№ 12 (160) 2018

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№ 12 (160) 2018

EDITORIAL

Уважаемые коллеги !
У вас в руках свежий номер журнала «Экспериментальная и клиническая гастроэнтерология», посвященный актуальным и нерешенным вопросам в гастроэнтерологии и адресованный широкому кругу врачей разных специальностей. Открывает номер передовая статья в которой описаны оригинальные исследования по проблемам коморбидности у современных пациентов. Так, статья Ткаченко Е. И., Орешко Л. С., Соловьева Е. А., Шабанова А. А., Журавлева М. С. посвящена ассоциации наиболее частых, генетически детерминированных заболеваний: целиакии и дисплазии соединительной ткани В разделе «клиническая гастроэнтерология» представлены: «Роль микробиоты кишечника в развитии ожирения в возрастном аспекте» (авторы М. Ю. Щербакова, А. В. Власова, Т. А. Роживанова), статья продолжает серию публикаций, о роли микробиоты при различных соматических заболеваниях. В актуальном обзоре содержатся сведения о популяционном и видом составе микроорганизмов у пациентов различного возраста, страдающих ожирением, представлен анализ публикаций о механизмах развития метаболического синдрома с учетом вклада кишечника и его значимой составляющей — микробиоты в каскад патологических реакций, приводящих к развитию ожирения. Приводятся данные о результатах комплексного лечения ожирения с включением пробиотиков. Работа Гриценко Т. А., Давыдкина И. Л., Осадчук А. М., Косталановой Ю. В. об особенностях ГЭРБ у пациентов с гемобластозами, получающих полихимиотерапию. Авторы отметили рефрактерность ГЭРБ к терапии ИПП, связанную с нарушениями процессов пролиферации и дифференцировки эпителоцитов на фоне агрессивной полихимиотерапии. Несомненный интерес и клиническую значимость представляет работа Л. П. Розумбаевой, И. В. Козловой, А. П. Быковой о коморбидности патологии печени, билиарного тракта и псориаза. Полученные авторами результаты необходимо учитывать при оценке эффективности и безопасности базисной терапии дерматоза. Ассоциация двух функциональных заболеваний — синдром раздраженного кишечника и функциональная диспепсия с анализом механизмов развития такой коморбидности с позиций нарушений нейрогуморальной регуляции описана в статье М. А. Осадчук, В. О. Бурдиной. Оригинальное исследование А. А. Марковой, Е. И. Кашкиной, Г. Н. Масляковой посвящено иммуногистохимической диагностике нарушений пролиферации кишечного эпителия у пациентов с язвенным колитом в сопоставлении с длительностью заболевания и активностью патологического процесса в кишке. В разделе «Хирургические аспекты гастроэнтерологии» публикуется статья О. И. Кита, Е. М. Франциянц с соавт., посвященная анализу тканевых факторов регуляции неоангиогенеза и фибринолиза при аденокарциноме прямой кишки, имеющих значимую роль в канцерогенезе. В разделе «Экспериментальная гастроэнтерология» — статья Жеребятьева А. С., Камышного А. М. о региональных различиях распределения популяции иммунных клеток в кишечнике, во многом определяющих специфику патологического процесса в эксперименте. В соответствующем разделе номера — две актуальные лекции, посвященные эозинофильному эзофагиту. В последнее десятилетие число публикаций по этой проблеме в зарубежной литературе возросло почти в 200 раз. Объединенными усилиями гастроэнтерологов, аллергологов и патоморфологов созданы международные согласительные и национальные документы, в которых рассмотрены современные клинико-диагностические критерии эозинофильного эзофагита. У российских пациентов разного возраста эозинофильный эзофагит диагностируют редко. Вниманию читателей представлены две взаимно дополняющие лекции «Особенности диагностики эозинофильного эзофагита» (авторы И. С. Садиков, Д. Ш. Мачарадзе, С. Г. Хомерики) и «Эозинофильный эзофагит у взрослых: особенности диетотерапии» (авторы И. В. Козлова, А. Л. Пахомова). Указанные публикации восполняют дефицит сведений по клиническим особенностям, методам диагностики и немедикаментозного лечения этой патологии. Всегда интересна и полезна врачам рубрика журнала «Случаи из практики». В этом номере представлены два клинических наблюдения. Материал Бабаевой А. И. с соавт. посвящен гемангиомам печени у ревматологических пациентов. Обобщая накопленный опыт, авторы трактуют выявленные при УЗИ гемангиомы печени у пациентов с ревматоидным артритом как системное проявление заболевания, отмечая при этом, что при остеоартрозе гемангиомы печени встречаются достоверно реже. В статье А. Ю. Рябовой с соавт. представлен случай острого холецистита под маской острого инфаркта миокарда. Данное клиническое наблюдение еще раз напоминает практикующим врачам, что холецисто-кардиальный синдром, впервые описанный С. П. Боткиным, часто встречается, но не всегда своевременно распознается у полиморбидных пациентов. В разделе «Материалы конференции» опубликованы материалы выездного пленума НОГР «Болезни органов пищеварения в 21 веке: мультидисциплинарный подход. Гастроэнтерология в возрастном аспекте». Пленум организован совместными усилиями научного общества гастроэнтерологов России и Саратовским государственным медицинским университетом им. В. И. Разумовского МЗ РФ. Саратовский государственный медицинский университет им. В. И. Разумовского — один из старейших медицинских вузов нашей страны. Он был основан более 100 лет назад — в 1909 году. За это время СГМУ преодолел огромный путь от единственного в составе университета факультета до солидного учебного заведения со сложившимися традициями, уникальным медицинским потенциалом и накопленным научным опытом. В университете на протяжении многих лет развивается, обогащаясь новыми идеями и результатами клинических наблюдений, научная гастроэнтерологическая школа, которую основали и продолжают развивать известные хирурги, терапевты, педиатры. В разделе история медицины — яркая и интересная статья об образцовой системе здравоохранения, созданной первым наркомом здравоохранения СССР Николаем Александровичем Семашко. В феврале 2015 года исполняется 80 лет со дня рождения профессора кафедры факультетской терапии Тверской государственной медицинской академии, видного ученого, заслуженного врача России, доктора медицинских наук, профессора Вячеслава Васильевича Чернина. От всего сердца Научное общество гастроэнтерологов России, редакция журнала и коллеги поздравляют Вячеслава Васильевича со славным юбилеем, желают здоровья, радости, интересной и плодотворной работы, творческих побед!
Ответственный за выпуск редактор,

