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Резюме. Бронхіальна астма (БА), асоційована із ожирінням, представляє окремий фенотип, для якого характерний важчий перебіг захворювання та нижча відповідь на базисну терапію. БА та ожиріння визнані як класичні мультифакторіальні захворювання, що виникають в осіб із певним генотипом під дією провокуючих факторів зовнішнього середовища. Дослідження генів-кандидатів БА та ожиріння сприятиме поглибленню наших знань і розумінь загальної генетичної основи даних захворювань. Мета. Огляд літератури, що містить результати досліджень Arg16Gly і Gln27Glu поліморфізмів гена β 2 -адренорецептора (β 2 -АР), які розглядаються, як спільні кандидати щодо виникнення БА та ожиріння, що дозволить зрозуміти та обгрунтувати напрямок подальших досліджень. Матеріали та методи дослідження. Проаналізовано публікації, що містять результати досліджень щодо ролі Arg16Gly і Gln27Glu поліморфізмів гена β 2 -АР у виникненні БА та ожиріння. Результати дослідження. Дані аналізу літератури за досліджуваною проблемою носять суперечливий, а іноді й дискордантний характер. Представлено, що сила взаємодії між Arg16Gly і Gln27Glu поліморфізмами та наявністю БА і ожиріння не завжди достатня, щоб пояснити цей зв'язок. Це підкреслює наявність невирішених запитань, які потребують подальших досліджень. Висновок. Проведений аналіз пошуку спільних генетичних маркерів на прикладі Arg16Gly і Gln27Glu поліморфізмів гена β 2 -АР у хворих на БА і ожиріння вказує на необхідність подальшого вивчення цієї проблеми для удосконалення діагностичних, лікувальних та профілактичних заходів. Ключові слова: бронхіальна астма, ожиріння, Arg16Gly і Gln27Glu поліморфізми гена β 2 -адрено рецептора.

The goal of our research was to analyze the role of transforming growth factor-β1 (TGF-β1 ) in airway remodeling, inflammation, clinical course, treatment efficacy in patients with bronchial asthma (BA) according to the literature data, as well as determination of this biomarkers level in the blood of BA patients. Material and research methods. The publications is containing the results of studies on the role of TGF-β1 in the course of BA have been analyzed. The level of TGF-β1 in the blood was determined within enzyme-linked immunosorbent assay using kits “IBL International GMBH, Germany” in 553 BA patients and in 95 healthy individuals. Results. The article presents data about TGF-β1 influence on the processes of airway remodeling in BA patients, its role in microcirculation disorders, mucus production, eosinophilic inflammation and severity of clinical symptoms of the disease. The level of TGF-β1 expression was associated with disease control, severity and duration of the disease, despite conflicting data that require further study. In addition, there were presented recent research data about TGF-β1 as a marker of airway remodeling and as a therapeutic target in the treatment of BA patients. Glucocorticoids, tiotropium bromide, methylxanthines, selective inhibitors of TGF-β1 , resveratrol, simvastatin and montelukast and their mechanisms of influence were presented in detail. Significantly higher level of TGF-β1 in the blood of patients with BA was found (38.5 ± 0.7) pg/ml compared with healthy individuals (33.9 ± 1.0) pg /ml, p = 0.007. Conclusion. A significantly higher level of TGF-β1 was revealed in the blood of BA patients. In our opinion, a differentiated analysis of the content of this marker depending on the phenotype of the disease is important, which would explain the conflicting results of different studies, deepen understanding of its pathophysiological and clinical role in order to develop methods for slowing airway remodeling. Key words: bronchial asthma, transforming growth factor-β1 (TGF-β1), airway remodeling.

