[General trends in design of drugs for chemotherapy of AIDS].
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
L P Ivanitskaia
Publications and source records attributed to L P Ivanitskaia.
[The status of and outlook for the creation of new preparations for the therapy and prevention of HIV infection and AIDS].
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Acquired Immunodeficiency Syndrome↗
[Effect of cyclosporin on various metabolic processes in fungi].
Sensitivity of the representatives of Aspergillus and Piricularia to various concentrations of cyclosporine (in the submerged culture) was studied for choosing the test object for the subcellular investigation of the mechanism of the cyclosporine antifungal action. Changes in the main physiological and biochemical parameters of the fungal cells under the action of cyclosporine in concentrations of 10 to 80 micrograms per 1 ml of the medium were characterized. Low concentrations of cyclosporine (10 to 20 micrograms/ml) did not inhibit the growth of Aspergillus niger but induced stimulation of the growth processes. Only at a concentration of 80 micrograms/ml the inhibitory effect was observed. At the same time there was detected a dramatic stimulation of the culture respiration via the basic respiration chain. In the culture of Piricularia oryzae only inhibition of the culture growth even at the minimum concentration of cyclosporine (10 micrograms/ml) was recorded. Both the cyclosporine sensitive test objects i.e. A. niger and P. oryzae had an alternative cyanide resistant system of the electron transport. In the experiments with A. niger the cyclosporine effect on the synthesis of protein and RNA was revealed. The study provided data on the changes in the morphogenesis of the A. niger cells under the effect of cyclosporine.
Aspergillus niger↗
[Immunomodulating action of peptidoglycan of microbial origin].
The action of a high molecular weight peptidoglycan produced by Agrobacter radiobacter sp. on the functional activity parameters in leukocytes and macrophages i. e. chemotaxis and adhesion was studied. It was shown that the peptidoglycan had a stimulating action on the chemotaxis of cells of the peritoneal exudate. A marked stimulating action of the drug on the primary immune response to the tissue antigen of sheep erythrocytes was observed. The peptidoglycan stimulated the antibody titers and delayed hypersensitivity when administered in various periods after an antigenic stimulus. Multifactorial experiments on the protective action of the peptidoglycan in experimental infections were carried out. Second-order polynomial statistic models characterizing the animal survival rate were constructed and the dose-time parameters of the drug use were optimized.
Adjuvants, Immunologic↗
[Study of the immunosuppressive effect of cyclosporine in experimental studies].
Specific immunosuppressive activity of cyclosporine prepared at the National Research Centre of Antibiotics by using its original producing culture was studied. It inhibited basic cellular immune responses such as DTH and transplant vs. host and prolonged the lifespan of tumor xenografts under the kidney capsule. Cyclosporine also suppressed the humoral immunity. Its inhibitory effect on lymphocyte blast transformation induced by lectins and in mixed lymphocyte cultures was shown in vitro. Cyclosporine inhibited activity of natural killer cells and T-suppressor cells induced by concanavalin A. It was demonstrated on the models of skin allotransplantation in mice and heterotopic transplantation of the heart in rats that cyclosporine prolonged the transplant lifespan. By the main indices of the cellular immunity and in the models of the transplantation immunity, cyclosporine prepared at the National Research Centre of Antibiotics was shown to be similar to that manufactured by Sandoz.
Abdomen↗
[Multifactorial analysis of combined use of an antibiotic and peptidoglycan of microbial origin in experimental plague].
The combined effect of doxycycline and microbial peptidoglycan was studied with multifactorial analysis. The drugs were used preventively and therapeutically. The preventive use of doxycycline in the subtherapeutic doses in combination with the immunomodulator resulted in a significant increase in the survival rate rather than the average life-span (ALS) of the experimental animals. The therapeutic use of the drugs was more efficient than the preventive one and resulted in higher survival and ALS. By the results of the experiments polynomial statistic models of the second order were developed and the equal level curves characterizing the survival rate and ALS were plotted. The dose-time regimens of the combined use of doxycycline an peptidoglycan were optimized.