	заведующая кафедрой терапии педиатрического и стоматологического факультетов ГБОУ ВПО «Саратовский государственный медицинский университет им. В. И. Разумовского» МЗ РФ доктор медицинских наук, профессор
	*И. В. Козлова*

01.Title page: Role of toxins in Clostridium diﬃ cile pathogenicity
Yu. F. Belyi ¹ 📧 . S. V. Fialkina ¹, V. I. Troitskii ²
1. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Public Health, Moscow, Russia
2. I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991, Moscow, Russia
Abstract:Clostridium diﬃ cile — Gram-positive microorganism and the frequent causative agent of colitis associated with the use of people with broad-spectrum antibiotics. The developing imbalance of the representatives of the normal ﬂ ora of the large intestine promotes reproduction of the pathogen and is accompanied by the production of protein toxins - single-chain multi-domain toxins TcdA and TcdB and binary toxin CDT. After penetration of TcdA, TcdB and CDT into eukaryotic cells by receptor-mediated endocytosis, the enzymatic domains of TcdA and TcdB modify the regulatory GTPases of the Rho family by monoglucosylation, while the A-subunit of the toxin CDT ADP-ribosylated monomeric molecules, Modiﬁ cation of target proteins leads to their inactivation and the development of a wide range of cellular disorders with signs of inﬂ ammatory lesions of the mucous membrane of the colon. Due to the particularly important role of toxins in the pathogenesis of diﬀ erential infection, these pathogenicity factors are considered as the main components of therapeutic, preventive and diagnostic drugs. On the other hand, the use of C. diﬃ cile toxins in the scientiﬁ c search tools allows obtaining fundamental data on the mechanisms of physiological and pathological processes in eukaryotic cells.
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Full text is published :
Belyi Yu. F., Fialkina S. V., Troitskii V. I. Role of toxins in Clostridium diﬃ cile pathogenicity. Experimental and Clinical Gastroenterology. 2018;160(12): 4–10. (In Russ.) DOI: 10.31146/1682-8658-ecg-160-12-4-10
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02.Title page: Clostridium diﬃ cile — from Bacillus diﬃ cilis to Clostridioides diﬃ cile, global molecular epidemiology and possible implications for the Russian Federation
Fabian Berger ^1,2 📧 . Nahid Kuhenuri-Chami ³, Lutz von Müller ^1,2,4, Alexander Mellmann ^1,5, Barbara Gärtner ^1,2
1. German National Reference Laboratory for Clostridium diffi cile, Germany
2. Institute for Medical Microbiology and Hygiene, University of Saarland Medical Centre, Homburg/Saar, Germany
3. Department for General, Visceral, Vascular, and Paediatric Surgery, Saarland University Hospital and Saarland University Faculty of Medicine, Homburg, Germany
4. Institute for Laboratory Medicine, Microbiology and Hygiene, Christophorus Kliniken, Coesfeld, Germany
5. Institute of Hygiene, University of Münster, Münster, Germany
Keywords: genotyping; splAST; MLST; surveillance; Russia; BI/NAP; whole genome sequencing (WGS); cgMLST

