Aim: to study the levels of fatty acids in the membranes of erythrocytes and blood serum in patients with inflammatory bowel diseases (IBD) examined over time, as possible predictors of exacerbation of the disease.Materials and methods. Over a period of 6–12 months, 24 patients (mean age — 38.2 ± 4.4 years) with IBD with of moderate and mild severity of the disease were examined, of which 10 patients had ulcerative colitis, 10 — Crohn’s disease, 4 — unclassified colitis: the first examination was in the acute stage, the second was in the remission stage. In 48 additionally examined patients with IBD in remission (25 patients with ulcerative colitis, 15 — with Crohn’s disease, 8 — with unclassified colitis), the course of the disease was monitored over the next 12 months. The comparison group included 53 people comparable to the main groups in age. The study of the composition of fatty acids (FAs) in the membranes of erythrocytes and blood serum was carried out using a gas chromatograph mass spectrometry system based on three quadrupoles Agilent 7000B (Agilent Technologies Inc., USA).Results. In the acute stage, patients with IBD have a higher total content of saturated fatty acids (SFAs) in erythrocyte membranes compared to the control group (p = 0.006), and, on the contrary, lower levels of unsaturated fatty acids (UFAs) (p = 0.005), mainly due to polyunsaturated FAs (PUFAs) (p = 0.026), namely omega-6 PUFAs (p = 0.011).Remission of IBD is associated with an increase in the level of a number of SFAs in the blood serum — margaric C17:0 (p = 0.024), arachidic acid (C20:0) — in erythrocyte membranes and serum (p = 0.0001 and p = 0.019, respectively), with a decrease in the total content of monounsaturated FAs in erythrocyte membranes (p = 0.022), an increase in the total concentration of PUFAs due to both omega-3 PUFAs (p = 0.0008) and omega-6 PUFAs (p = 0.033) in erythrocyte membranes compared with a group of healthy individuals.The exacerbation stage in patients with IBD examined over time is associated with higher levels of stearic FA C18:0 (p = 0.005), SFA/UFA (p = 0.034) and SFA/PUFA (p = 0.039) ratios in erythrocyte membranes, serum level of arachidic FA C20:0 (p = 0.008), and, on the contrary, lower content of UFAs in erythrocyte membranes — eicosapentaenoic C20:5n-3 (p = 0.0023), eicosadienoic C20:2n-6 (p = 0.0027), hexadecadienoic C16:2n-6 (p = 0.006), docosatetraenoic C22:4n-6 (p = 0.008) and alpha-linolenic C18:3n-3 (p = 0.039).A combined “panel” of fatty acids, including the levels of C20:2n-6, C18:0 in erythrocyte membranes and the content of C20:0 in blood serum, provided an AUC of 0.683 (95 % CI: 0.500–0.844), sensitivity 91.4 %, specificity 68.3 %.Levels of C20:5n-3, C20:2n-6, C18:0, C16:2n-6, C22:4n-6, C18:3n-3 fatty acids, SFA/UFA and SFA/PUFA ratios in erythrocyte membranes and content C20:0 in blood serum, used as biomarkers — predictors of the development of exacerbation in patients with IBD who were in remission, predicted the development of exacerbation of IBD after 2–4 months in the case of maximally changed levels of FAs, after 6–8 months — with moderately changed levels FAs, maintaining remission for 12 months — with minimally changed FAs levels.Conclusion. Fatty acids of erythrocyte membranes and blood serum should be considered as promising markers for further studies related to the diagnosis and prediction of exacerbation in IBD.

The purpose of the review is to analyze the role of different classes of fatty acids in the pathogenesis of inflammatory bowel diseases (IBD), the possibility of using levels of fatty acids and lipid mediators as biomarkers of IBD, and to consider possible therapeutic approaches for IBD based on information about fatty acids. Material and methods. A search was conducted using keywords in the text databases Scopus, Web of Science, PubMed using literary sources of the last 10 years on the role of fatty acids of various classes in the pathogenesis of IBD, their use as biomarkers of IBD, and possible therapeutic effects. Results. It has been established that fatty acids, as essential food components, have anti-inflammatory, immunoregulatory, modulating intestinal microbiota and supporting the intestinal barrier effect in the pathological processes of IBD. However, the mechanisms of action of specific fatty acids, such as medium-and very long-chain fatty acids, in IBD require further clarification. An analysis of epidemiological studies examining the effect of fatty acids on IBD revealed inconsistencies between the results of some of them, as well as between the results of animal experiments. The availability of evidence from large-scale cohorts and randomized controlled trials is limited, and translation of findings from animal models to human populations is challenging. The results of studies in which different classes of fatty acids are used as biomarkers of disease activity, predictors of complicated course, development of exacerbation, and also for the purpose of differential diagnosis of IBD are presented. As diseases influenced by genetics and environment, IBD exhibits varying sensitivities to different fatty acids or lipid mediators depending on different genotypes. Fatty acids may serve as complementary therapeutic agents in the treatment of IBD, as reflected in current dietary guidelines and complementary dietary strategies that utilize fatty acids for therapeutic purposes. Conclusion. Further study of fatty acids in IBD is promising both from the point of view of clarifying the pathogenesis of the disease and from the position of possible markers for diagnosis and additional possibilities for therapy.

