[Quantitative model of human erythrocyte glycolysis. II. Effect of arsenate on glycolysis. Experimental study of the relationship between the rate of glycolysis and the ATP concentration]. / Kolichestvennaia model' glikoliza éritrotsita cheloveka. II. Vliianie arsenata na glikoliz. Eksperimental'noe issledovanie zavisimosti skorosti glikoliza ot kontsentratsii ATF.

The effect of arsenate on human erythrocyte glycolysis was studied. The stationary rate of glucose consumption rises and then drops with a gradual increase of arsenate concentration while ATP and glucose-6-phosphate concentrations drop monotonically. A plot of glucose consumption rate against ATP concentration gives a bell-like curve. This curve is the same for different donors if it is plotted in relative units with values at zero arsenate concentration taking for 100%, while the absolute values obtained for separate donors are very different. The normal (physiological) point is situated on the steeply descending part of the curve.

[Analysis of geometric parameters and mechanical properties of erythrocytes by filtration through nuclear membrane filters. II. Experimental verification of a mathematical model]. / Analiz geometricheskikh parametrov i mekhanicheskikh svoistv éritrotsitov metodom fil'tratsii cherez membrannye iadernye fil'try. II. Eksperimental'naia proverka matematicheskoi modeli.

In the accompanying paper the process of erythrocyte passage through pores of membrane nuclear filters has been modelled. In order to test the model we have studied how the filtration rate of human erythrocyte suspension depends on osmoticity of the resuspending medium at various experimental conditions. We have tested and verified the model conclusion that the zero filtration rate is reached at the critical osmoticity value which depends only on geometrical parameters of the pore and the cell and not on other properties of the erythrocyte. It has been demonstrated that the relative filtration rate only weakly depends on the hydrostatic pressure, in agreement with the model predictions. There is a good correspondence between the model and the experimental data about how the filtration rate is influenced by the viscosity of the intracellular content and the mechanical characteristics of the erythrocyte membrane at various temperatures.

[Analysis of geometric parameters and mechanical properties of erythrocytes by filtration through nuclear membrane filters. I. A mathematical model]. / Analiz geometricheskikh parametrov i mekhanicheskikh svoistv éritrotsitov metodom fil'tratsii cherez membrannye iadernye fil'try. I. Matematicheskaia model'.

A mathematical model is constructed, which quantitatively describes the rate of erythrocyte passage through pores of nuclear membrane filters during filtration of a diluted erythrocyte suspension upon action of a constant hydrostatic pressure. The following main factors have been taken into account: geometrical constraints linking the surface area of the erythrocyte membrane, the erythrocyte volume and the geometrical parameters of the filter pores; mechanical characteristics of the erythrocyte membrane; viscosity of the intracellular content. Analysis of the model allows us to conclude that it is possible to extract information about all above erythrocyte characteristics from the experimental curves describing, dependency of the filtration rate of the erythrocyte suspension from the osmoticity of the outer medium.

[Quantitative model of human erythrocyte glycolysis. Relationship between erythrocyte energy metabolism and Na+, K+-ATPase activity]. / Kiolichestvennaia model' glikoliza éritrotsita cheloveka. Zavisimost' énergeticheskogo metabolizm éritrotsitov ot aktivnosti Na+, K+-ATFazy.

The influence of the changes of the transport Na+, K+-ATPase activity on the human red blood cell (RBC) glycolysis was studied. Two different types of energetic regulation were found out under the strophanthin inhibition. A decrease of ATP comsumption results in a drop of glucose consumption and lactate production in the first type regulation of RBC. In the second type regulation of RBC the glucose consumption does not change after ATPase inhibition and the excess metabolic flux is directed through the hexosemonophosphate shunt. In both cases the resulting decrease of ATP production leads to the ATP level stabilization. An increase of potassium ions concentration in the external medium does not influence the RBC glycolysis. The valinomycin added increases the glucose consumption and the lactate production. The cell volume decreases under the effect of valinomycin.

[Quantitative model of human erythrocyte glycolysis. Region of cell viability determined by ATP concentration]. / Kolichestvennaia model' glikoliza éritrotsita cheloveka. Oblast' zhiznesposobnosti kletki, opredeliaemaia kontsentratsiei ATF.

The boundaries of the cell vitality domain in the enzyme activity space are calculated on the basis of a mathematical model of erythrocyte glycolysis. The boundaries are determined by key metabolite concentrations. The results obtained are compared with experimental data related to erythrocytic enzymopathies. It is shown that theoretical boundary enzyme activities coincide with the activities of hexokinase and in some cases phosphofruktokinase in enzyme deficient erythrocytes.

[Quantitative model of human erythrocyte glycolysis. I. Relationship between the stationary rate of glycolysis and the ATP concentration]. / Kolichestvennaia model' glikoliza éritrotsita cheloveka. I. Zavisimost' statsionarnoi skorosti glikoliza ot kontsentratsii ATF.

