Correlation between miR-146a and miR-155 levels and concentration of cytokines in patients with allergopathy in chronic persistence of Epstein-Barr virus infection

Analysis of correlation between miR-146a and miR-155 levels and concentration of antiviral cytokines in patients with allergopathy in active and latent phases of chronic persistence of Epstein-Barr virus infection (EBV) has been conducted. Thus, 38 patients with allergopathy and chronic persistence of EBV of different genders, age 32.73.2 years have been examined, who were divided into groups depending on the phases of virus persistence. Control group included 20 healthy individuals. Reliable changes in IL12, IL33, IL1ß and IFN- were revealed in patients of both groups. The results: reliably higher levels of miR-146a expression, by 2.9 times (р=8.0E-04) and by 2.25 times (р=0.011), respectively, compared with control group; reliable difference in miR-155 levels in patients with EBV-infection in active and latent forms of virus persistence (р=1.0E-07) and significant decrease in the indicated miRNA (р=1.0E-07) by 55.8 times in patients with latent course of EBV-infection compared with control. A reliable reverse correlation of various intensities was detected between IL12, IL1ß, IFN- and miR-146a; absence of correlation between TNF-α, IL33 and miR-146a was observed. A direct correlation was revealed between all investigated cytokines IL12, TNF-α, IL33, IL1ß, IFN- and miR-155. the results of investigation showed that elevation of miR-146a can prognostically indicate inhibition of pro-inflammatory activity of cytokines and anti-inflammatory protection with the formation of pathological disorders, including allergopathy. Meanwhile, the presence of chronic persistence of EBV demonstrates an opposite direction of correlations between miR-155 and cytokines with pro-inflammatory properties, which confirms the ability of opportunistic infections to modulate immune response toward allergopathy

Acute intermittent porphyria case in clinical practice internist

Porphyria is group of eight metabolic disorders characterized by defects in hemebiosynthesis. The presentation of porphyria is highly variable, and the symptoms are non specific, which accounts in part for delay sinestablishing a diagnosis. Inthisstudy, were port the characteristics of one case acute porphyria patients in Ukraine. Case patient is femal, and the age was 20 years. The most frequent presenting symptoms was abdominal pain, dyspnoe, paresis and convulsion. Hyponatremia was the most common electrolyte abnormality. Testing provided a precise diagnosis of the patients:determination of сoproporphyrins in the urine (the survey was conducted three times) three times the figures were slightly increasing, the highest 172 (provision do 120)nmol / day,determination of porphyrins in the blood of 248.5 (rule 60) mcmol / day and intheurine of 422 mcg / L (normal 150mcg / L), and excretion in the urine δ-aminolevolinovoyacid 700 (normal 8-53) mcmol / day. Treatment. Drugs for the treatment of porphyria are not registered in Ukraine, because patients in stable condition was transferred to the Department of porphyria treatment Institute of Hematology and Transfusion (Warsaw, Poland)

Технічна експертиза наукових праць на наявність академічного плагіату: аналіз піврічного досвіду

The article is devoted to the technical aspects and software plagiarism expertise in scientific works of Lviv National Medical University.The purpose of the work. To specify the optimal software for the examination of scientific papers to identify academic plagiarism through the most objective sequence of individual application of some programs for the primary antiplagiarism expertise in the Internet.We reviewed 150 scientific publications, including 30 dissertations. Checking scientific papers and to search for matches performed by the method of the shingle – laying out text. Checking professional articles and dissertation abstracts carried software “Advego Plagiatus 1.3.1.7”. Also provided antiplagiat examination articles, abstracts and texts of dissertations using the software “AntiPlagiarism.net” (“Etxt Antiplagiat, version 3.72.0.0”) with optimized parameter settings for deep search, 5–7 search engines. Analyzed some of the advantages and disadvantages of certain plagiarism programs.У статті проаналізовано технічні аспекти та програмне забезпечення антиплагіатної експертизи наукових праць у Львівському національному медичному університеті імені Данила Галицького.Мета роботи – конкретизувати оптимальне програмне забезпечення для проведення експертизи наукових праць на предмет виявлення академічного плагіату, встановити найбільш об’єктивну послідовність застосування окремих програм для проведення первинної антиплагіатної експертизи у мережі “Інтернет”.Нами перевірено 150 наукових праць, з них 30 дисертацій. Перевірку наукових робіт та пошук збігів ви­конували методом шингл – розбивки тексту. Перевірка фахових статей та авторефератів дисертаційних робіт проводилася ПЗ “Advego Plagiatus 1.3.1.7”. Також здійснювали антиплагіатну експертизу статей, авторефератів та текстів дисертаційних робіт за допомогою ПЗ “AntiPlagiarism.net” (“Etxt Антиплагиат, версія 3.72.0.0”) з оптимізованими налашту­ван­нями параметрів глибокого пошуку по 5–7 пошукових системах. Проаналізовано деякі переваги та недоліки окремих антиплагіатних програм

