22 research outputs found
Immunomodulatory properties of recombinant human granulocyte-macrophage colony-stimulating factor
Granulocyte-macrophage colony stimulating factor (GM-CSF) is a myelopoietic growth factor that exerts pleiotropic effect not only on the differentiation of immature progenitor cells into polymorphonuclear neutrophils, monocytes/macrophages and dendritic cells, but also controls the functioning of differentiated cells. GM-CSF is currently being investigated in clinical trials as an immunomodulator and adjuvant. However, a wide range of biological activities and, sometimes, paradoxical effects of this cytokine require more thorough studies of its action, in order to predict its efficacy under different conditions of immunotherapy. In this work, we have studied the effect of recombinant human GM-CSF on metabolic activity of mouse peritoneal exudate cells in primary cell cultures. Metabolic (redox) activity of the cells was assessed by their ability to reduce nitroblue tetrazolium (NBT) in the course of MF- and Fc-dependent phagocytosis triggered by addition of opsonized zymosan, or sheep erythrocytes to the culture medium. We have shown the dose-dependent stimulatory effect of GM-CSF on the oxidative metabolism of phagocytic peritoneal macrophages and neutrophils. Upon culturing the pepton-elicited cells at wide range of GM-CSF concentrations (5 to 40,000 ng/mL) for 2 and 24 hours, a more pronounced effect of the substance was observed for neutrophils. The GM-CSF preparation caused a significant increase (by 13-17%) in the redox activity of neutrophils induced by opsonized zymosan that persisted at a low dose range, and was retained after 24 hours. The stimulatory effect of GM-CSF on macrophages with NBT index increase by 16% was observed in the short-term cultures. In general, the elicited cells of both types showed a more pronounced response to lower concentrations of GM-CSF (5-125 ng/mL), and weaker effect at higher doses of the preparation. A similar dependence was found when studying the resident macrophages. Culturing of resident cells with GM-CSF at the doses of 5,000 to 40,000 ng/mL for 24 hours caused a significantly increased redox activity of the cells induced by zymosan, or sheep erythrocytes (by 33-52%). In both cases, the maximal response was detected at a dose of 5,000 ng/mL and decreased with increasing dose. The stimulatory effect of GM-CSF upon resident macrophages was more pronounced as compared to elicited cells, which was characterized by the prolonged period of cell activation (up to 24 hours of culture). The data obtained are of interest, in view of prospective usage of GM-CSF as a component of immunomodulatory and adjuvant therapy for various infectious diseases
MEDICINAL FORM OF TNF-Ξ± FOR LOCAL ADMINISTRATION
Composite preparation of tumor necrosis factor alpha and rheopolyglukin and polyethylene glycol (TNF-Ξ±+PG+PEG) was obtained. The specific activity of the samples was 4,13 Ρ
