PubMed Health⌕ Search

Biomedical subjects

L Mussoni

Publications and source records attributed to L Mussoni.

At least 55 records · Page 3Linked to original sources
PubMed1987

Dermatan sulphate induces plasminogen activator release in the perfused rat hindquarters.

Heparin or heparin-like substances have been described to induce the release of plasminogen activator (PA) activity in different animal perfusion models. In this paper we report that Dermatan Sulphate (DS) is able to induce PA activity release in the perfused rat hindquarters. Perfusion of different doses of DS (0.1 to 0.8 mg/mL) stimulates a release of PA activity that is maximum after the initial two minutes of perfusion. The amount of PA activity released rises progressively within a certain concentration range of DS (0.1 to 0.4 mg/mL) and declines thereafter (0.6 to 0.8 mg/mL). The type of PA activity increased during DS perfusion was characterized by SDS-PAGE and fibrin autography as tissue-type PA (t-PA) on the basis of its mol wt (67,000 d) and inhibition by a specific anti t-PA antiserum. This effect might be considered as potentially contributing to the antithrombotic activity of DS, at least at the local level.

Animals↗
PubMed1986

Low dose aspirin does not prevent fibrinolytic response to venous occlusion.

Interest in the antithrombotic potential of low-dose aspirin is based on its ability to inhibit thromboxane (Tx)A2-related platelet function with concomitant sparing of vascular prostacyclin (PGI2) production. The aim of this study was to investigate the effect of low-dose aspirin (20 mg daily for 7 days) on the increase in fibrinolytic activity in healthy volunteers after venous occlusion. We also tested the effect of high-dose aspirin (650 mg X 2), of salicylate (569 mg X 2) and of indobufen (200 mg X 2), a new cyclo-oxygenase inhibitor unrelated to salicylates. Low-dose aspirin reduced serum TxB2 generation by about 90% and suppressed arachidonate-induced platelet aggregation. In contrast, fibrinolytic activity, measured by the euglobulin lysis area and the euglobulin lysis time, was not significantly affected. Both high-dose aspirin and indobufen significantly inhibited TxB2 generation and the rise in fibrinolytic activity induced by venous occlusion, without affecting the pre-occlusion values. Salicylate did not significantly affect any parameter studied. Besides offering a favorable solution to the "aspirin dilemma" related to the TxA2/PGI2 balance, low-dose aspirin might leave intact the fibrinolytic capacity of the vessel wall.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Enhancement by interleukin-1 (IL-1) of plasminogen activator inhibitor (PA-I) activity in cultured human endothelial cells.

Cultured human endothelial cells produce increased levels of PA-I when stimulated with IL-1. The stimulatory effect was elicited by both alpha (pI 5) and beta (pI 7) IL-1 molecules. The effect was both dose and time-dependent, plateau reached after 8 h. The PA-I measured in cell extracts was SDS-resistant with an apparent m.w. of 53 Kd and inhibited both tissue-type plasminogen activator (t-PA) and urokinase (UK). No change in t-PA antigen level was detected with any of the IL-1 preparations tested.

Cells, Cultured↗
PubMed1986

Procoagulant and fibrinolytic activity of human ovarian carcinoma cells in culture.

We have investigated here the coordinate expression of both procoagulant (PCA) and fibrinolytic (FA) activity of cells from 16 human ovarian carcinoma cases. To avoid interference of contaminating host cells, we used cells isolated in primary culture from ascitic fluid or from solid tumor. The FA was determined in cellular extracts by an amidolytic assay in the presence of fibrin monomers. FA, which was plasminogen dependent in almost all of the cases, showed a wide range of activity (from less than 0.001 to 2.30 UK units/mg protein). The molecular analysis of plasminogen activator (by SDS-PAGE and fibrin autography) showed a single molecular form of 52,000 daltons, inhibited by an antibody against human urokinase. PCA, studied with a one stage clotting assay in disrupted cells, was of tissue thromboplastin type in all instance and varied from 12.0 to 1300 thromboplastin units/10(4) cells. No simple correlation was found between FA and PCA in the cellular samples studied; moreover, for neither parameter was it possible to find any changes with the staging of the disease.

Adult↗
PubMed1984

A direct, plasmin-independent assay for plasminogen activator.

