Helicobacter pylori type 4 secretion systems as gastroduodenal disease markers.

Although the type 4 secretion system of the integrating and conjugative elements (tfs ICE) is common in Helicobacter pylori, its clinical association with the cag pathogenicity island (cagPAI) have not yet been well-investigated. In this study, Vietnamese patient H. pylori samples (46 duodenal ulcer (DU), 51 non-cardia gastric cancer (NCGC), 39 chronic gastritis (CG)) were fully sequenced using next-generation sequencing and assembled into contigs. tfs3, tfs4, and cagPAI genes were compared with the public database. Most (94%) H. pylori strains possessed a complete cagPAI, which was the greatest risk factor for clinical outcomes, while the prevalences of tfs3 and tfs4 were 45% and 77%, respectively. Complete tfs3 and tfs4 were found in 18.3% and 17.6% of strains, respectively. The prevalence of H. pylori strains with complete tfs3 ICE in DU patients was significantly higher than that in NCGC patients (30.4% vs 11.7%, P < 0.05). In addition, the prevalence of strains with complete tfs3 ICE and cagPAI was significantly higher in DU patients than that in NCGC (28.4% vs 9.8%, P = 0.038) and CG patients (28.2% vs 7.7%, P = 0.024). cagPAI and complete tfs3 increased the risk of DU compared to NCGC (OR = 3.56, 95%CI: 1.1-14.1, P = 0.038) and CG (OR = 4.64, 95%CI: 1.1-27.6, P = 0.024). A complete cluster of tfs3 ICE was associated with gastroduodenal diseases in Vietnam. However, there was a low prevalence of the dupA/complete dupA cluster (15.4%) in the Vietnam strains. The prevalence of cagPAI in Vietnam strains was significantly higher than in US (P = 0.01) and Indonesia (P < 0.0001); the prevalence of the dupA cluster was also higher in the Vietnam strains than in the Indonesian strains (P < 0.05). In addition, the prevalence of ctkA, an accessory gene of tfs3, was significantly different between Vietnam and US strains (28% vs 2%, P = 0.0002). In summary, the acquisition of tfs3/4 ICE was common in H. pylori strains in patients with gastroduodenal disease in Vietnam, and the complete cluster of tfs3 ICE was a reliable marker for the severity of disease in the H. pylori infected population.

Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia.

BACKGROUND & AIMS: Despite the growing recognition of duodenal alterations in the pathophysiology of functional dyspepsia (FD), the effect and mechanism of proton pump inhibitors (PPIs) or first-line therapy remain unclear. We studied duodenal and systemic alterations in relation to PPI therapy in patients with FD and healthy volunteers (HVs). METHODS: We performed a prospective interventional study assessing symptoms (Patient Assessment of Gastrointestinal Symptom Severity Index), duodenal alterations, and systemic factors in patients with FD ("FD-starters") and HVs before and after PPI therapy (pantoprazole 40 mg once daily for 4 weeks). Duodenal mucosal eosinophils, mast cells and permeability were quantified. Luminal pH and bile salts were determined in duodenal aspirates. Procedures were also performed in PPI-refractory patients with FD ("FD-stoppers") before and 8 weeks after PPI withdrawal. Between- and within-group changes from baseline and associations with duodenal or systemic factors were analyzed using linear mixed models. RESULTS: The study was completed by 30 HV, 27 FD-starters, and 18 FD-stoppers. Symptoms and duodenal eosinophils, mast cells (all, P < .0001), and paracellular passage (P = .02) were significantly higher in FD-starters vs HVs and reduced with PPI therapy. Symptoms and duodenal immune cells also decreased in FD-stoppers off PPIs. In contrast, immune cells and permeability increased in HVs on PPIs. Dyspeptic symptoms correlated with eosinophils before and during PPI therapy, and increased eosinophils and permeability in HVs on PPIs were associated with changes in bile salts. CONCLUSIONS: We provide the first prospective evidence for eosinophil-reducing effects as a therapeutic mechanism of PPIs in FD, with differential effects in HVs pointing to a role of luminal changes. ClinicalTrials.gov, Number: NCT03545243.

TRPA1 and substance P mediate stress induced duodenal lesions in water immersion restraint stress rat model.

