Hemostimualting properties of preparation containing ultralow doses of antibodies to stem cell factor in cytostatic myelosuppression.

Preparation containing ultralow doses of antibodies to stem cell factor considerably activates bone marrow myelopoiesis suppressed by cyclophosphamide. This effect of the preparation is based on stimulation of proliferation of committed hemopoietic precursors and increase in functional activity of adherent elements of hemopoiesis-inducing microenvironment.

Licorice preparations improve efficiency of chemotherapy and surgical treatment of transplanted tumors.

Experiments on animals with Lewis lung carcinoma and Ehrlich tumor showed that licorice (glycyrrhiza) extract and glyciram prepared from this plant improved the antitumor effect of cyclophosphamide. Glyciram reduced the toxic effect of the cytostatic on peripheral blood leukocytes. Licorice extract inhibited the growth of Ehrlich tumor and development of metastases in mice with Lewis lung carcinoma. Glyciram administered to mice after removal of Lewis lung carcinoma produced an antimetastatic effect and prevented relapses.

Adrenergic regulation of erythropoiesis during cytostatic-induced myelosuppressions.

The role of central adrenergic structures in the regulation of the erythroid hematopoietic stem was studied during administration of cyclophosphamide and 5-fluorouracil. The central nervous system contributed to suppression of erythropoiesis during cytostatic treatment. The suppressive effect of brain adrenergic structures on the erythron after treatment with cyclophosphamide and 5-fluorouracil was related to dysfunction of adherent cells in the hemopoiesis-inducing microenvironment (formation of hemopoietic islets and secretion of erythropoietic activity) and production of growth factors by myelokaryocytes, respectively. Brain norepinephrine had an inhibitory effect on proliferative activity and differentiation of erythroid precursors that were associated with the erythropoietin and peripheral alpha-adrenergic structures. However, stimulation of beta-adrenergic structures was followed by an increase in the rate of erythroid cell maturation.

Mechanisms of therapeutic effects of granulocytic colony-stimulating factor in experimental diabetes mellitus.

We studied the mechanisms of therapeutic effects of granulocytic colony-stimulating factor in experimental diabetes mellitus. It was found that this preparation increased the number of mesenchymal precursor cells in the bone marrow and peripheral blood with subsequent increase in the content of progenitor cells in the pancreas. These results attest to mobilization of mesenchymal progenitor cells and their migration into the damaged tissue accompanied by morphofunctional recovery of the insulin-producing apparatus.

Stem cells in experimental chronic hepatitis.

We studied the state of the pools of mesenchymal precursor cells in the bone marrow and peripheral blood and the dynamics of regional precursor cells in the liver in experimental chronic hepatitis. We showed that bone marrow mesenchymal stem cells are involved in liver regeneration in its chronic disease. Our results suggest that these mechanisms are insufficient for the recovery of liver tissue.

Role of serotonin in the regulation of granulocytopoiesis during cytostatic-induced myelosuppressions.

We studied the role of the serotoninergic system in the regulation of the granulocytic hemopoietic stem during cytostatic myelosuppressions caused by administration of cyclophosphamide or 5-fluorouracil. After cytostatic treatment, the state of granulocytopoietic precursors and functional activity of cells in the hemopoiesis-inducing microenvironment were regulated by serotoninergic structures of the brain. The regulatory influence of CNS was realized via serotonin receptors on precursors and microenvironment cells. The response of the granulocytic stem was determined by specific interaction between distant and local regulatory structures and inhibitory effect of cyclophosphamide and 5-fluorouracil on granulocytic cells and regulatory systems.

Mechanisms of regulation of hemopoiesis during experimental cytostatic myelosuppression induced by carboplatin.

The mechanisms of suppression and recovery of the bone marrow erythroid stem were studied on the model of myelosuppression induced by administration of carboplatin in the maximum tolerated dose. Single administration of the cytostatic led to the development of long-term hypoplasia of hemopoiesis. Despite enhanced proliferation of erythroid precursor caused by increased erythropoietic activity of blood plasma and bone marrow cells, inhibition of cell maturation prevented recovery of the content of morphologically recognizable erythrokaryocytes in the bone marrow.

