AGE-DEPENDENT IMMUNE STATUS CHANGES IN CHRONIC PANCREATITIS PATIENTS.

The negative consequences of constant stress exposure in patients with chronic pancreatitis (CP) develop an immune deficiency, which also depends on the nature of the body's immune response, which may vary at different ages.; The aim of the study - to study and analyze the state of the immune system of patients with chronic pancreatitis in the age aspect.; We examined the immune system (IS) of 161 patients with CP aged 21 to 78 years, mean age - (58.17±2.46) years, which were divided according to biological age into three groups: up to 45 years (54 patients), from 46 to 65 years (76 subjects), older than 65 years (31 patients). The following indicators of immunity were studied: the number of the total population of T-lymphocytes (CD3), B-cells (CD72), subpopulations of T-helpers/inducers (CD4) and T-suppressors/killers (CD8), natural killers (CD16), which determined in a cytotoxic test using monoclonal antibodies of classes CD3, CD4, CD8, CD16, CD72 by enzyme-linked immunosorbent assay according to the level of expression of membrane antigens.; Secondary immunodeficiency by T-suppressor type, insignificant nonspecific activation of humoral immunity, and decrease in complement activity was established in patients with CP. Changes in the T-cell level of immunity due to the probable decrease in the level of CD3, CD4, CD8, CD16, and CD 72 in young patients by 44.8; 36.1; 24.4; 32.2, and 18.4 %%, respectively (p<0.001); in middle age, immune deficiency deepened, which was manifested by a decrease in these indicators by 54.6; 37.2; 29.9; 41.4 and 25.6 %%, respectively (p<0.001); in patients over 65 years of age, probable T-lymphocytopenia was determined by 66.4; 47.8; 37.7; 70.8; 41.5 %% (p<0.001) compared with the control group.; Based on the regression-correlation analysis, it is proved that the age of patients, duration of CP, level of fecal α-elastase, and structural state of the pancreas according to ultrasound criteria are reliable predictors of immunodeficiency in CP.

[The analysis of immunoreactivity of individual B-cell epitopes of hepatitis C virus (Flaviviridae: Hepacivirus: Hepatitis С virus) NS4a antigen].

INTRODUCTION: Chronic viral hepatitis C (CHC) is a ubiquitous infectious disease, a significant limitation of which WHO attributes to the use of a new highly effective antiviral therapy. Previously, two B-cell epitopes were identified in NS4a antigen of the hepatitis C virus (HCV). It was shown that certain titers of antibodies (ABs) to the extended C-terminal epitope (1687-1718 a.a.) can predict a high probability of achieving a sustained virological response (SVR) to standard therapy with pegylated interferon-α and ribavirin.The aim of the work was to determine immunoreactivity of two B-cell epitopes (middle and C-terminal) of NS4a antigen, and to estimate a possible association of ABs to them with the achievement of SVR after standard interferon therapy and treatment with direct antiviral drugs (DAAs) daclatasvir and sofosbuvir (velpanat). MATERIALS AND METHODS: Blood serum samples of patients with CHC (n = 113), of which 55 participants received standard interferon therapy, 50 received velpanate treatment, the remaining 8 received no therapy were examined. The middle B-cell epitope (positions 24-34 a.a.) of NS4a was synthesized by the solid-phase method, while the C-terminal epitope (34-54 a.a.) was obtained using genetically engineered techniques. Enzyme immunoassay (ELISA) testing of the sera collected before treatment was performed for the two selected epitopes according to the conventional methods. RESULTS: The antibodies to the C-terminal epitope were detected significantly more frequently than those to the middle one (p = 0.01) when analyzing the blood sera of patients (n = 113). The presence of ABs to the C-terminal epitope in the serum samples of participants who completed standard interferon therapy was associated with the achievement of SVR (p = 0.0245). In the blood sera of participants who completed therapy with velpanate, an association of the presence of ABs to the C-terminal epitope with the achievement of SVR was also established (p < 0.0001). The presence of ABs to the middle B epitope was not associated with the achievement of SVR, regardless of the therapy used. DISCUSSION: The observed difference in the immunoreactivity of the two B-cell determinants may be associated with the localization of the nearest Th-epitopes, the sensitivity of NS4a antigen to proteolytic enzymes, and the peculiarities of epitope presentation by antigen-presenting cells. However, it should be noted that the immunoreactivity of the middle B-epitope is poorly studied. Although the association of ABs to the C-terminal epitope with the achievement of SVR has been shown by several scientific teams, the detailed molecular mechanism of their influence on the effectiveness of therapy is unclear. CONCLUSION: In CHC, ABs to the C-terminal epitope of NS4a are produced more frequently than those to the median epitope. The presence of ABs to the C-terminal epitope is a predictive marker of a high probability of achieving SVR, regardless of the type of therapy and antibody titer.