A mathematical model is presented of the Embden--Meyerhof pathway in the human red blood cell. The rate of the system stationary flux is determined by the first part of the chain including three enzymatic reactions. The function has been calculated which describes the dependence of the stationary rate of glucose consumption and ATP production on the concentration of ATP. The curve has a bell shape with the physiological normal point situated in the descending segment. The descending segment is a result of the inhibition of the phosphofructokinase by ATP and the strong inhibition of the hexokinase by glucose-6-phosphate.

[Effect of temperature, daunorubicin concentration and suspension hematocrit on daunorubicin binding by human erythrocytes]. / Vliianie temperatury, kontsentratsii daunorubitsina i gematokrita suspenzii na sviazyvanie daunorubitsina éritrotsitami cheloveka.

When incubated in the isotonic medium containing daunorubicin, human erythrocytes bound daunorubicin. At the initial concentration of daunorubicin in the medium of not higher than 1 mg/ml, the suspension hematocrit of about 30 per cent and the temperature of 25 degrees C the maximum binding of daunorubicin was achieved in approximately 30 minutes and was equal to about 80 per cent of the initial content. When the temperature was lowered from 30 to 15 degrees C the initial rate of the daunorubicin binding by the erythrocytes decreased several times. The increase in the initial concentration of daunorubicin in the medium from 1 to 5 mg/ml resulted in an increase in the absolute value of the initial rate of the daunorubicin binding by the erythrocytes. However, the relative rate of the binding decreased. By varying the value of the suspension hematocrit it is possible to provide either a more complete binding of daunorubicin (at higher hematocrit values) or rapid increasing of the daunorubicin concentration in the erythrocytes (at lower hematocrit values). When the erythrocytes were incubated in the presence of daunorubicin there was observed a marked leakage of hemoglobin from them (up to several per cent). The hemoglobin leakage increased with an increase in the temperature and daunorubicin concentration.

[Use of antibiotics and their combinations with immunomodulators in treatment of experimental salmonellosis in albino rats]. / Primenenie antibiotikov i ikh sochetanii s immunomoduliatorami s lechebnoi tsel'iu pri éksperimental'nom sal'monelleze u belykh krys.

Efficacy of the combined therapy of experimental salmonellosis was studied on albino rats with using ampicillin, gentamicin, tetracycline and immunomodulators such as levamisole and quadevite. The influence of the combined chemoimmunotherapy on the indices of the nonspecific resistance of the animals i.e. the titers of lysozyme and beta-lysines, the complement activity and the blood serum bactericidal index was investigated. An increase in the survival of the animals exposed to the combinations of tetracycline with levamisole and quadevite by comparison with the animal survival after the monotherapy was revealed. The combinations of gentamicin with quadevite and tetracycline with the immunomodulators significantly increased the blood serum bactericidal index.

[Detrimental effects of Daunorubicin and Doxorubicin on human erythrocytes in vitro]. / Povrezhdaiushchee vozdeistvie Rubomitsina i Doksorubitsina na ritrotsity cheloveka in vitro.

In isotonic medium, daunorubicin in the concentration range of 0.5-5.0 mg/ml of cells and doxorubicin in the concentration range of 0.2-1.0 mg/ml of cells caused hemoglobin (Hb) and K+ to efflux from red blood cells (RBC), to increase RBC size and to lower their deformability. Hb and K+ efflux rates were proportional to the antibiotic concentrations and remained stable for a few hours. Hb efflux did not change significantly in the 4-21 degrees C range (exempt at an experimental concentration of daunorubicin of 5.0 mg/ml of cells) but soared sharply at 37 degrees C. At the daunorubicin and doxorubicin concentration of 0.2 mg/ml of cells, Hb and K+ efflux virtually did not differ from control values. At the antibiotic concentration of 1.0 mg/ml of cells, 37 degrees C, Hb efflux rate was 0.34-5.6%, while that of K+(-) 1.0-8.2%, per hour, of possible maximum value. For the daunorubicin level of 5.0 mg/ml of cells, the respective values were 10 and 17%. At the daunorubicin concentration of 5.0 mg/ml, at 4 degrees C, Hb efflux from RBC was significantly higher than at 21 degrees C. RBC malleability, which was determined as their ability to pass through membrane filters having 3 mm dia pores, did not differ significantly from control values for a few hours antibiotic concentrations not exceeding 0.3 mg/ml of cells. At the antibiotic concentration of 1.0 mg/ml and higher RBC deformability dropped to zero within 10 min. ATP level in RBC practically remained identical to control values during incubation with the antibiotics for several hours.

