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      Plasma ghrelin level and plasma ghrelin/obestatin ratio are related to intestinal metaplasia in elderly patients with functional dyspepsia

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          Abstract

          Background

          Whether plasma ghrelin/obestatin levels are associated with Helicobacter pylori ( H. pylori) infection, subtypes of functional dyspepsia (FD), and gastric mucosal histology has not yet been established in elderly patients.

          Objective

          The aim of this study was to determine whether plasma ghrelin and obestatin levels are related to gastric mucosal histology, H. pylori infection, and FD subtypes in elderly patients with FD.

          Methods

          Ninety-two patients diagnosed with FD and older than 60 years (median age 69.4; range 60–88) were included. Clinical symptoms investigated included postprandial fullness, epigastric pain, epigastric soreness, nausea, and vomiting. According to the Rome III criteria, patients diagnosed with FD were divided into two subtypes: epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). Plasma ghrelin and obestatin levels were measured using enzyme immunoassay, and histological examination of gastric mucosa was performed. H. pylori infection was determined by histopathological examination of gastric mucosal biopsy and/or Campylobacter-like organism test.

          Results

          In our study, plasma ghrelin levels and plasma ghrelin/obestatin (G/O) ratio were significantly lower in subjects with intestinal metaplasia compared with those without intestinal metaplasia (ghrelin, p = 0.010; G/O ratio, p = 0.012). On the other hand, there were no significant differences in plasma ghrelin and obestatin levels between H. pylori–positive and H. pylori–negative groups. (ghrelin, p = 0.130; obestatin, p = 0.888). Similarly, no significant differences were detected between the EPS and PDS groups (ghrelin, p = 0.238; obestatin, p = 0.710).

          Conclusions

          Patients with intestinal metaplasia, a known precursor of gastric cancer, had significantly less plasma ghrelin levels and G/O ratio than those without intestinal metaplasia.

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          Most cited references33

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          Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994.

          The Sydney System for the classification of gastritis emphasized the importance of combining topographical, morphological, and etiological information into a schema that would help to generate reproducible and clinically useful diagnoses. To reappraise the Sydney System 4 years after its introduction, a group of gastrointestinal pathologists from various parts of the world met in Houston, Texas, in September 1994. The aims of the workshop were (a) to establish an agreed terminology of gastritis; (b) to identify, define, and attempt to resolve some of the problems associated with the Sydney System. This article introduces the Sydney System as it was revised at the Houston Gastritis Workshop and represents the consensus of the participants. Overall, the principles and grading of the Sydney System were only slightly modified, the grading being aided by the provision of a visual analogue scale. The terminology of the final classification has been improved to emphasize the distinction between the atrophic and nonatrophic stomach; the names used for each entity were selected because they are generally acceptable to both pathologists and gastroenterologists. In addition to the main categories and atrophic and nonatrophic gastritis, the special or distinctive forms are described and their respective diagnostic criteria are provided. The article includes practical guidelines for optimal biopsy sampling of the stomach, for the use of the visual analogue scales for grading the histopathologic features, and for the formulation of a comprehensive standardized diagnosis. A glossary of gastritis-related terms as used in this article is provided.
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            Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake.

            Ghrelin, a circulating appetite-inducing hormone, is derived from a prohormone by posttranslational processing. On the basis of the bioinformatic prediction that another peptide also derived from proghrelin exists, we isolated a hormone from rat stomach and named it obestatin-a contraction of obese, from the Latin "obedere," meaning to devour, and "statin," denoting suppression. Contrary to the appetite-stimulating effects of ghrelin, treatment of rats with obestatin suppressed food intake, inhibited jejunal contraction, and decreased body-weight gain. Obestatin bound to the orphan G protein-coupled receptor GPR39. Thus, two peptide hormones with opposing action in weight regulation are derived from the same ghrelin gene. After differential modification, these hormones activate distinct receptors.
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              Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans.

              Ghrelin, an endogenous ligand for the GH secretagogue receptor, was isolated from rat stomach and is involved in a novel system for regulating GH release. Although previous studies in rodents suggest that ghrelin is also involved in energy homeostasis and that ghrelin secretion is influenced by feeding, little is known about plasma ghrelin in humans. To address this issue, we studied plasma ghrelin-like immunoreactivity levels and elucidated the source of circulating ghrelin and the effects of feeding state on plasma ghrelin-like immunoreactivity levels in humans. The plasma ghrelin-like immunoreactivity concentration in normal humans measured by a specific RIA was 166.0 +/- 10.1 fmol/ml. Northern blot analysis of various human tissues identified ghrelin mRNA found most abundantly in the stomach and plasma ghrelin-like immunoreactivity levels in totally gastrectomized patients were reduced to 35% of those in normal controls. Plasma ghrelin-like immunoreactivity levels were increased by 31% after 12-h fasting and reduced by 22% immediately after habitual feeding. In patients with anorexia nervosa, plasma ghrelin-like immunoreactivity levels were markedly elevated compared with those in normal controls (401.2 +/- 58.4 vs. 192.8 +/- 19.4 fmol/ml) and were negatively correlated with body mass indexes. We conclude that the stomach is a major source of circulating ghrelin and that plasma ghrelin-like immunoreactivity levels reflect acute and chronic feeding states in humans.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 April 2017
                2017
                : 12
                : 4
                : e0175231
                Affiliations
                [001]Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
                Monash University, AUSTRALIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: JWK.

                • Formal analysis: JWK.

                • Funding acquisition: JWK.

                • Investigation: JB.

                • Methodology: JWK.

                • Supervision: JWK.

                • Visualization: SHK JB.

                • Writing – original draft: SHK.

                • Writing – review & editing: SHK JWK JB JBJ BGK KLL.

                Article
                PONE-D-16-30465
                10.1371/journal.pone.0175231
                5395142
                28419119
                30e64d78-6c24-4aa6-97c0-579a568ec878
                © 2017 Kim et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 July 2016
                : 22 March 2017
                Page count
                Figures: 0, Tables: 5, Pages: 11
                Funding
                Funded by: Seoul Metropolitan Government-Seoul National University(SMG-SNU) Boramae Medical Center
                Award ID: 03-2007-1
                Award Recipient :
                This study was supported by research funding from the Seoul Metropolitan Government-Seoul National University Boramae Medical Center (03-2007-1). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Hormones
                Peptide Hormones
                Ghrelin
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Atrophy
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Atrophy
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Medicine and Health Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Bacterial Pathogens
                Helicobacter Pylori
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Bacterial Pathogens
                Helicobacter Pylori
                Biology and Life Sciences
                Organisms
                Bacteria
                Helicobacter
                Helicobacter Pylori
                Biology and Life Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
                Geriatrics
                People and Places
                Population Groupings
                Age Groups
                Elderly
                Custom metadata
                All relevant data are within the paper and its Supporting Information file.

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