Development Of Peptic Ulcer Disease Research Articles

Gender-specific features of associations of polymorphic loci of candidate genes with the formation of peptic ulcer in the population of the Central Chernozem Region of Russia

Introduction. Peptic ulcer of the stomach and duodenum is a chronic recurrent multifactorial disease, the ethiopathogenesis of which is significantly contributed by hereditary predisposition. With this disease, a chronic inflammatory process develops, in which cell adhesion molecules take part. The incidence of peptic ulcer disease (PUD) depends on gender: men get sick 2-7 times more often than women. There are few works on the analysis of gender-specific features of associations of polymorphic loci of candidate genes of YB, therefore, further study of this issue is necessary.Aim: To study the role of two groups of candidate genes of PUD specially selected for the study of 9 polymorphic loci (SNPs): the first – GWAS-significant for peptic ulcer disease (rs2294008 PSCA, rs505922 ABO), the second - genes of cell adhesion molecules pathogenetically significant for the development of PUD (rs6136 SELP; rs8176720, rs2519093, rs507666 ABO; rs651007, rs579459, rs649129 ABO/RF00019), - in the formation of peptic ulcer disease in men and women of the Central Chernozem region of Russia. The sample consisted of 305 men (188 patients, 117 controls) and 441 women (211 patients, 230 controls).Methods. The regulatory potential of SNPs was assessed using Internet resources (HaploReg v4.1, PolyPhen-2, GTEx Portal), the analysis of associations was carried out by the method of logistic regression in the framework of allelic, additive, dominant and recessive genetic models.Results. The allele T rs2294008 of the PSCA gene in the group of men is a protective factor in the development of peptic ulcer disease (OR = 0.39-0.64). This pattern was not revealed in women. The rs2294008 polymorphism of the PSCA gene is located in the regions of histone proteins marking promoters and enhancers in the gastric and esophageal mucosa, in the area of hypersensitivity to DNAse in the stomach, binding sites with the POL2 regulatory protein and the CTCF regulatory motif; it affects the expression of 10 genes, including 4 (LY6K, LYNX1, PSCA, THEM6) in the target organ (stomach), alternative splicing of 3 genes, including 2 genes (JRK, LYNX1) in the tissues of the stomach and esophagus.Conclusions. The T allele of rs2294008 of the PSCA gene in the group of men is a protective factor in the development of ulcer disease. Polymorphism rs2294008 of the PSCA gene affects the expression of ten genes in the target organ (stomach), alternative splicing of three genes, including two genes in the stomach and esophagus tissues.

Elevated expression of the AIM2 gene in response to Helicobacter pylori along with the decrease of NLRC4 inflammasome is associated with peptic ulcer development.

Helicobacter Pylori (H. Pylori) cause peptic ulcer disease (PUD), but the inflammasome's role in PUD is not well understood. Therefore this study has investigated inflammasome compartment expression and IL-1β production in gastritis (G) and peptic ulcer disease. This study was based on gene expression of inflammasome compartments on stomach biopsies of 50 patients with PUD as cases and 50 individuals with gastritis as controls. The expression of NLRC4, ASC, IL-18, and serum IL-1β decreased in the PUD group compared to the control group. AIM2 gene expression increased, and NLRP12 gene expression decreased in H. pylori-seropositive positive (HP+ ) individuals compared to H. pylori-seronegative (HP- ) individuals. The G-HP+ subjects had higher serum IL-1β and AIM2 gene expression than G-HP- subjects but lower NLRP3 and NLRP12 gene expression. The PUD-HP+ had lower serum IL-1β, but higher AIM2 and IL-18 expression than PUD-HP- . The PUD-HP- patients had decreased IL-18 expression than G-HP- group. The PUD-HP+ had lower serum IL-1β and NLRC4 expression than G-HP+, while NLRP1 and NLRP3 were higher in expression in PUD-HP+ . The expression of caspase-1, NLRP3 and NAIP were correlated with IL-1β and IL-18. In conclusion, a decrease in NLRC4, IL-18, ASC genes, and IL-1β levels in PUD patients compared to gastritis may act in the development of PUD. H. pylori caused AIM2 induction and reduced NLRP12, indicating their contribution to bacterial responses. Decreased NLRC4 expression and IL-1β protein, together with enhanced NLRP1, and NLRP3 expression, promotes H. pylori to develop peptic ulcers.

