Biomedical subjects
Publications and source records attributed to V V Biriukov.
Results of the efficacy and safety analysis of low-molecular weight heparine clexane (sodium enoxaparine) in patients with urological diseases were adduced. Postoperative usage of clexane along with epidural anesthesy had prevented occurrence of hypercoagulation as well as epidural and spinal hematoma.
Results of comparative studying of influence of low-molecular weight heparin clexane (enoxaparine sodium) and nonfractionized heparin on coagulational properties of blood in patients with uncomplicated urosepsis are presented. It was established that application of clexane promotes an effective prophylaxis of thromboembolic complications without rising of the hemorrhage occurrence risk.
Clinical and bronchographic data were juxtaposed with the results of selective histological examination of the resected parts of lungs from 3 to 14-year-old children suffering for several years from persistent cough and recurrent pneumonias. The defects of small and mean bronchi branching are found in 66% of cases (out of 50) and in 64% there was diverticulosis of the mucous membrane of large and small bronchi that is followed by pseudopoliposis and the development of deep "pouches". All this is followed by bronchus-associated lymphoid tissue hyperplasia, development of peribronchial pneumonia foci, chronic bronchitis, obturation syndrome.
A mathematical model for continuous biosynthesis of a metabolite in a battery of two apparatuses with ideal agitation is described and analysed. In the first apparatus of the battery it is advisable to maintain a high specific rate of culture growth for continuous accumulation of young active biomass while in the second apparatus a low growth rate is expedient which provides a change in the culture metabolism to biosynthesis of the required product. To make the continuous two-stage process efficient, it is necessary to add an extremely concentrated solution of the nutrients to the second apparatus of the battery. Influence of the oxygen transport velocity on the maximum attainable concentration of the biomass and the process capacity by the required product was studied.
A theoretical method for estimating limiting stage of oxygen mass transfer is proposed. The method is based on calculation and comparison of particular resistance of separate stages of mass transfer: mass transfer through the gas-liquid boundary, oxygen transport in the liquid phase, mass transfer through the liquid-cell boundary and oxygen consumption by microbial cells. With the proposed method, particular resistance was calculated and conditions for oxygen mass transfer were analyzed in the biosynthesis of sisomicin as an example. As a result the conditions for reproducibility of the process in apparatus of various size were determined.
Conditions were experimentally studied for reproducing sisomicin biosynthesis by up-to-down scaling. It was shown that respiration intensity as a parameter of antibiotic biosynthesis scaling-down had certain limitations connected with multistage oxygen mass transfer. The parameter could be used only when the limiting stages of oxygen mass transfer coincided. It was confirmed experimentally that it was possible to apply the previously proposed theoretical method to estimation of the limiting stage of oxygen mass transfer.
It was shown possible to use feeding of hydrogen peroxide as a method for investigating the impact of dissolved oxygen concentrations on growth and development of microorganisms. The influence of pO2 on the respiration intensity was studied in penicillin- and erythromycin-producing cultures and it was found that dependence of the respiration intensity on pO2 had the form of a curve with saturation, at pO2 equal to zero the value of the culture respiration intensity being different from zero. A mathematical model accounting for the presence in the fermentation broth of microbial agglomerates with the average size depending on the agitation conditions is proposed for describing the relationships.
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Special methods of clinical examination and morphometrical studies were used to investigate the regional blood flow in 56 patients. The method of perfusion scintipneumography and electropneumoplethysmography were shown to be more informative. Differences in the state of peripheral hemodynamics in patients of different groups are shown. Considerable morphological alterations in the capillary network found in patients with a coarse deforming bronchitis confirmed the reasons for the surgical treatment of such patients.
The effect of the aeration levels in flasks on the rate of oxytetracycline biosynthesis and other kinetic characteristics was studied. It was shown that changes in the medium volume in flasks, dilution of the fermentation broth with water or its filtrate and the use of oxygen for aeration had a significant effect on the characteristics studied. Special experiments with low concentrations of the biomass were performed for investigation of the effect of dissolved carbon dioxide on the kinetics of the process.
Short-term experiments on the effect of temperature on the rate of oxytetracycline biosynthesis and consumption of carbohydrates, ammonium nitrogen and inorganic phosphorus were performed under various conditions of mass exchange. Complete fermentation cycles were also carried out at the same temperatures. It was shown that the temperature optimal under conditions of a short-term experiment was not optimal for the complete fermentation cycle. In the latter case the results also depended on the aeration and agitation conditions. It is suggested that temperature has a nonspecific effect by changing the conditions of oxygen supply to the microbial culture.
It was found that estimation of the samples of immobilized enzymes and cells by particular characteristics often produces contradictory results. This makes difficult the choice of the best biocatalyst. Integral criteria equally taking into account both the quality of the biocatalysts and the amounts of the native enzyme required for their production are described. Example confirming the advantages of the integral criteria in estimation of large lots of the samples of the biocatalysts are cited.
The possibility of using a simplified model of the kinetics of the enzymatic process catalyzed by the immobilized enzyme for definition of the integral criteria for the efficacy of the immobilization process is theoretically validated. The means for determination of the initial characteristics for these criteria, i.e. the constants of the inactivation rate of the immobilized enzyme and the critical value of the catalyst activity are discussed. The use of the catalyst under the manufacturing conditions at the value lower than the critical one is not advisable.
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Equations connecting the rate of metabolite biosynthesis and the specific growth rate were found analytically in the simplest case when both of the kinetic characteristics depended on the substrate concentration in the medium according to the Monod equation. The character of the relation in connection with the ratio of the kinetic constants for the growth and biosynthesis was analysed. It was shown that the equations based on the kinetic regularities were rather simple and correlated with the Luedeking and Piret equation when the kinetic constants were equal. The choice of the equation type was determined by the character of the curve convexicy of the relationship between q and mu. An example of experimental result approximation by one of the equations is presented.
Equations of relationship between the rate of metabolite biosynthesis q and specific rate of the culture growth mu were set up theoretically on the basis of kinetic equations connecting q and mu with the environment factor S. The inhibiting effect of S on q and/or mu was considered in the Ierusalimsky or Andrews equations. The equations of relation q (mu) provide consideration of various experimental relations. The equation choice is based on the character of the convexity of concavity of the experimental curves of relation q (mu). Equations q(mu) posess a less number of constants than both equations q (S) and mu (S). It was found that when S affected mu as a limiting or inhibiting factor depending on its value, relation q(mu) was not simple. In this connection it is not convenient for use in mathematical description of the process and control problems.
Theoretical analysis of the relationship between the rates of the biomass growth mu and biosynthesis of the metabolites q was performed, when the both kinetic characteristics depended not on one, but on two and more environmental factors. Apparently similar effects of the factors on the biomass growth and biosynthesis (limiting, inhibition or combined limiting-inhibition) at different values of the kinetic equation constants were studied. Examples of different character of the effects of one or both factors on the growth and biosynthesis are discussed. In all cases it was found that relationship q (mu) was uncertain. The relationship pattern was connected with the fact, by means of which the culture growth was controlled, while the absolute values of the kinetic characteristics depended on the value of the second unchangeable factor. When relationship q (mu) was obtained by means of correlation between the experimentally found values of q and mu at accidentally changed factors of the environment, the relationship form could be anyone and not connected with any regularities of the microbiological process. Setting up an equation for mathematical description of relationship q (mu) in such cases is not correct. The only exception is the process, in which biosynthesis is directly connected with the culture growth rate.
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