Predicting concurrent structural mechanical mechanisms during microstructure evolution.

The interdependence between structural mechanics and microstructure solidification has been widely observed experimentally as a factor leading to undesirable macroscopic properties and casting defects. Despite this, numerical modelling of microstructure solidification often neglects this interaction and is therefore unable to predict key mechanisms such as the development of misoriented grains. This paper presents a numerical method coupling a finite volume structural mechanics solver to a cellular automata solidification solver, where gravity or pressure-driven displacements alter the local orientation and thereby growth behaviour of the solidifying dendrites. Solutions obtained using this model are presented which show fundamental behaviours observed in experiments. The results show that small, localized deformations can lead to significant changes in the crystallographic orientation of a dendrite and ultimately affect the overall microstructure development. This article is part of the theme issue 'Transport phenomena in complex systems (part 2)'.

COMORBIDITY OF TYPE 1 DIABETES MELLITUS WITH OTHER CHRONIC PATHOLOGY IN CHILDREN.

In this study was to investigate the сoexistence of diabetes mellitus type 1 with other chronic pathology in children and adolescents and their impact on the course of diabetes mellitus type 1 (DM1). The 88 children from 3 to 17 years who had DM1 were observed. The study was conducted by survey with the aim of finding risk factors and associated comorbidties with a questionnaire-based, objective-subjective study. All patients had severe form of T1DM, with suboptimal and poor glycemic control. Comorbid pathologies observed in 71,6±4,8% of childrn included: thyroid pathology - 62,5±5,1%, disorders of the autonomic nervous system - 20,5±4,3%, gastro-pathology - 7,9±2,8%, atopic dermatitis - 6,8±2,6%, arthritis - 6,8±2,6%, bronchial asthma - 4,5±2,2%, allergic rhinitis - 3,4±1,9%, immune-deficient disorder - 2,3±1,5%. Conclusions. 1. The detected comorbid pathology in children with DM1 makes it necessary to collect an anamnesis and examination of children for the purpose of early finding a coexistence of chronic pathology. 2. The risk of development of the thyroid pathology enhances is 7,5 times, allergic pathology is 6,9 times in patients with DM1. 3. Coexistence of type 1 diabetes and other chronic diseases impairs glucose metabolism, impedes effective insulin therapy, and deteriorates diabetes control. 4. This accent the need for the improvement of the monitoring of patient with diabetes mellitus and comorbid pathology for the prognosis of the course and optimization of treatment and rehabilitation measures.

; LIVER LESION IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS WITH DIFFERENT DURATION OF METHOTREXATE TREATMENT.

The aim of the research was to determine liver lesion in patients with Oligoarticular and RF-negative Polyarticular forms of JIA by noninvasive methods depending on duration of Methotrexate treatment. The study included 42 patients with Rheumatoid factor (RF) negative oligo- and polyarticular joints forms of JIA from 3 to 18 years old. They were investigated by measurement of alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), haptoglobin, triglycerides, gamma glutamine transferase (GGT), apolipoprotein-A (Apo-A), a2-macroglobulin, cholesterine levels. The equation for calculating the FibroTest score regression coefficient had been done according U.S. patent 6.631.330. Student -Fisher Test, Mann - Whitney U-test were used for the statistical processing. In spite of MTX treatment progression of JIA was determined according assessment of joints functional class and radiological stage (p<0.05). Increased level of ALAT was prominent (40%) in children taken MTX for 1-5 years in comparison with other studied patients (p<0.05). 17 % of children who took MTX longer than 5 years had increased GGT content. Metabolic liver function was not changed because levels of Apo-A, haptoglobin, total bilirubin, cholesterine were within normal limits due to all stages of MTX taking. The increased level of a2-macroglobulin as a predictor of liver fibrosis was determined in all studying groups with the average frequency 36 % and it did not correspond to the duration of MTX treatment. According FibroTest score regression 14% of patients had liver fibrosis F1, which did not depend on duration of MTX treatment. According to our findings, patients using MTX for JIA management had joint damage progresses despite usage of MTX. Hepatic cytolysis is most frequently appeared within 15 years of MTX taking. Risk of liver fibrosis does not depend on duration of MTX treatment.

