Role of Endogenous Agonists of Opioid Receptors in the Regulation of Heart Resistance to Postischemic Reperfusion Injury.

Intravenous injection of nonselective antagonists of opioid receptors (OR) naltrexone (5 mg/kg) and naloxone methiodide (5 mg/kg), selective δ-OR antagonist BNTX (0.7 mg/kg), selective δ-OR blocker naltriben (0.3 mg/kg), selective κ-OR antagonist norbinaltorphimine (2 mg/kg), and selective blocker of ORL1 opioid receptors JTC-801 (0.

Mechanisms of the anti-inflammatory and antifibrotic activity of a sympatholytic agent during toxic pulmonary fibrosis.

The effect of a course treatment with a sympatholytic reserpine on the inflammatory response and connective tissue proliferation in the lungs of C57Bl/6 mice was studied on the model of toxic pulmonary fibrosis induced by intratracheal administration of bleomycin. This sympatholytic reduced infiltration of the alveolar interstitium and alveolar ducts with inflammatory cells (lymphocytes, macrophages, neutrophils, and plasma cells) and prevented connective tissue proliferation in the lungs. The anti-inflammatory effect of reserpine was associated with a decrease in activity of bone marrow granulocyte-erythroid-macrophage-megakaryocyte and granulocyte precursors (proliferation and mobilization).

Development of an experimental model of cardiac failure combined with type I diabetes mellitus.

The doses and mode of streptozotocin injection for modeling heart failure combined with type 1 diabetes mellitus have been determined. Combined disease was induced in animals by injecting the selected streptozotocin dose (60 mg/kg intraperitoneally) at the stage of heart failure formation (2 weeks after coronary occlusion). This protocol of experiment led to development of hyperglycemia, body weight loss, and formation of myocardial cicatrix and hypertrophy corresponding to signs of heart failure paralleled by diabetes mellitus.

Reactions of the blood system and stem cells in bleomycin-induced model of lung fibrosis.

On the model of toxic diffuse pulmonary fibrosis induced by intratracheal administration of bleomycin, we studied reactions of the blood system, content of stem cells, committed hemopoietic and stromal progenitor cells in the bone marrow, spleen and peripheral blood of C57Bl/6 mice. It was shown that the development of diffuse pulmonary fibrosis was accompanied by hyperplasia of bone marrow hemopoiesis and leukocytosis in the peripheral blood. Activation of the erythroid and granulocytic hemopoietic stems was related to stimulation of hemopoietic stem cells (polypotent cells, granulocyte/erythroid/macrophage/megakaryocyte precursor cells) and committed erythroid and myeloid progenitor cells in the bone marrow.

Comparative experimental evaluation of the efficacy of Prostamol Uno and Samprost on rat model of chronic aseptic prostate inflammation.

Comparative experimental evaluation of the efficiency of prostatotropic drugs Prostamol Uno and Samprost on the model of the chronic aseptic prostate inflammation in rats was performed. It was established that peptide drug Samprost decelerates sclerotic processes in the prostate gland to a greater extent than herbal preparation Prostamol Uno. Both products equally stimulate secretory activity of the gland.

Effect of non-starch polysaccharide calcium pectate on the growth and colonization of normal and pathogenic microflora in vitro.

In vitro experiments showed that calcium pectate added to the culture medium produces a dose-dependent prebiotic effect on lacto-and bifidobacteria cultures and on non-pathogenic strain of Escherichia coli. Calcium pectate produced a pronounced bacteriostatic effect on Candida albicans strain; the effects was more pronounced in a concentration of 4%.

Reactions of granulocytic lineage of hemopoiesis and mechanisms of their development in combined treatment with adriablastin and taxotere.

We studied myelotoxic effects of adriablastin and taxotere combination on granulocytic lineage cells and processes of their recovery in patients with stage III-IV breast cancer. Intensive maturation of granulocytic CFU provided regeneration of the hemopoiesis even under conditions of reduced proliferative activity of these cells, which, in turn, led to accumulation of mature and immature neutrophilic granulocytes in the bone marrow and improved reserve capacities of the neutrophil pool in the bone marrow.

Mechanisms of hemostimulating effects of granulocytic CSF and pantohematogen under conditions of cytostatic myelosuppression.

