Irritable bowel syndrome phenotypes: leading factors of genetics and epigenetics, mechanisms of formation

Aim. To develop individualized approaches to the treatment of irritable bowel syndrome (IBS) based on the interaction of genetic and epigenetic factors, to characterize the phenotypes of the disease. Materials and methods. According to the formulated concept of the authors, from the cohort of patients with IBS, subgroups were distinguished post-infectious IBS (n=45), IBS in overweight and obese people (n=49), comorbid IBS (n=75) and essential IBS (n=51). In each subgroup the prevalence of candidate gene polymorphisms associated with IBS (COMT, SLC6A4, FTO), nutritional habits, levels of anxiety and depression, secretion of cortisol, serotonin, dopamine and zonulin levels in feces were studied. Results. Patients with post-infectious IBS are characterized by the carriage of the S allele of the SLC6A4 gene, the val/val genotype of the COMT gene, the prevalence of diarrhea, a high level of anxiety and frequent refusal of milk and dairy products. The phenotype IBS in overweight and obese individuals is characterized by L/L genotypes of the SLC6A4 gene, met/met of the COMT gene and A/A of the FTO gene, constipation, low plasma dopamine levels, signs of depression, frequent episodes of overeating, addiction to fatty and sweet foods, excessive consumption of sugar, lack of vegetables in the diet. The comorbid IBS phenotype is characterized by more frequent detection of the val/val genotype of the COMT gene and the carriage of the S allele of the SLC6A4 gene, clinically pronounced anxiety and depression, early onset of the disease, severe course, significant food restrictions and significant increase in epithelial permeability. With the essential phenotype, there are no bright stigmas of the disease; it is not possible to identify distinctive genetic and epigenetic factors, as well as the leading pathogenetic mechanism. Conclusion. The analysis of genetic and epigenetic factors, the leading mechanisms of the formation and course of IBS allows us to identify additional (except for postinfectious) phenotypes of the disease: IBS in overweight and obese people, comorbid and essential

Eating Habits, Anxiety and Depression in Patients with Irritable Bowel Syndrome: Clinical and Laboratory Comparisons

Aim: to assess the level of stress hormones (cortisol in saliva), neurotransmitters (serotonin in blood serum, dopamine in blood plasma) in relation to eating habits, anxiety and depression levels in patients with IBS.Materials and methods. An open cohort prospective study was conducted with the inclusion of 263 patients with an established diagnosis of IBS, among them 189 (71.9 %) women and 74 (28.1 %) men. The average age of patients with IBS was 29 [25; 35] years. The control group included 40 healthy volunteers. All individuals included in the study were assessed for diet and eating habits using the WHO CINDI program questionnaire, “Information on Nutrition and Eating Behavior”, the severity of anxiety and depression according to the HADS questionnaire, the level of specific anxiety in relation to gastrointestinal symptoms according to the VSI questionnaire, quality of life according to the IBS-QoL questionnaire. In addition, the enzyme immunoassay method was used to assess the levels of cortisol in the morning and evening portions of saliva, serotonin in the blood serum and dopamine in the blood plasma.Results. Among patients with IBS there is a statistically significantly higher level of cortisol in the morning and evening portions of saliva (U = 19.5, p < 0.001 and U = 111.5, p < 0.001, respectively), serotonin in blood serum (U = 269.0, p = 0.042) and lower plasma dopamine levels (U = 93.5, p = 0.0002) compared with controls. The mean salivary cortisol level among patients with IBS was 45.39 [29.86; 70.10] ng/ml in the morning and 19.21 [13.98; 23.50] ng/ml in the evening, while in the group of healthy individuals it was 19.0 [16.5; 21.7] and 9.7 [8.5; 10.5] ng/ml, respectively. The average content of serotonin in blood serum in patients with IBS was 188.78 [150.41; 230.32] ng/ml, among healthy individuals — 142.80 [130.52; 154.15] ng/ml. The average content of dopamine in blood plasma in patients with IBS was 28.83 [20.08; 41.54] ng/ml, in healthy individuals — 58.20 [48.15; 66.62] ng/ml.Conclusion. In patients with IBS the secretion of the stress hormone (cortisol) and neurotransmitters (serotonin, dopamine) is closely related to the nature of nutrition, the level of anxiety and depression, and is also associated with the clinical variant and severity of the course of the disease