ОПИС КОРИСНОЇ МОДЕЛІ НА КЛІНІЧНИХ КАФЕДРАХ (ДЛЯ ОТРИМАННЯ ПАТЕНТУ УКРАЇНИ): АВТОРСЬКІ ПОГЛЯДИ)

The wording of the structural description of the circuit to obtain a patent of Ukraine in clinical departments is carried out in compliance with the State Service of Intellectual Property, based of the stylistic analysis of descriptions of 12 patents of Ukraine from the department of Danylo Halytskyi Lviv National Medical University. There was offered a description of the utility model in the clinical departments (for the patent of Ukraine) will help to overcome the objective difficulties of adequate consistent descriptions of clinical observations, methods of diagnosis and treatment of certain diseases in accordance with the declared requirements for patent.Формулювання структурної схеми опису для отримання Патенту України на корисну модель на клінічних кафедрах здійснене згідно з вимогами  Державної служби інтелектуальної власності на основі стилістичного аналізу описів 12 патентів України, отриманих працівниками кафедр Львівського національного медичного університету імені Данила Галицького. Запропонований нами опис корисної моделі на клінічних кафедрах (для отримання Патенту України) сприятиме подоланню об’єктивних труднощів щодо адекватного послідовного описання клінічних спостережень, способів діагностики та лікування окремих захворювань згідно з вимогами, задекларованими для патентування

Pathogenetic Mechanisms of the Occurrence of Rheumatoid Arthritis and Ankylosing Spondylitis with the Activation-Enzymatic and Phenotypic Features of Lymphocytes

