[WAYS TO SOLVE THE PROBLEM OF HOME PARENTERAL NUTRITION IN PATIENTS WITH SHORT BOWEL SYNDROME].

The purpose of the work is to identify the most optimal ways to solve the problem of home parenteral nutrition for patients with short bowel syndrome.Basics. Discussion of the current situation will help optimize the work of the Orphan Diseases Center, lead to a greater introduction of online technology, and aim at the search and implementation of new methods of treating patients in this category.Conclusion. The most optimal strategy has been proposed to improve the interaction between various specialists and patients in need of long-term parenteral nutrition.

Physiological Media in Studies of Cell Metabolism.

Changes in cell metabolism accompany the development of a wide spectrum of pathologies including cancer, autoimmune, and inflammatory diseases. Therefore, usage of inhibitors of metabolic enzymes are considered a promising strategy for the development of therapeutic agents. However, the investigation of cellular metabolism is hampered by the significant impact of culture media, which interfere with many cellular processes, thus making cellular models irrelevant. There are numerous reports that show that the results from in vitro systems are not reproduced in in vivo models and patients. Over the last decade a novel approach has emerged, which consists of adaptation of the culture medium composition to that closer to the composition of blood plasma. In 2017‒2019, two plasma-like media were proposed, Plasmax and HPLM. In the review, we have summarized the drawbacks of common media and have analyzed changes in the metabolism of cells cultivated in common and plasma-like media in normal and pathological conditions.

[Physiological Media in Studies of Cell Metabolism].

Changes in cell metabolism accompany the development of a wide spectrum of pathologies including cancer, autoimmune, and inflammatory diseases. Therefore, usage of inhibitors of metabolic enzymes are considered a promising strategy for the development of therapeutic agents. However, the investigation of cellular metabolism is hampered by the significant impact of culture media, which interfere with many cellular processes, thus making cellular models irrelevant. There are numerous reports that show that the results from in vitro systems are not reproduced in in vivo models and patients. Over the last decade a novel approach has emerged, which consists of adaptation of the culture medium composition to that closer to the composition of blood plasma. In 2017-2019, two plasma-like media were proposed, Plasmax and HPLM. In the review, we have summarized the drawbacks of common media and have analyzed changes in the metabolism of cells cultivated in common and plasma-like media in normal and pathological conditions.

[Comparison of measles incidence in different age groups with the intensity of specific humoral immunity in healthcare workers in Moscow].

INTRODUCTION: The study of the intensity of humoral immunity to the measles virus (Paramyxoviridae: Morbillivirus) (MV) remains relevant due to the ongoing registration of the cluster cases of measles (including nosocomial cases).The aim of the study was to analyze correlation between the intensity of the humoral immunity to measles virus and the measles incidence in different age groups of the Moscow residents. MATERIAL AND METHODS: A simple analytic study was carried out under the framework of measles prevention improvement program conducted in the subjects of the Russian Federation. The study included the analysis of the reasons for the increase in the proportion of seronegative individuals and the comparison of the results of seromonitoring with the data of age-related measles incidence. Throughout 2018, total 1,855 blood serum samples obtained from employees of a large hospital center in Moscow who were previously vaccinated against measles were tested for IgG antibodies (ABs) to MV. The subjects were divided into 11 groups according to their age. Statistical analysis of the obtained data was performed using nonparametric criteria. RESULTS AND DISCUSSION: The proportion of seronegative individuals among the staff of the medical facility decreased with age, from 38.5% in persons aged 19-23 to 0% among employees aged 64 and over. Persons aged 19-43 years were the most susceptible to measles infection, which was confirmed also by the highest incidence rate at these age groups (from 6.93 to 14.03 per 100,000 population). The age group most protected against measles was those over 64 years of age, who were all seropositive and had the lowest rates of incidence. This is probably due to the fact that by this age most of them have had a measles infection and have formed a sufficient immune response. At the same time, younger individuals living in the post-elimination era have only vaccine-induced ABs to MV, the level of which declines rapidly to non-protective values in the absence of boosterization due to the exposure to the wild-type strain of the pathogen. CONCLUSION: The monitoring of the MV-specific IgG- AB levels is required for employees in the medical institutions under the age of 35. Administration of the single dose of the appropriate vaccine is recommended for seronegative individuals.