The aim of the review is to highlight the main factors affecting the development of liver fibrosis and possible mechanisms of liver damage in patients who have experienced COVID-19. A search was carried out using keywords in the Scopus, Web of Science, and PubMed databases in literary sources of the last three years on factors associated with fibrogenesis in novel coronavirus infection. The review presents the main mechanisms of liver damage in COVID-19: direct effects on hepatocytes and cholangiocytes, hypoxia, and immune-mediated and drug-induced damage. We analyzed the significance of factors affecting fibrosis development in patients with COVID-19: chronic diffuse liver diseases, against which COVID-19 occurs, such as non-alcoholic fatty liver disease, alcohol-associated liver disease, chronic hepatitis B, C, and cirrhosis of the liver.Damage to the liver in coronavirus infection develops by several mechanisms. The development of COVID-19 against the background of diffuse liver pathology of various genesis is associated with progression of these diseases (increased fibrogenesis) and a poorer prognosis.

Purpose of the work: to analyze the research performed in the last decade on the study of serum markers used to diagnose inflammatory bowel diseases (IBD), differential diagnosis of nosological forms of IBD, to predict the course of the disease, response to ongoing therapy, as well as to predict the recurrence of the disease. Materials and methods. A search was carried out in the text databases “Scopus”, “Web of Science”, “PubMed” using keywords from the literature sources of the last 10 years about blood serum biomarkers used for diagnosis, evaluation of therapeutic efficacy, monitoring of disease activity and evaluation of prognosis in patients with IBD. Results. Information on serological biomarkers of IBD, which are well known and widely used in clinical practice (C-reactive protein), recently discovered biomarkers (cytokines, antibodies and non-coding RNA), as well as recent advances in serological biomarkers (metabolomics, proteomics, oncostatin M, galectins), were analyzed, which are used in various aspects of the diagnosis of IBD. Since intestinal fibrosis significantly affects the prognosis in patients with IBD, data on serum markers of intestinal fibrosis are presented separately. Conclusion. Recently, serum biomarkers in patients with IBD have become the object of close attention, since they are minimally invasive, convenient, and relatively inexpensive than markers in biopsy specimens, other biological fluids, fecal, and respiratory tests. Despite an extensive list of studies conducted over the past 10 years, there are still no ideal serum biomarkers for the diagnosis of IBD. Serum and non-coding RNA profiling techniques are just beginning to develop, but offer great promise for clinical practice. A combination of different biomarkers may be useful to improve the efficiency of IBD diagnosis.

Purpose of the work: to study liver elasticity indicators, hydrogen and methane levels in exhaled air, and their associations with clinical and biochemical parameters for patients who underwent COVID-19. Materials and methods. We examined 30 patients (mean age 51.8±2.91) who underwent COVID-19 (confirmed by SARS-CoV-2 RNA test or SARS-CoV-2 antigen) 12-16 weeks after the onset of the first symptoms, of which 11 were diagnosed with pneumonia. 19 people (mean age 47.1±3.09) who did not have COVID-19 made up the comparison group. The patients underwent a clinical and biochemical study, the degree of liver fibrosis was determined (FibroScan® 502 Echosens, France), the levels of hydrogen (H2) and methane (CH4) in the exhaled air were measured (baseline and after taking lactulose solution) (GastroCheck Gastrolyzer, Bedfont Scientific Ltd., England). Results. Past COVID-19 infection was directly correlated with age (r=0.331, p=0.022), male gender (r=0.324, p=0.025), and presence of liver fibrosis (r=0.291, p=0.044). COVID-19 survivors were more likely to have liver fibrosis (p<0.001) and higher liver elasticity in kPa (p=0.018) with overweight and obesity (63.3%) and elevated body mass index (p= 0.03) compared with the control group. The presence of liver fibrosis was associated with moderate pneumonia (p<0.001). Among those who had COVID-19, there were significantly more non-producers of methane (p=0.02), fewer people with an average level of methane in exhaled air (p=0.016). In COVID-19 convalescents, bacterial overgrowth syndrome (BOS) was detected less frequently than in controls (p=0.04), but signs of delayed intestinal transit were more often recorded (p<0.05). The presence of liver fibrosis in survivors of COVID-19 is associated with BOS detection (23.3% vs. 5.2%, p<0.001), which probably contributes to the pathogenesis of liver damage. Hydrogen levels at 120 min and methane at 60 min after ingestion of lactulose solution distinguished between COVID-19 convalescents and COVID-19 survivors with an AUC of 0.683 and 0.660, respectively. The associations of the levels of gases in the exhaled air with clinical and biochemical parameters were revealed: the presence of overweight and obesity showed inverse associations with the level of methane production (r= -0.342, p<0.05), its concentration after taking lactulose at various time intervals, and also the basic level of hydrogen (r= -0.313, p<0.05); the degree of obesity was also inversely correlated with the level of methane emission (r= -0.368, p=0.038). Direct links were established between indicators of liver elasticity in kPa and the level of hydrogen production (r=0.275, p<0.05). Conclusions. Obtained indirect signs of pronounced changes in the intestinal microbiome, which obviously contribute to a more severe course of COVID-19, the development of liver fibrosis, so the impact on the intestinal microflora can be considered as a potential target in the treatment of patients with COVID-19.

