Прогностичне значення маркерів ендотеліальної дисфункції в діагностиці ступеня атеросклеротичного ураження коронарних судин у хворих із гострим інфарктом міокарда з коронарним стентуванням

Мета. Оцінити рівні інгібітора активатора плазміногену 1 типу (ІАП-1) та асиметричного діметіларгініну (АДМА) у хворих із гострим інфарктом міокарда (ГІМ) в залежності від наявності або відсутності цукрового діабету 2-го типу (ЦД2) та характеру ураження коронарних артерій (KА), а також їх прогностичне значення щодо ступеня атеросклеротичного ураження коронарних судин. Матеріали і методи. Обстежено 130 хворих, 44 (33,85%) жінки та 86 (66,15%) чоловіків. Усіх пацієнтів розподілено на дві групи: основну - 73 хворих із ГІМ і супутнім ЦД2, серед них 43 чоловіки і 30 жінок, середній вік яких становив (62,73 ± 1,39) року, та порівняльну - 57 хворих із ГІМ без ЦД2, серед них 43 чоловіки і 14 жінок, середній вік яких становив (63,98 ± 1,47) року. Контрольну групу склали 20 практично здорових осіб (10 чоловіків і 10 жінок, середній вік яких становив (60,85 ± 1,37) року). Усім хворим проводили коронарографію вінцевих судин серця у стандартних проекціях за допомогою ангіографа Siemens Axiom Artis. Вміст АДМА встановлювали імуноферментним методом, використовуючи комерційну систему тестування «Immunodiagnostik» компанії ADMA Xpress ELISA Kit (Австрія), ІАП-1 - також імуноферментним методом, використовуючи комерційну тест-систему виробництва фірми Technoclone PAI-1 ELISA Kit (Австрія). Результати. У хворих із ГІМ незалежно від того, мали вони ЦД2 чи не мали, рівні ІАП-1 та АДМА підвищені у порівнянні з контрольною групою (р < 0,05). У хворих з гемодинамічно значущим стенозом (ГЗC) KА (70% і більше) визначено підвищення рівнів ІАП-1 та АДМА як за наявності, так і за відсутності ЦД2 (р < 0,05).У хворих із ГІМ та дифузним ураженням (ДУ) KА як із супутнім ЦД2, так і без нього рівні ІАП-1 та АДМА були достовірно вище, ніж у хворих без ДУ KА (р < 0,05). Висновки. Порівняння площ під ROC-кривими показало, що більшу діагностичну цінність для прогнозування ДУ KА у хворих із ГІМ та супутнім ЦД2 має ІАП-1, ніж АДМА. Рівні ІАП-1 та АДМА доцільно визначати для прогнозування ГЗC KА та діагностики ДУ коронарного русла з тим, щоб проводити профілактику розвитку ускладнень ГІМ

Complex application of certain micronatrients in men with androgen deficiency and pathosprimes

A complex approach was made for the deactivation of deuterine micronutrients, which include antioxidant and metabolic metabolism, in individuals with androgen deficiency and idiopathic pathospermia. It has been shown that is using the complex preparation «FEROLL» for 60 days leads to increase the parameters of the spermogram to normal values on the background of normal androgen levels of blood in these patients