JUVENILE IDIOPATHIC ARTHRITIS AND VITAMIN D STATUS IN UKRAINIAN PATIENTS.

Plenty of studies demonstrated an association between a Vitamin D deficiency and several autoimmune disorders, such as diabetes mellitus, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) in adult patients. This study was aimed to assess probable association between the 25-hydroxyvitamin D [25(OH)D] level and juvenile idiopathic arthritis (JIA) features and the possible relationship between serum vitamin D level and disease activity. 69 patients with JIA were examined and 15 healthy children were chosen as the control group. The mean age of patients was 10 years 8 months ±4 years 6 months (45 female, 24 male). 25 patients with oligoarthicular subtype of disease, 34 with poliarthicular sybtype and 10 patient with undifferentiated arthritis . The total duration of the disease was 4 years 1 month ± 1 year 1 month. Patients got methotrexate therapy (15mg/m2). Any of the patients were not treated by corticosteroids. The serum level of vitamin D was measured through blood test by chemiluminescence method. The relationship between the level of vitamin D and disease activity was analyzed based on juvenile arthritis disease activity score (JADAS27). The average level of vitamin D in serum was 22,69±7,8 ng/ml at the control group the vitamin D status was 28,67±5,06 ng/ml. In spite of the fact that a decrease in vitamin D status was observed in both groups, however in the group of healthy children it was significantly higher (p>0.05). Using the regression method, a significant relationship was established between the number of active joints and the age of patients, duration of disease, the level of vitamin D in serum, the number of injured joints, and disease activity (accordant to JADAS27 score) (number of active joints = - 1,144 + 0,005 x age of patients - 0,007x duration of disease + 0,292 x the number of injured joints + 0,033 x level of vitamin D + 0,077 x the number of points accordant to JADAS27). The monitoring of vitamin D level is advisable to carry out during observing the children with JIA. It can be useful for timely correction of vitamin D deficiency and preventions both skeleton and non-skeleton complications. That may improve the quality of life of patients and their families.

[Problem of mineral insufficiency at chronic pancreatitis in dependence on age].

The high incidence of chronic pancreatitis (CP) which arise at young people of working age, the development of serious complications are pushing for the development of new diagnostic methods and the search for effective ways to treat this disease. In this regard, a relevant and promising direction is the further study of the mechanisms of pathogenesis and the formation of trophological (including mineral) deficiency in CP, followed by the development of comprehensive programs for their correction. Aim is to study mineral status of patients with chronic pancreatitis, depending on their age. Material and methods. A sample of 218 patients (140 women, 78 men) with CP with exocrine insufficiency aged 18 to 72 years was examined. The control group consisted of 20 healthy individuals who underwent a planned outpatient examination. To assess the mineral status, macronutrients were determined photometrically, iron by the bathophenanthroline method, the remaining trace elements (Cu, Zn, Pb, Cd) were determined by atomic absorption spectrometry in blood serum. Results and discussion. Patients with CP at all age groups revealed a statistically significant (p<0.001) decrease in serum concentration of calcium, phosphorus, magnesium, potassium, copper, zinc, and iron compared to the level in healthy individuals, which increased with age. In the group of patients older than 60 years, the state of hypomineralemia was detected by the level of calcium, phosphorus, magnesium, potassium, copper, zinc, iron, which required correction of the mineral status. With increasing age of patients with CP, the content of toxic metals (lead and cadmium) increased compared with that in the group of healthy individuals. Сonclusions. The findings suggest that the age of patients with CP is a predictor of mineral deficiency and the accumulation of toxic elements, which must be considered when forming a complex treatment.

Thermal dependence of large-scale freckle defect formation.

