[Treatment of supraventricular tachyarrhythmias in children].
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Biomedical subjects
Publications and source records attributed to N V Orlova.
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The value of evaluating the protein levels at the acute stage was examined to define the clinical course and prognosis of myocardial infarction. The time course of hospital myocardial infarction was studied in 117 patients. The Manchini radial immunodiffusion with reference monospecific antisera was employed to determine individual proteins during the acute stage (orosomucoid, C-reactive protein, alpha 1-antitrypsin, C3 complement, ceruloplasmin). The level of circulating immune complexes was measured by polyethylene glycol precipitation. There was a close correlation between the circulating immune complex levels and some acute phase parameters, suggesting the relationship between immune and inflammatory processes. The changes in the magnitude of some acute phase parameters and circulating immune complexes were found to be significant in predicting the development of complications and the fatal outcome of the disease.
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The effect of some components of corn-steep liquor, such as biotin, organic nitrogen, inorganic phosphorus and other mineral elements on biosynthesis of polymyxin B by B. polymyxa, strain 1538 was studied. It was found that biotin and organic nitrogen had the most significant effect on the antibiotic accumulation. The effect of inorganic phosphorus and other mineral elements on accumulation of polymyxin by B. polymyxa, strain 1538 was less significant.
The effect of phosphorus on biosynthesis of polymyxin B by B. polymyxa 1538 was studied and its optimal concentration in the synthetic and two complex media was determined. Correlation between the culture growth and consumption of the main components, on the one hand, and concentration of phosphorus in the medium, on the other hand, was found. It was shown that the effect of phosphorus on biosynthesis of polymyxin B did not depend on the carbon source in the medium and aeration conditions.
The effect of a number of the most important amino acids on the growth of B. polymyxa 1538 and polymyxin B biosynthesis was studied. It was found that all of the amino acids tested except D-L-threonin and L-alpha-gamma-DABA inhibited the initial growth of the organism. D-L-threonine and L-alpha-gamma-DABA had some stimulating effect on the culture growth without affecting the final accumulation of the biomass. The antibiotic synthesis proceeded more vigorously when the medium contained D-L-threonine, L-alpha-gamma-DABA, L-asparagine, L-proline, L-glutamine, D-L-asparaginic acid and L-glutamic acid in the concentrations tested. Neither of the tested amino acids used alone or in combination provided the levels of polymyxin B biosynthesis observed on the media containing rich sources of organic nitrogen.
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Methodologic approaches to the development of methods for controlled biosynthesis of antibiotics are discussed with reference to oxytetracycline biosynthesis. The method of acute experiments in conjunction with mathematical methods of experiment planning was used for determination of the substrate concentrations optimal for the culture growth and biosynthesis of oxytetracycline. It was found that such mathematic procedure provided simultaneous determination of optimal concentrations of all the substrates.
It was found that under conditions of a short-term cultivation of the Co-deficient mycelium of M. purpurea var. violaces 1935 in the synthetic medium the level of gentamicin biosynthesis increased on the average by 2--2.5 times when cyancobalamine, methylcobalamine, L-methionine or L-serine were added to the medium. Glycine and H2-pholate increased the gentamicin yield on the average by 1.5--1.8 times. When the concentration of L-methionine in the medium was optimal, production of gentamicin by the Co-deficient mycelium markedly increased on addition of extra amounts of cyancobalamine into the medium. An analogous high level of gentamicin biosynthesis was observed in the absence of L-methionine, when combinations of H2-pholate and L-serine or cyancobalamine, H2-pholate and glycine were added to the medium. The data of the study indicate that the pholate-dependent neogenesis of -CH3 group and the methyl-B12-dependent resynthesis of L-methionine play an important functional role in biosynthesis of gentamicin.
Lincomycin added to the cultivation medium induced a number of changes in the organism producing it during its ontogenesis when grown recurrently on liquid media. It was found that lincomycin inhibited the culture growth and decreased the absolute amount of the antibiotic synthesized while the specific activity of the culture increased. A number of cytomorphological rearrangements relevant to the adaptive protective reactions was found. It is suggested that an increase in the resistance of the culture to the antibiotic produced by it at the late developmental stages is the result of the above protective reactions.
