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1.
Ter Arkh ; 73(9): 66-73, 2001.
Artículo en Ruso | MEDLINE | ID: mdl-11642086

RESUMEN

AIM: To study the effects of F(ab')2 fragments of the monoclonal antibody (monAB) FRaMon against glycoproteins (GP) IIb-IIIa on platelet aggregating activity in vitro and after injection to healthy volunteers. MATERIAL AND METHODS: In vitro experiments were performed to study effects of F(ab')2 and Fab fragments of FRaMon on platelet aggregation (PA) and 14C-serotonin secretion and characteristics of 125I-labelled F(ab')2 and Fab FRaMon binding to platelets. In vivo effects of F(ab')2 FRaMon (preparation FRAMON) were studied upon its bolus i.v. injection to 10 healthy volunteers at the doses of 0.025-0.2 mg/kg. PA was registered before and 1, 6, 12, 24 hours and 3 and 12-15 days after FRAMON injection. FRAMON binding to platelets in the vascular bed was evaluated by inhibition of 125I-FRAMON in vitro binding to platelets obtained from volunteers. Development of antibodies against FRAMON was evaluated by ELISA two weeks after FRAMON injection. RESULTS: In vitro F(ab')2 FRaMon completely blocked PA induced by ADP and thrombin at the concentrations < 4 and < 7.5 mcg/ml, respectively, and revealed higher inhibitory capacity than Fab FRaMon. F(ab')2 FRamon also inhibited 14C-serotonin secretion from ADP-activated platelets. F(ab')2 FRamon interacted with two GP IIb-IIIa molecules on one platelet and bound to platelets more tightly than Fab FRaMon. F(ab')2 FRaMon (preparation FRAMON) bolus i.v. injection to healthy volunteers at the doses of 0.025-0.2 mg/kg did not induce any signs of individual intolerance, including allergic reactions, bleeding and thrombocytopenia. FRAMON at 0.2 mg/kg almost completely inhibited ADP-induced PA of volunteer's platelets 1 h after injection and by more than 70% at 12 h and by more than 50% at 24 h after injection. PA ability recovered to normal 3 days after injection. Antibodies against FRAMON were detected in 1 out of 10 volunteers. CONCLUSION: F(ab')2 fragments of monAB FRaMon effectively inhibited aggregating ability both in vitro and after injection to healthy volunteers and could be suggested as a basis for development of a new GP IIb-IIIa antagonist.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Fragmentos Fab de Inmunoglobulinas/farmacología , Agregación Plaquetaria/efectos de los fármacos , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/inmunología , Animales , Humanos , Técnicas In Vitro , Ratones
2.
Biull Eksp Biol Med ; 106(12): 741-4, 1988 Dec.
Artículo en Ruso | MEDLINE | ID: mdl-3207886

RESUMEN

When injecting yeast, staphylococcus, polyacrolein microspheres, 3 microns in diameter, into the blood stream of white common rats, it was found that these tend to accumulate in the lumen of pulmonary capillaries, being disposed there in the cytoplasm of macrophages and neutrophils.


Asunto(s)
Pulmón/fisiología , Fagocitosis , Acroleína/administración & dosificación , Animales , Inyecciones Intravenosas , Tinta , Pulmón/citología , Masculino , Microesferas , Tamaño de la Partícula , Polímeros/administración & dosificación , Ratas , Albúmina Sérica Bovina/administración & dosificación , Staphylococcus , Levaduras
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