Gastroduodenal Mucosa Research Articles

Gastroduodenal effects of leflunomide under experimental adjuvant-induced rheumatoid arthritis and comorbid arterial hypertension

Use of leflunomide (LEF), a synthetic immunosuppressor, for the treatment of rheumatoid arthritis (RA), has become an innovation in the management of the disease. Despite the widely and successfully use of the LEF for RA treatment, its pharmacological properties and side effects are not well understood. The aim of the study was to examine the gastroduodenal effects of prolonged enteral use of the LEF in adjuvant-induced RA and comorbid arterial hypertension (AH). The experiments were carried out on male and female mature nonlinear rats, which were divided into five groups. The animals of control group (n = 10) were treated with starch suspension, the animals of the second group (n = 15) were injected with complete Freund’s adjuvant – adjuvant-induced arthritis (AA), the third group (n = 15) AA and comorbid AH (salt-loading model), the fourth group (n = 15) consisted of animals with AA treated with LEF, the fifth group (n = 15) – animals with comorbid condition (AA + AH), which were treated by LEF. Administering of starch-LEF suspension into the stomach was carried out through a special metal probe to rats with adjuvant-induced arthritis and comorbid pathology once daily for the first 3 days at a dose of 15 mg/kg (shock dose) and then at a dose of 1.5 mg/kg (therapeutic dose) for the next 53 days. After finishing the experiments, gastroduodenal toxic effects of the drug were determined according to the frequency of rats with pathological lesions (hyperemia, petechiae, edema, ulcers) and intensity of the damages using a point scale. It has been established that prolonged use of the LEF leads to high levels of gastroduodenal toxicity in rats with adjuvant-induced arthritis and combined pathological condition: an increase in the frequency of rats with gastroduodenal mucosal pathology and intensity of various types of damages (petechiae, edema, ulcers). LEF induced higher prevalence of duodenal than gastric toxicity in rats with both adjuvant-induced arthritis and arterial hypertension comorbidity. Thus, gastroduodenal mucosa pathology after prolonged use of LEF in adjuvant-induced arthritis and comorbid state increases a need for adjuvant therapy to prevent such adverse effects. Moreover, further pharmacological research in order to introduce appropriate drugs is recommended. Furthermore, conducting preclinical and clinical studies to understand the pharmacokinetics, mechanisms of action, and interaction of LEF, in particular, with antihypertensive and gastroprotective agents seem necessary. Implementation of the results of the study in healthcare practice will help to optimize the treatment regimen for rheumatoid arthritis and comorbidities.

Gastroduodenal injury and repair mechanisms.

Although the mucosal barrier serves as a primary interface between the environment and host, little is known about the repair of acute, superficial lesions or deeper, persistent lesions that if not healed, can be the site of increased permeability to luminal antigens, inflammation, and/or neoplasia development. Studies on acute superficial lesions have been sparse in the past year, with more focus given to novel mechanisms of mucosal protection, and the way in which mature epithelial cells or committed stem cells dedifferentiate, reprogram, proliferate, and then regenerate the gastroduodenal mucosa after injury. For this, adenoviral therapy showed organ specific targeting with mRNA and protein expression of effectors to protect against mucosal injury and ulceration. A large database of plant-based agents known to protect against injury and ulceration was published, along with studies using plant-based compounds delivered with alginates, polysaccharide/gel floating rafts, or incorporated into nanoparticles or green carbon dots to improve targeting and retention at the ulcerated lesion. With RNA technology developing rapidly, particularly single-cell RNA sequencing, important and novel data was forthcoming on mucosal regeneration. In particular, the role of interleukin-17 hub proteins in mucosal healing was highlighted. The presence and role of injury reserve cells was determined, as was the composition of ligand gradients for cell differentiation in both stomach and duodenum. The role of amphiregulin in parietal cell differentiation from lineage-restricted stem cells and the Yap1 gene signature in metaplasia vs. healing ulcers were of particular importance. Additionally, studies unveiled the important role of mesenchymal stromal cells in differentiation and repair mechanisms, in Muse cells as an exciting new therapy for mucosal repair after injury, and the role of sympathetic neurons in activating the immune system to regulate mucosal repair mechanisms. Recent studies highlight novel mechanisms that promote mucosal regeneration after injury of the gastroduodenal mucosa.