The fundamental mechanisms governing macroscopic freckle defect formation during directional solidification are studied experimentally in a Hele-Shaw cell for a low-melting point Ga-25 wt.% In alloy and modelled numerically in three dimensions using a microscopic parallelized Cellular Automata Lattice Boltzmann Method. The size and distribution of freckles (long solute channels, or chimneys) are shown to be strongly dependent on the thermal profile of the casting, with flat, concave and convex isotherms being considered. For the flat isotherm case, no large-scale freckles form, while for concave or convex isotherms, large freckles appear but in different locations. The freckle formation mechanism is as expected buoyancy-driven, but the chimney stability, its long-term endurance and its location are shown to depend critically on the detailed convective transport through the inter-dendritic region. Flow is generated by curved isopleths of solute concentration. As solute density is different from that of the bulk fluid, gravity causes 'uphill' or 'downhill' lateral flow from the sample centre to the edges through the mush, feeding the freckle. An excellent agreement is obtained between the numerical model and real-time X-ray observations of a solidifying sample under strictly controlled temperature conditions. This article is part of the theme issue 'Heterogeneous materials: metastable and non-ergodic internal structures'.

[ADAPTIVE CAPABILITIES OF THE CARDIOVASCULAR SYSTEM IN ADOLESCENTS WITH NON-INFLAMMATORY MYOCARDIAL PATHOLOGY, TAKING INTO ACCOUNT MORPHOFUNCTIONAL INDICATORS OF THE HEART].

THE AIM OF THE STUDY: to study the adaptive capabilities of the cardiovascular system in children with non-inflammatory myocardial pathologies, taking into account morphofunctional indicators of the right and left ventricles of the heart. MATERIALS AND METHODS: 62 patients with non-inflammatory myocardial pathology were examined, 30 of them with minor abnormalities of the heart, 32 with various rhythm disturbances. The average age of the subjects was 14.56 ± 0.24 years. The morphofunctional state of the myocardium was assessed by the results of ultrasound Doppler examination of the heart in the "M" and "B" modes. To study the tolerance to minimal physical activity and its effect on the state of the cardiovascular system in children, a six-minute walk test was performed. To assess the functional tension of the cardiovascular system before and after six-minute walk test, the following indices were calculated: Allgauer's index, endurance coefficient by the formula of A. Kwaas, Robinson index, coefficient of blood circulation efficiency. To assess the effect of the autonomic nervous system on the performance of the cardiovascular system, the Kerdo Vegetative Index was determined. At rest, the index of functional changes of the circulatory system, or adaptive potential was also determined. As a result of the study, it was noted that children with non-inflammatory heart diseases showed a decrease in systolic myocardial function of both ventricles. In patients with minor abnormalities of the heart, this is accompanied by the formation of dilatation of the left ventricular cavity and an increase in myocardial mass. As a result of the study, it was noted that in children with non-inflammatory heart diseases, a decrease in systolic myocardial function of both ventricles is noted. In patients with MARS, this is accompanied by myocardial remodeling with dilatation of the left ventricular cavity and an increase in myocardial mass. Subclinical decline in functionality is detected in samples with physical activity (six-minute walk test). At the same time, to assess the functional reserves of the circulatory system and the child's body as a whole, as well as its adaptive capabilities, it is advisable to use the Allgover, Robinson indices, endurance coefficient and efficiency of blood circulation.

[X-ray-surgery of diverticular disease complicated by abscess formation]. / Rentgenokhirurgiia divertikuliarnoi bolezni, oslozhnennoi abstsedirovaniem.

