ISSN:0957-5235    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To clarify a possible involvement of the vasoconstrictive peptide endothelin in the regulation of endothelial cell-mediated fibrinolytic system, confluent cultures of vascular endothelial cells from human umbilical vein were incubated in serum-free medium in the presence of endothelin-1 at 100 nM and below, and tissue plasminogen activator antigen (t-PA:Ag) in the medium was determined by enzyme immunoassay. Endothelin-l at 1 nM and above significantly decreased the release of t-PA:Ag from the endothelial cells after a 24 h incubation. The t-PA:Ag release was also decreased by either endothelin-2 or endothelin-3 at 10 nM. The activity of lactate dehydrogenase in the medium was not changed by endothelin-l at 100 nM and below, suggesting that the peptide did not cause nonspecific cell damage. The decrease in the t-PA: Ag release induced by endothelin-1 occurred in the presence or absence of 8-bromo cyclic AMP, which is an active congener of cyclic AMP; 3-isobutyl-l-methylxanthine, which is an inhibitor of phosphodiesterase; and forskolin, which is a stimulator of adenylate cyclase. These results strongly indicated that cyclic AMP which is known to down-regulate t-PA;Ag release was not involved in the endothelin-l effect. However, endothelin-l failed to decrease the t-PA:Ag release in the presence of either calcium ionophore A23187 or EGTA; the ionophore itself markedly decreased the release. The cytosolic calcium accumulation was significantly increased by endothelin-l. These results suggest that endothelin-l decreases the release of t-P A:Ag from human endothelial cells through an excess accumulation of intracellular, especially cytosolic calcium which would be mediated by an extracellular, calcium-dependent mechanism.

ISSN:0957-5235    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Concentrations of annexins I to VI were quantitatively determined in extracts of placenta and different human cell types. They were detectable in all extracts studied* but lymphocytes/monocytes, endothelial cells and fibroblasts had very high annexin contents. The results indicate cell type specific annexin-repertoires. Annexins are intracellular proteins lacking signal sequences but which are detectable in trace amounts in plasma of healthy humans. The majority of plasma samples drawn from 14 patients suffering from myocardial infarction had elevated annexin III, IV and V concentrations. Shortly after infarction increased annexin levels were detected, reaching maximal values 24 to 48 h later. In the course of the following days annexin concentrations returned towards normal plasma levels.

ISSN:0957-5235    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We investigated the effect of bacterial lipopolysaccharide (LPS) on phospholipid (PL) turnover in human monocytic leukaemia U937 cells. Cells were p re-la belled with [3H]choline, [14C]ethanoIamine and [3H]inositol for 24 h. By monitoring the radiolabel association with cellular PL, the data indicated that LPS (10 μg/ml) drastically altered the catabolism of choline-containing PL; it induced their breakdown by 50% within 20 min. The reutilization of choline or its phosphates for PL synthesis was also suggested as a result of regaining radiolabel in the next 40 min. Choline-containing PL then underwent a second degradation after 60 min; 50% decline in radiolabel was detected at 120 min. In contrast, LPS did not induce the breakdown of phosphatidylethanolamine and phosphatidylinositol through phospholipase C/phospholipase D (PLC/PLD). No significant redistribution of the radiolabel in PL was detected in any cases during chasing. The data clearly indicate that LPS stimulates phosphatidylcholine breakdown, implying that the liberation of phosphatidic acid or diacylglycerol via PLC/PLD reaction may be relevant to the initiation of LPS-induced monocytic activation.