Refractoriness to anti-Helicobacter pylori treatment attributed to phenotypic resistance patterns in patients with gastroduodenopathy in Guayaquil-Ecuador.

Treatment of Helicobacter pylori gastric infection is complex and associated with increased rates of therapeutic failure. This research aimed to characterize the H. pylori infection status, strain resistance to antimicrobial agents, and the predominant lesion pattern in the gastroduodenal mucosa of patients with clinical suspicion of refractoriness to first- and second-line treatment who were diagnosed and treated in a health center in Guayaquil, Ecuador. A total of 374 patients with upper gastrointestinal symptoms and H. pylori infection were preselected and prescribed one of three triple therapy regimens for primary infection, as judged by the treating physician. Subsequently, 121 patients who returned to the follow-up visit with persistent symptoms after treatment were studied. All patients had H. pylori infection. Histopathological examination diagnosed chronic active gastritis in 91.7% of cases; premalignant lesions were observed in 15.8%. The three triple therapy schemes applied showed suboptimal efficacy (between 47.6% and 77.2%), with the best performance corresponding to the scheme consisting of a proton pump inhibitor + amoxicillin + levofloxacin. Bacterial strains showed very high phenotypic resistance to all five antimicrobials tested: clarithromycin, 82.9%; metronidazole, 69.7%; amoxicillin and levofloxacin, almost 50%; tetracycline, 38.2%. Concurrent resistance to clarithromycin-amoxicillin was 43.4%, to tetracycline-metronidazole 30.3%, to amoxicillin-levofloxacin 27.6%, and to clarithromycin-metronidazole 59.2%. In vitro testing revealed resistance to all five antibiotics, indicating that H. pylori exhibited resistance phenotypes to these antibiotics. Consequently, the effectiveness of triple treatments may be compromised, and further studies are needed to assess refractoriness in quadruple and concomitant therapies.

Enfermedad ulcerosa péptica

A peptic ulcer (PU) is a loss of matter in parts of the digestive tract that are in contact with acid and pepsin and which extend beyond the muscularis mucosae. The most frequent location is the duodenum and stomach. The incidence of PU is between 0.1% and 0.3% of the general population and the mortality rate, which is in relation to its complications, is 2-3 cases per 100,000 inhabitants/year. The main causes are Helicobacter pylori (HP) infection and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) that cause an imbalance between the aggressive and defensive factors that regulate gastroduodenal mucosa function. The clinical spectrum of ulcer disease is highly variable, ranging from asymptomatic (70%), “ulcerative-rate epigastric pain,” nonspecific discomfort, or symptoms and signs related to its complications (upper gastrointestinal bleeding, perforation, pyloric-duodenal stenosis, and penetration to neighboring organs). Upper endoscopy allows for a diagnosis per se of PU as well as its etiology (collecting biopsies to rule out malignancy and investigate HP infection). Antisecretory treatment with proton-pump inhibitors (PPIs) is the mainstay of treatment for ulcer disease. The eradication of HP when the infection is detected and cessation of NSAID use are essential to promote healing and prevent ulcer recurrence.

Review on Gastroprotective Effect of Herbal Medicines

Herbal medicines are very important to cure the various ailments of human. Demands of the herbal
 medicines are increasing in both developed and under developed countries due to growing recognition of natural plants being lesser of side effect, easily available in surrounding place with low coast. Despite extensive research, the etiology ofpeptic ulcer disease remains unclear. Given the multiple processes that control acid and pepsin secretion and defense and repair of the gastroduodenal mucosa, it is likely that the cause of ulceration differs between individuals. Acid and pepsin appear to be necessary but not sufficient ingredients in the ulcerative process.. NSAIDs cause a significant number of gastric and duodenal ulcers; this is probably due to inhibition of prostaglandin production with loss of its protectiveeffects. In the absence of NSAIDs and gastrinoma, it appears that most gastric ulcers and all duodenal ulcers occur in the setting of H. pylori infection. Gastric ulcer often occurs with decreased acid-peptic activity, suggesting that mucosaldefensive impairments are more important. The combination of inflammation, protective deficiencies, and moderate amounts of acid and pepsin may be enough to induce ulceration. Many questions remain in understanding the pathophysiology of peptic ulcer disease. The physiology and pathophysiology of mucosal regeneration and the mechanisms by which H. pylori and inflammation disrupt normal gastroduodenal function will be fruitful areas of future investigation. In this review attempts have been made to know the antiulcer drug of natural origin with their suggestedmedicinal part.
 Key Words: Peptic ulcer , H.pylori , Herbal Medicines ,NSAID’s