Introduction. Significant prevalence of inflammatory diseases of the j oints, the tendency to steady increase in their severity, high indicators due to this temporary disability and disability, especially those of middle-aged, determine the important medical and social importance of these diseases. At the present stage, RA and AU are considered as diseases based on immune disorders. It is known that blood lymphocytes are the key cells of the immune system that play a leading role in providing compensatory and adaptive responses of the organism. The variety of visceral manifestations of inflammatory diseases testifies to the participation of universal mechanisms for the implementation of the systemic pathological process involving polypotent messengers with multifunctional effects. These universal messengers include nitrogen oxide (NO), calcium ions Ca2+, which directly or indirectly regulate various physiological and biochemical processes. Studies of biochemistry and physiology in recent decades have shown that precision control (NO) and (Ca2+) and the functioning of cellular enzymatic systems are provided. Among the latter, the leading role in maintaining NO- and ionic homeostasis of the cell belongs to NO synthase, arginase and ATP-bases. However, despite a significant number of studies devoted to the problem of the enzymatic spectrum of lymphocytes, the study of the functional activity of their arginase-NO-synthase and ATP-systems is extremely limited, and the pathophysiological and immune mechanisms of their dysfunction are unclear. The aim of the study. To find out the pathophysiologic mechanisms of the occurrence of rheumatoid arthritis and ankylosing spondylitis with the participation of arginase-NO-synthase and ATP-gidrolase systems of blood lymphocytes and cellular immunity. Materials and methods. The study involved in randomized manner with the preliminary statification the presence of 86 patients, [48 women (56.0 %) and 38 men (44.0 %); aged 18 to 56 years old], who were treated in Lviv Regional Clinical Hospital during 2012-2015. The study involved individuals with a diagnosis of RA or AS without the presence of concomitant lesions of connective tissue of inflammatory nature, other inflammatory diseases, oncological pathology at the time of the beginning of the study. The comparison (control) group consisted of practically (clinically) healthy persons (n = 30), representative by age and gender (57 % women, 43 % men, average age – 37.9 ± 2.2 years). Mononuclear lymphocytes of human peripheral blood were isolated from heparinized freshly-received blood in a density gradient of the ficol triumbras. The viability of lymphocytes, which in all experiments was not less than 95.0 %, was evaluated by the color of trypan blue. In order to permeabilize the blood lymphocyte membranes and to reveal latent enzymatic activity to the suspension of lymphocytes, 0.1-0.3 % saponin was added. Quantitative determination of the populations and subpopulations of lymphocytes was determined by the method of indirect immunofluorescence reaction with monoclonal antibodies to differentiating antigens of cell surface. Determination of phagocytic activity of neutrophils by absorption capacity was carried out on the basis of the method based on endocytosis with phagocytes of latex particles, which digitized cells in the cytoplasm in the form of round granules of blue color. The activity of NO-synthase was determined by the specific cleavage of NADPH(H+). The activity of blood lymphocytes arrhiza was determined by the formation of urea. Ca2+, Mg2+, and Na+, K+ -ATFase activity of blood lymphocytes were determined spectrophotometrically by recording the process of hydrolysis of ATP on the accumulation of Rh. The protein content of the lymphocyte mixture was determined using the modified O. Lowry method. Results. As a result of the conducted studies, changes in the activity of the arginase-NO-synthase system of the lymphocytes of the blood, the violation of the functional activity of the cells of the phagocytic system, and the change in the ratio of T-lymphocyte subpopulations in patients with inflammatory diseases of the joints have been detected. The growth of iNOS activity in these patients is accompanied by compensatory inhibition of the activity of the endothelial isoform NOS. Significant activation of iNOS activity leads to excessive NO formation in blood lymphocytes. NO in high concentrations triggers oxidative and nitrosisic stress, which leads to a disturbance of the antioxidant-antioxidant balance. As a result, activation of apoptotic mechanisms and initiation of destructive processes in the cells occur, leading to an increase in dysfunction. At the same time, inhibition of the activity of ATPase systems indicates an overload of lymphocyte cytosol by Na+ and Ca2+ ions and a violation of ionic homeostasis, which contributes to the occurrence of cellular disturbances. Conclusions. In patients with rheumatoid arthritis, due to the reduced number of T-cytotoxic lymphocytes, the number of T-helper cells, natural killer cells, and regulatory T-lymphocytes, cells with suppressive activation, activated, which indicates the activation of the cellular link of autoagression with the inclusion of regulatory mechanisms, and in patients for ankylosing spondylitis – activation of natural killer cells, activated T-lymphocytes, lymphocytes with suppressive activation and a decrease in the number of regular lymphocytes, indicating an increase in them. More pronounced changes in helper-cytotoxic (CD4+ and CD8+), activated (CD3+/CDHLA-DR+), suppressive (CD4/CD25+) T-lymphocytes and B-lymphocytes (CD19+), regulatory cells (CD4+/CD25+) were verified in patients with rheumatoid arthritis, as compared to patients with ankylosing spondylitis, indicating that there is a more powerful immune-dependent autoagression in patients with rheumatoid arthritis. Violation of the cellular level of immunity is accompanied by suppression of the activity of endothelial NO-synthase of blood lymphocytes in patients with rheumatoid arthritis by 34.9 ± 7.8 % (p < 0,05), in patients with ankylosing spondylitis – by 43.4 ± 6.2 % (p < 0.001) compared to practically healthy subjects with the simultaneous activation of its inducible isoform. The activity of the blood lymphocyte arrhythmias in rheumatoid arthritis patients increases by 178.3 ± 22.3 % (p < 0.001), with ankylosing spondylitis – by 272.6 ± 30.2 % (p < 0.001), compared with practically healthy subjects. NO synthesis was accompanied by suppression of the activity of Ca2+, Mg2+-ATPases of the plasma membrane of blood lymphocytes in patients with RA by 46.8 ± 5.7 % (p < 0.001), in patients with AS – by 39.4 ± 6.4 % (p < 0.001), activity of Ca2+, Mg2+ -ATPase of membranes of EPR of lymphocytes in patients with both pathologies by 35.6 ± 4.8 % (p < 0.001) and 20.0 ± 3.8 % (p < 0.001) respectively. The activity of Na+, K+-ATPase of blood lymphocytes in patients with both pathologies was 42.8 ± 7.2 % (p < 0.001) and 39.7 ± 6.5 % (p < 0.001), respectively, compared with practically healthy subjects. Changes in the activity of arginase-NO-synthase and ATPase system of lymphocytes in patients with rheumatoid arthritis are more pronounced than with ankylosing spondylitis, but the most sensitive parameter is the activity of iNOS, which indicates the crucial role of disorders in this regulatory system for the formation and increase of inflammatory joint damage

