Chronic gastritis and functional dyspepsia. Unity and struggle of two opposites

The review article describes the epidemiology, clinical picture, pathogenesis, approaches to the diagnosis and treatment of chronic gastritis and functional dyspepsia. Chronic gastritis is an unreasonably common diagnosis in our clinical practice, which is diagnosed in patients with disturbing dyspeptic complaints. According to the agreement documents, chronic gastritis is primarily a morphological concept. Chronic gastritis has no pathognomonic clinical signs and should be diagnosed during the histological examination of the gastric mucosa. Functional dyspepsia is a diagnosis that reflects the presence of a certain symptom complex (pain  or burning sensation in  the  epigastrium, a  feeling of  fullness or early satiety) in  the  absence of  diseases that could explain the symptoms. Secondary dyspepsia is diagnosed in patients with organic diseases of the upper gastrointestinal tract, metabolic or systemic diseases that cause dyspeptic syndrome. In the process of examining a patient with disturbing dyspeptic complaints, it is advisable for the doctor to use the diagnosis “unspecified dyspepsia” – a preliminary diagnosis before laboratory and instrumental examination aimed at identifying the cause of the dyspeptic syndrome. Dyspepsia associated with H. pylori is diagnosed in patients with H. pylori infection. The diagnosis is revised over time and is competent if complaints have been relieved within 6 months after effective H. pylori eradication.The main drugs for the treatment of patients with dyspeptic complaints are proton pump inhibitors and prokinetics. Omeprazole with domperidone sustained release (SR) in a fixed dose combination is characterized by optimal efficacy and a good safety profile in patients with both functional and secondary dyspepsia and ensures a high level of treatment adherence

Management of risk factors for gastrointestinal bleeding in patients receiving anticoagulant therapy

Direct oral anticoagulants (DOACs) are used to prevent and treat thrombosis and thromboembolic events in patients with various diseases. Despite its high efficacy and safety, DOAC therapy is accompanied by increased risk of hemorrhage, including gastrointestinal bleeding. Bleeding risk depends on individual patient profile and their risk factors. An increased risk of bleeding is associated with manifesting effect of DOACs on existing mucosal defects, active Helicobacter pylori infection. To reduce the risk of gastrointestinal bleeding in clinical practice, changing of following modifiable risk factors is required: H. pylori eradication; dose-adjusted DOAC therapy; prophylactic proton pump inhibitors (PPIs) administration to patients with HAS-BLED score ≥3, receiving dual or triple antithrombotic therapy, taking DOACs in combination with non-steroidal antiinflammatory drugs, to those with upper gastrointestinal diseases. In addition to PPIs, patients may be prescribed with rebamipide, bismuth tripotassium dicitrate, ursodeoxycholic acid. DOAC rivaroxaban (Xarelto®) has pharmacokinetic and pharmacodynamic advantages, a convenient single dosing regimen and a favorable safety profile, which provides effective protection against thrombosis and thromboembolic events in combination with low risk of gastrointestinal bleeding

DNA markers in oat breeding for crown rust resistance (a review)

Crown rust is the most harmful disease of oat (Avena sativa L.) around the world. The purpose of this review is to analyze and generalize the available information about DNA markers developed for oat breeding for resistance to crown rust. The review reveals the mechanisms of the A. sativa resistance to the fungus Puccinia coronata Corda f. sp. avenae Erikss. which causes crown rust disease. Special attention is paid to the race-specific resistance caused by the action of Pc genes and the nonspecific resistance controlled mainly by the loci of quantitative traits. Strategies for creating resistant genotypes and the role of molecular markers in oat breeding for crown rust resistance are discussed. Currently, research is focused mainly on the search for and development of molecular markers related to the oat race-specific resistance to P. coronata.The article presents the technological advantages and disadvantages of the existing DNA markers. KASP, TaqMan and HRM markers are currently the most promising technologies for identifying crown rust resistance genes. The validated SCAR and STS markers for the Pc39, Pc68, Pc91, Pc94 genes are recommended as the most available for implementation in practical oat breeding. The results of recent studies on identifying loci of nonspecific resistance to P. coronata are also presented. In general, the use of DNA markers has significant potential for creating oat genotypes resistant to crown rust under present-day conditions. DNA markers of various types are recommended for practical use, in particular for pyramiding genes and increasing the resistance period of new cultivars. Introduction of DNA markers into oat breeding will increase with the growth of molecular genetic data and the improvement of technologies for identifying genes and loci associated with both race-specific and nonspecific resistance of oat to P. coronata