BACKGROUND/AIMS: Transient receptor potential ankyrin 1 (TRPA1) and substance P (SP), both expression in sensory neurons, have important roles in stress-induced duodenal lesions. The possible contribution of TRPA1 and SP to stress-induced duodenal lesions was explored by using the water immersion restraint stress (WIRS) rat model. MATERIALS AND METHODS: Western blotting, Real-time polymerase chain reaction (RT-PCR), and immunohistochemistry assay were used to evaluate the changes of TRPA1and SP expression in the dorsal root ganglia (DRG, T8-11), the corresponding segment of the spinal cord (T8-11), and the duodenum in a duodenal lesions rat model. The SP concentrations of duodenal mucosa were investigated using an enzyme-linked immunosorbent assay (ELISA). Duodenal lesions were assessed according to histopathological changes. TRPA1 specific antagonist HC-030031 was intrathecally or intraperitoneally performed to suppress the expression of both TRPA1 and SP for evaluating the roles of TRPA1 and SP in duodenal lesions. RESULTS: In contrast to the control group, TRPA1 and substance P in the DRG (T8-11) and duodenum were up-regulated, and concentrations of SP in the duodenal mucosa were increased after WIRS (p<0.05), which are closely associated with duodenal lesions. SP concentrations in the duodenal mucosa were decreased and duodenal lesions were alleviated by pretreatment with TRPA1 antagonist HC-030031. We identified a protective role for HC-030031 in WIRS-induced duodenal lesions. Furthermore, we demonstrated that WIRS increased the concentrations of SP in the duodenal mucosa in a TRPA1-dependent manner. However, WIRS caused no significant changes of TRPA1 and SP in the spinal cord (T8-11) compared with the control group (p>0.05). CONCLUSION: Our study indicates that TRPA1 antagonist HC-030031 alleviates duodenal lesions. TRPA1 is activated and sensitized, therefore concomitant neuropeptide SP is released, which exerts a critical role in inducing and maintaining duodenal lesions following WIRS in rats. This provides evidence that neuroimmune interactions may control duodenal injury. TRPA1 may be a potential drug target to inhibit the development of duodenal lesions by stress-induced in patients.

Systemic amyloidosis with gastrointestinal involvement: Diagnosis from endoscopic and histological views.

Amyloid tends to deposit in the gastrointestinal tract, which, being easily accessible, is often the target organ for a pathological diagnostic examination. Although a mucosal biopsy is necessary for a definitive diagnosis and several studies have reported positive results for each possible biopsy site, there remain many unclear features in various aspects. This review focuses on the current literature to determine a better understanding of the diagnosis from endoscopic and histological views in patients with systemic amyloidosis with gastrointestinal involvement. A literature search was performed using PubMed to identify relevant studies; linked references were also reviewed. Endoscopic findings vary based on the organ and the depositing amyloids. A fine granular appearance or polypoid protrusions are likely to occur in the duodenum. AL, Aß2M, and ATTR amyloids are likely to deposit submucosally, while AA amyloid is easily deposited in the superficial layer of the mucous membrane. Furthermore, it is necessary to consider the collection of biopsy specimens from the duodenum, which has high positive biopsy rates. However, the difference in the positive biopsy rates depends on whether endoscopic findings are available or whether the appropriate number has not been fully elucidated. A duodenal biopsy is strongly recommended to confirm the deposition of amyloid in patients with systemic amyloidosis having gastrointestinal involvement. Because amyloidosis is a disease with a poor prognosis, early diagnosis and treatment are required; gastroenterologists and endoscopists play important roles.

Activation of epithelial proliferation induced by Eimeria acervulina infection in the duodenum may be associated with cholesterol metabolism.

Cell proliferation in the intestine is commonly occurred during infection and inflammation to replace damaged enterocytes, and cholesterol as an essential constituent of cell membrane, is required for cell proliferation and growth. Here we found that coccidium-challenged (CC) chickens showed severe damages in intestinal structure, a significant increase of cell proliferation, and an activation of genes expression involved in the innate immune response. Compared to control (CON), CC chickens showed a marked decrease of cholesterol (Tch) level in the circulating system, but a significant increase in local duodenum epithelium. Increase of LDLR protein combined with a significant decrease of CYP27A1 protein expression in duodenum epithelium may contribute to intestinal cholesterol accumulation in CC chickens. Moreover, we found miRNAs targeting to CYP27A1 gene participating in post-transcriptional regulation. Hence, these results provide a new insight for the intervention of epithelial proliferation and cholesterol metabolism in the gastrointestinal tracts.

[ABOUT CO-OCCURRENCE OF CRHONIC PANCREATITIS WITH GASTRODUODENAL DISEASES].