Animals↗
[Multifactor study of combined effects of an antibiotic and polysaccharide in experimental infection].
Multifactorial analysis was applied to the study of the combined effect of doxycycline and a polysaccharide of microbial origin in experimental plague infection. A marked synergistic action of the antibiotic and polysaccharide used in subtherapeutic doses in treatment of the infection was observed. By the results of the experiments polynomial statistic models of the 2nd order were designed and nomographs or equal level lines were plotted. The models and nomographs described the animal survival rate and lifespan within a wide range of the control parameters. The dose/time regimens for the use of the polysaccharide combination with doxycycline were optimized on the basis of the multifactorial analysis.
Animals↗
[Isolation and identification of an antibiotic from culture 8-86].
An antibiotic complex was isolated from culture 8-86 referred to Bacillus. The complex consisted of components 8-86A and 8-86B active against gram-negative organisms. By its physico-chemical properties such as IR and UV spectra, amino acid composition, specific rotation and fatty acid composition component 8-86B was shown to be close to polymyxin F.
Amino Acids↗
[Multi-factor analysis of combined effects of rifampicin and peptidoglycan of microbial origin on immune response].
Multifactorial analysis of the combined action of rifampicin and a microbial peptidoglycan on the immune response to antigens of the vaccine EV fraction 1 was performed. The results were computer-processed and the second order equations describing delayed hypersensitivity (DH) and antibody titers were derived. Nomographs or equal level curves showing interrelations of the investigated factors were plotted. The character of the combined action on DH and antibody titers was heterogeneous. The peptidoglycan had a pronounced immunostimulant action on DH and, to a lesser extent, influenced the humoral response. Conditions for the peptidoglycan use aimed at immunostimulation were optimized with application of multifactorial analysis.
Adjuvants, Immunologic↗
[A system for screening natural immunosuppressors].
Criteria for directed screening of antibiotics with immunosuppressive action were defined. The first stage included screening of cultures producing antiaspergillous antibiotics. At the second stage, the antibiotics whose antifungal activity decreases in the presence of insulin (at the background of calcium salts) and erythromycin and increases in the presence of verapamil were selected. The screening of antibiotic-producing cultures among 123 strains of mycelial fungi and 181 strains of actinomycetes resulted in isolation of 3 fungal cultures and 2 actinomycetes which produced antibiotics corresponding to cyclosporine A as evidenced by thin-layer and high performance liquid chromatographies.
Actinomycetales↗
[Multifactorial experiment on the combined action of doxycycline and a low molecular weight immunomodulator of microbial origin in experimental anthrax infection].
Chemotherapeutic efficacy of combined therapy of experimental anthrax infection with subtherapeutic doses of doxycycline and a low molecular weight immunomodulator of microbial origin was studied with mathematical design of the experiment and multifactorial analysis. A marked synergistic effect of oral doxycycline and the immunomodulator was observed. The results of the multifactorial experiment were computer processed and polynomial statistic models (the second order equations) describing the survival rate and mean lifespan (MLS) were derived. The equal level lines characterizing the survival rate and MLS were plotted against the fixed values of the time factor of administering the immunomodulator and the dose of the antibiotic. The doses of the immunomodulator and the time of its administration were optimized with respect to the maximum therapeutic effect with doxycycline subtherapeutic doses.
Adjuvants, Immunologic↗
[A multifactorial analysis of the combined action of an antibiotic and a low-molecular immunomodulator of microbial origin in experimental plague infection].
The combined effect of doxycycline and a low molecular weight immunomodulator of microbial origin was studied in experimental plague infection with mathematical design of the experiment. Synergism of the action of the antibiotic and immunomodulator used in subtherapeutic doses was observed. The action was the most pronounced when the drugs were applied therapeutically. On the basis of the multifactorial analysis the regimens for the use of the antibiotic and immunomodulator were optimized.