Drug-associated gastropathy: diagnostic criteria

Drugs are widely used to treat different diseases in modern medicine, but they are often associated with adverse events. Those located in the gastrointestinal tract are common and often mild, but they can be serious or life-threatening and determine the continuation of treatment. The stomach is often affected not only by drugs taken orally but also by those administered parenterally. Here, we review the mechanisms of damage, risk factors and specific endoscopic, histopathological and clinical features of those drugs more often involved in gastric damage, namely NSAIDs, aspirin, anticoagulants, glucocorticosteroids, anticancer drugs, oral iron preparations and proton pump inhibitors. NSAID- and aspirin-associated forms of gastric damage are widely studied and have specific features, although they are often hidden by the coexistence of Helicobacter pylori infection. However, the damaging effect of anticoagulants and corticosteroids or oral iron therapy on the gastric mucosa is controversial. At the same time, the increased use of new antineoplastic drugs, such as checkpoint inhibitors, has opened up a new area of gastrointestinal damage that will be seen more frequently in the near future. We conclude that there is a need to expand and understand drug-induced gastrointestinal damage to prevent and recognize drug-associated gastropathy in a timely manner

Системный подход в лучевой диагностике острой абдоминальной хирургической инфекции: проспективное исследование

INTRODUCTION: The relevance of this work is due to the complexity of the treatment of severe acute surgical, especially destructive, infections of the abdominal cavity. The basis for improving results is the improvement of early radiological diagnosis of these diseases.OBJECTIVE: Of this study was to systematize the approaches in the radiodiagnosis of acute abdominal surgical infection.MATERIALS AND METHODS: The study analyzed the results of studies of 300 observations (men — 182, women — 128) aged 36 to 72 years who were treated at the Budgetary Institution «Surgut Regional Clinical Hospital» in the period from 2019 to 2022. The mean age of the patients was 49.2 years (59.7 years for men and 51 years for women). In the course of the study, a comparative analysis of the results of various methods of radiological examination in acute abdominal surgical infection was carried out, and key aspects of the radiodiagnosis algorithm were presented.Statistics. Statistical processing and systematization of these methods of radiation diagnostics was carried out with the calculation of sensitivity and specificity. The description of categorical variables was carried out using absolute values and a fraction of the whole — n (%). The results of calculating the indicators did not reveal significant differences in the group of men and women examined.RESULTS: At the initial stage of diagnosis, two main X-ray morphological syndromes of acute abdominal surgical infection were identified: a widespread inflammatory process (peritonitis and pancreatic necrosis) and a delimited inflammatory process (abscesses of various localizations). Based on the syndromic approach, not only the nosological diagnosis of this pathology wassubsequently carried out, but also approaches to the tactics of surgical treatment of patients were determined.DISCUSSION: The choice of the method of radiation examination of these patients, justified by the leading clinical and radiological syndrome, leads to early diagnosis and treatment of acute abdominal surgical infection.ВВЕДЕНИЕ: Актуальность данной работы обусловлена сложностью лечения тяжелых острых хирургических, особенно деструктивных, инфекций брюшной полости. Основой улучшения результатов является усовершенствование ранней лучевой диагностики этих заболеваний.ЦЕЛЬ: Систематизация подходов в лучевой диагностике острой абдоминальной хирургической инфекции.МАТЕРИАЛЫ И МЕТОДЫ: Проанализированы данные 300 пациентов (мужчин — 182, женщин — 128) в возрасте от 36 до 72 лет, проходивших лечение в бюджетном учреждении «Сургутская окружная клиническая больница» в период с 2019 по 2022 г. Средний возраст пациентов составил 49,2 года (мужчин 59,7 года, женщин — 51 год). В ходе исследования проведен сравнительный анализ результатов различных методов лучевого обследования при острой абдоминальной хирургической инфекции, а также представлены ключевые аспекты алгоритма лучевой диагностики.Статистика. Статистическую обработку и систематизацию данных лучевой диагностики проводили с расчетом чувствительности и  специфичности. Описание категориальных переменных осуществлялось при помощи абсолютных значений и доли от целого — n (%). Результаты вычислений показателей не выявили значительных различий в группе обследованных мужчин и женщин.РЕЗУЛЬТАТЫ: На начальном этапе диагностики были выделены два основных рентгеноморфологических синдрома острой абдоминальной хирургической инфекции: распространенного воспалительного процесса (перитонит и  панкреонекроз) и  отграниченного воспалительного процесса (абсцессы различных локализаций). На основе синдромального подхода в дальнейшем не только проводилась нозологическая диагностика этой патологии, но и определялись подходы к тактике хирургического лечения больных.ОБСУЖДЕНИЕ: Обоснованный ведущим клинико-рентгенологическим синдромом выбор метода лучевого обследования больных с острой абдоминальной хирургической инфекцией приводит к ранней диагностике и лечению острой абдоминальной хирургической инфекции

