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https://www.readbyqxmd.com/read/29784661/linaclotide-attenuates-visceral-organ-crosstalk-role-of-guanylate-cyclase-c-activation-in-reversing-bladder-colon-cross-sensitization
#1
Ehsan N Mohammadi, Casey O Ligon, Ada Silos-Santiago, Pei Ge, Caroline Kurtz, Carolyn Higgins, Gerhard Hannig, Beverley Greenwood-Van Meerveld
INTRODUCTION: Bladder pain syndrome (BPS) is poorly understood, however there is evidence of a female predominance and co-morbidity with irritable bowel syndrome (IBS). Here we test the hypothesis that linaclotide, a guanylate cyclase-C (GC-C) agonist approved for the treatment of IBS with constipation (IBS-C), may represent a novel therapeutic for BPS acting through a mechanism involving an inhibition of visceral organ cross sensitization. METHODS: In female rats, infusion of dilute protamine sulfate (PS) into the bladder was employed to induce bladder and colonic hypersensitivity...
May 21, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29749705/fecal-clostridiales-distribution-and-short-chain-fatty-acids-reflect-bowel-habits-in-irritable-bowel-syndrome
#2
Giorgio Gargari, Valentina Taverniti, Claudio Gardana, Cesare Cremon, Filippo Canducci, Isabella Pagano, Maria Raffaella Barbaro, Lara Bellacosa, Anna Maria Castellazzi, Chiara Valsecchi, Sara Carlotta Tagliacarne, Massimo Bellini, Lorenzo Bertani, Dario Gambaccini, Santino Marchi, Michele Cicala, Bastianello Germanà, Elisabetta Dal Pont, Maurizio Vecchi, Cristina Ogliari, Walter Fiore, Vincenzo Stanghellini, Giovanni Barbara, Simone Guglielmetti
Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, is classified according to bowel habits as IBS with constipation (IBS-C), with diarrhea (IBS-D), with alternating constipation and diarrhea (IBS-M), and unsubtyped (IBS-U). The mechanisms leading to the different IBS forms are mostly unknown. This study aims to evaluate whether specific fecal bacterial taxa and/or short-chain fatty acids (SCFAs) can be used to distinguish IBS subtypes and are relevant for explaining the clinical differences between IBS sub-categories...
May 11, 2018: Environmental Microbiology
https://www.readbyqxmd.com/read/29742779/efficacy-and-tolerability-of-linaclotide-in-the-treatment-of-irritable-bowel-syndrome-with-constipation-in-a-real%C3%A2-world-setting-results-from-a-german-noninterventional-study
#3
Viola Andresen, Stephan Miehlke, Elmar Beck, Gwen Wiseman, Peter Layer
BACKGROUND:  Linaclotide is a minimally absorbed peptide guanylate cyclase-C agonist approved for the treatment of irritable bowel syndrome with constipation (IBS-C). This study assessed the efficacy and tolerability of linaclotide in IBS-C in routine clinical practice in Germany. METHODS:  This was a 52-week, noninterventional study of linaclotide in patients aged ≥ 18 years with moderate to severe IBS-C. Severity of abdominal pain and bloating and frequency of bowel movements were assessed over 5 study visits...
May 9, 2018: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/29687534/higher-prevalence-of-joint-hypermobility-in-constipation-predominant-irritable-bowel-syndrome
#4
A Zweig, V Schindler, A S Becker, A van Maren, D Pohl
BACKGROUND: Joint hypermobility syndrome (JHS) is characterized by excessive connective tissue laxity manifest as joint hypermobility (JH) together with musculoskeletal symptoms. Previous studies have shown an association between JH/JHS and gastrointestinal symptoms, including irritable bowel syndrome (IBS), although its association with specific IBS subtypes is incompletely understood. We aimed to determine the prevalence of JH according to the subtypes of IBS, in particular IBS-C and IBS-D...
