Role of diamine oxidase in the pathogenesis of chronic urticaria

Chronic urticaria is a polyetiological disease proceeding by various immunological and non-immunological (pseudo-allergic) mechanisms. Food intolerance is a distinct type of pseudo-allergies, manifesting, e.g., with histamine intolerance syndrome, caused by imbalance between the histamine accumulation and the ability to degrade it. The purpose of this article was to summarize results of recent studies, to discuss the difficulties of diagnosing this pathology, which primarily depends on the degree of impaired histamine degradation under the influence of diamine oxidase. Diamine oxidase is the main enzyme required for histamine destruction in the intestines, being synthesized by apical enterocytes. The review draws attention to the reasons leading to increased level of histamine not only with consumed food, given its different concentration in the same food products, depending, for example, on their processing and storage, but also with suppressing activity of the enzymes required for metabolism of histamine by various food additives, by the influence of microbiota. The results of studies in which the levels of histamine and/or diamine oxidase activity were determined, which depend on adherence to the diet confirming the association of diamine oxidase with the symptoms of histamine intolerance. According to most studies, the compliance with diet led to increased level of diamine oxidase. However, in some studies, no changes in the activity of this enzyme were found. There are several studies that have evaluated the levels of diamine oxidase in patients with true allergies. Moreover, some authors, in addition to adherence to the diet, evaluated the effectiveness of drugs containing diamine oxidase in patients with low levels of this enzyme in blood serum. The workers also confirm high proportion of histamine intolerance syndrome among various food reactions, suggesting a need for differential diagnosis with other non-immune reactions, including disorders of gastrointestinal tract and psychosomatic reactions. Thus, all the authors confirm the need for laboratory diagnosis of histamine intolerance syndrome, since this will not only increase the efficiency of dietary adherence, but also substantiate the usage of drugs containing diamine oxidase, which will improve quality of life in these cohorts. However, these patients are still treated with low-histamine diets. The literature data confirm the opportunity of using this histamine degradation enzyme as a biological marker of histamine intolerance syndrome, and recommend its assays for inclusion into the diagnostic algorithm for chronic urticaria

FEATURES OF IMMUNE RESPONSE AND BASOPHIL ACTIVATION IN CHILDREN WITH CHRONIC URTICARIA

Some features of peripheral bood basophil activation were studied in children with different types of chronic urticaria, in order to specify the sustaining mechanisms of chronic urticaria. This study presents comparative data concerning spontaneous basophil activation, IgE level and Th2 helper cells. We observed forty-seven children with chronic urticaria, seventy children with exacerbated atopic dermatitis with different disease severity, fifteen healthy children without signs of allergy, or pseudo-allergy. High degree of the basophil activation was detected in children with exacerbation of atopic dermatitis (a comparison group), which was different from the groups of healthy children and patients with chronic urticaria. Spontaneous basophile activation was higher in children with chronic urticaria than in healthy children, as influenced by immune and non-immune pathogenetic factors of the disease. A positive pairwise correlation was shown between total IgE level, and Th2 helper cell numbers in peripheral blood in patients with chronic urticaria, thus confirming a Th2 immune shift. The results obtained contribute to our understanding of immune pathology in chronic urticaria

T-lymphocytes of the 2nd type of the immune response and their role in enhancing inflammation during the professional activities of firefighters

T lymphocytes of the 2nd type of immune response contribute to the development and exacerbation of inflammation, mainly allergic. Increased inflammation with prolonged exposure to adverse factors during the work of firefighters can lead to the development of various diseases. Evaluation of the immunity of firefighters is important for the appointment of adequate treatment and prevention of infectious and allergic diseases. This paper aimed to analyze the indicators of immunity in employees of the state fire service of EMERCOM of Russia, depending on the age and intensity of the professional workload. The surveyed were men (n = 79), mean age 31 years, work experience from 1 to 22 years, with different workload intensity. In peripheral blood, flow cytometry (Navios, FC 500, Beckman Coulter) was used to evaluate subpopulations of monocytes, the relative number of T lymphocytes of the 2nd type of immune response CD3+CD294+. The concentration of total immunoglobulin E (Immulite) was determined. From nasal secretions, the content of secretory immunoglobulin A (Vector Best) was evaluated (n = 30). Statistical processing of the results was performed using the Statistica 12.0 package (StatSoft). An increase in the number of CD3+CD294+ cells was observed in 16.5%. A direct correlation was found between the number of T lymphocytes 2 and the age of the examined persons (р < 0.05). In the group of firefighters with a more intense workload, an increase in the number of CD3+CD294+ cells were 5 times higher (р < 0.05). Among patients who had any disease of the respiratory tract, an increase in this population was observed statistically significantly more often – in 26% of cases versus 11.5%. A strong direct correlation was found between the number of T lymphocytes 2 and the duration of smoking experience (р < 0.05). A direct correlation was established between the number of T lymphocytes 2 and the concentration of total IgE (р < 0.05). A decrease in secretory IgA in the secret from the nasal passages was observed in 23% of firefighters, in 13% of the examined, the indicator went beyond the upper limit of the reference interval. Significantly more often revealed the deviation of this indicator from the reference values in firefighters with a high workload. An increase in the subpopulation of classical monocytes was established in the group of those examined with a high number of CD3+CD294+ cells (p < 0.05). Thus, with an increase in the professional workload of firefighters in unfavorable conditions of service, inhibition of protection to infection and aggravation of damage to the respiratory tract with an increase in the 2nd type of immune response are noted. Evaluation of the number of type 2 T lymphocytes in peripheral blood will reveal a predisposition to the T2 profile of immune inflammation, which will contribute to a personalized approach to patient management