[Safety of enhanced recovery after surgery (ERAS) protocol in the treatment of patients undergoing pancreatoduodenectomy]. / Otsenka bezopasnosti protokola uskorennogo vosstanovleniya (ERAS) v lechenii bol'nykh, perenesshikh pankreatoduodenal'nuyu rezektsiyu.

OBJECTIVE: To study the effectiveness of enhanced recovery after surgery (ERAS) protocol versus traditional perioperative management in patients with hepatopancreatobiliary tumors undergoing pancreatoduodenectomy. MATERIAL AND METHODS: The study included 111 patients who have undergone pancreatoduodenectomy between January 2014 and December 2019. Patients were divided into 2 groups: perioperative ERAS protocol (85 patients) and traditional treatment (26 patients). Postoperative complications, length of hospital-stay and incidence of readmissions were analyzed. RESULTS: Mean length of hospital-stay for ERAS protocol was 13.4±7.6 days, conventional management - 16.5±7.5 days (p=0.004). Postoperative 30-day mortality was 8.24 and 7.7% in both groups, respectively (p=1.0). Intraoperative blood loss was significantly less in the ERAS group (248.24±214.0 vs. 321.15±155.0 ml, p=0.004). Overall incidence of postoperative complications was 56.5% and 65.4%, respectively (p=0.420). However, incidence of Clavien-Dindo grade IV complications was significantly higher in case of traditional treatment (19.2 vs. 4.7%, p=0.015). Readmission rate within 30 days was slightly less in the ERAS group (6.4 vs. 20.8%, p=0.052). CONCLUSION: Enhanced recovery after surgery protocol is safe, reduces the number of postoperative complications, length of hospital-stay and rate of readmissions.

[Histological remission of ulcerative colitis with combined anti-cytokine and cell therapy].

AIM: To conduct comparative analysis of histological remission in patients with moderate and severe ulcerative colitis (UC), receiving biological therapy vedolizumab, mesenchymal stem cell (MSC) treatment and combined stem cells and vedolizumab therapy. MATERIALS AND METHODS: We studied biopsies of 75 patients with total or left-sided moderate and severe ulcerative colitis, divided into groups depending on treatment. The first group of UC patients (n=29) received stem cell therapy 2 mln per kg; the second group of UC patients (n=27) received vedolizumab and the third group (n=19) MSC and vedolizumab. The efficacy of treatment was assessed by C reactive protein (CRP), Mayo score (MS), fecal calprotectin (FC) and Geboes score (GS). RESULTS: We determined medium correlation between basic FC and MS before treatment (r=0.6605, p0.05). After 12 weeks of treatment in the first group of UC patients (n=29) CRP was 7.82.1 mg/l, FC 409.344.85 g/g, medium GS 1.20.1 points. After 12 weeks of treatment in the second group of UC patients (n=27) CRP was 8.41.4 mg/l, FC 435.547.3 g/g, medium GS 1.350.15 points. After 12 weeks of treatment in the third group of UC patients (n=19) CRP was 6.41.1 mg/l, FC 290.617.5 g/g, medium GS 0.90.1 points. We proved strong direct relationship between FC and GS after 12 weeks of treatment in UC patients, receiving MSC (r=0.8392, p0.05). The statistically significant majority of patients, achieved histological remission, have less than 5-year duration of disease. CONCLUSION: Our study showed that clinical and endoscopic remission in UC patients does not always correlate with histological remission. Combined anti-cytokine and stem cells therapy contributes to achieve deep remission and decrease mucosa inflammation rather than single MSC or vedolizumab treatment. Deep remission could be achieved by earlier start of biological therapy. FC could be a predictor and marker of mucosa healing and histological remission.