PURPOSE: Show the possibility of an alternative use of interventional radiology techniques in complex treatment of patients with inflammatory complications of the diverticular disease of the colon. MATERIAL AND METHODS: In 2012-2016, there were 87 patients under our supervision with complicated diverticular disease. In 57 (65.5%) cases were diagnosed infiltrate, in 24 (27.6%) cases - abscess of paracolon area (Ib-II type by Hinchey), in 6 (6.9%) cases (III-IV type according Hinchey) generalized peritonitis have been identified. RESULTS: Emergency laparotomy was performed in 13 patients. Abscesses of paracolon (Ib-II type by Hinchey) area were diagnosed sonographically during the initial examination in 17 patients. 26 percutaneous drainage of diverticulogenous abscesses of different localizations self-locking drainage #8Fr 'pig tail' was carried out under the combined ultrasonic and X-ray control in this group of patients. The technical success of percutaneous drainaging of the abscesses was achieved in all manipulations. 13 patients had a single drainaging, and for diverticular disease - disease-free during the observation period of 1 year to 5 years. Resection of the colon in a planned manner after percutaneous drainage of recurrent abscess of paracolon area was performed in 4 patients. Complications related with the technique of installing drainage were not reported, mortality in the group of drained patients was absent. CONCLUSION: Ultrasound examination of patients with suspected inflammatory complications of diverticular disease - a necessary and sufficient method for initial diagnosis of the disease. Percutaneous drainage of diverticulogenous abscesses (Hinchey Ib-II) is represented by the pragmatic 'first line' choice in patients with complicated diverticular disease, that allows to treat the pathology steadfastly in most of the cases.

Effect of a synthetic indolicidin analogue on lipid peroxidation in thermal burns.

Experimental simulation of burn was followed by accumulation of LPO products and suppression of antioxidant enzyme activity in the burn wound. Application of a synthetic analogue of indolicidin led to an increase in MDA and acylhydroperoxide concentrations in the burn wound on experimental day 1. Further application of the peptide in a dose of 100 mg/kg had no significant effect on the studied parameters, while the peptide in a dose of 500 mg/kg was followed by a decrease in the level of LPO products on days 10 and 14. Changes in antioxidant enzyme activities in rats treated with 500 mg/kg indolicidin analogue had a two-phase pattern: an increase on day 4 was followed by a decrease.

[To the 175th anniversary of Irkutsk military hospital].

The article is dedicated to the 175th anniversary of the Irkutsk military hospital and highlights the key historical moments of the establishment and activity of the oldest hospital in Eastern Siberia and work of doctors, nurses, paramedical hospital. The article presents historical information about famous personalities which have worked and served in the hospital and have contributed to the development of military medicine.

[Efficiency of a new synbiotic drink in treatment of chronic diseases of gastrointestinal tract and concomitant dysbacteriosis].

The efficacy of a novel synbiotic drink in the complex therapy of patients withchronic diseases of the gastrointestinal tract and concominant intestinal dysbacteriosis was investigated in a randomized trial. The synbiotic drink contains a probiotic strain of bifidobacteria and Fucus evanescens polysaccharides with prebiotic activity and broad spectrum of the biological action on the patients. The use of the synbiotic drink provided more evident reduction of the clinical symptomes, more efficient recovery of the intestinal microflora and higher percentage of the patients cure vs. the routine therapy and the therapy with inclusion of sour milk bifidobacterin.

[Influence of intravenous injection of fucoidan from brown seaweed Fucus evanescens by plasma rabbits anticoagulant activity and neutralisation by sulphate protamin of fucoidans antithrombin activity in vitro].

With fucoidan from Fucus evanescens dose increase from 1 to 5 mg/kg plasma coagulation time in test A(see symbol)TB increases. Sulphate protamin in final concentration 0.67-1.35 mkg/ml will neutralise antithrombin activity of fucoidans from brown seaweed Fucus evanescens and Laminaria cichorioides. The gravimetrichesky relation for the investigated samples makes an antidot/anticoagulant 1.

Correlation between influence of polysaccharides on hydrolase activity and their antiviral effect in tobacco leaves.

The activities of hydrolases (acid phosphatase, RNase, and proteases) in healthy and tobacco mosaic virus-infected leaves of Nicotiana tabacum L. var. Samsun, both untreated and treated with polysaccharides (PS) (1,3;1,6-ß-D-glucan, fucoidan, and κ/ß-carrageenan), were determined. The PS lead to substantial increase in the hydrolase level. The percentage of viral particles undergoing destructive change also increases in leaves treated with PS 24 h before infection. We suppose that the PS-mediated hydrolase activation promotes intracellular destruction of the viral particles and, thus, comprises one of the PS-induced protective mechanisms limiting intracellular viral accumulation.

Evaluation of a resectable ultrasound liver phantom for testing of surgical navigation systems.

