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 the effectiveness of antibacterial substances in treating an experimental form of bubonic plague in monkeys]

The modelling of glandular plague and selection of the conditions for estimating the efficacy of new antibacterials for the treatment of the infection were performed on hamadryads (baboons). The experiments showed that the average LD50 of the culture of a highly virulent strain of Yersinia pestis on its subcutaneous administration to the animals was 2089 viable microbes. In 18 per cent of the episodes the experimental glandular plague in the animals was complicated by secondary plague pneumonia. Subcutaneous administration of 2 x 10(7) viable microbial cell of the plague pathogen caused acute sepsis and the animal death. The treatment of the experimental glandular plague in the hamadryads demonstrated that new antibacterials such as amikacin, netilmicin, ceftriaxone, cefotaxime, ceftizoxime, doxycycline, rifampicin, ofloxacin and ciprofloxacin were not inferior in their efficacy to streptomycin and tetracycline successfully used in the therapy of patients with plague.     

Effectiveness of cefotaxime in experimental plague infection]

Cefotaxime was shown highly efficient in prophylaxis and treatment of experimental plague infection in albino mice. The in vitro activity of cefotaxime against natural strains of the plague microbe was 32 to 64 times higher than that of cefazolin, cephalothin and cefmetazole. The combined use of cefotaxime with amikacin significantly increased the percentage of the survived albino mice with plague infection as compared to the use of the antibiotics alone.     

Anti-arrhythmic effect of tetrodotoxin in the late stage of experimental myocardial infarct]

The action of tetrodotoxin (TT), blocking the fast sodium current, on arrhythmias that occurred 24 hours after occlusion of the coronary artery was studied in 10 dogs. TT injected intravenously in doses of 0.5--3.0 micrograms/kg significantly decreased the number of ventricular extrasystoles, and completely restored sinum rhythm in 4 animals. The maximum antiarrhythmic effect was noted 3 to 5 minutes after TT adminstration. It is suggested that arrhythmias and the antiarrhythmic effect of the drugs in the late stage of myocardial infarction are connected with the fast inward sodium current.     

Clinical and experimental parallels in studying the effect of chymotrypsin on the pharmacokinetics of antibiotics]

The effect of intramuscular chimotripsin on the levels of methicillin and tetracycline administered respectively intramuscularly and orally was studied in patients with chronic pneumonia and in experimental rats. It was found that the dose of chimotripsin providing higher methicillin blood levels was many times lower than the enzyme doses providing analogous indices for the blood serum and organs of the rats. When the patients were treated with tetracycline and chimotripsin, increased blood levels of the antibiotic were observed. Administration of chimotripsin to the rats had no effect on tetracycline pharmacokinetics in the animals.     

Evaluation of modern antibiotics efficacy at experimental Northern Asia rickettsiosis]

Comparative investigation of antibiotics therapy efficacy at experimental murine Northern Asia rickettsiosis was performed. The efficacy was evaluated by the determination of protective activity in per cent and by the pathogen erradication. The investigated antibiotics may be ranged in the following order (by the diminishing efficacy): ansamycins (azorif, rifapentine, rifampicin), tetracyclines (doxycycline), macrolides (azitromycin, sumamed), carbapenems (imipenem/cilastatin), fluoroquinolones (lomefloxacin, pefloxacin). Rifampicin and its derivatives--azorif, rifapentine, along with doxycycline and azitromycm can be recommended for clinical trials at experimental rickettsiosis profilaxy and treatment in natural infection focus.     

Liver extract effect on liver microsomal system and on an experimental model of intoxication]

A lyophilized liver extract (FLR) lengthens hexobarbital action in control rats ; it decreases slightly the induction of hepatic microsomal enzymes and normalizes diphenylhydantoin protection against electroshock seizure in phenobarbital-treated animals ; in the event of a CC14 intoxication, this extract reestablishes values close to normal for mebubarbital metabolism in mice and for BSP clearance in rats. FLR could act in regularizing drug metabolism.     

Duration and intensity of postvaccinal immunity to plague in experimental animals]

Experiments were conducted on guinea pigs and Papio hamadryas; it was shown that a reduction of the intensity of postvaccinal immunity occurred at various periods after a single vaccination. In inhalation method of immunization in guinea pigs it decreased in 6 months 135 times, in monkeys in one year--133 times. However, at the mentioned periods vaccination provided protection of 50% of the animals from infection with Past. pestis in a dose constitutin 20 to 25 aerosol LD50 for nonimmunized animals. Despite the more pronounced (57--640 times) reduction of the intensity of immunity than in the animals vaccinated by inhalation, in the subcutaneously vaccinated guinea pigs in subcutaneously infected with Past. pestis protection level remained high (resistance index in 3 and 6 months constituted 37.10(6) and 3-3-10(6), respectively).     

