Antibiotiki i meditsinskaia biotekhnologiia = Antibiotics and medical biotechnology最新文献

Comparative antibacterial activity of two novel ureidopenicillins (azlocillin and piperacillin), carbenicillin and ampicillin against 170 clinical strains of Enterobacteriaceae and 43 strains of Pseudomonadaceae was studied. Higher antibacterial activity of azlocillin and piperacillin evident from lower frequency of resistant strains and lower MICs for the majority of the isolates was shown. Impact of the inoculum size on the MIC values was observed with respect to all the penicillins. The study on the kinetics of Pseudomonadaceae death under the effect of azlocillin and carbenicillin revealed an increase in the bacteria growth after 6- to 8-hour contact with therapeutic concentrations of azlocillin and 4-hour contact with carbenicillin. Nor renewal of the culture growth was observed within 10-hour contact with combinations of the penicillins and 2 micrograms/ml of gentamicin.

The chemically synthesized structure gene of human proinsulin was cloned in E. coli on the secretory vector containing regulatory elements of the Bacillus amyloliquefaciens alpha-amylase gene. The proinsulin gene was inserted by the EcoRI site located immediately after the DNA area encoding the alpha-amylase signal peptide. The E. coli cells transformed by such a plasmid produced hybrid protein consisting of the alpha-amylase signal peptide, five amino acid residues after the gene mating and human proinsulin. For accurate mating of the alpha-amylase gene leader sequence and proinsulin gene directed mutagenesis was performed on the filiform phage M13 mp9 with synthetic oligonucleotide. The hybrid gene was transferred to the vector molecule capable of replicating in Bacillus subtilis. It was shown that in the cells of both E. coli and B. subtilis there is synthesized protein interacting by the radio-immunological data with antibodies to porcine insulin, a large portion of immunologically active protein being detected in the periplasmic space of E. coli cells and in the culture fluid of B. subtilis cells which was indicative of proinsulin secretion directed by the alpha-amilase regulatory elements.

Sensitivity of 130 Proteus clinical strains was studied. Among beta-lactam antibiotics cefotaxime showed marked advantages with respect to various Proteus species. All the isolates of Proteus mirabilis were sensitive to cefuroxime. Cefamezin and cephapirin were inferior by their activity to cefotaxime and cefuroxime. They were characterized by close antibacterial activity and almost complete cross resistance. Ampicillin and carbenicillin proved to be the least efficient among the tested beta-lactam antibiotics. Isolates of Proteus vulgaris and Proteus penneri were more resistant to the penicillins and cephalosporins than the cultures of Proteus mirabilis. Sensitivity of separate Proteus species to gentamicin, tobramycin, sisomicin and amikacin was close. No cross resistance to the aminoglycosides was detected. Studies on the effect of different doses of the antibiotics revealed pronounced heterogeneity of Proteus by the feature of sensitivity to the tested antibiotics. The level of the heterogeneity was not the same for separate antibiotics. Cultures of Proteus mirabilis resistant to ampicillin, carbenicillin, cefamezin and cephapirin were more frequent in patients with urogenital infections as compared to patients with intestinal infections and suppurative-inflammatory processes of other localization.

Rifampicin pharmacokinetics in rats with acute affection of the liver with carbon tetrachloride did not alter. Chronic affection with carbon tetrachloride resulted in retarded elimination of the antibiotic from blood. There was observed no relationship between increased activities of transamination enzymes such as alanine aminotransferase and aspartate aminotransferase in blood serum of animals and changes in rifampicin pharmacokinetics.

Mechanism of interaction between separate levorin and nystatin component and lipid membranes was studied. It was shown that components A0, A1, A2 and A3 of levorin and components A1, A2, A3 and B1 of nystatin had a markedly pronounced membranotropic activity. Ion channel assembly and membrane conductivity were irreversibly controlled by concentration and membrane potential. Changes in selectivity of biomolecular lipid membranes depended on the structure of the antibiotics. The action of the levorin and nystatin components was based on increasing membrane conductivity by the mechanism of ion channel formation with parameters altering in relation to the antibiotic structure. Recommendations for directed synthesis of the antibiotic derivatives with high therapeutic efficacy are presented.

Gel diffusion regularities with respect to neomycin sulfate substances differing in their composition and the antibiotic separate components were studied on nutrient media of diverse composition. Optimal conditions for standardization of neomycin sulfate antimicrobial activity with using the agar diffusion method and synthetic medium are determined.

A method for determination of air-borne azlocillin in production areas was developed. The method is based on redox reaction proceeding with reduction of the molybdenum blue heteropolycomplex. The reaction involves the antibiotic preliminarily hydrolyzed by alkali with heating. The blue solutions are photometered at 750 nm. The detection limit in the assay sample volume is 0.005 mg. The method may be useful in development of maximum permissible concentration of azlocillin and its control in ambient air of production areas.

Benzylpenicillin interaction with amines in the nonaqueous phase was studied by pH dependence of the coefficient of the antibiotic distribution in the system of amine butyl acetate solution--water. A distribution scheme involving interaction of the amine molecular and cationic forms with benzylpenicillin and amine dissociation equilibrium in organic solution is described. On the basis of the experimental data the interaction and dissociation constants were determined for a number of aromatic and aliphatic amines.

Blood pharmacokinetics of the antitumor antibiotic aclarubicin and its metabolites was studied in rats with high performance liquid chromatography. The drug was administered intravenously in single doses of 5 and 10 mg/kg and orally in a single dose of 10 mg/kg. Aclarubicin pharmacokinetics was shown to be nonlinear. However, within every dose level it obeyed a two-compartment model. The nonlinearity could be due to saturation of aclarubicin binding to blood plasma proteins. The blood concentrations of metabolites MA144 N1 and MA144 T1 were close and after 12-18 hours exceeded those of unchanged aclarubicin. The half-lives of aclarubicin and its metabolites ranged from 16 to 21 hours. The MA144 T1 content was not significant. Following oral administration aclarubicin was rapidly absorbed and its bioavailability amounted to 35 per cent. Total bioavailability of aclarubicin, MA144 N1 and MA144 T1 was equal to 89 per cent. This enabled to consider the oral route of aclarubicin administration promising in tumor therapy.