Humoral immunity indicators as prediction factors for dysbiosis development risk

Diseases associated with bacterial vaginosis lead to chronic inflammatory processes of the internal genitals, the development of adhesions of the pelvic organs, infertility, spontaneous abortion at different times, as well as the development of malignant neoplasms. Vaginal microflora is an indicator of a woman's health which can form changing in hormonal and immunological status during various pathological conditions. The aim of the study was to create a system for prediction of the dysbiosis development according to the levels of nonspecific humoral factor of immune defence. The study was performed in 298 women aged 16 to 64 years, 53 of whom were diagnosed with normocenosis, and 245 have dysbiosis. Women were divided into 3 groups according to age. Regression analysis was used. Our previous researches have shown a correlation between increased levels of anti-inflammatory cytokines in the blood and vaginal secretions with the stage of dysbiosis. A logistic regression model was constructed during the study, which showed that the risk of developing dysbiosis in terms of normobiota increases with increasing levels of interleukin 2 in the blood, tumor necrosis factor α. Significant features of the three-factor model for predicting the risk of developing dysbiosis (IL2, IL4 and TNFα) were selected by the method of genetic algorithm. The levels of these indicators in the blood were related to the severity of dysbiosis according to the results of discriminant analysis. Thus, a linear neural network model was developed for determination of dysbiosis severity according to the levels of nonspecific humoral factors of immune defence such as the C4 component of the complement system and γ-interferon in vaginal secretions, as well as the amount of circulating immune complexes and tumor necrosis factor α in the blood. Kappa Cohen's agreement for this model on the training set was 0.87 (95% CI 0.82-0.91), and on the confirmatory set was 0.89 (95% CI 0.77-1.00). These indicators show the adequacy of the constructed model. The interface of the expert system for the dysbiosis severity prediction has been created

Changes in the system of asymmetric dimethylarginine - endothelial NO-synthase in patients with acute myocardial infarction and type 2 diabetes mellitus

The purpose of this study was the assessment of asymmetric dimethylarginine (ADMA) and its links with carbohydrate and lipid metabolism parameters in patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus following determination of asymmetric dimethylarginine and NO synthase plasma levels. Materials and methods. The study included examination of 73 patients with acute myocardial infarction and type 2 diabetes mellitus, 57 patients with AMI without type 2 diabetes and 20 conditionally healthy individuals. The content of ADMA and NO synthase was measured by using an enzyme-linked immunosorbent assay kit (ADMA Xpress ELISA kit;Immundiagnostik,Austria) and Bender MedSystem (Austria), respectively. The parameters of carbohydrate and lipid metabolism were determined by a standard biochemical method. Results. A significant 2.64 times increased level of ADMA (1.24 ± 0.04 μmol/L) was found in the patients with AMI and type 2 diabetes compared to the practically healthy persons (control group) (0.47 ± 0.05 μmol/L), and 2.53 times increased (P < 0.05) in comparison with the patients without type 2 diabetes. In the presence of type 2 diabetes the 40.1 % (P < 0.05) decrease in NOs level was noted compared to the control group (3.12 ± 0.11ng / ml and 5.21 ± 0.19 ng/ml, respectively) and the 26.1 % (P < 0.05) decrease compared to the patients with AMI without type 2 diabetes. The study provided a possibility to determine a direct correlation between ADMA and total cholesterol (r = 0.47; P < 0.05); LDL cholesterol (r = 0.28; P < 0.05), HDL cholesterol (r = -0.39; P < 0.05), triglycerides (P = 0.35; P < 0.05), glucose (P = 0.46; P < 0.05), insulin = 0.49; P < 0.05), glycosylated hemoglobin (r = 0.39; P < 0.05). Correlation analysis showed an inverse correlation between ADMA and NO synthase levels (r = -0.67; P < 0.05). Conclusions. The association between asymmetric dimethylarginine high levels and pathological changes in the parameters of carbohydrate, lipid metabolism and endothelial dysfunction has been established, which increases ischemia in the vessel wall and adversely affects the course and prognosis of acute myocardial infarction in patients with type 2 diabetes mellitus

Ways of enhancement of the surgical treatment efficacy in treatment of patients, suffering pulmonary tumors

