ABSTRACT
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.
Subject(s)
Disease Models, Animal , Doxycycline/administration & dosage , Peptidoglycan/administration & dosage , Plague/drug therapy , Rhizobium , Animals , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Drug Therapy, Combination , Mice , Plague/mortality , Plague/prevention & controlABSTRACT
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.
Subject(s)
Disease Models, Animal , Doxycycline/administration & dosage , Plague/drug therapy , Polysaccharides, Bacterial/administration & dosage , Rhodococcus , Animals , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Drug Synergism , Drug Therapy, Combination , Mice , Plague/mortality , Plague/prevention & controlABSTRACT
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.
Subject(s)
Adjuvants, Immunologic/therapeutic use , Doxycycline/therapeutic use , Plague/drug therapy , Animals , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Drug Synergism , Drug Therapy, Combination , Factor Analysis, Statistical , Mice , Molecular Weight , Plague/epidemiology , Plague/mortality , Time FactorsABSTRACT
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.
Subject(s)
Peptidoglycan/therapeutic use , Plague/drug therapy , Rhizobium , Rifampin/therapeutic use , Animals , Anti-Bacterial Agents , Data Interpretation, Statistical , Drug Synergism , Drug Therapy, Combination/therapeutic use , MiceABSTRACT
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.
Subject(s)
Plague/drug therapy , Polysaccharides, Bacterial/therapeutic use , Rhodococcus , Rifampin/therapeutic use , Animals , Anti-Bacterial Agents , Data Interpretation, Statistical , Drug Synergism , Drug Therapy, Combination/therapeutic use , MiceABSTRACT
Multifactorial analysis of the combined effect of rifampicin and a low molecular immunomodulator of microbial origin in experimental plague infection was performed. Synergism of the antibiotic used in the subtherapeutic doses and the immunomodulator was shown. By the results of the study polynomial statistic models of the second order describing the survival rate and average life-span of the experimental animals were developed and nomographs (equal level curves) were plotted for rapid estimating the therapy quantitative parameters. Optimization of the combined use of rifampicin and the immunomodulator on the basis of the multifactorial analysis was achieved.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Plague/drug therapy , Rifampin/administration & dosage , Adjuvants, Immunologic/biosynthesis , Animals , Bacteria/metabolism , Drug Synergism , Drug Therapy, Combination , Factor Analysis, Statistical , Life Expectancy , Mice , Models, Statistical , Molecular Weight , Plague/mortality , Survival RateABSTRACT
The effect of various antibiotics, such as streptomycin, gentamicin, ampicillin, benzylpenicillin, tetracycline, chlortetracycline and levomycetin on the plague bacteria (strain Y. pestis EV) located inside the cells was studied. Peritoneal macrophages of albino mice with aceptic inflammation of the abdominal cavity caused by intraperitoneal administration of 2 ml of sterile meat-peptone broth were used in the experiments. The ratio of the macrophages and microbes was 1 : 50. A part of the mice were treated with prodigiozan 24 hours before taking the exudate. The preparations of the macrophages of albino mice with the microbes absorbed by them served as the control. The effect of the antibiotics and their combinations with prodigiozan was stimated by the coefficient of multiplication suppression against the control. The observations were made in dynamics. The studies showed that the macrophage activity of the mice treated with prodigiozan after exposure to the antibiotics was reliably higher than that in the control and digestion of the microbes located inside the cells started earlier, providing more complete phagocytosis.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Plague/drug therapy , Prodigiosin/therapeutic use , Ampicillin/therapeutic use , Animals , Anti-Bacterial Agents/administration & dosage , Chloramphenicol/therapeutic use , Chlortetracycline/therapeutic use , Drug Combinations , Gentamicins/therapeutic use , In Vitro Techniques , Macrophages , Mice , Penicillin G/therapeutic use , Prodigiosin/administration & dosage , Streptomycin/therapeutic use , Tetracycline/therapeutic useABSTRACT
The advantage of the combined use of prodigiozan and tetracycline was observed in tissue culture of peritoneal macrophages of albino mice. Earlier digestion of the intracellular Y. pestis EV by the animal macrophages exposed to prodigiozan and treated with tetracycline was noted. It was shown that the macrophages preserved during several hours of cultivation in vitro their properties acquired in the animal organism under the effect of the substances administered.
