Chronic tubulointerstitial nephritis in children: New approaches to diagnosis and treatment

A survey of 120 children with HTIN, aged from 4 to 15 years, was conducted. Taking into account the clinical variant of HTIN, all patients were divided into 2 groups: group 1 –52 (43%) children with recurrent form of HTIN and group 2 -68 (57%) patients with latent HTIN. Among them, there were 65 boys (54%), 55 girls (46%). The conducted studies have shown that with the development of rHTIN and lHTIN, an important mechanism of damage to interstitial kidney tissue, the development of clinical symptoms and the course of the disease is both a metabolic disorder leading to structural shifts at the level of various elements of the nephron and changes in the functional state of the kidneys, and instability of the cytomembranes of tubular cells. The analysis of the results of the study showed that the method of treatment proposed by the authors is the most effective way of treating HTIN, due to accelerated recovery, both clinical and laboratory parameters of the disease and indicators of protein metabolism, as well as in relation to the restoration of the functional state of the kidneys, which leads to a reduction in the length of hospital stay, a reduction in the number of relapses of exacerbation, prevention complications of the chronic process. All this contributes to preventing the development of disability and reducing the number of child deaths from CRF

Effect of virulent and vaccine variants of influenza virus on the immunophenotype of dendritic cells generated from murine bone marrow

The aim of this study was to generate dendritic cells from the bone marrow of mice (DC) in vitro and to assess the effect of virulent and attenuated variants of influenza virus on the maturation of DCs. Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) were used in combination, to induce differentiation of mouse bone marrow (BM) mononucleocytes into DCs. On the 5th day, distinct variants of influenza virus were added to the cell culture, and the cells were additionally incubated for 2 days. The morphological characteristics of DCs, immunophenotype of DCs and expression of some Toll-like receptors were evaluated. On the 5th day of incubation. the DCs acquired typical morphological characteristics. DCs were large in size with an eccentrically located nucleous, often irregular in shape, with numerous processes. On the 7th day of incubation with influenza virus variants, their cytoplasm was somewhat denser. DCs acquired more processes, necessary for intercellular contacts. Expression levels of CD11c, a specific marker of BM-derived DCs, and of co-stimulatory molecules such as CD40, CD80, CD86, and MHC-II were elevated in mature DCs. Virulent versus attenuated strains of the influenza virus induced special variants of DCs differentiation, with respect to expression rates of differentiation markers, as well as expression of Toll-like receptors and costimulatory molecules. Conclusions. The in vitro cultured murine mononucleocytes derived from bone marrow can produce a large number of n-DCs, that can mature in the presence of different variants.During evolution of the DC immunophenotype treated with variant influenza viruses, we have found distinct signs of immunosuppression.The attenuated U-2 and M-26 influenza variants obtained by site-specific mutagenesis upon development of DCs immunophenotype, exhibited a decreased immunosuppressive activity and were not inferior to the cold-adapted (CA) reassortant for the most positions, but exceeded it in some instances. These studies can help to assess the criteria for evaluation the efficiency of in vitro developed influenza vaccines

Synthetic BSA-conjugated disaccharide related to the Streptococcus pneumoniae serotype 3 capsular polysaccharide increases IL-17A Levels, γδ T cells, and B1 cells in mice

The disaccharide (β-D-glucopyranosyluronic acid)-(1→4)-β-D-glucopyranoside represents a repeating unit of the capsular polysaccharide of Streptococcus pneumoniae serotype 3. A conjugate of the disaccharide with BSA (di-BSA conjugate) adjuvanted with aluminum hydroxide induced — in contrast to the non-adjuvanted conjugate — IgG1 antibody production and protected mice against S. pneumoniae serotype 3 infection after intraperitoneal prime-boost immunization. Adjuvanted and non-adjuvanted conjugates induced production of Th1 (IFNγ, TNFα); Th2 (IL-5, IL-13); Th17 (IL-17A), Th1/Th17 (IL-22), and Th2/Th17 cytokines (IL-21) after immunization. The concentration of cytokines in mice sera was higher in response to the adjuvanted conjugate, with the highest level of IL-17A production after the prime and boost immunizations. In contrast, the non-adjuvanted conjugate elicited only weak production of IL-17A, which gradually decreased after the second immunization. After boost immunization of mice with the adjuvanted di-BSA conjugate, there was a significant increase in the number of CD45+/CD19+ B cells, TCR+ γδ T cell, CD5+ В1 cells, and activated cells with MHC II+ expression in the spleens of the mice. IL-17A, TCR+ γδ T cells, and CD5+ В1 cells play a crucial role in preventing pneumococcal infection, but can also contribute to autoimmune diseases. Immunization with the adjuvanted and non-adjuvanted di-BSA conjugate did not elicit autoantibodies against double-stranded DNA targeting cell nuclei in mice. Thus, the molecular and cellular markers associated with antibody production and protective activity in response to immunization with the di-BSA conjugate adjuvanted with aluminum hydroxide are IL-17A, TCR+ γδ T cells, and CD5+ В1 cells against the background of increasing MHC II+ expression

MICE SERUM CYTOKINE LEVEL UNDER MUCOSAL IMMUNIZATION WITH OPPORTUNISTIC MICROBIAL ANTIGENS

An important parameter of immunotropic preparation effect is the influence on the production of cytokines that provide the interaction between the effectors of both congenital and adaptive immunity. Cytokine level was determined in the work while using the methods of mucosal immunization with Immunovac-VP-4 and compared with the subcutaneous introduction of this preparation. In case of intranasal and peroral methods of antigen application IL-5, IL-6, and IL-12 expression was found to be elevated, the same was true for IL-1β, IL-5, IL-6, IL-12, and IFN-γ under the subcutaneous immunization. Resulting mice cytokine profile confirmed that irrespective of the method of Immunovac introduction, the activation of immune effectors occurred that was manifested in the increase in proinflammatory and regulatory cytokine levels. It was concluded that the introduction of opportunistic microbial antigens initiated the activation of the cascade of immunologic reactions and under the influence of synthesized cytokines the polarization of immune response was involved that was predominantly of Th1 type

