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.     

Effect of prodigiozan and pyrimidine derivatives on the effectiveness of the antibiotic therapy of experimental infections]

The effect of prodigiozan and pyrimidine derivatives, such as methyluracyl, oxymetacyl and 2-methyl-4-amino-6-hydroxypyrimidine on the efficiency of antibiotic therapy of experimental infections caused by Staph. aures and E. Coli under conditions of immune depression due to levomycetin, prednisolone, 6-mercaptopurine and ionizing radiation was studied. The effect of prodigiozan on the efficiency of the antibiotic treatment of staphylococcal infection in the presence of the immune depression due to 6-mercatopurine, levomycetin and prednisolone was higher than that of pyrimidines. The combined use of prodigiozan and pyrimidines usually was not more effective than the use of every drug alone. The efficiency of the drugs in radiation disease was the same. After prednisolone administration prodigiozan increased the host resistance to the infection without the antibiotic use.     

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.     

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.     

Study of the effect of tetracycline, prodigiosin and their combination on the dynamics of phagocytosis of plague bacteria]

The advantage of the combined use of prodigiozan and tetracycline was observed in tissue culture of peritoneal macrophages of albino mice. Earlier digestion of the intracellular Y. pestis EV by the animal macrophages exposed to prodigiozan and treated with tetracycline was noted. It was shown that the macrophages preserved during several hours of cultivation in vitro their properties acquired in the animal organism under the effect of the substances administered.     

Prodigiozan aerosols in the treatment of nonspecific respiratory organ diseases in children]

High efficacy of prodigiozan, a bacterial polysaccharide used in the form of inhalation in combined therapy of 123 children at the age of 3 to 14 with nonspecific bronchopulmonary pathologic conditions was shown. The drug was administered by means of inhalators UI-I and PAI-I once every 4--5 days in the form of 0.02 per cent solution prepared in situ. The single and the course doses were 100--400 and 300--2000 micrograms respectively. The positive therapeutic effect was observed in 85.0 per cent of the patients: improvement of the patient state was registered 4--6 days earlier than that in the control group, the indices of the respiration mechanics and nonspecific immunity (titers of lysozyme and complement) also improved. The rate of viral respiratory diseases among the children treated with prodigiozan decreased 2.5 times. High efficacy and physiological character of the aerosol method for administration of prodigiozan used the the first time in pediatry provided its recommendation for wide use.     

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.     

New data on the tachyphylactic properties of sodium nucleinate]

Sodium nucleinate, when injected into mice in combination with killed E. coli or prodigiozan, caused a decrease in side effects produced by the vaccine or polysaccharide. The combined injection of sodium nucleinate and prodigiozan in doses, ineffective if introduced separately, was accompanied by the potentiation of their tachyphylactic action. The use of sodium nucleinate in combination with polyvinylprrolidone (hemodez) prolonged the tachyphylactic action of sodium nucleinate and increased its effectiveness. The proposed principle is supposed to be suitable for decreasing the reactogenicity of bacterial vaccines and polysaccharides.     

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.     

Effects of prodigiozan on post-radiation recovery of hemopoietic precursor cells and colony-stimulating factor level in long-term cultures of mouse bone marrow

Prodigiozan injected to long-term cultures of mouse bone marrow 24 h before irradiation increased CFUs and CFU-GM number and colony-stimulating factor (CSF) level by the time of delivery of ionizing radiation. As early as 60 min following irradiation of bone marrow structures with a dose of 2 Gy the number of CFUs and CFU-GM decreased considerably, and from day 3 on after irradiation the indices under study were gradually restored. By day 14 the cultures preinjected with prodigiozan exhibited higher recovery levels. The decrease in the number of precursor cells 60 min after irradiation was accompanied by a drastic increase in the CSF content of cultures; the CSF release in cultures protected with prodigiozan was more moderate than in the irradiated controls.     

Use of prodigiozan and tactivin for treatment of patients with chronic Klebsiella infections

Two-stage immunocorrection in patients with chronic Klebsiella infections by consecutive administration of prodigiozan and tactivin, has been shown to facilitate the restoration of the balance of immunoregulating cells, to enhance proliferative response to T- and B-mitogens, thus producing favorable clinical dynamics. The possibility of chronic Klebsiella infections therapy, based on the use of immunocorrecting preparations (prodigiozan and tactivin) and antibiotics capable of intracellular penetration (sumamed and cyprofloxacin) is discussed.     

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.     

The efficacy and outlook for the study of live vaccines for the prevention of melioidosis]

The effect of immunization with Burkholderia pseudomallei, (Pur- and Ts), heterologous vaccines and the recombinant culture of Francisella tularensis RM2, carrying a plasmid with fragments of B. pseudomallei chromosome, was studied on four species of experimental animals, essentially differing by their sensitivity to melioidosis. B. pseudomallei mutants formed the statistically significant level of protection in subcutaneously challenged animals, moderately sensitive to melioidosis, but were not effective when tested, under the same conditions, in animals, highly sensitive to melioidosis. The effect produced by the experimental vaccines under study in animals of all species, subjected to aerogenic challenge, was leveled. The study showed good prospects for the use of tularemia vaccine with a view to create heterologous immunity to melioidosis and the possibility of its use as the basis of bivalent gene engineering vaccine.     