The article summarizes clinical features of the course when chronic pancreatitis goes in combination with diseases of gastroduodenal and hepatobiliary systems and features of functional and morphological changes. The article also represents justification of need to include the combined medicine Doktovit (combination of Dexpanthenol and S-methylmethionine) into complex treatment of the pathology, describes mechanism of its gastro protective and reparative action.

Pseudomelanosis of stomach, duodenum, and jejunum.

Pseudomelanosis is a rare finding during upper gastrointestinal endoscopy, and is most commonly seen in the duodenum. Involvement of other organs in the upper gastrointestinal tract is extremely rare, with only 1 reported case involving the stomach, duodenum, and jejunum. We present a case of a 60-year-old woman with mild anemia and hematemesis, who was found to have characteristic speckled pattern of gray-black pigmentation on endoscopic examination. To the best of our knowledge, this is the second reported case of pseudomelanosis involving the stomach, duodenum, and jejunum.

Duodenal morphometry and small bowel permeability in children with portal hypertension.

OBJECTIVE: We prospectively studied children with portal hypertension (PHT) for portal hypertensive duodenopathy (PHTD) and small bowel intestinal permeability (SIP) with the objectives of defining histopathological parameters for PHTD and to find out whether any association existed among structural changes, SIP, and nutritional status. METHOD: SIP was assessed by using lactulose and mannitol sugar probes in 31 children with PHT (cirrhosis n = 15 and extrahepatic portal venous obstruction n = 16) and 15 healthy children as controls. Morphometric assessment from duodenal biopsies was done in children with PHT. SIP and morphometric parameters were correlated with nutritional status and dietary intake. RESULTS: Among children with PHT, 48% had PHTD defined as presence of villous atrophy (villous to crypt ratio < 2.5:1), dilated capillaries (capillary diameter > 16.8 µm, capillary area > 151 µm, capillary perimeter > 56 µm), and thickened muscularis mucosae (>22.2 µm). Lactulose excretion alone was increased in children with PHT as compared with healthy children (median %: 0.03, 0.02, and 0.01 for cirrhosis, extrahepatic portal venous obstruction, and controls, respectively [P < 0.01]) signifying increased paracellular permeability in PHT. Children with PHT had significantly lower z scores for height, weight, and triceps skin-fold thickness (<-2SD), whereas no differences were found in dietary intake between patients and controls. Increased SIP, nutritional compromise, and PHTD in our patients had no correlation. CONCLUSIONS: PHT is often associated with duodenopathy. SIP does occur as a result of increased paracellular permeability. Factors of increased SIP, undernutrition, and PHTD do not have correlation in childhood PHT.

Glucose absorption in small intestinal diseases.

Recent developments in the field of diabetes and obesity management have established the central role of the gut in glucose homeostasis; not only is the gut the primary absorptive site, but it also triggers neurohumoral feedback responses that regulate the pre- and post-absorptive phases of glucose metabolism. Structural and/or functional disorders of the intestine have the capacity to enhance (e.g.: diabetes) or inhibit (e.g.: short-gut syndrome, critical illness) glucose absorption, with potentially detrimental outcomes. In this review, we first describe the normal physiology of glucose absorption and outline the methods by which it can be quantified. Then we focus on the structural and functional changes in the small intestine associated with obesity, critical illness, short gut syndrome and other malabsorptive states, and particularly Type 2 diabetes, which can impact upon carbohydrate absorption and overall glucose homeostasis.

Inflammatory fibroid polyp in the duodenum of a common marmoset (Callithrix jacchus).

A 32-month-old male common marmoset had a firm and white-colored mass in the duodenal wall. The cut surface was smooth and grayish white in color. Histologically, the mass consisted of a proliferation of spindle cells with an oval to spindle-shaped nucleus and scant eosinophilic cytoplasm in a loose myxoid or fibrotic background. Most of the lesion displayed no specific growth pattern whereas some of the cells concentrated around the vessels and created an onion-bulb structure. Additionally, marked inflammatory cellular infiltration, mainly eosinophils, was observed throughout the lesion. Immunohistochemically, the spindle cells were positive for vimentin, α-smooth muscle actin, fascin, and cyclin D1, and negative for S-100, factor VIII-related antigen, and c-kit. These histological and immunohistochemical features did not meet any differential diagnoses such as gastrointestinal stromal tumor, inflammatory myofibroblastic tumor, solitary fibrous tumor/hemangiopericytoma, smooth muscle tumor, schwannoma, and hemangiosarcoma. Collectively, the authors diagnosed the mass as a lesion that corresponded to an inflammatory fibroid polyp (IFP) in humans. IFP is defined as a mesenchymal proliferation composed of spindle stromal cells, small blood vessels, and inflammatory cells, particularly eosinophils, and is currently classified as a nonneoplastic lesion. To the best of our knowledge, this is the first case of spontaneous IFP in nonhuman primates.

