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Biomedical subjects

M Bielawiec

Publications and source records attributed to M Bielawiec.

At least 19 recordsLinked to original sources

Comparative study on the in vitro and in vivo activities of heparinoids derivative investigated on the animal model.

In this study we compared the antithrombotic and anticoagulant properties of sodium and calcium derivatives of pentosan polysulfate (Na-PPS, Ca-PPS), unfractionated heparin (UFH), and low-molecular-weight heparin (Fraxiparin). The antithrombotic effects of these agents have been investigated in an experimental thrombosis model in which rat mesenteric venules with a diameter of 20-30 microm were injured by well-defined argon laser lesions. Furthermore, the in vivo and in vitro anticoagulant activities [activated partial thromboplastin time (aPTT), Heptest] of these agents have been studied. Thrombus formation was significantly inhibited after s.c. injection of Na-PPS and Ca-PPS in doses >10 mg/kg. The duration of the antithrombotic effect lasted 8 h for Na-PPS and 12 h for Ca-PPS. After oral administration of Na-PPS, an antithrombotic effect was not observed. Oral application of Ca-PPS in doses >20 mg/kg significantly inhibited thrombus formation. Na-PPS and Ca-PPS markedly prolonged clotting time in aPTT and Heptest in concentrations ranging from 0.01 to 0.2 mg/ml rat PTT. Two h after s.c. administration of these agents in a dose of 10 mg/kg, the aPTT increased threefold and the Heptest 2.5-fold compared with controls. After oral application of 50 mg/kg Na-PPS and Ca-PPS, no effect on the coagulation test could be measured. Intravenous injection of UFH prolonged the Heptest after 1 min and the aPTT after 30 min. In ex vivo studies of aPTT and Heptest performed in rat plasma between 2 and 24 h after s.c. injection of 0.2 mg/kg Fraxiparin, no inhibition of any coagulation test was measured. The antithrombotic effect of 0.2 mg/kg Fraxiparin after s.c. injection was significant. Intravenous injection of 20 U/kg UFH significantly inhibited thrombus formation. The smallest antithrombotic effect was after i.v. injection of UFH.

Animals↗

Experimental studies on the anticoagulant and antithrombotic effects of sodium and calcium pentosan polysulphate.

In the present study we have compared the antithrombotic and anticoagulant properties of sodium and calcium derivatives of pentosan polysulphate (Na-PPS, Ca-PPS). The antithrombotic effect of these agents have been investigated in an experimental thrombosis model in which rat mesenteric venules diameter of 20-30 microm were injured by well defined Argon laser lesions. Furthermore, the in vivo and in vitro anticoagulant activities (aPTT, Heptest) of these agents have been studied. Thrombus formation was significantly inhibited after s.c. injection of Na-PPS and Ca-PPS in doses above 10 mg/kg. The duration of the antithrombotic effect lasted 8 h for Na-PPS and 12 h for Ca-PPS. After oral administration of Na-PPS an antithrombotic effect was not observed. Oral application of Ca-PPS in doses higher than 20 mg/kg significantly inhibited thrombus formation. Na-PPS and Ca-PPS markedly prolonged clotting time in aPTT and Heptest in concentrations ranging from 0.01 to 0.2 mg/ml rat PTT. Two h after s.c. administration of these agents in a dose 10 mg/kg, the aPTT increased 3-fold and Heptest 2.5-fold compared to controls. After oral application of 50 mg/kg Na-PPS and Ca-PPS no effect on coagulation test could be measured.

Animals↗

Low molecular weight heparin versus acenocoumarol in the secondary prophylaxis of deep vein thrombosis.