Objective. Efficacy of endoscopic bronchosanation for prophylaxis of preoperative and postoperative complications in patients with pulmonary tumors. Маterials and methods. There was studied the efficacy of endoscopic photodynamic therapy in accordance to procedure, elaborated by the authors, including injection of the water solution of a methylene blue dye in concentration 0.04% into tracheobronchial tree, irradiated by laser with the wave length 0.63 mcm, independently and in conjunction with a standard anti-inflammatory therapy as preoperative preparation of tracheobronchial tree in patients, suffering pulmonary cancer. In the investigation 181 patients were included, suffering pulmonary cancer Stages II-III, morphologically confirmed, and with coexistent endobronchitis. Results. In accordance to analysis of the pathogenic microflora titer and character in lumen of bronchial tree after preoperative preparation there was established, that while application of independent endoscopic bronchosanation in 55 (87%) observations the pathogenic microflora was absent. While combination of photodynamical bronchosanation in accordance to standard therapy a pathogenic microflora was not revealed in 52 patients. While conduction of a standard preparation without application of a laser therapy microflora was not revealed only in 44.8% observations. Together with the bronchial mucosa metaplasia in some investigated patients the dysplastic changes of bronchial epithelium of various severity degree were registered. Independent endoscopic bronchosanation have leaded to trustworthy lowering of a general rate of the bronchial epithelial dysplasia in the patients tо 36.1%, together with standard anti-inflammatory therapy - tо 42.4%. Conclusion. Application of endoscopic photodynamic bronchosanation in accordance to the proposed procedure in preoperative period in the patients with objective to correct a concomitant endobronchitis, as independent option or together with standard anti-inflammatory therapy, leads to reduction  of the endobronchial complications rate after operative treatment for pulmonary cancer, comparing with a control group. Еndoscopic bronchosanation is accompanied by significant lowering of severity of endoscopic signs of coexistent endobronchitits and improvement of mucociliary transport. In accordance to microbiological tests in 87 - 88% of patients a complete sanation of bronchial tree and elimination of main histological criteria of inflammation were noted, while in 67.2 - 100% patients – restoration of normal structure of the bronchial tree mucosa

Prognostic markers in patients with thymus-independent and thymus-dependent myasthenia gravis

