Gn Gabrichevsky Institute Of Epidemiology And Microbiology

Moscow, Russia

Gn Gabrichevsky Institute Of Epidemiology And Microbiology

Moscow, Russia
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Shmarina G.,Russian Paediatric Clinical Hospital | Pukhalsky A.,Russian Paediatric Clinical Hospital | Avakian L.,Federal State Budgetary Institution | Semykin S.,Federal State Budgetary Institution | And 2 more authors.
International Archives of Allergy and Immunology | Year: 2017

Background: Anti-inflammatory therapy is a logical approach to slowing the inevitable lung function deterioration in cystic fibrosis (CF) patients. This study's aim was to evaluate inflammatory markers and disease progression in paediatric CF patients chronically treated with azithromycin or low-dose prednisolone. Methods: The study included 204 patients with CF and 100 healthy controls; 102 CF patients were treated with basic therapy only (without anti-inflammatory treatment; WAT), and 102 individuals received basic therapy along with azithromycin (n = 59) or low-dose prednisolone (n = 43). The median duration of therapy was 24 months (range 12-82) with azithromycin and 31 months (range 12-180) with prednisolone. A cross-sectional analysis of plasma and sputum biomarkers was performed. Results: Compared with the healthy controls, the WAT group showed elevated IFN-γ, IL-10 (total), and TGFβ1 concentrations, and decreased TNFα (total) and adrenocorticotropic hormone (ACTH) levels (all p < 0.05). Plasma TNFα (total) concentrations in azithromycin/prednisolone patients were significantly higher than those in WAT patients and similar to those of healthy children. In contrast, IL-10 (total) levels were significantly decreased in azithromycin/prednisolone-treated patients compared with WAT patients. Children from the azithromycin group demonstrated ACTH levels similar to those of healthy controls. Azithromycin-treated patients showed a significantly reduced rate of CF-related liver disease and a significantly increased incidence of glucose metabolism disturbances. Conclusions: Steady-state anti-inflammatory treatments may have a sustained immunomodulatory action at systemic and local levels in CF patients. Further investigations are needed to assess the effects of supportive azithromycin therapy on the hypothalamic-pituitary-adrenal axis and the incidence of non-pulmonary CF complications. © 2017 S. Karger AG, Basel. Copyright: All rights reserved.


Toptygina A.,Gn Gabrichevsky Institute Of Epidemiology And Microbiology | Alioshkin V.,Gn Gabrichevsky Institute Of Epidemiology And Microbiology
Archives of Physiology and Biochemistry | Year: 2012

60 children aged 1-2 years old (32 boys and 28 girls) were vaccinated with Priorix. Vaccinated children included healthy control (19 children, group 1), and children with immunological disturbances such as episodes of respiratory infection. From the latter group, 20 children did not receive (group 2), and 21 children received 0.15 mg/kg of Polyoxidonium simultaneously with the vaccine (group 3).On days 7 and 30 after vaccination, CD-markers on lymphocytes and concentration of specific antibodies, as well as levels of 11 cytokines in serum were evaluated by flow cytometry, ELISA, and multiplex techniques respectively. It was found that injection of Polyoxidonium skewed T helper differentiation to Th2 type. Antibody responses were significantly higher in children with preferable Th2 responses. Children from group 3 possessed higher titers of specific IgG-antibodies. Our study shows that Polyoxidonium could smooth out the immune reaction on vaccination. It is important for children with some immunological disturbances. © 2012 Informa UK, Ltd.


Pimenova A.S.,Gn Gabrichevsky Institute Of Epidemiology And Microbiology | Borisova O.Yu.,Russian National Research Medical University | Tsvircun O.V.,Gn Gabrichevsky Institute Of Epidemiology And Microbiology | Basov A.S.,Gn Gabrichevsky Institute Of Epidemiology And Microbiology | And 7 more authors.
Russian Journal of Infection and Immunity | Year: 2017