Peptic Ulcer Disease and Its Implications

Peptic ulcer disease (PUD) is one of the commonest diseases seen throughout the world. Peptic ulcers are open sores that develop on the inside lining of your stomach and the upper portion of your small intestine. The most common symptom of a peptic ulcer is stomach pain. There are various risk factors for the development of peptic ulcer disease, but the most important ones are Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs). Patients generally present with dyspepsia or peptic ulcer bleeding. Acid suppressant therapy, H. pylori eradication, and avoidance of nonsteroidal anti-inflammatory drugs are the cornerstones of treatment of peptic ulcer disease. Peptic ulcer bleeding could be life-threatening. It is managed by appropriate supportive care, intravenous proton pump inhibitor therapy, and endoscopic homeostasis. Trans arterial embolization (TAE), Herbal treated and surgery are rarely required if endoscopic therapy fails.

Study the Balance System Between Oxidants/Antioxidants in Patients with Peptic Ulcer in City of Tikrit and it's Suburb

This study aimed to find out the current role of free radical and oxidative stress in the events of this disease through the study the determined levels of lipid peroxidation and some of number antioxidents concentrations. The study included (100) patients with Peptic ulcer (50 males and 50 females) as well as (50) people (25) healthy males, 25 females) as a control group.
 (5) ml of blood from the Anticubital vein for the purpose of estimating the concentrations of malondialdehyde (MDA( and peroxinitrate radical (ONOO.-) and some enzymic antioxidants such as catalase (CAT), superoxidismutase (SOD), glutathion peroxidase (G-px) ,and non- enzymic antioxidants such as glutathion (GSH), ceruloplasmin (CP), uric acid , albumin.
 The results showed a significant increase (P≤0.01) in the concentration of the (MDA) and (ONOO.-) and a significant decrease in the concentration of the (CAT), (SOD), (G-px) , (GSH), (CP), Uric acid, Albumin in the blood serum of patients with peptic ulcer males and females compared to the control group.
 This study clear that the oxidative stress and free radicals a major role in the development of Peptic ulcer disease.

Expression Assessment of the Helicobacter pyloribabA and sabA Genes in Patients with Peptic Ulcer, Duodenal Ulcer and Gastric Cancer.

Helicobacter pylori as a common gastrointestinal (GI) pathogen must possess certain virulence characteristics to colonize the stomach, evade host immune responses, and subsequently induce GI diseases. This research aimed to investigate the expression level of two important genes, the sialic acid-binding adherence (SabA) and the blood group antigen-binding adhesion (BabA) in H. pylori strains isolated from adult patients living in the northern part of Iran, and their association with peptic ulcer disease (PUD) and gastric cancer (GC). This cross-sectional study was carried out on adult patients referring to the GI clinic of the hospitals affiliated to Babol University of Medical Sciences, Iran. New cases diagnosed with gastritis, peptic ulcer or gastric cancer were included. Endoscopic-guided gastric biopsies were examined and H. pylori positive colonies were analyzed to determine the expression of babA and sabA genes, utilizing specific primers and the SYBR Green dye. Among 175 patients with mean age of 51.6±15.6 years, 101 (57.7%) of the individuals tested positive for H. pylori infection. Statistical analysis revealed a significant correlation between sabA (P=0.003) and babA (P=0.002) gene expression and development of PUD and GC. Smoking (P=0.052), gender (P=0.004) and positive babA gene expression (P=0.009) had the greatest association with occurrence of PUD or GC in H. pylori positive patients. In summary, the presence of the sabA gene in people infected with H. pylori increased the risk of GC compared to gastritis, while, the presence of the babA gene was significantly increased in gastric ulcer patients. Considering the diversity of H. pylori isolates and the varying results observed in different geographical regions, further comprehensive studies are required to evaluate the function of these genes in H. pylori pathogenesis and their relationship with clinical outcomes.