МИАСТЕНИЯ ГРЭВИС /ТЕРМИАСТЕНИЯ ТЯЖЕЛАЯ ПСЕВДОПАРАЛИТИЧЕСКАЯ /ТЕРЭРБА-ГОЛЬДФЛАМА БОЛЕЗНЬ /ТЕРТИМУСА ГИПЕРПЛАЗИЯТИМОМАТИМУСНАЯ КАРЦИНОМААНТИЯДЕРНЫЕ АНТИТЕЛАКЛАСТЕРНЫЙ АНАЛИЗБИОЛОГИЧЕСКИЕ МАРКЕРЫЦель. Оценить наличие специфических маркеров у пациентов с тимуснезависимой и тимусзависимой миастенией для выбора тактики лечения. Материал и методы. Обследовано 138 пациентов с тимуснезависимой (М – миастения без морфо-функциональных изменений тимуса) и тимусзависимой (МГ – миастения на фоне гиперплазии тимуса, МТ – миастения на фоне тимомы) миастенией. Использовали методы иммуноферментного анализа (содержание антител к a1 и a7 субъединицам нАХР в сыворотке, к a7 субъединице нАХР в митохондриях тимоцитов, уровень антиядерных антител ANA), иммунофлуоресценции (тип свечения ANA), проточной цитометрии (экспрессия CD14+CD11c+ и CD14+HLA-DR+). Результаты. Выявлена взаимосвязь клинических фенотипов миастении с вариантами диплотипов лейкоцитарных антигенов HLA: у молодых пациентов с тимуснезависимой миастенией (М) выявили высокую гетерогенность генотипических маркеров HLA-DR (DR1, DR2, DR3, DR5, DR7). Пациенты с тимусзависимой миастенией (МТ) имели только дипло- и гаплотипы HLA DR2 и HLA DR7. Наличие гаплотипов HLA DR2 и HLA DR7 у части молодых пациентов с М при прогрессировании заболевания приводило к развитию миастении на фоне тимомы (МТ) в старшем возрасте. Патогенетическая роль также принадлежит инфекции (СMV, EBV, HBV, HCV, HSV-1, HSV-2, HHV-6, микоплазма) и пищевой непереносимости (IgE и IgG4) в развитии и прогрессировании миастении. В качестве дополнительной мишени аутоагрессии при миастении выявили четырехкратное преобладание a7 субъединицы никотиновых ацетилхолиновых рецепторов в митохондриях клеток тимомы. Специфические антинуклеарные антитела к центромерам хромосом были визуализированы у пациентов старшей группы с миастенией на фоне тимомы. Заключение. Прогноз прогрессирования миастении и развития ремиссии может быть осуществлен с помощью геномных (наличие определенных гаплотипов HLA-DR) и молекулярных (антитела ANA к центромерным белкам хромосом, экспрессия СD20+, CD14+CD11c+, CD14+HLA-DR+) биомаркеров, которые могут быть применены для выбора тактики лечения.Objective. To assess the presence of specific markers in patients with thymus-independent and thymus-dependent myasthenia gravis for choosing treatment tactics. Methods. The presence of specific markers was assessed in 138 patients with thymus-independent (M – myasthenia gravis without thymus changes) and thymus-dependent (MH – myasthenia gravis with thymus hyperplasia, MT – myasthenia gravis with thymoma). The method ELISA (the content of antibodies to subunits 1 and 7 nAChR in blood serum, to 7 nAChR subunit in thymocyte mitochondria, a detectable level of antinuclear antibody (ANA), immunofluorescence (ANA glow) and flow cytometry (expression of CD14+CD11c+and CD14 + HLA-DR +) has been used. Results. The relationship between the clinical phenotypes of myasthenia gravis and the variants of HLA diplotypes was revealed: in young patients with thymus-independent myasthenia gravis (M), a high heterogeneity of the genotypic markers HLA-DR (DR1, DR2, DR3, DR5, DR7) was detected. Patients with thymus-dependent myasthenia (MT) had only the HLA DR2 and HLA DR7 diplo- and haplotypes. The presence of HLA DR2 and HLA DR7 haplotypes in some young patients with progressive thymus-independent myasthenia gravis (M) led to the development of myasthenia gravis with thymoma (MT) in the elderly people. The pathogenic role also belongs to infection (СMV, EBV, HBV, HCV, HSV-1, HSV-2, HHV-6, mycoplasma) and food intolerance (IgE and IgG4) in the development and progression of myasthenia gravis. A four-fold prevalence of a7 subunit nicotinic acetylcholine receptors on the thymocyte mitochondria as an additional targets of autoimmune aggression in myasthenia gravis was determined. Specific antinuclear antibodies to centromere chromosome proteins were visualized in the elderly people with thymoma. Conclusion. The prognosis of the myasthenia gravis progression and the development of remission can be made using genomic (the presence of certain HLA-DR haplotypes) and molecular (ANA antibodies to centromere chromosome proteins, expression of CD20+, CD14+CD11c+, CD14+HLA-DR+) biomarkers, that can be used for the choice of treatment tactics

Surgical methods of prophylaxis of primary insufficiency of the bronchus stump sutures

Objective. To elaborate the effective  miniinvasive technically simple method of prophylaxis for primary insufficiency of the bronchus stump sutures (BSS) due to accomplishment of its transthoracic hermetization and creation of conditions for reduction of impact of the air-wave stream through the resected bronchus lumen onto the suture. Materials and methods. Complex analysis of the treatment results was conducted in 123 patients, in whom pulmonary resection or pulmonectomy was performed. All the patients were divided into two groups: comparative (n=66) and the main (n=57). In patients of the main group the elaborated procedures were applied, concerning determination of the occurrence risk for primary insufficiency of BSS and surgical measures for prophylaxis of this complication. Results. After estimation of risk for the primary insufficiency of the BSS occurrence in 41 patients of the main group the proposed two-staged surgical procedure was applied: endobronchial implantation of allotransplant into the zone of the resection and its mechanical suturing (stage I), and the bronchus stump covering, using bioactive bandage with additional fixing, using monofilament threads (stage II). In the main group the development of primary insufficiency was observed in 2 (3.51%) patients, no one patient died. In the comparison group primary insufficiency of BSS have occurred in 6 (9.09%) patients, and mortality have constituted 3.03%. Conclusion. Application of original method of surgical prophylaxis of the BSSI made it possible to reduce its occurrence rate in 2,6 times and escaping of mortality