Aim: to study fatty acid levels in erythrocyte membranes (RBC) and blood serum (BS) in patients with inflammatory bowel diseases (IBDs) to develop differential diagnostic models including fatty acids as biomarkers to distinguish between nosological entities of IBDs (ulcerative colitis — UC, Crohn's disease — CD, unclassified colitis — UCC).Materials and methods. We examined 110 patients (mean age 37,7 ± 12,1 years) with IBDs and 53 healthy patients in control group (43,3 ± 11,7 years). The IBDs group included 50 patients with UC, 41 patients with CD, 19 patients with UCC. An exacerbation of the disease was revealed in 42 patients (84 %) with UC, 34 patients with CD (82.9 %) and 11 people with UCC (57.9 %). The study of fatty acids (FA) composition of RBC membranes and BS was carried out using GC/MS system based on three Agilent 7000B quadrupoles (USA).Results. The most significant for distinguishing active UC from CD exacerbation were serum levels of elaidin (p = 0.0006); docosatetraenoic (n-6) (p = 0.004); docodienic (n-6) (p = 0.009); omega-3/omega-6 ratio (p = 0.02); docosapentaenoic (n-3) (p = 0.03); the sum of eicosapentaenoic and docosahexaenoic (p = 0.03), as well as the content of RBC lauric FA (p = 0.04) (AUC — 0.89, sensitivity — 0.91, specificity — 0.89, diagnostic accuracy — 0.91). To distinguish active UC from the same of UCC, the following serum FA were found to be significant: alpha-linolenic; saturated (pentadecanoic, palmitic, stearic, arachidic); monounsaturated (palmitoleic, oleic); omega-6 (hexadecadienic, arachidonic) (p = 0.00000011—0.03300000) (AUC — 0.995, sensitivity — 0.98, specificity — 0.96, diagnostic accuracy — 0.97). The most significant in distinguishing patients with active CD from UCC exacerbation were levels of the following FA: alpha-linolenic; palmitoleic; oleic; the amount of saturated fatty acids (SFA); total unsaturated fatty acids (UFA); stearic; monounsaturated fatty acids (MUFA) amount; SFA/UFA; SFA/PUFA (polyunsaturated fatty acids); linoleic; total PUFA n6; lauric; arachidic acid (p = 0.0000000017–0.030000000) (AUC — 0.914, sensitivity — 0.90, specificity — 0.87, diagnostic accuracy — 0.91).Conclusion. The study of FA levels in groups with different nosological forms of IBDs using complex statistical analysis, including machine learning methods, made it possible to create diagnostic models that differentiate CD, UC and UCC in the acute stage with high accuracy. The proposed approach is promising for the purposes of differential diagnosis of nosological forms of IBDs.

Purpose of the work: to present a method for diagnosing the activity of inflammatory bowel diseases based on a combination of electrical and viscoelastic parameters of erythrocytes and the level of fecal calprotectin.Materials and methods. We examined 109 patients (37.7±11.7 years) with IBD (50 with ulcerative colitis, 41 with Crohn’s disease, 18 patients with unclassified colitis), of which 36 patients were examined in dynamics for 0.5–1 years, and 53 surveyed comparison groups. Taking into account the observation in dynamics in 109 cases, the presence of exacerbation of IBD was established and in 36 cases — remission of the diseases. The electrical and viscoelastic parameters of erythrocytes were studied by dielectrophoresis. The level of fecal calprotectin was determined by ELISA (R-Biopharm, Germany).Results. Differentiating values have been established for a number of erythrocyte parameters: average cell diameter, polarizability at a frequency of 106 Hz, the velocity of movement of cells towards electrodes, amplitude of erythrocyte deformation at a frequency of 106 Hz, the summarized indicators of rigidity, viscosity, electrical conductivity, position of the crossover frequency and the level of fecal calprotectin to distinguish patients with IBD in stages of exacerbation and remission. The proposed method for the combined use of erythrocyte parameters and the level of fecal calprotectin provided sufficient diagnostic accuracy: sensitivity 91.9%, specificity 93.1%, accuracy index 92.3%. The advantages of this approach are minimally invasiveness, high productivity, independence of the definition from the qualifications and experience of a specialist, low cost and labor intensity, and acceptability for the patient. This approach allows to establish the presence of exacerbation or remission, regardless of the nosological form of IBD.Conclusion. The combined use of electrical and viscoelastic parameters of erythrocytes and the level of fecal calprotectin is promising for determining the activity of the disease in patients with IBD.

