[ECONOMIC BURDEN AND CURRENT STATUS OF THE DRUG SUPPLY MANAGEMENT FOR IMMUNE INFLAMMATORY DISEASES (BY EXAMPLE OF ULCERATIVE COLITIS AND CROHN'S DISEASE)].

AIM: to estimate the quality and availability of medical care for patients with ulcerative colitis (UC) and Crohn's disease (CD), to assess the impact of the economic burden of these diseases on the healthcare budget of Russia and to systematize the main problems in the organization of medical care and drug supply for patients with inflammatory bowel diseases (IBD). Regional IBD databases (2016-2018), official statistical databases, costs of treatment and results of expert interviews with specialists in IBD were used in the study. The analyzed databases showed 104,668 patients with UC in Russia in 2018 (prevalence rate 71 per 100,000 people) and 66,647 patients with CD (prevalence rate of 45 per 100,000 people). The economic burden including agents for biologic therapy (ABT) for the UC was 39.54 billion rubles a year (495 rubles per capita), and CD - 32.98 billion rubles a year (378 rubles per capita). It requires an additional 9.87 billion rubles annually for UC and 9.20 billion rubles annually for CD patients to provide the complete supply with ABT. The annual burden of IBD is 72.52 billion rubles, which is comparable to the costs of other socially significant diseases, including malignant tumors. It shows the high social and economic value of IBD for the country. The main problems of medical care and drug supply for IBD patients are the mismatch of official statistical data and real IBD prevalence in Russia due to absence of comprehensive register and the insufficient supply with ABT due to limited funding. A federal center for IBD should be founded for better quality of registration, for the precise monitoring and for the active management of personal drug supply.

[Rehabilitation program for patients with low anterior resection syndrome]. / Reabilitatsionnaya programma dlya bol'nykh rakom pryamoi kishki s sindromom nizkoi perednei rezektsii.

Surgical treatment of rectal cancer and sphincter-preserving low anterior resection results to evacuation disorders («low anterior resection syndrome¼ - LARS). There are no clinical recommendations for the treatment of patients with LARS as well as a rehabilitation program for them. OBJECTIVE: To develop a rehabilitation program for patients with low anterior resection syndrome. MATERIAL AND METHODS: The investigation was performed at 2 stages. During the first stage, 29 patients with LARS (17 (58.6%) men, mean age of the participants' 61.5±9.5 years), 12 (41.4%) women (mean age 61.2±7.8 years) were examined and received the course of conservative treatment with the use of biofeedback-therapy performed by the standard protocol. On the second stage, 17 patients (mean age 61.4±12.7 years) - 9 (52.9%) men, 8 (47.1%) women received biofeedback therapy in combination with tibial neuromodulation (TNM). Functional state of the rectum and the locking apparatus in all patients were evaluated by anorectal manometry: sphincterometry and studies of the reservoir function of the rectum before and after treatment. RESULTS: The developed complex of rehabilitation measures led to improved treatment results for patients with rectal cancer by improving the quality of life after low anterior resection, reducing the manifestations of LARS (by 47.8%). Stable positive results of treatment were maintained in 36.4% of patients, positive dynamics from the treatment according to the LARS scale decreased slightly in 54.5%, deterioration of indicators in 3-6 months after conservative rehabilitation was registered in 9.1% of cases. At the first stage maximal squeeze pressure improvement was reached in the whole cohort (p=0.047), at the second stage these trend was seen only for women for the pressure values at rest (p=0.01) and during squeeze (p=0.025). The data obtained allowed us to recommend a repeat course of treatment to 63.6% of patients. The authors modified and optimized a special complex of physical therapy for the rehabilitation of patients both in a medical institution and at home. These exercises are aimed at improving the functional state of the pelvic floor muscles and sphincter apparatus. CONCLUSION: Rehabilitation program for patients with low anterior resection syndrome should include: 1) biofeedback therapy to improve the holding function; 2) biofeedback therapy aimed at improving the reservoir function and sensitivity of the rectum to filling; 3) tibial neuromodulation. This program may help improving the contractility of the anal sphincter and reservoir function of the rectum, as well as the appearance of the urge to defecate.

[Intracellular Protein Degradation in Growth of Atlantic Salmon, Salmo salar L].