Крипторхізм та варикоцеле: ще один погляд на причини старту аутоагресії

Objective. To determine the role of oxidative stress and inflammation in the pathogenesis of subfertility/infertility and formation of autoimmunity in patients with cryptorchidism and varicocele.Material and metods. Blood levels of MDA and IL-6 were measured in 48 boys with cryptorchidism and 20 healthy subjects. The spermal parameters (motility, morphology), blood levels of MDA and IL-6 were measured in 22 men with varicocele and 21 healthy subjects. The statistical processing was performed with using noparametrical methods and standart computer programs (Statistica Version 6, StatSoft, Inc.; SPSS Statistics 17.0, IBM).Results. We showed that the level of МDA was significantly higher in blood of the cryptorchidism group compared with the control group (p=0.003). The blood serum concentration of IL-6 in the group with bilateral cryptorchidism as compared to the group with unilateral cryptorchidism was higher (p=0.001). We revealed that the levels of MDA, IL-6 and seminal parameters (low motility, sperm abnormalities) was higher in patients with varicocele compared to the control group (p&lt;0.05; p=0.011). In our opinion, MDA is the most reliable and decisive biochemical marker displaying oxidative damage in undescended testes and varicocele, and may be triggered by an autoimmune response.Conclusions. The level of МDA is higher in blood of groups with bilateral and unilateral cryptorchidism, as well as in blood and seminal plasma of patients with varicocele. The higher level of MDA correlates with low motility and higher level of sperm abnormalities in patients with varicocele. The tendency of increased IL-6 level in blood of groups with bilateral and unilateral cryptorchidism, also in blood and seminal plasma of patients with varicocele is a ponderable factor of oxidative stress and a trigger of automunity.Цель: определение роли оксидативного стресса и воспаления в патогенезе суб/инфертильности и формирования аутоиммунитета у пациентов с крипторхизмом и варикоцеле.Maтериалы и методы. Уровни малонового диальдегида (MДA) и интерлейкина 6 (ИЛ-6) определяли в крови 48 мальчиков с крипторхизмом и 20 здоровых лиц. Семинальные параметры (подвижность, морфологию), уровни MДA и ИЛ-6 в крови были определены у 22 парней с варикоцеле и 21 здорового лица. Статистическая обработка данных проводилась непараметрическими методами с использованием стандартных компьютерных программ (Statistica Version 6, StatSoft, Inc.; SPSS Statistics 17.0, IBM).Результаты. Установлено, что уровень МДA был достоверно выше в крови мальчиков с крипторхизмом по сравнению с контрольной группой (p=0,003). Концентрация ИЛ-6 в сыворотке крови пациентов в группе с двусторонним крипторхизмом была выше по сравнению с группой одностороннего крипторхизма (p=0,001). Уровни MДA, ИЛ-6 и семинальные параметры (низкая подвижность, большое количество патологических форм сперматозоидов) были выше у пациентов с варикоцеле по сравнению с контрольной группой (p&lt;0,05; p=0,011).Выводы. Уровень МДA повышен в крови лиц с односторонним и двусторонним крипторхизмом, а также в крови и семенной жидкости пациентов с варикоцеле. Повышенный уровень MДA коррелирует с низкой подвижностью и повышенным количеством патологических форм сперматозоидов у пациентов с варикоцеле. Тенденция к увеличению уровня ИЛ-6 в крови мальчиков с двусторонним и односторонним крипторхизмом, а также в крови и семенной жидкости пациентов с варикоцеле является весомым фактором наличия оксидативного стресса и триггером аутоиммунизации.Мета: визначення ролі оксидаційного стресу та запалення у патогенезі суб/інфертильності та формування аутоімунітету у пацієнтів з крипторхізмом та варикоцеле.Maтеріали і методи. Рівні малонового діальдегіду (MДA) та інтерлейкіну 6 (ІЛ-6) визначали в крові 48 хлопчиків з крипторхізмом та 20-ти здорових осіб. Семінальні параметри (рухливість, морфологію), рівні MДA та ІЛ-6 у крові визначалися у 22 хлопців з варикоцеле та 21 здорової особи. Статистична обробка проведена непараметричними методами з використанням стандартних комп’ютерних програм (Statistica Version 6, StatSoft, Inc.; SPSS Statistics 17.0, IBM).Результати. Виявлено, що рівень МДA був достовірно підвищеним у крові хлопчиків з крипторхізмом порівняно з контрольною групою (p=0,003). Концентрація ІЛ-6 у сироватці крові пацієнтів у групі з двостороннім крипторхізмом була вищою порівняно з групою одностороннього крипторхізму (p=0,001). Рівні MДA, ІЛ-6 та семінальні параметри (низька рухливість, велика кількість патологічних форм сперматозоїдів) були вищими у пацієнтів з варикоцеле порівняно з контрольною групою (p&lt;0,05; p=0,011).Висновки. Рівень МДA підвищений в осіб з одностороннім та двостороннім крипторхізмом, а також у крові та сім’яній рідині пацієнтів з варикоцеле. Підвищений рівень MДA корелює з низькою рухливістю та підвищеною кількістю патологічних форм сперматозоїдів у пацієнтів з варикоцеле. Тенденція до підвищення рівня ІЛ-6 у крові хлопчиків з дво- та одностороннім крипторхізмом, а також у крові та сім’яній рідині пацієнтів з варикоцеле є вагомим фактором наявності оксидаційного стресу та тригером аутоімунізації

