[MICROBIOCENOSIS, IMMUNE SYSTEM AND HEREDITY].

The formation of pro-/eukaryotic systems is the general biological mechanism of formation and variability of the phenotype of plants, animals, human beings under the influence of external wednesday, i.e. formation of adaptive potency conditions to external wednesday that increases the <> prokaryotic structures in sustaining body health. Prominent role in the formation of the phenotype of micro media, immunological tolerance (immunological programming), as a basis for the formation of individual pro-/eukaryotic interactions in perinatal age, the dominant role of maternal influence in this process on the one hand, micro-variability due to external stress impact on the other, makes it possible to consider pro-/eukaryotic interaction as a possible mechanism of perinatal programming and epigenetics inheritance and therefore, as one possible approach for correction of chronic and congenital pathology This points to the need to improve monitoring of the formation microbiocenosis of children, improve the methods of assessment and correction.

Phenotypic differences between mdx black mice and mdx albino mice. Comparison of cytokine levels in the blood.

In mdx mice, mutation in the muscle protein dystrophin gene results in the development of chronic degeneration of the muscle tissue. We performed a comparative analysis of blood cytokine levels in mdx mice, classical black mice and mice with additional genetic defect responsible for the manifestations of oculocutaneous albinism. In mdx albino mice, the total pool of cytokines (IL-10, IL-6, IL-5, IL-2, IL-1α, IL-4, IL-17, granulocyte-macrophage growth factor, TNF-α, and IFN-γ) was increased. This increase was not associated with selective release of one of the above cytokines into the blood. The fraction of pro-inflammatory cytokines (IL-6, IL-1α, TNF-α) was increased in the total pool and the percentage of antiinflammatory cytokines (IL-4) was reduced. Changes in cytokine pool probably reflect the differences in the severity of the pathological process in the muscle tissue of both genetic variations of mdx mice.

Cytokine profile of the blood in mice with normal and abnormal heart rhythm.

Differences in the pools of 10 cytokine were found in blood samples from the caudal vein of mice with normal and abnormal heart rhythm. Both groups were albino mice bred by us and differing from mdx albino mice by the absence of mutation in muscular dystrophin gene. Mice with normal heart rhythm had low IL-17 content and elevated concentrations of proinflammatory cytokines IL-6 and IL-1α in comparison with the normal (according to published data). In mice with bradyarrhythmias, increased blood levels of IL-10, IL-6, IL-5, IL-2, IL-1α, IL-17, IL-4, TNF-α, and granulocyte-macrophage colony-stimulating factor were detected. The relative content of IL-4 and IL-17 in the total cytokine pool increased. The lifespan of mice with bradyarrhythmias and cytokine hyperexpression was shorter by 2-3 months in comparison with mice without heart rhythm disturbances and moderate changes in the cytokine pool.

[A case of an effective application of probiotics in the complex therapy of severe type 1 diabetes mellitus and intestinal disbacteriosis].

The article presents a case illustrating an association between the severity of type 1 diabetes mellitus and disorder in the intestinal microbiocenosis. The authors stress that clinical signs of disbacteriosis are mostly manifested by disturbances in the metabolic processes. Clinical effectiveness of probioticotherapy in the complex treatment of the disease is shown.

[Dysbacteriosis and immunopathological process].

The poststress translocation of intestinal microflora to the internal environment of the body is proposed to be regarded as the mechanism of neuroimmune cooperation in the realization of adaptative raction. It is pointed out that the effectiveness of the adaptive process depends on the state of microbiocenosis as a mediating factor. The inclusion of remedies for the correction of intestinal microbiocenosis into the complex therapy of patients with chronic pathology (as a specific manifestation of dysadaptive state) makes it possible to achieve results which cannot be achieved by the standard approach. We should return to the initial interpretation of I.I.Mechnikov's thesis on the basic role of dysbacteriosis in the development of the pathological process.

Hereditary muscular dystrophy in MDX mice as a homologous model for introduction of cell technologies in the treatment of progressive muscular dystrophies in humans.

Life-time monitoring of the main clinical and laboratory manifestations of hereditary muscular dystrophy in mdx mice confirmed the presence of mutation in exon 23 of dystrophin gene and the absence of this protein in skeletal muscles of mutant animals. Muscular dystrophy in mice was similar to human progressive muscle disorder, which allows the use of this model for the development of cell technologies for the treatment of hereditary muscular diseases in humans.

Xenotransplantation of embryonic precursors of human myogenesis for the correction of dystrophinopathy in mice with hereditary muscular dystrophy.

Human embryonic myogenic precursors were transplanted into muscles of mdx mice with hereditary dystrophin-deficient muscular dystrophy. Transplantation induced the synthesis of human dystrophin. The number of dystrophin-positive fibers progressively decreased, however, some of them were preserved even 5 months after transplantation. Our results indicate that xenogeneic transplantation of embryonic myogenic precursors compensates the genetic defect in dystrophin-deficient mice.

Tissue hypoxia and intestinal dysbiosis in children with tuberculosis.