The aim of this work is to study the features of the electrical and viscoelastic parameters of erythrocytes in patients with inflammatory bowel diseases (ulcerative colitis, Crohn’s disease, unclassified colitis), taking into account the stage of the disease for possible use in differential diagnosis.The electrical and viscoelastic parameters of erythrocytes were studied using dielectrophoresis in 109 patients with IBD, mean age 37,7 + 11,7 years (50 patients with ulcerative colitis (UC), 41 with Crohn’s disease (CD), 18 with unclassified colitis (UCC) and 53 conditionally healthy, comparable in age and sex with the main groups.Red blood cells of individuals with IBD differed from those in the comparison group by a smaller average diameter, an increased proportion of deformed, spherocytic cells with a changed surface character with a reduced ability to deform, a lower level of surface charge of cells, an altered membrane structure with an increased ability to conduct electric current, prone to destruction and the formation of aggregates (p <0,0001–0,05).Analysis in individual groups with IBD in the acute stage, taking into account the therapy, revealed significant differences between the forms of IBD: in patients with Crohn’s disease, in contrast to patients with UC, red blood cells had lower values of the amplitude of deformation, capacity, dipole moment, and velocity of movement of cells towards electrodes, the proportion of discocytes, polarizability at most of the frequencies of the electric field (p <0,00001–0,05). On the contrary, the summarized indicators of rigidity, viscosity, electrical conductivity, aggregation and destruction indices were higher in CD than in UC (p <0,0001–0,05). CD patients had a greater number of deformed cells with altered surface character (p <0,00001).The features of the electrical and viscoelastic parameters of erythrocytes in patients with differentnosological forms of IBD can be used for the differential diagnosis of ulcerative colitis and Crohn’s disease in case of colon lesions, in the long term — for verification of the diagnosis in unclassified colitis.

The aim of this work is to study the electrical and viscoelastic parameters of erythrocytes for patients with inflammatory bowel diseases (IBD), examined in dynamics, as possible predictors of exacerbation of the disease. Material and methods. In dynamics, 23 patients with IBD (37.9 ± 4.3 years) were examined. The first examination was carried out in the stage of exacerbation, the second – after 6–12 months – in the stage of remission of IBD. Additionally, 36 patients with IBD in remission were examined to assess the predictive capabilities of erythrocyte parameters with subsequent monitoring of their condition for 6–12 months. The electrical and viscoelastic parameters of erythrocytes were investigated by dielectrophoresis. Statistical processing was carried out using a system of machine learning methods – Random Forest, MATLAB (R2019a, MathWorks). Results and discussion. The parameters of erythrocytes, which are predictors of exacerbation of IBD, were revealed: an increase in the proportion of deformed cells (p = 0.0001); altered nature of the erythrocyte surface (p = 0.011); increased electrical conductivity of membranes (p = 0.0019); reduced dipole moment (p = 0.0015), the rate of directional movement of erythrocytes to the electrodes (p = 0.005) (paired and unpaired Volcano plot methods), reduced deformation amplitude at a frequency of 5×105 Hz (p = 0.009), capacity of erythrocyte membranes (p = 0.029 ) (unpaired Volcano plot method). Indicators associated with changes in the charge of cells, the structure of erythrocyte membranes and the level of energy metabolism of the cell turned out to be significant. A high diagnostic accuracy of these indicators was established as predictors: the proportion of deformed cells (AUC 0.939), a summarized viscosity index (AUC 0.932). Cluster analysis of the values of erythrocyte parameters – predictors of exacerbation made it possible to stratify the risk of exacerbation: at the most altered levels of parameters – the development of exacerbation after 2.5–4.5 months, intermediate levels – after 4–6 months, minimally changed – after 8–12 months (predictive accuracy – 92 %). Conclusions. The revealed electrical and viscoelastic parameters of erythrocytes should be considered as promising predictors of exacerbation in patients with IBD.