107 IU/mg. The cytolytic activity of drugs TNF-Ξ±+PG+PEG and rhTNF-Ξ± did not change after 4 months when stored at 6 Β°Π‘. Preparation TNF-Ξ±+PG+PEG provided a moderately prolonged elevation of TNF-alpha in blood of laboratory mice in contrast to TNF-Ξ± when they applied to the skin. The composite preparation did not have toxic, allergic and locally irritating action in experiments on laboratory animals
ΠΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ ΡΠΎΡΠ½ΠΎΡΡΠΈ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½Π΅ΡΠ°ΡΠΈΠΈ ΡΠΎΡΠΎΡΠ»Π΅ΠΊΡΡΠΈΡΠ΅ΡΠΊΠΈΡ ΡΡΠ°Π½ΡΠΈΠΉ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ Π°Π»Π³ΠΎΡΠΈΡΠΌΠΎΠ² k-ΡΡΠ΅Π΄Π½ΠΈΡ ΠΈ k-Π±Π»ΠΈΠΆΠ°ΠΉΡΠΈΡ ΡΠΎΡΠ΅Π΄Π΅ΠΉ
Renewable energy sources (RES) are seen as a means of the fuel and energy complex carbon footprint reduction but the stochastic nature of generation complicates RES integration with electric power systems. Therefore, it is necessary to develop and improve methods for forecasting of the power plants generation using the energy of the sun, wind and water flows. One of the ways to improve the accuracy of forecast models is a deep analysis of meteorological conditions as the main factor affecting the power generation. In this paper, a method for adapting of forecast models to the meteorological conditions of photovoltaic stations operation based on machine learning algorithms was proposed and studied. In this case, unsupervised learning is first performed using the k-means method to form clusters. For this, it is also proposed to use studied the feature space dimensionality reduction algorithm to visualize and estimate the clustering accuracy. Then, for each cluster, its own machine learning model was trained for generation forecasting and the k-nearest neighbours algorithm was built to attribute the current conditions at the model operation stage to one of the formed clusters. The study was conducted on hourly meteorological data for the period from 1985 to 2021. A feature of the approach is the clustering of weather conditions on hourly rather than daily intervals. As a result, the mean absolute percentage error of forecasting is reduced significantly, depending on the prediction model used. For the best case, the error in forecasting of a photovoltaic plant generation an hour ahead was 9 %.ΠΠΎΠ·ΠΎΠ±Π½ΠΎΠ²Π»ΡΠ΅ΠΌΡΠ΅ ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΈ ΡΠ½Π΅ΡΠ³ΠΈΠΈ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡΡΡ ΠΊΠ°ΠΊ ΡΡΠ΅Π΄ΡΡΠ²ΠΎ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΡΠ³Π»Π΅ΡΠΎΠ΄Π½ΠΎΠ³ΠΎ ΡΠ»Π΅Π΄Π° ΡΠΎΠΏΠ»ΠΈΠ²Π½ΠΎ-ΡΠ½Π΅ΡΠ³Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ°, ΠΏΡΠΈ ΡΡΠΎΠΌ ΡΡΠΎΡ
Π°ΡΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅Ρ Π³Π΅Π½Π΅ΡΠ°ΡΠΈΠΈ ΠΎΡΠ»ΠΎΠΆΠ½ΡΠ΅Ρ ΠΈΡ