Abstract: Clostridium diﬃ cile, recently renamed to Clostridioides diﬃ cile is the main cause of nosocomial diarrhea in developed nations. In recent years the appearance of so called “hypervirulent” strains like ribotype 027 (RT027) originating from North America has shaped the epidemiology in many parts of the world posing a huge burden on the healthcare system. These hypervirulent strains among others (e. g. RT017) are associated with resistance towards several antibiotics (e. g. ﬂ uoroquinolones) favoring their selection. In Europe, Israel and the American continent RT027 seems to have become the most prevalent strain, while in other parts of the world other RTs dominate. In Far East Asia, RT017 is the predominant strain, while in Australia RT014/020 and RT002 are mostly prevalent. However, for most parts of the world the C. diﬃ cile world map is rather incomplete, such as in most African countries, Middle East Asia, South Asia but also Eastern Europe including the Russian Federation. Multi-center studies are therefore needed to assess the impact of this pathogen including its molecular epidemiology and corresponding resistance.
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Berger F., Kuhenuri-Chami N., von Müller L., Mellmann A., Gärtner B.. Clostridium diﬃ cile — from Bacillus diﬃ cilis to Clostridioides diﬃ cile, global molecular epidemiology and possible implications for the Russian Federation. Experimental and Clinical Gastroenterology. 2018;160(12): 11–18. (In Russ.) DOI: 10.31146/1682-8658-ecg-160-12-11-18
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09.Title page: Clinical aspects of nosocomial diarrhea associated with Clostridium (Clostridioides) diﬃ cile in coloproctologic patients
Achkasov S. I. ¹ Sukhina M. A. ¹ 📧 . Sushkov O. I. ^1,2 Frolov S. A. ¹, Kashnikov V. N. ¹, Saﬁ n A. L. ¹, Egorkin M. A. ¹
1. State Scientifi c Center of Coloproctology, 123423, Moscow, Russia, st. Salam Adil, 2
Keywords: Antibiotic-associated diarrhea, Clostridium diﬃ cile, clostridial colitis