Aim of work is to study the compositional features of fatty acids (FA) of erythrocyte membranes in patients with diff erent localization of the tumor in colorectal cancer (CRC). Materials and methods . Using a chromatography-mass spectrometric system (GC/MS) Agilent 7000B based on three quadrupoles (USA), the composition of erythrocyte (Er) membranes of 129 patients with CRC was studied: (average age 63.2±9.4 years, of which 68 men and 61 women; 25 with proximal, 98 with distal tumor localization) and 35 people in the comparison group. Results . A greater degree of decrease in the levels of saturated, monounsaturated FAs (MUFAs), and, conversely, an increase in the levels of polyunsaturated FAs (PUFAs) in patients with distal tumor localization compared to healthy ones, was established than the same ratio in the pair “proximal localization of tumor RCC — healthy”. A greater degree of increase in the level of omega-3 PUFAs was noted than omega-6, which aff ected the ratio n-6 / n-3, which was signifi cantly reduced in cancer patients, to a greater extent with distal tumor localization. The most signifi cant for distinguishing tumors located in diff erent parts of the intestine were: saturated fatty acids — myristic C14:0 (p<0,001) and pentadecanoic C15:0 (p=0,012), omega-3 a-linolenic (C18:3; n-3) (p=0,02), whose levels were signifi cantly higher and, conversely, most of the omega-6 PUFAs (C18:2 n-6, C20:3 n-6, C20:4 n-6) and one omega-3 PUFAs — C22:6 n-3 (p<0,05), whose levels were signifi cantly lower with proximal localization of the tumor than with distal. Conclusion . The results obtained indicate the importance of taking into account the localization of the tumor in patients with CRC when conducti ng studies of metabolic profiles.

Aim of work is to study the features of the fatty acid (FA) composition of the membranes of erythrocytes (Er) and blood serum (BS) in patients with Crohn’s disease (CD) for possible use for diff erential diagnosis. Materials and methods . Using a gas chromatography-mass spectrometric system (GC/MS) based on three Agilent 7000B quadrupoles (USA), the composition of erythrocytes (Er) and blood serum (SC) of 60 people was studied: 19 — with Crohn’s disease (CD, 34±6,2 years), 21 — with unclassifi ed colitis (UCC, 35,2±4,7 years) and 20 healthy individuals (32,9±5,7 years). Results . It was found that the levels of most saturated, monounsaturated omega-9, omega-6 PUFAs were signifi cantly higher, and the content of the predominant part of omega-3, a number of omega-6 (linoleic, eicosadienoic, arachidonic) was lower than in healthy individuals. The relative content of FA in patients with unclassifi ed colitis turned out to be intermediate between those in patients with CD and healthy (p <0,0001–0,02). The obtained diff erentiating values of FA levels and their indices in the erythrocyte membranes made it possible to identify patients with suspected Crohn’s disease from those who were diagnosed with unclassifi ed colitis, which indicates the high potential of this approach for diff erential diagnosis. Conclusion . The created diagnostic panels (FA of blood serum and erythrocyte membranes) made it possible to diff erentiate patients with CD from healthy individuals with fairly high levels of sensitivity and specifi city. The revealed features of the levels of FA membranes of Er and BS, as well as their ratio in patients with CD, are promising for the purposes of diff erential diagnosis, including in cases of unclassifi ed colitis.