Прогностическая сила МРТ-критериев в диагностике синдрома восстановления иммунитета у ВИЧ-инфицированных пациентов на примере сравнения классификации методом решающих деревьев и ROC-анализ

Introduction. Immune reconstitution inflammatory syndrome involving the central nervous system (CNS-IRIS) is a dangerous complication in HIV-infected patients on antiretroviral therapy (ART). The radiologic features of this syndrome have been little studied and are presented in isolated works. The diagnosis is difficult because there are no generally accepted criteria for IRIS. Our study is devoted to radiology of IRIS. Based on the results of brain MRI, together with clinical and laboratory data, MRI criteria for IRIS were formulated.Purpose and goals. To determine the prognostic value of MRI signs of CNS-IRIS using in a cohort of HIV-positive patients with neurological symptoms.Materials and methods. The analysis includes data from 68 HIV-infected patients who underwent brain MRI. In 14 of them were diagnosed IRIS with involvement of the central nervous system. To determine the diagnostic efficiency of the formulated MRI criteria, the STATISTICA program was used, decision trees were built, and a ROC analysis was performed.Results. Five decision tree models were built with different predictive values. The models took into account the categorical predictors (MRI criteria) in different order and quantity. The best performance has model #5, which can be considered a clinically useful predictive model.Conclusion. Brain MRI is an essential diagnostic step in HIV-infected patients on ART. It is necessary to expand the indications and conditions for radiological studies of the brain in patients with suspected immune reconstitution inflammatory syndrome.Введение. Синдром восстановления иммунитета с вовлечением центральной нервной системы (ЦНС-СВИ) является опасным осложнением у ВИЧ-инфицированных пациентов, принимающих антиретровирусную терапию (АРТ). Лучевая семиотика данного синдрома мало изучена и представлена в единичных работах. Отсутствуют общепринятые критерии СВИ, что затрудняет диагностику. Наше исследование посвящено изучению лучевой картины СВИ. По результатам МРТ головного мозга в совокупности с клиническими и лабораторными данными были сформулированы МРТ-критерии диагноза СВИ.Цели и задачи. Определить прогностическую силу совокупности лучевых признаков, выявляемых при ЦНС-СВИ с помощью МРТ головного мозга в когорте ВИЧ-положительных пациентов с неврологической симптоматикой.Материалы и методы. В анализ включены данные 68 ВИЧ-инфицированных пациентов, которым была выполнена МРТ головного мозга. У 14 из них был диагностирован СВИ с вовлечением ЦНС. Для определения диагностической эффективности сформулированных МРТ-критериев была использована программа STATISTICA, построены деревья решений, проведен ROC-анализ.Результаты. Были построены 5 моделей деревьев решений, обладающие различной прогнозирующей ценностью. Модели учитывали категориальные предикторы (МРТ-критерии) в различном порядке и количестве. Наилучшими характеристиками обладала модель № 5, которую можно считать клинически полезной прогностической моделью.Заключение. Проведение МРТ головного мозга у ВИЧ-инфицированных пациентов, принимающих АРТ, является неотъемлемым этапом диагностики. Необходимо расширение показаний и условий для проведения радиологических исследований головного мозга при подозрении на синдром восстановления иммунитета

Biochemical and technological properties of moose (<i>Alces alces</i>) recombinant chymosin

Recombinant chymosins (rСhns) of the cow and the camel are currently considered as standard milk coagulants for cheese-making. The search for a new type of milk-clotting enzymes that may exist in nature and can surpass the existing “cheese-making” standards is an urgent biotechnological task. Within this study, we for the first time constructed an expression vector allowing production of a recombinant analog of moose chymosin in the expression system of Escherichia coli (strain SHuffle express). We built a model of the spatial structure of moose chymosin and compared the topography of positive and negative surface charges with the correspondent structures of cow and camel chymosins. We found that the distribution of charges on the surface of moose chymosin has common features with that of cow and camel chymosins. However, the moose enzyme carries a unique positively charged patch, which is likely to affect its interaction with the substrate. Biochemical and technological properties of the moose rChn were studied. Commercial rСhns of cow and camel were used as comparison enzymes. In some technological parameters, the moose rChn proved to be superior to the reference enzymes. Сompared with the cow and camel rСhns, the moose chymosin specific activity is less dependent on the changes in CaCl2 concentration in the range of 1–5 mM and pH in the range of 6–7, which is an attractive technological property. The total proteolytic activity of the moose rСhn occupies an intermediate position between the rСhns of cow and camel. The combination of biochemical and technological properties of the moose rСhn argues for further study of this enzyme