Abstract:Aim. To assess etiologic factor of Clostridium genus associated infection and its inﬂ uence on the disease clinical course. Materials and methods. 549 in-hospital patients participated in the study. We evaluated clinical and biochemical parameters of blood, stool frequency or stoma function intensity, feces volume per day and length of in-hospital stay. We performed stool sampling three times: during 48 hours after admission, in case of diarrhea and prior discharge. We evaluated glutamate-dehydrogenase (GDH) and Clostridium diﬃ cile toxins A and B by means of immunological assays. All samples underwent cultivation in anaerobic conditions. Results. Analysis of clostridial infection ethiologic factor has revealed 38 (17,9%) cases of clostridial diarrhea associated with another Clostridium species. We discovered Clostridium perfringens in 32 (84%) cases, Clostidium novyi in 5 (13%) cases and Clostidium hathewayi in 1 (3%) patient. Diarrhea severity, clinical and laboratory inﬂ ammation markers did not diﬀ er signiﬁ cantly depending on the isolated etiological agent of clostridial infection and its titer. Clostridial infection signiﬁ cantly increased in-hospital post-surgery length of stay by 4 days (p < 0,01). Conclusions. Symptoms C. diﬃ cile-associated infection could occur not only in case of persisting C. diﬃ cile but also in cases of other Clostridium species. Clinical manifestation of C. diﬃ cile-associated infection increase in-hospital stay.
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Full text is published :
Achkasov S. I., Sukhina M. A., Sushkov O. I., Frolov S. A., Kashnikov V. N., Saﬁ n A. L., Egorkin M. A. Clinical aspects of nosocomial diarrhea associated with Clostridium (Clostridioides) diﬃ cile in coloproctologic patients. Experimental and Clinical Gastroenterology. 2018;160(12): 58–63. (In Russ.) DOI: 10.31146/1682-8658-ecg-160-12-58-63
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10.Title page: Evaluation of antioxidant activity of Clostridium (Clostridioides) diﬃ cile
Obraztsov I. V. ¹ Sukhina M. A. ¹ 📧 .
1. State Scientifi c Center of Coloproctology, 123423, Moscow, Russia, st. Salam Adil, 2
Keywords: Clostridium (Clostridioides) diﬃ cile, antioxidant activity, reactive oxygen species, chemiluminescence

Abstract:Aim: to develop and to evaluate a method for Clostridium (Clostridioides) diﬃ cile antioxidant activity (AOA) assessment via chemiluminescent (CL) analysis. Materials and methods: we investigated ten C. diﬃ cile strains, obtained from patients with antibiotic-associated diarrhea that were cultured for two days. AOA was assessed on the ﬁ rst and second day of cultivation by means of CL assay based on 2,2’-azo-bis (2-amidinopropane) dihydrochloride-luminol system. Results: our method for AOA estimation is characterized by high reproducibility and reliability (the average coeﬃ cient of variation between parallel samples is 2.0–18.2%, the calibration curve coeﬃ cient of determination is 80.5–89.4%). C. diﬃ cile AOA after the ﬁ rst day of cultivation is 6.95–9.93 units; it increases to 9.86–13.27 units after the second day (p <0.01). A negative correlation (η = –0.3, p <0.05) is shown between the initial AOA level and its growth rate during cultivation. Conclusion: we propose a simple and reliable method for C. diﬃ cile AOA assessment that is suitable for routine use in clinical bacteriology. Length of C. diﬃ cile culturing is associated with increase of its AOA.
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Obraztsov I. V., Sukhina M. A. Evaluation of antioxidant activity of Clostridium (Clostridioides) diﬃ cile. Experimental and Clinical Gastroenterology. 2018;160(12): 64–69. (In Russ.) DOI: 10.31146/1682-8658-ecg-160-12-64-69
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11.Title page: Mechanisms of antibacterial resistance of Clostridium (clostridioides) diﬃ cile (review)
Sukhina M. A. ¹ 📧 . Makesheva A. B. ^2,3, Shelygin Yu. A. ^1,4, Kashnikov V. N. ¹
1. State Scientifi c Center of Coloproctology, 123423, Moscow, Russia, st. Salam Adil, 2
2. Faculty of advanced training of medical workers Peoples' Friendship University of Russia, 117198, Moscow, st. Miklukho-Maklaya, 21, 3
3. City Polyclinic № 218 DZM, branch number 3 in Losinoostrovsky district, 1-ya Naprudnaya street, 15
4. Federal state budgetary educational institution additional professional education Ministry of Health of Russia, 125993, Moscow, Russia, st. Barrikadnaya, d. 2⁄1, p. 1
Keywords: Clostridium (Clostridioides) diﬃ cile, C. diﬃ cile-associated infection, antibiotic resistance, mechanisms of antibacterial resistance

