[Mechanisms of realization of protective effect of miliacin during experimental Salmonella infection: effect of endotoxinemia and cytokine production].

AIM: Evaluate the effect of miliacin on the intensity of endotoxinemia and features of cytokine production in experimental salmonella infection. MATERIALS AND METHODS: The studies were carried out in 128 male mice (CBAxC57Bl6)F1 divided into 4 groups: I--intact; II--infected; III--infected after administration of miliacin solvent: tween-21; IV--infected after administration of miliacin. Determination of the endotoxin in blood plasma was carried out by using chromogenic LAL-test. Cytokine production was studied in splenocyte culture by EIA method. RESULTS: Miliacin reduced the intensity of endotoxinemia in mice of group IV. Salmonella infection increased spontaneous (IFNγ) and induced (IL-12, IFNγ, IL-17) cytokine production. Miliacin ensured the most significant increase of spontaneous IL-10, IL-12 and IFNγ production compared with groups II and III. At the same time it limited the increase of induced IL-17 production compared with groups II and III. CONCLUSION: Protective effect of miliacin is determined by the reduction of endotoxinemia, mobilization of Th-1 response, stimulation of IL-10 production and limitation of IL-17 participation in the development of the inflammatory reaction.

[Protective effect of miliacin during experimental salmonellosis infection].

AIM: Evaluation of influence of triterpenoid miliacin on the development of experimental salmonellosis infection. MATERIALS AND METHODS: Studies were carried out in 330 male mice (CBAxC57Bl6)F1. Miliacin was administered 3 times intraperitoneally with the interval of 3 days between administrations at a single dose of 2 mg/kg. The animals were infected intraperitoneally by hospital origin Salmonella enteritidis strain (2x10(6) bacteria per mice). 4 groups of mice were used: I - intact; II - infected; III - infected after administering solvent for miliacin 3 times (tween 21 at final concentration of 1.6x 10(-7) mol/kg); IV - infected after administration ofmiliacin. RESULTS: Miliacin reduced the mortality of mice compared with groups II and III. Microbial contamination of mice spleen in group IV was significantly lower compared with group II at all the periods of the study, and liver - at days 10 and 15. Triterpenoid weakened cell depletion of bone marrow, thymus and limited hyperplasia of spleen compared with animals of groups II and III. Its protective effect did not correlate with increase of antibody titers. CONCLUSION: Miliacin weakens the severity of salmonellosis infection course.

[Risk factors for violations of the fertility in men living in urban areas].

The immunocytokine status of the reproductive tract was evaluated in men with different forms of gonorrhea, who lived in the urbanized areas of the Orenburg Region. The typical form of gonorrhea, which is a risk for infertility, is accompanied by the reduced levels of lysozyme and IL-10 and the increase content of lactoferrin and proinflammatory cytokines, such as IL-1, Ibeta-6, and IL-8 in the ejaculate.

[Effect of benzene and chromium on the trace element composition in biosubstrates in Wistar rats].

The chronic effects of benzene and chromium on the level of trace elements in the biospheres of Wistar rats were studied for 45, 90, and 135 days. As compared to the controls, the experimental groups of patients were found to have lower concentrations of copper (in blood) and iron (in blood and spleen) and higher levels of zinc (in blood, spleen) and chromium (in blood, spleen).

[Morphological features of the organs of the immune system in conditions of exposure to chromium and benzene].

Morphological features of the thymus, spleen and lymph nodes on the 45th--and 90th day of oral exposure to benzene, potassium dichromate and their mixtures were studied in 40 Wistar rats. A strong trend to a decrease in the activity of T lymphocytes has been established. Apoptotic thymocytes and lymphocytes in the T-dependent areas of spleen and lymph nodes have been revealed.

[Anti-cytokine activity of microorganisms].

