Osteoarthritis (OA) is the most common joint disease. Searching for new treatment methods and regimens for OA is relevant.Objective: to evaluate the efficiency and safety of therapy with a symptomatic sustained-release drug (Alflutop) in combination with intra-articular hyaluronic acid (HA) injection versus monotherapy with HA in patients with knee OA in routine clinical practice.Patients and methods. A post-registration open-labeled prospective comparative randomized study was conducted to assess the results of treatment in 76 patients (31 men and 45 women; mean age, 49.3±8.5 years; body mass index, 28.4±0.8 kg/m2 ) in two clinical centers in Yekaterinburg and Perm. The patients were randomized into two equal groups, were homogeneous in terms of gender, the frequency of comorbidities, and vital signs (blood pressure, heart rate, and respiratory rate).Group 1 patients received Alflutop as 1-ml daily intramuscular injections (a total of 20 injections) + 2 ml of 1% intraarticular (IA) HA solution injections three times at 1-week intervals; Group 2 patients were given 2 ml of 1% intraarticular HA solution injections three times at 1-week intervals. As an additional therapy, the use of meloxicam 7.5–15 mg/day was permitted, and, if non-steroidal anti-inflammatory drugs were contraindicated, paracetamol 1–3 g/day might be used.Results and discussion. During treatment, both groups of patients showed improvement (compared to the baseline levels). At the same time, evaluating the intergroup values revealed clear differences: a more pronounced decrease in all WOMAC indicators in Group 1 patients: pain scores, 2 [1; 3] vs. 4 [2; 5] in Group 2 (p<0.001); stiffness, 1 [0; 2] vs. 2 [1; 4] (p<0.001); functional insufficiency, 8 [3; 12] vs. 15.5 [12; 20] (p<0.001); and total WOMAC scores, 12 [7; 13] vs. 21.5 [15; 28] (p<0.001). Pain-intensity assessment using the visual analogue scale also showed the more pronounced positive effect of the combination therapy in Group 1 (p<0.001).Alflutop used in combination with HA was shown to be more preferable than HA monotherapy, which was confirmed by the results achieved for all WOMAC indicators. At 6 months, by the last visit, there were pronounced positive changes in all the analyzed parameters in both groups. At the same time, the most significant changes were recorded in the Alflutop + HA group than in the HA group (p<0.001). Perhaps, the mechanism in exhibiting the found synergistic effect of these drugs lies in their different effect on the pathogenesis of the disease. However, further study of this issue is required in multicenter randomized controlled trials.The good safety of the drugs was confirmed: not a single adverse event was revealed.Conclusion. The patients receiving the combination therapy with Alflutop + HA had the best treatment results in all the parameters assessed.

Резюме. Клинико-иммунологические исследования проведены у пациентов с повреждениями лицевого скелета до и после стабильного остеосинтеза нижней челюсти. Установлено, что сменяющиеся стадии регенерации костной ткани (воспаление, пролиферация остеобластов, коллагеногенез и оссификация) сопровождаются изменениями иммунологических параметров. У больных с замедленной консолидацией до операции было понижено количество моноцитов, уровень лактоферрина. Послеоперационный период характеризовался активацией лейкопоэза, увеличением уровня IgМ и TNFα. На основании проведенного исследования были разработаны критерии прогнозирования замедленной консолидации костной ткани в лечении повреждений нижней челюсти. Они позволяют на разных этапах лечения (до операции, на 3 или 10 сутки после операции) прогнозировать развитие осложнения. Для каждого из них по унифицированным формулам рассчитана диагностическая чувствительность, диагностическая специфичность и информативность тестов, то есть способность предсказать возможное развитие замедленной консолидации костной ткани.

Екатеринбург 2 ФБУН Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промышленных предприятий Роспотребнадзора, г. Екатеринбург 3 ФГБУ Институт иммунологии и физиологии Уральского отделения РАН, г. Екатеринбург 4 ГОУ ВПО Уральская государственная медицинская академия МЗиСР РФ, г. Екатеринбург Резюме. Фагоцитоз является ключевым механизмом в защите организма от микобактерий туберкулеза. Целью работы стало изучение возможностей оценки фагоцитарной активности клеток при туберкулезе легких методом проточной цитофлюориметрии. Обследовали 39 человек: 14-с инфильтративной формой туберкулеза, 15-с туберкуломой, 10 практически здоровых людей. В работе использовали прибор COULTER ® Epics ® XL, реагенты Phagotest ® (Orpegen Pharma), BurstTestKit (Glycotope Biotechnology) и моноклональные антитела для определения субпопуляций лимфоцитов. Статистическая обработка производилась с использованием программы STATISTICА. Установлено, что оценка фагоцитарной активности клеток является важным критерием определения активности туберкулеза легких на ранних стадиях наблюдения и в процессе лечения, проточная цитофлюориметрия позволяет быстро, точно и объективно оценить фагоцитарную активность клеток крови. Определено, что маркеры ранней активации клетки могут отражать активность патологического процесса и использоваться для прогнозирования течения туберкулеза легких.

