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A M Dygai,
G N Zyuz'kov,
V V Zhdanov,
E V Udut,
L A Miroshnichenko,
E V Simanina,
R V Gurto,
M Ju Minakova,
A V Chaikovsky,
T S Markova,
L A Stavrova,
A V Artamonov,
A A Bekarev,
P G Madonov,
D N Kinsht
[show abstract]
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ABSTRACT: Pegylated hyaluronate-endo-β-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.
Bulletin of Experimental Biology and Medicine 03/2013; 154(6):750-4. · 0.27 Impact Factor
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ABSTRACT: Phospholipid hepatoprotectors essentiale, eplir, and their combinations with succinic acid decreased the relative content of apoptotic lymphocytes and granulocytes in the blood, content of TNF-α, total and indirect bilirubin, and activities of transaminases and alkaline phosphatase and increase the content of IL-10 in rats with experimental intoxication induced by isoniazid and paracetamol. A combination of eplir and succinic acid was most effective in preventing the development of leukocyte apoptosis.
Bulletin of Experimental Biology and Medicine 02/2013; 154(5):614-7. · 0.27 Impact Factor
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[show abstract]
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ABSTRACT: The effects of nanotechnology (electron-beam) -PEGylated (or immobilized; Im) hyaluronidase (HD) on the state of the pool of bone marrow progenitor cells and their mobilization induced by granulocyte colony stimulating factor (G-CSF) were studied. A high specific activity of the drug Im-HD on progenitor cells of different classes was demonstrated using parenteral and enteral administration. An increase in the content of erythroid (E), granulomonocytic (GM), fibroblast (F) colony-forming units (CFU) and mesenchymal stem cells (MSC) in bone marrow was shown, as well as G-CSF-induced stimulation of mobilization of precursors into the peripheral blood under the influence of Im-HD. The detected activity of this novel drug on progenitor cells indicates the potential for a safe and highly effective treatment for hematology practice and regenerative medicine.
Stem cell reviews 01/2013; · 5.08 Impact Factor
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E G Skurikhin,
E S Khmelevskaya,
O V Pershina,
N N Ermakova,
V A Krupin,
A M Reztsova,
L A Ermolaeva,
V D Yakushina,
I E Stepanova,
V M Reztsova,
N V Cherdyntseva,
M N Stakheeva, A M Dygai
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ABSTRACT: We studied differentiation of multipotent mesenchymal stromal cells (MMSC) of the lungs of C57Bl/6 mice with bleomycin-induced pneumofibrosis. Adherent mononuclear cells found in mouse lungs demonstrated mesenchymal phenotype and expressed CD44, CD73, CD90, and CD106, but not CD31, CD34, and CD45. The cells with MMSC characteristics differentiate in vitro into various cells of stromal lines (chondrocytes, osteogenic cells, adipocytes, and fibroblasts). Bleomycin increased the growth rate of MMSC and selectively promoted their differentiation towards fibroblast cells.
Bulletin of Experimental Biology and Medicine 01/2013; 154(4):537-43. · 0.27 Impact Factor
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A M Dygai,
G N Zyuz'kov,
R V Gurto,
V V Zhdanov,
E V Udut,
L A Miroshnichenko,
A V Chaikovskiy,
T S Markova,
E V Simanina,
L A Stavrova,
M Yu Minakova,
V I Agafonov
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ABSTRACT: We studied the secretory function of the liver and bone marrow microenvironment cells under conditions of chronic CCl4-induced hepatitis. Enhanced production of substances stimulating parenchymal tissue-specific precursors and stem cell homing factors by liver cells was observed. In situ binding of stem cells by bone marrow elements increased due to production of various cooperation and adhesion factors against the background of reduced SDF-1 secretion.
Bulletin of Experimental Biology and Medicine 12/2012; 154(3):303-305. · 0.27 Impact Factor
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A M Dygai,
E G Skurikhin,
N N Ermakova,
O V Pershina,
V A Krupin,
A M Reztsova,
L A Ermolaeva,
E S Khmelevskaya,
I E Stepanova,
A V Artamonov,
A A Bekarev,
P G Madonov,
D N Kinsht,
V E Goldberg,
T A Semiglazova
[show abstract]
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ABSTRACT: 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.