Isepamycin in prophylaxis and treatment of experimental plague due to FI+ and FI- variants of plague microbe]

The efficacy of isepamycin vs. other aminoglycosides was studied in vitro and on albino mice with experimental plague due to natural antigen valuable strains of the plague microbe and the pathogen variants deprived of the ability to produce the capsular antigen fraction I (FI- phenotype). The MICs of isepamycin for the strains of the plague microbe (20 FI+ and 20FI-) were 1.0-4.0 mg\l, that did not differ from those of streptomycin, kanamycin, amikacin and tobramycin. The ED50 of isepamycin in the prophylaxis and treatment of the experimental plague of the mice had no statistically significant differences from the ED50 of the other aminoglycosides. The efficacy index of isepamycin was > 10(4), that did not differ from that of streptomycin, amikacin and gentamicin, irrespective of the strain phenotype (Y. pestis 231 FI+ or Y. pestis 231 FI-). The same as the other aminoglycosides, isepamycin in doses equivalent to the human average daily doses, protected 80-100% of the albino mice from death when used in the prophylaxis and therapy of plague irrespective of the strain phenotype. The results of the study made it possible to consider isepamycin as an agent promising for the prophylaxis and treatment of plague.     

Further study of the effectiveness of oral immunization against plague in experiments on animals]

It was shown in comparative experiments on guinea pigs that the oral method of immunization with plague vaccine was much less effective than the inhalation and subcutaneous. Guinea pigs were found to be a poor model for studying the efficacy of oral immunization with dry live plague vaccine rehydrated before use: with the use of this preparation the animals were 46 times less resistant to aerosol plague infection than in application of strain EB cultured in agar.     

Study of the effect of tetracycline, prodigiosin and their combination on the dynamics of phagocytosis of plague bacteria]

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.     

Effect of subinhibitory concentrations of antibiotics on catalase activity of plague microbes]

It was shown that the presence of subinhibitory concentrations of ampicillin, cefotaxime or gentamicin in the cultivation medium had a marked inhibitory effect on the catalase activity of plague microbe. The effect depended on the characteristic features of plague microbe strains and the incubation temperature. When the cells of a virulent strain of the plague microbe Y. pestis 1300 were cultivated at a temperature of 37 degrees C on a medium containing the subinhibitory concentrations of ampicillin or cefotaxime, the pathogen virulence for albino mice significantly decreased.     

Rifampicin effectiveness in experimental anaerobic gas infection]

The inhibitory effect of rifampicin against most of 82 strains of pathogenic Clostridia was evident at a concentration of less than 0.1 gamma/ml. The bactericidal concentrations were close to the bacteriostatic ones with respect to 74 strains. The protective effect of rifampicin in mice with experimental anaerobic gaseous infaction caused by different species of pathogenic Clostridia was evident at doses of 0.5 mg/kg. In infections caused by associations of Clostridia and Staph. aureus resistant to other antibiotics, rifampicin was effective, while ampicillin had no protective effect. Rifampicin administered 24 to 96 hours before the infection prevented the specific process. A number of other antibiotics, such as ampicillin, cephaloridin, morphocycline and 7-chlor-7-desoxylincomycin had no such a capacity. The prolonged prophylactic effect of rifampicin was associated with maintenance of low antibiotic levels in the blood and muscle tissues which were higher than the minimum inhibitory concentrations. The effect of rifampicin against the background of a rapidly developing process was less pronounced and limited in time.     

Action of tetracyclines on the pseudotuberculosis microbe in vitro experiments and their effectiveness in experimental pseudotuberculosis in white mice]

227 out of 228 strains of pseudotuberculosis microbes studied in vitro proved to be sensitive to tetracyclines. The MIC of tetracycline and morphocycline ranged within 0.25--25 gamma/ml. The MIC of chlortetracycline and oxytetracycline was somewhat lower, i. e. 1--50 gamma/ml. When administered intramuscularly all the tetracyclines had pronounced therapeutic effect in experiments with albino mice infected with the antibiotic sensitive strains of J. pseudotuberculosis. Chlortetracycline proved to be the most active drug in treatment of albino mice per os.     

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.