Cytokine status in posttraumatic synovitis on the background of systemic and intra-articular use of NSAID and ozone

Joint  damage  initiates aseptic  self-sustaining inflammation, which  contributes the  progression of post-traumatic destruction of tissues  not  only  in the  pathological focus,  but  also outside  it,  significantly expanding the zone of degenerative changes due to secondary alterations. One of the leading roles in pathogenesis of the inflammation belongs  to secreted  mediators-cytokines – that  impart to the cells the proinflammatory potential and  promote the  long-term inflammation. These  effects  lead  to  disorganization of extracellular matrix and progressive  disintegration of cartilage.  In this regard,  the development and implementation of new pathogenetic treatment methods of post-traumatic synovitis permits  to limit the area of secondary alterations and activate  reparative mechanisms in the lesion  from the early terms,  thus potentially improving the results of  rehabilitation treatment and  increasing efficiency  of  conventional therapy   in  post-traumatic synovitis. Numerous experimental and  clinical  studies  have proven  the  effectiveness and  safety of ozone  therapy, e.g., in degenerative joint  diseases.  Despite extensive  data  highlighting effectiveness of ozone  therapy  in articular pathology, the  study of cytokine profile  when  using this treatment of posttraumatic synovitis  was performed only in few works, thus emphasizing the prospects for further research in this direction. The study was aimed for investigation of cytokine status in the patients with posttraumatic synovitis subjected to intravenous and intraarticular ozone  therapy  in combination with intra-articular administration of xefocam.The  work is based  on  the  results  of examination and  treatment of 69 patients with  traumatic injuries  of the  knee  joint,  complicated by development of  post-traumatic synovitis.  Two  study  groups  were  formed, comparable in volume  and  type  of joint  injury.  The  patients from  group  I (35 cases)  received  conventional combined treatment. Among  the  mandatory measures, evacuation of a synovial-hemorrhagic punctate was performed from the cavity of damaged joint. Conservative therapy included NSAIDs, medications that improve microcirculation, at standard dosages, as well as physical therapy. In group II (34 patients), traditional therapy was supplemented with a 10-day  course of intravenous injectable ozone  therapy  with 200 ml of NaCl  solution at a concentration of 2.0 mg/l daily and intra-articular ozone injection at a concentration of 5 mg/l in a volume of 20 ml 5 times  in a day. During arthroscopy, lavage of the joint  cavity was performed with ozonated saline solution at a concentration of 2.0 mg/l.  The ozone  therapy  was combined with three  intra-articular injections of xefocam  at a dose of 8 mg, once  every 4 days. A patent for the  invention was obtained for this treatment technology (No.  2456988 of 27.07.12).  The cytokine profile was evaluated by the content of Pro-inflammatory (TNFα, IL-1β, IL-6, IL-17), regulatory (IL-2), Il-1β receptor antagonist, and anti-inflammatory (IL-4, IL-10) cytokines by solid-phase enzyme  immunoassay with an indicator label in the  form  of peroxidase. Statistical analysis of the results was carried  out using the Student criterion. Combined therapy  of intravenous and intraarticular ozone therapy  in combination with intra-articular injections of xefocam  contributed to the inhibition of the  inflammatory response, which  is reflected in  the  dynamics of depression of the  studied  cytokines: simultaneous reduction of proinflammatory cytokines with the limitation of the growth of anti-inflammatory mediators. The final measurements showed a decrease in the content of proinflammatory cytokines: TNFα by 24.6% (p2   < 0.001);  IL-17, by 17.3% (p2   < 0.01);  IL-6, by 20.1% (p2   < 0.001);  IL-1β, by 19.1% (p2   < 0.001), with a decrease in regulatory IL-2  by 25.7% (p2   < 0.001) and anti-inflammatory cytokines IL–10, by 21.3% (p2  < 0.001); Il – 4, by 25.7% (p2  < 0.001); IL-1ra, by 24.4% (p2  < 0.001), when compared to the data obtained with conventional treatment. The  results  obtained allow us to evaluate  this method as highly effective  in the treatment of post-traumatic synovitis,  thus contributing to suppression of inflammatory response  and reduces the secondary alteration of joint tissue structures, preventing the progression of post-traumatic osteoarthritis