Bulletin of Experimental Biology and Medicine 12/2012; 154(3):329-333. · 0.27 Impact Factor
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A M Dygai,
E G Skurikhin,
N N Ermakova,
O V Pershina,
V A Krupin,
A M Reztsova,
L A Ermolaeva,
E S Khmelevskaya,
A V Artamonov,
A A Bekarev,
P G Madonov,
D N Kinsht
[show abstract]
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ABSTRACT: 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.
Bulletin of Experimental Biology and Medicine 12/2012; 154(3):388-392. · 0.27 Impact Factor
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A M Dygai,
G N Zyuz'kov,
R V Gurto,
V V Zhdanov,
E V Udut,
L A Miroshnichenko,
E V Simanina,
L A Stavrova,
A V Chaikovskii,
T S Markova,
M Yu Minakova,
A V Artamonov,
A A Bekarev,
P G Madonov,
D N Kinsht
[show abstract]
[hide abstract]
ABSTRACT: We studied the effect of mobilization of bone marrow multipotent stem cells induced by intragastric administration of pegylated hyaluronate-endo-β-N-acetylhexosaminidase (Peg-HEAHA) on hemopoiesis under conditions of experimental chronic hepatitis. Peg-HEAHA increased the counts of hemopoietic precursors in the hemopoietic tissue against the background of their decelerated maturation. This was paralleled by a short-term decrease in the count of neutrophilic granulocyte in the bone marrow and a slight increase of neutrophil count in the peripheral blood.
Bulletin of Experimental Biology and Medicine 11/2012; 154(2):278-282. · 0.27 Impact Factor
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G N Zyuz'kov,
A V Krapivin,
Yu V Nesterova,
T N Povetieva,
V V Zhdanov,
N I Suslov,
T I Fomina,
E V Udut,
L A Miroshnichenko,
E V Simanina,
A A Semenov,
S S Kravtsova, A M Dygai
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ABSTRACT: Regeneratory activities of Baikal aconite alkaloids were studied on the excision skin wound model. Manifest wound healing effects of songorine, napelline, and hypaconitine were detected. The therapeutic efficiency was based on activation of residual mesenchymal progenitor elements. The development of this phenomenon was explained by the direct effects of alkaloids on precursors and by higher production of growth factors by the skin stromal cells. Songorine exhibited the most pronounced specific activity due to more significant stimulation of progenitor cell differentiation associated with maximum activation of the secretory function of the microenvironment cells.
Bulletin of Experimental Biology and Medicine 10/2012; 153(6):846-50. · 0.27 Impact Factor
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ABSTRACT: 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). The antifibrotic effect of reserpine was due to a decrease in the number of committed precursors for mesenchymopoiesis.
Bulletin of Experimental Biology and Medicine 09/2012; 153(5):638-43. · 0.27 Impact Factor
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A M Dygai,
G N Zyuz'kov,
V V Zhdanov,
E V Udut,
R V Gurto,
L A Miroshnichenko,
E V Simanina,
T Iu Khrichkova,
L A Stavrova,
A V Chaikovsky,
A V Artamonov,
A A Bekarev,
P G Madonov,
M Iu Minakova,
T S Markova
[show abstract]
[hide abstract]
ABSTRACT: Pegylated hyaluronate-endo-β-N-acetylhexosaminidase considerably potentiates the hemostimulating effects of erythropoietin due to intensification of proliferation and differentiation of erythroid precursors against the background of enhanced secretion of hemopoietins by nonadherent hemopoiesis-inducing environment cells and elevation of serum erythropoietin concentration. The use of the enzyme allows 10-fold reduction of the maximum effective erythropoietin dose.
