Decreased Prevalence of <i>Helicobacter pylori</i> Infection in Gastroesophageal Reflux Disease

Varanasi, Ravikant V.; Fantry, George T.; Wilson, Keith T.

doi:10.1046/j.1523-5378.1998.08001.x

Cited by 81 publications

(55 citation statements)

References 32 publications

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“…H. pylori infection was not associated with this group of patients. However, some studies found that H. pylori prevalence was significantly lower in patients with reflux esophagitis compared to age-matched asymptomatic subjects [14,15]. A mechanism was proposed that H. pylori infection was associated with gastric hyposecretion.…”

Section: Discussionmentioning

confidence: 99%

Epidemiology of upper gastrointestinal bleeding and Helicobacter pylori infection: review of 3,488 Thai patients

et al. 2015

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Background:The current epidemiology of upper gastrointestinal bleeding (UGIB) in Thailand is poorly understood and the reported prevalence of Helicobacter pylori infection is outdated. Objectives: To investigate the etiologies of UGIB and prevalence of H. pylori infection in Thailand, including its association with UGIB. Methods: We retrieved information regarding patients attending the endoscopic unit of King Chulalongkorn Memorial Hospital from June 2007 to January 2013. A database search using keywords "upper gastrointestinal bleeding" and "iron deficiency" was used. From 4,454 diagnoses, after exclusion criteria, 3,488 patients (2,042 male (58.5%) and 1,446 female (41.5%); mean age 63.3 ± 15.94 years, range 13-103 years) were included. Results: The three most common causes of UGIB were peptic ulcer (38.2%), nonulcer-mucosal lesions (23.4%), and esophageal-related causes (20.4%). The 5 year-incidence of H. pylori was 25%−30%. The overall prevalence was 27%. The prevalence of H. pylori infection was found to decrease with age from 43.8% at <40 years to 21.7% at >79 years old. H. pylori infection was significantly associated with duodenal and gastroduodenal ulcers. Cirrhosis and nonulcer-mucosal lesions were significantly unrelated to H. pylori infection. Patients with concurrent cirrhosis with peptic ulcer were found to be negative for H. pylori infection. Conclusion: Peptic ulcer is the leading cause of UGIB in Thailand. However, its incidence is declining. Patients who presented to hospital with UGIB were older, compared with those a decade ago. H. pylori infection plays an important role in UGIB and its incidence was stable during the past 5 years.

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Section: Discussionmentioning

confidence: 99%

Epidemiology of upper gastrointestinal bleeding and Helicobacter pylori infection: review of 3,488 Thai patients

et al. 2015

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“…Helicobacter pylori is a gram-negative, microaerophilic bacterium that colonizes the human stomach, infects ϳ30 to 40% of the population in the United States (46), and has a higher prevalence in underdeveloped regions. H. pylori infection induces a chronic lymphocytic response and an innate immune response in neutrophils, monocytes, and macrophages (21-23, 33-35, 47).…”

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confidence: 99%

l -Arginine Availability Regulates Inducible Nitric Oxide Synthase-Dependent Host Defense against Helicobacter pylori

Chaturvedi

Asim

Lewis³

et al. 2007

Infect Immun

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100

142

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Helicobacter pylori infection of the stomach causes an active immune response that includes stimulation of inducible nitric oxide (NO) synthase (iNOS) expression. Although NO can kill H. pylori, the bacterium persists indefinitely, suggesting that NO production is inadequate. We determined if the NO derived from iNOS in macrophages was dependent on the availability of its substrate, L-arginine (L-Arg). Production of NO by H. pylori-stimulated RAW 264.7 cells was dependent on the L-Arg concentration in the culture medium, and the 50% effective dose for L-Arg was 220 M, which is above reported plasma L-Arg levels. While iNOS mRNA induction was L-Arg independent, iNOS protein increased in an L-Arg-dependent manner that did not involve changes in iNOS protein degradation. L-Lysine, an inhibitor of L-Arg uptake, attenuated H. pylori-stimulated iNOS protein expression, translation, NO levels, and killing of H. pylori. While L-Arg starvation suppressed global protein translation, at concentrations of L-Arg at which iNOS protein was only minimally expressed in response to H. pylori, global translation was fully restored and eukaryotic translation initiation factor ␣ was dephosphorylated. H. pylori lacking the gene rocF, which codes for a bacterial arginase, induced higher levels of NO production by increasing iNOS protein levels. When murine gastric macrophages were activated with H. pylori, supraphysiologic levels of L-Arg were required to permit iNOS protein expression and NO production. These findings indicate that L-Arg is rate limiting for iNOS translation and suggest that the levels of L-Arg that occur in vivo do not permit sufficient NO generation by the host to kill H. pylori.

