Circulating concentration of interleukin-37 in Helicobacter pylori-infected patients with peptic ulcer: Its association with IL-37 related gene polymorphisms and bacterial virulence factor CagA.

The immunopathologic responses play a major role in the development of H. pylori (HP)-related gastrointestinal diseases. IL-37 is an anti-inflammatory cytokine with potent suppressive effects on innate and adaptive immune responses. Here, we investigated the IL-37 levels and two single nucleotide polymorphisms (SNPs) including rs3811047 and rs2723176 in IL-37 gene in HP-infected peptic ulcer (PU) patients to identify any relationship. Three groups, including 100 HP-infected PU patients, 100 HP-infected asymptomatic (AS) subjects and 100 non-infected healthy control (NHC) subjects were enrolled to study. Serum IL-37 levels and the genotyping at rs3811047 and rs2723176 were determined using ELISA and SSP-PCR methods, respectively. Significantly higher IL-37 levels were observed in PU patients compared with AS and NHC groups (P < 0.0001). In both PU and AS groups, the CagA+ HP-infected participants displayed higher IL-37 levels compared with those infected with CagA- strains (P < 0.0001). There were significant differences between PU, AS and NHC groups regarding the distribution of genotypes and alleles at rs3811047 and rs2723176 SNPs. The genotype GG and allele G at IL-37 rs3811047 SNP, and the genotype CC and allele C at IL-37 rs2723176 SNP more frequently expressed in PU patients than total healthy subjects (AS + NHC groups) and were associated with an increased risk of PU development (genotype GG: RR = 3.08, P < 0.009; allele G: RR = 2.94, P < 0.01; genotype CC: RR = 5, P < 0.01; and allele C: RR = 5.0, P < 0.02, respectively). The PU patients with allele A at IL-37 rs2723176 SNP expressed higher amounts of IL-37 compared with patients carried allele C at the same position (P < 0.05). In AS carriers and NHC individuals, the IL-37 levels in subjects carried genotype AA or allele A at IL-37 rs2723176 SNP were higher than those carried genotype CC or allele C at the same location (P < 0.01 and P < 0.02 for AS group; P < 0.0001 and P < 0.001 for NHC subjects, respectively). The increased IL-37 levels may be considered as a valuable marker of PU development in HP-infected individuals. The SNPs rs3811047 and rs2723176 were associated with PU development. The CagA status of HP and IL-37 rs2723176 SNP may affect the IL-37 levels.

Variation in descriptors of patient characteristics in randomized clinical trials of peptic ulcer repair: a systematic review.

BACKGROUND: The ability to compare findings across surgical research is important. Inadequate description of participants, interventions or outcomes could lead to bias and inaccurate assessment of findings. The aim of this study was to assess consistency of description of participants using studies comparing laparoscopic and open repair of peptic ulcer as an example. METHODS: This systematic review is reported in line with the PRISMA checklist. Searches of MEDLINE and Embase databases were performed to identify studies comparing laparoscopic and open repair of perforated peptic ulcer in adults, published in the English language. Manuscripts were dual-screened for eligibility. Full texts were retrieved and dual-screened for inclusion. Data extracted from studies included descriptors of participants in studies from tables and text. Descriptors were categorized into conceptual domains by the research team, and coverage of each domain by study was tabulated. RESULTS: Searches identified 2018 studies. After screening, 37 full texts were retrieved and 23 studies were included in the final synthesis. A total of 76 unique descriptors were identified. These were classified into demographics (11 descriptors), vital signs (9 descriptors), disease-specific characteristics (10 descriptors), presentation and pathway factors (4 descriptors), risk factors (8 descriptors), laboratory tests (14 descriptors) and baseline health (28 descriptors). The number of descriptors in a single study ranged from three to 31. All studies reported at least one demographic descriptor. Laboratory tests was the least frequently described domain. CONCLUSION: Study participants are described inconsistently in studies of a single example surgical condition.