AIM: Development of a method of determination of anti-cytokine activity (ACA) of microorganisms, study of the prevalence and intensity of ACA to pro- and anti-inflammatory cytokines in pathogenic and opportunistic bacteria. MATERIALS AND METHODS: ACA was determined in 72 strains of microorganisms including members of the intestinal microflora and strains of pathogenic bacteria (salmonellae andgonococci). Study of the ability of supernatants and live cell cultures of microorganisms to induce changes in pro- (IFN-gamma, TNF-alpha, IL-6) and anti-inflammatory cytokines (IL-4, IL-10) was performed by using co-incubation of exometabolites and live cell bacteria, fungi with recombinant cytokines. RESULTS: Amethodological approach allowing the determination of ACA, the prevalence of which among studied microorganisms was 50 - 62%, was developed. A decrease of cytokine concentration in the medium was registered in co-incubation of them with supernatants (in 56% of cases) and to a lesser degree--with live cell cultures (44%) of the studied bacteria and fungi. Expression ofanti-cytokine activity was the most pronounced to TNF-alpha (Bifidobacterium spp. and Lactobacillus spp., Neisseria gonorrhoeae), IFN-gamma (N. gonorrhoeae and Salmonella enterica) and IL-10 (Bifidobacterium spp. and Lactobacillus spp.). CONCLUSION: The data obtained expand the conception of modification of cytokine dynamic by pathogenic and opportunistic microorganisms, that can influence the course and outcome of an infectious process.

[The thyroid status in the healthy population of the South-Urals region].

The aim of the investigation was to study the parameters of the thyroid and antithyroid status in the healthy population of different age, living under the conditions of mild iodine deficiency and trace element imbalance in the South Urals (Orenburg). The serum levels of total and free triiodothyronine, total and free thyroxin, thyroid-stimulating hormone (TSH), and antithyroid antibodies were determined and the compensation index and the sensitivity index of thyroid cells to TSH were calculated in 458 apparently healthy individuals aged 7-40 years. TSH levels varied from 0.27 to 3.97 IU/l, amounting to 1.41 +/- 0.03 IU/l. The patients with TSH levels of 0.27 to 0.5 IU/l were found to have a lower compensation index and a higher sensitivity index for thyrocytes to TSH, suggesting the hyperproduction of thyroid hormones in response to low TSH stimulation. The decreased sensitivity index in patients with a TSH level of 2.0 to 4.0 IU/l is a borderline condition. These patients may further develop thyroid hyperplasia if iodine deficiency is not corrected and other strumogenic factors are not used. Higher free T3 levels and decreased compensation index were detected in 83% of the apparently healthy individuals with increased antithyroid antibodies to thyroid peroxidase, which is indicative of the thyroid hyperproduction of T3 and the risk factor of autoimmune diseases.

[Immunopathology in the children and adolescents living in regions with a varying anthropogenic load].

The prevalence and pattern of immunopathology were analyzed in the children and adolescents living in the Orenburg Region's areas having a varying anthropogenic load. The children and adolescents were found to have high morbidity rates for allergic, infectious-and-inflammatory diseases upon anthropogenic exposure. In the examinees, the immunological parameters corresponded to the stereotypic changes that were characteristic of infectious-and-inflammatory and allergic syndromes. There was a correlation between the incidence of airway allergic and infectious-and-inflammatory diseases and the degree of ambient pollution.

[Effects of chromium and benzene on cell immunological parameters and the content of trace elements in rats].

The effects of potassium bichromate, benzene, and their mixture on cell immunological parameters and the blood content of trace elements were studied in Wistar rats. Oral administration of benzene, potassium bichromate, and their mixture to Wistar rats was found to result in reductions in cell immunological parameters (the count of leukocytes, thymocytes, splenocytes, myelokaryocytes, the level of phagocytic indices) and the levels of copper, iron, nickel, and, on the contrary, increases in the concentrations of zinc and chromium in blood.

[Phenotypic characteristic of staphylococci and local immunity during bacterial carriage].