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It was shown that addition of cobalt ions or vitamin B12 to the fermentation medium resulted in an increase in the level of gentamicin accumulation, the relative content of the most methylated components C1 and C2 in the gentamicin complex being increased, while the content of the least methylated components CIa and "minors" decreased. Addition of sulphodimezine lowered the gentamicin biosynthesis rate and the relative content of gentamicins C1 and C2. It was supposed that cobalt stimulated the B12-dependent synthesis of methionine, being the source of the methyl groups for biosynthesis of the methylated components of gentamicin complex.
Dependence of biosynthesis of gentamicin and vitamin B12 on complex and "synthetic" media under conditions of decreased aeration, increased phosphorus levels and non-optimal content of carbon source was studied. The decreased levels of vitamin B12 production under conditions of the non-optimal content of the carbon source and increased phosphorus levels in the medium resulted in decreased production of the antibiotic complex as a whole and decreased relative content of the most methylated gentamicins C1 and C2 in the complex. Decreased aeration lowered the mycelium productivity with respect to the antibiotic production without changing the ratio of the components in the complex and the level of vitamin B12 production.
The effect of starch and ammonium sulphate on the growth of the oxytetracycline-producing organism was studied using the procedure of acute experiments. It was proposed to use a mathematical model for description of the dependences taking into account the possibility of limiting or suppressing the growth of the culture by any of the above substrates as dependent on their ratio in the medium. Satisfactory confirmity of the model to the experimental data was shown. It was noted that similar models may be successfully used for description of such dependences as curves with flat plateau in the region of the maximum which are often met in microbiological processes.
A synthetic medium for biosynthesis of gentamicin was developed. It includes maltose, gelatine, potassium phosphate, ammonium sulphate, cobalt chloride, sodium chloride, magnesium sulphate and zinc sulphate. The dynamics of the biochemical changes in the above medium was studied.
The effect of different inorganic sources of reduced and oxidized nitrogen on biosynthesis of gentamicin was studied. It was shown that both the ammonium and the nitrate nitrogen were consumed by the antibiotic-producing organism. Out of all the salts tested only ammonium sulfate stimulated the biosynthesis of gentamicin. The positive role of this salt was due to both the ammonium and the sulfogroup, since the presence of the sulfogroup alone in sodium sulfat, magnesium or sulfuric acid resulted only in partial stimulation of gentamicin biosynthesis. Simultaneous addition of sulfuric acid ammonium nitrate which suppressed the antibiotic biosynthesis when used alone was equal to introduction of ammonium sulfate.
Consumption of oxygen by Act. rimosus depending on the medium composition was studied. It was shown that the level of dissolved oxygen in the fermentation broth decreased as the level of carbohydrates in the fermentor increased from 6 to 7.5 per cent. Under such conditions oxytetracycline biosynthesis appeared to be limited by oxygen and the maximum level of the antibiotic was not attained. A 2-fold increase in the concentration of the medium components resulted in an almost 2-fold increase of the biomass, while the potency level increased only by 54 per cent. The oxygen deficiency lowered the mycelium productivity with respect to the antibiotic biosynthesis to a greater extent that the rate of the culture growth.
The effect of cobalt on growth of Micromonospora purpurea var. violacea 1935 and biosynthess of gentamicin in complex soy-bean meal or "synthetic" gelatin medium was studied. In optimal concentrations cobalt increased the activity level of the culture fluid almost 6 times in both media having practically no effect on the amount of the mycelium formed. Addition of cobalt to the medium resulted in retardation of the organism growth and consumption of the nutrients. Stimulation of gentamicin biosynthesis by cobalt was inversely proportional to the time of the trace element addition. The cobalt effect depended on the aeration conditions, inorganic phosphorus level in the medium and physiological condition of the mycelium.