ANTECEDENTES: La capacidad de comparar los hallazgos en la investigación quirúrgica es importante. Una descripción inadecuada de los participantes, las intervenciones o los resultados podría conllevar sesgos y una evaluación incorrecta de los hallazgos. El objetivo de este estudio fue evaluar la consistencia en la descripción de los participantes utilizando los estudios comparativos de la cirugía laparoscópica con la cirugía abierta en el tratamiento de la úlcera péptica, como modelo. MÉTODOS: Esta revisión sistemática se presenta de acuerdo con la lista de verificación PRISMA. Se realizaron búsquedas en las bases de datos MEDLINE y EMBASE para identificar estudios, publicados en inglés, que compararan el tratamiento quirúrgico laparoscópico y abierto de la úlcera péptica perforada en adultos. Los artículos elegibles fueron sometidos a un doble cribaje para su selección. Se recuperaron los textos completos de los artículos y se evaluaron por partida doble para su inclusión. Los datos extraídos correspondían a los términos que describían las poblaciones de estudio en el texto y en las tablas de los artículos. Dichos términos descriptores fueron clasificados por el equipo de investigación en dominios conceptuales, registrándose la cobertura de cada dominio en cada estudio. RESULTADOS: Las búsquedas bibliográficas identificaron 2.018 estudios. Después de la selección, se recuperaron 37 artículos de texto completo y se incluyeron 23 estudios en la síntesis final. Se identificaron un total de 76 descriptores únicos. Dichos descriptores se clasificaron en demográficos (11 variables), signos vitales (9 variables), características específicas de la enfermedad (10 variables), factores de presentación y del proceso (4 variables), factores de riesgo (8 variables), pruebas de laboratorio (14 variables) y estado de salud basal (28 variables). El número de descriptores en un solo estudio varió de 3 a 31. Todos los estudios presentaron al menos un descriptor demográfico. Las pruebas de laboratorio fueron el dominio descrito con menor frecuencia. CONCLUSIÓN: Esta revisión demuestra que los participantes en los estudios se describen de manera inconsistente, tras haber tomado como modelo los estudios de una sola patología quirúrgica.

Impact of Helicobacter pylori Virulence Factors on the Host Immune Response and Gastric Pathology.

Helicobacter pylori chronically infects nearly half the world's population, yet most of those infected remain asymptomatic throughout their lifetime. The outcome of infection-peptic ulcer disease or gastric cancer versus asymptomatic colonization-is a product of host genetics, environmental influences, and differences in bacterial virulence factors. Here, we review the current understanding of the cag pathogenicity island (cagPAI), the vacuolating cytotoxin (VacA), and a large family of outer membrane proteins (OMPs), which are among the best understood H. pylori virulence determinants that contribute to disease. Each of these virulence factors is characterized by allelic and phenotypic diversity that is apparent within and across individuals, as well as over time, and modulates inflammation. From the bacterial perspective, inflammation is probably a necessary evil because it promotes nutrient acquisition, but at the cost of reduction in bacterial load and therefore decreases the chance of transmission to a new host. The general picture that emerges is one of a chronic bacterial infection that is dependent on both inducing and carefully regulating the host inflammatory response. A better understanding of these regulatory mechanisms may have implications for the control of chronic inflammatory diseases that are increasingly common causes of human morbidity and mortality.

NFKB2 gene expression in patients with peptic ulcer diseases and gastric cancer.

Gastric cancer is one of the most common worldwide types of cancer. It is a multifactorial disease and both environmental and genetic factors play an important role in its etiology. Evaluation of the relative expression level of NFKB2 gene in two groups of patients: peptic ulcer and gastric cancer and its role in the pathomechanism of these diseases was the aim of this study. RNA was isolated from: 79 samples of peptic ulcer, 22 gastric cancer and 11 control tissue. The real-time PCR technique was used to study the expression of NFKB2 gene. The relative expression level of NFKB2 gene was a variable in all three studied groups. The relative NFKB2 gene expression depends on the type of a disease. Peptic ulcer cases showed the increased relative NFKB2 gene expression to control group (p = 0.0000). Cancer cases presented decreased relative NFKB2 gene expression to normal stomach tissue (p = 0.0183). There are statistically important differences in the investigated gene expression between peptic ulcer, where the expression level is higher comparing to gastric cancer and control tissue which confirmed that such an activation is connected with an inflammatory process. The relative expression level of NFKB2 is decreased in cancer cases as opposed to control tissue and peptic ulcer cases which could suggest that during carcinogenesis of gastric cancer inhibition of NF-kB pathway takes place which could be a promising factor for patients.

Perforation of anastomotic peptic ulcer following pancreaticoduodenectomy: a report of three cases.