The aim of this study was to determine the efficacy and safety of subcutaneous weight-adjusted dose low molecular weight heparin (LMWH) compared with oral anticoagulant (OA) in the prevention of recurrent venous thromboembolism. In a prospective multicenter trial, 202 patients with symptomatic proximal deep vein thrombosis (DVT) were included. As soon as the diagnosis of DVT was confirmed by phlebography, 101 were randomly assigned to receive LMWH (nadroparin) for secondary prophylaxis and 101 to receive OA (acenocoumarol). Patients in both groups were initially treated with nadroparin in a dose of 85 anti-Xa IU/kg s.c. every 12 h. Secondary prophylaxis with either nadroparin, 85 anti-Xa IU/kg s. c. once daily, or acenocoumarol was continued for at least 3 months. Three patients in the LMWH group and 6 in the OA group were excluded from analysis for various reasons. During the one-year combined secondary prophylaxis and surveillance period, 7 of of the 98 evaluable patients (7.1%) in the LMWH group and 9 of the 95 evaluable patients (9.5%) in the OA group had a documented recurrence of venous thromboembolism (Fisher's exact test, p = 0.61). Of these, 2 patients who received LMWH and 7 patients on acenocoumarol had recurrences in the 3-month period of secondary prophylaxis. Four patients (4.1%) in the LMWH group developed bleeding complications during this study period, as compared with 7 (7.4%) in the OA group (Fisher's exact test, p = 0.37). There were two major bleedings, one in the LMWH group and one in the OA group. Eleven patients died, 5 (5.1%) in the LMWH group and 6 (6.3%) in the OA group. It is concluded that nadroparin in a dose of 85 anti-Xa IU/kg s.c. once daily provides an effective and safe alternative to oral anticoagulants in the secondary prophylaxis of DVT.

Acenocoumarol↗

The role of epidermal growth factor in platelet-endothelium interactions.

The objective of this study was to determine whether endogenous EFG released after submaximal physical exercise, affects platelet-endothelium interactions. Sixteen healthy male volunteers, aged 23-26 years, were submitted to a submaximal bicycle ergometry test. Blood for determination of EGF concentrations, platelet function studies (concentrations of beta-TG, PF4 and TXB2) and endothelium activity (LTC4 and endothelin-1,2 concentrations) was taken via an intravenous catheter before starting exercise and 15, 30 and 60 min after. A similar scheme was followed to investigate changes in the same parameters induced by a slow intravenous infusion of 0.3 mg/kg b.w. phentolamine (an alpha-adrenergic blocker) before exercise. Plasma concentrations of EGF and the markers of platelet function-beta-TG and PF4 as well as LTC4 concentrations increased only 15 min following exercise. The concentrations of TXB2, and endothelium-1,2 were almost unchanged 15 min after the submaximal bicycle ergometry test. Phentolamine markedly decreased the EGF concentrations in plasma (15 min following exercise) while at 30 and 60 min after exercise it had no effect on this parameter. No significant changes in concentrations of beta-TG, PF6, LTC4 and endothelin-1,2 after phentolamine infusion were found. These results show that increase of plasma EGF following exercise was accompanied with increase of beta-TG, PF4 and LTC4 concentrations. Inhibition of alpha-adrenergic receptors with phentolamine abolished the exercise-induced increase in plasma EGF concentration. The findings suggest that endogenous EGF may affect the platelet function and changes the reactivity of the vascular endothelium.

Adult↗

[Case report presentation for treatment of pure red cell aplasia].

We presented a case of a 34 year old male patient with pure red cell aplasia. He was treated with antithymocyte globulin (Pasteur Merieux, France) at a dose of 175 mg in 350 ml 0.9% NaCl in intravenous drip infusion--10 drip/min for 5 consecutive days. The therapy resulted in normalization of morphological parameters. Patient was under clinical observation. After 9 years when hemoglobin level decreased monoclonal antibody OKT3 og IgG 2a type (Cilag Ag International, Switzerland) at a dose of 5 mg intravenous for 10 consecutive days was applied. During the first and second therapy course symptoms of serum sickness and "flu like" syndrome was observed. The results of the two treatment appeared positive. We received normalization of morphological parameters.

Adult↗

The role of monocytes in the platelet release of von Willebrand factor.

Circulating blood monocytes, which are a source of foam cells contribute to the vascular lesions. Von Willebrand factor (vWF) is an adhesive multimeric glycoprotein that is synthesized only by endothelial cells and megakaryocytes. In the present study we assessed the ability of human platelets to secrete vWF after incubation with blood monocytes in vitro. Monocytes derived from blood of healthy adults were cultured and next incubated with washed platelets. von Willebrand factor antigen (vWF:Ag) was measured in the supernatant by Laurell immunoelectrophoresis. The study showed that Triton X-100 treated platelets released 82-112% of vWF:Ag. The levels of vWF:Ag in the supernatant with untreated platelets and incubated with monocytes without LPS were respectively 36-48% and 45-72%. After incubation washed platelets with LPS stimulated monocytes a significant decrease in vWF:Ag level was observed (7-11%).