Domestic researchers who have made important contributions to the study of digestive system diseases: images in art. Georgiy Yosypovych Burchynsky

Georgiy Yosypovych Burchynsky (1908 — 1993) — Doctor of Medical Sciences, Professor, Honored Scientist of Ukraine, and laureate of the State Prize of Ukraine. G. Y. Burchynsky, throughout his life, was brought up on the traditions of the Kyiv therapeutic school. A close relationship with the Kyiv therapeutic school largely determined his personality as a doctor, teacher, scientist, and head of the department. In the years 1954 — 1962, Georgiy Yosypovych was the head of the Department of Therapy at the School of Dentistry. Since 1962, he had been the head of the Department of Faculty Therapy at the Kyiv Medical Institute for 24 years. G. Y. Burchynsky paid much attention to the study of pulmonary pathology. Based on the research materials, the monograph «Suppurative processes in the lungs» was issued in 1950. In particular, G. Y. Burchynsky developed a pathogenetic classification of pulmonary suppurations. One of the first in Ukraine, he applied the technique of endobronchial administration of antibiotics, He developed and introduced into practice the technique of zonal, or local, instillation using a bronchoscope. Gastrointestinal diseases have always been in the focus of Kyiv therapeutic school. G. Y. Burchynsky paid special attention attention to the problems of peptic ulcers. As a result, new data were obtained about this disease, which is outwardly clear but inwardly mysterious. G. Y. Burchynsky and his colleagues did a detailed study on the course of peptic ulcers, even during wartime. They looked at the etiology, pathogenesis, changes in the ultrastructure of the gastric mucosa, general changes, and questions about pathogenetic therapy for this disease. Experimental studies on the model of reproduction of a hypothalamic ulcer, as well as the results of studying the ultrastructure of gastroduodenal mucosa, confirmed the importance of the disturbances of nervous trophism. An experimental study on the pharmacodynamics of anticholinergics, which suppress cholinergic stimulation of the stomach and duodenum, showed that they can be used in clinical practice as a way to treat peptic ulcer disease. Under the supervision of G. Y. Burchynsky, two doctoral dissertations on the problem of peptic ulcers were defended at the department. Observations and results of the studies, performed by Georgiy Yosypovych and his colleagues, are reflected in the papers and monographs, such as “Peptic Ulcer,” “Clinical Gastroenterology,” and the relevant chapters of multi­volume guidelines and the Big Medical Encyclopedia.

Cytoprotection in gastroesophageal reflux disease and prospects for the use of cytoprotective agents

The analysis of publications is devoted to the problem of treatment and prevention of gastroesophageal reflux disease with the use of cytoprotectors. Special attention is paid to Gastrotop, the new complex of plant origin. Gastrotop (Еrвоzета S.p.A, San Marino) is a new medication with cytoprotective action, containing Mucosave CG, a standardized complex of polysaccharides from the stems of Indian prickly pear (Opuntia ficus‑indica, 33.5%), leaves of European olive (Olea europaea, 24.0%); a mixture of sodium alginate and salts (sodium alginate — 50 mg, potassium bicarbonate — 10 mg, calcium carbonate — 10 mg), an extract of the leaves of Malva sylvestris L. 50 mg. Its action is aimed at the increasing of protection of esophageal and gastroduodenal mucosa from irritating effects of hydrochloric acid, pepsin, and the detergent effect of bile during reflux by means of formation of a strong mucoadhesive biofilm on the walls of the esophagus. The authors present the results of a randomized, double‑blind, controlled clinical trial evaluating the efficacy and safety of a preparation based on alginate/sodium bicarbonate in combination with extracts obtained from Opuntia ficus indica and Olea europaea related to polyphenols on the dynamics of GERD symptoms. It has been established that Gastrotop is well tolerated and effective in controlling symptoms associated with mild GERD manifestations. The results demonstrated the perspective of administration of a standardized complex of polysaccharides as part of Gastrotop in cases when it’s necessary to cancel antisecretory drugs (in particular, proton pump inhibitors PPIs), for example, before assessing the persistence of Helicobacter pylori infection or for the purpose of monitoring of the eradication effectiveness. The use of cytoprotectors in GERD promotes the reduction of incidence and prevention of possible complications, caused by the long‑term PPIs’ use.