4 Федеральное государственное бюджетное учреждение науки Новосибирский

Background: Epidemiological studies performed in different countries have identified a number of trends that allow to predict the problems related to the prevalence of inflammatory bowel diseases (IBD), their severity and healthcare resources utilization. Aim: To present comparative results of two large epidemiological studies of IBD in the Russian Federation (RF), i.e. ESCApe and ESCApe-2. Materials and methods: Two multicenter cross-sectional cohort studies with a similar design were performed at three-year interval. The studies had the common aim: to identify social and demographic and clinical particulars of ulcerative colitis (UC) and Crohn’s disease (CD) in RF, as well as treatment options. Twenty (20) centers of gastroenterology from 17 RF regions participated in the ESCApe (2010–2011) and 8 centers from 7 RF regions in the ESCApe-2 study (2013–2014). Results: The ESCApe study included 1797 patients (1254 UC and 543 CD), whereas the ESCApe-2 included 1000 patients (667 UC and 333 CD). Patient demographic and social characteristics: In both studies, female: male ratio was similar in UC and CD. Patients’ age was almost identical: in UC, median age was 38 years and 40 years in ESCApe and ESCApe-2, respectively; in CD the corresponding values were 36 and 35 years. In ESCApe, the peak UC onset was at the age of 21 to 40 years, whereas in CD it was shifted towards younger age (22.5% of the patients manifested before 20 years) and the peak incidence was in three age groups (below 20 years, 21 to 30 and 31 to 40 years). A statistically significant difference between CD and UC was found only in the age group of 11 to 20 years (22.5% vs. 13.6%, respectively, p < 0.01). In ESCApe-2, median age of disease onset in UC and CD was approximately 30 years. In both studies, urban:rural ratio for UC and CD was 4:1. In ESCApe, the proportion of current smokers among CD patients was almost two-fold higher than among those with UC (15.6 and 8.8%, respectively, p < 0.001); the same trend was found in ESCApe-2 (15 and 7.3%, p < 0.001). Socioeconomic characteristics of patients in both studies were similar: 50 to 60% were at work (professional occupation and income levels were not studied); in ESCApe 30.9% of UC patients and 40.9% of CD patients had legal disability due to various reasons (including that related to UC and CD in 12,6 and 14.9%, respectively), whereas in ESCApe-2 the respective proportions were 35.7 and 51.1%. Clinical characteristics of patients: The time from the first UC symptoms to diagnosis was similar in both studies (median, 5 months in ESCApe and 4 months in ESCApe-2); in CD patients these parameters were significantly different in both studies (12 vs. 1 month). As for the severity of the disease, the UC patients in ESCApe had mild disease in 16%, moderate in 53%, and severe in 31%, whereas the respective proportions among the CD patients were 21, 44, and 35%. In ESCApe-2, there were no patients with severe disease; mild and moderate UC were diagnosed in 51.3 and 46.6% of the patients, respectively, and mild and moderate CD, in 52.3 and 47.3%. The frequency of left-side UC was similar: 38% in ESCApе and 34% in ESCApе-2. Proctitis was more frequent in the first study (33 vs. 11%, p < 0.01), and total UC was more frequent in the second study (29 vs. 55%, p < 0.02). There were no significant differences between ESCApe and ESCApe-2 in the main CD localizations: terminal ileitis was seen in 31.3 and 35.4% of the patients, respectively, ileocolitis in 33.4 and 37.8%, colitis in 25.6 and 32.1%. The upper gastrointestinal involvement In ESCApе was found 4.4%, and mixed involvement in 5.3%. In both studies, extra-intestinal manifestations were more frequent in CD, than in UC: in ESCApe, 33.1% and 23% (р < 0.05), and in ESCApe-2 in 41.7 and 29.4%, respectively (р < 0.05). Peripheral arthropathies were most frequent. Ankylosing spondylitis was found in CD only, and primary sclerosing cholangitis, only in UC. Aphthous stomatitis was significantly more prevalent in CD in both studies. There were no significant differences in all other extra-intestinal symptoms (eye and skin involvement). Treatment characteristics: Treatment options before the study entry, as well as at the study inclusion visit were analyzed. In ESCApe, the majority of the patients had not been given any treatment before the study entry (49.1% with UC and 40.5% with CD). Three years later the situation was changing: in ESCApe-2, the proportion of treatment-naïve patients was 2.5 to 3-fold lower (15.3% with UC and 14.4% with CD), which was most probably related to increasing awareness of physicians. Before the study entry, most patients (40 to 70%) had been treated with 5-aminosalicylic acid (5-ASA). Before the second study, the patients were more frequently treated with glucocorticosteroids (GCS), immunosuppressors and genetically engineered biological agents (GEBA), but with no significant differences from the first study. 5-ASA prevailed also among the agents that were administered during the inclusion visits in both studies (80 to 90% UC patients and about 70% of CD patients). Compared to ESCApe, in ESCApe-2 there was a trend towards lower rate of GCS administration in UC and CD, but the differences did not reach the significance level. It may be explained by the absence of severe IBD types in ESCApe-2. In ESCApe, immunosuppressors were rarely used (in 14.4% of the UC patients and in 26.8% of the CD patients); however, in ESCApe-2 there were administered more frequently: up to 35.9% of the UC patients and 55.1% of the CD patients (р < 0.01 for both cases). It was unknown if immunosuppressors were used as monotherapy or in combination with GCS. Three years later, the rate of GEBA administration was also higher, but this increase was significant only in CD: 28.3% in ESCApe-2 vs. 9.2% in ESCApe (р < 0.01). According to the results of ESCApe, in the UC patients steroid resistance was seen in 23% and steroid dependency in 21%, whereas in the CD patients these values were 24 and 27%, respectively. In ESCApe-2 these parameters were not assessed. Conclusion: Both studies showed a number of patterns coinciding with the world trends, such as age and gender distribution of UC and CD patients, age at manifestation, the proportion of urban to rural residents, smoking status, prevalence and types of extra-intestinal symptoms. Unlike in European countries, moderate and severe forms of UC with extensive involvement are prevalent in RF. Low prevalence of mild and limited types of IBD is to be explained by underdiagnosis. Of note is the high proportion of patients with UC and CD treated with 5-ASA, although in CD these agents have demonstrated low efficacy. The rates of immunosuppressors and GEBA administration significantly increased in the second study, most likely, due to the implementation of a system of educational measures. Nevertheless, the rate of GEBA use in IBD remains low, which is to be related to their insufficient availability. In total, steroid resistance / steroid dependency rate amount to almost half of UC and CD cases. In general, some positive changes in the patient management are obvious in the second study. However, monitoring these changes over time could only be possible if similar studies would be performed at regular intervals.

