Antibiotiki最新文献

The effect of the aeration conditions on the mass exchange according to carbon dioxide in biosynthesis of various antibiotics was studied. On the basis of the results an equation for its estimation was developed. It was also shown that the effect of the aeration conditions on the intensity of the mass exchange according to carbon dioxide was much higher than that of the mass exchange according to oxygen.

The effect of doxycycline on R. prowazekii and R. sibirica was studied in comparison with that of tetracycline on two infection models, i. e. chick embryos and guinea pigs. The activity of doxycycline in the experiments with chick embryos was higher than that of tetracycline, the drug being more active against R. prowazekii than R. sibirica. The use of doxycycline in the treatment of the guinea pigs infected with R. prowazekii resulted in very rapid and stable decrease of the temperature. When used within the incubation period the drug prevented the infection development. Doxycycline was less effective in infections caused by R. sibirica.

The quantum-chemical estimation of the highest occupied molecular orbital energy for the aglycons of carminomycin, rubomycin, adriamycin and aclacinomycin A in the neutral and ionized states was performed with a semiempirical method. It was shown that the aglycon ionization amplified the electron donor properties of the antibiotics. On the basis of the difference in the absorption spectra of the neutral and ionized chromophores their ionization constants were determined spectrophotometrically. For comparison of the electron donor properties of the anthracyclines at the physiological pH value the reaction of their oxidation with potassium ferricyanide accompanied by decoloration of the solutions was studied. On the basis of the quantum-chemical and experimental data it was concluded that the electron donor properties amplified as follows: aclacinomycin A less than adriamycin-rubomycin less than carminomycin. At the same time their acute toxicity increased (a decrease in the LD50). Therefore, the toxicity of the anthracycline antibiotics could be also due to formation of the radicals with high reactivity on the monoelectronic oxidation.

The substrate profiles of beta-lactamases defected in 46 clinical polyresistant strains of gram-negative bacteria were determined. By the substrate profile and sensitivity to inhibitors (dicloxacillin and p-CMB) beta-lactamases were considered to belong to classes I, II, III, IV and V of the Richmond classification. The molecular weights of the enzymes were measured. Enterobacter aerogenes 6803, Enterobacter aerogenes 11030 and Klebsiella pneumoniae 970 produced simultaneously two beta-lactamases belonging to different classes. beta-Lactamases of classes I and III were detected in the cells of Enterobacter aerogenes 6803. The cells of Enterobacter aerogenes 11030 contained beta-lactamases of classes V and III and the cells of Klebsiella pneumonia 970 beta-lactamases of classes II and III. Therefore, in all the cases one of beta-lactamases belonged to the class III enzyme close to TEM beta-lactamases by its substrate profile, molecular weight and sensitivity to the inhibitors. Cephalexin and dicloxacillin were most frequently stable to the effect of the above beta-lactamases. The enzymes from 26 strains did not hydrolyse or hydrolysed slightly cephalexin and the enzymes from 19 strains did not hydrolyse of hydrolysed slightly dicloxacillin.

Stability of aminoglycoside phosphotransferases, adenylyltransferases and acetyltransferases isolated from various sources was studied. The enzymes were characterized by different substrate profiles. They were stored at a temperature of -10 degrees C in the form of frozen solutions or at a temperature of 4 degrees C in the lyophilized form. It was shown that lyophilization markedly increased the stability of the enzymes inactivating aminoglycoside antibiotics. Aminoglycoside phosphotransferases and adenylyltransferases with streptomycin as substrate were less stable than aminoglycoside phosphotransferases with neomycin as substrate. Aminoglycoside acetyltransferases from Streptomyces fradiae 918 producing neomycin were least stable among the enzymes studied. Lyophilized enzymes as a possible stabilizer of ATP added to the preparations had no significant effect on their stability during storage.

The experiments were performed on intact rabbits weighing 2.5-3 kg. The animals were treated with penicillin or streptomycin injected intramuscularly in doses of 20 000 units or 17 000 micrograms a day per kg bw for 12 days. The concentrations of lactic and pyruvic acids, cytochrome c, activity of cytochrome c oxidase and thiol spectrum were investigated in the lungs and liver immediately after the antibiotic use in 10 rabbits of every experimental series. To follow the period of persisting of the antibiotic-induced changes the other 10 rabbits were killed 29 days after the last injection of the drugs. It was shown that penicillin induced significant changes in the concentrations of lactic and pyruvic acids in the lung tissue, activated cytochrome c oxidase and decreased the concentrations of free SH and S-S groups immediately after its administration. 29 days after discontinuation of penicillin the activity of cytochrome c oxidase returned to normal, while the other biochemical indices remained changed. Penicillin induced changes in the concentrations of lactic and pyruvic acids and the activity of cytochrome c oxidase in the liver. The concentrations of free masked SH and S-S groups also changed. 29 days after discontinuation of penicillin the enzymatic system of cytochrome c-cytochrome c oxidase alone returned to normal. Like penicillin, streptomycin induced changes in the tissue respiration of the lungs and liver. The character of the streptomycin-induced changes was more pronounced both immediately and 29 days after discontinuation of the drug use.

The data on the absorption and bactericidal function of macrophages are presented. It was shown in vivo that bioglycans 42 and 106 had a stimulating action on phagocytosis of Y. pseudotuberculosis and S. typhimurium capable of persisting in macrophages for prolonged periods. Addition of the bioglycans to the cultures of the macrophages from intact animals increased the absorption activity of the macrophages and somewhat potentiated their bactericidal activity. Under the action of the bioglycans the level and rate of the carbon clearance in the blood flow increased. The results of the study are promising for adequate control of infections caused by intracellularly located pathogens.

One hundred and fifty-one patients with bronchopulmonary diseases were examined and it was shown that they had secondary immune deficiency mainly in the T-cells which could not be recovered with the routine therapeutic agents. The use of hemodez, levamisole or sodium nucleinate in the combined therapy promoted correction of the immune deficiency and increased the treatment efficacy. Sodium nucleinate proved to be the most efficient.