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)

Factor VIII (FVIII) and plasminogen activator activity (PAA) rise during hypoglycaemia, and this might contribute to the vascular complications of diabetes. Similar changes in haemostasis accompany raised plasma levels of vasopressin (aVP) and adrenaline. To investigate the effects of these hormones on haemostasis during hypoglycaemia and the role of plasma insulin concentrations, eight insulin-dependent diabetic patients underwent controlled hypoglycaemia for 20 min and 13 diabetic patients were investigated during hyperinsulinaemia with blood glucose maintained at 8.0 mmol/l. During hypoglycaemia, insulin levels increased to median values of 114 mU/l, a VP rose from 0.5 to 4.4 (p less than 0.005) pg/ml and adrenaline from 0.4 to 4.4 nmol/l (p less than 0.005). FVIII coagulant activity (FVIII:C) rose from 0.75 to 1.09 IU/ml (p less than 0.01) and the ristocetin co-factor (FVIIIR:Co) and von Willebrand factor antigen (vWF:Ag) showed similar responses. PAA increased from 156 to 745 units (p less than 0.005). During hyperinsulinaemia, insulin rose following infusion from 24 to 52 and 118 mU/l, maintained for an hour at each level. Despite this, plasma aVP, FVIII:C, FVIIIR:Co, vWF:Ag and PAA remained unchanged. This study indicates that the marked changes in FVIII, vWF and PAA concentrations which accompany hypoglycaemia depend on low blood glucose and not raised plasma insulin. The response in probably mediated by increases in adrenaline and aVP, which are part of the physiological response to hypoglycaemia.
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PMID:Hormonal control of haemostasis during hypoglycaemia in diabetes mellitus. 311 5

Haemostatic variables were assessed in 43 patients, 28 insulin-dependent and 15 non insulin-dependent. Maximum aggregation by low concentrations of adenosine diphosphate (ADP) or arachidonic acid and elevated plasma concentrations of TxB2, Factor VIII, vWF:Ag, RCoF and fibronectin (Fnct) indicated a hypercoagulable state. The manifestation of vasculopathy was associated with elevated concentrations of RCoF, Fnct, Hbalc, cholesterol and triglycerides, while impaired fibrinolysis was demonstrated by decreased t-PA levels and the absence of crosslinked fibrin degradation products (XL-FDP).
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PMID:Diabetes mellitus as a hypercoagulable state: its relationship with fibrin fragments and vascular damage. 311 98

A comparison was made of intranasal administration of 300 micrograms desmopressin (DDAVP) by spray, with intravenous administration of 0.2, 0.3 and 0.4 microgram DDAVP/kg in 10 healthy volunteers. The effect of DDAVP was measured on F VIII/vWF complex and on plasminogen activator release. In addition, plasma levels of DDAVP were determined using a specific and sensitive radioimmunoassay. Moreover, the reproducibility of the spray effect in 10 healthy volunteers was tested after administration of 300 micrograms DDAVP intranasally by spray on 5 different occasions. Plasma levels of DDAVP showed a clear dose-response with the maximum levels at 0.4 microgram/kg i.v. The effect of the spray approximated the 0.2 microgram/kg response. However, the maximum response in both F VIII/vWF complex and plasminogen activator release was obtained after 0.3 microgram/kg i.v. The response to 0.4 microgram/kg i.v. was not significantly different from the response to 0.3 microgram/kg indicating that maximum stimulation was reached with 0.3 micrograms/kg. There was no correlation between plasma levels of F VIII/vWF and DDAVP indicating that the biological response to DDAVP is subjected to saturation kinetics. The reproducibility of the effect of the spray dose on VIII:C was 21% (c.v.) and 27% for the intra-individual and inter-individual variation, respectively, and compared favorably with intravenous administration. Intranasal DDAVP (300 micrograms) is as effective as 0.2 micrograms/kg intravenously and provides an accurate, reproducible and convenient alternative to parenteral administration.
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PMID:Intranasal and intravenous administration of desmopressin: effect on F VIII/vWF, pharmacokinetics and reproducibility. 312 15

