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These recommendations are intended for primary care professionals: internists, general practitioners, paramedics and include a statement of the basic requirements for the follow-up of patients with a number of diseases of the digestive system. The main material of the methodological recommendations is presented by adapted sections from modern clinical recommendations of specialized societies on certain nosological forms of diseases and current regulatory federal documents on dispensary supervision of the adult population. The guidelines were approved by the Perm Regional United Organization “Professional Medical Community of the Perm Region” and the Ministry of Health of the Perm Region. Also, the main provisions of the recommendations were presented and approved at the National Congress of the Society of Therapists (November 19, 2021).

Objective: To present a clinical description of the observation of a patient with Crohn’s disease (CD) with extraintestinal manifestations in the form of granulomatous alveolitis.Materials and Methods: A brief review of the literature on the current understanding of the prevalence and clinical manifestations of lung lesions in inflammatory bowel diseases (IBD) and CD, as well as a description of a patient with this pathology with the results of autopsy is presented.Results: The rare presence of granulomatous lung lesions in a patient with CD was proved.Conclusion: Difficulties in the differential diagnosis and treatment of CD lung lesions are shown. In particular, suspicion of tuberculous lesion, lung abscess creates potential risks of generalization of the process when using such therapeutic effects as glucocorticosteroids, cytostatics, immunosuppressants, biological genetically engineered drugs and active surgical intervention. The authors hope that the described observation will alert doctors in terms of possible systemic pulmonary lesions in CD.

Aim. To study significance of platelet count and values of aspartate aminotransferase and tumor necrosis factor-α in the evaluation of the severity of liver fibrosis in chronic hepatitis C and for the development of fibrosis index calculation formula.Material and Methods. The study included 70 patients with chronic hepatitis C end 30 healthy persons. Liver density was estimated by ultrasound elastography.Results. The correlation analysis revealed strong relationships between the ultrasound elastography findings of fibrosis stage and the platelet count (r=0.83), aspartate aminotransferase (r=0.83), and tumor necrosis factor-α (r=0.81). The optimal separation points of laboratory tests for fibrosis exclusion were identified as follows: platelet count>270×109 /L (test sensitivity=96.2%), aspartate aminotransferase level2.5 corresponded to the severe fibrosis/cirrhosis of the liver (F3-4) with diagnostic sensitivity of 83% and specificity of 78%.Conclusion. Platelet count, the values of aspartate aminotransferase and tumor necrosis factor-α levels, fibrosis index, and laboratory test data can be used for ruling out fibrosis in chronic hepatitis C patients as well as for stratification of liver fibrosis stages.

Aim. To study the blood serum interleukin-6 (IL) and circulating immune complexes (CIC) levels in patients with ulcerous colitis (UC), depending on the severity of disease attack, colonic inflammation dissemination, and presence of abenteric manifestations. Materials and methods. One hundred patients with UC in the phase of active inflammation were examined. Blood serum IL-6 and CIC concentrations were studied with IFA method. Results. 88,5 % of UC patients in the phase of active inflammation showed an elevated mean IL-6 index, 80 % had increased CIC concentration as compared with normal values. The highest IL-6 and CIC levels were obtained in case of severe forms of disease (11,50 (7,30–23,65) pg/ml and 115,50 (105,00–118,00), respectively); CIC and IL-6 levels were significantly higher in patients with abenteric manifestations and frequently relapsing course in comparison with patients, having rare UC relapses (p < 0,005). Strong direct correlations of IL-6 and CIC with each other (r = 0,65; p = 0,001) as well as with the severity of pathological changes in the colon were established. Conclusions. Among patients with UC, significantly elevated blood serum IL-6 and CIC concentrations were determined. Patients with severe attack of disease as well as those with abenteric manifestations and frequent relapses demonstrated reliably higher levels of these indices. It is recommended to use determination of blood serum IL-6 and CIC levels as an available and informative method, permitting to estimate the degree of severity of inflammatory process in the colonic wall among patients with ulcerous colitis.