Bulletin of Experimental Biology and Medicine 09/2012; 153(5):684-8. · 0.27 Impact Factor
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A M Dygai,
G N Zyuz'kov,
A A Churin,
V V Zhdanov,
A V Artamonov,
A A Bekarev,
P G Madonov,
D N Kinsht,
T I Fomina,
T V Vetoshkina,
T Yu Dubskaia,
L A Ermolaeva,
E V Udut,
L A Miroshnichenko,
E V Simanina,
L A Stavrova,
A V Chaikovskiy,
T S Markova,
M Yu Minakova,
D V Reihart
[show abstract]
[hide abstract]
ABSTRACT: Pharmacological characteristics of somatotropin pegylated using electron-beam synthesis nanotechnology (PEG-STH) were studied. Oral PEG-STH stimulated the intensity of protein and lipid metabolism and endochondral bone growth without modifying the processes of periosteal and endosteal bone formation. Specific activity of this substance administered orally significantly surpassed that of parenteral non-modified growth hormone.
Bulletin of Experimental Biology and Medicine 06/2012; 153(2):263-5. · 0.27 Impact Factor
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A M Dygai,
G N Zyuz'kov,
V V Zhdanov,
E V Udut,
L A Miroshnichenko,
T J Khrichkova,
E V Simanina,
L A Stavrova,
R V Gurto,
M Yu Minakova,
A V Chajkovskij,
T S Markova,
A V Artamonov,
A A Bekarev,
P G Madonov,
D N Kinsht
[show abstract]
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ABSTRACT: Hypoglycemic effect of hyaluronate-endo-β-N-acetylhexosaminidase immobilized by electron-beam synthesis nanotechnology (imHEA-HA) was studied in experimental insulin-dependent and insulin-independent diabetes mellitus. The drug exhibited a hypoglycemic effect of its own and potentiated the pharmacological effect of exogenous insulin injected in vivo. Studies on liver cell culture demonstrated an increase of cell sensitivity to insulin after treatment with imHEA-HA.
Bulletin of Experimental Biology and Medicine 05/2012; 153(1):94-7. · 0.27 Impact Factor
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A M Dygai,
V V Zhdanov,
G N Zyuzkov,
L A Stavrova,
L A Miroshnichenko,
E V Udut,
T Yu Khrichkova,
E V Simanina,
A V Artamonov,
A A Bekarev,
P G Madonov,
D N Kinsht,
R V Gurto,
A V Chaikovskiy,
T S Markova,
T I Fomina,
L A Ermolaeva,
T V Vetoshkina,
T Yu Dubskaya
[show abstract]
[hide abstract]
ABSTRACT: High hepatoprotective activity of granulocytic CSF and hyaluronidase immobilized using electron-beam immobilization technology was demonstrated on the model of CCl(4)-induced hepatitis: the preparations produced anticholestatic, anti-inflammatory, and antisclerotic effects. These effects developed against the background of stimulation of bone marrow multipotent precursor cells and their mobilization into circulation accompanied by an increase in the content of parenchymatous progenitor cells in the liver. The most pronounced positive effect was observed in combined treatment with the test preparations.
Bulletin of Experimental Biology and Medicine 05/2012; 153(1):129-33. · 0.27 Impact Factor
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A. M. Dygai,
G. N. Zyuz’kov,
V. V. Zhdanov,
A. V. Artamonov,
A. A. Bekarev,
P. G. Madonov,
D. N. Kinsht,
E. V. Udut,
L. A. Miroshnichenko,
T. Yu. Khrichkova,
E. V. Simanina,
L. A. Stavrova,
A. V. Chaikovskiy,
T. S. Markova,
M. Yu. Minakova
[show abstract]
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ABSTRACT: 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.
Key Wordserythropoiesis–immobilized erythropoietin–nanotechnologies–cytostatic-induced myelosuppression
Bulletin of Experimental Biology and Medicine 04/2012; 151(2):243-246. · 0.27 Impact Factor
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A. M. Dygai,
V. V. Zhdanov,
G. N. Zyuz’kov,
E. V. Udut,
T. Yu. Khrichkova,
E. V. Simanina,
L. A. Stavrova,
L. A. Miroshnichenko,
A. V. Chaikovskii,
T. S. Markova,
R. V. Gurto,
A. V. Artamonov,
A. A. Bekarev,
P. G. Madonov
[show abstract]
[hide abstract]
ABSTRACT: We evaluated whether immobilized hyaluronidase can modify the hematotropic effect of immobilized granulocyte CSF (G-CSF).