Response of Human Small Intestinal Epithelium to Fractionated Irradiation: Dynamical Modeling Approach.

A biologically motivated mathematical model of the dynamics of the small intestinal epithelium in humans treated with fractionated radiotherapy has been developed and is further investigated here. This model, originating from our previous work, is implemented as a system of nonlinear ordinary differential equations, in which the variables and parameters have a clear biological meaning. The model also includes, as input, the key parameters of fractionated irradiation. The modeling results on the dynamical response of the human normal small intestinal epithelium to fractionated radiation therapy regimens were in agreement with the corresponding empirical data, which, in turn, demonstrates the capability of the developed model for predicting the dynamics of this vital body system in humans receiving fractionated radiotherapy. It is also revealed that the cumulative damage effects of hypofractionated radiation therapy regimens on the human normal small intestinal epithelium are somewhat less pronounced than those of conventional fractionated radiation therapy regimens with the same total doses.

Analysis of the Domains of Hepatitis C Virus Core and NS5A Proteins that Activate the Nrf2/ARE Cascade.

The hepatitis C virus (HCV) triggers a chronic disease that is often accompanied by a spectrum of liver pathologies and metabolic alterations. The oxidative stress that occurs in the infected cells is considered as one of the mechanisms of HCV pathogenesis. It is induced by the viral core and NS5A proteins. It is already known that both of these proteins activate the antioxidant defense system controlled by the Nrf2 transcription factor. Here, we show that this activation is mediated by domain 1 of the NS5A protein and two fragments of the core protein. In both cases, this activation is achieved through two mechanisms. One of them is mediated by reactive oxygen species (ROS) and protein kinase C, whereas the other is triggered through ROS-independent activation of casein kinase 2 and phosphoinositide 3-kinase. In the case of the HCV core, the ROS-dependent mechanism was assigned to the 37-191 a.a. fragment, while the ROS-independent mechanism was assigned to the 1-36 a.a. fragment. Such assignment of the mechanisms to different domains is the first evidence of their independence. In addition, our data revealed that intracellular localization of HCV proteins has no impact on the regulation of the antioxidant defense system.

Synthesis and evaluation of novel lipopeptide as a vehicle for efficient gene delivery and gene silencing.

Nucleic acid-based therapeutics have recently emerged as a new class of next generation agents for treatment and prevention of viral infection, cancer, and genetic disorders, but their wide use is limited by their relatively weak delivery into target cells. Usage of synthetic cationic amphiphiles with peptide hydrophilic domain as agents for non-viral gene delivery is an attractive approach. We developed the schemes for the synthesis of aliphatic peptides with different length of the hydrocarbon chains in hydrophobic domains and different amino acids in polar head. For the obtained derivatives we determined transfection efficiency, critical vesicle concentration, particle size, ζ-potential and aggregates stability. We have found that the transfection efficiency is increased if the ornithine is a part of polar head in an amphiphile. The most promising amphiphile for liposomal formation OrnOrnGlu(C16H33)2 was examined more carefully. It has been shown that the lipopeptide possesses low toxicity (in vitro and in vivo) and high transfection efficiency with pDNA and siRNA in different cell lines. In addition, the production of liposomes based on this lipopeptide is simple, quick and cheap. Thus OrnOrnGlu(C16H33)2 is a promising vehicle for gene delivery and gene silencing.

[CHANGE OF ANTICOAGULANT EFFECT OF RIVAROXABAN DURING A DAY].

The article presents an assessment of anticoagulant effect of rivaroxaban in 35 patients with thromboembolic diseases. The results of expressed anticoagulant effect of rivaroxaban were obtained during a day (or more). The data of increase in sensitivity to thrombomodulin indicated about work enchancement of protein C system against the background of rivaroxaban therapy.

[THE CLINICAL ORGANIZATIONAL SUBSTANTIATION OF NEW TECHNOLOGY OF HOSPITAL PSYCHIATRIC CARE].