Aim. To study the possibility of using MELD scale for determining the degree of severity of hepatic cirrhosis (HC) and determine its diagnostic characteristics. Materials and methods. Thirty patients with HC, including 15 patients with compensated HC stage (class A+B) by Child-Pugh scale and 15 persons with decompensated HC (class C), were examined. Total blood bilirubin and creatinine concentrations were assessed, INR and MELD index were calculated. Results. Meld index with use of total bilirubin, creatinine indices and INR is increasing as HC is progressing from 5 at the compensated stage to 26 at the decompensated stage ( p < 0,001) and directly correlates with the degree of severity of cirrhosis, estimated by Child-Pugh scale ( r = 0,64; p = 0,005). The threshold value of MELD index to differentiate the compensated HC stage from the decompensated one was 11. Conclusions. Design parameter of MELD permits to differentiate the degrees of HC severity with sensitivity equal to 73,3 % and specificity - 84,6 %. When MELD index is less than or equal to 11, the compensated stage of HC is diagnosed, when it exceeds 11, the decompensated cirrhosis is specified.

The study was carried out to evaluate significance of interleukin-6 (IL-6) and polymorphism of gene IL-6 (C174G) under liver cirrhosis of viral, alcoholic and mixed etiology. The blood of patients with liver cirrhosis of viral (n=48), alcoholic (n=11) and mixed (n=10) genesis was used for analyzing indices, level of IL-6 and polymorphism of gene IL-6 (C174G). In patients with liver cirrhosis independently of etiology increasing of concentration of IL-6 was established as compared with control group (p0.001). The gene reliably correlated with marker of cytolysis (r=0.32; p=0.009), direct bilirubin (r=0.26; p=0.04), gamma-glutamyltranspeptidase (r=0.36; p=0.004), albumin (r=0.59; p0.001) and degree of severity of liver cirrhosis according the Child-Pugh scale (r=0.76; r0.001). The concentration of IL-6 was significantly higher in patients with alcoholic liver cirrhosis tahn in patients with viral and mixed genesis of disease (p=0.02 and p=0.02 correspondingly). The analysis of prevalence of genotypes and alleles of polymorphism of gene IL-6 (C174G) in groups of donors and patients with liver cirrhosis in the Permskii Kraii established no reliable differences in rate of occurrence of minor allele G and its association with production of IL-6 in examined cohorts (p=0.82 and p=0.29 correspondingly). This result indicates absence of relationship of probability of immune disorders and their genetic determination. The development of liver cirrhosis independently of etiologic factor is characterized by hyper-production of anti-inflammatory cytokine reflecting severity of lesion of hepatocytes, intensity of inflammatory process and progression of disease. The more intensive production of IL-6 was observed in case of alcoholic genesis of disease that conditioned fast progression of cirrhosis.

To develop a mathematical model and evaluate its prognostic significance for determining the severity of attack (SA) in patients with ulcerative colitis (UC) on the basis of minimally invasive laboratory inflammatory tests and albumin. The study involved 64 patients (33 men and 31 women) with UC in the stage of active inflammation. The method for diagnosing SA was performed by determining the concentration in the blood of tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), α2-globulin and albumin. Truelove and Witts criteria (1955) were used as a reference method for the evaluation of SA in patients with UC. In constructing a mathematical model, the severity of the attack of the UC emerged as a dependent variable. As independent variables or predictors - five laboratory parameters: TNF-α, CRP, ESR, α2-globulins and albumin, which had a high relationship with SA. At SA value in the range from 0 to 0.5, absence of attack or remission of the disease is determined, SA value in the range from 0.5 to 1.2 corresponds to mild severity of UC attack, SA value in the range from 1.2 to 2.2 corresponds to the moderate severity of the attack of the UC, at SA more than 2.2 one should speak of a severe attack of the UC. The model is statistically significant: the Fisher test F = 439.9; p0.0001, multiple R = 0.981; R2 = 0.961. The diagnostic sensitivity of this mathematical model was 98.4%, specificity - 96.7%. The index of the severity of the attack, calculated by the formula proposed by us, is able to differentiate the mild, moderate and severe SA, including the isolation of patients with a stage of remission. In this case, the method is non-traumatic, has a low cost and high sensitivity and specificity.