A brief review on the common characteristics and specific features of proteolytic machinery in fish skeletal muscles (based on Atlantic salmon, Salmo salar L., Salmonidae) has been given. Among a variety of proteases in the muscle tissue, those determining protein degradation level in developing and intensively growing muscles in salmon young and by this way regulating protein retention intensity and growth at all namely lysosomal cathepsins B and D and calcium-dependent proteases (calpains) were comprehensively studied. Revealed age-related differences in intracellular protease activity in salmon skeletal muscles indicate the role of proteolysis regulation in growth in general and a specific role of the individual proteolytic enzymes in particular. The data on negative correlation of cathepsin D and calpain activity levels in muscles and the rate of weight increase in juvenile salmon were obtained. A revealed positive correlation of cathepsin B activity and morphometric parameters in fish young presumably indicates its primary contribution to non-myofibrillar protein turnover.

[Activity of Enzymes Involved in the Energy and Carbohydrate Metabolism and the Level of Some Molecular-Genetic Characteristics in Young Salmons (Salmo salar L.) with Different Age and Weight].

In order to investigate the metabolic regulation in Atlantic salmon fries (Salmo salar L.) during their growth, development, and in the course of size divergence, age-related changes in the activity of enzymes involved in the energy and carbohydrate metabolism, including myosin heavy chain isoform expression, RNA/DNA ratio in the white muscles and liver of specimens at ages of 0+; 1+, and 2+, as well as correlations of these characteristics with the body weight of fish specimens were analyzed. Multidirectional changes in the activity of enzymes taking part in aerobic and anaerobic energy metabolism, as well as a decrease in the protein synthesis with age, were revealed. There was a positive correlation between the activities of cytochrome oxidase, lactate dehydrogenase, aldolase, and myosin gene expression in the muscles, cytochrome oxidase activity, glucose-6-phosphate dehydrogenase, and glycerol-3-phosphate dehydrogenase in the liver with the body weight of salmon specimens within the age groups.

[Comparative Characteristics of the Lipid and Fatty Acid Status of Eyed-Stage Atlantic Salmon Embryos Reared in Natural and Artificial Environments].

The lipid status of Atlantic salmon (Salmo salar L.) embryos has been compared between embryos developing in incubator nests installed in the natural environment (UmbaRiver, Kola Peninsula) and those developing in a laboratory (in aquaria). The developmental stage of eye pigmentation selected for comparison is characterized by the highest sensitivity of the embryos to environmental factors. The content of certain classes of total lipids and fatty acids was different between the two groups of embryos, and the ratios between the relative content values for some of the compounds were different as well. The difference may be due to environmental factors (temperature, oxygen levels, running water in the nests, etc.) affecting the developing embryos, and they may determine the subsequent embryonic and postembryonic development of the fish.

[Production of mycobacterial antigenes merged with cellulose binding protein domain in order to produce subunit vaccines against tuberculosis].

Protein genes Ag85A, Esat-6, and Cfp10 of Mycobacterium tuberculosis were sequenced using the database GenBank to implement selection and synthesis of primer pairs of given genes. PCR was used to obtain target amplicons of the genes. Chromosome DNA of M. tuberculosis H37Rv was used as the DNA amplification matrix. The PCR products were obtained using the plasmid pQE6, cloned, and amplified in the Escherichia coli M15 strain. Chimere products containing mycobacterial genes and cellulose binding protein domain (CBD), were obtained using the plasmid treated with restriction endonucleases. CBD fragment obtained using similar treatment of the ptt10 plasmid. The plasmids containing merged sequences of mycobacterial genes-antigenes and CBD were selected. The 3 mycobacterial genes were expressed in the E. coli M15 cells resulting in biosynthesis of corresponding recombinant proteins of expected molecular weight. Concentration of CBD, Cfp10-CBD, Ag85A-CBD, and ESAT6-CBD was 20%, 15%, and 15% total protein, respectively. The resulting chimere proteins provide high affinity for cellulose and high stability. Immobilization of CBD-containing recombinant proteins proceeds as one-stage process providing target protein purification and adsorption on cellulose. The vaccines produced using this technology are inexpensive because of low cost of cellulose sorbents as well as simultaneous use of cellulose for purification and immobilization of protein. Many cellulose preparations are not toxic, biocompatible, and widely used in medicine.

Candida krusei, a multidrug-resistant opportunistic fungal pathogen: geographic and temporal trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005.