A formerly developed ultrasound liver phantom for testing of surgical navigation systems and liver resection trainings was evaluated experimentally. The phantom was scanned with CT and the dataset was analyzed with existing segmentation techniques. A virtual 3D model was generated on the basis of the segmentation; it was later used for phantom registration in a surgical assistance navigation system. Within an experiment, ten test persons have tried to touch three tumor models hidden in the phantom with the tip of a resection instrument. In 67% of overall 30 touch trials it was a successful touch at the first go. It means that the developed liver phantom is appropriate for testing of surgical navigation systems, as well as for computer assisted liver resection trainings.

MiMed liver: a planning system for liver surgery.

In clinical routine of liver surgery there are a multitude of risks such as vessel injuries, blood loss, incomplete tumor resection, etc. In order to avoid these risks the surgeons perform a planning of a surgical intervention. A good graphical representation of the liver and its inner structures is of great importance for a good planning. In this work we introduce a new planning system for liver surgery, which is meant for computer tomography (CT) data analysis and graphical representation. The system is based on automatic and semiautomatic segmentation techniques as well as on a simple and intuitive user interface and was developed with the intention to help surgeons by planning an operation and increasing the efficiency in open liver surgery.

[Production of cytokines by murine bone marrow dendritic cells in vitro mediated by sulfated polysaccharides obtained from sea brown algae].

AIM: To assess in vitro cytokine production by murine bone marrow dendritic cells (DC) matured under the effect of sulfated polysaccharides--fucoidanes from sea brown algae Laminaria cichorioides and Laminaria japonica. MATERIALS AND METHODS: CBA line mice were used to obtain bone marrow origin precursors of DC. Isolation and study of chemical composition and structure of fucoidanes were performed using modern research methods. Expression of surface markers was determined by flow cytometry (FACS-analysis) using monoclonal antibodies to respective antigens. Levels of cytokine production were measured by t-ELISA using kits manufactured by Biosource (Belgium). RESULTS: I was determined that fucoidans induce maturation of DC that was evident by expression of terminal differentiation marker CD83, activation marker CD38, enhanced expression of costimulating CD86, antigen-presenting MHC II and adhesive CD11c molecules. Fucoidanes stimulate DC to produce proinflammatory (TNF-alpha, IL-6, IL-1beta) and regulatory (IL-12) cytokines. Fucoidanes enhance expression of TLR-2 and TLR-4 but do not influence on expression of TLR-9. CONCLUSION: It was shown that fucoidanes from sea brown algae L. cichorioides and L. japonica activate innate immunity system that is evident by enhanced expression of surface molecules associated with DC maturation and increased production of proinflammatory and regulatory cytokines by DC. Enhanced expression of TLR-2 and TLR-4 allows to suppose that studied fucoidanes could have anti-infective effect in vivo.

Multicity HIV seroprevalence in street youth, Ukraine.

We conducted the first systematic, community-based, multicity assessment outside the USA of HIV seroprevalence, risk factors and linkage into clinical services among 929 street youth. After city-wide mapping, we used time-location sampling and randomly selected 74 venues in Odesa, Kyiv and Donetsk, Ukraine. Rapid HIV testing with post-test counselling was offered to all eligible youths aged 15-24 years. Overall, 18.4% (95% confidence interval 16.2-20.2) were HIV positive and 85% had previously unknown status. Rates were identical by sex. Subgroups with highest rates included orphans (26%), youths with histories of exchanging sex (35%), sexually transmitted infections (STIs) (37%), injection drug use (IDU) (42%) and needle sharing (49%). Independent predictors, similar across age groups and city, included being orphaned, time on the street, history of anal sex, STIs, exchanging sex, any drug use, IDU and needle sharing. Two-thirds (68%) of HIV-positive youths were linked to services. This high-risk population has many immediate needs.

[Evaluation of the activity of hydrolases and their inhibitors using substrates immobilized on agarose gel].

A simple and convenient method for the quantitative evaluation of the activity of hydrolytic enzymes and their inhibitors has been proposed. This method is based on the immobilization of a substrate on agarose gel and the following evaluation of the enzyme activity by measuring the hydrolysis area around the well containing the enzyme solution. The method was shown to be applied to the evaluation of the activity of proteinases and amylases and the inhibitors of these enzymes in different biological objects.