Effectiveness of Treatment of Patients with Systemic Autoimmune Diseases on the Background of Reactivation of Persistent Epstein-Barr Virus Infection

The article presents the study of effectiveness of inosine pranobex (IP) in patients with systemic autoimmune diseases (SAD) on the background of reactivation of persistent Epstein-Barr (EBV) infection. Among 380 patients with SAD (systemic lupus erythematosus, systemic vasculitides, rheumatoid arthritis, psoriasis), in 144 patients (37.9%) the reactivation of persistent EBV infection was detected through virus DNA identification using polymerase chain reaction (PCR) in three biological matrices (blood, saliva, scraping from the lesion site). 48 patients were receiving inosine pranobex at a dose of 50 mg/kg per day for three months. Treatment efficacy was controlled by studying the levels of expression of miR-146а, miR-155, miR EBV (BART-13 and BART-15), TLR9, the quantity of lymphocytes populations and subpopulations. After treatment, PCR results showed a decrease in viral replication in 66.7% of cases. The use of IP contributed to a significant decrease in the level of IgM, IgG specific antibodies, an increase in the level of expression of anti-inflammatory miR-146a, a decrease in the level of expression of pro-inflammatory miR-155 which may signify the strengthening of antiviral control. The study data demonstrated the decrease in the expression of miR EBV (BART-13 and BART-15) and TLR9 on the immunocompetent cells that can also be attributed to the criteria for IP effectiveness. The effectiveness of IP was also proved by the stabilization of cell mechanisms, namely the tendency to normalizing T and B cell populations, decrease in the number of natural killer cells and activated cells (CD25+, CD3+ HLA DR+). On the other hand, the number of lymphocytes with suppressor activity (CD4+25+) remained significantly high mitigating autoimmune aggression. The results of the study show that the use of IP for treating the acute phase of EBV infection contributed to the decrease of repliсative activity of the virus; suppressing the aggressiveness of autoimmune reactions. The decrease in the expression of miR EBV (BART-13 and BART-15) can be recommended as a criterion for the IP effectiveness; the decrease in the expression of TLR9 on immunocompetent cells –as a criterion for suppressing autoimmune reactions