The stay of humoral immunity in bacterial dysbiosis and bacterial vaginosis

Introduction. The state of dysbiosis and bacterial vaginosis (BV) is characterized by the formation of both systemic and local immune deficiency, which corresponds to the increase in the number of pathogenic microbiota. An important reason of bacterial vaginosis’ development is local immunodeficiency corresponding with decreasing of colonization resistance of vaginal fluid.  This phenomenon develops due to disturbance of normal vaginal microbiocenosis, secretion of antimicrobial substances and provision of normal immune defense. Recognition of the role and mechanisms of local immunodeficiency’s development can be very important scientific achievement in the field of microbiology, immunology and pathology of human vaginal microflora. However, nowadays ratio of systemic and local immune reactions in bacterial vaginosis isn’t revealed completely.  Thus, the aim of the investigation was to determine the stay of humoral immunity according to the content of immunoglobulins (Ig) in the blood and vaginal fluid in different degrees of bacterial dysbiosis and BV. Material and methods. Data from 298 women were divided into groups according to index of pathogenic microbiota condition (IPMC) and the pathogenic microbiota indicator (PMI): normocenosis (n=53), dysbiosis I (n=128) and II degree (n=117), among the last allocated 83 patients with PMI&gt;1 lg gE/sample, where was drawn diagnosis “Bacterial Vaginosis”. The criterion of exclusion there was presence of pathogenic microorganisms in vaginal epithelium scrapings. These representatives were: Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis та Herpes Simplex Virus 1,2. Presence of leucocytes more than 15-20 cells in the field of vision in vaginal smears indicated inflammatory reaction also was the criterion of exclusion. Molecular genetic studies of posterolateral wall of the vagina epithelium scrapings was performed by Real-time polymerase chain reaction. A content of facultative and obligate anaerobic bacteria, myco- and ureaplasma, yeast-like fungi was studied quantitatively. With the help of Enzyme-Linked Immunoassay (ELISA) contents of  IgA, IgM, IgG, IgG2, secretory IgA (sIgA) were determined in blood and vaginal fluid. Spectrophotometry was used for quantitative evaluation of circulating immune complexes (CIC) contents in the blood and immune complexes in vaginal fluid (ICVF).For descriptive statistics of data there were used arithmetical mean (М) and average error (mistake). Paired independent data samplings were compared according to Mann-Whitney  U-test (U). Significance of all differences accepted when p&lt;0,05. For statistic and regressive analyses package of software “Statistica 10” (StatSoft, Inc., USA) was applied. Results and discussion. While development of bacterial dysbiosis and BV there was observed progressive increasing of CD22 lymphocytosis, contents of IgM, IgG і IgG2. In our investigations quantity of CD22+ lymphocytes was constantly larger in manifested dysbiosis in comparison with normocenosis. Maximal content of CD22+ lymphocytes was noted in BV. Contents of IgA, sIgA and CIC had tendency to decreasing. In general, it’s possible to conclude that blood CIC level decreases according to the progressing of dysbiosis. Hence, its more level in 2 subgroup of 2 group and in 1 subgroup of 3 could indicate reactive changes in immune system.Content of ICVF in I degree dysbiosis in comparison with normocenosis was not change significally. Simultaneously, in I degree dysbiosis and in 1-st subgroup of II degree dysbiosis this inex was significally more. In BV content of ICVF was twice less than in normocenosis. These phenomena were synchronous with blood CIC levels, and reflected sharp parallel decreasing of CIC formation both in the bloodstream and in vaginal fluid during BV. Local immunodeficiency with immunoglobulins’ (especially, IgA and sIgA) and ICVF levels decreasing progressed while development of bacterial dysbiosis and BV also. Therefore, the stay of systemic humoral immunity in BV didn’t correlate always with such one in vaginal fluid.  Conclusion. Systemic humoral immunity while development of BV was changed, but it wasn’t reflected completely the stay of defences in vaginal fluid. In general, there was present dissonance of these two systems’ reaction: activation of systemic level and suppression on local level.DOI: 10.5281/zenodo.3885147