8-D-arginine vasopressin (desmopressin, DDAVP) after intravenous, subcutaneous and intranasal administration has been studied in man. Using a sensitive, specific radioimmunoassay for DDAVP, the AUC was determined for each route of administration. It was not significantly different for the i.v. and s.c. routes. There was no effect of the route on the plasma half-life of DDAVP which ranged from 2.7 to 4.6 h. Absorption of DDAVP after intranasal (i.n.) administration was poor. Based on AUC data, bioavailability via the two s.c. methods and the i.n. route was 112%, 94% and 2%, respectively. DDAVP has a pronounced effect on coagulation and fibrinolytic parameters, causing a 4.0- (i.v.), 2.9- (s.c.), 3.1- (s.c.; 40 micrograms/ml) and 1.2- (i.n.) fold increase in factor VIII: Ag. The corresponding effect on tissue-type plasminogen activator (t-PA) was 1.9- (i.v.), 1.3- (s.c.), 2.2- (s.c.; 40 micrograms/ml) and 1.0- (i.n.) increase over the basal value. There was also a 1.4- to 1.6-fold increase in leukocyte count 4 h after s.c. and i.v. DDAVP. At plasma DDAVP levels greater than 300 pg/ml no correlation was found between the AUC and the maximum plasma DDAVP and biological response, which indicates a ceiling limit for exogenous stimulation of the coagulation and fibrinolytic systems.
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PMID:Pharmacokinetics and haematological effects of desmopressin. 314 Nov 99

The aim of the study was to investigate the long-term chronic effects of smoking on the fibrinolytic enzyme system by comparing two groups of healthy male volunteers (aged 30 to 40 years). One group consisted of 15 habitual smokers who consumed 20 or more cigarettes a day; the other consisted of 15 nonsmokers. Fibrinolysis was studied at rest (baseline) and after infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; 0.4 micrograms/kg body weight). Smokers had significantly lower baseline blood fibrinolytic activity as determined by the overall assays: dilute blood clot lysis (p less than or equal to 0.05) and euglobulin-fibrin plate assay (p less than or equal to 0.05). Further analysis showed that these low activities could be attributed to a lower baseline level of extrinsic tissue-type plasminogen activator (t-PA) activity (p less than or equal to 0.05) in the smokers. There were no significant differences between the groups in various fibrinolytic inhibitors or in the intrinsic fibrinolytic activation pathways. The increased levels of t-PA activity and factor VIII R:Ag in response to DDAVP were also reduced in the smokers (p less than or equal to 0.01). The relative increase (ratio of post-DDAVP activity/baseline activity) for these parameters was not significantly different for the two groups. Smokers also had significantly higher levels of the acute phase reactants, alpha 1-antitrypsin (p less than or equal to 0.02) and plasminogen (p less than or equal to 0.02) and C-reactive protein (p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of chronic smoking on fibrinolysis. 387 92


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