Abdominal Pain in Young Adults

Aim. A study of abdominal pain incidence in young adults in relation to dietary habits and psychological profile for advancement of health-promoting technologies.Materials and methods. An anonymous quiz survey covered 3,634 students enrolled at Omsk State Medical University in higher and secondary vocational education programmes via online use of the GSRS and WHO CINDI programme questionnaires to assess eating patterns and dietary preferences, as well as a brief multifactor personality inventory scale. Respondents with abdominal pain were divided into subcohorts by pain severity according to GSRS scores (mild, moderate or severe pain).Results. Abdominal pain was reported by 2,300 (63.29%) respondents, of whom 1,243 (54.0%) rated symptoms as mild, 996 (43.3%) and 61 (2.7%) — as moderate to severe. Abdominal pain complaints were more frequent in women (2I = 33.96, p <0.001), but gender had no effect on pain intensity. Pain associated with abdominal bloating and distention (57.65%), gastroesophageal reflux symptoms (38.75%), constipation (30.54%) or diarrhoea (28.4%). The presence and severity of abdominal pain was distinctive of individuals spending the most of average monthly income on food purchase and those actively consuming tea, coffee, added sugar, extra salt in cooked food, while having low intake of fruit and vegetables. A typical personality in severe abdominal pain is hypothymic depressive, hypochondriac in moderate and psychasthenic in mild pain.Conclusion. Abdominal pain is common among medical students predominating in females, associates with the eating pattern, dietary habits and psychological profile

Effect of metabolic syndrome on the state of the liver parenchyma and biliary system in patients with cholelithiasis

We estimated the analysis ot biochemical, immunological and sonographic parameters in 54 patients with cholelithiasis in association with metabolic syndrome. The results in this group of patients had demonstrated a statistically significant direct correlation between the severity of the average force changes in the liver according to sonography and increasing levels of low density lipoprotein cholesterol (LDL-C) (r = 0,578, p <0,01); plasma glucose levels of venous blood (r = 0,536, p <0,01) and increased levels of serum matrix metalloproteinase - 9 ( M M P-9) (r = 0,615, p <0,01). In addition, the level of LDL-C showed a statistically significant positive correlation with the thickness of the left lobe of the liver (r = 0,399, p <0,05) and a wall thickness of the gallbladder (r = 0,543, p <0,01); and elevated levels of serum MMP-9 with a wall thickness of the gallbladder (r = 0,421, p <0,05).Проведён анализ биохимических, иммунологических и сонографических параметров у 54 пациентов с желчнокаменной болезнью и проявлениями метаболического синдрома. В ходе исследования у данной группы пациентов выявлены статистически значимые прямые корреляционные связи средней силы между выраженностью изменений в печени по данным сонографии и увеличением уровня холестерина липопротеидов низкой плотности (ХС-ЛПНП) (г = 0,578, р < 0,01); уровнем глюкозы плазмы венозной крови (г = 0,536, р < 0,01) и повышением уровня сывороточной концентрации матриксной металлопротеиназы - 9 (ММП-9) (г = 0,615, р < 0,01). Кроме того, уровень ХС-ЛПНП демонстрировал статистически значимую положительную корреляционную связь с толщиной левой доли печени (г = 0,399, р < 0,05) и толщиной стенки жёлчного пузыря (г = 0,543, р < 0,01); а повышенный уровень в сыворотке крови ММП-9 с толщиной стенки жёлчного пузыря (г = 0,421, р < 0,05)

Association Study of TRPC4 as a Candidate Gene for Generalized Epilepsy with Photosensitivity

Photoparoxysmal response (PPR) is characterized by abnormal visual sensitivity of the brain to photic stimulation. Frequently associated with idiopathic generalized epilepsies (IGEs), it might be an endophenotype for cortical excitability. Transient receptor potential cation (TRPC) channels are involved in the generation of epileptiform discharges, and TRPC4 constitutes the main TRPC channel in the central nervous system. The present study investigated an association of PPR with sequence variations of the TRPC4 gene. Thirty-five single nucleotide polymorphisms (SNP) within TRPC4 were genotyped in 273 PPR probands and 599 population controls. Association analyses were performed for the broad PPR endophenotype (PPR types I-IV; n = 273), a narrow model of affectedness (PPR types III and IV; n = 214) and PPR associated with IGE (PPR/IGE; n = 106) for each SNP and for corresponding haplotypes. Association was found between the intron 5 SNP rs10507456 and PPR/IGE both for single markers (P = 0.005) and haplotype level (P = 0.01). Three additional SNPs (rs1535775, rs10161932 and rs7338118) within the same haplotype block were associated with PPR/IGE at P < 0.05 (uncorrected) as well as two more markers (rs10507457, rs7329459) located in intron 3. Again, the corresponding haplotype also showed association with PPR/IGE. Results were not significant following correction for multiple comparisons by permutation analysis for single markers and Bonferroni-Holm for haplotypes. No association was found between variants in TRPC4 and other phenotypes. Our results showed a trend toward association of TRPC4 variants and PPR/IGE. Further studies including larger samples of photosensitive probands are required to clarify the relevance of TRPC4 for PPR and IGE

