Gastroesophageal reflux disease (GERD) is characterized by impaired motility at the gastroesophageal junction and the development of inflammatory changes in the mucosa of the distal esophagus. The aim of this review is to discuss the mechanisms contributing to the development of GERD. A literature search was conducted using the eLibrary.Ru and PubMed databases, focusing on articles published after 2000. Following the application of selection criteria, a total of 80 articles were included in the final literature review. Current understanding suggests that reflux esophagitis begins with damage to the esophageal epithelium caused by the reflux of acid and pepsin, leading to increased epithelial permeability. This allows hydrochloric acid and pepsin to penetrate deeper into the epithelial layer, attacking intact cells. Research indicates that the mechanisms of epithelial damage in the esophagus induced by acidic and bile reflux differ. Acid reflux causes tissue damage through protein denaturation, degradation by proteases, activation of cyclooxygenase-2 (COX-2), c-myc, and mitogen-activated protein kinase pathways, while simultaneously limiting prostaglandin synthesis. In contrast, bile acids induce cytotoxic mechanisms, activating oncogenes and c-myc, which contribute to epigenetic carcinogenic processes. Alterations in the esophageal microbiome trigger the activation of both innate and adaptive immune systems, as well as the sensory nervous system. Immune competent cells express receptors for numerous mediators released by sensory and autonomic nerves, enabling the nervous system to directly regulate the functional activity of the immune system. Conversely, immune cells can produce neuroactive substances and modulate nervous system functions, including pacemaker cells, leading to the development of reflux and exposing the esophageal mucosa to hydrochloric acid and pepsin or bile acids, resulting in inflammation and creating a vicious cycle.
This article describes the role of Moritz Hoffmann, anatomist and professor of medicine and surgery, in the history of the discovery of the pancreatic duct, later named after Johann Georg Wirsung. Translations of original texts in Latin are provided, their authors were contemporaries, eyewitnesses, and scientists who were directly acquainted with the participants of those events.
Objective: To determine the changes in organs and systems associated with connective tissue dysplasia (CTD) that affect gastric acid production in patients with CTD presenting symptoms of dyspepsia. Materials and Methods: A randomized controlled cross-sectional comparative study was conducted involving a total of 151 participants using a cross-sectional design. Inclusion criteria included presence of dyspeptic symptoms, absence of severe organic pathology capable of manifesting as dyspeptic symptoms (fever, hematemesis, anemia, leukocytosis, elevated ESR, melena), peptic ulcers or erosions in the stomach and duodenum mucosa, age between 18 to 29 years old, no history of Helicobacter pylori eradication therapy, discontinuation of medications affecting gastric acidity according to their half-life period, informed consent for participation in the study. All enrolled subjects underwent general clinical examination (collection of complaints, medical history, physical examination), screening for CTD, assessment of vegetative vascular reactivity (“Nerosoft,” Russia). Since there are no clear reference values for gastric acid-producing function, two additional groups without dyspepsia were formed using the same inclusion criteria except for the presence of dyspeptic symptoms. The research cohort consisted of four groups: Group 1-42 patients with dyspepsia and CTD; Group 2-36 patients with dyspepsia but no CTD; Group 3-37 patients with CTD but no dyspeptic complaints; Group 4-37 healthy volunteers free from both CTD and dyspeptic symptoms. All four groups received comprehensive clinical evaluation including symptom questionnaires using the Gastrointestinal Symptom Rating Scale (GSRS), 24-hour pH-metry (“Gastronscan-24,” Fryazino, Moscow Region, Russia), measurement of serum levels of pepsinogens I and II, gastrin-17, anti-H. pylori IgG antibodies (“Vector-Best,” Novosibirsk, Russia), endoscopic laser Doppler flowmetry (“LAKK-2,” Russia). Results: Among patients with CTD experiencing dyspeptic symptoms, postprandial distress syndrome occurred in 77% of cases. Clinico-functional markers specific to biliary type dysfunction include reflux-gastritis (17.8%) and gallbladder deformation (30%). Markers indicative of hypoacid condition include impaired microcirculation in the gastric wall (26.2%), gastropathy (gastric ptosis, 42%), thoracic cage deformities (23%), hypergastrinemia (25.6%). Conclusion: Decreased gastric acid secretion in patients with CTD is caused by two primary mechanisms. The most common factor involves disturbed gastric motility leading to duodenogastric reflux, resulting in bile entering the stomach and disrupting its secretory activity. In some patients, this process progresses to atrophic changes in the gastric mucosa accompanied by true deficiency in hydrochloric acid production. Both mechanisms significantly reduce the stomach's ability to produce acid, thereby influencing digestive processes and gastrointestinal protective properties.