Burkholderia mallei and Burkholderia pseudomallei. Study of immuno- and pathogenesis of glanders and melioidosis. Heterologous vaccines]

Parameters of the infectious activity of B.mallei and B.pseudomallei for animals of various species were determined. Pathomorphological characteristics of the process of malleus and melioidosis were studied on golden hamsters, mice, guinea pigs, rats and monkeys. Tularemia, plague and salmonellosis vaccines were shown to have protective effects in experimental malleus and melioidosis. An insignificant cross immune response between the malleus and melioidosis pathogens was observed.     

Kinetic studies of bioactive products nitric oxide and 8-iso-PGF(2alpha) in Burkholderia pseudomallei infected human macrophages, and their role in the intracellular survival of these organisms

The oxidative response of Burkholderia pseudomallei and Escherichia coli infected macrophages from normal and melioidosis subjects was determined by measuring the production of nitric oxide which is one of the reactive nitrogen intermediates, and the activation state of these macrophages was determined by measuring the generation of 8-iso-PGF(2alpha), a bioactive product of free radical induced lipid peroxidation. Macrophages obtained from the melioidosis patients generated significantly lower levels of nitric oxide and 8-iso-PGF(2alpha) compared to macrophages obtained from the normal subjects (P<0.001). The reduced efficiency of the oxygen dependent microbicidal mechanism in macrophages of melioidosis patients may be one of the survival strategies developed by B. pseudomallei to remain viable intracellularly.     

Antibiotic therapy of Salmonella infection in infants during the first year of life and methods if its correction]

The efficacy of antibiotic therapy of salmonellosis was studied and functional activity of peripheral blood leukocytes from electron microscopic data was estimated in 200 infants. It was shown that the use of antibiotics in combination with immunostimulants such as leukocyte mass, lysozyme and prodigiozan in complex therapy of salmonellosis in infants had a favourable effect on both the time course of the clinical signs and the functional state of the neutrophil leukocytes. The duration of the treatment decreased by 6.14 +/- 0.34 days and repeated isolation of the pathogen from the host appeared to be less frequent.     

The effect of prodigiozan on the postradiational recovery of hemopoiesis in long-term bone morrow cultures of mice of different genotypes

The influence of prodigiozan on the processes of postirradiation recovery of hemopoiesis in long-term bone morrow cultures of two strain mice, having genetic distinctions in the condition of systems of the reparation DNA was investigated. It was showh, that the irradiation of long-term bone morrow cultures of mice reparation-defective strain 101/H resulted in the greater degree damage of early haemopoietic precursors (GM-CFC), reduction of the amount of the immature and of the mature granulocytes and of the decrease of the number of stromall cells in the comparison with the bone morrow of reparation-capable mice (CBA x C57B1)F1. Under the introduction in cultures of prodigiozan for 24 hours prior to an radiation the distinctions of the speed of postirradiation recovery of hemopoiesis substantially smoothed out, and the protective effect of the drag in bone morrow cultures of mice 101/H was comparable to those, marked in bone morrow cultures of reparation-capable strain mice (CBA x C57B1)F1. It is supposed, that this effect can be caused by the activation of the hematopoietic microenvironment cellular elements and inclusion of the mechanisms of intercellular of interactions, which provide stimulation of the regenerative processes at action radioprotective drags and can in the certain degree to compensate the defect of the systems of the reparation DNA.     

Obtaining spheroplasts from the agents of glanders and melioidosis and separation of membrane structures from them]

Spheroplasts were obtained from the causative agents of glanders and melioidosis under the effect of lysozyme and antibiotics. In the capacity of an inducing agent lysozyme was effective in high concentration only (0.4%); preliminary washing and incubation in sucrose were necessary to obtain glanders spheroplasts. Of the antibiotics studied penicillin was more useful for obtaining melioidosis spheroplasts and ampicillin--for glanders spheroplasts. Membrane preparations were derived from the spheroplasts of glanders and melioidosis causative agents.     

Demonstration of acid phosphatase activity in antigenic glycoprotein fractions obtained from the culture filtrate of Pseudomonas pseudomallei.

Pseudomonas pseudomallei, the causative microorganism of melioidosis, was grown in Mueller-Hinton liquid medium, and glycoprotein fractions were separated from the culture filtrate by ammonium sulfate precipitation, gel-filtration with Sephadex G-75, and column chromatography with DEAE-cellulose. The fractions revealed acid phosphatase activity, and reacted to the sera from melioidosis patient in gel-diffusion precipitation assay.     

Evaluation of liposomal forms of rifampicin and prodigiozan in the treatment of experimental chronic tonsillitis

Therapeutic effect of liposomal dosages of rifampicin and prodigiozan was studied on rabbits with simulated chronic tonsillitis in comparison to that of commercial ones of the drugs. The treatment schemes included daily intra-tonsillar++ injections of the dosage forms for 5 days. A high efficacy of their liposomal dosage forms in treatment of experimental chronic tonsillitis was confirmed microbiologically and immunologically. Approval of the liposomal dosage forms used in the therapy of patients with chronic tonsillitis requires clinical trials.