DDAVP was administered at 0.4 microgram kg-1 intravenous (i.v.) and subcutaneous (s.c.) routes to 6 healthy subjects in a double blind crossover study. Both study treatments were well tolerated. Flushing occurred after both treatments but was more prominent after i.v. than after s.c. DDAVP. Mild transient local discomfort at the s.c. injection site occurred in 5 of 6 subjects. The mean peak factor VIII (FVIII) response was 369% and 247% of baseline after i.v. and s.c. DDAVP respectively and the maximum increase in FVIII occurred earlier with the i.v. route. Changes in FVIII antigen (FVIII:Ag) and von Willebrand factor antigen (vWF:Ag) were also monitored. Tissue-type plasminogen activator (t-PA) activity measured by a chromogenic assay employing soluble fibrin had a median peak value of 2.9 IU ml-1 at 20 min after i.v. and of 1.9 IU ml-1 at 60 min after s.c. DDAVP. t-PA antigen was also measured so that the specific activity of circulating t-PA could be determined. Preinjection median values of 14,650 and 13,700 IU mg-1 increased to peak median values of 236,200 IU mg-1 at 20 min after i.v. and 202,400 IU mg-1 at 60 min after s.c. DDAVP. Plasminogen activator inhibitor (PAI) activity fell following DDAVP and became undetectable in some subjects during the sampling period. The ratio of maximum fibrinolytic response was similar to the ratio of maximum haemostatic responses obtained by two routes of injection. Our results indicate that s.c. DDAVP might successfully replace i.v. DDAVP in several applications such as confirmation of haemostatic or fibrinolytic responsiveness in patient groups; for obtaining FVIII enriched plasma; as well as its obvious potential usefulness in home treatment of haemophilia A and von Willebrand's disease.
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PMID:Fibrinolytic and haemostatic responses to desamino-D-arginine vasopressin (DDAVP) administered by intravenous and subcutaneous routes in healthy subjects. 312 7

We studied a series of hemostasis factors in a group of patients selected from a cohort of 916 patients affected by MI from the GISSI-2 study population. Following a case-control design, 73 patients with a family history of thrombosis (the presence of at least two first degree relatives affected by MI and/or stroke before 65 years) were matched with MI patients with no family history of thrombosis. Blood collection could be performed 6 +/- 1 months after the acute phase following MI in 53 pairs of such patients. The presence of mixed disulphides (MDS) was significantly higher in patients with family history than in controls; MDS were detected in 7 cases and only in 1 control. No difference was found in contrast in the distribution of fibrinogen, factor VII, factor VIII, vWF, protein C, protein S, AT III, HC II, PAI-1, lipoprotein (a). Nevertheless, independently from the family history, in the whole population of MI patients studied, 21 cases of suspected deficiency of protein C were found. Sixteen out of 53 patients with family history of MI and/or stroke had a family history of MI only. In patients with family history of MI the t-PA antigen levels were significantly lower than in the control group (7.5 +/- 4.4 vs 11.1 +/- 3.5 ng/ml, t = -2.6, p < 0.02). In the whole population of MI patients and in patients with a family history of thrombosis t-PA antigen was positively correlated with PAI-1 antigen and vWF. The correlation with PAI-1 was lost in patients with family history of MI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hemostatic factors and family history of thrombosis in patients with a myocardial infarct: a case-control study. The participants in GISSI-2-Efrim. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico]. 764 26

Endothelial cell damage in systemic lupus erythematosus (SLE) was evaluated by measuring fibrinolytic activity and von Willebrand factor levels. Tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) activity, and von Willebrand factor antigen (vWF:Ag) and activity (vWF:RCof) were measured in 21 SLE patients (12 of whom were therapy free) and 22 controls. In addition, the relationship between such parameters and Raynaud's phenomenon, disease activity [according to personal criteria, Systemic Lupus Activity Measure (SLAM) and European Consensus Lupus Activity Measurement (ECLAM) scores] inflammatory indices [ESR, C-reactive protein (CRP), alpha 2-globulin], anticardiolipin antibodies and corticosteroid therapy was investigated. Lower levels of t-PA antigen (P = 0.003) and higher levels of vWF:Ag (P = 0.001) were found in SLE patients in comparison with controls. Moreover, t-PA antigen was lower (P = 0.02) in steroid-free patients in comparison with those taking steroids. No relationship was found between fibrinolysis and coagulation abnormalities and Raynaud's phenomenon, disease activity, inflammatory indices and anticardiolipin antibodies. Endothelial cell damage is probably a common feature in SLE patients; nevertheless, we were unable to clarify the nature of such abnormality. It is worth noting that low doses of steroids seem to be effective in improving endothelial cell function in SLE patients.
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PMID:Fibrinolysis and coagulation abnormalities in systemic lupus erythematosus. Relationship with Raynaud's phenomenon, disease activity, inflammatory indices, anticardiolipin antibodies and corticosteroid therapy. 772 97

