Use of sodium nucleinate and its combinations with bacterial polysaccharides for preventing the nephrotoxic action of aminoglycoside antibiotics

Possible prevention of the nephrotoxic effect of different doses of aminoglycoside antibiotics, such as monomycin, kanamycin and gentamicin was studied experimentally on chinchilla rabbits. Substances increasing the cell resistance (sodium nucleinate, prodigiosan and pyrogenal alone and sodium nucleinate combinations with the bacterial polysaccharides) were used. It was shown that sodium nucleinate prevented nephrotoxicity of the aminoglycosides in the doses 2.5 times higher than the therapeutic ones. The combined use of sodium nucleinate with pyrogenal or prodigiosan was most effective. It prevented the nephrotoxic effect of the antibiotics in the doses 5 times higher than the therapeutic ones.     

Immunomodulating activity of RNA mononucleotides

The immunological action of RNA mononucleotides was studied in animal experiments. The most pronounced activation of macrophagal glycolysis urea cycle, oxidative phosphorylation, lysosomal hydrolases was induced by uridine 5'-monophosphate (5'-UMP) and guanosine 5'-monophosphate (5'-GMP); 5'-GMP also induced the maximum increase of the expression of FC gamma receptors. 5'-UMP ensured cell activation comparable with the total action of all mononucleotides. 5'-UMP and 5'-GMP, used in combination, produced the highest stimulating effect on macrophages, and the addition of low-active adenosine 5'-monophosphate (5'-AMP) to active 5'-UMP did not decrease the stimulating potency of the latter. The stimulating activity of sodium nucleinate exceeded that of all mononucleotides and their combinations. 5'-GMP and 5'-AMP induced the maximum activation of oxygen metabolism, evaluated by chemiluminescence, while 5'-UMP and cytidine 5'-monophosphate (5'CMP) proved to be inactive. The shift of the phosphate group to the third carbon atom or the production of the oligonucleotide 5'-UMP consisting of 5-15 nucleotides resulted in the appearance of the capacity for stimulating oxygen metabolism in macrophages. Their in vitro cultivation with 5'-GMP and 5'-AMP induced the maximum increase of cell spreading in comparison with other mononucleotides, while the maximum increase of phagocytosis was ensured only by 5'-UMP and 5'-GMP.2+ 5'-UMP and 5'-GMP enhanced nonospecific resistance to Salmonella typhi infection, and sodium nucleinate, to Pseudomonas pseudomallei and Pseudomonas mallei infections.     

Correction of immunologic reactivity depending on ABO system antigens in patients with purulent infections of soft tissue and shigellosis

The immunological study of more than 300 patients with purulent infection of soft tissues and shigellosis was carried out. The character and manifestation of the immunocorrecting action of sodium nucleinate were found to depend on the antigens of the AB0 system, which proved to be different in various type of pathology.     

Comparative effectiveness of immunomodulators in the therapy of bronchopulmonary diseases

One hundred and fifty-one patients with bronchopulmonary diseases were examined and it was shown that they had secondary immune deficiency mainly in the T-cells which could not be recovered with the routine therapeutic agents. The use of hemodez, levamisole or sodium nucleinate in the combined therapy promoted correction of the immune deficiency and increased the treatment efficacy. Sodium nucleinate proved to be the most efficient.     

Combined use of prodigiozan and methyluracil with immunosuppressive drugs in adjuvant arthritis in rats

The effect of the combined use of prodigiozan (0.5 mg/kg bw) prodigiozan with immunosuppressants on the development of adjuvant arthritis was studied on rats. The drugs were given during the prearthritis period from the 1st to the 16th day after injection of complete Freund's adjuvant. It was shown that the combined use of prodigiozan and cyclophosphamide (5 mg/kg) induced significant inhibition of the arthritis development and extraarticular signs of the disease. The efficacy of the combination was higher than that of cyclophosphamide alone. Azathioprine (4 mg/kg/bw) produced no immunosuppressant effect and did not influence the inhibitory effect of prodigiozan on the development of the adjuvant disease. Prednisolone (1.6 mg/kg) either did not inhibit the arthritis development. However, it eliminated the prodigiozan effect. Methyluracil did not change the effect of the immunosuppressants on the articular syndrome. Still, it increased the number of nodular affections in the animals treated with cyclophosphamide and prednisolone. The data obtained show the possibility of prodigiozan combination with certain immunosuppressants in autoimmune affections and confirm the suggestion that the inhibitory effect of this drug is mediated through macrophages.     