Cytoprotectant Doctovit: perspectives of the use at acid-dependent gastroduodenal diseases

The paper presents analysis of publications devoted to the use of cytoprotectant Doctovit at acid‑dependent gastroduodenal diseases and prospects of its use at inflammatory and erosive injuries of the esophagus, stomach and duodenum. A pathogenetic substantiation of the expediency of using the Doctovit (a complex of vitamins U (methylmethionine) and B5 (dexpanthenol)) is presented for cases of erosive and ulcerative (Helicobacter pylori‑associated) gastroduodenal lesions and at NSAID‑gastropathy, as well as at preservation of inflammatory changes in the gastric mucosa after antihelicobacter therapy (posteradication syndrome). The mechanism of action of Doctovit components is described. The review of investigations has been presented that showed normalization of secretory stomach function (in particular due to vitamin U methylation of histamine and its transformation into an inactive form), faster ulcers’ healing, analgesic, gastroprotective, antioxidant and lipotropic effects, which contribute to the stimulation of healing of mucosal erosions and ulcers in the digestive tract, positive dynamics of the histological picture of the gastroduodenal mucosa in patients who received Doctovit as a part of complex therapy. The positive effects included decrease in the severity of inflammatory cellular infiltration of the mucosa own lamina, disappearance of lymphoid follicles due to improvement in the condition of the epithelium due to an increase in its compensatory reparative regeneration, improvement in the condition of the integumentary pit epithelium of the stomach after treatment and strengthening of its mucin‑producing function with improvement in the quality of mucus The expediency of further use of Doctovit in patients with acid‑dependent pathology of the digestive tract is substantiated.

Assessment of morphological changes in the gastroduodenal area of patients with chronic pancreatitis in comorbidity with chronic viral hepatitis C

Background. Viral hepatitis C (HCV) is not only as a liver disease but also as a systemic (generalized) infection that affects ot­her organs, in particular, the pancreas and gastroduodenal zone. The state of the gastrointestinal mucosa in combined course of chronic pancreatitis (CP) and chronic HCV is little studied, but extremely relevant, as it is important for the clinical course, the quality of life of patients, as well as for assessing the safety of the performed (etiotropic, etc.) and planned restorative comprehensive treatment of such patients. The purpose is to evaluate the morphological changes of the gastroduodenal mucosa of patients with chronic pancreatitis associated with chronic viral hepatitis C who were treated etiotropically. Materials and methods. Thirty patients with CP and 65 patients with CP in comorbidity with chronic HCV after etiotropic treatment of HCV were examined. Regardless of the HCV genotype, they received a course of treatment with sofosbuvir at a dose of 400 mg and velpatasvir 100 mg in the morning after meals for 3 months (some patients took daclatasvir at a dose of 60 mg also in the morning after meals for 3 months instead of velpatasvir). The period after diagnosed and treated HCV before the examination was on average (2.35 ± 0.61) years. All patients underwent a morphological study of gastric and duodenal biopsy samples obtained by esophagogastroscopy. The prepared samples were evaluated according to the international OLGA and OLGIM systems based on the evaluation of 5 gastric biopsies (1 from the corner of the stomach, 2 from the body, and 2 from the antrum) with a description of the main pathomorphological changes evaluated on a visual analog scale. Alcian yellow and toluidine blue were used to detect H.pylori. An own system for assessing the morphological state of the gastroduodenal mucosa was also proposed. Results. The detected structural changes indicate the presence of chronic atrophic gastritis with moderate dysplasia of the glandular epithelium. Stage of chronic gastritis according to the OLGA system was III. Stage of chronic gastritis according to the OLGIM system was III. Thus, the practically asymptomatic course of quite significant gastroduodenal changes in CP combined with chronic HCV requires additional therapeutic influence, as well as an assessment of comprehensive treatment based on the effect on the gastroduodenal mucosa. In case of changes in gastroduodenal mucosa in CP on the background of chronic HCV, in contrast to those with isolated CP, a significantly higher level of inflammatory infiltrate density (moderate (2+) vs. mild (1+)) is determined, which is accompanied by moderate neutrophilic infiltration (2+) vs. mild (1+) and mild lymphohistiocytic infiltration (1+) versus no such infiltration (0), the appearance of intestinal metaplasia (2+) and moderate non-metaplastic glandular atrophy (2+) versus the absence of metaplasia (0) and mild non-metaplastic glandular atrophy (1+), as well as zones of metaplastic atrophy (1+), which was manifested by the appearance of Paneth cells and goblet cells. In CP with chronic HCV, mucosa has atrophic changes. Metaplasia is manifested by a change in cellular phenotype: complete intestinal metaplasia type I–II is manifested by the appearance of Paneth cells and goblet cells; incomplete — by the presence of columnar epithelium and goblet cells; colonic metaplasia — by enlargement of the glands and the absence of Paneth cells. Conclusions. It was proved that the state of the gastric and duodenal mucosa in the group of patients with CP and chronic HCV was significantly severe than that in isolated CP: lymphohistiocytic infiltration of the mucous membrane was detected 2.68 times more often, non-metaplastic infiltration glandular atrophy (there was practically no glandular atrophy in the group of isolated CP) — 12.65 times more often, metaplastic atrophy (it was not detected in the group of CP) — 10.64 times more often, acute leukocyte infiltration — 2.31 times more often, dysplasia of the mucosal epithelium (with isolated CP, mild dysplasia was detected) — 7.30 times more often, erosion of the mucosal epithelium — 3.07 times more often, focal hyperplasia of the glands — 3.88 times more often, intestinal metaplasia — 12.89 times more often, which was practically absent in CP. In general, the total number of pathological signs of the mucous membrane in the group of CP with comorbid chronic HCV was found to be 2.76 times higher than that in isolated CP.