Background:During last years we are seeking for new biomarkers of early or even preclinical diseases stages, precise definition of disease activity and accurate prediction of the disease course as well as biomarkers of treatment efficiency. Nailfold capillaroscopy (NFC) considering as a method for early or even preclinical diagnostic tool for systemic scleroderma, at the same time there is enough data that dermatomyositis (DM) characterized with similar NFC changes along with other idiopathic inflammatory myopathies (IIM) due to the peripheral vascular involvement.Objectives:The goal of our research was aimed to analyze possible association between capillaroscopic alterations and angiogenic, tissue remodeling factors in patients with DM.Methods:44 patients with DM were examined and included in the study. NFC we performed usingDino-Lite CapillaryScope with 200 magnification.We assessed nailfold capillary density (NCD), presence of microhemorrhages, giant, dilated and ramified capillaries, scleroderma patterns (defined as an early, active or late pattern) and neovascular pattern (defined as an active and late scleroderma patterns). We use Manual Muscle Testing 8 (MMT8), Health Assessment Questionnaire (HAQ), Myositis Disease Activity Assessment Tool (MDAAT), Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), physician’s VAS, patient’s VAS, serum muscle enzymes levels to asses disease activity. The level of transforming growth factor alpha (TGF-α) and vascular endothelial growth factor (VEGF) were assayed by the enzyme immunoassay system in the blood serum. We divided patients into 4 groups: 1stgroup – 17 DM patients with early NFC scleroderma pattern, 2ndgroup included 11 DM patients with active NFC scleroderma pattern, 3rdgroup – 6 DM patients with late NFC scleroderma pattern and 4thgroup included 10 DM patients with no any significant NFC alterations.Results:We didn’t find any significant difference of the VEGF level between examined groups, though the level of VEGF in the 1stgroup was – 473,65±48,24 pg/ml, 2nd– 412,89±106,24 pg/ml, 3rd– 283,0±71,93 pg/ml, 4th– 305,9±45,89 pg/ml (p=0,12, F=2,06), however at the same time we compare the level of VEGF between patients with long disease duration and newly onset disease and VEGF was higher among newly onset active DM patients – 465,32±54,54pg/ml VS 324,96±41,16 pg/ml (p=0,042, F=4,365). The level of TGF-α in the 1stgroup was 100,82±8,98 ng/ml, 2nd– 65,78±9,21 ng/ml, 3rd– 56,9±5,01 ng/ml, 4th– 65,5±10,2 ng/ml, though it was significantly higher in the 1stgroup patients (p=0,002, F=5,88).Conclusion:According to our results we can assume that VEGF and TGF-α could be applied as biomarkers of disease activity and duration, however more data is required.Disclosure of Interests:None declared

Background:Nailfold capillaroscopy (NFC) is a useful, noninvasive, widely available diagnostic tool in rheumatology practice. We commonly use it to describe patterns of abnormalities in systemic sclerosis however we have enough data which proves NFC usefulness for monitoring idiopathic inflammatory myopathies (IIM) considering it as diagnostic tool, monitoring of disease activity and treatment efficiency. Despite evident clinical relevance of NFC in IIM patients we still do not have clear capillaroscopic images for IIM definition.Objectives:That’s why, the goal of our research was aimed to analyze capillaroscopic peculiarities among IIM patients and find possible associations with clinical and activity data.Methods:69 patients with IIM were examined and 47 IIM patients with capillaroscopic alterations were included in the study, 26 patients with dermatomyositis (DM) and 21 patients with polymyositis (PM) according to the Targoff Criteria (1997). NFC we performed usingDino-Lite CapillaryScope with 200 magnification. We assessed nailfold capillary density (NCD), presence of microhemorrhages, giant, dilated and ramified capillaries, scleroderma patterns (defined as an early, active or late pattern) and neovascular pattern (defined as an active and late scleroderma patterns). To asses disease activity we use Manual Muscle Testing 8 (MMT8), Health Assessment Questionnaire (HAQ), Myositis Disease Activity Assessment Tool (MDAAT), Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), physician’s VAS, patient’s VAS, serum muscle enzymes levels. We divided patients into 4 groups: 1stgroup – 17 DM patients with active disease (8 of them with newly onset disease), 2ndgroup included 9 DM patients with inactive disease, 3rdgroup – 11 PM patients with active disease (5 of them with newly onset disease) and 4thgroup included 10 PM patients with inactive disease.Results:The most common finding was low NCD, 70% of all patients had NCD lower than 6 per 1 mm. NCD for the 1stgroup was 4,4±1,12, 2ndgroup – 6,0±1,0, 3rdgroup – 5,8±1,1, 4thgroup – 9,2±2,1 (F=26,27, p<0,001). Hemorrhages were significantly more common among DM patients and active disease and were observed among 47,1% (p=0,036,χ2=8,574) with no significant difference with regard to the disease onset. Analyzing scleroderma patterns, among 1stgroup of patients – 17,6% had early, 47,1% – active, 35,3% – late pattern, in the 2ndgroup – 66,7% had early pattern, in the 3rdgroup – 27,3% patients with early and 18,2% with active pattern and in the 4thgroup – 50% of patients presented with early pattern (p=0,001,χ2=31,87). Neovascular pattern was found significantly more often among patients with active DM (p=0,001) with no regard to the disease onset. No statistically significant difference in giant and ramified capillaries distribution was found.Conclusion:According to our results, we can admit that the most common capillaroscopic finding was decreased NCD, which were significantly lower among patients with active DM, the same as microhemorrhages and neovascular scleroderma pattern. This data suggests that NCD, microhemorrhages and neovascular scleroderma pattern could be consider as biomarkers of DM activity but not PM, therefore more detailed research with larger numbers of patients are required.Disclosure of Interests:None declared