Treatment of gastroesophageal reflux disease (GERD) is an urgent problem of modern gastroenterology. According to numerous studies carried out from 2000 to 2011, the prevalence of GERD varies depending on the region of the world from 2.5% (in East Asia) to 33.1% (in the Middle East). Moreover, according to various authors, the rate of failure of GERD therapy can reach 40%. Today there is no general accepted definition of “refractoriness” in all professional communities. In the clinical guidelines for the diagnosis and treatment of GERD of the Russian Gastroenterological Association (RGA), refractoriness is understood as the persistence of typical symptoms of the disease and/or incomplete healing of the esophageal mucosa while taking a standard dose of proton pump inhibitors (PPIs) once a day for 8 weeks. It should be noted that it is legitimate to talk about the refractory form of GERD in the case when the diagnosis of GERD was verified according to current clinical recommendations, treatment was prescribed according to the identified phenotype of the disease, but the therapy administered to the patient is accompanied by a partial effect. The article presents the basic principles of treatment a patient with gastroesophageal reflux disease refractory to proton pump inhibitor therapy. An algorithm for identifying and eliminating possible causes of refractoriness is proposed, taking into account the phenotype of the disease and the presence of concomitant pathology.
The article provides information on the role of the FTO (A+23525T) fat mass-associated gene polymorphism, the leptin receptor gene LEPR (Arg223Gln) in BEN syndrome in patients with DST. The results of the study of the trophological status of patients with DST and the severity of BEN syndrome are shown. It has been proven that genetic mutations exacerbate genetically determined disorders of the trophological status. In practice, the doctor must take into account the mechanisms of the formation of BEN syndrome in patients with DST and the risks associated with the presence of this syndrome.
Aim of the investigation. To study the relationship of blood levels of vitamin D-binding protein (VDBP) with clinical and laboratory manifestations of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus. Materials and methods. The study included 80 patients with type 2 diabetes mellitus aged 33 to 69 years (67 women, 13 men). NAFLD was detected in 75.0% patients with type 2 diabetes mellitus. Severe liver steatosis was observed in 40.0% cases of NAFLD, fibrosis F3-4 in 23.3%. Serum levels of VDBP were determined by enzyme-linked immunosorbent assay. Results. The presence of NAFLD in patients with type 2 diabetes mellitus was characterized by lower blood levels of VDBP. Biochemical syndromes of liver pathology, as well as manifestations of diabetes mellitus (except for its duration) did not affect serum levels of VDBP in NAFLD. In patients with NAFLD and obesity, abdominal obesity or dyslipidemia, a lower concentration of VDBP in blood was determined. VDBP values did not depend on the presence of arterial hypertension and metabolic syndrome in NAFLD. Patients with severe liver steatosis or fibrosis F3-4 had lower blood levels of VDBP. Conclusion. Thus, in NAFLD associated with type 2 diabetes mellitus, there is a decrease of blood levels of VDBP, which is associated with the duration of diabetes, the presence of obesity, abdominal obesity and dyslipidemia. Cases of NAFLD with severe steatosis or severe fibrosis/liver cirrhosis are characterized by a lower serum concentration of VDBP.
Iron deficiency conditions are caused by disorders of iron metabolism due to its deficiency in the body and are characterized by clinical and laboratory signs, the severity of which depends on the stage of iron deficiency. The development of iron deficiency anemia (IDA) in pregnant women is due to increased iron intake by the mother and fetus against the background of insufficient exogenous intake and / or assimilation and occurs at any stage of pregnancy. The presence of anemia in pregnant women adversely affects the course of pregnancy, childbirth, the postpartum period, the condition of the fetus and newborn. It should be noted that the effectiveness of the treatment of pregnant and maternity women with IDA depends on the daily dose of elemental iron and on the level of endogenous erythropoietin (EPO). With an adequate level of EPO, the effectiveness of treatment is 2.5 times higher. In addition, the use of EPO drugs in combination with ferrotherapy in pregnant women and maternity patients leads to a more pronounced clinical effect.