To study the rs1001179 polymorphism of the catalase (CAT) gene and to estimate the serum levels of the enzymes catalase and glutathione peroxidase (GP) in patients with chronic hepatitis C (CHC) and in those with ulcerative colitis (UC) in the Perm Territory.Ninety patients with reactivation-phase CHC and 50 patients with exacerbation-phase UC were examined. The serum levels of catalase and GP were determined and the polymorphic variants of the marker of CAT gene rs1001179 in the DNA isolated from whole blood were found in all the patients.In the CHC and UC groups, the levels of catalase and GP were found to be lower than that in apparently healthy individuals. Furthermore, both groups showed a direct correlation between the activities of the enzymes. In the patients with CHC and in those with UC, the spread of genotypes and alleles generally failed to virtually differ from that in the control group. The G/G genotype was prevalent in all the groups. In the patients with CHC, the minor A allele demonstrated a significant inverse correlation with the enzyme catalase (r = -0.16; p = 0.02) and GP (r = -0.13; p = 0.047).The lower serum levels of catalase and GP are indicative of oxidative stress in the patients with CHC or UC. In the patients with CHC, the significant correlation of the pathological rs1701179 A allele marker with the processes of synthesis of antioxidant enzymes may suggest that CAT gene polymorphism in the A/A homozygotes might affect the regulation mechanism involved in the antioxidant system in the liver.Цель исследования. Изучить полиморфизм rs1001179 гена каталазы (CAT) и оценить уровень ферментов каталазы и глутатионпероксидазы (ГП) в сыворотке крови у больных хроническим гепатитом С (ХГС) и язвенным колитом (ЯК) в Пермском крае. Материалы и методы. Обследовали 90 пациентов с ХГС в фазе реактивации и 50 больных ЯК в фазе обострения. У всех больных определяли уровень каталазы и ГП в сыворотке крови и выявляли полиморфные варианты маркера rs1001179 гена САТ в ДНК, выделенной из цельной крови. Результаты. Уровень каталазы и ГП в группах пациентов с ХГС и ЯК оказался достоверно ниже, чем у практически здоровых лиц. Кроме того, в обеих группах выявлена прямая корреляция активности ферментов между собой. Распространенность генотипов и аллелей у больных ХГС и ЯК в целом практически не отличалась от таковых в контрольной группе. Во всех группах преобладал генотип G/G. У больных ХГС минорный аллель А демонстрировал достоверную обратную корреляцию с ферментом каталазой (r=–0,16; р=0,02) и ГП (r=–0,13; р=0,047). Заключение. Снижение в сыворотке крови уровня каталазы и ГП свидетельствует о наличии оксидантного стресса у больных ХГС и ЯК. Наличие у больных ХГС достоверной корреляции патологического аллеля А маркера rs1001179 с процессами синтеза антиоксидантных ферментов позволяет сделать предположение о возможном влиянии полиморфизма гена САТ у гомозигот А/А на механизмы регуляции антиоксидантной системы в печени.