Healthy endothelium is a metabolically active interface between the blood and extravascular tissues. Its intimal surface is anticoagulant and antithrombotic, and it secretes a variety of molecules involved in regulating platelet function and blood coagulation. The rapid interactions between platelets, their secreted components, or thrombin and endothelial cells at sites of vessel damage ensure the local secretion of mediators such as prostacyclin and nitric oxide that limit the intravascular growth of the haemostatic plug. There is considerable evidence that a decreased ability of endothelial cells to synthesize NO contributes to the pathogenesis of arterial disease. Local deficiency of PGI2 synthesis has also been implicated in the thrombotic problems in haemolytic uraemic syndrome. Endothelium is also the source of circulating von Willebrand factor, important for efficient platelet adhesion. Chronically elevated plasma levels of vWF in a series of diseases where there is vascular pathology apparently reflect endothelial cell damage or activation, and may contribute to the prothrombotic tendency they exhibit. They may be compounded by decreased levels of the surface anticoagulant thrombomodulin, if the increased concentrations of the soluble forms of thrombomodulin detected in the circulation under similar conditions are a reflection of loss from the endothelium. Further alterations of function in a procoagulant/prothrombotic direction take place when endothelial cells are exposed to certain cytokines or lipopolysaccharide. Tissue factor synthesis is induced, thrombomodulin expression is decreased, and there is enhanced sensitivity of vWF secretion. In addition, the balance of tissue-type plasminogen activator and plasminogen activator inhibitor type I secretion is changed in favour of the latter. These processes are each likely to contribute to the occurrence of disseminated intravascular coagulation which can accompany septic shock.
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PMID:Endothelial cell function and thrombosis. 784 94

The vascular endothelium plays a pivotal role in regulating the hemostatic system. Various cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) are known to perturb endothelial cells to reduce antithrombogenicity. On the other hand, blood flow has been shown to affect the endothelium to maintain its antithrombogenicity under some levels of shear stress in the laminar flow system. We examined the role of hemodynamic forces on the vascular system under cytokine stimulation using a cone-plate type viscometer. Treatment of endothelial cells with either IL-1 beta or TNF-alpha under static conditions increased PAI-1, vWF and prostacyclin release, while t-PA secretion was unchanged. When cells were exposed to steady shear stress of 0, 6, 12, 18 and 24 dyne/cm2, the release of t-PA, t-PA-PAI complex and prostacyclin elevated with the increase of shear stress intensity, while a gradual decrease of total PAI-1 secretion was observed and vWF secretion was unchanged. On the contrary, active PAI-1 secretion was significantly decreased under the shear stress of over 18 dyne/cm2. Interestingly, cytokines, which did not affect t-PA secretion of resting cells, increased the t-PA secretion and had an additive effect on prostacyclin secretion with shear stress under the shear stress of over 18 dyne/cm2. PAI-1 elevation induced by cytokines was markedly abolished under the same shear forces. No additive effect was observed in the secretion of vWF. Thus, shear stress attenuates the alteration of the balance in the fibrinolytic and coagulation system induced by cytokines. These findings clearly indicate that hemodynamic forces play a crucial role in regulating the hemostatic activity in vivo.
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PMID:[Effect of shear stress on hemostatic regulation in endothelium]. 784 84

Commercial aurintricarboxylic acid (ATA) was separated into molecular-weight (MW) fractions of < 210 to > 25,000, using gel permeation chromatography. Fractions with MW > 1,300 effectively inhibited both botrocetin-induced vWF and bovine vWF binding to fixed human platelets. These activities decreased with a MW > 17,000. Platelet retention for a human in vitro was reduced by ATA at 150 microM, as was that for rats ex vivo at 3 mg/kg. ATA prolonged tail transection bleeding time in rats but had only a weak effect on buccal mucosal bleeding time in dogs. ATA had no effect on platelet count but markedly prolonged PTT. ATA at 10 mg/kg exhibited antithrombotic activity and caused a marked improvement in patency status following successful thrombolysis by t-PA in electrically and copper coil-induced thrombosis models. These results suggest that specific inhibitors of the vWF-GPIb interaction such as ATA may prove useful as antithrombotic agents.
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PMID:Inhibition by aurintricarboxylic acid of von Willebrand factor binding to platelet GPIb, platelet retention, and thrombus formation in vivo. 804 18

The influences of mechanical force during physical exercise on blood coagulation and fibrinolysis were investigated and the effects of sports equipment, especially shoes were also examined. As an experimental model, local mechanical vibration was applied to the palm of the hand. General coagulation parameters did not change, but fibrinolytic activity was elevated due to the tissue plasminogen activator (t-PA) released from vascular endothelial cells stimulated by vibration. The influence of mechanical stimulation by repeated side-jumping with bare feet was examined on the sole of the foot. As with t-PA, the von Willebrand Factor antigen (vWF:Ag) derived from vascular endothelial cells also tended to increase, but not as much as when wearing sports shoes. Sports shoes protected the blood vessels of the feet from damage by mechanical force during physical exercise. Changes in fibrinolytic activity and t-PA could be useful for assessing local mechanical stimulation during physical exercise and also as indexes for the development of new sports equipment and its improvement.
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PMID:Change in fibrinolytic activity as a parameter for assessing local mechanical stimulation during physical exercise. 807 27


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