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“…In addition to a chronic lymphocytic response, H. pylori infection induces activation of an innate immune response in neutrophils, monocytes, and macrophages (2)(3)(4)(5)(6)(7)(8). Inducible NO synthase (iNOS) 1 -derived NO is a central effector molecule in the innate immune response to pathogens, with essential antimicrobial functions in host defense. We have reported that H. pylori induces iNOS expression and activity in macrophages (4 -7).…”

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confidence: 99%

Spermine Causes Loss of Innate Immune Response to Helicobacter pylori by Inhibition of Inducible Nitric-oxide Synthase Translation

Bussière¹,

Chaturvedi

Cheng

et al. 2005

Journal of Biological Chemistry

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127

147

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Helicobacter pylori infection of the stomach elicits a vigorous but ineffective host immune and inflammatory response, resulting in persistence of the bacterium for the life of the host. We have reported that in macrophages, H. pylori up-regulates inducible NO synthase (iNOS) and antimicrobial NO production, but in parallel there is induction of arginase II, generating ornithine, and of ornithine decarboxylase (ODC), generating polyamines. Spermine, in particular, has been shown to restrain immune response in activated macrophages by inhibiting proinflammatory gene expression. We hypothesized that spermine could prevent the antimicrobial effects of NO by inhibiting iNOS in macrophages activated by H. pylori. Spermine did not affect the upregulation of iNOS mRNA levels but in a concentrationdependent manner significantly attenuated iNOS protein levels and NO production. Reduction in iNOS protein was due to inhibition of iNOS translation and not due to iNOS degradation. ODC knockdown with small interfering (si) RNA resulted in increased H. pylori-stimulated iNOS protein expression and NO production without altering iNOS mRNA levels. When macrophages were cocultured with H. pylori, killing of bacteria was enhanced by transfection of ODC siRNA and prevented by addition of spermine. These results identify a mechanism of immune dysregulation induced by H. pylori in which stimulated spermine synthesis by the arginase-ODC pathway inhibits iNOS translation and NO production, leading to persistence of the bacterium and risk for peptic ulcer disease and gastric cancer.Helicobacter pylori is a Gram-negative, microaerophilic bacterium that selectively colonizes the human stomach. Current prevalence of H. pylori is ϳ30 -40% of the population in the United States (1) and substantially higher in underdeveloped regions. H. pylori infection induces a vigorous mucosal immune response that fails to eradicate the organism and results in chronic gastritis that can lead to peptic ulcers and gastric cancer. In addition to a chronic lymphocytic response, H. pylori infection induces activation of an innate immune response in neutrophils, monocytes, and macrophages (2-8). Inducible NO synthase (iNOS) 1 -derived NO is a central effector molecule in the innate immune response to pathogens, with essential antimicrobial functions in host defense. We have reported that H. pylori induces iNOS expression and activity in macrophages (4 -7). H. pylori is considered a noninvasive pathogen, but it can disrupt epithelial integrity, and its antigens are present in the lamina propria (3). H. pylori can induce iNOS and other innate immune response genes in macrophages even when separated by filter supports or when water extracts are used (6). Although H. pylori-induced NO production can kill the bacterium in vitro (7, 9), it survives in the stomach, despite detection of iNOS in infected gastric mucosa (10).Production of NO by macrophages can be limited by H. pylori arginase that competes with iNOS for the same substrate, L-arginine (7) under conditions ...

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Decreased Prevalence of Helicobacter pylori Infection in Gastroesophageal Reflux Disease

Cited by 81 publications

References 32 publications

Epidemiology of upper gastrointestinal bleeding and Helicobacter pylori infection: review of 3,488 Thai patients

Epidemiology of upper gastrointestinal bleeding and Helicobacter pylori infection: review of 3,488 Thai patients

l -Arginine Availability Regulates Inducible Nitric Oxide Synthase-Dependent Host Defense against Helicobacter pylori

Spermine Causes Loss of Innate Immune Response to Helicobacter pylori by Inhibition of Inducible Nitric-oxide Synthase Translation

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