The aim: The objective of our study was to evaluate the features of ultramorphometric characteristics of exocrine parenchyma and microvasculature of the pancreas in the presence of moderate dehydration by means of an experiment in laboratory rats. Materials and methods: The experiment involved 20 mature white male rats divided into 2 groups: control and experimental (10 rats each). In the experimental group, moderate dehydration was simulated, i.e. the animals were deprived of water for 7 days, while the control rats were provided with a normal water supply during the study. Pancreatic parenchyma samples were fixed in phosphate-buffered glutaraldehyde solution and post-fixed in osmium tetroxide solution, dehydrated and embedded in a mixture of epoxy resins. Ultrastructural analysis was performed using JEOL JEM-1230 transmission electron microscope (Japan). Results: Pancreatic electron microscopy in the presence of moderate dehydration demonstrated statistically significant changes in exocrinocytes area and exocrinocyte nucleus area which increased by 8.02% (p = 0.028) and 40.28% (p &#60; 0.001), respectively. Among the vessels of microcirculation, the largest changes occurred in the capillaries: their lumen narrowed by 22.34% (p = 0.002) as compared with the control group. The cytoplasm of endothelial cells contained a large number of vacuoles and micropinocytotic vesicles. Conclusions: Among the organelles of exocrinocytes, mitochondria appeared the most vulnerable to the effects of dehydration. They demonstrated polymorphic changes: a part of the mitochondria was hypotrophic and had partially reduced cristae, and another part was hypertrophic.

The aim: The objective of the study was to analyze the frequency of Arg16Gly polymorphism in the β2 -adrenoceptor (β2 -АR) gene in patients with bronchial asthma (BA) and to assess the association of the polymorphism with BA risk. Materials and methods: We examined 553 BA patients and 95 apparently healthy individuals. Arg16Gly polymorphism in the β2 -АR gene (rs1042713) was determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Statistical analysis of obtained results was performed using SPSS–17 program. Results: It was established that distribution of Arg/Arg, Arg/Gly, and Gly/Gly genotypes for Arg16Gly polymorphism in the β2 -АR gene was 44.2%, 40.0%, 15.8% in the control group vs. 31.3%; 45.7% and 23.0 among BA patients, respectively (χ2 = 6.59; р = 0.037). No significant difference was observed with regards to the distribution of genotypes for Arg16Gly polymorphism in the β2 -АR gene in men and women controls (χ2 = 4.05; р = 0.13) and BA patients (χ2 = 4.34; р = 0.11). BA risk was 1.74 times higher in the minor allele carriers (Arg/Gly + Gly/Gly genotypes) for Arg16Gly polymorphism in the β2 -АR gene. Conclusions: Analysis of Arg16Gly polymorphic variants in the β2-AR gene showed a statistically significant difference in the distribution of Arg/Arg, Arg/Gly, and Gly/Gly genotypes in patients with BA and apparently healthy individuals due to the higher frequency of Arg/Arg genotype in controls and higher frequency of Gly/Gly genotype in patients with asthma. No difference with regard to gender was found in the distribution of genotypes.