The preparation of immobilized hyaluronidase (50 arb. units per mouse) potentiated the specific effect of immobilized G-CSF
on granulomonocytopoiesis. The preparation was shown to facilitate the indirect effect of immobilized G-CSF on hemopoiesis
(stimulation of the erythroid and lymphoid hemopoietic stems). These changes were accompanied by an increase in functional
activity of hemopoietic precursor cells, secretion of humoral factors by bone marrow myelokaryocytes, and concentration of
hemopoietins in the serum.
Key Wordshemopoiesis–immobilized granulocyte colony-stimulating factor–immobilized hyaluronidase
Bulletin of Experimental Biology and Medicine 04/2012; 151(3):324-329. · 0.27 Impact Factor
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A. M. Dygai,
V. V. Zhdanov,
G. N. Zyuz’kov,
L. A. Stavrova,
E. V. Simanina,
E. V. Udut,
T. Yu. Khrichkova,
L. A. Miroshnichenko,
E. I. Vereshchagin,
P. G. Madonov,
D. N. Kinsht,
T. I. Fomina,
T. V. Vetoshkina,
T. Yu. Dubskaya,
L. A. Ermolaeva
[show abstract]
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ABSTRACT: The effect of immobilized granulocyte CSF on morphological characteristics and functional state of the liver was studied during
chronic toxic hepatitis. The mechanisms of the therapeutic action of this agent were evaluated. The product had a strong hepatoprotective
effect and exhibited the antiinflammatory and antisclerotic properties. The mechanism of activation of reserve systems for
cell renewal (involved in restoration of the liver tissue) is probably related to an increase in proliferative activity of
early precursor cells in the bone marrow, mobilization of these cells into the peripheral circulation, and directed homing
into the liver tissue where they activate local regenerative mechanisms and prevent hepatocyte destruction. It should be emphasized
that the concentration of SDF-1 increases in the liver tissue, but decreases in the bone marrow. These changes create the
concentration gradient, which determines the migration of undifferentiated precursor cells to the liver.
Keywordschronic hepatitis–granulocyte colony-stimulating factor–cell therapy
Bulletin of Experimental Biology and Medicine 04/2012; 150(4):401-405. · 0.27 Impact Factor
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N. N. Ermakova,
V. V. Zhdanov, A. M. Dygai,
G. N. Zyuz’kov,
L. A. Stavrova,
L. A. Gur’yantseva,
T. Yu. Khrichkova,
E. V. Udut,
T. V. Vetoshkina,
T. I. Fomina,
L. A. Ermolaeva,
E. D. Goldberg
[show abstract]
[hide abstract]
ABSTRACT: 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 antiinfl ammatory and antisclerotic effects associated with activation of stem cells and their determined homing
into the pancreas.
Bulletin of Experimental Biology and Medicine 04/2012; 148(3):549-552. · 0.27 Impact Factor
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A. M. Dygai,
E. I. Vereshchagin,
G. N. Zyuz’kov,
V. V. Zhdanov,
P. G. Madonov,
E. V. Simanina,
L. A. Stavrova,
E. V. Udut,
T. Yu. Khrichkova,
L. A. Miroshnichenko,
M. Yu. Minakova,
N. N. Ermakova,
T. V. Firsova
[show abstract]
[hide abstract]
ABSTRACT: The effects of granulocytic CSF immobilized on polyethylenoxide by nanotechnology on the bone marrow and circulating pools
of mesenchymal and hemopoietic precursors were studied. Immobilized granulocytic CSF caused the release of progenitor cells
of different classes into the blood. The effect of injected immobilized granulocytic CSF was superior to that of nonconjugated
granulocytic CSF. Specific activity of oral immobilized granulocytic CSF after oral administration was demonstrated.
Bulletin of Experimental Biology and Medicine 04/2012; 147(4):499-502. · 0.27 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: 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. A higher therapeutic efficiency of cell material obtained after combined use
of granulocytic CSF and hyaluronidase was shown.
Bulletin of Experimental Biology and Medicine 04/2012; 148(1):120-125. · 0.27 Impact Factor