We studied the role of autochthonous microflora from body cavities in the development of tissue hypoxia and instability of cell membranes. In children with tuberculosis dysbiosis manifested in nonspecific quantitative changes in the intestinal microflora and the presence of coxsackievirus antigens in the urine. DNA-containing viruses with pronounced immunosuppressive activity (e.g., herpesvirus, measles virus, and rubella virus) were found in most children. Microbiological and virological changes were accompanied by the appearance of laboratory signs for tissue hypoxia, which included inhibition of Krebs cycle dehydrogenases and alpha-glycerophosphate pathway in blood lymphocytes. Regression analysis revealed a relationship between the content of extraintestinal coxsackieviruses and inactivation of alpha-glycerophosphate dehydrogenase, succinate dehydrogenase and ratio of facultatively anaerobic bacteria in microbiocenosis, and expression of acid phosphatase and total population of malonate-positive enterobacteria, staphylococci, yeasts, and enterococci.

Pathogenetic role of dysbacteriosis in the development of complications of type 1 diabetes mellitus in children.

A relationship between enteric microbiocenosis and severity of type 1 diabetes mellitus was detected. Microbiological analysis showed II-IV degree dysbacteriosis in all diabetic children. Long-term therapy with probiotics aimed at eradication of opportunistic microflora resulted in recovery of microbiocenosis, which was paralleled by improvement of the clinical status, regression of complications in children who were ill for a long time, and prevention of complications in children with newly detected diabetes. These results indicate the leading role of chronic enteric toxic infectious process in the development of complications of type 1 diabetes. The significance of infection in the pathogenesis of other noninfectious diseases in man is discussed.

[Level of serum antibodies to opportunistic microflora as a marker of the secondary immunodeficiency processes in children]. / Uroven' syvorotochnykh antitel k uslovnopatogennoi mikroflore kak marker protsessa formirovaniia vtorichnogo immunodefitsita u detei.

Examination of children with different noninfectious diseases resulted in obtaining the data base on the state of health of 201 children belonging to the potential risk group of the development of secondary immunodeficiency. The children were subdivided into several groups which differed by the type of immune disturbances and accompanying metabolic shifts. The level of antibodies to one of the fragments of peptidoglycan-N-acetylmuramyldipeptide was compared with the character of changes in the immune system. Different titers of serum antibodies to peptidoglycan were found to correspond to different forms of immune disturbances. The study showed that from the group with the absence of definite signs of immunodeficiency to the group with the pronounced deficiency of T lymphocytes and monocytes expressing CD14 antigen changes in the immune system increased in parallel to a rise in the concentration of alpha 2-macroglobulin, the development of hypercholesterolemia and a decreased level of antibodies to peptidoglycan. Opportunistic microflora was seemingly an important factor in the formation of definite forms of disturbances of the immune system and accompanying metabolic shifts.

[Pathogenetic role of intestinal microbiocenosis in the pathogenesis of hereditary myodystrophy]. / Patogeneticheskaia rol' kishechnogo mikrobiotsenoza v klinike nasledstvennykh miodistrofii.

The effect of the inclusion of probiotic preparations for the correction of disturbances in normal intestinal microflora into the complex therapy of patients wish Duchenne's childhood muscular dystrophy and Becker's myopathy was analyzed. Probiotic therapy made it possible to improve the clinical state of patients, manifested by an increase in muscular strength and accompanied by positive shifts in electromyographic, immunological, biochemical, hormonal characteristics. Intestinal microbiocenosis plays seemingly a certain role in the formation of hereditary pathology.

[Role of dysbacteriosis in the formation of chronic noninfectious pathology in children]. / Rol' disbakterioza v formirovanii khronicheskoi neinfektsionnoi patologii u detei.

The results of clinical observations and laboratory data make it possible to regard dysbacteriosis as an important factor in the pathogenesis of chronic noninfectious pathology in children. The adequate complex correction of intestinal dysbacteriosis on the basis of probiotic therapy facilitates the prolonged remission of the disease in children with diabetes mellitus of type 1 (DM1) and myopathy, decreases severity of late complications of DM1. A suggestion is made on the role of dysbiotic microflora in the development of chronic non-infectious pathology in children.

[The action of tuftsin on the reaction of macrophage-suppressor formation in vitro and in vivo]. / Deistvie taftsina na reaktsiiu obrazovaniia makrofagov-supressorov in vitro i in vivo.

A cell suspension consisting of nonadhering and adhering spleen cells in the ratio 30:1 was incubated in a 10(-4) M tuftsin's solution during 15-30 min. The addition of 10(7) cells incubated in tuftsin syngeneic recipients resulted in the suppression of the immune response of the latter to sheep red blood cells. It was noted that this effect may be induced by using adhering cells only of intact donors and only when incubated together with nonadhering cells. The addition of tuftsin one hour after transplantation of the nonadhering spleen cells resulted in the suppression of the immune response. It was proposed, that suppression effect released through generation of the macrophage-suppressors.