Adult↗

[Examination of interleukin levels and growth factor from blood platelets in leukemia].

Plasma concentrations of interleukines 1, 3, 6, 8 and platelet derived growth factor (PDGF) were estimated in 45 patients with leukaemias. Among patients were 12 with acute myeloblastic leukaemia-AML (type M1 according to FAB classification), 9 with chronic granulocytic leukaemia-CGL, 10 with blastic crisis of CGL (CGL-BC) and 14 with chronic lymphocytic leukaemia-CLL (in 1 and 2 stage according to Rai classification). Additionally the concentration of IL-3 was measured in 10 patients with exacerbation of CLL. Control group consisted of 12 health volunteers. The concentrations of interleukines and PDGF were determined by means of radioimmunoassay or immunoradiometric assay. In the patients with AML, CGL-BC and CLL significant increase of concentrations of IL-1B, IL-6 were found. The patients suffers from CGL and CGL-BC had increase concentrations of IL-3, but patients with CLL-interleukin 8. The concentrations of PDGF were significantly decreased in the patients with AML, CGL-BC, and CGL. The differences of concentrations of studied interleukines can confirm their great significance in proliferation of leukaemic cells. The decrease of concentrations of PDGF in myelocytic leukaemias may reflect thrombopoietic disturbances in these illnesses.

Blood Platelets↗

[Tissue plasminogen activator and plasminogen activator inhibitor in aqueous humor].

BACKGROUND: In the anterior segment of the eye, fibrin clots must be rapidly resorbed to prevent fibrosis. Tissue-type plasminogen activator (t-PA), a serine protease that catalyzes the conversion from plasminogen to plasmin, plays an important role in the fibrinolytic system and has therefore in recent years attracted attention in the field of ophthalmology. MATERIAL AND METHODS: The aqueous humor of patients undergoing cataract surgery was analyzed for the presence of components of the fibrinolytic cascade. The quantities of t-PA and plasminogen-activator inhibitor (PAI) were determined using enzyme-linked immunosorbent assays. We determined t-PA and PAI in the aqueous humor of 64 patients between 59 and 82 years of age. RESULTS: The t-PA levels ranged from 0.65 to 1.75 ng/ml and PAI activity from 3.24 to 5.1 AU/ml. Association between t-PA levels and PAI activity and accompanying diseases or metabolic disorders was noted. The highest concentration of t-PA and the lowest activity of PAI has been observed in aqueous humor of patients with senile cataract. The knowledge about the presence of t-PA in aqueous humor is significant for the recognition of pathological events following intraocular fibrin formation and may be an important basis for therapeutic use of t-PA.

Aged↗

Stimulated monocytes release factor XIII subunit A and fibronectin in vitro.

Factor XIII catalyses the formation of covalent bonds between several proteins involved in wound healing. Subunit A of factor XIII has been found inside and on the surface of monocytes and macrophages. In our study we investigated the ability of cultured monocytes to release factor XIII A subunit and its substrate-fibronectin. Human monocytes were cultured for up to 36 hours with lipopolysaccharide (LPS) from Escherichia coli. In supernatants of LPS stimulated monocytes we found 22 +/- 4 nM/ml and 40 +/- 6 nM/ml of factor XIII subunit A after 24 and 36 hours of incubation respectively. We also observed an increase of fibronectin concentration in supernatants of stimulated monocytes. The obtained results suggest that activated monocytes might be a source of factor XIII and fibronectin, which are critical for tissue repair processes.

Cells, Cultured↗

Von Willebrand factor antigen in assessment of vasculitis in patients with connective tissue diseases.

Von Willebrand factor antigen (vWF:Ag) is synthesized and secreted by endothelial cells. In the present study we tried to assess the relationship between plasma level of vWF:Ag and vascular damage in patients with vasculitis. The study was carried out on 59 patients with connective tissue diseases. Vasculitis was diagnosed by biopsies of the skin. The patients with vasculitis had a significantly elevated level of vWF:Ag; however, no significant correlation between the amount of plasma vWF:Ag and the degree of vasculitis was found. The obtained results show that the plasma level of vWF:Ag may reflect the presence of vascular, especially endothelial, damage in patients with connective tissue diseases.