Role of reactive oxygen and nitrogen species in formation of acute and chronic experimental arthritis

Free radical oxidation processes is an important link of rheumatoid arthritis pathogenesis. Reactive oxygen species and reactive nitrogen species are formed during cellular oxidative phosphorylation. They perform an important role in the transmission of cellular signals, destroy of foreign agents, regulation of cell proliferation. The hyperproduction of the reactive oxygen species can lead to a damage of proteins, lipids, nucleic acids and cell matrix components, including the synovial membrane and extra-articular tissues. Objective: to determine the reactive oxygen and nitrogen species roles in rats’s blood serum at experimental carrageenan- and collagen-induced inflammatory arthritis. Method: spectrophotometry with using biochemical analysis. Results: Rate of the reactive oxygen species (NO2–, •OH, H2O2) generation in the group of animals with collagen arthritis was higher than in the group of animals with carrageenan inflammation. In the same experimental group the nitrosative stress products and activities (cNOS, iNOS, NO2–, NO3–, ARG) were higher too. Conclusion: Products of the oxidative and nitrosative stresses contribute actively to development of pathological changes in tissues of animals with collagen arthritis which is an analogue of rheumatoid arthritis in humans, compared to the carrageenan-induced model of the immunoinflammatory process

Дослідження регуляторних імунних механізмів та можливостей їх корекції у дітей, що часто хворіють