THE ROLE OF GROWTH FACTORS IN THE FORMATION AND PROGRESSION OF PTERYGIUM

Purpose. To determine a role of epidermal growth factors and vasal proliferative proteins in the pathogenesis of progressive pterygium based on data of immunohistochemical and morphological studies of tissues.Material and methods. The study included a main group of patients with primary pterygium of the progressive stage III-IV (30 eyes, 28 patients), the mean age was 57±7 years. The surgical procedure the pterygium removal was performed according to the Cermak method in all cases for therapeutic purposes and for a further morphological and immunohistochemical study of pterygium tissue. The clinical assessment of postoperative condition was carried out in the early postoperative period and in 6 and 12 months after surgery. The immunohistochemical study was made with the use of monoclonal antibodies and the visualization system (the DAKO company, Denmark): CD 31 (clone JC70A), CD 34 ClassII (clone QBEnd 10), Vascular Endothelial Growth Factor VEGF (clone VG1), Epidermal growth factor EGF (clone DAK-H1-WT). The intensity of coloration of objects was estimated by colorimetric index on a 4-point scale and reflected the quantity of the studied factors. For histological examination the removed pterygium with the tissues of the cornea and conjunctiva was stained with hematoxylin-eosin with a subsequent analysis and a micro-photographing.Results and discussion. The pterygium concerning the structure and function is characterized by an impaired homeostasis of the tissues of the conjunctiva and cornea, expressed in a change of epithelial-stromal relations, disorganization of the fibrous structures of connective tissue, violations in the microcirculatory bed. As a result of the immunohystochemical research, the expression of growth factors was identified in all cases of main group. The expression of epidermal factor was diagnosed in 27 objects with the index (++) and 3 objects with the index of (+). The CD31 expression was revealed: ++++ in 28 objects, in 1 object +++, and in 1 object ++. CD34 expression was revealed: ++++ in 26 objects, in 4 objects ++. The VEGF expression was revealed: ++++ in all 30 objects. In the control group the above-described changes were not revealed, that is the expression of epidermal and vascular growth factors were determined.Conclusion. Thus, the analysis of the peculiarities of growth of the conjunctive epithelium, angioarchitectonique in the tissues of the pterygium and underlying cornea allows assuming that the starting factor of the pathological process is the primary growth of conjunctive epithelium with the accompanying growth of vasculature. The expressive level of epidermal and vasoproliferative growth factors in pterygium can serve as a prognostic sign of pterigium recurrence. The identification of VEGF expression can be a condition on the use of anti-VEGF therapy in the prevention of recurrence

Диагностическое значение определения поверхностных антигенов лимфоцитов у больных атопической бронхиальной астмой (опыт использования моноклональных антител серии ЛТ)

The determination of surfase lymphocyte antigens in patients with atopic bronchial asthma has been carried out using the monoclonal antibodies of the home series LT. The examined patients have been found to have some disorders of the expression antigens under investigation on immunoregulating cells. These disorders are more strongly marked during acute periods of the disease. The decrease of the expression of CD8 antigen is typical of bronchial asthma patients, the amount of CD8+ lymphocytes being 15,6=b0,3 % in the acute period and 17,04hl,8 % during period of remission against 23,84=0,6 % in healthy donors.The results obtained confirm the opinion about insufficiency of supressor T-lymphocytes in the cases of atopic bronchial asthma and enable to recommend the determination of surface lymphocyte antigens as one of the immunological criteria when this disease takes play.

Способ увеличения межремонтного пробега грузовых вагонов за счет модернизации тележки

The authors participated in MIIT University’s researches aimed at refining mathematical and computer models of cars were refined, describing a motion along railway lines with normalized irregularities in plan and profile. The models consider spatial oscillations of each node, details of solid body, structure, material properties, as well as predict abrasive wear of critical parts and components of a bogie. The article justifies a possibility to increase overhaul life of a car by a simple upgrade of a bogie model 18-100 from 160 to 250 thousand km, and by a comprehensive modernization – up to 500 thousand km.С участием авторов в МИИТ уточнены математические и компьютерные модели вагонов, описывающие движение по железнодорожному пути с нормируемыми неровностями в плане и профиле. Особенностью моделей являются учет пространственных колебаний каждого узла и детали как твердого тела, свойств конструкции, материалов, а также прогнозирование абразивного износа ответственных элементов тележки. Обосновывается возможность увеличения межремонтного пробега вагона с простой модернизацией тележек модели 18-100 от 160 до 250 тыс. км, при комплексной модернизации – до 500 тыс. км

