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Biomedical subjects

J Lasierra

Publications and source records attributed to J Lasierra.

At least 19 recordsLinked to original sources

Effects of oral contraceptives on fibrinolytic response to exercise.

In this study the influence of low-dose oral contraceptives (OC) on the different components of the fibrinolytic system before and immediately after maximal exercise was examined in a group of 18 moderately active women. Nine women using OC and nine control women performed a maximal effort treadmill protocol. Comparison of the resting parameters revealed higher plasma FbDP, plasminogen, alpha 2-antiplasmin and protein C concentrations, and lower PAI activity in the OC group. No differences were observed in plasma concentrations of t-PA antigen, t-PA activity, PAI antigen, antithrombin III, and protein S. Acute maximal exercise resulted in significant increases in t-PA antigen, t-PA activity, t-PA/PAI complexes, and FbDP in both groups of subjects, while PAI activity was reduced. No significant differences were found for the change in those parameters between control and OC users. Exercise induced no variation in any of the groups for PAI antigen, alpha 2-antiplasmin, plasminogen, protein C, or protein S. Our data suggest that changes in the fibrinolytic system induced by physical exercise are not affected by oral contraceptives.

Adolescent

Effects of aerobic and anaerobic physical conditioning on fibrinolysis.

The effects of aerobic and anaerobic physical conditioning on fibrinolysis were studied before and immediately after physical exercise. Moderately active controls (group A) were compared with aerobically- (group B) or anaerobically-conditioned (group C) subjects. Comparison of the resting parameters revealed that FgDP were significantly higher in group B as a compared to groups A and C. FbDP did not significantly differ between groups B and C and were significantly lower in group A. t-PA antigen and PAI antigen did not significantly differ between the three groups, but t-PA activity was elevated and PAI activity and t-PA/PAI complexes were reduced in group B. Following a maximal exercise test on the treadmill both FbDP and FgDP were significantly increased in all groups, although values for FbDP in group B and values for FgDP in group C reached a higher level than in group A. t-PA antigen and t-PA activity were also increased in the three groups. PAI activity was significantly reduced in groups A and C. t-PA/PAI complexes were significantly enhanced in all cases, but increased to a lower degree in group B. These results indicate that both aerobic and anaerobic physical conditioning induce activation of the fibrinolytic system.

Adult

Proteolytic processing of von Willebrand factor subunit: heterogeneity in type-IIA von Willebrand disease.

Type IIA von Willebrand disease (vWD) is a heterogeneous disorder for which two different pathogenetic mechanisms have been proposed: increased proteolytic susceptibility of von Willebrand factor (vWF), and/or interference of its post-translational processing. Subunit analysis of vWF in type-IIA vWD has revealed an increased relative proportion of the 176- and 140-kDa subunit-derived fragments, suggesting an augmented fragmentation of vWF, even in the resting state. We analyzed the subunit pattern of vWF in plasma from five previously described patients with type-IIA vWD. All of them showed the above-mentioned pattern. In addition, the presence of a new band with an apparent molecular mass of 200 kDa, not described in normal individuals or in patients with vWD, was repeatedly observed in one of these patients. This patient also exhibited an abnormal vWF multimeric structure in platelets and in plasma, before and after desmopressin administration, when the blood was collected either in the presence or in the absence of proteinase inhibitors. We believe that an abnormal primary structure of vWF could be responsible for this abnormal proteolytic fragmentation pattern, as well as for the abnormal multimerization of vWF. Moreover, an abnormal susceptibility to proteolysis appears to be present, as suggested by the increase in the relative proportion of the 176-kDa fragment observed in the same patient. Future sequencing studies and genetic analysis may clarify whether there are one or two different defects related to the vWF of that patient. Our results indicate that the subunit analysis of vWF may reveal additional defects present in type-IIA vWD that may help our understanding of the pathogenesis of such disease.

Blood Platelets

Changes of the fibrinolytic system in liver dysfunction: role of portal hypertension.

The contribution of hemodynamic changes to the pathogenesis of accelerated fibrinolysis in liver disease was investigated in rats. In animals with hepatic lesions induced by a 7-week inhalation of carbon tetrachloride there was a significant increase in blood t-PA activity and PAI activity, with no significant change in portal pressure. Following a 10-min portal vein occlusion there was a marked increase in portal pressure and t-PA activity and a significant decrease in PAI activity. Following ligation of both portal vein and hepatic artery, t-PA activity increased to a higher extent and PAI activity was reduced to a lesser extent than changes found in portal-stenosed rats. Our data suggest that high t-PA circulating levels in liver disease could be related not only to the reduced t-PA clearance as a consequence of liver injury but also to hemodynamic changes.

Amino Acid Sequence

Changes in the fibrinolytic system associated with physical conditioning.