AIM: To assess prevalence and intensity of antilactoferrin and slgA-protease activity in strains of staphylococci and to study the state of local immunity in resident and transitory bacterial carriers. MATERIALS AND METHODS: Strains of Staphylococcus aureus and S. epidermidis isolated from 67 healthy persons, who were tested for staphylococcal carriage with subsequent differentiation of types of carriage according to Chistovitch's method, were studied. Antilactoferrin and slgA-protease activity as well as levels of lactoferrin and slgA in nasal secretions were determined using fluoroimmunoassay. RESULTS: Higher prevalence as well as intensity of antilactoferrin and slgA-protease activity and combination of these characteristics was determined for strains of S. aureus from resident carriers compared with strains from transitory carriers. Higher levels of lactoferrin and slgA were observed in nasal secretions of resident carriers compared with transitory carriers. CONCLUSION: Studied factors could be the markers of resident type of carriage that should be considered for the development of effective measures for sanation in persons with prolonged bacterial carriage.

[Characteristic of biological properties of Neisseria gonorrhoeae and parameters of local immunity during urogenital gonococcal infection].

AIM: To study the prevalence and expression of antilactoferrin, IgA- and slgA-protease activity of gonococci and state of local immunity during various forms of urogenital gonorrhea. MATERIALS AND METHODS: Ability to inactivate lactoferrin (ALfA), IgA and secretory IgA (slgA) was studied in 28 Neisseria gonorrhoeae strains isolated from patients with localized gonorrhea and 26 strains isolated from patients with systemic signs of gonorrhea. State of the local immunity was assessed on the lactoferrin, IgA and slgA levels, which were measured by immunofluorescence assay in ejaculate of 54 patients with gonorrhea and 18 healthy males. RESULTS: Penetrance of ALfA, IgA- and slgA-protease activity of gonococci did not depend from form of infection. Expression of studied characteristics of gonococci as well as combination of ALfA and slgA-protease activities were more prominent in patients with systemic signs of gonorrhea. The same patients had higher level of lactoferrin in semen and, in contrast, lower levels of IgA and slgA compared with patients with localized gonorrhea. CONCLUSION: Strains of gonococci inactivating lactoferrin, IgA and slgA depress mucosal barrier of urogenital biotope and create conditions for the development of disseminated forms of gonococcal infection.

[Algorithm for prediction of reconvalescent salmonellosis carriage].

Of total of 181 patients with Salmonella infection were examined by clinical and laboratory methods. As many as 124 indices characterizing biological properties of Salmonellae, a large intestine microbiocenosis status, systemic and local immunity, were investigated as well. Among these indices, the most revealing signs were defined to prognosticate the reconvalescent carrier state. Conclusion was made on the prevalence of immune mechanisms in the development of reconvalescent salmonella carriage and on the important role of the ability of a causative agent to inactivate the factors of host innate immunity in this process. Diagnostic prognosis algorithm for Salmonella bacterial carriage was worked out. Clinical testing confirmed its effectiveness.

[Influence of plasmid pR50 controlling bacterial protease activity on Salmonella experimental infection].

The comparative analysis of the infectious process and immunological parameters in (CBA x C57BL/6)F1 mice infected with S. typhimurium isogenic strains differing by the presence of plasmid pR50 determining protease activity, was carried out. A growth in the expression level of antilactoferrin, anticomplementary and anti-immunoglobulin activity in bacteria isolated from the spleen in the course of the infectious process was detected. In mice infected with S. typhimurium having plasmid pR50, in contrast to nonplasmid recipients, a higher level of contamination of organs, the suppression of spontaneous, stimulated production of interferon-gamma and the bactericidal properties of peritoneal macrophages were noted. The data obtained in this investigation suggested that the acquisition of R-plasmid of 50 MD, controlling protease activity and multiple medicinal resistance, contributed to the persistence of intracellular bacteria.

[Biological properties of salmonellae and local immunity in Salmonella infection].

The comparative study of the biological properties of S. enteritidis and S. typhimuruim, isolated from patients and convalescent carriers, was carried out. Factors inactivating the components of the local immunity of the intestine (lysozyme, complement, lactoferrin, IgG, IgM and IgA) were detected in the causative agents of Salmonella infections. The spread and expression degree of properties of a causative agent were serovar-depended: high penetration characteristics and the expression of anti-lactoferrin and anti-immunoglobulin activity were characteristic of S. typhimurium. S. enteritidis strains isolated from patients with carrier state formed in the convalescence period were found to have higher persistence level. In co-profiltrates obtained from carriers at the peak of the disease and during convalescence lower levels of IgM, IgG, sIgA, complement and lactoferrin were determined in comparison with those in coprofiltrates obtained from patients in whom no subsequent carrier state was formed. These results indicate that an increase in the persistence of salmonellae, occurring simultaneously with the local immunodeficiency, contributes to the prolonged survival of bacteria in the intestine.