ΠΈΠ½ΡΠ΅Π³ΡΠ°ΡΠΈΡ Ρ ΡΠ»Π΅ΠΊΡΡΠΎΡΠ½Π΅ΡΠ³Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΠΈΡΡΠ΅ΠΌΠ°ΠΌΠΈ. ΠΡΠ° ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½Π°Ρ ΡΡΡΠ΄Π½ΠΎΡΡΡ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»ΠΈΠ²Π°Π΅Ρ Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΡ ΡΠΎΠ·Π΄Π°Π²Π°ΡΡ ΠΈ ΡΠΎΠ²Π΅ΡΡΠ΅Π½ΡΡΠ²ΠΎΠ²Π°ΡΡ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½Π΅ΡΠ°ΡΠΈΠΈ ΡΠ»Π΅ΠΊΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΡΠ°Π½ΡΠΈΠΉ, ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΡΡΠΈΡ
ΡΠ½Π΅ΡΠ³ΠΈΡ ΡΠΎΠ»Π½ΡΠ°, Π²Π΅ΡΡΠ° ΠΈ Π²ΠΎΠ΄Π½ΡΡ
ΠΏΠΎΡΠΎΠΊΠΎΠ². ΠΠ°ΠΈΠ±ΠΎΠ»Π΅Π΅ Π²Π°ΠΆΠ½ΡΠΌ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ΠΌ, ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ²Π°ΡΡΠΈΠΌ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ ΡΠΎΡΠ½ΠΎΡΡΠΈ ΠΏΡΠΎΠ³Π½ΠΎΠ·Π½ΡΡ
ΠΌΠΎΠ΄Π΅Π»Π΅ΠΉ, ΡΠ²Π»ΡΠ΅ΡΡΡ Π³Π»ΡΠ±ΠΎΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΌΠ΅ΡΠ΅ΠΎΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΡΠ»ΠΎΠ²ΠΈΠΉ ΠΊΠ°ΠΊ Π³Π»Π°Π²Π½ΠΎΠ³ΠΎ ΡΠ°ΠΊΡΠΎΡΠ°, Π²Π»ΠΈΡΡΡΠ΅Π³ΠΎ Π½Π° Π²ΡΡΠ°Π±ΠΎΡΠΊΡ ΡΠ»Π΅ΠΊΡΡΠΎΡΠ½Π΅ΡΠ³ΠΈΠΈ. Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½ ΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ ΠΌΠ΅ΡΠΎΠ΄ Π°Π΄Π°ΠΏΡΠ°ΡΠΈΠΈ ΠΏΡΠΎΠ³Π½ΠΎΠ·Π½ΡΡ
ΠΌΠΎΠ΄Π΅Π»Π΅ΠΉ ΠΏΠΎΠ΄ ΠΌΠ΅ΡΠ΅ΠΎΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΡΠ»ΠΎΠ²ΠΈΡ ΡΠ°Π±ΠΎΡΡ ΡΠΎΡΠΎΡΠ»Π΅ΠΊΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΡΠ°Π½ΡΠΈΠΉ Π½Π° Π±Π°Π·Π΅ Π°Π»Π³ΠΎΡΠΈΡΠΌΠΎΠ² ΠΌΠ°ΡΠΈΠ½Π½ΠΎΠ³ΠΎ ΠΎΠ±ΡΡΠ΅Π½ΠΈΡ. ΠΡΠΈΒ ΡΡΠΎΠΌ Π²Π½Π°ΡΠ°Π»Π΅ Π²ΡΠΏΠΎΠ»Π½ΡΠ΅ΡΡΡ ΠΎΠ±ΡΡΠ΅Π½ΠΈΠ΅ Π±Π΅Π· ΡΡΠΈΡΠ΅Π»Ρ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ k-ΡΡΠ΅Π΄Π½ΠΈΡ
Π΄Π»Ρ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΊΠ»Π°ΡΡΠ΅ΡΠΎΠ². ΠΠ»Ρ ΡΡΠΎΠΉ Π·Π°Π΄Π°ΡΠΈ ΡΠ°ΠΊΠΆΠ΅ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½ΠΎ ΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΎ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ Π°Π»Π³ΠΎΡΠΈΡΠΌΠ° ΠΏΠΎΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΡΠ°Π·ΠΌΠ΅ΡΠ½ΠΎΡΡΠΈ ΠΏΡΠΎΡΡΡΠ°Π½ΡΡΠ²Π° ΠΏΡΠΈΠ·Π½Π°ΠΊΠΎΠ² Π΄Π»Ρ Π²ΠΈΠ·ΡΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΠΎΡΠ½ΠΎΡΡΠΈ ΠΊΠ»Π°ΡΡΠ΅ΡΠΈΠ·Π°ΡΠΈΠΈ. ΠΠ°ΡΠ΅ΠΌ Π΄Π»Ρ ΠΊΠ°ΠΆΠ΄ΠΎΠ³ΠΎ ΠΊΠ»Π°ΡΡΠ΅ΡΠ° ΠΏΠΎΡΡΡΠΎΠ΅Π½Π° ΡΠ²ΠΎΡ ΠΌΠΎΠ΄Π΅Π»Ρ ΠΌΠ°ΡΠΈΠ½Π½ΠΎΠ³ΠΎ ΠΎΠ±ΡΡΠ΅Π½ΠΈΡ Π΄Π»Ρ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΎΠ² ΠΈΒ Π°Π»Π³ΠΎΡΠΈΡΠΌ k-Π±Π»ΠΈΠΆΠ°ΠΉΡΠΈΡ
ΡΠΎΡΠ΅Π΄Π΅ΠΉ Π΄Π»Ρ ΠΎΡΠ½Π΅ΡΠ΅Π½ΠΈΡ ΡΠ΅ΠΊΡΡΠΈΡ
ΡΡΠ»ΠΎΠ²ΠΈΠΉ Π½Π° ΡΡΠ°ΠΏΠ΅ ΡΠΊΡΠΏΠ»ΡΠ°ΡΠ°ΡΠΈΠΈ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΊ ΠΎΠ΄Π½ΠΎΠΌΡ ΠΈΠ· ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΊΠ»Π°ΡΡΠ΅ΡΠΎΠ². ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π±ΡΠ»ΠΎ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ Π½Π° ΠΏΠΎΡΠ°ΡΠΎΠ²ΡΡ
ΠΌΠ΅ΡΠ΅ΠΎΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π΄Π°Π½Π½ΡΡ
Π·Π° ΠΏΠ΅ΡΠΈΠΎΠ΄ Ρ 1985 ΠΏΠΎ 2021 Π³. ΠΠ΄Π½ΠΎΠΉ ΠΈΠ· ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ ΡΡΠΎΠ³ΠΎ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Π° ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΊΠ»Π°ΡΡΠ΅ΡΠΈΠ·Π°ΡΠΈΡ ΠΌΠ΅ΡΠ΅ΠΎΡΡΠ»ΠΎΠ²ΠΈΠΉ Π½Π° ΡΠ°ΡΠΎΠ²ΡΡ
, Π° Π½Π΅ ΡΡΡΠΎΡΠ½ΡΡ
ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»Π°Ρ
. ΠΒ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΡΠ΅Π΄Π½ΠΈΠΉ ΠΌΠΎΠ΄ΡΠ»Ρ ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΎΡΠΈΠ±ΠΊΠΈ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ ΡΠ½ΠΈΠΆΠ°Π΅ΡΡΡ Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡΒ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΡ. ΠΠ»Ρ Π½Π°ΠΈΠ»ΡΡΡΠ΅Π³ΠΎ Π²Π°ΡΠΈΠ°Π½ΡΠ° ΠΎΡΠΈΠ±ΠΊΠ° ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½Π΅ΡΠ°ΡΠΈΠΈ ΡΠΎΡΠΎΡΠ»Π΅ΠΊΡΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΡΠ°Π½ΡΠΈΠΈ Π½Π° ΡΠ°Ρ Π²ΠΏΠ΅ΡΠ΅Π΄ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 9Β %
Study on Hemostimulating Properties of Granulocyte-Macrophage Colony Stimulating Factor
The hemostimulating properties of granulocyte-macrophage colony-stimulating factor (GM-CSF) make possible its clinical use in alleviating side effects of anti-cancer radio- and chemotherapy, in bone marrow transplantation, and in the treatment of some primary immunodeficiency conditions associated with leukopenia. The State Research Center of Virology and Biotechnology βVectorβ of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing has developed a high-performance technology for production of recombinant human GM-CSF (rhGM-CSF) based on a recombinant E. coli strain. The aim of the study was to assess hemostimulating activity of the rhGM-CSF preparation obtained using the new developed technology, as observed in cell culture and in the mice model of myelosuppression induced by cyclophosphamide administration. Materials and methods: in vitro evaluation of rhGM-CSF hemostimulating activity was performed by MTT assay in the commercial HL-60 promyelocytic leukemia cell culture with preliminary suppression of cell growth rate by adding a low concentration of dimethyl sulfoxide to the medium. In vivo studies were carried out in CBA/CaLac mice with cyclophosphamide-induced myelosuppression. The hemostimulating properties of the drug were evaluated after subcutaneous administration of 1β175 Β΅g/kg doses for 4β5 days, following administration of a cytostatic agent. The total number of leukocytes and the content of their morphological forms were determined in blood samples taken at different time points after the drug administration. The statistical processing of the experimental data was based on analysis of variance using Statgraphics v. 5.0 software. Results: the proliferative activity of HL-60 cells incubated with the rhGM-CSF preparation for 72 hours was shown to be dose-dependent. The highest values of the increase in proliferative activity associated with an increase in the drug dose were observed in the concentration range from 0.04 to 0.64 ng/mL (proliferative activity increased by 11β18% when the dose was increased twofold). The experiments in mice demonstrated a two-phase pattern of the dose-dependent effect. The drug showed the highest hemostimulating effect at the dose of 90 Β΅g/kg. Conclusions: the rhGM-CSF preparation obtained using the new developed technology has a pronounced hemostimulating activity confirmed by both in vitro and in vivo test systems
ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅ΠΌΠΎΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠΈΡ ΡΠ²ΠΎΠΉΡΡΠ² ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΠΎΠ³ΠΎ Π³ΡΠ°Π½ΡΠ»ΠΎΡΠΈΡΠ°ΡΠ½ΠΎ-ΠΌΠ°ΠΊΡΠΎΡΠ°Π³Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠΎΠ»ΠΎΠ½ΠΈΠ΅ΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠ΅Π³ΠΎ ΡΠ°ΠΊΡΠΎΡΠ° ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°
The hemostimulating properties of granulocyte-macrophage colony-stimulating factor (GM-CSF) make possible its clinical use in alleviating side effects of anti-cancer radio- and chemotherapy, in bone marrow transplantation, and in the treatment of some primary immunodeficiency conditions associated with leukopenia. The State Research Center of Virology and Biotechnology βVectorβ of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing has developed a high-performance technology for production of recombinant human GM-CSF (rhGM-CSF) based on a recombinant E. coli strain. The aim of the study was to assess hemostimulating activity of the rhGM-CSF preparation obtained using the new developed technology, as observed in cell culture and in the mice model of myelosuppression induced by cyclophosphamide administration. Materials and methods: in vitro evaluation of rhGM-CSF hemostimulating activity was performed by MTT assay in the commercial HL-60 promyelocytic leukemia cell culture with preliminary suppression of cell growth rate by adding a low concentration of dimethyl sulfoxide to the medium. In vivo studies were carried out in CBA/CaLac mice with cyclophosphamide-induced myelosuppression. The hemostimulating properties of the drug were evaluated after subcutaneous administration of 1β175 Β΅g/kg doses for 4β5 days, following administration of a cytostatic agent. The total number of leukocytes and the content of their morphological forms were determined in blood samples taken at different time points after the drug administration. The statistical processing of the experimental data was based on analysis of variance using Statgraphics v. 5.0 software. Results: the proliferative activity of HL-60 cells incubated with the rhGM-CSF preparation for 72 hours was shown to be dose-dependent. The highest values of the increase in proliferative activity associated with an increase in the drug dose were observed in the concentration range from 0.04 to 0.64 ng/mL (proliferative activity increased by 11β18% when the dose was increased twofold). The experiments in mice demonstrated a two-phase pattern of the dose-dependent effect. The drug showed the highest hemostimulating effect at the dose of 90 Β΅g/kg. Conclusions: the rhGM-CSF preparation obtained using the new developed technology has a pronounced hemostimulating activity confirmed by both in vitro and in vivo test systems.