CHARACTERISTICS OF CYTOPROTECTIVE EFFECT ON THE GASTRIC MUCOSA OF CRYOPRESERVED PLACENTA EXTRACT UNDER WATER-IMMOBILIZATION STRESS

Various stressors are currently considered to play a significant role among the etiological factors for development of peptic ulcer disease. Along with psycho-emotional stressing experiences, the causes of formation of stress ulcers include major surgical interventions, thermal or mechanical injuries, severe blood loss, progressive syndrome of endogenous intoxication and more. Among patients in intensive care units, the incidence of stress ulcers is 5.0%, and in 30.0-50.0% of cases stress ulcers are complicated by bleeding and perforation.
 Aim. The research aims at characterizing the gastrocytoprotective effect of cryopreserved placenta extract (CEP) on the model of water-immobilization stress in rats according to macroscopic data and the results of biochemical study of homogenates of the gastric mucosa (GM).
 Materials and Methods. In vivo experimental studies were performed on 28 nonlinear laboratory male rats weighing 200-220 g. Stress-induced gastric ulcer was simulated under water-immobilization stress (WIS) in rats. WIS simulation according to the method of Takagi K.Y. et al. The activity of NO synthases (NOS) in GM was determined spectrophotometrically by the amount of oxidized NADPH+H+.
 Results and Discussion. The use of CEP, as well as esomeprazole, led to a weakening of GM ulcers. This was indicated by a statistically significant (p<0.05) decrease in ulcer index (UI) relative to the indicators of control rats by 9.8 and 3.3 times, respectively. At the same time, this indicator was three times lower on the background of preventive use of CEP than in rats treated with esomeprazole, respectively, antiulcer activity (AUA) was 96.4% and 69.2%. The study of the activity of constitutive (cNOS) and inducible (iNOS) isoforms of NOS showed that at the pathobiochemical level against the background of stress-induced ulcerogenesis in the tissues of the central nervous system there is a statistically significant (p<0.001) increase in iNOS activity in 5.2 times was 0.89±0.01 NADPH2/min´g protein. According to the degree of modulation of the activity of both total NOS and its individual isoforms, the study showed that preventive five-day administration of esomeprazole is inferior to the effectiveness of CEP. Thus, the activity of total NOS in rats administered esomeprazole was statistically significantly (p<0.001) decreased by only 17.1%, while the activity of this enzyme decreased (p<0.001) by 35.8% due to the use of CEP.
 Conclusions. Prophylactic five-day administration of CEP modulated the activity of the NOS system in the central nervous system, which in a macroscopic study appeared statistically significant (p<0.05) reduction in UI relative to rats in the control group by 9.8 times. Thus, NOS activity statistically significantly (p<0.001) decreased by 35.8%, and iNOS activity statistically significantly (p<0.001) decreased by 58.4% relative to the control animals. CEP under the prophylactic regimen showed more pronounced anti-ulcer activity than esomeprazole, which was 96.4% and 69.2%, respectively.

Peptic ulcer: the current state of the problem

Peptic ulcer disease (PUD) is a chronic polyetiological recurrent disease of gastroduodenal region. In most cases, the pathogenesis of PU is caused by imbalance between the aggressive factors and protective factors of the gastric or duodenal mucosa. Helicobacter pylori (H. pylori) infection and the use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, are the major causative factors leading to PUD development. 65% of gastric ulcers and 80% of duodenal ulcers were found to be associated with H. pylori infection. In turn, NSAIDs account for 30% of gastric ulcers and 15% of duodenal ulcers. About 0.1–1% of all PUs are caused by Zollinger-Ellison syndrome. Abdominal pain is the leading symptom in the clinical findings of patients with exacerbation of PUD. Dyspeptic syndrome (vomiting, nausea, belching, abnormal bowel pattern) is much less common in patients with PUD. Endoscopic examination of the upper gastrointestinal tract is currently the gold standard test used in the diagnosis of PUD and is recommended for all patients suspected of having this disease (unless contraindicated). Antisecretory therapy including proton pump inhibitors is the main approach to the treatment of PUD, as well as the prevention of its complications. Integral to the treatment of patients with H. pylori-associated PU is the eradication therapy of the infection. It is reasonable to use a cytoprotector rebamipide, which accelerates ulcer healing and improves the resulting scar quality, as part of the pharmacotherapy of PUD. In addition, the use of rebamipide in H. pylori eradication therapy regimens contributes to increased efficiency of elimination of the microorganisms.