Abstract:Aim of the review. To study and consolidate recent data on Clostridium (Clostridioides) diﬃ cile antibacterial resistance mechanisms. Key points. There is objective data about the spread of antimicrobial resistant Clostridium (Clostridioides) diﬃ cile strains. Mechanisms of antimicrobial resistance in bacteria determined by genetic resistance or metabolic pathways are described. Spread of antimicrobial resistance in clinically relevant С. diﬃ cile is aggravated by its ability to form bioﬁ lms. Moreover, being a spore-forming bacterium, С. diﬃ cile can resist microbicidal action staying in the form of spore. After antibiotic cessation С. diﬃ cile returns to vegetative state and causes recurrence of thee disease. Understanding of С. diﬃ cile antibacterial resistance mechanisms is one of the key points in disease prevention strategy. Besides antibiotic stewardship, monitoring for the С. diﬃ cile antibacterial resistance spread is needed. We argue that the research on С. diﬃ cile antibacterial resistance and on the development of novel antibacterial agents eﬀ ective against С. diﬃ cile must be continued.
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Full text is published :
Sukhina M. A., Makesheva A. B., Shelygin Yu. A., Kashnikov V. N. Mechanisms of antibacterial resistance of Clostridium (clostridioides) diﬃ cile (review). Experimental and Clinical Gastroenterology. 2018;160(12): 70–79. (In Russ.) DOI: 10.31146/1682-8658-ecg-160-12-70-79
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12.Title page: The experience of the fecal microbiota transplantation in a patient with clostridial infectio
Schreiner E. B. ¹ 📧 . Morozov V. V. ¹, Khavkin A. I. ², Vlasov V. V. ¹, Kulikov V. D. ¹, Koltsova S. T. ¹
1. Institute of General Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia
2. Yu.E Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, Moscow 125412, Russia
Keywords: CDI, clostridial infection, fecal microbiota transplantation, diarrhea

Abstract:In recent decades, against the background of widespread and, often, unfounded antibiotic therapy, an increase in Clostridium difﬁ cile infection (CDI) due to hypervirulent strains has been observed. According to international CDI treatment protocols, metronidazole and vancomycin are starting therapy for patients with newly diagnosed infections, even though the likelihood of a relapse is about 65%. In addition, the increased interest in CDI is associated with the need to develop and use alternative strategies aimed at preventing and increasing the eﬀ ectiveness of treatment. In this regard, we ﬁ rst transplanted fecal microﬂ ora for this group of patients in Russia. This alternative method of treatment removes the spores of C. diﬃ cile, replenishes the normal intestinal ﬂ ora, reduces the level of vegetative forms of C. diﬃ cile in the intestines, and supports the patient’s own immune response.
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Full text is published :
Schreiner E. B., Morozov V. V., Khavkin A. I., Vlasov V. V., Kulikov V. D., Koltsova S. T. The experience of the fecal microbiota transplantation in a patient with clostridial infection. Experimental and Clinical Gastroenterology. 2018;160(12): 80–83. (In Russ.) DOI: 10.31146/1682-8658-ecg-160-12-80-83
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13.Title page: Gastrointestinal debut of acute staphylococcal endocarditis
Drobysheva V. P. ¹ 📧 . Demin A. A. ¹, Osipenko M. F. ¹
1. Federal state budgetary institution of higher education “Novosibirsk State Medical University” of the Russian Ministry of Health, Novosibirsk, Russia
Keywords: staphylococcal endocarditis, gastrointestinal debut

