ABSTRACT
Pegylated hyaluronate-endo-ß-N-acetylhexosaminidase was shown to potentiate significantly the hemostimulatory effect of pegylated erythropoietin. It was found that enhanced production of hemopoietin by adherent and non-adherent cells of the hemopoiesis-inducing microenvironment and elevated serum content of endogenous erythropoietin along with increased susceptibility of erythroid precursors to pegylated erythropoietin underlay this phenomenon.
Subject(s)
Anemia/drug therapy , Erythropoietin/pharmacology , Hematinics/pharmacology , Polyethylene Glycols/pharmacology , beta-N-Acetylhexosaminidases/pharmacology , Anemia/chemically induced , Animals , Bone Marrow Cells/drug effects , Carboplatin , Cell Differentiation , Cell Proliferation , Cells, Cultured , Drug Synergism , Drug Therapy, Combination , Erythroid Cells/drug effects , Erythropoietin/administration & dosage , Hematinics/administration & dosage , Mice , Mice, Inbred CBA , Polyethylene Glycols/administration & dosage , Recombinant Proteins/administration & dosage , Recombinant Proteins/pharmacology , Stem Cells/drug effects , Stem Cells/physiology , beta-N-Acetylhexosaminidases/administration & dosageABSTRACT
Experiments were performed on the model of cyclophosphamide-induced myelosuppression. We showed that regeneration of the granulocytic hemopoietic stem is related to activation of multipotent, granulocyte-erythroid-macrophage-megakaryocyte, and granulocyte-macrophage precursors. The division and maturation of granulocyte colony-forming cells and significant decrease in the number of these cells in the bone were suppressed under these conditions. The granulocytopoiesis-stimulating effect of granulocyte CSF during myelosuppression was associated with an increase in functional activity of multipotent and granulocyte-erythroid-macrophage-megakaryocyte precursors (primarily of differentiation). In the period of regeneration, this effect was attributed to activity of granulocyte precursors.
Subject(s)
Cell Differentiation/drug effects , Cell Proliferation/drug effects , Granulocyte Colony-Stimulating Factor/pharmacology , Animals , Colony-Forming Units Assay , Cyclophosphamide , Cytostatic Agents/pharmacology , Granulocytes/drug effects , Hematopoiesis/drug effects , Macrophages/drug effects , Male , Megakaryocytes/drug effects , Mice , Regeneration/drug effectsABSTRACT
Neuroprotective activity of immobilized granulocyte CSF (nanotechnology with electron-beam synthesis) and hyaluronidase was studied on the model of posthypoxic encephalopathy. Oral administration of immobilized granulocyte CSF had no effect on manifestations of posthypoxic psychoneurological disorders in animals. Combined treatment with immobilized granulocyte CSF and hyaluronidase prevented impairment of orientation and exploratory behavior and development of amnesia in mice with hypoxic injury.