[Effect of a polyoxydonium immunoregulator on the biological properties of microorganisms]. / Vliianie immunomoduliatora polioksidoniia na biologicheskie svoistva mikroorganizmov.

The effect of the synthetic immunomodulator polyoxydonium (PO) on some biological properties of pathogenic bacteria (Shigella flexneri, Salmonella enteritidis), opportunistic bacteria (Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacteroides fragilis, Peptostreptococcus anaerobius, Prevotella melaninogenica, Propionibacterium propionicum, Clostridium difficile) and fungi (Candida albicans), isolated during enteric infections, enteric dysbiosis, pyoinflammatory diseases, was evaluated in a number of in vitro experiments. The study revealed that the recommended therapeutic concentration of PO decreased antilysozyme activity (ALA) and the anticomplement activity in Klebsiella, Shigella, Propionibacterium, Clostridium, bacteroids, fungi of the genus Candida, but increased ALA in nonhemolytic Escherichia. Under the action of PO an increased sensitivity of the microorganisms under study to definite antibiotics of the lincosamide, fluoroquinolon, carbapenem and cephalosporin groups was noted. The data obtained in this study reveal one of the possible mechanisms of the corrective action of PO on the microbiocenosis of the intestine in dysbiosis, enteric infections and pyoinflammatory diseases.

[Evaluation of immunity in children from rural localities and the levels of trace elements in environmental objects]. / Otsenka immunnogo statusa u detei sel'skikh naselennykh punktov i soderzhanie mikroélementov v ob"ektakh okruzhaiushchei sredy.

Immunity was evaluated in 890 schoolchildren living in rural localities of the Central and Western lands of the Orenburg Region. There was a correlation between the immunological parameters of the examinees and the levels of trace elements in environmental objects. The children's immunity showed unilateral changes in the studied parameters as compared with the regional standards. The closest correlation was found between the absolute count of T lymphocytes, stab neutrophils, the levels of IgA, IgM in children and the content of I, Sr, Mn, Cr in cereals and vegetables, as well as between the levels of IL-2 and alpha-TNF and the blood concentrations of Cu, Fe, Cr, Ni, Co in the examined children. The immunological changes may result from the imbalance of trace elements in the studied environmental objects and biological substrates.

[Characteristics of immunologic disorders in patients with acute destructive pancreatitis]. / Kharakteristika immunnykh narushenii u bol'nykh ostrym destruktivnym pankreatitom.

Examination of immunological status in patients with acute destructive pancreatitis with uncomplicated (14 patients) and complicated (infectious-inflammatory processes--18 patients) postoperative period illustrated depression of T- and B-links of immunity, reduction of absolute and relative number of TFU- and TFC-lymphocytes. All the patients demonstrated reliable elevation of phagocytic rate, phagocytic index and number of circulating immune complexes. These changes were more significant in patients with complicated postoperative period. Level of lactoferrin in patients with complicated period was by 10% higher than in patients without complications. Significant elevation of tumor necrosis factor Ia in blood was registered in patients of both groups. During all the periods of examination the level of interleukin-8 was higher in patients with complicated postoperative period than in the patients with favorable postoperative period. This interleukin-8 is a reliable marker of postoperative complications in acute destructive pancreatitis.

[A comparative evaluation of the immune status of patients with squamous-cell cancer of the oral mucosa at different stages of combined treatment]. / Sravnitel'naia otsenka immunnogo statusa bol'nykh ploskokletochnym rakom slizistoi obolochki organov polosti rta na razlichnykh étapakh kombinirovannogo lecheniia.

Shifts in immunity values were detected in 160 patients with oral cancer before specific therapy and at all stages of multiple-modality treatment. High diagnostic significance of measuring concentrations of circulating immune complexes in the serum for prediction of tumor relapse or metastases is demonstrated.