RESUMEN
The phenomenon of a hundredfold more rapid blood clearance of biotinylated immunoglobulins after post-injection of an equiponderate dose of avidin is described. The concentration of 125I-labeled biotinylated IgG in rat circulation slowly decreased to 20% of the initial level in 24 hours. Avidin injection at any moment of this period induced a 90-95% reduction of blood radioactivity in 15 minutes. Up to 70% of the radioactivity was recovered in the liver. The technique of enhanced blood clearance developed in rats was checked in dogs using biotinylated monoclonal anti-human fibrinogen antibodies, capable of concentrating in dog thrombus. The results obtained offer the possibility of thrombus/blood contrast increase in radioimmunoimaging.
Asunto(s)
Anticuerpos Monoclonales , Avidina , Biotina , Inmunoglobulina G/análisis , Radioisótopos de Yodo , Animales , Perros , Humanos , Ligandos , Masculino , Ratas , Ratas Endogámicas , Trombosis/diagnósticoRESUMEN
[125I]-labelled rabbit antibodies against rat type I collagen and non-immune IgG were injected into rat circulation. The kinetics of their clearance and the biodistribution in different organs were studied. Both preparations showed very similar clearance rate, the kinetics fitting bi-exponential approximation with characteristic parameters t1,1/2 = 201 +/- 20 min before 320 min and t2,1/2 = 1350 +/- 450 min at times over 320 min for antibodies and 258 +/- 45 min and 890 +/- 140 min for IgG. The specific affinity of the circulating antibodies did not decrease within 24 hours. The antibodies were specifically accumulated in spleen, where their accumulation was 5-fold higher than that of non-immune IgG. Accumulation of antibodies was maximal 3 hours after the injection. The localization ratio (i.e. the ratio of the amount of the antibodies per g of tissue to that per g of blood) reached a maximum 24 hours after the injection and remained stable for 120 hours. Immunofluorescent staining of spleen sections resulted in a bright fluorescence of dense collagenous structures in the trabeculae and in the wall of the central follicular arterium, bright spot fluorescence in the marginal zone of the follicle, and diffuse fluorescence in the red pulp. These findings suggest an unusually high accessibility of collagen type I in spleen to circulating blood plasma components.
Asunto(s)
Anticuerpos/farmacocinética , Colágeno/metabolismo , Bazo/metabolismo , Animales , Sitios de Unión de Anticuerpos , Colágeno/inmunología , Técnica del Anticuerpo Fluorescente , Inmunoglobulina G/farmacocinética , Técnicas de Inmunoadsorción , Riñón/metabolismo , Tasa de Depuración Metabólica , Miocardio/metabolismo , Ratas , Bazo/inmunología , Distribución TisularRESUMEN
The effect of cardio- and neurotropic drugs was studied on beta 2-adrenergic receptors and coupled adenylate cyclase (AC) from rat reticulocytes. Trifluperazine, chlorpromazine, levomepromazine, metaphenazine, haloperidol, (+) and (-) isomers of butaclamol, as well as imipramine, vinblastine and verapamil, at a concentration of 10(-4) M failed to influence AC stimulation by isoproterenol. Thioproperazine and trifluperidol inhibited isoproterenol-stimulated AC with Ki = 4.0.10(-5) M and Ki = 4.5.10(-5) M, respectively. This inhibitory effect was due to the direct action of thioproperazine and trifluperidol on the beta-adrenergic receptors, since this drugs displace the receptor-bound (3H) dihydroalprenolol with Ki = 5.10(-6) M and 9.10(-6) M, respectively. The results obtained suggest that adrenolytic effect of trifluperidol and thioproperazine might play a significant role in their side effects.