The purpose of the study: To study the capabilities of the original method of collecting and analyzing complaints “Universal complaint questionnaire” in a pilot study Materials and methods: A continuous one-stage study was conducted, in which 186 young people (men 36.56% and women 63.44%) took part, each of whom completed a survey using a universal questionnaire of complaints of a gastroenterological profile, describing 20 complaints, using CAWI technology. Results: The most common gastrointestinal complaints in adolescence are fatigue and decreased performance (45.16%), general weakness (34.95%), aversion to certain foods (24.19%), decreased appetite (21.51%), belching, aerophagia, regurgitation and heartburn (17.74%), epigastric pain syndrome (16.67%) and abdominal pain (12.5%). A statistically significant difference by gender was obtained for complaints of general weakness, fatigue and decreased performance, epigastric pain syndrome, postprandial distress syndrome and constipation. The earliest complaint is aversion to certain foods (11.95±5.24 years), at 12-14 years, complaints from the upper gastrointestinal tract arise, and at about 16 years, general complaints join in, including abdominal pain. Most complaints at a young age are ongoing. Conclusion: The universal complaint questionnaire can be used by any clinical discipline both in practical activities and in scientific and educational ones, but requires modification for specific tasks.
Due to the lack of clear criteria in the diagnosis of gastroesophageal reflux disease (GERD) in children, it becomes appropriate to study the pathology, the factors of its formation and clinical course, including the association with manifestations of diseases of adjacent organs. The ethnic aspect is poorly studied. Aim: to evaluate the population characteristics of comorbidity of clinical manifestations of GERD with SD (dyspepsia syndrome) and IBS (irritable bowel syndrome) in schoolchildren of the Republic of Tyva with erosive and ulcerative defects of the gastroduodenal mucosa. Material and methods. The study was conducted in the Republic of Tyva: 1079 schoolchildren aged 7-17 years were clinically examined. GERD was defined in accordance with the pediatric consensus on pathology. IBS and SD were diagnosed based on Rome IV criteria. Subsequently, 129 children with gastrointestinal complaints underwent endoscopic examination of the upper gastrointestinal tract. The subjects were divided into two groups depending on the presence of GERD. Results. Erosive and ulcerative pathology of the gastroduodenal mucosa was more often detected in schoolchildren with GERD (p=0.032), mainly in the form of erosions (p=0.010) and significantly more often among Tuvans compared to Caucasians (p=0.004). The highest frequency of defects of the gastroduodenal mucosa was detected in schoolchildren with GERD, who also had manifestations of dyspepsia (in 27.8%). In children with GERD, the frequency of the destructive process was 2 times higher when associated with the clinical picture of IBS (p=0.185) and significantly higher than in children without GERD, but with IBS (p=0.036). In general, in children with an association of GERD and IBS, erosions were diagnosed more than 3 times more often than in other children. Conclusion. An association of GERD and erosive changes in the gastroduodenal mucosa is observed. The expediency of endoscopic examination of schoolchildren in the presence of an overlap of GERD with IBS for the purpose of diagnosing erosive pathology increases.
The article presents a clinical case of a complicated course of erosive and ulcerative lesions of the colon with the development of phlegmon of the cecum in a patient with HIV infection in the AIDS stage. According to the results of a comprehensive examination, including histological examination, inflammatory bowel diseases and colitis caused by CMVI were excluded. The association with NSAID use was assessed as probable on the Naranjo scale. The outcome of the disease was a dynamic intestinal obstruction caused by phlegmonous colitis, which led to the death of the patient. The purpose of the publication was to draw the attention of specialists to the peculiarities of the course of colitis in HIV-infected patients, the difficulties of differential diagnosis, and risk factors for the development of colon phlegmon.