Candida krusei is well known as a fungal pathogen for patients with hematologic malignancies and for transplant recipients. Using the ARTEMIS Antifungal Surveillance Program database, we describe geographic and temporal trends in the isolation of C. krusei from clinical specimens and the in vitro susceptibilities of 3,448 isolates to voriconazole as determined by CLSI (formerly NCCLS) disk diffusion testing. In addition, we report the in vitro susceptibilities of bloodstream infection isolates of C. krusei to amphotericin B (304 isolates), flucytosine (254 isolates), anidulafungin (121 isolates), caspofungin (300 isolates), and micafungin (102 isolates) as determined by CLSI broth microdilution methods. Geographic differences in isolation were apparent; the highest frequency of isolation was seen for the Czech Republic (7.6%) and the lowest for Indonesia, South Korea, and Thailand (0 to 0.3%). Overall, 83% of isolates were susceptible to voriconazole, ranging from 74.8% in Latin America to 92.3% in North America. C. krusei was most commonly isolated from hematology-oncology services, where only 76.7% of isolates were susceptible to voriconazole. There was no evidence of increasing resistance of C. krusei to voriconazole from 2001 to 2005. Decreased susceptibilities to amphotericin B (MIC at which 90% of isolates were inhibited [MIC(90)], 4 microg/ml) and flucytosine (MIC(90), 16 microg/ml) were noted, whereas 100% of isolates were inhibited by < or =2 microg/ml of anidulafungin (MIC(90), 0.06 microg/ml), micafungin (MIC(90), 0.12 microg/ml) or caspofungin (MIC(90), 0.25 microg/ml). C. krusei is an uncommon but multidrug-resistant fungal pathogen. Among the systemically active antifungal agents, the echinocandins appear to be the most active against this important pathogen.

[Tissue and bacterial sensitization in patients with bone pathology]. / Tkanevaia i bakterial'naia sensibilizatsiia u bol'nykh a kostnoi patologiei.

The author studied sensitization to normal tissues (bone, muscle, spleen) and tissues altered by pathological process (sequestrum, scars), and also to allergens of widespread causative agents of purulent infection (staphylococcus, streptococcus, Proteus, E. coli) in 87 patients with different bone pathology and in 24 donors. Leukocytolysis reaction (modified by Karapaty) was used for ascertaining the sensitization; a total of 592 tests were conducted. With the development of infection in soft tissues and then in the bone there was an increase in frequency of positive reactions and their manifestation in interaction with the antigens of both normal tissues and those altered by pathological process. The incidence of positive reactions and their manifestation with bacterial allergens coinciding with the microbial flora of the focus of infection was also increased.

[Effect of the ABO blood group phenotype on the Staphylococcus aureus bacterial carrier state]. / Vliianie fenotipa gruppy krovi ABO na bakterionositel'stvo Staphylococcus aureus.

326 employees of 4 medical institutions (1 regional hospital, 2 city hospitals and a maternity clinic) were examined for the presence of S. aureus carriership. Examinations were made every 3 months for 3 recent years. The results of these examinations were compared with the distribution of the blood groups in the AB0 system among the carriers. Constant and malignant carrier state was detected mainly in persons with blood group A.

[Pathogenetic characteristics of experimental traumatic osteomyelitis (immunological and bacteriological aspects)]. / Nekotorye osobennosti patogeneza éksperimental'nogo travmaticheskogo osteomielita (immunologicheskii i bakteriologicheskii aspekty).

The model of osteomyelitis was created in dogs by the method of Ilizarov, Stetsula and Kramer; as a result, a typical picture of the disease was obtained. The maximum survival time of the animals was 1 year. The inoculation of the infective agent into the osteotomy zone at an early period (1 hour after the operation) resulted in the complete suppression of the phagocytic activity of leukocytes and in the rapid rise of the lysozyme level. The staphylococcal strain causing the disease could be detected in the blood during 19 weeks, and in discharges from wounds and fistulas during 14 weeks of observation. The failure of the phagocytic activity of leukocytes at the initial stage resulted seemingly in the appearance and further development of the infectious process. The humoral nonspecific immunity factors under the study (complement and lysozyme) seemed to play no essential role at the initial stage. In the course of traumatic osteomyelitis at a later stage the specific factor, staphylococcal antitoxin, acquired the primary importance.

[Serum immunoglobulin content in donors as related to the ABO blood group]. / Soderzhanie syvorotochnykh immunoglobulinov u donorov v zavisimosti ot gruppy krovi sistemy ABO.

