Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
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Neurogastroenterol. Motil. · Aug 2015
Emerging treatments in Neurogastroenterology: Perspectives of guanylyl cyclase C agonists use in functional gastrointestinal disorders and inflammatory bowel diseases.
Functional gastrointestinal disorders (FGID) and inflammatory bowel diseases (IBD) are the most frequent pathologic conditions affecting the gastrointestinal (GI) tract and both significantly reduce patients' quality of life. Recent studies suggest that guanylyl cyclase C (GC-C) expressed in the GI tract constitutes a novel pharmacological target in the treatment of FGID and IBD. Endogenous GC-C agonists - guanylin peptides: guanylin and uroguanylin, by the regulation of water and electrolyte transport, are involved in the maintenance of homeostasis in the intestines and integrity of the intestinal mucosa. Linaclotide, a synthetic agonist of GC-C was approved by Food and Drug Administration and European Medicines Agency as a therapeutic in constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation (CIC). Lately, several preclinical and clinical trials focused on assessment of therapeutic properties of synthetic agonists of uroguanylin, plecanatide, and SP-333. Plecanatide is currently tested as a potential therapeutic in diseases related to constipation and SP-333 is a promising drug in ulcerative colitis treatment. ⋯ Here, we discuss the most recent findings and future trends on the development of GC-C agonists and their use in clinical trials.
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Neurogastroenterol. Motil. · Jul 2015
Breath methane in functional constipation: response to treatment with Ispaghula husk.
Colonic fermentation produces hydrogen (H2 ), and also produces methane (CH4 ) in subjects with methanogenic flora (M+). Methane production has been associated with chronic constipation (CC) and with changes in gut motility. To determine CH4 production in CC compared to controls, and to assess whether the therapeutic response to Ispaghula husk in CC differs between CH4 -producers and non-producers. ⋯ Although CH4 production has been associated with CC pathophysiology, we found that CH4 status did not negatively affect the response to Ispaghula husk treatment. The measurement of CH4 levels as a biomarker tool for CC requires further appraisal.
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Neurogastroenterol. Motil. · Jul 2015
Predictive value of routine esophageal high-resolution manometry for gastro-esophageal reflux disease.
Using conventional manometry, gastro-esophageal reflux disease (GERD) was associated with a reduced lower esophageal sphincter (LES) pressure and impaired peristalsis. However, with a large overlap between GERD patients and controls, these findings are of limited clinical relevance. It is uncertain whether the more detailed information of high-resolution manometry (HRM) can discriminate GERD patients. Therefore, we aimed to determine to which extent HRM findings can predict GERD. ⋯ Hiatal hernia, low contraction amplitude and LES pressure are associated with GERD, but do not predict the disease with sufficient accuracy. Routine esophageal HRM can therefore not be used to distinguish GERD patients from healthy subjects.
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Neurogastroenterol. Motil. · Jun 2015
Estradiol modulates visceral hyperalgesia by increasing thoracolumbar spinal GluN2B subunit activity in female rats.
We previously reported estrogen modulates spinal N-methyl-d-aspartate (NMDA) receptor processing of colorectal pain through changes in spinal GluN1 subunit phosphorylation/expression. The purpose of this study was to investigate whether spinal GluN2B containing NMDA receptors are involved in estrogen modulation of visceral pain processing. ⋯ These data support the hypothesis that estrogen increases spinal processing of colonic inflammation-induced visceral hyperalgesia by increasing NMDA receptor activity. Specifically, an increase in the activity of GluN2B containing NMDA receptors in the TL spinal cord by estrogen underlies visceral hypersensitivity in the presence of colonic inflammation.
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Neurogastroenterol. Motil. · Jun 2015
ReviewIrritable bowel syndrome: an integrated explanatory model for clinical practice.
Although irritable bowel syndrome (IBS) is a symptom-based diagnosis, clinicians' management of and communication about the disorder is often hampered by an unclear conceptual understanding of the nature of the problem. We aimed to elucidate an integrated explanatory model (EM) for IBS from the existing literature for pragmatic use in the clinical setting. ⋯ It was possible to elucidate an integrated, three-component EM as a basis for clinicians to conceptualize the nature of IBS, with the potential to contribute to better diagnosis and management, and dialog with sufferers.