Factors of successful diversification for machine-building enterprises

The relevance of the study is due to the need to diversify production in order to increase competitiveness and strengthen the economic sustainability of enterprises. Increasing the output of high-tech civil and dual-use products by enterprises of the military-industrial complex as part of the conversion is complicated by the lack of enterprises work experience in the market. Conversion of defense industry enterprises is an important and promising task, the solution of which is connected with the future of defense industry enterprises, the development of import substitution, the expansion of high-tech exports. The purpose of the study is to analyze the world experience of conversion, to study existing approaches to solving conversion implementation problems, creating a system of conversion success factors, monitoring the effect of external and internal conversion implementation factors, identifying actual problems of this process. The author's approach to solving conversion problems consists of identifying external and internal conversion success factors and combining them into a single system for the interaction between the state and defense enterprises. The study of the implementation of the indicated factors showed the degree of their development, as well as the directions that will contribute to the development of diversification. © Published under licence by IOP Publishing Ltd

THE MODERN CONCEPTIONS ABOUT IMMUNOPATHOGENESIS OF INFECTION CAUSED BY THE EPSTEIN–BARR VIRUS

Abstract. The current review summarizes modern data about structural and functional organization of the Epstein–Barr virus (EBV) and stages of its reproduction. The information concerning immune pathogenesis and clinical features of infection caused by EBV and EBV-associated diseases is presented in the article

Clinical significance of sensitization to house dust mite allergens using flow cytometry-based basophil activation test

Respiratory allergy takes a significant place among allergic diseases. Similar clinical manifestations occur in sensitized patients in response to various airborne allergens. Accordingly, the allergen testing by means of in vivo and in vitro techniques is necessary to identify a causally significant allergen. The main laboratory assay to estimate sensitization to the airborne allergens is based on detection of specific immunoglobulin E (sIgE). However, clinical manifestations cannot be always confirmed by this test. The aim of this work was to evaluate the potential of basophil activation test (BAT) using flow cytometry, in order to confirm sensitization to house dust mite allergens. The BAT was carried out with allergens from Dermatofagoides in 34 volunteers, 130 patients were examined at the Russian Centre of Emergency and Radiation Medicine (33 people with household and 97 people with polysensitization), and 10 patients with allergy to house dust mites confirmed by skin testing. The sensitization was assessed using two laboratory kits (Allergenicity and BD FastImmune). The total IgE and sIgE to house dust mites, as well as concentrations of eosinophilic cationic protein, were determined. Specificity of the BAT with Allergenicity kit for the house dust mites was 94%. The sensitivity was 88% in the patients with household sensitization, thus being comparable with skin testing results available from the literature. An absolute correlation was found between positive results of skin testing and the BAT. In patients with household sensitization, sIgE levels > 0.35 UA/mL were detected in 39% of cases. A positive correlation was shown between the indices of basophil activation in response to testing allergens, and total immunoglobulin E and sIgE concentrations. High degree of correlation was found between the results of Dermatofagoides sensitization testing with both BAT kits. It was shown that the use of H1 histamine receptor blockers had no effect on BAT results. A decrease in sensitivity assay for airborne allergens was revealed upon therapy with glucocorticosteroids. Due to the proven clinical significance of the basophil activation test for diagnosing sensitization to inhaled allergens, one may require to supplement the range of approved assays in Russian Clinical Guidelines with BAT testing to prove sensitization in patients with allergic rhinitis and bronchial asthma, thus contributing to better diagnosis of causally significant allergens and, accordingly, administration of proper therapy

Marketing aspect in the 'Value Engineering' in the new products development of machine-building enterprises