A direct assay for plasminogen activator (PA) was developed. It employed polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and beta-mercaptoethanol to monitor PA-mediated conversion of single chain, 125I-plasminogen to two chain plasmin. By incorporating Triton X-100, albumin and trasylol in the reaction buffer, we were able to minimize the adsorptive and autolytic loss of reactants frequently associated with similar approaches. Under these conditions, plasmin formation was linear for at least 24 hours, dose-dependent over a 20-fold range of urokinase concentrations, and at least 100-fold more sensitive (0.05 units/ml) than previously reported direct assays for PA. The versatility of the assay was demonstrated by its ability to distinguish between urokinase-like and tissue-type PA, and to quantitate the effects of agents like fibrin and epsilon-amino caproic acid on their respective activities. The assay was readily adapted to detect inhibitors of PA in various samples, and was employed to demonstrate the presence of such inhibitors in both rabbit and bovine endothelial cells. Interestingly, the rabbit inhibitor was found to block the activity of urokinase but not that of tissue-type PA, while the bovine inhibitor neutralized the activities of both molecules. These results demonstrate that cleavage of 125I-plasminogen can be employed as a direct, sensitive and quantitative assay for various PAs, and thus offers a new approach for studying plasminogen activation and agents that stimulate or inhibit it.

Aminocaproic Acid↗
PubMed1983

Plasminogen activator activity of metastatic variants from a murine fibrosarcoma; effect of thrombin in vitro.

In order to investigate the possible correlation between plasminogen activator (PA) activity and metastatic potential of tumour cells, we studied cultured cells from the murine fibrosarcoma mFS6 and from its two sublines M4 and M9 which differ markedly in their capacity to cause spontaneous metastases in the lung. PA activity was detected in all the sublines by an amidolytic method and was almost completely inhibited by treatment with antiurokinase antiserum. No significant differences were shown between mFS6, M4 and M9. Moreover, molecular analysis of PA by SDS-PAGE electrophoresis and fibrin overlay revealed in all the cell types a single species having a mol. wt. of approximately 48,000 daltons. Thrombin treatment dramatically inhibited the amidolytic activity of all cells, suggesting a role for this enzyme in the modulation of fibrin formation and dissolution within the primary neoplasm.

Animals↗
PubMed1983

Stroke in two young siblings with congenital dysfibrinogenemia.

Two young siblings (a male of 21 and his sister of 26 years) suffered from arterial thrombosis episodes of the carotid and abdominal aorta documented by angiographic studies. In the absence of any known predisposing factor in the family and personal history, the laboratory investigation of both patients revealed coagulation abnormalities compatible with a dysfibrinogenemia. The occurrence of a similar defect also in plasma of one of the propositi's asymptomatic relatives is suggestive of an inherited fibrinogen disorder.

Adult↗
PubMed1983

Interactions between fibrin and the plasminogen activators produced by cultured endothelial cells.

Serum-free conditioned medium (CM) from cultured bovine aortic endothelial cells (BAEs) was fractionated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and analyzed for plasminogen activator (PA) activity by fibrin autography. Distinct size forms of PA with molecular weights (mol wt) of 100,000, 74,000, and 52,000 were readily identified by this approach. When fibrinogen and thrombin were added to CM containing these forms, approximately 55% of the total activity was found to associate with the resultant fibrin clot. The other 45% remained free in the supernatant. This relationship did not change at higher fibrin concentrations. Subsequent analysis revealed that only the larger PA forms (mol wt 74,000-100,000) were recovered in the clot. The 52,000 form did not bind to the polymerizing fibrin under these conditions. The fibrin-binding forms also bound to immobilized concanavalin-A and could be separated from those forms that did not interact with fibrin by concanavalin-A affinity chromatography. The PA activity of the separated forms was then compared by assessing their ability to cleave 125I-plasminogen. Although cleavage by the 52,000 mol wt form was apparent, little if any cleavage was initiated by the mixture containing the 74,000-100,000 forms. The addition of fibrin to this sample resulted in the generation of a potent PA activity. These results indicate that cultured BAEs produce multiple forms of PA that differ both in size and in behavior toward fibrin and concanavalin-A. These forms include molecules that functionally and immunochemically resemble human urokinase, and others that resemble human tissue-type PA.

Animals↗
PubMed1981

Severe thrombocytopenia delays but does not prevent the occlusion of an arterial prosthesis in rats.

