Doxycycline in the prevention of experimental plague induced by plague microbe variants]

A comparative study was performed on the efficacy of doxycycline in experimental plague infection induced in albino mice by strain 231 of the plague microbe and its variant 231 Fra- deprived of the ability to produce the fraction I antigen. It was shown that the LD50 for strain 231 during animal treatment with doxycycline was significantly higher than that for variant 231 Fra-. Prophylaxis of the plague infection caused by the Fra- forms of the plague microbe required significantly higher doses of doxycycline (ED50) than that of the infection caused by the Fra+ forms. The use of the daily maximum permissible doses of doxycycline (50 to 100 mg/kg a day) for 10 days in treatment of albino mice infected with the strain Fra- did not provide animal survival at the level higher than 60 to 70 per cent while the survival rate in the animals infected with the strain Fra+ of the plague microbe and treated according to the same scheme amounted to 90-100 per cent. The lower therapeutic efficacy of doxycycline in the treatment of the infection caused by the fractionless variant of the plague microbe should be considered in development of rational schemes for prophylaxis and treatment of plague.     

Evaluation of outcomes of combined specific prophylaxis with the antibiotic resistant immunogenic plague pathogen strain and emergency prophylaxis with aminoglycosides in the experimental plague model in white mice]

It was shown that aminoglycosides (streptomycin, kanamycin, gentamicin, sisomicin, tobramycin, amikacin) prevented manifestation of postvaccine immunity in albino mice immunized by vaccine strain Yersinia pestis EV. Avirulent strain Y. pestis 363 Monr with chromosome resistance to aminoglycosides of the 1st, 2nd and 3rd generations provided manifestation of antiplague immunity when streptomycin, kanamycin, gentamicin and amikacin were administered for prophylaxis. ED50 achieved 1.0-1.2 x 10(3) CFU and in control group (without treatment) 9.3 x 10(2) CFU. Gentamicin and amikacin were highly effective for experimental plague prophylaxis (90-100% animal survival), but inhibited development of postinfective immunity. Protective index (PI) value was 1.1 x 10(2). It was demonstrated that combination of specific prophylaxis (Y. pestis 363 Monr) and emergency prophylaxis with aminoglycosides in albino mice infected with approximately 1000 LD50 of virulent strain Y. pestis 358 (5 hours after infection) was highly effective and provided protective effect against subsequent infection with plague pathogen. Value of PI was 1.1 x 10(5) and practically did not differ from PI (1.7 x 10(5)) in control group (intact mice, immunized with strains EV [symbol: see text] 363 Monr).     

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.     

Antibiotics of the aminoglycoside group (gentamicin, sisomicin and amikacin) in the prevention and treatment of experimental plague]

Activity of aminoglycosides such as gentamicin, sisomicin and amikacin against plague microbe strains of natural origin was studied in vitro. It was also studied in prophylaxis and treatment of experimental plague infection in albino mice. The MAC of gentamicin and sisomicin for 50 strains of the plague microbe was 0.2-1.6 micrograms/ml. For the majority of the strains it was 0.4 micrograms/ml. The amikacin MICs were 0.4-3.2 and 0.8 micrograms/ml, respectively. High efficacy of gentamicin, sisomicin and amikacin was shown in prophylaxis and treatment of experimental plague infection in albino mice. The optimal doses of the antibiotics were determined. Under definite conditions such as the use of short-term regimens and higher intervals, advantages of sisomicin over gentamicin and amikacin in prophylaxis of experimental plague infection were observed.     

Sensitivity of Pseudomonas mallei to fluoroquinolones and their efficacy in experimental glanders]

Thirteen strains of P. mallei were found to be highly sensitive to ciprofloxacin and ofloxacin and resistant to norfloxacin. Ciprofloxacin and ofloxacin showed a high efficacy on models of malleus in guinea pigs and hamsters. The animals were infected with various strains of P. mallei. In the in vitro experiments, ciprofloxacin proved to be the most active and efficient. Norfloxacin appeared to be inefficient.     