Purpose: whooping cough diagnostics by molecular-genetic methods. Materials and methods. Under observation there were 4930 people during the period from 2012 to 2015. All samples were received in 8 schools of Moscow and the Moscow region: in 3 schools had been found children with whooping cough, in other 5 schools - only children with prolonged cough. Whooping cough diagnosis had been given earlier by bacteriological and serological methods. 430 clinical samples were studied by 2 methods: PCR with fluorescent hybridized detection of amplified products and isothermal amplification. Results. In three of eight schools whooping cough cases at 7 children at the age of 7, 9, 11 and 15 years were revealed earlier. The diagnosis of whooping cough at them was confirmed by means of bacteriological and serological methods. 33 positive DNA samples (7.7%) are revealed. DNA-positive samples are allocated from 18 pupils and 15 employees of schools. In two schools where earlier infection sources were established, 15 DNA-positive samples from which in three cases clinical manifestations were observed are revealed. In those schools where it wasn't earlier established a source of an infection and examinations conducted it is long the coughing children, 18 DNA-positive samples are revealed, and in two cases clinical manifestations in the form of cough were observed. Conclusion. Performed research confirmed high efectiveness of molecular-genetic methods during pertussis infection foci examination in schools for infection source identification also amongst long coughing children.


Pukhalsky A.L.,Research Center for Medical Genetics | Shmarina G.V.,Research Center for Medical Genetics | Kapustin I.V.,Gn Gabrichevsky Institute Of Epidemiology And Microbiology | Stukalov S.V.,Research Center for Medical Genetics | And 2 more authors.
Cell and Tissue Biology | Year: 2011

The relationship between the levels of 70 kDa family heat shock protein (Hsp) synthesis and lymphocyte sensitivity to stressors was investigated. Lymphocyte cultivation in mitogen deprived culture medium and/or the cell treatment with alkylating agents have been used as a stress challenge. Model experiments with two inbred murine strains genetically contrasting by the sensitivity to alkylating agents demonstrated that the basic level of Hsp synthesis depends on genotype. The quantity Hsp70 mRNA, as well as intracellular level of the proteins, in BALB/c was significantly higher than those in C57BL/6 mice. The mice, which were characterized by higher Hsp levels, demonstrated higher resistance to alkylating agent action. The induction of surplus amount of Hsp by heat shock increased the cell resistance to an alkylating agent melphalan. Lymphocyte isolated from high Hsp producers BALB/c mice were more resistant to apoptotic signals induced by mitogen deprivation. © 2011 Pleiades Publishing, Ltd.


Pukhalsky A.,Research Center for Medical Genetics | Shmarina G.,Research Center for Medical Genetics | Alioshkin V.,Gn Gabrichevsky Institute Of Epidemiology And Microbiology
OMICS A Journal of Integrative Biology | Year: 2012

Surplus accumulation of regulatory T cells (Tregs) is known to be at the bottom of many morbid conditions, among them being neuropsychiatric diseases. In particular, Tregs may inhibit Th1 cells, including brain autoimmune lymphocytes, controlling the local microglial response and brain tissue homeostasis. The present study was undertaken in an attempt to suggest a novel approach for the treatment of maladaptation to mental stress associated with excessive Treg accumulation. Recently it was shown that alkylating drugs (ADs), such as melphalan and cyclophosphamide (Cy) in the dose 100-fold lower than cytostatic one are capable to disturb signal transduction by IL-2R. In this study we demonstrated that IL-2R is not a unique receptor, which may be blocked with ADs. Similar effect has been shown for two other surface receptors: TNFR and Fas. Molecular mechanisms of the receptor blockage were investigated on the model of TNF signaling. Study of NF-κB activity in nuclear extracts showed that alkylating agents act at the level of surface receptor or of the receptor platform. It was also shown that ADs administration in ultralow doses results in selective elimination of Tregs. In this study we used a new laboratory model of Treg accumulation in mice. Such Treg accumulation was associated with cognitive and behavioral abnormalities, which may be prevented by Cy administration. © Copyright 2012, Mary Ann Liebert, Inc.


Pukhalsky A.L.,Research Center for Medical Genetics | Shmarina G.V.,Research Center for Medical Genetics | Alioshkin V.A.,Gn Gabrichevsky Institute Of Epidemiology And Microbiology
Vestnik Rossiiskoi Akademii Meditsinskikh Nauk | Year: 2011