Background : Epidemiological studies  performed in different countries  have identified a number  of trends  that  allow to predict  the problems  related to the  prevalence  of inflammatory  bowel  diseases  (IBD),  their  severity  and  healthcare resources utilization. Aim :  To  present   comparative   results of two large epidemiological  studies of IBD in the Russian Federation (RF), i.e. ESCApe and ESCApe-2. Materials     and     methods :     Two    multicenter cross-sectional cohort studies with a similar design were performed  at three-year interval. The studies had the common aim: to identify social and demographic and clinical particulars of ulcerative colitis (UC) and Crohn’s disease (CD) in RF, as well as treatment options. Twenty (20) centers of gastroenterology from 17 RF regions participated in the ESCApe (2010–2011) and 8 centers from 7 RF regions in the ESCApe-2 study (2013–2014). Results : The ESCApe study included 1797 patients (1254 UC and 543 CD), whereas   the   ESCApe-2  included   1000  patients (667 UC and 333 CD). Patient demographic and social characteristics : In both  studies, female: male ratio was similar in UC and CD. Patients’ age was almost identical: in UC, median  age was 38 years and 40 years in ESCApe and ESCApe-2, respectively; in CD the  corresponding  values were  36 and 35 years. In ESCApe, the peak UC onset was at the age of 21 to 40 years, whereas in CD it was shifted towards younger age (22.5% of the patients  manifested before 20 years) and the peak incidence was in three age groups (below 20 years, 21 to 30 and 31 to 40 years).  A statistically significant difference between CD and  UC was found  only in the  age group  of 11 to 20 years (22.5% vs. 13.6%, respectively, p u003c 0.01). In ESCApe-2, median age of disease onset in UC and CD was approximately 30 years. In both  studies, urban:rural ratio for UC and CD was 4:1. In ESCApe, the proportion of current  smokers among  CD patients  was almost  two-fold  higher than  among  those  with  UC (15.6  and  8.8%,  respectively, p u003c 0.001); the same trend was found in ESCApe-2 (15 and 7.3%, p u003c 0.001). Socioeconomic characteristics of patients in both studies were similar: 50 to 60% were at work (professional occupation and income levels were not studied); in ESCApe 30.9% of UC patients and 40.9% of CD patients had legal disability due  to various reasons  (including that related to UC and CD in 12,6 and 14.9%, respectively), whereas in ESCApe-2 the respective proportions  were  35.7 and  51.1%.  Clinical characteristics of patients : The time from the  first UC symptoms to diagnosis  was similar in both  studies  (median, 5 months  in ESCApe and 4 months  in ESCApe-2); in CD patients  these parameters were significantly different in both studies (12 vs. 1 month). As for the severity of the disease, the UC patients  in ESCApe had  mild disease  in 16%, moderate in 53%, and severe in 31%, whereas the respective proportions among  the  CD patients  were 21, 44, and  35%. In ESCApe-2, there were no patients  with severe disease;  mild and  moderate UC were  diagnosed  in 51.3 and  46.6% of the  patients, respectively, and mild and moderate CD, in 52.3 and 47.3%. The frequency of left-side UC was similar: 38% in ESCApе and 34% in ESCApе-2. Proctitis was more frequent in the  first study  (33 vs. 11%, p u003c 0.01), and  total UC was more frequent  in the second  study (29 vs. 55%, p u003c 0.02). There were no significant differences between ESCApe and ESCApe-2 in the main CD localizations: terminal ileitis was seen  in 31.3 and 35.4% of the  patients,  respectively,  ileocolitis in 33.4 and 37.8%, colitis in 25.6 and 32.1%. The upper gastrointestinal involvement In ESCApе was found 4.4%, and mixed involvement  in 5.3%. In both studies, extra-intestinal  manifestations were more frequent  in CD, than  in UC: in ESCApe, 33.1% and 23% (р u003c 0.05), and in ESCApe-2 in 41.7 and 29.4%, respectively   (р u003c 0.05).   Peripheral   arthropathies were  most  frequent. Ankylosing spondylitis  was found in CD only, and primary sclerosing cholangitis, only in UC. Aphthous  stomatitis  was significantly more prevalent in CD in both studies. There were no significant differences in all other extra-intestinal symptoms  (eye and skin involvement). Treatment characteristics : Treatment options before the  study entry, as well as at the  study inclusion visit were analyzed. In ESCApe, the majority of the patients  had not been given any treatment before the study entry (49.1% with UC and 40.5% with CD). Three years later  the  situation  was changing: in ESCApe-2, the  proportion of treatment-naive patients was 2.5 to 3-fold lower (15.3% with UC and 14.4% with CD), which was most probably related to increasing  awareness  of physicians. Before the study entry, most  patients  (40 to 70%) had  been treated with 5-aminosalicylic acid (5-ASA). Before the  second  study,  the  patients   were  more  frequently  treated with  glucocorticosteroids (GCS), immunosuppressors and  genetically  engineered biological agents  (GEBA),  but  with no significant differences  from the  first study. 5-ASA prevailed also  among  the  agents  that  were  administered during  the  inclusion visits in both  studies  (80 to 90% UC patients  and  about  70% of CD patients). Compared   to  ESCApe,  in  ESCApe-2  there   was a trend  towards  lower rate of GCS administration in UC and CD, but the differences did not reach the significance level. It may be explained  by the absence of severe IBD types in ESCApe-2. In ESCApe, immunosuppressors were rarely used (in 14.4% of the UC patients  and in 26.8% of the CD patients); however, in ESCApe-2 there were administered more  frequently: up to 35.9% of the  UC patients and 55.1% of the CD patients  (р u003c 0.01 for both cases). It was unknown  if immunosuppressors were used as monotherapy or in combination with GCS. Three years later, the rate of GEBA administration was also higher, but  this increase  was significant only in CD: 28.3%  in ESCApe-2 vs. 9.2% in ESCApe (р u003c 0.01). According to the results of ESCApe, in the UC patients steroid resistance was seen in 23% and steroid dependency in 21%, whereas in the CD patients these values were 24 and 27%, respectively. In ESCApe-2 these  parameters were not assessed. Conclusion :  Both studies  showed  a  number   of patterns coinciding  with  the  world  trends,  such as age and gender  distribution  of UC and CD patients, age at manifestation, the proportion of urban to rural residents, smoking status, prevalence and types of extra-intestinal  symptoms. Unlike in European countries, moderate and severe forms of UC with extensive involvement are prevalent in RF. Low prevalence  of mild and limited types of IBD is to be explained by underdiagnosis. Of note is the high proportion of patients  with UC and CD treated with 5-ASA, although in CD these  agents  have demonstrated low efficacy. The rates of immunosuppressors  and GEBA administration significantly increased  in the second  study, most likely, due to the  implementation of a  system  of educational measures. Nevertheless, the rate of GEBA use in IBD remains low, which is to be related to their insufficient availability. In total, steroid resistance / steroid dependency rate amount  to almost half of UC and CD cases. In general, some positive changes  in the patient  management are  obvious  in the  second study. However, monitoring  these  changes  over time could only be possible if similar studies would be performed at regular intervals.