BACKGROUND: Perforation of a marginal peptic ulcer after pancreaticoduodenectomy (PD) can lead to severe conditions, although its clinical features have not been well reported. In this article, we present three cases of marginal peptic ulcer perforation after PD that we experienced in our institute and attempt to clarify its appropriate treatment and prevention. CASE PRESENTATION: Marginal ulcer perforation confirmed with computed tomography and/or surgical exploration occurred in 3 (1.8%) of 163 consecutive patients who underwent PD (including 160 patients who underwent a total or subtotal stomach-preserving procedure) at our institution. The three patients (one man and two women) had a median age of 77 (65-79) years. Two of these patients had a medical history of duodenal peptic ulcer. All three patients had biliary neoplasms. Two of the patients underwent subtotal stomach-preserving PD with antro-jejunal anastomosis, and the other patient underwent pylorus-preserving PD with duodenal jejunostomy. The perforation occurred with a sudden and severe onset of abdominal pain 34, 94, and 1204 days, respectively, after the PDs. At the time of the perforation, all of the patients had been withdrawn from postoperative prophylactic antipeptic ulcer agents, with the cessation periods ranging from 12 to 1008 days. In addition, all the patients were in fasting conditions for 1 to 13 days just before the perforation. Surgical treatment with direct suturing of the perforated ulcer was performed for two patients, while conservative therapy was performed for one patient. Their primary treatment courses were satisfactory. Chronic antisecretory agent therapy was prescribed for 562, 271, and 2370 days, respectively, from marginal ulcer perforation, and no ulcer recurrence was noted in any of the patients. CONCLUSIONS: Lack of antisecretory therapy and fasting were considered an essential cause of marginal peptic ulcer perforation after PD. In addition, unlike the native duodenum, the jejunal limb used for reconstruction to a preserved stomach may be at increased risk of ulceration. Chronic permanent administration of antisecretory agents and fasting avoidance are desirable for patients who have undergone stomach-preserving PD to prevent marginal ulcer perforation.

The expression profiling of circulating miR-204, miR-182, and lncRNA H19 as novel potential biomarkers for the progression of peptic ulcer to gastric cancer.

Deregulation of noncoding RNAs, microRNAs (miRNAs) and long noncoding RNA (lncRNA), are implicated in the initiation and progression of gastric cancer (GC). This study is a pilot case-control study carried out on 75 subjects, 40 of them were Helicobacter pylori-gastric ulcer patients and 35 were GC patients recruited from the Gastrointestinal Endoscopy Unit in Al-Kasr Al-Aini Hospital, Cairo University in Egypt. Real-time PCR was performed to evaluate the expression level of serum miR-204, miR-182, and lncRNA H19 in patients with peptic ulcer-progressed GC vs nonprogressed peptic ulcer patients. Fibroblast growth factor 18 (FGF-18)/FGF receptor 2 (FGFR2) expression and their downstream immunological and inflammatory signaling markers were assessed and their association with the addressed noncoding RNAs investigated. As regards miR-204 and miR-182, they were significantly increased (12.5 and 2.6 folds, respectively) in GU samples, compared with those of healthy control levels. The elevated levels of these miRNAs were significantly de-escalated in GC samples compared with GU and the fold decrease valued 2.2 fold for miR-204 and 1.8 folds for miR-182. On the other hand, the significant escalation in the level of lnRNA H19 in GU recorded a 16.6 fold increase and further elevation in its levels was evident in GC samples. The herein assessed miRNAs are correlated with disease duration and FGFR2 with miR-182 being significantly correlated with all inflammatory markers, TAC, INF-γ, matrix metallopeptidase 9, and FGF-18. In terms of diagnostic accuracy of assessed miRNAs (stages III to IV), the receiver operating characteristic analysis indicated that serum lncRNA H19 showed the highest diagnostic accuracy (95.5%), specificity (100%), and sensitivity (90.9%), compared with miR-204 and miR-182, which showed the same specificity (60%), sensitivity (72.7%), and diagnostic accuracy (68.8%). Our findings conclude that lnRNA H19, miR-204, and miR-182 may function as novel prospective plasma biomarkers to detect GC and its progression from H. pylori-peptic ulcer, which would be helpful to improve the theranostics of GC.

The influence of the Chuyou Yuyang granule on the Toll-like receptor/nuclear factor-κB signal pathway in Helicobacter pylori-positive peptic ulcer patients.