Иммунопатогенез формирования атопических заболеваний

The aim of this investigation is the comparative study of changes in the surface phenotype of lymphocyte in patients with different forms of atopic diseases and latent sensitization.Materials and methods. The study was conducted on peripheral blood lymphocytes from 22 latent sensitization patients, 30 pollinosis patients, 44 atopic bronchial asthma patients and 36 atopic dermatitis patients. The control group consisted of 26 healthy people.The results of our studies demonstrate that atopic diseases are different not only in clinical manifestations, but also in mechanisms of disturbances in the functions of the immune system. Comparative study of surface markers of lymphocytes in patients with different forms of atopic diseases revealed a significant increase of surface changes of lymphocyte phenotype according to the severity of the clinical manifestations of the disease. All patients with studied forms of atopy had an increase in content of B-lymphocytes expressing CD72 marker in the peripheral blood and of lymphocytes expressing early activation antigens CD23, CD25, CD71 and adhesion receptor CD54. The developments of pollinosis, atopic bronchial asthma and atopic dermatitis are accompanied by an additional increase levels of lymphocytes expressing the late activation marker HLADR, the CD38+ precursors of plasma cells, and of lymphocytes carrying surface immunoglobulins in peripheral blood. In the blood of patients with atopic disease during exacerbation with evident clinical symptoms revealed a significant increase in all the studied populations and subpopulations of B-lymphocytes. Patients with latent sensitization had increasing blood lymphocytes expressing the CD95 receptor of Fas inducing apoptosis and low content of cells expressing its ligand CD178. Content of CD95+ lymphocytes in peripheral blood at atopic bronchial asthma and atopic dermatitis patients is reduced, and CD178+ lymphocytes increased, reflecting infringement of Fas-dependent apoptosis in severe atopic diseases.Цель работы – сравнительное изучение изменений поверхностного фенотипа лимфоцитов крови у больных с различными формами атопических заболеваний и латентной сенсибилизацией.Материал и методы. Исследование проведено на лимфоцитах периферической крови 22 больных с латентной сенсибилизацией, 30 больных поллинозом, 44 больных атопической бронхиальной астмой и 36 пациентов с атопическим дерматитом. Контрольную группу составили 26 здоровых людей.Результаты проведенных исследований убедительно свидетельствуют, что атопические болезни различаются не только клиническими проявлениями, но и механизмами нарушений функций иммунной системы. Сравнительное изучение поверхностного фенотипа лимфоцитов у больных с различными формами атопии позволило выявить существенное нарастание изменений их субпопуляционного состава по мере усиления тяжести клинических проявлений заболеваний. У больных всеми исследованными формами атопии отмечалось повышение содержания в периферической крови В-лимфоцитов, экспрессирующих маркер CD72, и лимфоцитов, несущих ранние активационные антигены CD23, CD25, CD71 и рецепторы адгезии CD54. Развитие поллиноза, атопической бронхиальной астмы и атопического дерматита сопровождалось дополнительным повышением содержания в периферической крови лимфоцитов, экспресси- рующих поздний маркер активации HLA-DR,предшественников плазматических клеток и лимфоцитов CD38+, несущих поверхностные иммуноглобулины. В крови у больных атопией с выраженными клиническими проявлениями выявлено достоверное повышение содержания всех изученных субпопуляций В-лимфоцитов. У больных с латентной сенсибилизацией зарегистрировано повышенное содержание в крови лимфоцитов, экспрессирующих CD95-рецептор запуска Fas-индуцированного апоптоза, и снижение количества клеток, экспрессирующих его лиганд – рецептор CD178. У больных с атопической бронхиальной астмой и атопическим дерматитом содержание в крови CD95+ лимфоцитов, напротив, снижено, а CD178+-лимфоцитов – повышено, что отражает нарушение Fas-зависимого апоптоза при тяжелых атопических заболеваниях.

Prerequisites for the creation of an atlas of postcovid inflammation as a way of personalized pharmacotherapy, as well as predicting and preventing organ and systemic dysfunctions

SARS-CoV-2 is a novel coronavirus that has been identified as the cause of the 2019 coronavirus infection (COVID-19), which originated at Wuhan city of PRC in late 2019 and widespread worldwide. As the number of patients recovering from COVID-19 continue to grow, it’s very important to understand what health issues they may keep experiencing. COVID-19 is now recognized as an infectious disease that can cause multiple organ diseases of various localization. It is against this background that a new term was introduced: post-acute post-COVID-19 syndrome characterized by several persistent symptoms inherent in the acute phase of the disease, as well as the occurrence of delayed and (or) long-term complications beyond 4 weeks from the onset of the disease. The work reflected in this article revealed a portrait of a patient with post-COVID-19 syndrome, the most common complications of this period, as well as the mechanisms of their development and the resulting metabolic, cellular, tissue disorders leading to the tissue and organ dysfunctions. A comprehensive biochemical and immunological screening was carried out using the example of three clinical cases to identify the most significant disorders in these patients and to correlate with their clinical status over time. In point of fact, such patients were diagnosed with vascular dysfunction factors (development of endothelial dysfunction), metabolic dysfunction factors (metabolic acidosis, mitochondrial dysfunction, carbohydrate metabolism disorder, insulin resistance, altered branched-chain and aromatic amino acid metabolism), neurological disorder factors (neurotoxicity of the resulting metabolites), immunological disorder factors (decreased efficiency of detoxification systems, secondary immunodeficiency, risk of secondary bacterial infection)