The study was carried out to evaluate biological reaction of endothelium-depended vasodilation and disorder of its regulation by humoral mediators of inflammation in patients with ulcerous colitis. And also to compare disorders of function of endothelium with content of cytokines in blood plasma and severity of inflammation in intestine. The examined sampling consisted of 90 patients with diagnosis of ulcerous colitis at the phase of exacerbation of disease. The concentration of humoral mediators of inflammation was established: tumor necrosis factor-alpha, interleukins-6 and -4, monocyte chemo-attractant protein-1. The content of endothelium growth factor of vessels in blood serum was determined as a marker of damage of endothelium. The functional condition of endothelium of vessels was evaluated on the basis of photoplethysmography and software support Pulsware (Samara). In case of ulcerous colitis hyper-secretion of humoral mediators of inflammation was established in blood serum: tumor necrosis factor-alpha, interleukins-6, monocyte chemo-attractant protein-1. The median of concentration of endothelium growth factor of vessels thrice exceeded the level specific for control group of healthy individuals. The disorder of biological reaction of endothelium-depended vasodilation was established in 95% of patients with ulcerous colitis. The reliable correlation relationship between concentration of humoral mediator of inflammation, endothelium growth factor of vessels and severity of destructive alterations in large intestine wall. The combination of disorders of humoral regulation of biological reaction of endothelium-depended vasodilation and markers of dysfunction of endothelium reflects activity of local destruction of tissue. The severity of clinical manifestation of ulcerous colitis substantiates functional interaction of inflammation reaction and angiogenesis. The detection of humoral mediators of inflammation and endothelium growth factor of vessels is reasonably to implement as non-invasive techniques of evaluation of severity of inflammation in wall of large intestine under ulcerous colitis.

In most fluorescent proteins absorbing and emitting light in the red and far-red spectral region (550–650 nm), the chromophore π system is extended by an acylimine substituent due to additional oxidation of a GFP-like structure. In contrast, photoactivatable protein asFP595 contains a chromophore, in which the acylimine substituent is replaced by a keto-group. Here we have investigated reactions bringing about the bathochromic shift in asFP595 spectra. Maturation kinetics analysis shows that, similarly to common red fluorescent proteins, asFP595 forms an intermediate with a protonated chromophore (absorbance at 420 nm), which isosbestically converts to the final mature form (568 nm). Mass-spectrometric analysis of the chromopeptide isolated from immature asFP595 indicates that the intermediate contains a GFP-like chromophore. It was also found that, upon GFP-like intermediate oxidation, an equimolar amount of hydrogen peroxide is generated. To further identify intermediate products of this oxidation reaction, mutagenesis of the first chromophore-forming amino acid residue was performed. It was found that in all mutants tested, the reaction does not entail acylimine formation and directly leads to protein fragmentation and keto derivative formation.

Practical aspects of preparation and prospects for practical use of a series of the metal oxide whiskers were studied. The procedures for the synthesis were proposed, and the phase composition, micromorphology, and electrochemical and sensor characteristics of the macroscopic (up to 5–10 mm long) whiskers in the Ba-V-O, Ba-Mn-O, and Sn-O systems were analyzed. The electroconducting BaV8O21-δ whiskers were prepared by the hydrothermal treatment. These whiskers possess stable electrochemical characteristics appropriate for the development of novel secondary current sources. The protonated form of the Ba6Mn24O48 whiskers produced by the isothermal vaporization of chloride fluxes is a mixed conductor with the proton and electron conductivity at a level of mS units at 25 °C. A new procedure by the thermal disproportionation of tin(ii) oxide under nitrogen was proposed for the growth of SnO2 whiskers of various morphology. The produced whiskers have substantial sensor sensitivity toward a series of toxic components of the gaseous medium, such as nitrogen dioxide.

Having analyzed the results obtained in the work, it is possible to conclude that the flux density of fast and thermal neutrons in the shell of fuel elements in EFA in REU-zone decreased on average by 5% for UO2 fuel and by 7% for U9%Mo fuel. Change of neutrons flux density during the cycle does not exceed 4% for both fuel types. On average the fuel burnup in reactor core during the cycle for UO2 and U9%Mo increased by 2.8%. It is 1% less that in HEU-zone, which is conditioned by higher initial loading of 235U in fuel assembly with REU fuel.