Antibiotiki最新文献

The cytostatic effect of rubomycin and N-ethyl-13-dihydrorubomycin, its semisynthetic derivative, was studied with a radiometric method based on measuring the intensity of labeled thymidine incorporation into the tumor cells of NK/Ly, sarcoma 37 and leukemia P-388 and a method for total determination of nucleic acids in the cell hydrolysates of these tumor strains. Spectrophotometric determination of the total content of DNA and RNA in the tumor cells of NK/Ly showed that the inhibitory effect of the derivative was 6 times higher than that of rubomycin. Radiometric estimation of their cytostatic activity and the studies with the cells of ascitic sarcoma 37 and leukemia P-388 demonstrated that the inhibitory effect of N-ethyl-13-dihydrorubomycin was lower than that of rubomycin.

The growth of gram-negative sporulating bacteria and yeast-like fungi used in a microbilogical assay of antibiotic activity was studied on solid synthetic media of simple composition. Their reproduction with the microbial growth of different density was shown to be possible on media containing available and strictly standardized components, such as salts, glucose and disubstituted sodium phosphate. The cultures tested were not similar by their growth requirements.

Two hundred and thirty-two strains of Staph. aureus isolated from patients with staphylococcal infections were studied. The strains were isolated from the blood of patients with sepsis, from the purulent foci on the skin and in the subcutaneous fat, from the nasopharyngeal mucosa of patients with tonsillitis and inflammation of the upper respiratory tract, from the sputum of patients with the pneumonia signs and from the pus of patients with otitis. The pathogens were identified with the routine methods. The quantitative content of protein A in the strains was determined by the method of indirect hemagglutination with red blood cells sensitized with the hemolytic serum. The data obtained were analysed with regard to the strain group and characteristics of the strain resistance or sensitivity to benzylpenicillin, erythromycin, oleandomycin, chloramphenicol, streptomycin, neomycin, kanamycin, monomycin, ristomycin and furagin K. Statistically significant differences in the protein A content in certain strain groups were observed. These differences might be correlated with the strain antibiotic resistance but not sensitivity. Pronounced changes in the levels of protein A were detected in the staphylococcal hemocultures resistant to erythromycin and streptomycin. The cultures resistant to erythromycin were characterized by decreased content of protein A and those resistant to streptomycin were characterized by increased content of protein A. Comparison of the antibiotic sensitivity of the strains of 5 groups by variation statistics revealed significant differences in the levels of sensitivity to streptomycin, neomycin, kanamycin, monomycin, ristomycin and furagin K but not to erythromycin, oleandomycin and chloramphenicol in the strains of certain groups. The staphylococcal hemocultures isolated from patients with sepsis proved to be the most sensitive to the antibiotics.

The effect of carminomycin on the activity of liver monohydroxygenases was estimated. It mas noted that in doses of 2, 3 and 4 mg/kg the antibiotic had no effect on the sleep duration in mice treated with hexenal. This meant that it did not change the activity of the enzymatic system. Induction and inhibition of liver monohydroxygenases did not influence the toxic effect of carminomycin used in doses of 5 and 10 mg/kg. It was also shown that the toxicity of both rubomycin and adriamycin decreased on induction and increased on inhibition of liver monohydroxygenases. Like adriamycin rubomycin lowered the activity of this enzymatic system. Administration of rubomycin in a dose of 5 mg/kg prolonged the duration of the hexenal sleep almost 1.5-2 times as compared to the control. The possible participation of liver monohydroxygenases in metabolic transformations of the antracycline antibiotics is discussed.

The efficacy of the combined use of immunostimulants and anti-inflammatory agents, such as acetylsalicylic acid, voltaren, indomethacin and naproxen was studied in carragenin-induced experimental inflammation. Noninbred albino mice of both sexes were used in the experiments. It was shown that prodigiosan as a therapeutic agent had a pronounced anti-inflammatory action. It potentiated the effect of voltaren used in a dose lower than the ED50 and did not change the anti-inflammatory activity of naproxen, indomethacin and acetylsalicylic acid used in the doses equal to the ED50. The potentiating effect of prodigiosan on voltaren was statistically significant Methyluracil used as a prophylactic agent had an anti-inflammatory effect. Levamisole used as a prophylactic agent or a therapeutic agent did not decrease the edema level. The anti-inflammatory effect of naproxen, indomethacin, acetylsalicylic acid and voltaren did not change, when the drugs were administered to the animals treated with methyluracil and levamisole.