Inflammatory bowel diseases (IBD) are chronic recurrent immune-mediated inflammation of the gastrointestinal tract. Now it is not unified system of monitoring patients with IBD in Russia, but there is information from different regions about the prevalence of disease. There are the registers in few big cities. From 2003 the registers of IBD have been done in Novosibirsk. The register data can give us the possibility to estimate the various real-time data of the disease, to analyze the effect of the treatment , to evaluate risk factors for the disease in real clinical practice. Among the patients with ulcerative colitis decreased the number of patients with recurrent and continuous increase in the number of patients with distal forms, which is probably due to the more skillful conduct of patients. In general, it decreased the number of patients with Crohn's disease with continuously relapsing course option, reflecting, perhaps, improved treatment. Decline in the proportion of persons with the localization process, only in the colon, which is associated with greater availability of diagnostic methods for destruction of the small intestine. The registry was created in April 2012 and includes patients registered up to October 2015.

Inflammatory bowel diseases (IBD) are chronic recurrent immune-mediated inflammation of the gastrointestinal tract. Now it is not unified system of monitoring patients with IBD in Russia, but there is information from different regions about the prevalence of disease. There are the registers in few big cities. From 2003 the registers of IBO have been done in Novosibirsk. The register data can give us the possibility to estimate the various real-time data of the disease, to analyze the effect of the treatment, to evaluate risk factors for the disease in real clinical practice. Among the patients with ulcerative colitis decreased the number ofpatients with recurrent and continuous increase in the number of patients with distal forms, which is probably due to the more skillful conduct of patients. in general, it decreased the number of patients with Crohns disease with continuously relapsing course option, reflecting, perhaps, improved treatment. Decline in the proportion of persons with the localization process, only in the colon, which is associated with greater availability of diagnostic methods for destruction of the small intestine. The registry was created in April 2012 and includes patients registered up to October 2015.

This review deals with the relationship between red blood cells and nitric oxide, the role of erythrocytes as participants of vasoregulation. There were the results of studies on the physiological origin of vasoactive NO under hypoxic conditions, sources of nitric oxide associated with erythrocytes. The data of the NO effect on the erythrocyte deformability have been analyzed. The hypothesis of insufficient NO bioavailability during blood storage caused by degenerative changes in red blood cells (increased levels of free hemoglobin and microparticles from erythrocytes) was presented. The results of evaluation of hemoglobin associated with NO by means of Raman-spectroscopy were given. Prospects have been identified in the diagnosis and therapy related to the definition and changes in levels of erythrocyte-derived NO and ATP.