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Biomedical subjects

M Samama

Publications and source records attributed to M Samama.

At least 55 records · Page 3Linked to original sources
PubMed1990

[Anistreplase. Pharmacology and biological data].

Anistreplase is a second generation thrombolytic agent, an equimolecular streptokinase lys-plasminogen complex the active site of which is temporarily blocked by a p-anisoyle group. Acylation enables the drug to be administered as a bolus intravenous injection over 2 to 5 minutes, and it protects anistreplase against circulating inhibitors, hence a plasma elimination half-life of 90 minutes. Deacylation is slow and progressive (deacylation half-life: 105 minutes), and it begins as soon as the product is injected. It reduces the hypotensive effect of streptokinase, permits a prolonged action in the thrombus and limits the risk of reocclusion. Using lys-plasminogen increases the affinity of the drug for fibrin and potentiates its accumulation and retention in the thrombus. In vitro studies have shown that the affinity of anistreplase for fibrin is similar to that of t-PA. In doses used for myocardial infarction, anistreplase induces a pronounced fibrinogenolysis. The effectiveness of the drug has been demonstrated on numerous animal models and subsequently by clinical trials.

Anistreplase↗
PubMed1989

Effect of standard heparin and a low molecular weight heparin on thrombolytic and fibrinolytic activity of single-chain urokinase plasminogen activator in vitro.

The effect of unfractioned heparin (UH) and low molecular weight heparin (LMWH) (Kabi 2165 - Fragmin) on in vitro scu-PA thrombolytic and fibrinogenolytic activity was investigated. Thrombolytic activity was evaluated by following lysis of radiolabeled plasma clot immersed in plasma in presence of scu-PA alone or with either form of heparin. A 200 IU/ml scu-PA concentration produced clot lysis within 7 hr. UH or LMWH led to a slightly faster clot lysis which was statistically significant only at the 2nd and 3rd hour. No significant difference could be evidenced between UH and LMWH effect. During clot lysis, plasmin, generated within the clot led to a gradual transformation of scu-PA to tcu-PA, specially after a 4-hr incubation. Appearance of tcu-PA activity in the plasma surrounding the clot was significantly inhibited by either form of heparin. This finding contrasts with results observed in purified systems and suggests the presence of heparin-dependent plasma factor(s) inhibiting tcu-PA formation or its activity. Possible candidates might be anti-thrombin III and PAI-3. No fibrinogen breakdown was observed when plasma was incubated for 7 hr at 37 degrees C in presence of scu-PA alone (200 IU/ml) or with either form of heparin. However, in presence of a plasma clot, an important fibrinogen breakdown was observed during clot lysis reflecting the action of plasmin and/or tcu-PA generated within the clot, in the surrounding plasma. Fibrinogenolysis was less pronounced in the presence of both heparin preparations possibly as a consequence of the reduction in the tcu-PA level. These results underline the importance of plasma factors in the interaction of heparin with plasminogen activators such as scu-PA.

Fibrinogen↗
PubMed1989

Calcium rise in human platelets elicited by anti-CD9 and -CD41 murine monoclonal antibodies.

Three murine monoclonal antibodies (anti-CD9: ALB6, anti-CD41: VI-PL3 and PL2-49/GPIIb - final concentration: 7.5 micrograms/mL) are shown to elicit after a lag time aggregation of washed platelets and a calcium signal (as detected by light emitted by loaded aequorin), which is only partially inhibited by aspirin. By comparison the rise induced by thrombin is greater and almost instantaneous. In the presence of EGTA a calcium mobilization from internal stores can be detected with thrombin and with ALB6, but neither with PL2-49 nor with VI-PL3, whereas platelets still change their shape and release ATP. It is tempting to speculate that although all the antibodies induce a calcium change, they activate platelets by different pathways: calcium may be not primarily involved in the activation induced by the anti-CD41 antibodies.

Adenosine Triphosphate↗
PubMed1989

Immunoreactivity of tissue plasminogen activator and of its inhibitor complexes. Biochemical and multicenter validation of a two site immunosorbent assay.