Abstract:Staphylococci are now the most common cause of infective endocarditis (IE). The onset of staphylococcal endocarditis (SE) is acute, with high fever, severe intoxication, and therefore, during the initial visit to the doctor, there is an erroneous assumption of inﬂ uenza, meningitis, hepatitis and other acute diseases. Sometimes the cause of the development of SE remains unclear, the initial clinical manifestations are characterized by high activity of the process, severe general condition of patients, hectic fever, stunning chills, sweats, yellow staining of the skin and mucous membranes, vomiting with blood, leukocytosis, anemia. A clinical case of gastrointestinal SE debut is described with signs of hepatitis and gastric ulcer. Hemorrhages and necrosis of the mucous membrane led to the formation of erosions and ulcers in the antrum and pyloric regions of the stomach, which was manifested by the sudden appearance of severe pain in the abdomen, vomiting with blood. Gastrointestinal manifestations of necrotic vasculitis at the beginning of the SE complicated its timely diagnosis. Hemorrhagic rash was characterized by extensive lesions with the transition to necrosis or suppuration. Cerebral embolism led to multiple brain abscesses, the symptoms of which became leading in the clinical picture. Coronary emboli caused the formation of myocardial abscesses. The use of a chemotherapeutic combination of vancomycin, amikacin and rifampicin with a highly virulent pathogen was ineﬀ ective: signs of severe heart damage with perforation of the coronary valve of the aortic valve developed. Progressive multi-organ failure has been fatal.
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  1. 2015 ESC Guidelines for the management of infective endocarditis: Th e Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Th oracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Habib G, Lancellotti P, Antunes MJ, et al; ESC Scientifi c Document Group. Eur Heart J. 2015; 36 (44): 3075–3128.
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Full text is published :
Drobysheva V. P., Demin A. A., Osipenko M. F. Gastrointestinal debut of acute staphylococcal endocarditis. Experimental and Clinical Gastroenterology. 2018;160(12): 84–86. (In Russ.) DOI: 10.31146/1682-8658-ecg-160-12-84-86
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15. Title page : Report on the work of the jubilee XX Congress of the Scientiﬁ c Society of Gastroenterology of Russia (Moscow, November 21–23, 2018)
Golovanova E. V. ¹
1. Moscow State University of Medicine and Dentistry named after A. I. Evdokimov, Moscow, Russia
Abstract: С 21 по 23 ноября 2018 года в Выставочном центре Крокус Экспо (Москва) в рамках XIII Национального конгресса терапевтов состоялся юбилейный XX съезд Научного общества гастроэнтерологов России (НОГР). Съезд открыл президент Научного общества гастроэнтерологов России, профессор Леонид Борисович Лазебник, который тепло приветствовал членов НОГР и гостей со всех регионов России. Далее с актовыми лекциями выступили: профессор И. А. Морозов (Москва) и Е. И. Ткаченко (Санкт-Петербург). Профессор Морозов изложил фундаментальные основы диагностики хеликобактерной инфекции в сопровождении демонстрации морфологических препаратов из личного архива, а также подходы к лечению в условиях современности. Профессор Ткаченко посвятил свое выступление основам нутрициологии и его значению в гастроэнтерологии. Первый научный симпозиум съезда «Многоликий аммиак: актуальность диагностики и лечения гипераммониемии у пациентов с хроническими заболеваниями печени (ХЗП)» открыл Л. Б. Лазебник., который представил предпосылки для создания рекомендаций НОГР по данной проблеме. Были подробно освещены основные механизмы образования и метаболических преобразований аммиака в организме при различных физиологических и патологических состояниях. В докладе Голованова Е. В. (Москва) сконцентрировала внимание слушателей на влиянии повышенных доз аммиака на прогрессирование хронических заболеваний печени даже в отсутствие выраженного токсического влияния на центральную нервную систему. Алексеенко С. А. (Хабаровск) рассказал о собственном опыте диагностики гипераммониемии с помощью нового портативного аппарата для экспресс-диагностики аммиака, который позволяет провести диагностику у постели больного, в частности, у больных с неалкогольной жировой болезнью печени (НАЖБП) на стадии стеатоза. Коррекция уровней аммиака препаратом L-орнитин-L-аспартат была успешной при проведении лечения с использованием различных схем (непрерывный прием в течение 4-х недель или 10-дневный прием каждого из трех месяцев лечения). и т.д

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Golovanova E. V. Report on the work of the jubilee XX Congress of the Scientiﬁ c Society of Gastroenterology of Russia (Moscow, November 21–23, 2018). Experimental and Clinical Gastroenterology. 2018;160(12): 91–93. (In Russ.) DOI: 10.31146/1682-8658-ecg-160-12-91-93

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