Нейрорадиологические признаки синдрома восстановления иммунитета при ВИЧ-инфекции

The introduction of antiretroviral therapy has changed the human immunodeficiency virus pandemic. Some patients with HIV infection after starting or resuming ART develop a paradoxical worsening of clinical status, called Immune Reсоnstitution Inflammatory Syndrome (IRIS). However, if clinical and laboratory criteria for the diagnosis of this syndrome have been formulated, IRIS neuroradiological criteria do not exist yet. The present study presents neuroradiological features and diagnostic algorithm for identification of IRIS involving central nervous system.Внедрение антиретровирусной терапии изменило характер пандемии вируса иммунодефицита человека. У некоторых пациентов с ВИЧ-инфекцией после начала или возобновления АРВТ развивается парадоксальное ухудшение клинического статуса, названное синдромом восстановления иммунитета. Однако если клинико- лабораторные критерии диагноза данного синдрома сформулированы, то радиологических критериев не существует. В настоящем исследовании сформулирован диагностический алгоритм выявления синдрома восстановления иммунитета с вовлечением ЦНС, определены его нейрорадиологические особенности

Community-wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008

Recent breakthroughs in the determination of the crystal structures of G protein-coupled receptors (GPCRs) have provided new opportunities for structure-based drug design strategies targeting this protein family. With the aim of evaluating the current status of GPCR structure prediction and ligand docking, a community-wide, blind prediction assessment - GPCR Dock 2008 - was conducted in coordination with the publication of the crystal structure of the human adenosine A2Areceptor bound to the ligand ZM241385. Twenty-nine groups submitted 206 structural models before the release of the experimental structure, which were evaluated for the accuracy of the ligand binding mode and the overall receptor model compared with the crystal structure. This analysis highlights important aspects for success and future development, such as accurate modelling of structurally divergent regions and use of additional biochemical insight such as disulphide bridges in the extracellular loops

МЕЖДИСЦИПЛИНАРНЫЙ ПЕРСОНАЛИЗИРОВАННЫЙ ПОДХОД И ТЕХНОЛОГИИ ИЗУЧЕНИЯ ГОЛОВНОГО МОЗГА ПРИ ВИЧИНФЕКЦИИ

There was made an attempt to link interdisciplinary research methodically, from clinical diagnostic techniques, modern instrumental, laboratory and basic research to their implementation in practice. The experience of several partner groups studying the brain in HIV infection was analyzed and summarized. It was based on an interdisciplinary approach, the goals and authorities of infectious disease specialists,  psychiatrists, neurologists, radiologists, laboratory doctors, clinical examination algorithm, the role of history and interview, express-diagnostic of cognitive functions, specialized psychiatric, neurological  diagnosis, conclusion of clinical psychologists, indications for radiology methods. The choice and analysis of radiological and instrumental methods, the volume and structure of laboratory methods of central nervous system study were justified. The role of molecular genetic studies of HIV in blood and cerebrospinal fluid, the identification of drug-resistant forms of the virus was determined when choosing the therapy.Сделана попытка методически связать междисциплинарные исследования, начиная с клинических диагностических приемов, современных инструментальных, лабораторных и фундаментальных исследований до их реализации в практике. Проанализирован и обобщен опыт нескольких партнерских коллективов по методологии изучения головного мозга при ВИЧ-инфекции. В основу легли междисциплинарный подход, задачи и полномочия инфекционистов, наркологов-психиатров, неврологов, радиологов, врачей лабораторной службы, алгоритм клинического обследования, роль анамнеза и опроса, экспресс-диагностики когнитивных функций, специализированный диагноз психиатрический, неврологический, заключение клинических психологов, показания для радиологических исследований. Обоснованы выбор и анализ радиологических и инструментальных методов оценки ЦНС, объем и структура лабораторных методов для оценки процессов в ЦНС. Определена роль молекулярно-генетических исследований ВИЧ в крови и спинномозговой жидкости, выявления фармакорезистентных форм вируса, учет при выборе терапии

Effectiveness of empirical <i>Helicobacter pylori</i> eradication therapy with furazolidone in Russia: results from the European Registry on <i>Helicobacter pylori</i> Management (Hp-EuReg)