The new technology of hospital psychiatric care, developed and implemented in the Mordovia republican clinical hospital, permits resolving problems of hospitalism, lethality, pharmaceutical resistance and others. The essence of this technology is in staging of hospital care under condition of intensification and standardization of curative diagnostic process, implementation of complex approach to treatment of psychiatric disorders. The patient sequentially passes through three stages: intensive diagnostics and intensive treatment (intensive care department, intensive therapy department), supportive therapy (general psychiatric department); rehabilitation measures (curative rehabilitative department). The concentration of resources at the first stage, application of intensive therapy techniques permit in the shortest period to arrest acute psychotic symptomatic. The described new technology of hospital psychiatric care permits enhancing effectiveness of treatment, significantly shorten period of hospitalization (37.5 days), to obtain lasting and qualitative remission, to rehabilitate most fully social working status of patient and to significantly decrease lethality.

Myeloid leukemia risk assessment and dynamics of the granulocytopoietic system in acutely and continuously irradiated humans: modeling approach.

A dynamic modeling approach to the risk assessment of radiogenic myeloid leukemia is proposed. A basic tool of this approach is a biologically motivated mathematical model of the granulocytopoietic system, which is capable of predicting the dynamics of blood granulocytes and bone marrow granulocytopoietic cells in acutely and chronically irradiated humans. The performed modeling studies revealed that the dose dependence of the scaled maximal concentration of bone marrow granulocytopoietic cells with radiation-induced changes, which make a cell premalignant, and the dose dependence of the scaled integral of the concentration of these cells over the period of the response of the granulocytopoietic system to acute irradiation conform to the dose dependence of excess relative risk for myeloid leukemia among atomic bomb survivors in a wide range of doses and in a range of comparatively low doses, respectively. Additionally, the dose dependence of the scaled integral of the concentration of these cells over the period of the response of the granulocytopoietic system to continuous irradiation with the dose rate and durations, which were used in brachytherapy, conforms to the dose dependence of excess relative risk for leukemia among the respective groups of exposed patients. These modeling findings demonstrate the potential to use the proposed modeling approach for predicting the excess relative risk for myeloid leukemia among humans exposed to various radiation regimes. Obviously, this is especially important in the assessment of the risks for radiogenic myeloid leukemia among people residing in contaminated areas after an accident or explosion of a radiological device, among astronauts on long-term space missions, as well as among patients treated with radiotherapy.

[METABOLIC COMPLICATIONS IN PARENTERAL-ENTERAL NUTRITION].

Analysis and prevention of complications of parenteral and enteral nutrition recently receiving more attention. This is because a full infusion-nutritive correction ensures shorter postoperative period and can be used as the protector of metabolic damage, aggravating, and sometimes determining operating.

[GENETIC ASPECTS OF INFLAMMATORY BOWEL DISEASE AND TREATMENT USING SURGICAL AND NUTRITIONAL CORRECTION].

Currently nutrigenetics is an independent high technology. Patients with genetically caused and complicated ulcerative colitis needs earlier surgery treatment than patient without genetically caused ulcerative colitis. Patients with no genetic predisposition can be treated conservatively over a long time.

Analysis of hematopoiesis dynamics in residents of Techa riverside villages chronically exposed to nonuniform radiation: modeling approach.

A profound approach to the analysis of clinical data on the dynamics of major hematopoietic lineages (granulocytopoietic, thrombocytopoietic, and erythrocytopoietic systems) in chronically irradiated humans is proposed. It is based on recently developed mathematical models of these systems in humans, which enable one to study and interpret clinical hematological data. The developed approach is applied to the analysis of statistically processed clinical data, which were obtained under hematological examinations of residents of Techa riverside villages. These people were exposed to chronic irradiation with varying dose rate due to the radioactive contamination of the river basin by the Mayak Production Association. In the course of modeling studies, the relationship between the dynamics of aforementioned systems in examined individuals and the variation of chronic exposure dose rate over the considered period of time is revealed. It is found that the models are capable of reproducing common regularities and peculiarities of the dynamics of systems on hand, including the decreased stationary levels of blood cell concentrations during the period of maximum radiation exposure, the recovery processes during the period of decrease of exposure dose rate, and the prevalence of younger bone marrow granulocytopoietic cells over more mature ones during the entire period. The mechanisms of such effects of chronic irradiation on the hematopoietic lineages are revealed on the basis of modeling studies. All this testifies to the efficiency of employment of the developed models in the analysis, investigation, and prediction of effects of chronic irradiation on human hematopoietic system.