Further research on an experimental justification for the emergency prophylaxis of typhoid]

Experiments were conducted on mice. A possibility was demonstrated of express prophylaxis of typhoid fever by subcutanoues injection of the vaccine and by oral administration of sodium nucleinate, of lowering the dose by half and replacement of revaccination by sodium nucleinate alone. An increase in the titre of typhoid agglutinins and of preventive activity of the blood serum was revealed on volunteers.     

The effect of sodium nucleinate on allergic and immunological reactions

Experiments on immunized rabbits and guinea pigs indicated that sodium nucleinate (SN) was capable of weakening or entirely eliminating anaphylactic and skin reactions of delayed type hypersensitivity to repeated administration of staphyloanatoxin, APDT vaccine. The findings on patients with the infectious form of bronchial asthma and chronic rheumatism showed that sodium nucleinate attenuated reactions to the subcutaneous administration of staphylococcal and streptococcal allergens. The treatment of patients suffering from infectious-allergic bronchial asthma and rheumatism with SN resulted in the recovery of deficient T cells, T-suppressors, normalization of immunoglobulin concentrations. In children with acute glomerulonephritis sodium nucleinate normalized decreased T-suppressor cells and increased IgG and circulating immune complexes (CIC), resulting in a pronounced remission of disease. The mechanism of desensitization and elimination of CIC by SN has not been explored, however, the parameters of SN-induced immunomodulation are known rather completely. It is suggested that SN brings about accumulation in the cell of cyclic AMP which diminished membrane permeability, activates monoaminooxidase resulting in the degradation of histamine and other biogenic amines, enhances the synthesis of endogenous corticosteroids with their desensitizing properties. All these effects contribute to the elimination of delayed type hypersensitivity. The role of SN in the inhibition of delayed type hypersensitivity remains obscure.     

Comparative effectiveness of immunomodulators in the therapy of rheumatic heart defects

A total of 166 patients with rheumatic heart diseases were examined. It was shown that the patients had secondary immune deficiency mainly with respect to the T-cells, which could not be eliminated with the routine therapeutic agents. The use of hemodes, decaris or sodium nucleinate in the combined therapy of such patients promoted correction of the immune deficiency and increased the treatment efficacy. Sodium nucleinate proved to be the most active.     

Effect of combinations of immunomodulators on phagocytosis

The effect of levamisole, prodigiozan and lithium carbonate combinations on antimicrobial activity of blood neutrophils and peritoneal macrophages was studied on mice. The combinations were used in single doses. An increase in stimulation of phagocytosis with respect to staphylococci was observed after the use of prodigiozan in combination with lithium carbonate. Levamisole and lithium carbonate were antagonistic with respect to macrophagal phagocytosis. No advantage of the combined use of prodigiozan and levamisole to their use alone was shown.     

Increase in the sensitivity of Shigella to antibiotics

Passages of 10 Shigella strains for 10 times in meat-peptone broth supplemented with sodium nucleinate provided an increase in sensitivity of the cultures to levomycetin for a period of 264 hours. In three strains of S. sonnei, S. flexneri and S. newcastle the authors observed an increase in sensitivity to tetracycline, benzylpenicillin and streptomycin. Some nitrous bases included in sodium nucleinate were also able to increase antibiotic sensitivity in Shigella.     