A comparative study of stimulation of erythropoiesis during renal anemia with the preparation of antibodies against erythropoietin in ultralow doses and Recormon.

We compared the stimulatory effects of a preparation of antibodies against erythropoietin in ultralow doses (Poetam) and recombinant erythropoietin (Recormon) on erythropoiesis that was suppressed by carboplatin. Both drugs possessed high erythropoiesis-stimulating activity, which was manifested in an increase in the number of erythrokaryocytes and erythroid precursors in hemopoietic tissue and count of erythrokaryocytes and reticulocytes in the peripheral blood during postcytostatic recovery. Recormon produced a rapid and short-term stimulatory effect on the erythron. The effect of Poetam developed slowly, but persisted for a longer time.

Role of hyaluronidase in the regulation of hemopoiesis.

We evaluated the possibility of hemopoiesis stimulation with hyaluronidase. The response of the blood system depended on the dose of this enzyme. Functional activity of hemopoietic precursor cells increased under the influence of hyaluronidase in a dose of 20 arb. units, which was accompanied by an increase in the secretion of hemopoietins by adherent myelokaryocytes and elevation of hemopoietic activity in blood plasma. The number of erythrokaryocytes and mature neutrophilic granulocytes in the bone marrow, as well as the count of reticulocytes and neutrophils in the peripheral blood increased under these conditions. Administration of hyaluronidase in a high dose (100 arb. units) led to uncoupling of proliferation and differentiation of hemopoietic precursors and produced no considerably changes in the blood.

Role of Thy-1,2+ cells in hemopoiesis regulation during hypoxia.

We studied the role of Thy-1,2+ cells in the regulation of hemopoiesis during oxygen deficiency of different genesis. These cells of the hemopoiesis-inducing microenvironment play an important role in the compensatory and adaptive reactions of the blood system to hypoxia. Thy-1,2+ cells directly or indirectly (via interaction with adherent myelokaryocytes) stimulated hemopoietic precursors. The effect of these cells on committed erythroid precursors was most pronounced.

Monoaminergic regulation of proliferation and differentiation of granulomonocytopoietic precursors during neuroses.

We studied the role of monoamines in the regulation of functional activity of granulocyte-macrophage precursors during neuroses. Under conditions of conflict situation and paradoxical sleep deprivation, monoamines of the central nervous system regulate proliferation and differentiation via alpha-adrenergic structures on granulomonocytopoietic precursors and cells of the hemopoiesis-inducing microenvironment.

Neurosis-associated changes in the granulocytic hemopoietic stem in mice with different learning capacity.

We studied the local mechanisms of neurosis-associated changes in the granulocytic hemopoietic stem in CBA/CaLac mice with different learning capacity. It was found that in good learners hyperplasia of the bone marrow granulocytopoiesis during neurosis was related to enhanced proliferative activity and accelerated maturation of granulocyte-macrophage precursors resulting from increased formation of granulocytic and erythrogranulocytic hemopoietic islets. In poor learners primary suppression of the bone marrow granulocytopoiesis was associated with impaired formation of hemopoietic islets (conflict situation) and inhibition of differentiation of granulocyte-macrophage precursors (paradoxical sleep deprivation followed by T-maze learning). Then, recovered ability of bone marrow cells to form granulocyte complexes even against the background of inhibition of precursor differentiation (conflict situation) and accelerated maturation of granulocytic cells (paradoxical sleep deprivation and maze learning) lead to hyperplasia of the granulocytic hemopoietic stem.

Immunity parameters in mice of different strains.