Interest in the study of cell population heterogeneity among immune system grows with advances in multicolor flow cytometry techniques. Natural killer cells are represented by several subpopulations. Their maturation is a continuous process that begins with CD27-CD11b--cells and ends with mature cells with the CD27-CD11b+-phenotype. Phthisiology is one of the areas for studying the NK-cell polymorphism due to the fact that the mechanism of prolonged persistence of M. tuberculosis in the human body is not fully understood. Moreover, there is increasing number of patients with infectious comorbidities, including the human immunodeficiency virus (HIV) infection. The aim of this study was to determine some subpopulations of NK cells in the patients with pulmonary tuberculous granuloma, as well as in the absence of a synergistic HIV infection.The study involved 46 people grouped in three cohorts. The 1st group included 24 practically healthy people, the 2nd group consisted of 12 patients with pulmonary tuberculous granuloma without clinical and laboratory signs of HIV infection, and the 3rd group was represented by 10 patients with pulmonary tuberculous granuloma infected with HIV. The causative agent of pulmonary tuberculosis in all patients was drug-resistant. All the patients with HIV infection had stage 4 disease. Immunological status was assessed by flow cytometry. The following cell populations were detected: CD45+CD3+CD19-, CD45+CD3-CD19+, CD45+CD3-CD16+CD56+, CD3+CD16+CD56+, CD45+CD3-CD8+, CD45+CD3-HLA-DR+, CD45+CD3-CD16+CD56+CD11b+. Leukocytosis and leukogram were determined with a 5 Diff Mythic 22 AL clinical analyzer (Cormay, Poland). Statistical studies of the data were performed in the Windows 10 operating environment (Microsoft Corp., USA); the computer program Statistica v. 12.5 (StatSoft, USA) was used. The normality of the data distribution was also evaluated. Kruskal–Wallis one-way analysis of variance (pk-w) was used as criterion for assessing differences between the compared groups at a significance level of differences p 0.017 (between three unrelated groups), as well as Wald–Wolfowitz test (pw-w) with a significance level of differences p 0.05. Factor analysis was performed.We have found that the presence of pulmonary tuberculous granuloma is accompanied by a decrease of NK-cells number by 33%, a two-fold decrease in the number of NKT-cells, a 34.3% decrease in the population of CD3-HLA-DR+-cells, and a 21.7% decrease in the number of CD3-CD16+CD56+CD11b+-cells. Coinfection with HIV in cases of pulmonary tuberculous granuloma was associated with a three-fold decrease in the leukocyte numbers, significant variability in lymphocyte counts, e.g., 3-fold decrease in NK-cell counts, with NK-cells expressing α-chain of the CD8 antigen decreased by 2.3 times; 6-fold drop of NKT-cell, CD3-HLA-DR+-cells decreased by 42.9%; 2.3-fold decline in CD3-CD16+CD56+CD11b+-cells. Decreased control of M. tuberculosis infection was observed both in patients with pulmonary tuberculous granuloma, and in presence of HIV infection as associated comorbidity.

Over recent years, the number of patients with tuberculosis has not decreased in the country and in worldwide. This is due to high resistance of the pathogen and changing mechanisms of bacterial perception by the human immune system thus requiring closer examination of the issue. Cell fusion during the formation of pulmonary tuberculous granuloma involves a large number of adhesive events. Importance of α1β1 integrin has been shown for the granuloma integrity during the chronic phase of infection. It has been proven that pulmonary tuberculous granuloma should be monitored, including with the detection of cells expressing CD11c, since they support the continuous priming of T cells at different stages of infection. The aim of this study was to answer the question, if there is a different expression of integrin receptors by immune cells from the patient’s peripheral blood at different stages of the existence of pulmonary tuberculous granuloma? The study involved 38 people: the first group (control) consisted of 15 practically healthy people; a second group included 11 subjects with pulmonary tuberculous granuloma; the condition was first diagnosed 2 to 10 months before the present study. A third group consisted of 12 patients with pulmonary tuberculous granuloma, with primary diagnosis established 12 to 219 months before this study. All the participants underwent a general clinical blood tests using a 5 Diff Mythic 22 AL analyzer (Cormay, Poland). The adhesion markers CD11b, CD11c were detected with a Coulter Epicx XL instrument (Beckman Coulter, USA). The following peripheral blood cell populations were determined: CD14- CD13lowCD11b+, CD14- CD13lowCD11c+, CD14+CD11b+, CD14+CD11c+, CD45+CD3- CD16+CD56+, CD45+CD3- CD16+CD56+CD11b+. Statistical processing of the results was performed in the Windows 10 operating environment (Microsoft Corp., USA), using Statistica v. 12.5 software (StatSoft, USA). Kruskal–Wallis one-way analysis of variance (pk-w), with differences significant at p < 0.017, as well as the Wald–Wolfowitz test (pw-w) at a significance level of p < 0.05 were used as criteria for assessing differences between the compared groups. In addition, cluster and factor analysis were implemented. When studying the role of β2-integrins, we have found that they play an important role in maintaining the existence of pulmonary tuberculous granuloma. An increase in total number of granulocytes, and CD11b-expressing granulocytes, a decrease in the population of lymphocytes, NK cells and NK cells expressing CD11c proved to be distinctive in cases of pulmonary tuberculous granuloma detected 0.5 years before the study. Characteristic changes observed in the study of peripheral blood in the patients with pulmonary tuberculous granuloma detected 9.5 years before the study were as follows: an increase in the leukocyte population, total monocyte number, as well as CD11band CD11c-expressing monocytes.