ISSN:0957-5235    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Levels of plasma crosslinked fibrin derivatives, a sensitive and direct marker of the lysis of intravascular crosslinked fibrin, were measured serially in 135 patients undergoing major abdominal surgery to determine their behavior and their use as a screening test for postoperative venous thrombosis. Preoperative levels and levels on the first postoperative day were significantly higher by both enzyme immunoassay and latex assay in 31 patients who developed venous thrombosis (positive venography) than in 104 patients who did not (negative125I fibrinogen leg scan). Preoperative XLFDP levels 400 ng/ml (enzyme immunoassay) had a sensitivity to the diagnosis of postoperative venous thrombosis of 58%, specificity 74%, positive predictive value 41% and negative predictive value of 85%. The sensitivity of XLFDP levels over 1200 ng/ml on the first postoperative day was 65%, specificity 73%, positive predictive value 38% and negative predictive value 89%. These cutoff values were chosen (high negative predictive value) to allow identification of patients who were unlikely to have venous thrombosis. Measurement of plasma XLFDP, a simple inexpensive test, could be used as a screen to select patients for surveillance procedures (IPG or duplex ultrasonography). A substantial increase in XLFDP levels (> 500 ng/ml) occurred in virtually all patients, suggesting that fibrinolysis is not ‘shutdown’ postoperatively and that these assays reflect lytic activity at the fibrin surface more accurately than do measurements of plasminogen activators and their inhibitors.

ISSN:0957-5235    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The aim of the present study was to compare plasma levels of urokinase-type plasminogen activator (u-PA), before and after 20 min of venous stasis, with those of tissue-type plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1) and t-PA/PAI-1 complexes, to determine whether both plasminogen activators and their inhibitor respond similarly to the same stimulus. We studied 36, patients with recurrent venous thrombosis in whom no coagulation defects predisposing them to thrombosis had been detected (mean age 38.2 years, range 15–70 years). Twenty healthy individuals (mean age 34.3 years, range 20–60 years) served as a control group. t-PA, PAI-1 and u-PA activity and antigen, as well as the t-PA/PAI-1 complex antigen, were measured before and after venous stasis. Post-stasis fibrinolytic parameters were corrected for the haemoconcentration which occurred during the venous occlusion test. Pathologically high PAI-1 levels (antigen and activity) were found in four out of 36 patients who were excluded from study. Functional and antigenic u-PA increased significantly after venous stasis when analysed as the absolute differences between paired samples (P< 0.01). This increase in u-PA did not correlate with changes in t-PA or PAI-1 (r = 0.28 and r = 0.3fc respectively). This leads us to suggest that different mechanisms relating to clearance and/or release from diverse sources might be involved in elevations of u-PA in response to a local endothelial stimulus. We conclude that venous stasis might not be the elective choice when evaluating ‘bad responders' predisposed to thrombosis.

ISSN:0957-5235    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The effect of the binding of the single-chain chimeric plasminogen activator t-PA/scu-PA, which contains amino acids 1 to 274 of tissue-type plasminogen activator (t-PA) and amino acids 138 to 411 of single-chain urokinase-type plasminogen activator (scu-PA), to fibrin on its biochemical properties was investigated in a purified system. In contrast to the binding of single-chain tissue-type plasminogen activator (sct-PA) on fibrin, which causes an increase in its intrinsic activity, t-PA/scu-PA enzyme activity is not elevated. In contrast to sct-PA which retains its single-chain form during fibrin-binding, t-PA/scu-PA is converted to its more active two-chain form. The activation process of t-PA/scu-PA is accelerated by increasing fibrin concentrations. With constant concentrations of fibrin monomer, the activation velocity also increases with time. Since this effect is inhibited by epsilon-aminocaproic acid and by a monoclonal antibody directed against the fibrin-binding site of t-PA, the activation process depends on the fibrin-binding of the molecule. The results point to the fact that t-PA/scu-PA is autocatalytically converted to its two-chain form during fibrin-binding. The conspicuous differences of the effect of the fibrin-binding on the biochemical properties of sct-PA and t-PA/scu-PA are caused obviously by small differences in the structures of the protease-domains and/or by different communications between the identical A-chains and the protease domains of the enzymes.