Association of Helicobacter Pylori With Development of Peptic Ulcer Disease Among Cirrhotic Patients: An Evidence From Population-Based Study.

Background: Helicobacter pylori (H. pylori) plays an important role in causing peptic ulcer disease (PUD) in the general population. However, the role of H. pylori in cirrhotic patients for causing PUD is obscure. There are various studies evaluating H. pylori association with PUD in cirrhotic patients, but the results have been controversial. We sought to analyze the association of H. pylori with the development of PUD in cirrhotic patients from the largest United States population-based database.Methods: We analyzed Nationwide Inpatient Sample (NIS) and Healthcare Cost and Utilization Project (HCUP) data from 2017. Adult hospitalizations due to cirrhosis were identified by previously validated ICD-10-CM codes. PUD and H. pylori were identified with the presence of ICD-10-CM codes in primary and secondary diagnosis fields, respectively. We performed weighted analyses using Chi-Square and paired Student’s t-test to compare the groups. Multivariable survey logistic regression was performed to find an association of H. pylori with PUD in cirrhotic patients.Results: Our study showed that the prevalence of H. pylori infection was 2.2% in cirrhotic patients with PUD. In regression analysis, H. pylori was found to be associated with PUD in cirrhotic patients (OR 15.1; 95% CI: 13.9-16.4; p <0.001) and non-cirrhotic patients (OR 48.8; 95% CI: 47.5-50.1; p <0.001). In the studied population, H. pylori was more commonly seen in the age between 50 and 64 years (49.4% vs 44.1%; p <0.0001), male (63.4% vs 59.9%; p <0.0413), African American (16.3% vs 10.6%; p <0.0001), and Hispanic (26.2% vs 14.9%; p <0.0001). H. pylori is more likely to be associated with complicated PUD hospitalizations (51.2% vs 44.2%; p <0.0067). Alcoholism and smoking were more common in H. pylori group compared to those without (43.6% vs 35.8%; p <0.0001 and 33.7% vs 24.8% p <0.0001, respectively). Factors associated with increased odds of H. pylori infection include African American (OR 2.3, 95% CI: 1.5-3.6), Hispanic (OR 2.6, 95% CI: 1.7-4.0), and smoking (OR 1.5, 95% CI: 1.1-2.2).Conclusion: H. pylori are associated with PUD and concurrent cirrhosis, although it is less prevalent than general population. African American, Hispanic, and smoking were independently associated with increased odds of H. pylori infection. Further studies are required to better understand the epidemiology and confirm our findings.

Gender-Specific Features of Associations of Polymorphism of Matrix Metalloproteinase Genes with the Development of Peptic Ulcer Disease in the Population of the Central Chernozem Region of Russia

Gender-Specific Features of Associations of Polymorphism of Matrix Metalloproteinase Genes with the Development of Peptic Ulcer Disease in the Population of the Central Chernozem Region of Russia

Functionally significant polymorphisms of the MMP-9 gene are associated with peptic ulcer disease in the Caucasian population of Central Russia

