Transforming growth factor beta in human milk and allergic outcomes in children: A systematic review
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01.09.2019 |
Khaleva E.
Gridneva Z.
Geddes D.
Oddy W.
Colicino S.
Blyuss O.
Boyle R.
Warner J.
Munblit D.
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Clinical and Experimental Allergy |
10.1111/cea.13409 |
4 |
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© 2019 John Wiley & Sons Ltd Background: Human milk (HM) transforming growth factor beta (TGF-β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF-β levels are associated with allergic outcomes. Objective: We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF-β and allergic outcomes in children. Methods: Electronic bibliographic databases (MEDLINE, EMBASE and Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. Results: A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF-β and risk of eczema; 14, allergic sensitization; nine, wheezing/asthma; six, food allergy; three, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF-β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF-β2 on eczema. Meta-analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. Conclusion and clinical relevance: In contrast with previous findings, we did not find strong evidence of associations between HM TGF-β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF-β influences the risk of allergy development. Future studies on diverse populations employing standardized methods, accurate phenotyping of outcomes and evaluation of the effect of TGF-β in combination with other HM immune markers, microbiome and oligosaccharides are required.
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Multiple modulation of acid-sensing ion channel 1a by the alkaloid daurisoline
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01.08.2019 |
Osmakov D.
Koshelev S.
Lyukmanova E.
Shulepko M.
Andreev Y.
Illes P.
Kozlov S.
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Biomolecules |
10.3390/biom9080336 |
2 |
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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Acid-sensing ion channels (ASICs) are proton-gated sodium-selective channels that are expressed in the peripheral and central nervous systems. ASIC1a is one of the most intensively studied isoforms due to its importance and wide representation in organisms, but it is still largely unexplored as a target for therapy. In this study, we demonstrated response of the ASIC1a to acidification in the presence of the daurisoline (DAU) ligand. DAU alone did not activate the channel, but in combination with protons, it produced the second peak component of the ASIC1a current. This second peak differs from the sustained component (which is induced by RF-amide peptides), as the second (DAU-induced) peak is completely desensitized, with the same kinetics as the main peak. The co-application of DAU and mambalgin-2 indicated that their binding sites do not overlap. Additionally, we found an asymmetry in the pH activation curve of the channel, which was well-described by a mathematical model based on the multiplied probabilities of protons binding with a pool of high-cooperative sites and a single proton binding with a non-cooperative site. In this model, DAU targeted the pool of high-cooperative sites and, when applied with protons, acted as an inhibitor of ASIC1a activation. Moreover, DAU’s occupation of the same binding site most probably reverses the channel from steady-state desensitization in the pH 6.9–7.3 range. DAU features disclose new opportunities in studies of ASIC structure and function.
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Maternal sensitization and sensitization of the child at 1 year: How significant they are for atopic dermatitis development in early childhood?
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01.03.2018 |
Treneva M.
Munblit D.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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0 |
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© 2018, Pediatria Ltd.. All rights reserved. In 2011, a cohort for prospective follow-up was chose from the general population of newborns in Moscow. In 3 years of life, information on atopic dermatitis (AtD) symptoms was collected. Skin tests with allergens were performed in mothers and in children aged 1 year. Objective of the research – to correlate the sensitization of a child at the age of 1 year and sensitization of his mother with subsequent possible development of AtD in his early childhood. Study materials and methods: mother's sensitization and sensitization of a child at 1 year of age were examined separately for the possible appearance of AtD diagnostic signs at the age of 1, 2, 3 years of a child and in general in early childhood. The results of each study are presented by several methods of statistical processing: 1) analysis of conjugation tables, incl. hierarchical log-linear; 2) logistic regression models in which: a) the sensitization degree was considered, b) the sensitization was analyzed as a qualitative sign, in the presence of a papule. Results and discussion: рrospective monitoring of the cohort shows the dynamics of AtD frequency in early childhood, the number of sensitized mothers and their children. Mother's sensitization was not significant for AtD signs appearance in a child in early childhood. The sensitization of a child at the age of 1 year showed the importance of chicken egg allergen in relation to AtD signs appearance in early childhood. Study result: conclusions about the possible relationship of sensitization with AtD development in a child in early childhood.