ISSN:0957-5235    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Monitoring coagulation parameters during thrombolytic therapy could be useful for prediction and treatment of haemorrhagic episodes. Technology based on dry reagent chemistry has been developed that allows rapid (< 10 min) assays on small samples of whole blood. The assay principle is based on the restriction of motion of paramagnetic particles during fibrin polymerization, and subsequent liberation of particle motion during fibrinolysis. This technology was used to monitor prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen levels and fibrinolysis profiles during thrombolytic therapy with tissue plasminogen activator for acute myocardial infarction. The PT and aPTT obtained with the COAG-1(tm) correlated well with conventional assays (r = 0.93 and 0.92 for PT and aPTT, respectively;/) = 0.0001). Fibrinogen estimates, obtained by COAG-2(tm) also correlated well with modified Clauss assays (r = 0.86, P= 0.0001). The rapid determination of the aPTTmay improve management of adjunctive anticoagulant therapy following thrombolysis. The fibrinolysis profile may be useful during thrombolytic therapy to verify that a lytic state has been achieved, to monitor the lytic state throughout therapy, and to verify that the lytic state normalizes once therapy has been completed.

ISSN:0957-5235    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

In a randomized double-blind placebo-controlled study, plasma levels of prothrombin fragment 1 and 2 and total fibrin/fibrinogen degradation products were measured preoperatively and on days 1, 3, 5 and 7 postoperatively in 131 patients undergoing total hip replacement. Patients received a subcutaneous injection of either a low molecular weight heparin (Logiparin™) or placebo once daily. Postoperative deep vein thrombosis was diagnosed by bilateral phlebography 7 to 10 days after operation. In the placebo group postoperative levels of prothrombin fragments 1 and 2 and total fibrin/fibrinogen degradation products were significantly higher in patients with postoperative thromboembolic complications, whereas in the low-molecular-weight heparin group no statistical differences were observed. Compared with placebo the administration of a low-molecular-weight heparin was associated with a significant reduction in the levels of prothrombin fragments 1 and 2 and total degradation products. Our observations suggest that the postoperative thrombin generation is moderated by thromboprophylaxis with Logiparin(tm).

ISSN:0957-5235    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The correlations between the cardiovascular risk factors hypertension, overweight, hyperlipidemia and fibrinolysis parameters were studied in a group of 54 otherwise healthy patients (age 19 to 70 years) with essential hypertension of moderate severity. Of the 54 patients 43 were treated with antihypertensive drugs and eleven were not. The patients included in this study who were treated with antihypertensive drugs were, in spite of their treatment, still hypertensive. Lipoprotein levels and fibrinolysis parameters did not differ between the untreated and treated patients. In the patient group we found significant incidences of hypertriglyceridemia (46%) elevated LDL-choles-terol (28%) and elevated lipoprotein (a) levels (43%). In comparison with a healthy control group the hypertensive patient group showed a decreased median tissue plasminogen activator activity (interquartile range): 0.23 (0.79) IU.1031vs1.5 (0.47) IU.1031 in the controls(p< 0.0001), an increased tissue plasminogen activator antigen concentration: 8.2 (4.5)μg/lvs 5.1 (3.9) μg/1 in the controls(p< 0.0001), an elevated plasminogen activator inhibitor-1 level: 2.8 (2.5) AU.1031vs1.1 (2.0) AU.1031 in the controls (p < 0.01) and a slightly increased ct2-antiplasmin concentration: 110 (8)%vs98 (16)% in the controls(p< 0.0001). Median D-dimer concentration levels were substantially increased in the hypertensive patients: 315 (263) μg/lvs199 (146) μg/1 in the controls(p< 0.0001). Median plasminogen concentrations did not differ significantly between the hypertensive patients 101 (16)% and controls 108 (16)%. Triglycerides were correlated with tissue plasminogen activator antigen (r = 0.44,p= 0.003) and with plasminogen activator inhibitor-1 levels (r = 0.47, p = 0.004) and tended to correlate with plasminogen (r = 0.26, p = 0.07) and D-dimer levels (r = 0.24, p = 0.10). The Quetelet-index correlated with tissue plasminogen activator antigen (r = 0.32, p = 0.03). In conclusion, this group of mildly hypertensive patients showed a disadvantageous blood lipid profile in correlation with signs of an impaired fibrinolysis indicated by a decreased tissue plasminogen activator activity and an elevated plasminogen activator inhibitor-1 concentration. These data link fibrinolysis parameters with hypertension and hyperlipidemia and are as such compatible with a multifactorial interaction of cardiovascular risk factors.

ISSN:0957-5235    

出版商:OVID    

年代:1992

数据来源: OVID