Adult↗

The antithrombotic effect of thromboxane receptor antagonist HN 11500 on thrombus formation in laser thrombosis model and platelet function tests.

The effect of thromboxane receptor antagonist HN 11500 (Chemie Linz AG, Austria) on thrombus formation in laser thrombosis model and platelet function test has been studied. In this study HN 11500 was a potent antithrombotic agent significantly inhibiting thrombus formation in venules in doses higher than 5 mg/kg after i.v. and 10 mg/kg after oral administration. Lower doses were needed to obtain the same antithrombotic effect when arterioles were investigated. The antithrombotic effect of minimal effective doses of HN 11500 lasted longer than 8 hours in venules and more than 12 hours in arterioles. After oral feeding of this thromboxane receptor antagonist in doses 5 mg/kg, antithrombotic effect in investigated arterioles lasted longer than 16 hours but less than 20 hours. When different doses of HN 11500 were injected i.v. together with r-Hirudin or LMWH CY 216 the inhibitory effect on thrombus formation in venules was stronger and observed with lower doses of HN 11500. In vitro study HN 11500 inhibited platelet adhesion to the siliconized glass, bovine extracellular matrix as well as ADP and collagen mediated platelet aggregation. Lower concentration of this agent were needed to inhibited platelet adhesion to the extracellular matrix than platelet adhesion to the siliconised glass, and ADP and collagen induced aggregation.

Animals↗

[Antithrombotic properties of heparin independent of its anticoagulant activity].

Antithrombotic effects of two glycosaminoglycans: LMWH-Fraxiparin (Sanofi) and UFH Heparinum (Polfa) have been studied in the laser-induced rat thrombosis model. The investigations were carried out on male Wistar rats. Thrombus formation was induced in small mesenteric venules 25-30 microns in diameter using argon laser. An interference contrast system based on a Leitz Orthoplan microscope was used for the evaluation of thrombus formation. The number of laser injuries needed to induce a defined thrombus proved to be a useful way to quantitate the results in this thrombosis model. Fraxiparin and UFH showed doses dependent antithrombotic effect in the laser model. Fraxiparin in minimal dose 16 aXa/kg and UFH in minimal dose 15 IU/kg 30 min after i.v. injection to the rats markedly inhibited thrombus formation in small mesenteric venules. Antithrombotic effect of the administration of minimal effective doses of both glycosaminoglycans lasted longer than 4 hours but less than 6 hours. Protamine injected in a dose 1 ml per 5000 U/heparin neutralized anticoagulant activity of both heparins in rat plasma but did not inhibit the antithrombotic effect in laser thrombosis model. After the injection of protamine antithrombotic effect of the investigated glycosaminoglycans was weaker but still observed. Further studies are needed to clarify the factors which are responsible for the antithrombotic effect of heparins after neutralization of their anticoagulant activity (inhibition factors: IIa and Xa).

Animals↗

[Antithrombotic effects of molsidomine, isosorbide dinitrate and verapamil in a laser-induced thrombosis model].

Antithrombotic effects of molsidomine, isosorbide dinitrate and verapamil obtained from the Casela Riedel Pharma GmbH, Frankfurt/Main, Germany have been studied in the laser-induced rat thrombosis model. The investigations were carried out on male Wistar rats weighing 200-300 g. Thrombus formation was induced in small mesenteric arteries--25-35 microns diameter using argon laser. An interference contrast system based on a Leitz Orthoplan microscope for the evaluation of thrombus formation was used. The number of laser injuries needed to induce a defined thrombus proved to be a useful way to quantitate the results in this thrombosis model. All agents showed dose dependent antithrombotic effect in our laser model. Molsidomine and verapamil inhibited 30 min after single i.v. injection in minimal dose 1 mg/kg and in dose 5 mg/kg 2 hours after oral administration thrombus formation in small mesenteric arteries. Isosorbide dinitrate in higher doses: 10 mg/kg 30 min after i.v. injection and 20 mg/kg after oral feeding showed significant antithrombotic effect. Antithrombotic effect of administration of minimal effective doses of all agents lasted longer than 4 hours but less than 6 hours. All drugs in effective antithrombotic doses after intravenous injection showed also inhibitory effect on rat platelet adhesion to the siliconized glass and bovine subendothelial extracellular matrix.

Animals↗