BACKGROUND: The cure rate of Helicobacter pylori (HP)-positive peptic ulcer has appeared to downward trend, and the resistance of the ulcer relapse has become a hot issue. METHODS: Hematoxylin and eosin staining was used to detect the repair of the damaged tissues in patients after treatment with the Chuyou Yuyang granule (CYYY). Elisa was used to analyze the expression of cytokine interleukin 18 (IL-18) and tumor necrosis factor α (TNF-α) in the patients' serum. Western blot analysis was used to explore the mechanism of the CYYY. Reverse-transcription polymerase chain reaction (RT-PCR) was used to detect the expression of microRNA-155a (miR-155a) and miR-146a in the blood of the patients and to confirm whether CYYY could cure peptic ulcer through regulation of miR-155a and miR-146a. RESULTS: The damaged gastric mucosal tissues of ulcer patients were significantly repaired by treating with CYYY. The pro-inflammatory cytokine IL18 and TNF-α were notably repressed after treating with CYYY. In addition, CYYY played a key role in regulation of the Toll-like receptor (TLR4)/nuclear factor-κB (NF-κB) signal pathway and the expression of miR-155a and miR-146a. CONCLUSION: CYYY was a highly effective therapeutic method for peptic ulcer patients by inhibiting the activation of the TLR4/NF-κB signal pathway and suppressing the expression of miR-155a and miR-146a.

Decreased circulating interleukin-33 concentration in Helicobacter pylori-infected patients with peptic ulcer: Evaluation of its association with a cytokine gene polymorphism, gender of patients and bacterial virulence factor CagA.

IL-33 has powerful immunoregulatory activities such as reinforcement of Th2 cell responses. The aim was to assess the circulating IL-33 levels and IL-33 rs1929992 polymorphism in H. pylori-infected peptic ulcer (PU) patients and asymptomatic (AS) subjects. Blood samples were obtained from 100 PU patients, 100 AS subjects and 100 uninfected individuals. Circulating IL-33 levels were detected by ELISA. After DNA extraction, the IL-33 rs1929992 polymorphism was determined using PCR-RFLP method. Serum IL-33 quantities were significantly lower in PU patients compared with AS and uninfected groups. IL-33 levels were higher in AS subjects compared with uninfected group. In PU, AS and uninfected groups, IL-33 levels were significantly higher in women than men. In PU and AS groups, the CagA+H. pylori-infected subjects exhibit higher IL-33 levels compared with carriers of CagA-H. pylori strains. In PU patients, the frequency of genotype GG and allele G at IL-33 rs1929992 was significantly higher compared with all healthy subjects (AS + uninfected groups). The presence of genotypes GG and AG, and allele G in rs1929992 conferred greater risk for PU. In whole H. pylori-infected population (PU + AS groups), IL-33 levels in individuals with genotype AA or allele A at rs1929992 were higher than subjects with GG genotype or allele G. The reduced IL-33 production could contribute to the PU development during H. pylori infection. The IL-33 levels may be affected by individual gender, rs1929992 polymorphism, and the CagA status of bacteria. The rs1929992-related GG genotype and G allele may be associated with PU development.

Automatic detection of erosions and ulcerations in wireless capsule endoscopy images based on a deep convolutional neural network.

BACKGROUND AND AIMS: Although erosions and ulcerations are the most common small-bowel abnormalities found on wireless capsule endoscopy (WCE), a computer-aided detection method has not been established. We aimed to develop an artificial intelligence system with deep learning to automatically detect erosions and ulcerations in WCE images. METHODS: We trained a deep convolutional neural network (CNN) system based on a Single Shot Multibox Detector, using 5360 WCE images of erosions and ulcerations. We assessed its performance by calculating the area under the receiver operating characteristic curve and its sensitivity, specificity, and accuracy using an independent test set of 10,440 small-bowel images including 440 images of erosions and ulcerations. RESULTS: The trained CNN required 233 seconds to evaluate 10,440 test images. The area under the curve for the detection of erosions and ulcerations was 0.958 (95% confidence interval [CI], 0.947-0.968). The sensitivity, specificity, and accuracy of the CNN were 88.2% (95% CI, 84.8%-91.0%), 90.9% (95% CI, 90.3%-91.4%), and 90.8% (95% CI, 90.2%-91.3%), respectively, at a cut-off value of 0.481 for the probability score. CONCLUSIONS: We developed and validated a new system based on CNN to automatically detect erosions and ulcerations in WCE images. This may be a crucial step in the development of daily-use diagnostic software for WCE images to help reduce oversights and the burden on physicians.