The content of IgG and IgM has been studied in the sera of 120 donors making up 4 groups of 30 subjects each in accordance with the ABO blood grouping. As regards the amount of immunoglobulins of different classes in the serum of donors having blood of different groups, the donors with group O blood have shown the highest content of IgA and the lowest content of IgM, inthe donors with group A blood the highest content of IgA and the lowest content of IgM, in the donors with group A blood the highest content of IgG and the lowest content of IgA have been established, and the donors with group B blood have been found to have the maximum content of IgM and the low content of IgG. The donors with group AB blood have been found to occupy an intermediate position, being similar to the donors with group B blood in the content of IgG and IgA in their sera and to the donors with group A blood in the content of IgM.

[Microflora of suppurative inflammatory foci in surgical patients and its sensitivity to antibiotics]. / Mikroflora gnoino-vospalitel'nykh ochagov khirurgicheskikh bol'nykh i chuvstvitel'nost' ee k antibiotikam.

Materials from 1134 patients with various surgical infections were tested. From the materials collected from purulent inflammatory foci 2137 cultures were isolated. Many of them belonged to Micrococcaceae (63.7 per cent). Cultures belonging to Enterobacteriaceae and Streptococcaceae were isolated from 50.9 and 25.2 per cent of the patients respectively. Isolates belonging to other families were less frequent: diphtheroids were isolated from 13.3 per cent of the patients and Pseudomonas spp. were isolated from 10.6 per cent of the patients. The majority of the isolates of diverse taxons were sensitive to gentamicin (73 to 98.4 per cent). As the second active antibiotic the following should be indicated: fusidin, active against staphylococci (S. epidermidis and S. aureus, 70.5 and 83.3 per cent respectively); ristomycin, active against micrococci and diphtheroids (75.3 and 79.1 per cent respectively); ampicillin, active against S. faecalis (61.3 per cent); polymyxin, active against the trib microbes Escherichia, Klebsiella and Pseudomonas (75.5, 64.3 and 71.4 per cent respectively). No second antibiotic active against a significant percentage of various species of Proteus, fecal alkali forming bacteria, and A. calcoaceticus was stated. Sporulating aerobes were sensitive to the majority of the antibiotics.

[Microflora of gastric juice and its sensitivity to antibiotics in post-gastrectomy gastritis]. / Mikroflora zheludochnogo soka i chuvstvite'lnos't ee k antibio- tikam pri postrezektsionnykh gastritakh.

Fifty four patients with postresection gastritis and 13 healthy adults were examined. 141 microbial cultures belonging to 33 species were isolated from the gastric juice of the patients. In the healthy persons 27 cultures belonging to 7 species were isolated from the gastric juice. In the gastric juice of the patients there predominated enteric bacteria and enterococci (64.8 +/- 6.5 and 57.4 +/- 6.7 per cent respectively). Among the enteric bacteria Escherichia coli and Proteus spp. were the most frequent. Contamination of the gastric juice by such microbes amounted to 10(5)-10(9) microbial bodies per 1 ml. The isolates were mainly sensitive to gentamicin (84.8 +/- 2.9 per cent).

[Drug resistance of Mycobacterium tuberculosis]. / Lekarstvennaia rezistentnost' mikobakterii tuberkuleza.

Drug resistance of Mycobacterium tuberculosis was followed up within a period of 1986 to 1989. There was a tendency to stabilization of resistance to streptomycin (42 per cent), tubazid (45.2 per cent) and ethionamide (up. to 1.4 per cent). Resistance to kanamycin slowly increased (by 3 to 6 per cent every year). Resistance to rifampicin markedly increased (almost 15 times). Resistance to ethambutol decreased (10 times). It was shown that the drug resistance could be lowered by using the drug combinations.

[Current problems in the reconstructive surgery of the locomotor apparatus in children]. / Aktual'nye voprosy rekonstruktivnoi khirurgii oporno-dvigatel'nogo apparata u detei.

The authors analyze results of treatment of 778 children with malignant and benign tumors of the bones, pseudoarthroses, amputations of lower extremities and fingers, injuries of the tendons, vessels and contused-lacerated wounds of distal phalanges of fingers. The possibility to use a precision technique for the reconstructive operations of the vessels in children is shown.

[The epidemiological validation of the MPEL for grain dust in the atmosphere]. / Epidemiologicheskoe obosnovanie PDK zernovoi pyli v atmosfernom vozdukhe.

The use of calculating and gravimetric methods for examining the grain dust pollution of the ambient air at the site of an elevator determined the maximum single, mean daily, and mean annual concentrations at different distances from the source of dust emission. The mean ratio of these concentrations was 12.1:4.3:1, respectively. The calculated concentration-effect and concentration-time relationships provided evidence for the maximum single, mean daily, and mean annual allowable concentrations for grain dust in the ambient air.