Intensification of antibacterial and antiviral nonsusceptibility and of the immune response with an officinal RNA preparation]

Sodium nucleinate increased essentially the insusceptibility of mice to pathogenic escherichia, strain O26, Pr. vulgaris, Ps. aeruginosa, Ser. marcescens, and produced a total stimulating effect on the nonspecific bacterial resistance; analogous stimulating activity was found in the homologous low polymeric RNA from the liver. Sodium nucleinate intensified the insusceptibility of the animals to the tick-born encephalitis and encephalomyelitis viruses, and increased the antibody-forming cells count. The side-effect of heat-inactivated vaccine from pathogenic escherichia was reduced in animals inoculated with sodium nucleinate preliminarily.     

Sodium nucleinate increase of nonspecific macroorganism resistance to conditionally pathogenic and pathogenic microorganisms

Sodium nucleinate significantly increased the non-specific resistance of mice to E. coli O26, Ps. vulgaris, Ser. marcesens, Ps. aeruginosa, Kl. ozaenae and their associations and total resistance also accompanied by a significant decrease in the number of the bacteria in the spleen and blood, the total number of the cells in the peritoneal exudate and the number of the cells adhering to the glass (macrophages). The preparation is a low molecular RNA consisting mainly of fraction 3S and a small amount of fraction 4S. It contains 1.5 per cent of protein and 2 per cent of DNA and does not contain any polysaccharides. Repeated purification of sodium nucleinate lowering the levels of the admixtures 5 times did not change its efficacy. The low molecular RNA of the rat liver (4S) had a pronounced stimulating activity. On infection of the host stimulated with sodium nucleinate, formation of the post-infection immunity was not decreased.     

The effect of an artificial magnetic field on Salmonella infection in mice]

Experimental Salmonella infection in mice, developing simultaneously with the prolonged action of an artificial constant magnetic field with induction equal to 3 x 10(-4) T, was found to induce a pronounced decrease in nonspecific resistance in the animals. The study of Salmonella population structure revealed that the cells selected the animals subjected to the action of the artificial magnetic field had mostly a lesser number of signs of antibiotic resistance. By the end of the experiment Salmonella cultures isolated from the mice subjected to the action of the artificial magnetic field were characterized by greater virulence and resistance to the bactericidal action of blood serum. The use of sodium nucleinate under the conditions of the action of the artificial magnetic field enhanced the level of anti-infectious protection in the animals, which changed the direction of cell selection in Salmonella population towards cells with a greater number of markers of antibiotic resistance.     

Interferonogenic properties of prodigiozan and its effectiveness in treating acute respiratory diseases in children

The capacity of prodigiozan to stimulate interferon production in the cell culture of the human palatine tonsil lymphocytes was studied. The interferonogenic properties of prodigiozan administered in the form of aerosols to children were also investigated. The efficacy of the prodigiozan aerosols in treatment of children with viral respiratory diseases was estimated. It was shown that prodigiozan stimulated interferon production in the cell culture of the tonsil lymphocytes (the titers of 1 : 2--1 : 8) and induced formation of endogenic interferon in the host (in the tonsils and blood serum) 24 hours after the aerosol administration. 100 micrograms of prodigiozan administered in the form of aerosols in a single dose or in 2 doses at an interval of 1--2 days had a pronounced therapeutic effect 1--2 days after the administration. The use of prodigiozan in treatment of children with acute viral respiratory infections promoted a decrease in the frequency of complications, such as pneumonia and otitis. The data are indicative of the validity of prodigiozan in treatment of children with acute respiratory infections.     

Antibiotic therapy of acute dysentery in children with immunologic deficiency conditions

One hundred children with acute Sonnei and flexneri dysentery were followed up with respect to the infection process and main immunity indices. In 32 children the immunity indices were physiological (group 1) and in 68 children secondary immune deficiency was observed (group 2). The children were treated with aminoglycoside antibiotics and prodigiozan and it was stated that the time of recovery in the children with immune deficiency was longer by 5.2 days as compared to that in the children without immune deficiency. In the children with immune deficiency the combined use of one of the aminoglycosides, prodigiozan and lysozyme, led to a reduction of the host immunological reactivity and recovery within the same periods as those recorded for children with the physiological immunity status. It is recommended to use the antibiotic combination with prodigiozan and lysozyme in the treatment of all the forms of dysentery in children with secondary immune deficiency.     