Objective. To evaluate the effect of Fluvir symbiotic on the regulatory parameters of the immune system in frequently ill children of primary school age in the period of unstable remission of respiratory diseases.Patients and methods. A total of 40 children of primary school age (6-11 years) were under observation. According to the basis of medical history, the results of clinical, instrumental and laboratory examinations they were related to the dispensary group of frequently ill children with the frequency more than eight times a year. All patients had received «Fluvir» (kid) by course of one month. The studies were conducted before and after treatment by Fluvir.Results. Due to the application of Fluvir was improved the general condition and regression of clinical manifestations in 70% of patients; increasing of mucosal, anti-infective and also antiviral immunity, the regulatory ability of the adaptive immune response; antigen-presenting processes, reduction of the inflammatory process and autoimmune alertness of protective systems.Conclusions. On the base of obtaining data the effectiveness of Fluvir symbiotic can be evaluated as moderate, with the positive dynamics of the studied parameters of the immune system, at an average of 58.6% of patients. These disorders of the immune system in frequently ill children can be a predictor of the development of autoimmune diseases. Therefore, it is recommended to use Fluvir within two-three months under the supervision of immunological parameters.Key words: frequently ill children, immunological regulatory mechanisms, mucosal immunity, Fluvir symbiotic.Цель: оценить влияние синбиотика Флувира на регуляторные показатели иммунной системы у часто болеющих детей младшего школьного возраста в период нестойкой ремиссии респираторных заболеваний.Пацииенты и методы. Под наблюдением находились 40 детей младшего школьного возраста (6–11 лет), которые на основании данных анамнеза, результатов клинического, инструментального, лабораторного обследования были отнесены к диспансерной группе часто болеющих с частотой респираторных заболеваний свыше восьми раз в год. Все больные получали препарат «Флувир» (детский) курсом один месяц. Исследования проводились до начала и после окончания лечения Флувиром.Результаты. На фоне применения Флувира произошло улучшение общего состояния и регрессия клинических проявлений у 70% пациентов; усиление мукозального, противоинфекционного, в том числе противовирусного, иммунитета, регуляторной способности адаптивного иммунного ответа; стабилизация антигенпрезентирующих процессов, уменьшение активности воспалительного процесса и аутоиммунной настороженности защитных систем организма.Выводы. На основании полученных данных можно оценить эффективность симбиотика Флувира как умеренную, с положительной динамикой изученных показателей иммунной системы в среднем у 58,6% пациентов. Выявленные нарушения в иммунной системе часто болеющих детей могут стать предиктором развития аутоиммунных болезней. Поэтому рекомендовано использовать Флувир в течение двух-трех месяцев под контролем иммунологических показателей.Ключевые слова: часто болеющие дети, регуляторные иммунологические механизмы, мукозальный иммунитет, симбиотик Флувир.Мета: оцінити вплив синбіотика Флувіру на регуляторні показники імунної системи дітей молодшого шкільного віку, що часто хворіють, у період нестійкої ремісії респіраторних захворювань.Пацієнти і методи. Під спостереженням знаходилися 40 дітей молодшого шкільного віку (6–11 років), які на підставі даних анамнезу, результатів клінічного, інструментального, лабораторного обстеження були віднесені до диспансерної групи дітей, що часто хворіють, з частотою респіраторних захворювань понад вісім разів на рік. Усі хворі отримували синбіотик «Флувір» (дитячий) курсом один місяць. Дослідження проводилися до початку та після закінчення вживання Флувіру.Результати. На тлі застосування Флувіру відбулося покращання загального стану та регресії клінічних проявів у 70% пацієнтів; посилення мукозального, протиінфекційного, у тому числі противірусного, імунітету та регуляторної здатності адаптивної імунної відповіді; стабілізація антигенпрезентуючих процесів, зменшення активності запального процесу та аутоімунної настороженості захисних систем організму.Висновки. На основі отриманих даних можна оцінити ефективність синбіотика Флувіру як помірну, з позитивною динамікою вивчених показників імунної системи в середньому у 58,6% пацієнтів. Виявлені порушення в імунній системі дітей, що часто хворіють, можуть стати предиктором розвитку аутоімунних хвороб. Тому рекомендовано використовувати Флувір протягом двох-трьох місяців під контролем імунологічних показників.Ключові слова: діти, що часто хворіють, регуляторні імунологічні механізми, мукозальний імунітет, симбіотик Флувір

Аdvanced Glycation End-products as Novel Biomarkers of Eosinophil-derived Lung Inflammatory Diseases (Literature Review)

Advanced glycation end-products (AGEs) are created during the process of glycation of cells from various tissues and fluids and are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with the amino group of proteins, lipids, and nucleic acid. In normal conditions, they play the immunoregulatory role. In pathologic conditions AGEs activate the receptors for advanced glycation end products (RAGE) and cause long-lasting inflammation. RAGE participates actively in various disorders such as rheumatoid arthritis, diabetes, etc. However, there is relatively small number of scientific studies on the possibility of using the role of AGE in the pathogenesis of allergic diseases. RAGE transcript and protein are expressed in the lung by pulmonary type I alveolar epithelial cells, suggesting that RAGE has an important role in lung pathophysiology. They repress some endogenous autoregulatory functions leading to many diseases, including allergy. Oxidative stress increases the inflammatory reaction in asthma and allergies. Long-lasting inflammation followed by free radicals production are important factors involved in allergic reactions, they negatively influence the incidence and prognosis of allergy. RAGEs are expressed on circulating immune cells, they activate NF kappaB and intracellular oxidative stress also increases the inflammatory reaction in asthma and allergies. The membrane RAGE (mRAGE) signaling is proinflammatory, whereas soluble RAGE (sRAGE), a secreted form of RAGE, is generally anti-inflammatory. The study of AGEs, soluble RAGE, ligands of RAGE HMGB1, and S100A8/A913 and IL-33 is useful in the context of their considering as biomarkers to the differentiation diagnostic between eosinophils-derived and neutrophil-derived asthma/AAD. The mean serum levels of RAGE may be the target of new therapeutic interventions