Quantitative composition and functional activity of immunocompetent cells differ in mice of different strains. The counts of T cells in the bone marrow and spleen, proliferative activity of T cells in the spleen, levels of IL-2 and IL-10 production by splenic T cells, number of antigen-specific T cells and their functional activity are low in C57Bl/6, BALB/c, and CC57W mice and high in CBA/CaLac, DBA/2, and C3H animals. Low phagocytic activity of peritoneal macrophages was detected in BALB/c and CC57W mice and high activity in C3H animals. The content of antibody-producing cells in the spleens of C57Bl/6, BALB/c, and CC57W mice is higher than in CBA/CaLac, DBA/2, C3H, A/SN, and AKR/JY mice. Functional activity of B cells is lower in BALB/c and CC57W compared to CBA/CaLac and DBA/2 mice.

Role of adrenergic mechanisms of erythropoiesis regulation during severe hypoxia.

We studied the role of beta-adrenergic mechanisms of regulation of erythropoiesis in the formation of the erythron system reaction during severe hypoxia. Blockade of beta-adrenoceptors after the incidence of hypoxic encephalopathy of different genesis was followed by an increase in the number of committed precursors in the bone marrow, hyperplasia of the erythroid hemopoietic stem, and rise in the count of peripheral blood erythrocytes. These changes were accompanied by decreased formation of abnormal erythrocytes.

Role of Thy 1,2+ cells in the regulation of hemopoiesis during experimental neuroses.

We studied the direct and stromal cell-mediated effects of bone marrow Thy 1,2+ cells on the growth of granulocyte-macrophage and erythroid colonies from the bone marrow of CBA/CaLac mice with experimental neuroses (conflict situation and paradoxical sleep deprivation). Proliferation and differentiation of hemopoietic precursors during neuroses are controlled by regulatory T cells. In conflict situation Thy 1,2+ cells stimulate the growth of hemopoietic precursors, which is associated with their direct effect and interaction with adherent cells of the hemopoiesis-inducing microenvironment. The interaction of Thy 1,2+ cells with adherent bone marrow cells during paradoxical sleep deprivation stimulates the formation of only granulocyte-macrophage colonies.

Humoral mechanisms of regulation of erythropoiesis during hypoxia.

We studied the dynamics of erythropoietin content and erythropoietic activity of the serum during hypoxia of different genesis and severity. Our results show that humoral factors play an important role in the regulation of erythropoiesis during oxygen deficiency. Serum erythropoietic activity underwent similar changes in different types of hypoxia associated with similar hematological shifts. A discrepancy was observed between erythropoietic activity and serum erythropoietin concentration.

Changes in granulocytic hemopoietic stem and their mechanisms during hypoxia of different genesis.

We studied reactions of the granulocytic hemopoietic stem during hypoxia of different genesis and severity. Stimulation of granulocytopoiesis was determined by an increase in functional activity of granulomonocytic precursors due to changes in feeder capacity of cells in the hemopoiesis-inducing microenvironment and colony-stimulating activity of the plasma. The development of encephalopathy caused by oxygen deficiency was accompanied by a decrease in the number of bone marrow granulomonocytic precursors due to reduction of proliferative activity (despite the increase in secretory activity of microenvironmental cells and increase in plasma colony-stimulating activity). Severe hypoxia accelerated maturation of hemopoietic cells and produced neutrophilic leukocytosis.

Effect of granulocyte colony-stimulating factor on myocardium recovery in postinfarction period.

The effect of Neutrostim (preparation of granulocytic colony-stimulating factor) on recovery of myocardial tissue after acute myocardial infarction was studied in rats. A course of Neutrostim after ligation of the left coronary artery led to normalization of electrocardiographic and morphological parameters of the myocardium after one month.

Mechanisms of psychopharmacological effects of granulocytic colony-stimulating factor during severe hypoxia.

Granulocytic colony-stimulating factor produced a strong therapeutic effect during encephalopathy of different genesis. The preparation improved the psychoneurological status and increased the number of neural precursors in the paraventricular area of cerebral hemispheres in animals.

A method for cellular stimulation of thyroid transplant for correction of thyroid system function.

The efficiency of autotransplantation of the thyroid tissue into the greater omentum was demonstrated in experiments on rats. High viability of the transplant and restoration of the hormonal thyroid activity were attained after a single injection of the cell suspension of autologous adherent bone marrow cells directly into the transplant.