This study analyzed the association of functionally significant SNPs of matrix metalloproteinase (MMP) genes in the development of peptic ulcer disease (PUD) in Caucasians from Central Russia. Ten SNPs of the MMP-1, MMP-2, MMP-3, MMP-8, and MMP-9 genes were analyzed for association with PUD in a cohort of 798 patients with PUD (including 404 H. pylori-positive and 394 H. pylori-negative) and 347 H. pylori-negative controls using logistic regression and assuming the additive, recessive, and dominant genetic models. The variants of MMP-1, MMP-2, MMP-3, and MMP-8 did not manifest any significant associations with the diseases. Five SNPs of the MMP-9 gene demonstrated such association. Allele G of the rs17576 MMP-9 locus conferred a higher risk for PUD (ORadj = 1.31, pperm = 0.016), haplotype AACG of loci rs17576-rs3787268-rs2250889-rs17577 of the MMP-9 gene decreased risk for PUD (ORadj = 0.17, pperm = 0.003). Also, allele C of rs3918249, allele G of rs17576 and haplotype CG of rs3918249-rs17576 of the MMP-9 gene increased risk for H. pylori-positive PUD (ORadj = 1.82, pperm = 0.002; ORadj = 1.53–1.95 pperm = 0.001–0.013 and ORadj = 1.49 pperm = 0.009 respectively). The above loci and 50 linked to them possess significant regulatory effects and may affect the alternative splicing of four genes and the expression of 17 genes in various organs and tissues related to the PUD pathogenesis.

Peptic Ulcer Disease: An Overview of Aetiology, Pathophysiology, Clinical Presentation, Diagnosis and Treatment Options

Introduction: Peptic ulcer disease (PUD) is endemic in all parts of the world. It is estimated that as high as 5-10% of the world’s population is affected by PUD. Disruption in the gastric protective factors within the gastrointestinal lumen is responsible for the development of PUD. Aggravating factors that promote formation of peptic ulcers include gastric acids, decreased bicarbonate and general decrease in mucosal defences. Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) infection are the two major aetiologic factors contributing to damages to the mucosal defence. The major clinical symptom of PUD is epigastric pain. Others includes bloating, heartburn, nausea or vomiting. Testing for H. pylori is important in treatment of PUD. The major complications of H pylori-associated and NSAID-induced ulcers include upper gastrointestinal bleeding, perforation, penetration, gastric outlet obstruction and gastric adenocarcinoma. Purpose: The purpose of this review is to present a general overview of the aetiology, pathophysiology, clinical presentation, diagnosis and treatment options for peptic ulcer disease (PUD). Conclusion: PUD remains a global health challenge requiring that all patients should be treated. Conventional treatments include gastric acid suppressing agents such as proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists as well as mucosal protective agents. Eradication of H. Pylori is critical in pharmacotherapy of H. pylori associate PUD. New approaches to treatments may include the use of antioxidants containing medicinal plants.

S1371 Association of Cirrhosis With Development of Peptic Ulcer Disease: A Population-Based Perspective

S1371 Association of Cirrhosis With Development of Peptic Ulcer Disease: A Population-Based Perspective