We compared hemostimulating activity of pantohematogen and granulocytic CSF under conditions of 5-fluorouracil-induced cytostatic myelosuppression. It was found that activation of hemopoiesis regeneration under the effect of the test preparations was accompanied by the development of hyperplasia of the granulocytic and monocytic hemopoietic bone marrow lineages and more rapid recovery of the count of pholymorphonuclear leukocytes and monocytes in the peripheral blood (more marked under the effect of pantohematogen) followed by neutrophilia and monocytosis.

Lipid peroxidation during cardiac remodeling in 12-month-old rats with experimental infarction.

Blood serum was from 12-month-old Wistar rats with experimental myocardial infarction caused by occlusion of the upper third of the left coronary artery was analyzed. The content of conjugated dienes by the 45th day after primary experimental myocardial infarction returned to normal and did not differ from that in intact animals of the same age group. MDA concentration in rats of the treatment group was lower compared to normal.

Manifestation of adaptive changes during combined development of postinfarction remodeling of the heart and diabetes mellitus.

Oxidative phosphorylation in isolated cardiomyocytes was studied under conditions of postinfarction remodeling and diabetes mellitus. Oxidation-phosphorylation uncoupling in the mitochondria in this disease combination was less pronounced than in each of these diseases alone. Combined development of the diseases was paralleled by less severe hyperglycemia and myocardial hypertrophy and lesser body weight loss.

Hemorheological effects of ortho-isobornyl phenol derivative under conditions of brain ischemia in rats.

Hemorheological activity of 4-methyl-2,6-di-isobornyl phenol, a new o-isobornyl phenol derivative, was studied under conditions of experimental prolonged partial cerebral ischemia. Brain ischemia is associated with hemorheological disorders which can be characterized as blood hyperviscosity syndrome: increased viscosity of the whole blood (within a wide range of shear rates), plasma viscosity, fibrinogen content in blood plasma, and platelet aggregation; deterioration of platelet deformability and reduced availability of oxygen for tissues. A course (5 days) of intragastric 4-methyl-2,6-di-isobornyl phenol (100 mg/kg) prevented the development of blood hyperviscosity syndrome by modulating blood macrorheology (reduction of plasma viscosity and fibrinogen content) and microrheology (reduction of erythrocyte aggregation and improvement of their deformability).

Evaluation of the efficacy of granulocyte colony-stimulating factor for the treatment of experimental myocardial destruction in mice.

We studied the effects of recombinant granulocytic CSF on heart remodeling in BALB/c mice after cryodestruction. Administration of granulocytic CSF was started 1 day after cryodestruction (subcutaneously, 10 μg/kg/day, for 4 days). As early as after the first injection, leukocytosis in the peripheral blood started to develop, leukocyte count peaked on days 4-6 and returned to normal on day 14.

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.

Role of mesenchymal precursor cells in the stimulation of wound healing under the effect of ultralow doses of antibodies to granulocytic colony-stimulating factor.

On the model of skin flap we studied the possibility of stimulating the processes of wound healing with a preparation containing ultralow doses of antibodies to granulocytic colony-stimulating factor. The preparation accelerated tissue regeneration against the background of mobilization of bone marrow mesenchymal precursor cells into circulation accompanied by an increase in the number of stromal precursor cells in the area of lesion.

Mechanisms underlying the effects of ultralow doses of antibodies to granulocytic colony-stimulating factor on recovery of damaged pancreatic tissue in experimental diabetes mellitus.

Using the model of alloxan-induced diabetes mellitus on rats we demonstrated the effect of ultralow doses of antibodies to granulocytic colony-stimulating factor on recovery of the pancreas and normalization of blood glucose concentration. The preparation produced an antiinflammatory and antisclerotic effects associated with activation of stem cells and their determined homing into the pancreas.

Preclinical study of proproten-100 for mutagenicity.

Experiments on CBA/CaLac mice showed that single and course administration of proproten-100 did not increase the percent of abnormal metaphases in red bone marrow cells and produced no genotoxic effects in Drosophila melanogaster wing cells in the test of somatic mosaicism.

Preclinical studied of general toxic properties of preparations containing ultralow doses of antibodies to endogenous regulators.

Preclinical study of the safety of 6 preparations containing ultralow doses of antibodies to endogenous regulators showed that they are relatively safe, are well tolerated by animals in doses more than 1000-fold surpassing the therapeutic dose for humans, and produce no general toxic effect on the organism of laboratory animals.

Effect of ultralow doses of antibodies to histamine on the development of chronic ulcerative process in the stomach of experimental animals.