An enzyme linked immunosorbent assay (ELISA) based on goat polyclonal antibodies against human tissue plasminogen activator (tPA) was evaluated. The relative immunoreactivity of tPA in free form and tPA in complex with inhibitors was estimated by ELISA and found to be 100, 74, 94, 92 and 81% for free tPA and tPA in complex with PAI-1, PAI-2, alpha 2-antiplasmin and C1-inhibitor, respectively. Addition of tPA to PAI-1 rich plasma resulted in rapid and total loss of tPA activity without detectable loss of ELISA response, indicating an immunoreactivity of tPA in tPA/PAI-1 complex of about 100%. Three different treatments of citrated plasma samples (acidification/reneutralization, addition of 5 mM EDTA or of 0.5 M lysine) prior to determination by ELISA all resulted in increased tPA levels. The fact that the increase was equally large in all three cases along with good analytical recovery of tPA added to plasma, supported the notion that all tPA antigen present in plasma samples is measured by the ELISA. Analysis by ELISA of fractions obtained by gel filtration of plasma from a patient undergoing tPA treatment identified tPA/inhibitor complexes and free tPA but no low molecular weight degradation products of tPA. Determinations of tPA antigen were made at seven French clinical laboratories on coded and randomized plasma samples with known tPA antigen content. For undiluted samples there was no significant difference between the tPA levels found and those known to be present. The between-assay coefficient of variation was 7 to 10%. In conclusion, the ELISA appeared suited for determination of total tPA antigen in human plasma samples.

Antigen-Antibody Reactions↗
PubMed1989

Overall study of the in vitro plasma clotting system in an invertebrate, Liocarcinus puber (Crustacea Decapoda): considerations on the structure of the Crustacea plasma fibrinogen in relation to evolution.

An overall study of the in vitro plasma coagulation system in the crab Liocarcinus puber has been carried out using various analytical methods, namely thromboelastography, spectrophotometrical examination, and a new one based on changes of the mechanical impedance of the developing clot. From the results reported here the clotting pattern in this species appears surprisingly complex for an invertebrate and unexpectedly closer to that of the vertebrates. Indirect evidences suggest that the fibrinogen polypeptide chains in this species and very likely in the other crustacean, are very different from those of the vertebrates. This would imply that crustacean and vertebrate fibrinogen would have diverged from one another in a far remote past, far beyond the individualization of the vertebrate alpha chain, that is, over 1.5 million years ago.

Animals↗
PubMed1989

PL2-49, a monoclonal antibody against glycoprotein IIb which is a platelet activator.

PL2-49 is a murine monoclonal IgG1 antibody obtained after immunization of Balb/c mice with EDTA washed platelets. Binding could be detected on Zwa(+) as well as Zwa(-) platelets, but not on type I Glanzmann's thrombasthenia platelets using an ELISA screening test. Immunoprecipitation studies showed that PL2-49 bound to glycoprotein IIb when the glycoprotein IIb/IIIa complex dissociation was performed after the monoclonal antibody binding. Experiments with a human alloantibody against Zwa antigen were run in parallel to control the complex dissociation. Ascitic fluid, as well as the purified antibody, induced activation and aggregation of washed platelets and ATP release. PL2-49-induced aggregation did not require exogenous fibrinogen and was inhibited, partially, in the presence of aspirin, apyrase, isosorbide dinitrate. Raising intra-platelet cyclic AMP with a stable PGI2 analogue, iloprost, and/or a phosphodiesterase inhibitor, RA 233, suppressed the responses to PL2-49. F(ab')2 fragments did not induce aggregation of normal platelets but inhibited the response to the whole immunoglobulin. Finally PL2-49 was shown to induce aequorin-detected elevations in intraplatelet Ca++ levels. Thus PL2-49 seems to differ from monoclonal antibodies so far described, since it binds to glycoprotein IIb in a complex-dependent manner at least under our experimental conditions for immunoprecipitation studies, and it induces platelet Ca++ mobilization and platelet aggregation after a lag-time. These reactions depend both on Fab and Fc domains of the antibody and require neither complement nor exogenous fibrinogen.

Animals↗
PubMed1989

Evaluation of a method to assess red blood cell aggregation.

Reversible aggregation of red blood cells (RBC) plays an important role in determining the flow properties of blood. To study different factors affecting RBC aggregation we used a new commercially available erythro-aggregameter (SEFAM, Nancy, France). The method allows the photometric quantitation of the kinetics of RBC aggregation and the estimation of the shear resistance of the aggregates. Modification of the hematocrit acts mostly on the determination of the disaggregation shear rate, while plasma composition strongly affects all measurements. Anticoagulants per se do no influence the aggregation process, but can alter the value of the parameters through a plasma dilution effect. Presence of white blood cells and platelets in the sample did not modify the data. Study on the effects of low concentration of heparin and low molecular weight heparin showed that at therapeutical doses these drugs did not alter the values of the aggregation parameters. Provided that precise guidelines are followed for the processing of blood samples, this method may serve to investigate RBC aggregation in various diseases and to search for adequate hemorheologic treatment.

Anticoagulants↗
PubMed1989

[Erythrocyte aggregation and retinal vein occlusion. Preliminary data for a randomized study on the efficacy of anti-erythrocyte aggregation (troxerutin) in retinal vein occlusion].