Β ΠΠ΅ΠΌΠΎΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π° Π³ΡΠ°Π½ΡΠ»ΠΎΡΠΈΡΠ°ΡΠ½ΠΎ-ΠΌΠ°ΠΊΡΠΎΡΠ°Π³Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠΎΠ»ΠΎΠ½ΠΈΠ΅ΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠ΅Π³ΠΎ ΡΠ°ΠΊΡΠΎΡΠ° (ΠΠ-ΠΠ‘Π€) ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°ΡΡ Π΅Π³ΠΎ Π² ΠΊΠ»ΠΈΠ½ΠΈΠΊΠ΅ Π΄Π»Ρ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΠΏΠΎΠ±ΠΎΡΠ½ΡΡ
ΡΡΡΠ΅ΠΊΡΠΎΠ² ΡΠ°Π΄ΠΈΠΎ- ΠΈ Ρ
ΠΈΠΌΠΈΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, ΠΏΡΠΈ ΡΡΠ°Π½ΡΠΏΠ»Π°Π½ΡΠ°ΡΠΈΠΈ ΠΊΠΎΡΡΠ½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π°, Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΡΡ
ΠΈΠΌΠΌΡΠ½ΠΎΠ΄Π΅ΡΠΈΡΠΈΡΠ½ΡΡ
ΡΠΎΡΡΠΎΡΠ½ΠΈΠΉ, ΡΠ²ΡΠ·Π°Π½Π½ΡΡ
Ρ Π»Π΅ΠΉΠΊΠΎΠΏΠ΅Π½ΠΈΠ΅ΠΉ. Π Π€ΠΠ£Π ΠΠΠ¦ ΠΠ Β«ΠΠ΅ΠΊΡΠΎΡΒ» Π ΠΎΡΠΏΠΎΡΡΠ΅Π±Π½Π°Π΄Π·ΠΎΡΠ° ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π° Π²ΡΡΠΎΠΊΠΎΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΠΈΡΠ΅Π»ΡΠ½Π°Ρ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΡ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΠΎΠ³ΠΎ ΠΠ-ΠΠ‘Π€ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° (ΡΡΠΠ-ΠΠ‘Π€) Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΠΎΠ³ΠΎ ΡΡΠ°ΠΌΠΌΠ° E. coli. Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ: ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π³Π΅ΠΌΠΎΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠ΅ΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΠΎΠ³ΠΎ ΠΠ-ΠΠ‘Π€ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΠΎΠ³ΠΎ ΠΏΠΎ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½ΠΎΠΉ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ, Π² ΠΊΡΠ»ΡΡΡΡΠ΅ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΈ Π½Π° ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΌΠΈΠ΅Π»ΠΎΡΡΠΏΡΠ΅ΡΡΠΈΠΈ Ρ ΠΌΡΡΠ΅ΠΉ, Π²ΡΠ·Π²Π°Π½Π½ΠΎΠΉ Π²Π²Π΅Π΄Π΅Π½ΠΈΠ΅ΠΌ ΡΠΈΠΊΠ»ΠΎΡΠΎΡΡΠ°Π½Π°. ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ: ΠΎΡΠ΅Π½ΠΊΡ Π³Π΅ΠΌΠΎΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠ΅ΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΡΠΠ-ΠΠ‘Π€ in vitro ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΠ’Π’-ΡΠ΅ΡΡΠ° Π½Π° ΠΊΠΎΠΌΠΌΠ΅ΡΡΠ΅ΡΠΊΠΎΠΉ ΠΊΡΠ»ΡΡΡΡΠ΅ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΡΠΎΠΌΠΈΠ΅Π»ΠΎΡΠΈΡΠ°ΡΠ½ΠΎΠΉ Π»Π΅ΠΉΠΊΠ΅ΠΌΠΈΠΈ HL-60, ΡΠΊΠΎΡΠΎΡΡΡ ΡΠΎΡΡΠ° ΠΊΠΎΡΠΎΡΡΡ
ΠΏΡΠ΅Π΄Π²Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΠΏΠΎΠ΄Π°Π²Π»ΡΠ»ΠΈ Π΄ΠΎΠ±Π°Π²Π»Π΅Π½ΠΈΠ΅ΠΌ Π² ΡΡΠ΅Π΄Ρ Π½ΠΈΠ·ΠΊΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π΄ΠΈΠΌΠ΅ΡΠΈΠ»ΡΡΠ»ΡΡΠΎΠΊΡΠΈΠ΄Π°. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ in vivo ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Π½Π° ΠΌΡΡΠ°Ρ