Antiulcer activity of ultralow doses of antibodies to histamine was demonstrated on the model of chronic acetate-induced gastric ulcer in rats. Course therapy with the preparation accelerated healing of chronic experimental ulcer by correcting hemodynamic disturbances and stimulating mucus formation in the gastric wall.

Influence of poetam preparation on the state of autonomic nervous system in patients with severe anemia caused by dysfunctional uterine bleedings.

The use of poetam in the treatment of anemia in patients with dysfunctional uterine bleedings promotes recovery of the major parameters of the tone and reactivity of the autonomic nervous system.

Complex application of preparation containing ultralow doses of antibodies for the treatment of anemia caused by pubertal uterine bleedings.

Poetam and anaferon (pediatric formulation) administered in combination with iron preparation to patients with anemia induce pronounced positive shifts in metabolic and morphological status of mature erythrocytes: the number of sulfhydryl groups and lipoprotein complexes in cell membranes and dry weight of erythrocytes increased, while the number of forms at different stages of degeneration decreased.

Rhythmoinotropic myocardial reactions in rats with postinfarction cardiosclerosis against the background of streptozotocin-induced diabetes.

We studied rhythmoinotropic reactions of the myocardium in rats with postinfarction cardiosclerosis and in rats with postinfarction cardiosclerosis against the background of streptozotocin-induced diabetes. Inotropic myocardial response in rats with postinfarction cardiosclerosis was significantly inhibited after rest periods, while in streptozotocin diabetic rats the rhythmoinotropic myocardial reaction was comparable with the reaction of intact myocardium. The combination of postinfarction cardiosclerosis and diabetes paradoxically contributed to preservation of contractile function of the myocardium in rats.

Effect of granulocytic colony-stimulating factor on cytostatic-suppressed granulocytopoiesis under conditions of exhausted catecholamine depot.

Exhaustion of catecholamine depot in the CNS before modeling of cytostatic myelosuppression potentiates the stimulatory effect of granulocytic CSF on regeneration of the granulocytic hemopoiesis stem. The increase in granulocyte count in the blood system under these conditions is caused by recovery of the structural and functional organization of the hemopoietic tissue (at the expense of reduction of the suppressive effect of catecholamines on the formation of granulocytic hemopoietic islets) and simultaneous stimulation of division and maturation of granulomonocytic precursors.

Effect of transplantation of peripheral blood mononuclears obtained using granulocytic colony-stimulating factor and hyaluronidase on regeneration of hemopoietic tissue during myelosuppression.

The mechanisms of hemopoiesis recovery after transplantation of peripheral blood mononuclears obtained using granulocytic CSF and granulocytic CSF in combination with hyaluronidase were studied on the model of cytostatic myelosuppression. It was found that regeneration of the hemopoietic tissue resulted from an increase in the pool of erythroid and granulomonocytic precursors and in their functional activity. The increase in the count of fibroblast precursors in the bone marrow, higher production of hemopoietins by adherent myelokaryocytes, and an increase in the level of humoral factors in the serum were detected after injection of the transplants.

Mechanisms of granulocytopoiesis-stimulating activity of immobilized granulocytic colony-stimulating factor in cytostatic myelosuppression.

The hemostimulatory effects of granulocytic CSF, immobilized on polyethyleneglycol using radiation synthesis nanotechnology, were studied on the model of cyclophosphamide-induced myelosuppression. Immobilization of granulocytic CSF led to stimulation of granulomonocytopoiesis by increasing functional activity of granulomonocytic precursors and secretion of humoral factors by elements of hemopoiesis-inducing microenvironment, and due to more intensive formation of hemopoietic islets. The granulocytopoiesis-stimulating effect of immobilized granulocytic CSF was comparable to the effect of standard nonconjugated granulocytic CSF.

Potentiation of the stimulatory effect of erythropoietin on erythropoiesis by antiserotonin drug during cytostatic myelosuppression.

Combined stimulatory effect of antiserotonin drug and erythropoietin on the bone marrow erythropoiesis was studied under conditions of cytostatic myelosuppression. The stimulatory effect of erythropoietin on regeneration of the hemopoietic erythroid stem increased, if serotonin mediation in the CNS was disordered before induction of cytostatic myelosuppression. The stimulatory effect of a combination of cyproheptadine and epocrine (experimental group) significantly surpassed that of cyproheptadine and epocrine monotherapies.