Using the model of lung fibrosis induced by intratracheal administration of bleomycin we studied anti-fibrotic activity of combined treatment with neuroleptic haloperidol and hyaluronidase immobilized on polyethylene oxide using electron-beam synthesis. It was shown that successive administration of immobilized hyaluronidase and the neuroleptic drug inhibits deposition of collagen fibers in the bleomycin-treated lungs. Combined treatment with the test compounds reduced swelling of the alveolar epithelium, exudation and infiltration of the alveolar interstitium and alveolar passages by inflammatory cells, and desquamation of alveolocytes into alveolar lumen, so that the alveolar-capillary membrane function was preserved.
We studied the antithrombotic and thrombolytic effects of Trombovazim, a highly-purified proteolytic enzyme preparation obtained by immobilization of bacterial proteinases (Bacillus) on polyethylene oxide with a molecular weight of 1.5 kDa. Blood absorption of the preparation was evaluated after intragastric administration. In vitro experiments showed that Trombovazim produces anticoagulant and thrombolytic effects, which manifested in inhibition of fibrin clot formation and acceleration of its lysis. Drug concentration in the blood was elevated from the 4th to the 7th hour after intragastric administration of Trombovazim in a dose of 2250 U/kg, being maximum by the 5th hour (0.044+/-0.011 U/ml). Course treatment with Trombovazim (1000 U intragastrically, twice daily for 3 days) had a thrombolytic effect on rats with experimental intravascular thrombosis. This effect was manifested in a decrease in thrombus weight and increase in the percent of rats with recanalization of the occluded carotid artery.
The hemostimulating effect of erythropoietin immobilized by the nanotechnology method of electron-beam synthesis was studied on the model of carboplatin-induced myelosuppression. Subcutaneous injection or oral administration of immobilized erythropoietin was followed by stimulation of erythropoiesis. The effect was most pronounced after parenteral treatment with this agent. The increase in proliferative activity and maturation of erythroid precursor cells serve as a factor determining acceleration of reparative processes in the hemopoietic tissue.
Productivity of spermatogenesis and the population of spermatogonial cells were substantially reduced in male Wistar rats 3 months after administration of cytostatic drug paclitaxel, damaging stem spermatogonia. However, signs of reparative regeneration appeared in the testicular tissue. In animals receiving paclitaxel in combination with granulocyte CSF, the same period of observation, the number of spermatogonia and the efficiency of spermatogenesis at the same terms of the study did not differ from those in intact animals. Intensive recovery processes started 1 month earlier than after administration of paclitaxel alone. These data attest to pronounced potentiating effect of granulocyte CSF on reparative regeneration of the testicular tissue.
Hyaluronidase immobilized on polyethylenoxide obtained by electron bean synthesis was administered intranasally and intravenously to C57Bl/6 mice after intratracheal bleomycin and the enzyme effects on the development of pneumofibrosis in animals were studied. Intranasal immobilized hyaluronidase prevented connective tissue growth in the lungs exposed to bleomycin and virtually did not modulate the infiltration of the alveolar and alveolar duct interstitium by inflammatory cells (lymphocytes, macrophages, neutrophils, plasma cells). The antifibrotic effect developed sooner after intranasal inoculation of immobilized hyaluronidase and was more pronounced than after intranasal native hyaluronidase. Intravenous injection of immobilized hyaluronidase did not modify the inflammatory process and deposition of collagen fibrils in the lung parenchyma in pneumofibrosis.
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