[Effect of cyclosporin on various metabolic processes in fungi]. / Vliianie tsiklosporina na nekotorye metabolicheskie protsessy gribov.

Sensitivity of the representatives of Aspergillus and Piricularia to various concentrations of cyclosporine (in the submerged culture) was studied for choosing the test object for the subcellular investigation of the mechanism of the cyclosporine antifungal action. Changes in the main physiological and biochemical parameters of the fungal cells under the action of cyclosporine in concentrations of 10 to 80 micrograms per 1 ml of the medium were characterized. Low concentrations of cyclosporine (10 to 20 micrograms/ml) did not inhibit the growth of Aspergillus niger but induced stimulation of the growth processes. Only at a concentration of 80 micrograms/ml the inhibitory effect was observed. At the same time there was detected a dramatic stimulation of the culture respiration via the basic respiration chain. In the culture of Piricularia oryzae only inhibition of the culture growth even at the minimum concentration of cyclosporine (10 micrograms/ml) was recorded. Both the cyclosporine sensitive test objects i.e. A. niger and P. oryzae had an alternative cyanide resistant system of the electron transport. In the experiments with A. niger the cyclosporine effect on the synthesis of protein and RNA was revealed. The study provided data on the changes in the morphogenesis of the A. niger cells under the effect of cyclosporine.

[Effect of H-ATPase stimulators on cyclosporin biosynthesis]. / Vliianie stimuliatorov H-ATFazy na biosintez tsiklosporina.

An analogy was observed between the mechanisms of action of phytohormones on plant cells and cells of the fungus producing cyclosporine. Fusicoccin and cytokinin were shown to have a high stimulating action on the biosynthesis of cyclosporine. The stimulating concentrations of the phytohormones and the time of their maximum effect were determined. The electron microscopic studies demonstrated that an increase in the level of the cyclosporine synthesis correlated with a significant increase in the number of the cells in the state of the coagulation necrosis.

[A system for screening natural immunosuppressors]. / Sistema skrininga immunosupressorov prirodnogo proiskhozhdeniia.

Criteria for directed screening of antibiotics with immunosuppressive action were defined. The first stage included screening of cultures producing antiaspergillous antibiotics. At the second stage, the antibiotics whose antifungal activity decreases in the presence of insulin (at the background of calcium salts) and erythromycin and increases in the presence of verapamil were selected. The screening of antibiotic-producing cultures among 123 strains of mycelial fungi and 181 strains of actinomycetes resulted in isolation of 3 fungal cultures and 2 actinomycetes which produced antibiotics corresponding to cyclosporine A as evidenced by thin-layer and high performance liquid chromatographies.

[Cyclosporin biosynthesis and dynamics of bioenergetic processes in cyclosporin-producing strain]. / Biosintez tsiklosporina i dinamika bioénergeticheskikh protsessov u produtsenta tsiklosporina.

An attempt was made to show a correlation between definite bioenergetic parameters of the cells of the cyclosporine-producing culture and biosynthesis of cyclosporine. It was found that the three strains producing cyclosporine used in the study had an alternative cyanide-resistant pathway along with the classical cytochrome chain. In the strain forming only traces of the cyclopeptide during fermentation of the cyanide-resistant respiration constituted 60 to 80%. In the isogenic highly productive strains the cyanide-resistant respiration appeared to be markedly decreased beginning from the 1st day of fermentation and during the maximum biosynthesis of cyclosporine (on day 4 or 5 of fermentation) it reached zero. The ATP content in the cells of the highly productive strain, despite its decrease by the antibiotic biosynthesis peak, remained at a much higher level than that in the strain producing only traces of cyclosporine. A procedure for isolating functionally active mitochondria from the protoplasts was developed and a bioenergetic characterization of the mitochondria isolated from the strains with different antibiotic productions is presented.

[Identification of Mycobacterium tuberculosis by the method of gas-liquid chromatography]. / Identifikatsiia mikobakterii metodom gazozhidkostnoi khromatografii.

Gas-liquid chromatography was used to study the composition of fatty acids and hydrocarbons of different types of Mycobacteria, including M. tuberculosis, opportunistic Mycobacteria and acid-fast saprophytes. In terms of composition of fatty acids and hydrocarbons, clinical and laboratory strains of M. tuberculosis are very similar. The cellular higher fatty acids of M. tuberculosis differ much from those of opportunistic Mycobacteria and acid-fast saprophytes. The findings can be used for the identification and differentiation of different types of Mycobacteria.

[Regulation of the biosynthesis of secondary metabolites in Streptomyces galbus]. / Reguliatsiia biosinteza vtorichnykh metabolitov Streptomyces galbus.