Π»ΠΈΠ½ΠΈΠΈ Π‘ΠΠ/CalaΡ Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΠΌΠΈΠ΅Π»ΠΎΡΡΠΏΡΠ΅ΡΡΠΈΠΈ, Π²ΡΠ·Π²Π°Π½Π½ΠΎΠΉ Π²Π²Π΅Π΄Π΅Π½ΠΈΠ΅ΠΌ ΡΠΈΠΊΠ»ΠΎΡΠΎΡΡΠ°Π½Π°. ΠΠ΅ΠΌΠΎΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π° ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° ΠΎΡΠ΅Π½ΠΈΠ²Π°Π»ΠΈ ΠΏΡΠΈ Π΅Π³ΠΎ ΠΏΠΎΠ΄ΠΊΠΎΠΆΠ½ΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ Π² Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅ Π΄ΠΎΠ· ΠΎΡ 1 Π΄ΠΎ 175 ΠΌΠΊΠ³/ΠΊΠ³ Π² ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ 4β5 ΡΡΡΠΎΠΊ ΠΏΠΎΡΠ»Π΅ Π²Π²Π΅Π΄Π΅Π½ΠΈΡ ΡΠΈΡΠΎΡΡΠ°ΡΠΈΠΊΠ°. Π ΠΎΠ±ΡΠ°Π·ΡΠ°Ρ
ΠΊΡΠΎΠ²ΠΈ, Π²Π·ΡΡΡΡ
Π² ΡΠ°Π·Π½ΡΠ΅ ΡΡΠΎΠΊΠΈ ΠΏΠΎΡΠ»Π΅ Π²Π²Π΅Π΄Π΅Π½ΠΈΡ, ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ»ΠΈ ΠΎΠ±ΡΠ΅Π΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠΎΠ² ΠΈ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ ΠΈΡ
ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠΎΡΠΌ. ΠΠ°Π½Π½ΡΠ΅ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ° ΠΎΠ±ΡΠ°Π±Π°ΡΡΠ²Π°Π»ΠΈ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌΠΈ Π²Π°ΡΠΈΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΉ ΡΡΠ°ΡΠΈΡΡΠΈΠΊΠΈ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΏΠ°ΠΊΠ΅ΡΠ° ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌ Statgraphics, v. 5.0. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ: ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½Π°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ HL-60, ΠΈΠ½ΠΊΡΠ±ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Ρ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠΌ ΡΡΠΠ-ΠΠ‘Π€ Π² ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ 72 Ρ, Π½ΠΎΡΠΈΠ»Π° Π΄ΠΎΠ·ΠΎΠ·Π°Π²ΠΈΡΠΈΠΌΡΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅Ρ. ΠΠ°ΠΈΠ±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠΈΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΈ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠΈ Π΄ΠΎΠ·Ρ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° Π½Π°Π±Π»ΡΠ΄Π°Π»ΠΈΡΡ Π² Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΉ ΠΎΡ 0,04 Π΄ΠΎ 0,64 Π½Π³/ΠΌΠ» (ΠΏΡΠΈΡΠΎΡΡ Π·Π½Π°ΡΠ΅Π½ΠΈΠΉ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Ρ ΠΏΡΠΈ Π΄Π²ΡΠΊΡΠ°ΡΠ½ΠΎΠΌ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠΈ Π΄ΠΎΠ·Ρ ΡΠΎΡΡΠ°Π²Π»ΡΠ» 11β18%). Π ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Ρ
Π½Π° ΠΌΡΡΠ°Ρ
ΠΏΡΠΎΠ΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΠΎΠ²Π°Π½ Π΄Π²ΡΡ
ΡΠ°Π·Π½ΡΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅Ρ Π΄ΠΎΠ·ΠΎΠ²ΠΎΠΉ Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΡΡΡΠ΅ΠΊΡΠ°. ΠΠ°ΠΈΠ±ΠΎΠ»ΡΡΡΡ Π³Π΅ΠΌΠΎΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ ΠΏΡΠΎΡΠ²Π»ΡΠ» Π² Π΄ΠΎΠ·Π΅ 90 ΠΌΠΊΠ³/ΠΊΠ³. ΠΡΠ²ΠΎΠ΄Ρ: ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ ΡΡΠΠ-ΠΠ‘Π€, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΠΉ ΠΏΠΎ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½ΠΎΠΉ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ, ΠΎΠ±Π»Π°Π΄Π°Π΅Ρ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΠΉ Π³Π΅ΠΌΠΎΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠ΅ΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ, ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π΅Π½Π½ΠΎΠΉ Π² ΡΠΈΡΡΠ΅ΠΌΠ°Ρ
in vitro ΠΈ in vivo