Examining immune arms in mice immunized with site-specific influenza virus mutants

Site-specific mutants as candidates for live influenza vaccines were resulted from directly introducing into the genome of the pathogenic influenza virus A/WSN/33 (H1N1) strain ts mutations derived from the genes encoding the polymerase complex proteins from some cold-adapted strains serving as attenuation donor. Here we present the data of a comparative study examining immune system arms in mice immunized intranasally with influenza virus mutants and classical cold-adapted reassortant obtained by crossing cold-adapted strain Donor A/Krasnodar/101/35/59 (H2N2) with strain A/WSN/33 (H1N1) bearing surface antigens (hemagglutinin and neuraminidase) similar to mutants. Immunophenotyping mononuclear leukocytes from immunized mice indicated at moderate suppressive effect after using site-specific mutant and the HA reassortant viruses on some immune cell subsets. All viruses in immunized mice resulted in activation of certain lymphocyte subsets including MHC II-positive cells, CD45+/CD19+ B lymphocytes and natural killer cells (CD16/32+/CD3–). Timescale and magnitude of activation markedly differed for each cell subsets. Mice immunized with mutants M26 and U2 peaked with count of CD16/32+/CD3– expressing cells on day 2 after the second immunization compared with control (p < 0.05) that may suggest about an important role for NK cells in activating immune response. In contrast, no significant changes were observed during the study in percentage of CD4+/CD25+/Fox P3 regulatory T cells, CD4+ T helpers and CD8+ cytotoxic cells, except for a sharply decreased count of activated CD4+/CD25+ cells (4-fold) on day 7 after immunization with mutant virus M26. Moreover, mutants U2 and M26 more moderately increased percentage of TLR2- and TLR4-positive cells. The viruses studied ambiguously affected count of TLR9-expressing cells in immunized animals. All viruses increased phagocytic activity in monocytes, but not neutrophils. Despite the moderate activation of innate and adaptive immunity arms, site-specific mutants more profoundly affected humoral reactions inducing increased antibody titers, so that immunogenicity of mutant viruses was higher than that of the cold-adapted reassortant. Thus, the findings hold a promise of using site-specific mutants as live influenza vaccines

MORPHOFUNCTIONAL PECULIARITIES OF MUCOSAL IMMUNITY DEPENDING ON METHODS OF OPPORTUNISTIC MICROBIAL INTRODUCTION

Immunophenotypic and morphological peculiarities of immune reactions under intranasal, peroral and subcutaneous introduction of multicomponent vaccine Immunovac VP-4 containing a group of opportunistic bacterial antigens were investigated. The investigated preparation was found to cause marked activation of congenital immunity effectors both in parenteral and mucosal immunization. It is manifested in the expression of differential, costimulatory, adhesive molecules on the surface of mononuclear leukocytes in proliferation of key mucosal immunity effectors (γδТ, В1, NK cells), and changes in structure, cellular composition of immunocompetent organs both regional and distant as to the site of introduction. Currently existing data on effects and mechanisms of vaccine and immunomodulator mucosal introduction allows considering the development of mucosal mono- and associated vaccines as the priority direction in modern vaccinology

Effect of vitamin D and interferon α-2b on cytokine profile in pregnant women with vaginal infections

A study was conducted to evaluate effectiveness of vitamin D and interferon α-2b preparations on cytokine profile in pregnant women with vaginal infections. It was shown that pregnant women with vs. without bacterial vaginosis were featured with low vitamin D level in 53.8–60.5% cases. Administration of vitamin D and interferon α-2b preparations in combination with antibacterial therapy in pregnant women with bacterial vaginosis conferred anti-inflammatory effect resulting in normalized IL-8 level corresponding to that one in healthy subjects. Use of vitamin D altered interferon status and augmented antimicrobial activity in pregnant women confirmed by reduced rate of ARI episodes

A clinical case of demyelinating lesions of the brain: Central pontine myelinolysis

In the scientific review a rare demielinizirute disease of the brain - central pontine myelinolysis is presented. Prior to the introduction of the technique of visualization, diagnosis of the disease was through autopsy. Clinical case, which describes the variety neurological and somatic symptoms, was presented. The attention is focused on the importance of an integrated approach to diagnosis and management of the patient with the disease.В научном обзоре представлено редкое демиелинизрующее заболевание головного мозга: центральный потинный миелинолиз. До внедрения визуализирующих методов исследования оно диагностировалось только при аутопсии. Приведен клинический случай, описано многообразие неврологической и соматической симптоматики. Акцентировано внимание на значимость комплексного подхода к диагностике и ведения пациента с редким заболеванием

To Moscow with Love: Partial Reconstruction of Vygotsky’s Trip to London

The Russian psychologist Lev Vygotsky (1896–1934) left the Soviet Union only once to attend a conference on the education of the deaf in London. So far almost nothing was known about this trip, which took place in a period when Vygotsky was still completely unknown as a psychologist, both inside his own country and abroad. Making use of a newly discovered notebook, it proved possible to partially reconstruct Vygotsky’s journey and stay in London. Vygotsky’s very personal remarks show him to have been a very sensitive and spirited man, who was prey to strong emotions during the conference and afterwards. Rather surprisingly, Vygotsky’s own paper about the education of the deaf was never presented during the conference and the stay in London appears to have had a limited value for his own scientific development