Cytoprotective agent for peptic ulcer prevention in patients taking dual antiplatelet agents: A randomized, double-blind placebo-controlled trial.

BACKGROUND AND AIM: Long-term use of dual antiplatelets is increasing, and most patients need primary peptic ulcer prophylaxis. The long-term use of proton pump inhibitors (PPIs) is associated with adverse events. We evaluated the efficacy of rebamipide for peptic ulcer prevention. METHODS: This randomized controlled trial was conducted between July 2014 and November 2017. Patients receiving dual antiplatelets for ≥ 1 year with no history of peptic ulcer bleeding or perforation were recruited and randomly assigned to the rebamipide (300 mg/day) group or the placebo group. Patients who used proton pump inhibitors were excluded. The primary endpoint was a new mucosal break on esophagogastroduodenoscopy at 3 or 12 months after treatment initiation. The secondary endpoints were hematocrit changes from the baseline, gastrointestinal bleeding, and chest pain. Antiplatelet function was assessed. RESULTS: In total, 95 eligible patients were identified; 12 were excluded, and 83 patients were randomized, with 66 (79.5%) and 59 (71.1%) patients eligible at the 3- and 12-month follow ups, respectively. The baseline characteristics were equivalent between the groups. During the 12 months of follow up, 13 patients (43.3%) taking rebamipide and 19 (65.5%) taking the placebo experienced mucosal injury (P = 0.07). Two patients (6.7%) taking rebamipide and eight (27.6%) taking the placebo had peptic ulcers ≥ 5 mm or < 5 mm with pigmented spots (P = 0.03). The changes in hematocrit were not different between the two groups. Neither bleeding ulcers nor chest pain was observed. CONCLUSION: Rebamipide is safe and may prevent peptic ulcers ≥ 5 mm in diameter or those with pigmented spots in patients receiving dual antiplatelets for 1 year (NCT02166008).

Oil-entrapped ranitidine HCl beads heal peptic ulcers via local and systemic mechanisms.

OBJECTIVE: Oral gastroretentive system is one of the site-specific drug delivery system, which is designed to be retained in upper GIT for a prolonged time. Ranitidine hydrochloride (RHCl), which is used frequently in treatment of peptic ulcer, is a suitable candidate for gastroretentive delivery systems. Dependently, floating oil-entrapped alginate beads of RHCl were developed and evaluated as an approach to site-specific delivery avoiding colonic degradation and enhancing both bioavailability and the proposed local effect. METHODS: Different formulations of floating beads were suggested and randomized using 24 full factorial design. Optimized formulation was subjected for in vivo studies to measure the oral bioavailability and the healing effect of induced peptic ulcers. RESULTS: Beads size ranged from 1.32 to 2.3 mm. All beads revealed excellent floating capabilities. Optimum formulation (F12) has entrapment efficiency of 70%, drug loading of 7% and 71% RHCl released after 6 h. SEM of F12 shows a grossly spherical structure with presence of oil droplets distributed throughout structure. AUC obtained from F12 was nonsignificantly higher than that of a commercial tablet. Signs of ulcer healing appeared clearly with F12 through appearance of granulation tissue, collagen fibers and newly formed blood vessels. Healing rate and extent obtained with a commercial tablet were less than F12. Quantitative analysis confirmed histopathological findings. CONCLUSION: Floating oil-entrapped beads are a promising approach for RHCl delivery to remain in stomach for a longer time ensuring site-specific delivery and consequently, enhancing local healing effect of peptic ulcers.

Helicobacter pylori and nonmalignant upper gastrointestinal diseases.