Effects of essentiale forte on biosynthesis of nucleic acids and several hemodynamic parameters of the damaged myocardium in rabbits

Normalization of heart muscle phospholipid metabolism and reactivation of the activity of membrane-bound enzymes participating in the reactions of biosynthesis of nucleic acids have been studied. These investigations were carried out under the conditions of experimental myocardial infarction. The effects of essential forte have been examined when it was combined with both a tocopherol, and sodium nucleinate. It was pointed out that essential forte using without other reagents leads to the depression of nucleic acids biosynthesis in affected heart muscle, while the combinations of it with a-tocopherol, and especially with sodium nucleinate are accompanied by the significant intensification of reactions of formation of desoxynucleic and ribonucleic acids biosynthesis in necrotic areas as well as in peripheral regions of affected myocardial tissue. These positive changes are accompanied also by the pronounced normalization of haemodynamic activity of infarcted myocardium.     

Effect of gentamycin in combination with prodigiozan on the immunological reactivity of the body

The effect of gentamicin sulphate and its combination will prodigiozan on antibody formation in experiments and the levels of the immunobiologic reactivity of patients with purulent inflammatory processes was studied with a purpose of developing rational schemes of antibiotic therapy of infectious diseases. A decrease in the titers of the antibodies to Aeromonas and the number of antibody-forming cells in the spleen was noted on repeated administration of gentamicin to albino mice in a dose of 20 mg/kg. This was prevented by the use of prodigiozan in a dose of 500 micrograms/kg once every 4 days. The use of gentamicin in patients with purulent inflammatory diseases in doses of 40 or 80 mg twice a day for 7--10 days had no significant effect on the titers of IgA, IgG, IgM, lysozyme blood serum levels, serum bactericidal activity and absorption activity of the peripheral blood neutrophils. Still, it induced a marked suppression of the neutrophil digestive capacity as compared to the initial levels, especially on administration of gentamicin in a dose of 40 mg twice a day. An increase in the level of IgM and no suppression of the neutrophil digestive capacity were noted after completion of the therapy in the patients treated with gentamicin administered in a dose of 40 mg twice a day and prodigiozan administered in a dose of 50 micrograms once every 4 days. It is recommended to use prodigiozan in combinaed therapy with gentamicin for correction of the changes in the specific and nonspecific protective forces of the host.     

Prolongation of the effect of immunostimulators as means of increasing resistance to causative agents of infection

Possible prolongation of the biological effect of some available immunostimulators such as prodigiozan, salmozan, polyribonate and thymalin by their sorption on aluminium hydrate was studied. It was shown that in comparison to the native immunostimulators the sorbed ones had a more pronounced biological action and provided a more prolonged increase in the host resistance to the causative agents of gas gangrene and typhoid fever. Using prodigiozan as an example it was demonstrated that the observed increase in the anti-infective activity of the sorbed drugs was associated with more intensive stimulation of some immunological factors involved in regulation of host nonspecific resistance. The results of the study are likely to indicate that it was experiment to further investigate the drugs to reveal their efficacy in other infection models and to optimize the schemes of their use.     

Cardiomyocytes of the left ventricle of the heart in experimental infarct and pharmacostimulation (histochemical study)

Contents and activity of lactate dehydrogenase and succinic dehydrogenase of cardiomyocytes have been studied histochemically and cytophotometrically in the left ventricle of the rabbit heart under conditions of myocardial infarction experimentally induced by alpha-tocoferol and sodium nucleinate. The substances mentioned produce a protective effect on the energic metabolism of cardiomyocytes.     

Correction of secondary immunologic deficiency by using yeast RNA

In patients with rheumatism, chronic alcoholism and peptic ulcer immune deficiency mainly with respect to T-lymphocytes has been detected. The injection of sodium nucleinate simultaneously with the use of traditional therapeutic remedies induces the correction of secondary immune deficiency for a period of 6-9 months.