Purpose of the study. To evaluate the interaction of polymorphic variants rs1042713 (Arg16Gly) and rs1042714 (Gln27Glu) of the β2-adrenoreceptor (β2-AR) gene with the development of liver cirrhosis (LC). Materials and methods. A total of 137 patients with liver cirrhosis and 143 healthy volunteers, who were Caucasian and unrelated to each other, participated in the observational case-control study. Genotyping of polymorphic variants Arg16Gly and Gln27Glu of the β2-AR gene was performed using the polymerase chain reaction (PCR) method by analyzing restriction fragment length polymorphism of amplicons (PDRF analysis). Results. Genotypes AG, GG and AA of the Arg16Gly polymorphism and genotypes CG, CC and GG of the Gln27Glu polymorphism of the β2-AR gene are not predictors of LC development (OR = 0.86; 95% CI: 0.53-1.37; p=0.52; OR=0.88; 95% CI:0.55-1.41; p=0.59; OR=1.81; 95% CI:0.91-3.62; p=0.09; OR=0.74; 95% CI:0.46-1.19; p=0.22; OR=1.55; 95% CI:0.93-2.58; p=0.09; OR=0.91; 95% CI: 0.52-1.57, p=0.72, respectively, p>0.05). Carrying the Arg16Arg/Gln27Gln haplotype increased the chance of developing LC by 2,4-fold (OR=2.42; 95%DI:1.13-5.18; p=0.02). Arg16ArgGln27Gln haplotype is associated with LC severity according to Child-Pugh classification (χ2=3.27; p=0.007) and severity of liver fibrosis according to APRI index (χ2=4.46; p=0.03). Conclusion. Haplotype Arg16ArgGln27Gln of β2-AR gene is a predictor of LC development, increasing the risk of disease development 2,4 times.
Francis Kiernan (1800-1874) was an eminent Irish anatomist and physician. He is best known for his detailed work on the anatomy of the liver, for which he received the Copley Medal from the Royal Society in 1836. Kiernan also successfully founded a private course in anatomy in London, establishing himself as an excellent lecturer and teacher, but this later led to resistance from the authorities of the Royal College of Surgeons. In 1836, F. Kiernan was one of the founders of the Senate of the University of London and for several years served as an examiner in anatomy and physiology. He was also a Fellow of the Royal College of Surgeons. His work “The Anatomy and Physiology of the Liver” was published in 1833 and included detailed anatomical descriptions of the structures of the liver with detailed illustrations. Kiernan's studies of the liver brought clarity to problematic aspects of liver morphology and served as a springboard for further study of this organ by subsequent generations of scientists.
Metabolically associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has become the most prevalent cause of liver disease worldwide. MAFLD is an independent risk factor for cardiovascular diseases and associated mortality. Despite its prevalence, MAFLD is often underestimated and does not receive adequate attention during clinical visits. MAFLD is a hepatic manifestation of metabolic syndrome and affects approximately 55% of individuals living with diabetes. The new definition emphasizes bidirectional connections and raises awareness about identifying fatty liver disease in patients with diabetes and cardiovascular diseases or cardiovascular risk factors, as well as searching for these conditions in patients with MAFLD. Liver dysfunction significantly contributes to the development of diabetes. Although these mechanisms are not fully understood, fat accumulation in the liver leads to changes in energy metabolism and inflammatory signals, which promote insulin resistance. Furthermore, chronic hyperinsulinemia observed in diabetic patients also contributes to fat accumulation in the liver. Diabetes patients may benefit from medications that potentially have a positive impact on MAFLD and liver diseases. This article discusses the potential use of hypoglycemic drugs in MAFLD and their effects on liver fat content, liver enzymes used as markers of steatosis, and tissue inflammation indices, although existing data on structural liver changes are limited, requiring further research in this area.
The review article provides information on the mechanisms of functioning of the "gut-brain microbiota" axis, which supports bidirectional communication. The factors influencing this axis are noted, in particular diet, physical activity, and the administration of pre- and probiotic supplements. The results of studies on the effect of changes in the microbiota on the course of neurodegenerative diseases are presented, confirming that the onset and progression of neurodegenerative diseases are partially regulated by the intestinal microbiota. The results of both animal and human studies in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis are presented, showing an altered composition of the intestinal microbiota and its metabolites. Measures to improve the state of the microbiota using transplantation of fecal microbiota and psychobiotics, presented as potential therapeutic agents for Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, depression and autism spectrum disorders, are considered.