[Solved and unsolved problems of nutritional support in surgical gastroenterology].

The article has revealed the relevance of nutriciology as a science, classification and types of nutritional support. Nutritional support--diagnostics and the metabolic correction of arising violations of various kinds of homeostasis, aimed at ensuring the functioning of the systems of protein-energy synthesis and intermediate exchange of nutrients, vitamins, macro--and microelements, or a temporary replacement therapy of their failure. The notions of "lack of food", "artificial" food, protein-energy insufficiency with the exception of the syndromes of malabsorption, alimentary anemia, the effects of protein-energy malnutrition, consumptive disease, starvation have been interpreted. It was noted that nutriciology has taken place as a science. The problems of prognostification of nutritional deficiency, assessment of nutritional risk, the organization of nutritional support in the hospital and at home have been presented. Some fundamental bases of enteral probe feeding have been described.

[Prospects for nutritional support of patients with ulcerative colitis].

The article presents the data on the assessment of the degree of severity of ulcerative colitis and the selection of nutritional support with the account of the violations of the nutrition status with ulcerative colitis.

[Comparative analysis of the immune response to DNA constructions encoding hepatitis C virus nonstructural proteins].

A promising approach to construction of antiviral vaccines consists in activation of cellular immunity with the DNA vaccines. The goal of this work was to evaluate the efficacy of genetic immunization of mice with DNA pcNS3-NS5B encoding five hepatitis C virus (HCV) nonstructural proteins: NS3, NS4A, NS4B, NS5A, and NS5B in comparison with plasmids containing genes of same individual nonstructural proteins. The DNA constructions were injected intramuscularly in DBA mice three times. The humoral immune response was assessed with ELISA; cellular immune response--in blast transformation reaction, by quantitation of CD4+ and CD8+ T cell proliferation using flow cytofluorometry, by intracellular synthesis and secretion of IFN-gamma and IL-2 in ELISpot and ELISA. It was found that the functionally active T cell response was achieved to antigens presenting NS3, NS4, NS5A, and NS5B epitopes of different HCV genotypes in response to pcNS3-NS5B plasmid and was stronger than that to plasmids carrying individual genes. A high proliferation rate of CD4+ T cells, secretion of IL-2 and IFN-gamma, induction of anti-NS3 and anti-NS5B IgG2a were demonstrated. These findings indicate that DNA construction pcNS3-NS5B is one of promising candidates for anti-HCV vaccine developing.

[Immunological criteria for evaluation of nutritional support in ulcerative colitis].

The article presents the data on the assessment of nutritional status, taking into account humoral immunologic criteria of patients with ulcerative colitis.

[Use of thrombin generation assay for the evaluation of coagulation and anticoagulant activity of hemostasis system in patients with abdominal sepsis].

Generally recognized factor, which complicates the course of sepsis, is the development of hypercoagulation syndrome. The increase of thrombin coagulation indicates on the elevation of risk of thrombus formation in microcirculation vessels, which could cause the formation of multiple organ failure. The thrombin generation assay is a new method of the evaluation of homeostasis system status. The test reflects the fermentation activity of thrombin and shows the functional condition, which arises in the interaction of procoagulant and anticoagulant. The diagnosis of generalized peritonitis had 30 patients (18 men and 12 women, aged 61+/-18,3 years) and they were included in the research. It was shown, that the use of thrombin generation assay in patients with the abdominal sepsis could give the well-timed analysis of hypercoagulation changes and the assessment of protein C system investment in the thrombin generation.