The review of the most important recent publications concerning the relation of Helicobacter pylori with peptic ulcer disease (PUD), noninvestigated and functional dyspepsia, and gastroesophageal reflux disease (GERD) is presented. H. pylori remains the main etiopathogenetic factor in complicated and uncomplicated PUD. Nevertheless, the role of nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin is increasing. The novel data did not confirm that PUD caused by NSAIDs and aspirin is less symptomatic. The role of glucocorticoids, immunosuppressants, and antidepressants seems to be of some importance. Although the involvement of H. pylori in functional dyspepsia is controversial, several data support the importance of H. pylori-induced gastritis in the pathogenesis of dyspeptic symptoms. Recent interventional studies have reported that H. pylori eradication improves dyspepsia mainly in areas with a high prevalence of this bacterium. Novel data regarding the relation of gastrointestinal peptides, ghrelin and obestatin, with H. pylori infection are also presented. Intriguing findings support the involvement of the gastric microbiota in the causation of chronic functional dyspepsia. Finally, some data concerning negative, positive, or neutral associations of H. pylori with gastroesophageal reflux disease (GERD) were published. In this context, today there is no evidence indicating that H. pylori eradication could worsen the symptoms or the course of GERD.

Downregulated regulatory T cell function is associated with increased peptic ulcer in Helicobacter pylori-infection.

BACKGROUND: Helicobacter pylori (H. pylori) chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease such as gastritis and peptic ulcer and induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. The objective of this study was to determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis and peptic ulcer and determined the relationship between main virulence factor of H. pylori and Tregs. METHODS AND MATERIALS: A total of 89 patients with gastritis, 63 patients with peptic ulcer and 40 healthy, H. pylori-negative subjects were enrolled in this study. Expression of CD4 and Foxp3 was determined by immunohistochemistry. Antrum biopsy was obtained for detection of H. pylori, bacterial virulence factors and histopathological assessments. TGF-ß1, IL-10 and FOXP3 expressions were determined by real-time polymerase chain reaction (qPCR). RESULTS: The numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-ß1, FOXP3, INF-γ and IL-17A in infected patients were significantly higher than the ones in uninfected patients. Also, the number of CD4+ T cells was independent on the vacuolating cytotoxin A (vacA) and outer inflammatory protein A (oipA), but it was positively correlated with cytotoxin-associated gene A (cagA). Instead, the number of Foxp3+ T cells was dependent on the vacA and oipA, but it was independent on cagA. The number of Foxp3+ T cells and the expression of IL-10, TGF-ß1 and FOXP3 in infected patients with gastritis were significantly higher than the ones in infected patients with peptic ulcer. Moreover, the number of CD4+ T cells and the expression of IL-17A and INF-γ was the lowest in the gastritis patients, however, increased progressively in the peptic ulcer patients. Additionally, the numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-ß1, FOXP3 and INF-γ were positively correlated with the degree of H. pylori density and chronic inflammation. CONCLUSION: Tregs are positively associated with vacA alleles and oipA status of H. pylori and histological grade but negatively associated with peptic ulcer disease.

No evidence to support a role for Helicobacter pylori infection and plasminogen binding protein in autoimmune pancreatitis and IgG4-related disease in a UK cohort.

BACKGROUND AND OBJECTIVES: Helicobacter pylori (H.pylori) plasminogen binding protein (PBP) has been proposed as an antigen triggering autoimmune pancreatitis (AIP), the pancreatic manifestation of IgG4-related disease (IgG4-RD). We investigated exposure to H. pylori infection, cytokine response and immunological memory to H. pylori PBP in a prospective IgG4-RD cohort in the UK. METHODS: Clinical and endoscopic evidence of peptic ulceration, serological H. pylori exposure and serum IgG4 levels were obtained in 55 IgG4-RD patients and 52 disease controls (DC) with autoimmune or inflammatory conditions with an elevated serum IgG4. Gastric and duodenal tissues were assessed for H. pylori and immunostained for IgG4. B and T cell ELISpot and cytokine luminex assays were used to detect immune responses to H. pylori PBP. RESULTS: 85% of IgG4-RD patients had pancreatic and/or biliary disease, 89% had extra-pancreatic manifestations, and 84% had an increased serum IgG4. Clinical dyspepsia (35.2%), gastritis (58%), peptic ulceration (7.4%) and H. pylori colonisation (24%) in IgG4-RD was similar to DC. In IgG4-RD, gastric tissue contained a chronic inflammatory infiltrate with a low IgG4+ plasma-cell count (<10/HPF; range 1-4/HPF), and duodenal specimens had an increased IgG4 count (>10/HPF; range 7-54) compared with DC (p < 0.01). Th1 and Th2 cytokine response and immunological B-cell memory to H. pylori PBP did not differ between IgG4-RD and DC. CONCLUSIONS: In a prospective UK cohort, the prevalence of gastric ulceration, exposure to H. pylori, cytokine response and immunological memory to H. pylori PBP did not differ in IgG4-RD patients compared with DC. This study does not support a role for H. pylori PBP as a microbial antigen in IgG4-RD. KEYWORDS FOR ABSTRACT: Peptic ulceration, Antigens, B cells, T cells, Interleukins, Helicobacter pylori.