Objective - The aim of the study was to experimentally assess the preventive effect of a complex of oxidized pectin and oxymethyluracil on chronic aluminum-induced hepatotoxicity in rats based on molecular and biochemical parameters. Materials and Methods. The experiment was conducted on 56 outbred female rats that received oral administration of aluminum hydroxide at a dose of 15 mg/kg and a chelate complex of oxidized pectin with oxymethyluracil (50 mg/kg) under various preventive and post-exposure regimens for 3-4 months. The expression of metallothionein genes (Mt1, Mt2, Mt3) and zinc transporter genes (Zip1, Zip8) in liver tissue was determined by real-time PCR using specific primers, SYBR Green intercalating dye, and the reference gene Gapdh. Serum activity of AST, ALT, ALP, and LDH was measured; statistical analysis was performed using IBM SPSS Statistics 21 software with one-way ANOVA at a critical significance level of p=0,05. Results. In our study, chronic aluminum exposure was associated with an increase in Zip1 gene expression in the liver, whereas continuous administration of the oxidized pectin-oxymethyluracil complex normalized its expression to control levels. The expression of Zip8 and metallothionein genes (Mt1a, Mt2a, Mt3a) did not change significantly among the experimental groups. At the biochemical level, this complex, when used preventively, contributed to a reduction in AST and LDH activity. Conclusion. The oxidized pectin-oxymethyluracil complex in a rat model of chronic aluminum hydroxide exposure normalizes Zip1 gene expression and reduces AST and LDH activity. Further studies using an expanded set of morphological and molecular markers are required to clarify the organoprotective mechanisms of the complex.
The review highlights current understanding of the role of air pollution with particulate matter (PM) in the pathogenesis of chronic non-infectious liver diseases (CLD). For this purpose, the materials of articles indexed in the PubMed and Russian Science Citation Index (RSCI) databases were used. PM with an aerodynamic diameter of ≤2.5 μm are recognized as the most dangerous. It was found that long-term exposure to fine particulate matter (PM2.5), especially those containing metals, significantly increases the risk and mortality from liver cancer, cirrhosis, and non-alcoholic fatty liver disease. Exposure to PM2.5 can contribute to the development of CLD by causing oxidative stress, systemic inflammation, and dysregulation of lipid metabolism. Damage to the intestinal epithelium and disruption of microbiotic homeostasis causes stress to the endoplasmic reticulum of cells, inducing abnormal expression of specific microRNAs or inflammatory factors. The review discusses modern terminology and hypotheses of the pathogenesis of the most common chronic non-infectious liver diseases. Unfortunately, no hypothesis clearly characterizes the role of PM in the pathogenesis of the discussed liver diseases, in particular, at the molecular genetic level. Creating a formalized description of the processes mediating the effect of PM on the human body helps to better understand their role in the pathogenesis of various diseases, in particular CLD, which can contribute to the improvement of early diagnostic methods, treatment, and preventive measures.
Heritable and undifferentiated connective tissue disorders (HCTD/UCTD), including Marfan syndrome and related phenotypes, are increasingly recognized as independent risk factors for malignancy. Population-based studies demonstrate a significantly higher incidence of neoplastic diseases among these patients, with a particularly elevated relative risk for gastric adenocarcinoma (~4.6). Clinical observations, including the author’s own data, confirm a tendency toward the early development of tumors of various localizations, indicating a pathogenetic link between connective tissue dysplasia and oncogenesis. A key molecular driver is the constitutive paradoxical activation of the TGF-β signaling pathway: mutations in extracellular matrix genes (e. g., FBN1) and receptor components (TGFBR1/2) do not suppress but rather enhance systemic TGF-β expression and activity - a phenomenon known as the “TGF-β paradox” in HCTD. In oncology, however, TGF-β exhibits a well-known dual role: acting as a tumor suppressor in early carcinogenesis while promoting invasion and metastasis at advanced stages - a context-dependent switch confirmed in both in vitro and in vivo models. The unique pathogenetic background of chronic TGF-β hyperactivation in HCTD (the first paradox), combined with the context-dependent oncologic second paradox, creates a profibrogenic and pro-transforming microenvironment that predisposes connective tissue to neoplastic remodeling. Together, these mechanisms underscore the systemic role of the TGF-β axis in tissue homeostasis and cancer initiation. Part I discusses the clinical and epidemiological evidence for increased cancer risk in HCTD/UCTD and the pathogenetic relationship between the TGF-β paradox and gastric carcinogenesis, focusing on early molecular events within the Correa cascade that establish the groundwork for neoplastic transformation of the gastric mucosa.
This work provides a comprehensive study and systematic review of liver steatometry and elastometry techniques used following traditional ultrasonography (US). The mechanisms and principles of each method are presented along with their comparative characteristics, areas of application, regulatory aspects, and potential directions for development. Special attention is given to improving diagnostic accuracy and reducing risks of false-positive and false-negative results.