Expression of P-glycoprotein in the intestinal epithelium of dogs with lymphoplasmacytic enteritis.

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory disease of the stomach, the small intestine and/or the large intestine. Loss of integrity of the intestinal barrier may be an important factor in the pathogenesis of IBD. In dogs, lymphoplasmacytic enteritis (LPE) is one of the recognized forms of IBD. P-glycoprotein (P-gp) is a membrane-bound efflux pump constituting an important component of the intestinal barrier. Changes in P-gp expression at the level of the intestinal barrier may be important in the pathogenesis of canine LPE, as this may lead to variable protection against xenobiotics and bacterial products in the intestine. The aim of the present study was to evaluate the expression of epithelial P-gp in the intestine in dogs with LPE compared with disease-free animals. Formalin-fixed intestinal biopsy samples from 57 dogs with histopathological evidence of LPE were immunolabelled with anti-P-gp antibodies (C494 and C219). Endoscopic biopsy samples of the duodenum and colon from 16 healthy beagles were used as controls. None of the control dogs had P-gp expression in the apical membrane of duodenal enterocytes, but all had P-gp labelling at the colonic epithelial surface. Twenty out of 57 dogs with LPE had P-gp expression at the apical surface membrane of villus epithelial cells in the duodenum, jejunum and/or ileum. Six out of 16 colonic samples from dogs with LPE had decreased P-gp expression at the epithelial surface compared with controls. It is unclear whether these changes in P-gp expression in dogs with LPE are a cause or a consequence of the inflammation. The observed changes could affect bioavailability of therapeutic drugs used in LPE.

[Gastric secretory function in patients with chronic renal insufficiency and gastroduodenal hemorrhage].

Gastric hypersecretion occurrence in patients, suffering chronic renal insufficiency (CHRI), creates conditions for acido-peptic gastroduodenal zone affection with possible formation of erosive-ulcerative defects, complicated by hemorrhage. In 116 patients, suffering CHRI, the state of gastric mucosa secretory function was studied up. In patients with an acute gastrointestinal hemorrhage and CHRI in conservative and terminal stages the analysis of acidity was conducted.

Selective COX-2 inhibition affects fatty acids, but not COX mRNA expression in patients with FAP.

Familial adenomatous polyposis (FAP) provides a model for sporadic colorectal cancer development. Cyclooxygenase (COX) inhibition may ameliorate polyp development, but rofecoxib was withdrawn due to cardiovascular side effects. Although this selective COX-2 inhibitor, like diet, may alter the fatty acid and eicosanoid pattern, data on the potential alteration in tissues after use, are scarce. The aims were to study if rofecoxib might influence the fatty acid distribution in serum phospholipids and duodenal lesions, mRNA for COX-1 and COX-2 in leucocytes and duodenal lesions, and finally plasma levels of PGE(2) in a randomized, double-blind, placebo controlled study (n = 38). Significant reductions were found for essential fatty acid index both in serum phospholipids (P = 0.01, 95% CI = -0.9; -0.1), and in duodenal lesions (P = 0.04, 95 CI % = -0.9; -0.1) after treatment. No treatment effects were found on the COX mRNA expression, or in the plasma PGE(2) levels. Dietary AA/EPA ratio was inversely associated with all the indicators of EFA status (all P < 0.01). These findings suggest that the effects of COX chemoprevention should be further investigated in FAP and that dietary needs should be included in the treatment of FAP.

[Time course of changes in the gastric juice levels of nitric oxide in patients with upper digestive tract diseases].

AIM: to study the time course of changes in the gastric juice levels of nitric oxide (NO) in patients with esophagogastroduonenal diseases (EGDD). SUBJECTS AND METHODS: One hundred and seventy-four patients with EGDD were examined. RESULTS: In patients with chronic atrophic gastritis, the level of NO was significantly lower than the normal levels and correlated with the magnitude of mucosal atrophy. Elevated gastric juice NO levels were noted at exacerbations of gastroesophageal reflux disease (GERD), chronic nonatrophic gastritis (CNAG), and duodenal ulcer disease (DUD). At the end of a therapy course, the gastric juice levels of NO did not achieve the control values in patients with GERD, reduced to the normal values in those with CNAG, although became lower, but remained above the normal values in DUD in a remission phase. CONCLUSION: The patients with EGDD were observed to have heterodirectional changes in the content of NO in gastric juice. In the patients with DUD, the remaining gastric juice NO levels above the normal values after ulcerative defect cicatrization are indicative of incomplete reparative processes in the gastric mucosa, i.e., delayed morphological remission. In chronic atrophic gastritis, the gastric juice levels of NO did not achieve normal values after treatment despite the onset of clinical remission which may be caused by a continuous gastric mucosal atrophic process.