Review of Toxic Chemical Factors Influence in Gastric and Duodenal Ulcers

ABSTRACT Peptic ulcer is a lesion most often located in the stomach or the proximal duodenum. The incidence, the hospitalization rate and the associated mortality in the last decades is decreasing due to modern therapy and hygiene measures. Approximately half of the population is colonized by H. Pylori, which is one of the main causes of ulcers. Other contributing factors are diet and stress. Non-steroidal anti-inflammatories cause damage to the gastro-duodenal mucosa by inhibiting cyclooxygenase-1. Concomitant consumption of proton pump inhibitors can be a solution. Natural evolution can lead to healing or complications. Ulcer perforation is one of the loudest and most serious complications of ulcers. Alcohol consumption has been shown to be a strong risk factor. Various studies have shown that smokers have a double risk of developing gastro-duodenal ulcers.

THE DIAGNOSTIC ACCURACY OF H. PYLORI CULTURE AND RAPID UREASE TEST IN THE DIAGNOSIS OF H.PYLORI INFECTION KEEPING HISTOPATHOLOGY AS THE GOLD STANDARD

Objective: The aim of this study was to determine the diagnostic accuracy of biopsy-based tests in the detection of Helicobacter Pylori infections keeping histopathology as a gold standard. Materials and Methods: This validation study was conducted from August 2018 to February 2019 at Khyber medical college, pathology department, Peshawar, and comprised biopsy samples of 87 patients obtained via endoscopy which was done at the gastrointestinal endoscopy department, Hayatabad medical complex (HMC). Patients with a history of prior antibiotics and PPIs were excluded from the study. Rapid urease test (RUT) and culture of gastroduodenal biopsies were validated against the histopathological examination of gastroduodenal mucosa. Results: Out of 87 patients, 57.47% (50/87) were male and 42.52% (37/87) were female patients with an age range of 18 -80 years and a mean age of 45 years. Endoscopic findings showed 64.36% (56/87) of patients with gastritis, duodenitis with 6.89% (6/87), peptic and duodenal ulcers with 22.98% (20/87), erosion with 4.59% (4/87) and adenocarcinoma of stomach with 2.29% (2/87). The sensitivity and specificity of culture were 45.45% and 90.7% respectively, while positive and negative predictive values were 62.5% and 83% respectively. The sensitivity and specificity of the rapid urease test (RUT) were 81.81% and 90% while positive and negative predictive values were 90% and 94% respectively. Conclusion: The sensitivity and specificity of the rapid urease test were 82 and 90% respectively, while that of culture was 45 and 91% respectively. Keys Words: Helicobacter Pylori, Gastritis, Rapid urease test, Adenocarcinoma

Phytotherapy of Gastric Ulcer (Literature Review)