S2162 Hemorrhagic Shock Following a Secretin Stimulating Test

INTRODUCTION: Zollinger-Ellison Syndrome (ZES) is a rare disorder resulting from inappropriate gastrin release, which causes acid hypersecretion and the development of peptic ulcer disease (PUD), severe gastroesophageal reflux, and diarrhea. Diagnosing ZES is challenging in the age of PPIs. Furthermore, discontinuing PPI therapy in patients with suspected ZES can be dangerous and even life-threatening. CASE DESCRIPTION/METHODS: A 44 y.o. male with a history of PUD presented for evaluation for ZES. Due to concern for ZES, a secretin-stimulating test was ordered. One week prior to his test he was instructed to stop his PPI and start Ranitidine 450 mg every 6 hours until 24 hours prior to the test. Immediately following the secretin-stimulating test he presented to the emergency room with nausea, vomiting, and profuse watery diarrhea. A pantoprazole infusion at 8 mg/ hr was started. Overnight he became tachycardic and developed about 400cc of hematemesis. His Hbg dropped from 10.3 g/dL to 7.7 g/dL. He subsequently developed hemorrhagic shock requiring intubation and transfer to the ICU. On EGD, he had a large clot in the second portion of the duodenum. He had hematin in the stomach and over 10 ulcers in the duodenum (Image 1). The pantoprazole infusion was increased to 12 mg/hr with no further recurrence of hemorrhage. The secretin stim test returned, confirming the diagnosis of ZES. This was followed up with an Octreotide scan, which revealed increased radiotracer near the second portion of the duodenum, confirming the location of the gastrinoma (Image 2). DISCUSSION: This case illustrates a rare complication of a patient with suspected ZES undergoing a secretin stimulating test. In patient’s with ZES, a secretin stimulating test causes a paradoxical gastrin response to secretin, likely from secretin receptors on tumor cells (Image 3). Furthermore, PPI withdrawal can cause rebound acid secretion, which can lead to exaggerated acid hypersecretion in patient's with ZES. Our patient had an exaggerated response to secretin leading to acid hypersecretion causing PUD, diarrhea, and hemorrhagic shock. Although complications from a secretin stimulating test are rare, in patients with prior UGIB and high suspicion for ZES, a secretin-stimulating test may need to be performed in a controlled hospitalized setting to minimize complication. This case further illustrates how the diagnosis of ZES has become difficult and whether we need to propose new diagnostic criteria to avoid complications in establishing a diagnosis.Figure 1.: Image 1. Large Clot and Multiple Ulcers (Yellow Arrows) in the Duodenum.Figure 2.: Image 2. Markedly increased radiotracer uptake in a soft tissue nodule medial to the second portion of the duodenum, suggestive of a neuroendocrine tumor (confirmed to be gastrinoma by surgical resection).Figure 3.: Image 3. A. In the antrum, exogenous secretin stimulates gastrin secretion directly and concomitantly inhibits gastrin secretion by stimulating somatostatin (SST) secretion, resulting in little or no gastrin release. B. In patients with ZES, because the gastrinoma does not contain functionally coupled SST cells, the effect of secretin is solely to stimulate gastrin secretion from the tumor.

Improving H Pylori Testing in Inpatients With Peptic Ulcer Disease: A Quality Improvement Initiative

Helicobacter pylori (HP) infection is an important, and modifiable, risk factor for the development of peptic ulcer disease (PUD). Therefore society guidelines recommend testing for HP in patients with PUD. The aims of this quality improvement initiative were (1) to determine the testing rates for HP in inpatients with endoscopically confirmed PUD, and (2) to identify variables associated with low rates of testing that could be actionable items for future quality improvement initiatives.

Up-regulated CCL18, CCL28 and CXCL13 Expression is Associated with the Risk of Gastritis and Peptic Ulcer Disease in Helicobacter Pylori infection

BackgroundHelicobacter pylori (H. pylori) infection causes inflammation and increases the risk of developing peptic ulcer disease (PUD); however, the exact molecular mechanisms of PUD development remain unclear. The aim of this study was to investigate the expression of CCL18, CCL28, and CXCL13 in H. pylori-positive subjects in comparison with H. pylori-negative subjects, and to determine its association with different clinical outcomes and virulence factors. MethodsIn total, 55 H. pylori-positive subjects with gastritis, 47 H. pylori-positive subjects with PUD, and 48 H. pylori-negative subjects were enrolled in this study. CCL18, CCL28, and CXCL13 expression were determined using real time polymerase chain reaction (PCR). The virulence factors of H. pylori such as cytotoxin-associated gene A (cagA), outer inflammatory protein A (oipA), blood group antigen-binding adhesin (babA), and vacuolating cytotoxin A (VacA) genes were evaluated using PCR. ResultsCCL18, CCL28, and CXCL13 expression in H. pylori-positive subjects were significantly higher than H. pylori-negative subjects. CCL18 and CXCL13 expression in H. pylori-positive subjects with oipA+ and babA2+were significantly higher than H. pylori-positive subjects with oipA¯ and babA2¯. CCL18 and CXCL13 expression were found to be significantly elevated in H. pylori-positive subjects with gastritis compared with H. pylori-positive subjects with PUD. CCL28 expression was significantly higher in H. pylori-positive subjects with PUD compared with H. pylori-positive subjects with gastritis. ConclusionsThe increased of CCL18 and CXCL13 may be involved in the pathogenesis of H. pylori-associated gastritis, while the increased of CCL28 may be involved in the pathogenesis of H. pylori-associated PUD.