Regulatory T-cells (Tregs) are important components of the complex adaptive system of the body responsive to environmental challenges. Tregs ensure peripheral tolerance and play an important role in control of inflammatory reactions. Several subsets of Tregs have been described. Naturally occurring CD4+CD25+ Tregs are recognized as a major subset of immune cells responsible for peripheral immune selftol-erance. Another subtype of Tregs is inducible. Such Tregs are generated in the periphery and realize their suppressive potential largely in the form of anti-inflammatory activity. The latter plays an important role in cooperation of three principal anti-inflammatory mechanisms that developed in the course of evolution: macrophages possessed of suppressive activity, Tregs, and stress hormones. Normally, all the three mechanisms of inflammation control are in equilibrium. However, the balance may be disturbed with ageing due to repeated episodes of stress and HPA axis activation. As a result, secretion of stress hormones coupled to antigen overload leads to Treg accumulation. In the course of time activation of the HPA axis is replaced by its inhibition manifested both as a decrease of the baseline Cortisol level and a reduction of stress-induced Cortisol response. Cortisol present in blood at low concentrations is no longer capable of controlling inflammation and Tregs become a principal mechanism of anti-inflammatory machinery. Superfluous Treg accumulation results in the development of functional somatic syndromes, such as chronic fatigue syndrome, and (in some patients) in the growth of tumours resulting from the suppression of anticancer immunity. On the other hand, the lack of adequate antigen loading in the childhood may delay Treg maturation. Allergy and asthma manifestations may be a consequence of such Treg insufficiency. Thus, both excess and deficiency of Tregs may be at the bottom of morbid conditions. The advances in modern pharmacology open up opportunities for developing new methods to control the Treg level.


Pukhalsky A.,Gn Gabrichevsky Institute Of Epidemiology And Microbiology | Shmarina G.,Gn Gabrichevsky Institute Of Epidemiology And Microbiology | Alioshkin V.,Gn Gabrichevsky Institute Of Epidemiology And Microbiology
Advances in Neuroimmune Biology | Year: 2012

The brain and immune system being the two principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain, which is separated from the rest of the body by blood-brain-barrier (BBB), produces the cytokines by itself and the latter along with other neurotransmitters regulate various brain functions including cognition, memory, and neuronal differentiation. The stress of different origin increases the serum cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Long-term stress as well as physiological aging result in hormonal disturbance, first of all in the form of HPA axis depletion and dehydroepiandrosterone (DHEA) decrease. Thus, the changes observed in stressed subject form a picture typical of the aging brain. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets. Clinical and experimental studies confirm efficiency of such choice although in some instances we can say only about indirect evidences. © 2012-IOS Press and the authors. All rights reserved.


PubMed | GN Gabrichevsky Institute of Epidemiology and Microbiology
Type: Journal Article | Journal: Epidemiology and infection | Year: 2011

The rate of case investigation for measles-like illness (MLI) is an important indicator for the quality of measles surveillance in countries targeting measles elimination. However, a benchmark rate is still being discussed. We assessed different rates of investigation in 11 territories of the Russian Federation with low reported measles incidence during the previous 4-7 years. Each territory maintained their existing surveillance activities and also undertook additional surveillance activities for MLI over a 3-year period. The annual routine rate of investigation varied from 006 to 18/100,000 population; the overall rate of investigation, including enhanced surveillance, varied from 14 to 72/100,000. Forty-nine (308%) of 159 measles cases detected were identified through enhanced surveillance. Based on the results of this study, the Russian Federation concluded that a rate of routine investigation of 2/100,000 provided the best balance between available resources and sensitivity for detection of measles cases.


PubMed | Gn Gabrichevsky Institute Of Epidemiology And Microbiology
Type: Journal Article | Journal: Archives of physiology and biochemistry | Year: 2012

60 children aged 1-2 years old (32 boys and 28 girls) were vaccinated with Priorix. Vaccinated children included healthy control (19 children, group 1), and children with immunological disturbances such as episodes of respiratory infection. From the latter group, 20 children did not receive (group 2), and 21 children received 0.15 mg/kg of Polyoxidonium simultaneously with the vaccine (group 3).On days 7 and 30 after vaccination, CD-markers on lymphocytes and concentration of specific antibodies, as well as levels of 11 cytokines in serum were evaluated by flow cytometry, ELISA, and multiplex techniques respectively. It was found that injection of Polyoxidonium skewed T helper differentiation to Th2 type. Antibody responses were significantly higher in children with preferable Th2 responses. Children from group 3 possessed higher titers of specific IgG-antibodies. Our study shows that Polyoxidonium could smooth out the immune reaction on vaccination. It is important for children with some immunological disturbances.

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