Pharmacotherapy of diseases of the stomach and duodenum should be aimed at restoring and normalizing the interaction of acid-pepsin and gastroduodenal mucosa protectors in the gastric mucosa. Peptic ulcer disease is a common disease that affects millions of people and has a high recurrence rate. "No stomach acid, no ulcer" is a false assumption. Excessive secretion of gastric acid is only one factor in the pathogenesis of peptic ulcer disease. Their etiology is multifactorial, both offensive and defensive. It develops when the balance of its components is disturbed. Due to the limited efficacy and serious side effects of currently available drugs, its treatment faces great difficulties. Natural products such as plants and their isolated compounds have been widely used in experimental models of gastric ulcer. In these studies is a literature review of flavonoid-containing herbal plants showing ulcer activity in experimental models using different mechanisms of action

Gastroduodenal injury and repair: novel targets for therapeutic intervention.

Although the mucosal barrier serves as a primary interface between the environment and host, little is understood about the repair of acute, superficial lesions or deeper, persistent lesions that if not healed, can be the site of increased permeability to luminal antigens, inflammation and/or neoplasia development. Recent studies have focused on focal adhesion kinase, which regulates controlled matrix adhesion during restitution after superficial injury. Actin polymerization regulates cell migration and the importance of actin-related proteins was also highlighted. Work on SARS-CoV-2 infection lent important new insights on gastroduodenal mucosal injury in patients with Covid-19 infection and work done with organoids and intestine-on-a-chip contributed new understanding about how coronaviruses infect gastrointestinal tissues and its resulting barrier dysfunction. A novel risk stratification paradigm was proposed to assist with decision making about repeat endoscopy for patients with gastric or duodenal ulcers and new therapeutic options were studied for ulcer disease. Lastly, work to support the mechanism of metaplasia development after deep injury and parietal cell loss was provided using novel transgenic mouse models. Recent studies highlight novel molecular targets to promote mucosal healing after injury of the gastroduodenal mucosa.

A Novel Method for Detecting Lanthanum Phosphate Deposition in the Gastroduodenal Mucosa Using Fluorescence Microscopy.

Diagnostic utility of fluorescence microscopy for lanthanum phosphate deposition in the gastrointestinal mucosa has not been reported previously. In this study, we comparatively assessed the light, electron, and fluorescence microscopy features of gastroduodenal lanthanum phosphate deposition in 10 patients with deposits in the stomach and 5 patients with deposits in the duodenum. During light microscopy, lanthanum deposits were observed as dark-brown, needle-shaped, or crystalloid structures and pale red amorphous materials. During electron microscopy, the deposited material appeared as bright aggregates. Fluorescence microscopy also revealed lanthanum deposits as bright areas under green, red, and blue filters. The deposits were more easily recognizable on electron and fluorescence microscopy than on light microscopy. Furthermore, during fluorescence microscopy, the green filter provided the most clear visualization of lanthanum phosphate. In conclusion, fluorescence microscopy with a green filter is useful in determining the degree and extent of lanthanum deposition in the gastroduodenal mucosa.

Electroacupuncture ameliorates peptic ulcer disease in association with gastroduodenal microbiota modulation in mice.

Peptic ulcer disease (PUD) is a common disease and frequently encountered in the clinic. Accumulating evidence suggests that PUD is associated with the gastrointestinal microbiota. Electroacupuncture (EA) is an improved version of acupuncture, which can improve the clinical effect by increasing the stimulation and delivering appropriate electrical pulses to needles. This method has been widely used in the treatment of peptic ulcer disease. However, its effect on gastrointestinal microbiota remains unclear. Therefore, in the present study, the ameliorative effect of EA was evaluated on the gastroduodenal mucosa, and the regulatory effect of the gastroduodenal microbiota was assessed in PUD mice. A total of 48 male Kun Ming mice were randomly divided into the following groups: normal control group (NC), PUD model group (PUD), Shousanli group (LI10), and Zusanli group (ST36) (n=12). The mice in groups LI10 and ST36 were treated with EA at LI10 and ST36, respectively. This intervention was continued for 7 days. Subsequently, we evaluated the morphological changes in the gastric and duodenal mucosa, and specific indices were measured, including the contents of serum dopamine (DA), the trefoil factor (TFF), and the vasoactive intestinal peptide (VIP). In addition, the gastric and duodenal microbiota were assessed via 16S ribosomal DNA sequencing. The results indicated that EA at LI10 or ST36 significantly reduced the injury of the gastroduodenal mucosa in PUD mice. The gastric microbial community structure of the groups LI10 and ST36 was similar to that of the NC group following comparison with the microbial community structure of the PUD model group. Moreover, the abundance of Firmicutes in the stomach was decreased, whereas that of Bacteroidetes was increased, and the abundance of Firmicutes in the duodenum was decreased. Furthermore, the microbial diversity and richness of the gastric microbiota in group LI10 were also significantly increased, and the serum dopamine and trefoil factor levels in group ST36 were significantly increased. Therefore, it is suggested that EA ameliorating PUD is in association with improving the levels of DA and TFF and regulating the relative abundances of Firmicutes and Bacteroidetes in the gastric microbiota.