Four Chromosomal Type IV Secretion Systems in Helicobacter pylori: Composition, Structure and Function.

The pathogenic bacterium Helicobacter pylori is genetically highly diverse and a major risk factor for the development of peptic ulcer disease and gastric adenocarcinoma in humans. During evolution, H. pylori has acquired multiple type IV secretion systems (T4SSs), and then adapted for various purposes. These T4SSs represent remarkable molecular transporter machines, often associated with an extracellular pilus structure present in many bacteria, which are commonly composed of multiple structural proteins spanning the inner and outer membranes. By definition, these T4SSs exhibit central functions mediated through the contact-dependent conjugative transfer of mobile DNA elements, the contact-independent release and uptake of DNA into and from the extracellular environment as well as the secretion of effector proteins in mammalian host target cells. In recent years, numerous features on the molecular functionality of these T4SSs were disclosed. H. pylori encodes up to four T4SSs on its chromosome, namely the Cag T4SS present in the cag pathogenicity island (cagPAI), the ComB system, as well as the Tfs3 and Tfs4 T4SSs, some of which exhibit unique T4SS functions. The Cag T4SS facilitates the delivery of the CagA effector protein and pro-inflammatory signal transduction through translocated ADP-heptose and chromosomal DNA, while various structural pilus proteins can target host cell receptors such as integrins or TLR5. The ComB apparatus mediates the import of free DNA from the extracellular milieu, whereas Tfs3 may accomplish the secretion or translocation of effector protein CtkA. Both Tfs3 and Tfs4 are furthermore presumed to act as conjugative DNA transfer machineries due to the presence of tyrosine recombinases with cognate recognition sequences, conjugational relaxases, and potential origins of transfer (oriT) found within the tfs3 and tfs4 genome islands. In addition, some extrachromosomal plasmids, transposons and phages have been discovered in multiple H. pylori isolates. The genetic exchange mediated by DNA mobilization events of chromosomal genes and plasmids combined with recombination events could account for much of the genetic diversity found in H. pylori. In this review, we highlight our current knowledge on the four T4SSs and the involved mechanisms with consequences for H. pylori adaptation to the hostile environment in the human stomach.

Effect of work-related factors on the prevalence of peptic ulcer disease among Korean workers: a nationwide population-based study.

Working environment such as psychosocial factors impacts the health of workers. However, few studies have assessed the association of work-related factors with the prevalence of peptic ulcer disease (PUD) in large population based study. After exclusion of military personnel, 16,099 wage workers (20 ≤ age ≤ 65years) from the Fourth Korea National Health and Nutrition Examination Survey (2008-2011) were included in this study. Job status was defined as the place of employment of longest duration. To evaluate the working environment, we used a comprehensive work-stressor measure. Univariate and multivariable regression analyses were performed to assess the effect of occupation type on the prevalence of PUD. Among the subjects, 5540, 3398, and 7161 were white-, pink-, and blue-collar workers, respectively. The prevalence of PUD was highest among blue-collar workers (n = 336, 7.1%), followed by pink-collar (n = 116, 5.1%) and white-collar (n = 180, 4.9%) workers. In the multivariable analysis, work type and uncomfortable gestures were independently associated with the risk of PUD. Compared with office workers, operators in industrial plants and machine operators had a significantly higher prevalence of PUD (odds ratio, 1.9; 95% confidence interval, 1.1-3.3) after adjusting for age, socioeconomic factors, sex, smoking, alcohol consumption, daily exercise, sleep duration, and working conditions. In conclusion, work-related factors, particularly blue-collar work and uncomfortable job gestures, are independently associated with the risk of PUD. Therefore, it is important to monitor the development of PUD in workers exposed to these factors.

Detection of Anti-CagA Antibodies in Sera of Helicobacter pylori-Infected Patients Using an Immunochromatographic Test Strip.