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Application of bacterial therapeutic vaccine Immunovac-VP4 in the treatment of pollinosis
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01.01.2018 |
Kostinov M.
Poddubikova A.
Magarshak O.
Poddubikov A.
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Terapevticheskii Arkhiv |
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0 |
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© 2018 Media Sphera Publishing Group. All rights reserved. In-depth study of the function and structure of the lymphoid tissue of the gastrointestinal tract and respiratory tract opens wide opportunities for the use of mucosal vaccines to improve immunity to various infectious agents. One such drug is The immunovac-VP4 vaccine containing pathogen-associated molecular structures (PAMSs) of microorganisms. They are the antigens of Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Staphylococcus aureus. Discovered in many studies and experiments, the ability of the vaccine to induce innate immunity provides opportunities for prevention and treatment of both infections and allergic diseases, because it promotes the switching of Th2 immune response to Th1. The aim of the study was to study the effectiveness of the complex use of bacterial therapeutic vaccine Immunovac-VP4 and allergen-specific immune therapy (ASIT) in pollinosis in children and adults. Materials and methods. Bacterial therapeutic vaccine Immunovac-VP4 was used annually, nasal and oral administration in patients before the course of ASIT standardized aqueous-salt solutions of allergens. Results. The therapeutic application of bacterial vaccines, Immunoac-ÂÏ4 before the course ASIT has helped to reduce the frequency of acute respiratory infections in 8,5 times in comparison with the control group. Clinical efficacy of complex treatment according to the results of the survey of patients in 7 years after the start of therapy was 90%. There was a significant decrease In IgG4 to causally significant allergens, General immnunoglobulin E (IgE) and a tendency to decrease IgE. Conclusion. The use of bacterial therapeutic vaccine Immunovac-VP4, which is a natural ligand of toll-like receptors in combination with ASIT, seems to be an effective and promising direction in the treatment of allergic diseases.
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Food allergy in children with inherited epidermolysis bullosa. the results of the observational study
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01.01.2018 |
Makarova S.
Namazova-Baranova L.
Murashkin N.
Epishev R.
Chumbadze T.
Kogevnikova O.
Snovskaya M.
Vishneva E.
Ereshko O.
Balabekova F.
Yasakov D.
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Vestnik Rossiiskoi Akademii Meditsinskikh Nauk |
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0 |
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© 2018 Izdatel'stvo Meditsina. All rights reserved. Background: Inherited epidermolysis bullosa (EB) refers to a group of rare inherited disorders characterized by severe damage of skin and in most patients - the gastrointestinal mucosa, what leads to a violation of skin and mucosal barrier properties in relation to allergens. However, the issues of food sensitization and food allergy in this category of patients have not been studied, and the study of this problem is important. Aim: To evaluate the clinical manifestations of food allergy (FA) and IgE-response to food proteins in children with EB. Methods: 82 patients with EB aged from 2 months to 16 years were entered this open non-randomized observational prospective study, including 20 patients with simple form of EB and 62 patients with dystrophic form of EB. We analyzed allergic history and clinical manifestations of the FA in all the patients. Every patient in this study underwent of determination of the concentration of total serum IgE and specific serum IgE to the most important food allergens, as well as to mixtures of household allergens in some cases (UniCAP System, Phadia AB). Results: Skin lesion in patients with EB masks allergic skin manifestations, causing a hypodiagnosis of the FA in this category of patients, which in turn leads to erroneous organization of nutritional support. FA (clinical manifestations) was identified in 20.7% of children with EB (in 10% of cases with simple form of EB and in 24.2% - in patients with dystrophic form of EB). Products containing cow's milk protein, cereals, and eggs were identified as etiologic factors of FA in most cases. In the group of children with comorbidity FA and EB high and very high levels of total IgE (>1000 kUA / l) were detected most frequently. The main cause-significant allergens are cow's milk proteins, cereals, eggs. Conclusions: Comorbidity with FA is high in patients with dystrophic form of EB. The main cause-significant allergens are cow's milk proteins, cereals, eggs.
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