Preclinical safety assessment of MV-s-NAP, a novel oncolytic measles virus strain armed with an H. pylori immunostimulatory bacterial transgene

Despite recent therapeutic advances, metastatic breast cancer (MBC) remains incurable. Engineered measles virus (MV) constructs based on the attenuated MV Edmonston vaccine platform have demonstrated significant oncolytic activity against solid tumors. The Helicobacter pylori neutrophil-activating protein (NAP) is responsible for the robust inflammatory reaction in gastroduodenal mucosa during bacterial infection. NAP attracts and activates immune cells at the site of infection, inducing expression of pro-inflammatory mediators. We engineered an MV strain to express the secretory form of NAP (MV-s-NAP) and showed that it exhibits anti-tumor and immunostimulatory activity in human breast cancer xenograft models. In this study, we utilized a measles-infection-permissive mouse model (transgenic IFNAR KO-CD46Ge) to evaluate the biodistribution and safety of MV-s-NAP. The primary objective was to identify potential toxic side effects and confirm the safety of the proposed clinical doses of MV-s-NAP prior to a phase I clinical trial of intratumoral administration of MV-s-NAP in patients with MBC. Both subcutaneous delivery (corresponding to the clinical trial intratumoral administration route) and intravenous (worst case scenario) delivery of MV-s-NAP were well tolerated: no significant clinical, laboratory or histologic toxicity was observed. This outcome supports the safety of MV-s-NAP for oncolytic virotherapy of MBC. The first-in-human clinical trial of MV-s-NAP in patients with MBC (ClinicalTrials.gov: NCT04521764) was subsequently activated.

Influence of comorbidity of peptic ulcer of duodenum and erosive-ulcerative changes of the mucous gastroduodenal system on functional and morphological manifestations

Peptic ulcer of the duodenum and stomach is one of the most common diseases of internal organs. The clinical picture of peptic ulcer is characterized by polymorphism and depends on the localization of the ulcerative defect, its size and depth, the secretory function of the stomach, the age of the patient. The purpose of this study is to determine the size and shape of the ulcerative defect in the duodenum in case of erosive and ulcerative changes in the gastroduodenal mucosa, as well as to study the pH of the environment in the duodenum, which is necessary to optimize the treatment of this pathology, this will prevent the development of complications.

Distribution of transient receptor potential vanilloid-1 channels in gastrointestinal tract of patients with morbid obesity.

BACKGROUNDTransient receptor potential vanilloid-1 (TRPV1), a nonselective cation channel, is activated by capsaicin, a pungent ingredient of hot pepper. Previous studies have suggested a link between obesity and capsaicin-associated pathways, and activation of TRPV1 may provide an alternative approach for obesity treatment. However, data on the TRPV1 distribution in human gastric mucosa are limited, and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown.AIMTo clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals.METHODSForty-six patients with a body mass index (BMI) of > 40 kg/m2 and 20 patients with a BMI between 18-25 kg/m2 were included. Simultaneous biopsies from the fundus, antrum, and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy. Age, sex, history of alcohol and cigarette consumption, and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly. Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus, antrum, and duodenum tissues using an immunoreactivity score. Data were analyzed using SPSS 17.0.RESULTSTRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum. Unlike foveolar cells in the antrum, TRPV1 was relatively low in foveolar cells in the fundus (4.92 ± 0.49 vs 0.48 ± 0.16, P < 0.01, Mann-Whitney U test). Additionally, the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum (1.33 ± 0.31 vs 2.95 ± 0.46, P < 0.01, Mann-Whitney U test). TRPV1 expression levels of different cell types in the fundus, antrum, and duodenum tissues of the morbidly obese group were similar to those of the control group. Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged ≥ 45 years than in patients < 45 years (3.03 ± 0.42, 4.37 ± 0.76, 2.28 ± 0.55 vs 1.9 ± 0.46, 1.58 ± 0.44, 0.37 ± 0.18, P = 0.03, P < 0.01, P < 0.01, respectively, Mann-Whitney U test). The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension (diabetes: 2.11 ± 0.67 vs 1.02 ± 0.34, P = 0.04; hypertension: 2.42 ± 0.75 vs 1.02 ± 0.33, P < 0.01 Mann-Whitney U test).CONCLUSIONThe expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients.