The cagA gene of Helicobacter pylori that encodes an immunodominant CagA protein provokes severe mucosal damage and acts as a risk factor for the development of peptic ulcer disease and gastric cancer. Our aim is to develop an immunochromatographic test strip (ICTS) using our previously developed recombinant CagA (rCagA) protein and anti-rCagA monoclonal antibody (Mab) for the detection of anti-CagA antibodies in sera of infected patients. The rCagA was firstly conjugated to gold nanoparticle and placed into the conjugate pad. A nonconjugated rCagA and anti-rCagA Mab (CK-02) were immobilized on the test line and control line, respectively. Biopsy and serum samples from 30 H. pylori-infected patients were used. The presence of cagA gene in biopsy samples was first detected by PCR (Polymerase Chain Reaction), and 22 patients were found positive while 8 were negative. When serum samples were tested by our developed ICTS, 21 were positive for anti-CagA antibodies while 9 were negative. The serum samples were also tested by a commercial ELISA (Enzyme Linked Immunosorbent Assay), and when compared to the ICTS a sensitivity of 95% and a specificity of 100% were obtained. The ICTS can be used for rapid detection of CagA-positive H. pylori infection instead of expensive, time consuming and laborious invasive approaches.

Gastroduodenal pathology in the light of Helicobacter pylori genotype in Egyptian patients

ContextInfection with Helicobacter pylori is associated with gastroduodenal diseases such as gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and mucosa-associated lymphoid tissue lymphoma.AimThe aim of this study was to detect the nature of gastroduodenal pathology in the light of the genotype of the associated H. pylori organism.Materials and methodsThe study was conducted on 100 patients with upper gastrointestinal tract symptoms; infection with H. pylori was detected by stool antigen test. Moreover, 20 asymptomatic patients, infected with H. pylori, were included in the study as controls.Upper gastrointestinal tract endoscopy was performed in all participants to take biopsies to diagnose the disease microscopically and to determine H. pylori virulence factors [cytotoxin-associated protein A (CagA) and VacA] by PCR.ResultsPatients infected by H. pylori organisms having CagA-positive genes (41 patients) developed gastritis in 53.7%, peptic ulcer disease (PUD) in 36.6%, and gastric malignancy in 9.8%. Patients infected with organisms that have VacA s1 in addition to CagA genes (19 patients) were found to have gastritis in 21.1%, PUD in 63.2%, and gastric malignancy in 15.8%. However, patients infected with H. pylori organism that have VacAs2 in addition to CagA genes (34 patients) developed gastritis in 79.4%, PUD in 20.6%, and no malignancy.DiscussionThe presence of VacA s1 gene in addition to CagA significantly increases the virulence of the organism toward development of PUD and gastric malignancy. The presence of VacA s2 gene significantly decreases the virulence of CagA gene to develop PUD and prevent completely its carcinogenicity.

Review: Helicobacter: Inflammation, immunology, and vaccines.

Chronic inflammation induced by Helicobacter pylori infection is a critical factor in the development of peptic ulcer disease and gastric cancer. Central to this inflammation is the initiation of pro-inflammatory signaling cascades within epithelial cells, in particular those mediated by two sensors of bacterial cell wall components, nucleotide-binding oligomerization domain-containing protein 1 (NOD1) and alpha-protein kinase 1 (ALPK1). H pylori is, however, also highly adept at mitigating inflammation in the host, thereby restricting tissue damage and favoring bacterial persistence. Hpylori modulates host immune responses by altering cytokine signaling in epithelial and myeloid cells, which results in increased proliferation of regulatory T cells and downregulation of effector T-cell responses. H pylori vacuolating cytotoxin A (VacA) has been shown to play an important role in the dampening of immune responses and induction of immune tolerance capable of protecting against asthma. It is also possible to generate protective immune responses by immunization with various Hpylori antigens or their epitopes, in combination with an adjuvant, though this for now has only been shown in mouse models. Novel non-toxic adjuvants, consisting of modified bacterial enterotoxins or nanoparticles, have recently been developed that may not only enhance vaccine efficacy, but also help translate candidate vaccines to the clinic. This review will summarize the main discoveries in the past year regarding host immune responses to Hpylori infection, as well as the design of new vaccine approaches against this infection.