[Changes in the regulatory characteristics of glycolysis in erythrocytes during storage of donor blood]. / Izmeneniia reguliatornoi kharakteristiki glikoliza v éritrotsitakh pri khranenii donorskoi krovi.

Changes in the glycolysis regulatory pattern (dependence of the glycolysis rate on ATP concentration) in erythrocytes were studied during donor blood storage using glucose-citrate hemoconservant 7b. During the first two weeks of storage the glycolysis regulatory pattern in the erythrocytes remained practically unchanged being represented by a bell-shaped curve similar to that found in fresh erythrocytes. At the same time, the physiological point of glycolysis shifted towards the maximal level on the curve. When the physiological point reached the maximal value, the shape of the curve began to change. The maxima on the curve became less distinct and shifted down and to the left from the initial position. These changes occurred within two-four weeks of storage. In some cases at the latest steps of storage the maxima on the glycolysis regulatory pattern disappeared leading to the monotony of the curve. The changes observed occurred in blood of different donors at various periods of storage. The nature of the changes observed and their influence on the erythrocyte viability are discussed.

[Immunomodulating effect of levamisole in antibiotic therapy]. / Immunomoduliruiushchee vliianie levamizola v usloviiakh antibiotikoterapii.

The use of ampicillin, benzylpenicillin, gentamicin, erythromycin, cefamezine or cephaloridine in combination with levamisole aimed at increasing their efficacy and correcting the adverse reactions was studied. Immunological activity of the antibiotics was comparatively characterized by using standard methods. It was shown that the character of the antibiotic effect on the basic factors of nonspecific resistance and immunity was heterogeneous. Schemes for using the antibiotics in combination with levamisole for correcting the detected disorders in the immunity status of the experimental animals were developed.

[Effect of combined preventive use of quadevit with antibiotics on the survival and humoral immune response in experimental studies]. / Vliianie kombinirovannogo profilakticheskogo primeneniia kvadevita s antibiotikami na vyzhivaemost' i gumoral'nyi immunnyi otvet v éksperimente.

An attempt to correct with quadevit immunodepression due to prophylactic administration of benzylpenicillin and gentamicin for 6 days provided positive results. There was a significant increase in the quantities of Ig 19S and Ig 7S after the animal immunization with the bacterial antigen, an increase in the number of the AFCs in the spleen of the albino mice in response to administration of sheep erythrocytes and an increase in the survival rate of the animals with salmonellosis. The simultaneous use of quadevit with cefamezine and erythromycin did not lower the unfavourable influence of the antibiotics on the immune status of the animals.

[Immobilized forms of daunorubicin in patients with acute leukemia]. / Primenenie immobilizirovannykh form daunorubitsina u bol'nykh ostrymi leikozami.

AIM: To study pharmacokinetics of liposomal daunorubicine DaunoXome and daunorubicine (rubomycin) associated with red cells: to assess their effectiveness and toxicity in patients with acute leukemia. MATERIALS AND METHODS: 7 patients with resistant or recurrent acute leukemia entered the trial. Of them 2 patients had acute myeloid leukemia. They received DaunoXome in dose 100 mg in days 1, 2 and 3 of 7 + 3 program. 1 patient had pretreated acute promyelocytic leukemia. This patient received 5-day course of DaunoXome in a dose 100 mg in the presence of ATRA therapy. 4 patients were given single dose daunorubicin associated with autoerythrocytes in the courses RACOP and 7 + 3 in a dose 45 mg/m2. Concentrations of free, bound and liposomal daunorubicin were determined spectrofluorimetrically in chlorophorm extracts of plasm, blood, liquor and bone marrow specimens. RESULTS: Immobilization of daunorubicin on the red cells and liposomes changes pharmacokinetics of the drug: peak concentrations change and the area under the concentration curve increases. Tolerance of DaunoXome and daunorubicine associated with red cells was satisfactory in all the cases: clinical and echo-CG signs of cordiotoxicity were absent, myelotoxicity was similar to that of free daunorubicine. DaunoXome was effective in 2 of 3 patients with acute myeloblastic leukemia. CONCLUSION: The findings are of practical interest for physicians designing new programs of therapy of acute leukemia.

[A filtration study of erythrocyte deformability]. / Filtratsionnoe issledovanie deformiruemosti éritrotsitov.

The study of two flow methods (constant flow method and initial flow rate method) has been conducted to specify and compare methodological approaches to quantitation of red cell deformability. Washed red cells were resuspended in saline medium with glucose and albumin and examined for deformability by the above methods under different conditions. The parameters are presented to characterize flow curves obtained with the constant flow method. The authors have established optimal conditions for the measurements: the composition of the medium, the suspension HCT, leukocyte number, filtrate types, etc. With meeting of the above methodological requirements, both the methods permit quantitation of red cells deformability and can be utilized for stored blood and erythrocyte mass quality control.