Background. First-line therapy does not always provide a high level of Helicobacter pylori eradication due to the increase of H. pylori resistance to antibiotics; therefore, it remains necessary to identify the most effective rescue treatments. The purpose of this study was to evaluate the efficacy and safety of empirical H. pylori furazolidone-containing regimens. Materials and methods. Adult H. pylori infected patients empirically treated with furazolidone-containing eradication regimens were registered in an international, prospective, multicenter non-intervention European registry on H. pylori management (Hp-EuReg). Data were collected at AEG-REDCap e-CRF from 2013 to 2021 and the quality was reviewed. Modified intention-to-treat (mITT) effectiveness analyses were performed. Results. Overall 106 patients received empirical furazolidone-containing therapy in Russia. Furazolidone was prescribed in a sequential scheme along with amoxicillin, clarithromycin and a proton pump inhibitor in 68 (64%) cases, triple regimens were prescribed in 28 (26%) patients and quadruple regimens in 10 (9.4%). Treatment duration of 7 days was assigned to 2 (1.9%) patients, 10-day eradication therapy in case of 80 (75%) and 14 days in 24 (23%) patients. Furazolidone was mainly used in first- (79%) and second-line (21%) regimens. The methods used to diagnose H. pylori infection were: histology (81%), stool antigen test (64%), 13C-urea breath test (6.6%), and rapid urease test (1.9%). The mITT effectiveness of sequential therapy was 100%; 93% with the triple therapy and 75.5% with quadruple therapy. Compliance was reported in 98% of cases. Adverse events were revealed in 5.7% of patients, mostly nausea (3.8%). No serious adverse events were reported. Conclusion. Furazolidone containing eradication regimens appear to be an effective and safe empirical therapy in Russia

Новая мутация в гене TYMP: клинико-морфологическая характеристика пациента с синдромом MNGIE

Mitochondrial neurogastrointestinal encephalomyopathy is an extremely rare (1–9:1 000 000, Orphanet, 2021) multisystem genetic disease caused by mutations in the TYMP gene encoding the enzyme thymidine phosphorylase.The article presents the data of a thirteen‑year survey on 40‑year‑old patient D. with clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy syndrome associated with the previously undescribed missense mutation c.1301G&gt;T (p.Gly434Val) of the TYMP gene. Detailed clinical picture (gastrointestinal dysfunction, cachexia, blepharoptosis, ophthalmoparesis, peripheral polyneuropathy and leukoaraiosis), electroneuromyography data (demyelination with secondary axonopathy), high blood serum level of dihydrothymine together with normal levels of thymidine and deoxyuridine made it possible to verify the diagnosis. Histopathological examination revealed atrophy of the longitudinal (outer) muscle layer of the small and large intestines and a significant decrease in the number of CD117+ cells (telocytes), signs of damage to the striated skeletal muscles of a mixed nature with a predominance of the myogenic pattern, as well the destruction of the myelin sheaths of peripheral nerves. Histochemical examination did not reveal “ragged red fibers” characteristic of mitochondrial pathology. Transmission electron microscopy demonstrated the presence of megalomitochondria in the myocardium.Синдром митохондриальной нейрогастроинтестинальной энцефаломиопатии – редкое (1–9:1000000, Orphanet, 2021) генетическое мультисистемное заболевание, обусловленное мутациями в ядерном гене TYMP, кодирующем фермент тимидинфосфорилазу.Представлены данные 13‑летнего наблюдения пациентки Д., 40 лет, с синдромом митохондриальной нейрогастроинтестинальной энцефаломиопатии, связанным с ранее не описанной миссенс‑заменой c.1301G&gt;T (p.Gly434Val) в гене TYMP. Диагноз синдрома митохондриальной нейрогастроинтестинальной энцефаломиопатии был поставлен на основании клинических проявлений (дисфункция желудочно‑кишечного тракта, кахексия, блефароптоз, офтальмопарез, периферическая полинейропатия и лейкоэнцефалопатия), результатов электронейромиографии (демиелинизация с вторичной аксонопатией), а также повышения уровня дигидротимина в сыворотке крови при нормальных уровнях тимидина и дезоксиуридина. Патогистологическое исследование выявило атрофию продольного (наружного) мышечного слоя тонкой и толстой кишок и значимое уменьшение количества CD117+‑клеток (телоцитов), поражение скелетных мышц смешанного характера с преобладанием миогенного паттерна, а также деструкцию миелиновых оболочек периферических нервов. Исследование S100‑положительных вегетативных образований кишечной стенки не выявило патологических изменений. При гистохимическом исследовании не были обнаружены «рваные красные волокна», характерные для митохондриопатий. Трансмиссионная электронная микроскопия продемонстрировала наличие полиморфизма митохондрий кардиомиоцитов и мегаломитохондрий лейомиоцитов кишечника