Lymphocytic gastritis and its relationships with other gastrointestinal disorders.

Lymphocytic gastritis (LyG) is a histopathologic finding of unknown clinical relevance. To explore the clinical epidemiology of LyG and its associations with Helicobacter pylori (Hp) infection, coeliac disease (CD) and microscopic colitis (MC) METHODS: In a cross-sectional study, the demographic, clinical, and histopathologic data of patients with and without LyG were compared. Between 2008 and 2020, 1.5 million patients with endoscopic biopsies of the gastroduodenal mucosa were extracted from a database. LyG diagnoses were reviewed to collect detailed information regarding its topographic distribution within the stomach. In a large subgroup of 400000 patients, tissue samples from the colon were also available. Of 1481336 patients, 341 had LyG with Hp and 2697 had Hp-negative LyG (with an overall prevalence of 0.21%). In patients with Hp-negative LyG, 450 (17%) had corpus-predominant LyG, 1068 antrum-predominant LyG (40%), and 1179 pangastric LyG (44%). LyG was more common in males and in subjects aged 50-70years. There was no significant ethnic variation. Anaemia, diarrhoea, and weight loss were more common in patients with than without LyG. In 35% and 19% of patients, LyG was associated with CD and MC, respectively. All 72 patients with Hp-positive LyG and 280 of 310 patients with Hp-negative LyG with follow-up biopsies became free of LyG within a year. Most cases of LyG may represent a self-limited expression, frequently associated with other GI conditions, such as Hp infection, CD, and MC. In most patients, LyG is likely to resolve within a year after its initial diagnosis.

Safety and efficacy of acetylsalicylic acid in the secondary prevention of cardiovascular diseases in combination with comorbid diseases. COVID-19 treatment options

Secondary prevention of cardiovascular disease with aspirin is a very important issue. Аcetylsalicylic acid ensures the prevention of premature death, inhibition of progression and the achievement of partial regression of coronary atherosclerosis, prevention of clinical complications and exacerbations of the disease, reduction of the number of cases and the duration of hospitalization. The most promising direction of modern cardiology is considered to be the prevention of cardiovascular diseases (CVD) and their complications (CVD). This is due to two factors: an increase in the life expectancy of the world’s population as a whole and the persistent leadership of coronary heart disease and brain stroke as the leading causes of death, and disability. The pathogenetic aspects of the administration of acetylsalicylic acid are discussed. The most common dosage form of low-dose (ld) preparations of acetylsalicylic acid (ASA) for preventive use is an intestinal-soluble tablet — 80.6% in the structure of ldASK preparations. Low-dose ASK preparations are mainly presented (84.4%) in the form of monopreparations containing only ASA as the active substance, most often at a dose of 100 mg. However, the side effects of aspirin limit drug intake. This is also due to the high frequency of comorbid diseases such as bronchial asthma and stomach ulcer. The article discusses the issue of prescribing acetylsalicylic acid and the possibility of treating patients with concomitant bronchial asthma, gastric ulcer and obesity. The prevalence of gastroduodenal lesions was significantly lower with intestinal-coated ASA than with buffered acetylsalicylic acid. It was demonstrated that endoscopic lesions of the gastroduodenal mucosa were significantly less likely when using intestinal-coated ASA (100 mg / day) than when using conventional аcetylsalicylic acid, and the assessment of the lesion when using intestinalcoated ASA was similar to the assessment of placebo without аcetylsalicylic acid. In addition, the issue of the possibility of including аcetylsalicylic acid in the treatment regimen for COVID 19 is being discussed.