The effect of virazole on the antiviral activity of poly (G) X poly (C), poly (G, A) X X poly (C) and poly(G, I) X poly (C) was studied in cell cultures and on mice. It was shown that virazole in concentrations not sufficient for significant inhibition of the development of vesicular stomatitis virus or Sindbis virus in chick embryo cell cultures markedly increased the antiviral effect and allowed decreasing the minimum effective doses of the synthetic polyribonucleotide complexes with respect to the above viruses. Combined administration of poly (G) X poly (C) and virazole to mice 1-2 or 24 hours after infection with tick-borne encephalitis virus provided a much more pronounced decrease in the death rate of the animals than the use of the interferonogen alone. Virazole per se was little active and had no significant effect on the intensity of interferonogenesis promoted by the use of poly (G) X poly (C). A possibility of successful therapy of viral infections with polyribonucleotide interferonogens in combination with virazole or other chemotherapeutic drugs with broad antiviral spectrum is discussed.

Extraction of CuCl2, NiCl2, CoCl2 and MnCl2 from the aqueous phase to the organic gramicidin S containing phase (the phase ratio of 1:1) was studied with the method of molar ratios at constant concentrations of the salts and changing concentrations of the antibiotic. The composition of the forming intracomplex compounds was determined with the equilibrium shift method. It was shown that 2 ions of chlorine and 2 molecules of gramicidin S bound with 1 ion of the metals. The extraction constants were measured. The complex compounds of gramicidin S with copper chloride were the most stable.

Soluble rifampicin and isoniazid injected rapidly by the intravenous route and streptomycin injected intramuscularly to dogs with disseminated destructive tuberculosis of the lungs provided sterilization of the organs with respect to M. tuberculosis for the period of their use for 2 months. This was confirmed microbiologically. The treatment resulted in resolution of the dissemination foci in the organs and stimulation of immunomorphological and connective tissue reactions in the lungs until the foci cicatrized. The shifts in liver function (bilirubin, ALT and AST) and coagulograms during the treatment were temporary and came to normal by the end of the treatment. The organotropic effect of soluble rifampicin in combination with isoniazid injected rapidly by the intravenous route and streptomycin injected intramuscularly was not observed during the treatment of the dogs with disseminated destructive tuberculosis of the lungs. Rapid intravenous injection of rifampicin in combination with other antimicrobial drugs will provide a significant decrease in the periods of chemotherapy of patients with disseminated destructive tuberculosis of the lungs.

Two beta-lactam antibiotics with different serum protein binding were studied for penetration into the tissues of rats with aseptic inflammation. It was found that the pharmacokinetics of the drugs in the blood serum differed only in the elimination rate. The levels of the free fraction of cephaloridin were much higher than those of carbenicillin. The maximum concentrations of free cephaloridin in the inflammation exudate, intact and inflamed tissues and the areas under its pharmacokinetic curves were higher than those of carbenicillin. The elimination rate of both the drugs was the same for all the tissues studied.

Ruboxyl, a paramagnetic analog of rubomycin, was synthesized and subjected to a preliminary investigation at the Institute of Chemical Physics of the Academy of Sciences of the USSR. The drug is characterized by a higher antitumor activity, broader spectrum and lower general and cardiac toxicity. This is the first attempt of comparative biochemical investigation of rubomycin, ruboxyl and the nitroxyl radical at the level of DNA replication. The effect of these drugs on the synthesis of DNA in the cells of leukemia P-388, the bone marrow and heart of mice was studied. It was shown that the degree and duration of the DNA synthesis inhibition in the tumor cells correlated well with the antitumor activity of the drugs. On the 3rd day after administration rubomycin and ruboxyl induced stimulation of the DNA synthesis in the cells of the bone marrow. This might be explained by transfer of a part of the population of the bone marrow cells from Go phase due to the cytotoxic damages of the proliferating cells. The DNA synthesis stimulation in the bone marrow was most likely associated with the toxic effect of the drugs. No correlation between the cardiotoxicity and inhibition of the DNA synthesis in the heart cells of the mice was observed. The nitroxyl radical showed no biological activity on this model. The average lifespan of the mice treated with the nitroxyl radical was the same as that of the control animals. A decrease in the incorporation of 2-14C-thymidine into DNA of the tumor, bone marrow and heart was observed in the tumor carriers with development of the tumor.