Endoscopic characteristics of infection-associated peptic ulcers.

BACKGROUND: Aside from Helicobacter pylori, another cause for the development or worsening of gastrointestinal ulcers is scrub typhus, an acute febrile disease caused by Orientia tsutsugamushi. We aimed to compare the endoscopic characteristics of peptic ulcers caused by these infectious agents. METHODS: This retrospective case-control study involved patients who underwent upper gastrointestinal endoscopy at Chosun University Hospital in Korea. We compared endoscopic features and demographic characteristics between patients with H. pylori infection and those with O. tsutsugamushi infection. RESULTS: A total of 141 patients with peptic ulcer were included in the study. Compared to patients with O. tsutsugamushi infection (n = 62; age, 63.8 ± 12.1 years; male sex, 42%), those with H. pylori infection (n = 79; age, 53.0 ± 14.8 years; male sex, 81%) were younger and more likely to be male (P < .001 for both). Patients with O. tsutsugamushi infection were more likely to have multiple lesions (40/62, 64.5% vs 37/79, 46.8%; P = .042) and irregular-shaped lesions (27/62, 43.6% vs 20/79, 25.3%; P = .031). Patients with H. pylori infection had higher incidence of hemorrhagic ulcers (26/79, 32.9% vs 8/62, 12.9%; P = .007), and lesions occurred most often in the duodenum (43.0%), followed by the antrum (36.7%), body (34.2%), and angle (12.7%) of the stomach. In patients with O. tsutsugamushi infection, lesions occurred most often in the antrum (70.97%), followed by the duodenum (35.5%), body (22.6%), and angle (14.5%) of the stomach. In both groups, gastric ulcer lesions occurred most often in the antrum, followed by the body and angle of the stomach (36.7% vs 70.97%, 34.2% vs 22.6%, and 12.7% vs 14.5% for gastric ulcers associated with H. pylori and O. tsutsugamushi infection, respectively). Patients with O. tsutsugamushi infection had significantly higher incidence of ulcers on the antrum (70.97% vs 36.7%, P < .001) and the greater curvature (45.2% vs 24.0%, P = .012). Finally, 35.5% of patients with gastric ulcer caused by scrub typhus also had duodenal ulcer. CONCLUSION: This is the first study to compare endoscopic features of peptic ulcers caused by H. pylori and O. tsutsugamushi. Peptic ulcers in patients with H. pylori infection occurred predominantly in the antrum/body/lesser curvature and presented with single, round/oval lesions, while ulcers in patients with scrub typhus occurred predominantly in the antrum/greater curvature and presented with multiple, irregular lesions. Scrub typhus should be considered as a cause of duodenal ulcer in scrub typhus-endemic areas.

Helicobacter pylori infection and nonmalignant diseases.

A substantial decrease in Helicobacter pylori-associated peptic ulcer disease has been observed during the last decades. Drug-related ulcers as well as idiopathic ulcers are becoming predominant and are more refractory to treatment; however, H. pylori infection still plays an important role in ulcer bleeding and recurrence after therapy. The effect of H. pylori eradication upon functional dyspepsia symptoms has been reviewed in this article and generally confirms the results of previous meta-analyses. Additional evidence suggests a lack of impact upon the quality of life, in spite of improvement in symptoms. The association of H. pylori with gastroesophageal reflux disease and Barrett's esophagus remains controversial with a majority of published studies showing a negative association. Furthermore, a strong inverse relationship between the presence of H. pylori and the esophageal eosinophilia was also reported. Several studies and a review addressed the role of H. pylori in autoimmune gastritis and pernicious anemia. The association of the above still remains controversial. Finally, the necessity of routine endoscopy and H. pylori eradication before bariatric surgery is discussed. Several studies suggest the rationale of preoperative upper endoscopy and H. pylori eradication prior to surgery. However, the prevalence of H. pylori infection prior to surgery in these studies generally reflects the overall prevalence of the infection in the particular geographic area. In addition, results on the role of H. pylori in developing postoperative complications remain controversial.

Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs.

BACKGROUND AND AIM: Video-capsule endoscopy (VCE) has shown that intestinal ulcers are common in non-steroidal anti-inflammatory drugs (NSAIDs) users, although the mechanisms and management have not been clearly defined. To explore the contribution of oxidative stress and potential of anti-oxidants for NSAIDs-induced intestinal ulcers, we assessed human serum oxidative stress balance and the effect of anti-oxidants using a mouse model. METHODS: A total of 30 NSAIDs users (17 aspirin and 13 non-aspirin users) received VCE. Serum reactive oxygen metabolite (d-ROM) and antioxidative OXY-adsorbent test (OXY) were measured. The indomethacin (IND)-induced mouse intestinal ulcer model was used to assess the effect of anti-oxidants. Eight-week-old mice were divided into four groups; control diet and diet including IND (N group), IND and L-carnitine (NC group), and IND and vitamin E (NE group). RESULTS: Serum OXY levels among non-aspirin users were lower in the mucosal injuries positive group than the negative group (P < 0.05). In the mouse models, the degree of mucosal injuries was lower in NC and NE than N (P < 0.01). Serum d-ROM levels were lower in NC and NE than N (P < 0.01), and OXY levels were higher in NC than N and NE (P < 0.01). The degeneration of intestinal mitochondria was mild in NC and NE. The serum KC/CXCL-1 level and hepatic expression of the anti-oxidant molecule Gpx4 were lower in NC than N. CONCLUSIONS: Non-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers.

Co-administration of Magnesium Ion Prevents Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rats.

In a study to find ways to prevent the side effects of indomethacin (IMC), we previously reported that magnesium ion (Mg2+) can prevent the onset of IMC-induced gastric mucosa in adjuvant-induced arthritis (AA) rats, a model for rheumatoid arthritis (RA). In this study we investigated whether the co-administration of IMC and Mg2+ prevents the formation and aggravation of intestinal ulcerogenic lesions in AA rats. The single oral administration of an excessive dose of IMC (40 mg/kg) induces hemorrhagic lesions and nitric oxide (NO) production via inducible nitric oxide synthase (iNOS) in the jejunal and ileal mucosa of AA rats, and the extent of the lesions, as well as iNOS and NO levels in AA rats are higher than in normal rats. On the other hand, the co-administration of 200 mg/kg Mg2+ attenuates intestinal ulceration and the elevation in the iNOS and NO levels in AA rats. Further, hemorrhagic lesioning and enhanced iNOS and NO levels in AA rats also result from the repetitive oral administration of 3 mg/kg IMC (therapeutic dose) for 42 d (once a day), and these changes are also prevented by the co-administration of 200 mg/kg Mg2+. In conclusion, the co-administration of Mg2+ suppresses the ulcerogenic response to IMC in the jejunal and ileal mucosa of AA rats, probably by preventing the elevation of iNOS and NO levels in the region.

Fatty acid composition and mechanisms of the protective effects of myrtle berry seed aqueous extract in alcohol-induced peptic ulcer in rat.

This study aimed to investigate the antiulcer and antioxidant activities of myrtle berry seed aqueous extract (MBSAE) in a peptic ulcer model induced by ethanol in male Wistar rats. MBSAE is rich in total polyphenols, total flavonoids, and unsaturated fatty acids, particularly linoleic (18:2) and oleic (18:1) acids. MBSAE also exhibited in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 172.1 µg/mL) and superoxide anion (IC50 = 200.24 µg/mL) scavenging activities. In vivo, MBSAE provided dose-dependent protection against ethanol-induced gastric and duodenal macroscopic and histological alterations. Also, it inhibited secretory profile disturbances and lipid peroxidation, and preserved normal antioxidant enzyme activities and nonenzymatic antioxidant levels. More importantly, we showed that acute alcohol intoxication increased gastric and duodenal calcium, hydrogen peroxide, and free iron levels, whereas MBSAE treatment protected against intracellular mediator deregulation. In conclusion, we suggest that MBSAE has potent protective effects against alcohol-induced peptic ulcer in rat. This protection might be related in part to its antioxidant properties as well as its opposite effects on some studied intracellular mediators.