The effect of inhibiting and stimulating agents on the biosynthesis of secondary metabolites (actinomycin X and melanoid pigments) was studied in Streptomyces galbus as a function of the growth temperature. D-Valine was shown to inhibit actinomycin synthesis and to stimulate production of melanoid pigments. Tryptophan stimulated the synthesis of both actinomycin and melanoid pigments. The temperature of growth was found to regulate the biosynthesis of secondary metabolites by the culture. The organism synthesized actinomycin at 28 degrees C, but it switched to the production of melanoid pigments at 42 degrees C. This may be considered as a protective reaction of the organism to an increase in the temperature of the environment and in UV radiation which is possible under natural conditions as a consequence of temperature elevation. The paper presents a hypothetical scheme for the regulation of biosynthesis of actinomycin and melanoid pigments by temperature. According to the scheme, the culture synthesizes secondary metabolites from tryptophan to hydroxykynurenine via a general pathway which is then bifurcated: at 28 degrees C--through methylhydroxyanthranilic acid to actinocin to actinomycin; at 42 degrees C--through hydroxyanthranilic acid, o-aminophenol, pyrocatechol, and possibly, o-benzoquinone, to melanin.

[Nature of the brown pigment and the composition of the phenol oxidases of Streptomyces galbus]. / O prirode burogo pigmenta i sostave fenoloksidaz Streptomyces galbus.

The culture of Streptomyces galbus ISP-5089 has a yellow-green colour caused by the accumulation of actinomycin X when it is grown in synthetic media at 28 degrees C; the colour turns dark-brown at 42 degrees C due to the synthesis of melanoid pigments. The population composition does not undergo any noticeable changes in that case, an no specific melanin-synthesizing mutants appear as a result of autoselection . The biosynthesis of actinomycin X (at 28 degrees C) and melanoid pigments (at 42 degrees C) is regulated by temperature. At 42 degrees C, L-DOPA oxidase is synthesized and laccase is activated; these two enzymes are involved in the synthesis of melanoid pigments. The organism does not has tyrosinase. The synthesis of melanoid pigments, when the mesophilic culture of S. galbus ISP-5089 is grown in the regime of superoptimal temperatures (42 to 47 degrees C), may be considered as a protective ecological reaction of the organism to unfavourable conditions of the environment.

[Screening of beta-lactamase inhibitors among representatives of the genus Micromonospora and the genus Streptoverticillium]. / Poisk ingibitorov beta-laktamaz sredi predstavitelei roda Micromonospora i roda Streptoverticillium.

A total of 123 cultures of the genus Micromonospora and 89 cultures of the genus Streptoverticillium were studied for their capacity to produce beta-lactamase inhibitors. It was shown that streptoverticilla were highly resistant to beta-lactam antibiotics. No organisms producing beta-lactamase inhibitors were detected among the cultures of this genus. As for Micromonospora, 30 cultures (24.4 per cent) of this genus produced inhibitors. They were most frequently isolated from orange and brown cultures of Micromonospora. The inhibitors had no antibacterial activity, inhibited beta-lactamases of gram-negative bacteria and did not inhibit exogenic beta-lactamases of staphylococci. Their inhibitory activity was evident only with the use of isolated enzymes. With the use of intact growing cultures of gram-negative bacteria producing the same enzymes (Pseudomonas, Klebsiella, Enterobacter) no inhibitory activity was observed. Though the inhibitors had some features in common, they did not seem to be similar, since they had different spectra with respect to their effect on various beta-lactamases of gram-negative bacteria.

[Effect of different food rations on nonspecific immunological reactivity indices in guinea pigs]. / Vliianie razlichnykh pishchevykh ratsionov na nekotorye pokazateli nespetsificheskoi immunologicheskoi reaktivnosti morskikh svinok.

The highest activity of nonspecific immunity factors (phagocytic activity of the blood leucocytes, lysozyme and complementary activity of the blood sera) was defected in guinea pigs receiving food rations containing 19% of protein and 16% of roughage. These data jestify recommending to feed the test guinea pigs on granulated products, this being more convenient and suitable than using natural ones.

[Some natural immunity indices in mice against a background of varied fat and carbohydrate correlations in the diet]. / Nekotorye kokazateli estestvennogo immuniteta u myshei na fone razlichnykh sootnoshenii zhirov i uglevodov v ratsione

In mice of the SWR, C3HA, CBA/j and non-inbred lines kept on diets with different combinations of carbohydrates and fats some characteristics of the natural immunity (phagocytic activity of leucocytes, bactericidal and lysozyme activity of the blood serum) were studied. It is shown that the proportions of the fatty and carbohydrate components in the diet is of a definite significance for the defensive forces of the organism.