Редкое клиническое наблюдение аденокарциномы толстой кишки с метастазами в легкие у пациентки средних лет

A rare case of colonic adenocarcinoma with metastatic lung lesion in a female patient of 43 years old is reported in the article. The diagnostic difficulty of this case was due to absolute lack of both respiratory and gastrointestinal clinical symptoms and signs. Timely scheduled chest fluorographic examination was the starting point of the diagnostic work-up resulted in diagnosis of colon cancer with metastasis to the lungs.Представленное клиническое наблюдение является редким казуистическим случаем метастатического поражения легких аденокарциномой ободочной кишки у пациентки 43 лет. Диагностическая сложность данного клинического случая обусловлена практически полным отсутствием у пациентки клинических симптомов со стороны бронхолегочной системы и желудочно-кишечного тракта, а также отсутствием каких-либо физикальных проявлений, указывающих на вовлечение данных органов и систем, что не позволяло даже заподозрить наличие патологического процесса.Своевременное плановое проведение флюорографического обследования органов грудной клетки явилось отправным пунктом диагностического процесса, по результатам которого был диагностирован рак толстой кишки с метастазами в легкие

ВОЗМОЖНОСТИ МУЛЬТИСПИРАЛЬНОЙ КОМПЬЮТЕРНОЙ ТОМОГРАФИИ В ОБОСНОВАНИИ ВЫБОРА ХИРУРГИЧЕСКОЙ ТАКТИКИ ЛЕЧЕНИЯ ПЕРИТОНИТА У БОЛЬНЫХ С ТЕРМИНАЛЬНОЙ СТАДИЕЙ ВИЧ-ИНФЕКЦИИ

Research is devoted to the development of criteria for surgical treatment of peritonitis in 32 patients with end-stage HIV infection on the basis of the characteristics of the course of the inflammatory process according to multislice computed tomography (MSCT) of the abdominal cavity. Particular attention was paid to topical localization of the inflammatory process, its prevalence, the involvement of other organs and systems. In the analysis of morphological data tuberculous infection of the abdominal cavity was present in all patients. Studies have shown the need for MSCT in all patients with suspected acute abdominal surgical pathology on the background of the terminal stage of HIV infection for the objectification of the indications for the choice of optimal primary surgical approach, as well as - to assess the dynamics of the inflammatory process in the abdominal cavity, a characteristic feature of which is unpredictable and atypical course in the postoperative period.Исследование посвящено разработке хирургических критериев лечения перитонитов у 32 больных с терминальной стадией ВИЧ-инфекции на основании особенностей течения воспалительного процесса по данным мульти-спиральной компьютерной томографии (МСКТ) брюшной полости. Особое внимание уделяли топической локализации воспалительного процесса, его распространенности, вовлечению других органов и систем. Туберкулезная инфекция брюшной полости присутствовала у всех пациентов. Выполненная работа показала необходимость использования МСКТ у всех больных при подозрении на острую абдоминальную хирургическую патологию на фоне терминальной стадии ВИЧ-инфекции для объективизации показаний к выбору оптимальной первичной хирургической тактики, а также для оценки динамики воспалительного процесса в брюшной полости, характерной особенностью которого является непредсказуемость и атипичность течения в послеоперационном периоде

The influence of anesthetics, neurotransmitters and antibiotics on the relaxation processes in lipid membranes

In the proximity of melting transitions of artificial and biological membranes fluctuations in enthalpy, area, volume and concentration are enhanced. This results in domain formation, changes of the elastic constants, changes in permeability and slowing down of relaxation processes. In this study we used pressure perturbation calorimetry to investigate the relaxation time scale after a jump into the melting transition regime of artificial lipid membranes. This time corresponds to the characteristic rate of domain growth. The studies were performed on single-component large unilamellar and multilamellar vesicle systems with and without the addition of small molecules such as general anesthetics, neurotransmitters and antibiotics. These drugs interact with membranes and affect melting points and profiles. In all systems we found that heat capacity and relaxation times are related to each other in a simple manner. The maximum relaxation time depends on the cooperativity of the heat capacity profile and decreases with a broadening of the transition. For this reason the influence of a drug on the time scale of domain formation processes can be understood on the basis of their influence on the heat capacity profile. This allows estimations of the time scale of domain formation processes in biological membranes.Comment: 12 pages, 6 figure