Постковидный синдром ассоциирован с повышением внеклеточных пуриновых оснований и нейтрофильных экстраклеточных ловушек в плазме крови

Post-COVID syndrome is characterized by fatigue, reduced exercise tolerance, muscle and joint pain, and psychoemotional disorders. In the development of a generalized body response in a viral infection, abnormal defense responses are of great importance. We studied neutrophils, neutrophil extracellular traps (NETs), DNA degradation products (purine nitrogenous bases, PNBs), and traditional biochemical parameters.Aim. To determine biochemical parameters and the number of NETs and PNBs in the peripheral blood of patients with post-COVID syndrome.Materials and methods. The study included outpatients (n = 21) aged 18–59 years (36 [27 ÷ 50]). The control group consisted of 20 individuals aged 18–59 years (38.5 [29 ÷ 51.5]) without a past medical history of the coronavirus infection. All patients underwent a physical examination, their medical history was assessed, and the level of NETs and PNBs in the venous blood was determined.Results. 11 patients had a mild form of the disease in their past medical history, 7 – moderate, and 3 – severe. The most common symptoms in the patients were fatigue, headache, epigastric pain, dizziness, and joint pain. Hair loss and dyspnea were less common. The concentration of NETs and PNBs was higher in the patients with post-COVID syndrome than in the control group (p < 0.05). We detected NETs in the patients with post-COVID syndrome only in the form of filamentous structures. The concentration of extracellular purine bases in the blood of the patients with post-COVID syndrome was the highest in patients with moderate and severe acute periods. In patients with a mild acute period, the concentration of PNBs was 7.38 [0.0 ÷ 60.7] mg / ml, and in patients with moderate and severe acute periods – 19.15 [0.0 ÷ 33.5] and 34.19 [3.35 ÷ 70.0] mg / ml, respectively.Conclusion. Extracellular purine bases in concentrations capable of causing secondary alteration of cells are found in the peripheral blood of patients with post-COVID syndrome. Post-COVID syndrome is accompanied by the formation of filamentous NETs in the blood of patients. Постковидный синдром характеризуется высокой утомляемостью, снижением толерантности к физической нагрузке, болями в мышцах и суставах, наличием психоэмоциональных проблем. В развитии генерализованной реакции организма при вирусном инфицировании большое значение имеют аномальные реакции защитных систем. Мы исследовали нейтрофилы и формируемые ими экстраклеточные ловушки (НЭЛ) совместно с продуктами деградации волокон ДНК (пуриновые азотистые основания, ПАО), а также традиционные клинико-лабораторные показатели.Цель. Определение ряда лабораторных показателей, а также количества НЭЛ и уровня ПАО в периферической крови больных с постковидным синдромом.Материалы и методы. В исследование включены амбулаторные пациенты (n = 21) в возрасте 18–59 лет (36 [27÷50]). Группу сравнения составили 20 лиц в возрасте 18–59 лет (38,5 [29÷51,5]) без перенесенной коронавирусной инфекции. Всем пациентам проводились сбор жалоб, оценка анамнеза, физикальный осмотр, определение НЭЛ и ПАО в венозной крови.Результаты. Легкое течение заболевания в анамнезе имелось у 11, среднетяжелое – у 7, тяжелое – у 3 пациентов. Наиболее частыми симптомами в нашей группе обследованных пациентов были слабость, головная боль, боль в эпигастрии, головокружение, боль в суставах. Более редкими симптомами являлись выпадение волос и одышка. Концентрация НЭЛ и ПАО была выше в основной группе, чем в группе сравнения (p < 0,05). Мы выявляли НЭЛ у больных с постковидным синдромом только в нитевидной форме. Концентрация внеклеточных пуриновых азотистых оснований в плазме крови больных с постковидным синдромом была наиболее высокой у больных со среднетяжелым и тяжелым течением острого периода. У больных, перенесших острый период заболевания в легкой форме, концентрация ПАО составляет 7,38 [0,0÷60,7] мг/мл, а у больных со среднетяжелой и тяжелой формой острого периода – 19,15 [0,0÷33,5] и 34,19 [3,35÷70,0] мг/мл соответственно.Заключение. В периферической крови больных с посткоронавирусным синдромом обнаруживаются внеклеточные ПАО в концентрации, способной вызвать вторичную альтерацию клеток. Постковидный синдром сопровождался формированием в периферической крови больных НЭЛ в нитевидной форме