Adjuvants, Immunologic↗
[Multifactorial study of the combined effect of rifampicin and microbial peptidoglycan in experimental plague infection].
The combined effect of rifampicin and a microbial peptidoglycan was studied in multifactorial experiments on noninbred mice with plague infection. The effect of rifampicin and the immunomodulator was shown to be synergistic. The results of the multifactorial experiments provided designing of polynomial statistic models of the second order characterizing the animal survival rate and mean life-span and plotting of nomograms or equal level lines useful in optimization of the combined therapy parameters.
Animals↗
[Multifactorial experiment on the combined effect of rifampicin and microbial polysaccharide in experimental plague infection].
Multifactorial analysis was applied to the study of the combined effect of rifampicin and a microbial polysaccharide in experimental plague infection. The effect of the antibiotic and immunomodulator was shown to be synergistic. On the basis of the study results polynomial statistic models of the second order were designed and nomograms or equal level lines were plotted which provided optimization of the combined chemo- and immunotherapy.
Animals↗
[Screening of pharmacologically active compounds among inhibitors of enzymes of microbial origin].
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Analgesics↗
[Comparative multifactorial analysis of combined administration of injection and peroral forms of an antibiotic with a microbial immunomodulator in experimental anthrax].
Comparative efficacy of the use of injection and oral dosage forms of rifampicin in the subtherapeutic doses in combination with peptidoglycan , an immunomodulator of microbial origin, was studied in respect to experimental anthracic infection with application of multifactorial analysis. It was shown that the antibiotic and immunomodulator had a pronounced synergistic effect. Polynomial statistic models were developed and nomograms or equal level curves defining the survival rate and average life-span (ALS) of the experimental animals within a wide range of the antibiotic and immunomodulator doses and the peptidoglycan dosing time were plotted. The combined use of the injection rifampicin in the subtherapeutic doses and the immunomodulator provided a significant increase in the survival rate and ALS, whereas the use of the oral antibiotic in combination with the immunomodulator increased only the ALS and not the survival rate. Multifactorial analysis proved to be an optimal methodical approach to comparative study of various antibiotic dosage forms used in combination with immunomodulators under experimental conditions.
Adjuvants, Immunologic↗
[Optimal combined use of rifampicin and immunomodulator of microbial origin in experimental Q-Rickettsia infection].
Multifactorial analysis of the combined use of rifampicin and an immunomodulator of the microbial origin, such as peptidoglycan, was performed on a model of experimental Q fever in albino mice. On the basis of the experimental results, statistic polynomial models describing the weight of the murine spleens and the titers of the complement-binding antibodies were designed. It was shown that the action of the immunomodulator and antibiotic was highly synergistic with respect to the chemotherapeutic activity and antibody titers. The preventive use of the immunomodulator yielded a 30-fold decrease in a rifampicin therapeutic dose. The use of the immunomodulator also provided a pronounced immunomodulating effect with respect to humoral immunity. Nomographs for optimizing the dose-time parameters of the antibacterial and immunomodulating therapy were plotted.
Adjuvants, Immunologic↗
[Multifactor analysis of the combined action of doxycycline and a peptidoglycan of microbial origin on the immune response].
Multifactorial analysis of the combined action of a microbial peptidoglycan and doxycycline on the immune response to antigens of the vaccine EV fraction 1 was made. Nomograms or equal level curves characterizing delayed hypersensitivity (DH) and antibody titers in various doses of the peptidoglycan and the antibiotic were plotted by the experimental data with a computer. The peptidoglycan had a pronounced immunomodulatory action on DH and antibody titers. However, the types of regulation of the both responses markedly differed. With multifactor analysis, the range of the values of the operating parameters, i.e. the drug doses and the time of their administration providing the required levels of DH and antibodies under the conditions of the combined therapy were defined.
Animals↗