Erythrocyte aggregation (EAg) is one of the principal determinants of blood viscosity at low shearing rates (slow flow). The retinal venous circulation, characterised by a slow circulatory rate and a high resistance to flow, creates a favourable environment for the formation of erythrocyte aggregates. EAg and other laboratory parameters (haematocrit, fibrinogen, plasma proteins, clotting) were measured in 64 patients presenting with retinal vein occlusion (RVO) and 64 controls matched for age, sex, risk factors (HT, diabetes, smoking) and concomitant vascular disease. Statistical analysis of the results demonstrated a significant difference between the RVO group and the control group for fibrinogen (p = 0.03) and erythrocyte aggregation (p = 0.00003 for the aggregation index at 10 sec and p = 0.0002 for the threshold of partial dissociation). The rise in the fibrinogen level alone cannot explain the increased erythrocyte aggregation. These results demonstrate that the increased EAg largely explains the hyperviscosity reported by other authors and suggest that it plays an important role in the pathogenesis of RVO.

Adult↗
PubMed1989

[AL amyloidosis and primary fibrinolysis. Study of the mechanism of fibrinolysis].

A 45 years old woman with AL amyloidosis presented with a hypofibrinogenemia (fibrinogen 100 mg/dl) without severe bleeding. There was laboratory evidence of fibrinolysis with shortened euglobulin lysis time, decreased alpha-2 plasmin inhibitor and decreased plasminogen. The mechanism of this primary fibrinolysis remains unclear, since there is no enhancement of the tissue-type plasminogen activator. Analysis of the 8 cases related in the literature of excessive fibrinolysis associated with amyloidosis demonstrated improvement of bleeding manifestations and abnormal fibrinolysis following the administration of antifibrinolytic agents.

Amyloid↗
PubMed1989

[Dermatan sulfate and the prevention of experimental venous thrombosis].

Although the specific anticoagulant activity of dermatan sulphate is seventy times less than that of standard heparin, its venous antithrombotic activity, tested on a great number of experimental models, appears at gravimetric doses which are only seven fold higher. This antithrombotic activity is not correlated with the factor Xa inhibition, but is associated with thrombin generation inhibition and potentiation of heparin cofactor II. Meanwhile, others factors, still non entirely identified, i.e. like the release of endogenous tissue plasminogen activators, must probably be involved in the antithrombotic activity of dermatan sulphate. In contrast to heparin, dermatan sulphate possesses hemorrhagic properties only at doses which are forty times higher than the antithrombotic dose. These hemorrhagic properties seem associated with an inhibition of collagen induced platelet aggregation. Finally, the pharmacokinetic profile of dermatan sulphate after intravenous injection in the rabbit, is different from that of standard heparin, and close to that of low molecular weight heparins.

Animals↗
PubMed1989

[Value of moderate doses of urokinase combined with heparin in the treatment of massive pulmonary embolism. A retrospective study of 33 cases].

The aim of this retrospective study was to evaluate the efficacy and tolerance of a moderate dose of urokinase (UK : 2000 IU/kg/h) for at least 24 h in a series of 23 patients with massive pulmonary emboli (PE) (mean pulmonary vascular obstruction = 70 +/- 7%). All patients received heparin in conjunction with UK. A control pulmonary angiography, performed at the end of UK therapy, revealed an important decrease in pulmonary obstruction (-50%). One patient died before the end of UK therapy from shock due to PE (early mortality = 4.3%). Severe hemorrhagic complications occurred in 3 patients (13%) and dictated the stoppage of UK administration, but bleeding was never the cause of death or sequelae. Thus, moderate doses of UK associated with heparin appear to effectively induce clot lysis in patients with massive pulmonary emboli. The incidence of hemorrhagic complications should be decreased by strictly respecting all contraindications to the use of thrombolytic agents and by avoiding excessive heparinization.

Adult↗
PubMed1989

Life-threatening intracranial bleeding associated with the presence of an antifactor VII autoantibody.

This is a report of a 62-year-old male patient who had a bleeding disorder due to the presence of a factor VII (proconvertin) inhibitor. After treatment with a high-dose intravenous (IV) immunoglobulin failed and a life-threatening intracranial hemorrhage occurred, plasma exchanges were performed and immunosuppressive therapy was given. The factor VII inhibitor promptly disappeared, and the patient's parameters of hemostasis became normal. Even though a relapse occurred some months later, the patient responded to immunosuppressive therapy. No underlying disorder was evidenced after 17 months of follow-up.

Autoimmune Diseases↗