This study shows that experimentally-induced immune thrombocytopenia significantly delayed occlusion of an arterial prosthesis inserted in rat abdominal aorta. Thrombocytopenia was effective when induced several hours or shortly, or even several hours after the insertion of the prosthesis. Maintenance of severe thrombocytopenia by daily administrations of antiplatelet antiserum appeared to further delay thrombotic occlusion. However, though delayed, occlusion eventually occurred in all rats, even in those with very low platelet count. This would imply that any attempt to prevent arterial prosthesis thrombosis solely by interfering with platelets is ultimately bound to fail.

Animals↗
PubMed1981

Role of leucocyte procoagulant activity in endotoxin-induced DIC: evidence from comparative studies in rats and rabbits.

We have investigated the ability of rat and rabbit leucocytes to generate coagulant activity (PCA) in response to endotoxin in vitro and in vivo. On prolonged incubation with endotoxin (10 microgram/ml f.c.) isolated rabbit leukocytes developed strong PCA as measured by clotting and amidolytic assay. In contrast, rat leucocyte failed to produce any PCA even in the presence of huge amounts of endotoxin (200 microgram/ml f.c.) When rabbits were given two spaced endotoxin injections (25 microgram/kg b.w., 24 h apart) blood leucocytes harvested 30--60 min after the second injection consistently showed marked PCA. Again, unlike injections (up 2 mg/kg b.w.) were completely devoid of PCA. These findings support the view that leucocytes are involved in endotoxin-induced disseminated intravascular coagulation in rabbits. On the other hand the poor response of rat leucocytes to endotoxin might help explain the resistance of rats to DIC and Sanarelli-Shwartzman reaction.

Animals↗
PubMed1981

Rat blood leucocytes, unlike rabbit leucocytes, do not generate procoagulant activity on exposure to endotoxin.

We have investigated the ability of rat and rabbit leucocytes to generate procoagulant activity (PCA) in response to endotoxin in vitro and in vivo. On prolonged incubation with endotoxin (10 micrograms/ml f.c.) isolated rabbit leucocytes developed strong PCA as measured by clotting and amidolytic assay. In contrast, rat leucocytes failed to produce any PCA even in the presence of huge amounts of endotoxin (200 micrograms/mol f.c.). When rabbits were given two spaced endotoxin injections (25 micrograms/kg consistently showed marked PCA. Again, unlike in the rabbit, rat leucocytes obtained after 2 endotoxin injections (up to 2 mg/kg body wt) showed absolutely no PCA. These findings support the view that leucocytes are involved in endotoxin-induced disseminated intravascular coagulation (DIC) in rabbits. On the other hand the poor response of rat leucocytes to endotoxin might help explain the resistance of rats to DIC and Sanarelli-Shwartzman reaction.

Animals↗
PubMed1980

Plasmatic and vascular factors of the hemostatic system in rats receiving an estrogen-progestogen combination.

Treatment of rats for 10 estral cycles with an estrogen-progestogen combination giving 100% infertility triggered a vascular response characterized by increased prostacyclin activity in arterial walls and increased systolic blood pressure. In contrast, plasma fibrinolytic activity and physiological coagulation inhibitors as well as vascular fibrinolytic activity were not changed by this treatment. The same rats tended to have shorter occlusion times of an aortic prosthesis, and could represent a useful model to study the blood-vessel-wall interplay during oral contraceptive treatment.

Animals↗
PubMed1980

Intermittent heparin treatment does not induce hypercoagulability in haemodialysed patients.

Antithrombin-III (AT-III) and factor VIII coagulant (F VIII:C) and antigenic (F VIII:RA) activities have been studied in nine conservatively treated and 26 dialysed uraemic patients. AT-III levels were not significantly different from those of controls in either group. Among dialysed patients, those who had experienced thrombotic occlusions of the vascular accesses could not be distinguished from the remaining patients on the basis of their AT-III levels. Both F VIII:C and F VIII:RA were slightly higher than in controls in conservatively treated patients, but significantly higher in haemodialysed patients, especially in those who had never experienced thrombotic complications of the vascular accesses. No acute changes were observed in either the AT-III or F VIII:C/F VIII:RA ratio in five patients given heparin therapy during a dialytic session or in the interdialytic period. Thus repeated intermittent heparin treatment does not induce a hypercoagulable state in haemodialysed patients.

Adult↗