The dynamism of the engineering products markets is determined by a high level of competition, frequent changes in technology. One of the key problems of Russian machine-building enterprises is the long term of development and putting the product into the production which leads to the fact that 'yesterday's product is launched on tomorrow's markets'. So, we see an arising need for a fundamental change in the product development process by including future consumers in it and ensuring verification of the results at each stage, from the formation of the technical task to the testing of the finished product. Such an approach will allow balancing consumer value and product characteristics, determining the significance and cost of functions, and substantiating a fair price. These problems are solved by the method of value engineering of a product. Application of this method requires reliable information on consumer characteristics, conditions and process of product operation, parameters of similar products. The tools of classical marketing research and new products engineering development should be combined into one system. As a result, the use of value engineering reduces the time required to bring a new product to the market and increases the competitiveness of the product. © Published under licence by IOP Publishing Ltd

MONOCYTE SUBSETS IN HEALTHY ADULTS AND SEPSIS PATIENTS

Monocytes play a key role in the development of immune response in bacterial infection, because of their phagocytic, antigen-presenting and secretory functions. There are three subpopulations of monocytes: “classical” CD14+CD16-, “intermediate” CD14+CD16+, and “nonclassical” CD14+dimCD16+. These monocyte subtypes have different phenotypes and functions. The ratio of appropriate subpopulations varies with development of the antibacterial response. The aim of the present research was to study phenotypes of the monocyte subpopulations in the patients with sepsis, and changes in the monocyte subpopulation ratio, depending on the presence of bacteria in circulating blood of the patients, as well as to estimate contribution of the monocyte subpopulations to the cytokine production. We observed 16 patients with sepsis (10 men and 6 women; mean age, 58±14 years, SOFA 9.4±2.1; a total of 44 blood samples) examined in dynamics. The control group included healthy adults (n = 23, 12 men and 11 women; mean age, 51±13 years). Laboratory studies included bacteriological cultures, determination of absolute and relative numbers of subpopulations of classical, intermediate and non-classical monocytes and their expression of HLA-DR and CD64, determination of IL-6, TNFα, IL-1β, IL-10 concentration in blood serum. Absolute number of monocytes was increased in the sepsis patients, the ratio of classical monocytes was also increased, like as relative and absolute numbers of  intermediate cells. Meanwhile, the subpopulation of non-classical monocytes did not change significantly. The monocyte subpopulation ratio depended on the presence of bacteria in blood, i.e., a higher proportion of intermediate cells was observed in the samples positive for bacteria in blood cultures. The ratio of subpopulations was restored after elimination of bacteria from the circulation. The expression density of LPS receptor (CD14), IgG receptors (CD16 and  CD64) was found to be increased, especially in the subpopulations of intermediate and nonclassical monocytes. In all subpopulations of monocytes, expression of HLA-DR is reduced, most notably in classical monocytes, least in intermediate cells. There was a significant increase in serum levels of IL-6, IL-1β, TNFα and IL-10 cytokines. Direct correlation between the absolute number of classical monocytes and IL-6 concentration was revealed, as well as intensity of multiple organ dysfunction. Increase in absolute amount of classical monocytes and IL-6 concentration might serve as an indirect criterion for evaluation of endothelial activation, an active producer of IL-6 and myeloid cell growth factors. A direct correlation between the percentage of CD14+CD16+ cells and IL-10 concentration in blood serum indicates to an important role of intermediate monocytes in IL-10 production. IL-10 suppresses the antigen-presenting function of intermediate cells, namely, expression of HLA-DR molecules, as suggested by inverse correlation between the IL-10 concentration and HLA-DR expression density on CD14+CD16+ cells. We have also determined an inverse correlation between the degree of multi-organ dysfunction  and relative amount of HLA-DR+ monocytes. The larger was a classical monocyte subpopulation, the more noticeable was a decrease of this index. The studies in ratios of monocyte subpopulations help to understand the mechanisms of antibacterial protection in sepsis. Monitoring of classical monocyte numbers and serum concentrations of IL-6 is necessary for a comprehensive assessment of inflammatory response in sepsis. Determination of HLADR expression on monocytes allows us to evaluate the intensity of immune suppression in critically ill patients

Diversification instruments for machine-building enterprises

Improving the competitiveness of engineering products, import substitution and increasing high-tech exports are priority government tasks. The development of the high-tech products production is ensured through the diversification of engineering enterprises. The study revealed a number of problems that machine-building enterprises are facing when mastering the production of new products. The diversification methods and tools used largely determine the effectiveness of activities throughout the entire product life cycle. The authors consider the value analysis method as a key instrument for implementing the diversification strategy. Value analysis includes a variety of instruments, such as conducting marketing and patent research, reverse engineering, cooperative chain design, and others. The determination of the company's preparedness for diversification is of particular importance. The article presents an approach to assessing the key functional areas of the enterprise that indicate its preparedness for diversification. © Published under licence by IOP Publishing Ltd