Detoxifying effect of antibiotics and their effectiveness in experimental plague at the stage of explicit intoxication]

The effect of antibiotics such as amikacin, rifampicin, doxycycline, polymyxin B and cefotaxime on the toxins of the plague microbe (lipopolysaccharide + fraction II according to Beiker) was studied in vitro and in vivo. The study on the antibiotic neutralization of plague toxins revealed that only polymyxin had toxin neutralizing capacity which depended on the dose. Investigation of the polymyxin effect at various stages of plague infection showed that when polymyxin in a dose of 1250 units and a mixture of plague toxins in lethal doses were administered simultaneously to albino mice, the positive effect amounted to 100 per cent. When the antibiotic was administered 30 or 60 minutes later, the antibiotic efficacy proved to be lower by 90 or 76.6 per cent, respectively. The intoxication in later periods (in 90-120 minutes) resulted in a decrease in animal survival up to 40-15 per cent. It was demonstrated on the model of the plague infection in albino mice that the use of amikacin, cefotaxime, rifampicin or doxycycline during polymyxin therapy at the stage of marked generalization of the infection provided a significant increase in the animal survival (60 to 80 per cent) as compared to that after the use of the same drugs alone (0 to 20 per cent).     

Ultrastructural changes in plague microbes, strain EV, and splenic cells of guinea pigs in their interaction in vitro]

Dilatation of the endoplasmic reticulum cavities, an increase in the number of ribosomes near bacteria, deformation of mitochondria and coarsening of cristae were revealed in phagocytosis of Past. pestis, strain EV, by reticular cells in the tissue culture of the spleen of intact guinea pigs. Lipophanerous "reticular" inclusions were found in the differentiated reticular cells of the infected cultures. In the reticular cell cytoplasma besides the intact bacteria there were revealed Past. pestis at the initial stages of involution.     

The use of immunoenzyme analysis in the laboratory diagnosis of plague]

The possibility of using the enzyme immunoassay (EIA) for the early diagnosis of pneumonic plague was studied in experiments on monkeys. EIA was shown to be more effective than the passive hemagglutination test. The diagnostic value of blood serum samples was found to be higher than that of nasopharyngeal mucus samples taken from the sick animals. The conclusion on the suitability of EIA for the early laboratory diagnosis of this disease was made.     

Morphological structure of Yersinia pestis populations (strain EV) in the process of live plague vaccine production

Morphological structure of the population of Yersinia pestis strain EV and the pattern of its changes during deep cultivation and in different stages of the live plague vaccine production was under study. The size range of cells most resistant to external influences was established.     

Multifactor analysis of the combined use of an antibiotic and a low molecular weight immunomodulator of microbial origin in experimental plague infection

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.     

Resistance of experimental antibiotic resistant variants of Yersinia pestis EV76 (NIIEG line) to modern marker antibiotics]

Lower susceptibility of previously designed experimental polyresistant variants of Yersinia pestis EV76 (NIIEG line) with inserted R plasmid or transposons to some present antibiotics efficient in the treatment of plague, i. e. doxycycline, amikacin and ceftriaxone, was shown. Clones, more resistant to them vs. the initial variants, were selected. They accustomed in vivo in laboratory animals per se and after administration of antibiotics. The data on the protective activity of the new variants in the treatment of experimental plague after combined vaccination and antibiotic prophylaxis are presented.     

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.     

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.     

The use of enkephalins for the prevention of stress-induced experimental heart damage

The experiments on white rats have shown that Dala2-Leu5-arg-enkephalin preinjection reduced the degree of serum creatine phosphokinase increment and decreased labeled pyrophosphate accumulation in the myocardium during the onset of anxiety neurosis, according to O. Desiderato. Enkephalins are suggested to prevent stress-induced heart lesions.     

The phages of halophilic vibrios and their use]

The range of the lytic activity of 46 phages of parahemolytic vibrios isolated from lysogenic strains, sea water samples, crabs and mussels has been studied. The phages are represented by virions belonging to morphological groups II, IV, V according to the phage classification currently used in Russia and to different serological groups. No relationship between the sensitivity of vibrio strains to the phages under study and the specificity of serotypes O and K has been established. The preparation of diagnostic phage [see text] suitable for the identification of 82% of strains of parahemolytic vibrios has been proposed.