The effects of physical conditioning on plasma fibrinolytic activity were studied in two groups of subjects. Volunteers not engaged in any sport were compared with individuals having been subjected to aerobic conditioning (middle-distance runners, defined as men running more than 80 km per week). Plasma concentrations of the different components of the fibrinolytic system were evaluated before and immediately after a maximal effort treadmill protocol. Comparison of the resting parameters revealed that under basal conditions for plasma concentrations of plasminogen, fibrinogen, alpha 2-antiplasmin, protein C and protein S there were no differences between the two groups. Concentrations of the fibrin degradation products (FbDP) and fibrinogen degradation products (FgDP) were significantly higher in the runners than in the control group, indicating an increased fibrinolytic potential that seemed to be a consequence of the reduced formation of tissue plasminogen activator-plasminogen activator inhibitor (t-PA-PAI) complexes. Acute maximal exercise resulted in pronounced fibrinolysis, evidenced by the elevation of FbDP and FgDP concentrations, in both groups of subjects. The acceleration of the fibrinolytic activity was larger in conditioned individuals, which could be accounted for by a higher t-PA release and reduced formation of t-PA-PAI complexes when compared to the untrained subjects.

Adult

Inhibition of fibrinolysis by cellular glutathione depletion in the rabbit.

The effect of cellular glutathione depletion on fibrinolytic activity in the arterial wall and on the levels of components of the plasma fibrinolytic system was studied in rabbits. Intraperitoneal administration of buthionine sulphoximine (4.5 mmol/kg body wt), an inhibitor of gamma-glutamyl cysteine synthetase, induced a significant reduction in liver glutathione concentrations with a peak decrease of 51% at 7 hours and a progressive return to normal values. The glutathione concentration in aortic tissue was also significantly reduced 7 h after administration of the depleting agent. Fibrinolytic activity in the arterial wall was inhibited following buthionine sulphoximine administration and only reappeared at 24 hours postinjection. Diethyl maleate administration (3.2 mmol/kg body wt i.p.) also depleted liver and aortic glutathione and inhibited fibrinolysis in the arterial wall. Treatment with both glutathione-depleting agents induced a significant reduction in the functional activity of tissue plasminogen activator (t-PA) (-61% and -27% respectively for buthionine sulphoximine or diethyl maleate) and a significant increase in that of plasminogen activator-inhibitor (PAI) (+61% and +27% respectively), while alpha-2-antiplasmin activity was not modified. Our data suggest a modulatory role of glutathione in the release and/or clearance of the components of the fibrinolytic system in the rabbit.

Animals

Spontaneous atherosclerotic lesions and prostacyclin formation in rabbits: effects of combined dipyridamole and aspirin.

The influence of dipyridamole and lysine acetylsalicylate on the incidence of atherosclerotic lesions and on arterial prostacyclin formation was studied in rabbits. Male New Zealand rabbits received i.m. for 16 months dipyridamole (12.5 mg/kg/day) and lysine acetylsalicylate (0.5 mg/kg/day). The incidence of spontaneous atherosclerotic lesions in the aorta was reduced by 16.4% with respect to untreated animals. Administration of the drugs significantly increased prostacyclin formation with respect to the untreated rabbits both in animals developing (1124 +/- 197 pg/mg/3 min vs 316 +/- 49 pg/mg/3 min) or not developing lesions (499 +/- 40 pg/mg/3 min vs 246 +/- 19 pg/mg/3 min). The observed increase in prostacyclin formation could account for the lowered incidence of atherosclerotic lesions in rabbits receiving the combination of dipyridamole and lysine acetylsalicylate.

6-Ketoprostaglandin F1 alpha

von Willebrand disease type IIC with different abnormalities of von Willebrand factor in the same sibship.

A family with von Willebrand disease has been identified in which different members of the same sibship exhibit different abnormalities of von Willebrand factor (vWF). The two most severely affected sibs (bleeding time over 20 min) had abnormalities of vWF similar to those seen in type IIC. The smallest detectable multimer was increased and the triplet structure of individual multimers was replaced with a single band. The largest multimers could not be detected and there were relatively more small multimers than intermediate sized forms. vWF antigen (vWF:Ag) was decreased to 12.5-17% by electroimmunoassay (EIA) and to 3.2-5.5% by immunoradiometric assay (IRMA). In the less severely affected sibling (bleeding time 12.5 min) there was a similar relative increase in the smallest detectable multimer. However, the larger multimers were present and the relative concentration of large to small multimers was similar to normal. The triplet structure was altered in that the relative proportion of satellite bands to the central predominant band was decreased. vWF:Ag concentrations were moderately decreased (40-80% by EIA and 25-35% by IRMA). The father and grandfather showed a vWF multimeric pattern similar to the less severely affected sibling but there was no decrease in vWF:Ag concentration and their bleeding times were normal. These observations suggest that the interplay of several genetic factors is responsible for the expression of von Willebrand disease in this family.

Humans

Plasmin inhibitors in different fibrinolytic treatment patterns.

The variations of different antiplasmins were studied in a group of patients suffering from thromboembolic conditions and receiving three different regimens of thrombolytic treatment with streptokinase and urokinase. The evaluation of the antiproteases was carried out by chromogenic substrate and radial immunodiffusion. The different administration patterns of the fibrinolytic agents were followed by a clear drop in fast antiplasmin and alpha 2-macroglobulin, while alpha 1-antitrypsin was increased. Antithrombin-III activity was reduced while its protein rose in the intermittent treatment with streptokinase. In the conventional treatment with streptokinase, both the activity and the protein of antithrombin-III increased. With urokinase both the protein and the activity of antithrombin-III were slightly reduced. Plasminogen and fibrinogen decreased in the different regimens of thrombolytic treatment, being more evident in continuous administration of streptokinase.

Antithrombin III