[Etiology and pathogenesis of duodenal mucosa lesion in chronic pancreatitis].

AIM: To measure content of neuromediators (acetylcholine-Ach, serotonin-5-NT) and gastrointestinal hormones (cholecystokinine-CCK and secretin) in the blood serum of patients with chronic pancreatitis (CP); to study protective properties of the mucus in the duodenum in CP. MATERIAL AND METHODS: CCK and secretin concentrations were estimated by enzyme immunoassay, Ach and 5-NT were measured biochemically basally and after standard meal in 65 CP patients and in the control group. Proteolytic activity of the mucus was assessed by Anson's method. An inhibitory property of the mucus was studied by residual proteolytic activity of pepsine after its incubation with mucus. RESULTS: In AP patients the response of biologically active substrates to standard meal changed: 5-NT concentration rose from 0.40 +/- 0.07 to 0.55 +/- 0.05 mcg/ml (p < 0.05) while Ach dropped from 1.7 +/- 0.3 to 1.6 +/- 0.3 mmol/l (p > 0.05). BP patients responded to the standard meal with 5-HT concentration rise from 0.28 +/- 0.04 to 0.43 +/- 0.05 mcg/ml (p < 0.05), Ach changed insignificantly (from 1.5 +/- 0.12 to 1.45 +/- 0.21 mmol/l, p > 0.05, reselectively). CCK after standard meal significantly rose both in AP and BP. AP and BP patients had strong direct correlation between concentrations of 5-HT and CCK (r = 0.875439) and weak negative correlation with Ach level (r = -0.2209). In AP and BP patients secretin level weakly negatively correlated both with 5-NT and Ach levels (r = -0.4839 and r = -0.33207, respectively). Reduction of secretin secretion diminished secretion of bicarbonates and mucus with simultaneous change in the quality of mucous gel. CONCLUSION: In CP of various etiology there are changes in the level and proportions of neuromediators and hormones causing alterations in the regulation system. These disorders correlate with disturbances in pancreatic excretory function and destructive tissue changes. Bicarbonates secretion decreases and changes quality of the secreted mucus.

Presence of thrombin-activatable fibrinolysis inhibitor in Helicobacter pylori-associated gastroduodenal disease.

Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in the regulation of coagulation and inflammation. In addition to inhibiting the fibrinolytic system, TAFI may also regulate the bradykinin and complement systems. We hypothesized that TAFI also plays a role in defense mechanisms of the gastric mucosa during Helicobacter pylori infection. This study comprised 65 patients with gastroduodenal disorders: 41 patients with H. pylori infection, 13 without, and 11 patients with cured H. pylori infection. The gastric intramucosal concentrations of TAFI were measured by enzyme immunoassay. The gastric levels of TAFI and plasminogen activator inhibitor-1 were significantly increased in patients with H. pylori compared to those without infection or cured H. pylori. The presence of TAFI was detected in gastric mucosal epithelial cells. The concentration of TAFI was correlated with the degree of gastric mucosal atrophy, inflammation, and disease activity. These results show that TAFI is present in the gastric mucosa and that it may play a role in the pathogenesis of H. pylori infection-associated gastroduodenal disorders.

[Clinical and morphological characteristics and some mechanisms of portal gastroduodenopathy in liver cirrhosis].

We have found out the clinical presentations and peculiarities of endoscopic and morphologic view of pathologies of mucous membrane of gastroduodenal zone caused by liver cirrhosis. We have examined 74 patients with liver cirrhosis of viral and nonviral etiology using the clinical, endoscopic, morphologic and immunohistochemical methods.We have found that during liver cirrhosis morphometric rates of epithelial cells of mucous coat of stomach that produce somatostatin and endothelin-1 decrease and morphometric rates of epithelial cells that produce nitrogen oxide synthase increase. We have also found out that during liver cirrhosis proliferate activity decrease and apoptosis of epithelial cell of mucous coat of stomach increase.