April 23, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29605985/lower-and-upper-gastrointestinal-symptoms-differ-between-individuals-with-irritable-bowel-syndrome-with-constipation-or-chronic-idiopathic-constipation
#5
Eric D Shah, Christopher V Almario, Brennan M R Spiegel, William D Chey
Background/Aims: We evaluated the distribution of lower and upper gastrointestinal (GI) symptoms among individuals with irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in a nationwide survey. Methods: Individuals (≥ 18 years of age) were identified from a nationwide sample of > 70 000 United States adults. Participants completed the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire...
April 30, 2018: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/29575454/different-perception-of-chronic-constipation-between-patients-and-gastroenterologists
#6
M Bellini, D Gambaccini, S Salvadori, R Bocchini, F Pucciani, A Bove, P Alduini, E Battaglia, G Bassotti
BACKGROUND: There is a certain number of subjects that consider themselves to be constipated (self diagnosed constipation; SDC). The Rome Criteria separate FC from IBS-C, but some SDC patients do not meet the Rome criteria (no Rome Constipation; NRC). Our aims were to evaluate the percentage of SDC subjects with a diagnosis of FC and IBS-C and to compare demographic and clinical features, symptoms, and quality of life in the different SDC groups (FC, IBS-C, NRC). METHODS: During a 2-month period, 934 patients and 980 accompanying persons (AP) were asked to complete a survey...
March 25, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29565640/sigmoid-colon-mucosal-gene-expression-supports-alterations-of-neuronal-signaling-in-irritable-bowel-syndrome-with-constipation
#7
Elizabeth J Videlock, Swapna Mahurkar-Joshi, Jill M Hoffman, Dimitrios Iliopoulos, Charalabos Pothoulakis, Emeran A Mayer, Lin Chang
OBJECTIVE: Peripheral factors likely play a role in at least a subset of irritable bowel syndrome (IBS) patients. Few studies have investigated mucosal gene expression using an unbiased approach. Here, we performed mucosal gene profiling in a sex-balanced sample to identify relevant signaling pathways and gene networks and compare to publicly available profiling data from additional cohorts. DESIGN: 20 Rome III+ IBS patients (10 IBS with constipation (IBS-C), 10 IBS with diarrhea (IBS-D) 5 men/women each) and 10 age/sex-matched healthy controls (HCs) underwent sigmoidoscopy with biopsy for gene microarray analysis, including differential expression, weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis and comparison with publicly available data...
March 22, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29545635/efficacy-safety-and-tolerability-of-plecanatide-in-patients-with-irritable-bowel-syndrome-with-constipation-results-of-two-phase-3-randomized-clinical-trials
#8
Darren M Brenner, Ronald Fogel, Spencer D Dorn, Richard Krause, Paul Eng, Robert Kirshoff, Anhthu Nguyen, Robert A Crozier, Leslie Magnus, Patrick H Griffin
OBJECTIVES: Two identical, phase 3, randomized, double-blind, placebo-controlled trials evaluated the efficacy and safety of plecanatide in patients with irritable bowel syndrome with constipation (IBS-C). METHODS: Adults meeting Rome III criteria for IBS-C were randomized (1:1:1) to placebo or plecanatide (3 or 6 mg) for 12 weeks. The primary efficacy end point was the percentage of overall responders (patients reporting ≥30% reduction from baseline in worst abdominal pain plus an increase of ≥1 complete spontaneous bowel movement (CSBM)/week from baseline in the same week for ≥6 of 12 treatment weeks)...
March 15, 2018: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/29492744/painful-or-mild-pain-constipation-a-clinically-useful-alternative-to-classification-as-irritable-bowel-syndrome-with-constipation-versus-functional-constipation
#9
Michel Bouchoucha, Ghislain Devroede, Florence Mary, Cyriaque Bon, Bakhtiar Bejou, Robert Benamouzig
PURPOSE: Abdominal pain is not used to characterize constipated patients. This study aimed to compare clinical, psychological, and physiological features in patients with IBS-constipation (IBS-C) with those in patients with functional constipation (FC) according to the intensity of abdominal pain. METHODS: All patients filled a standard Rome III questionnaire. In addition, they indicated the intensity of constipation, diarrhea, bloating, and abdominal pain on a 10-point Likert scale, and their stool form with the Bristol Stool Form Scale...
February 28, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29491683/gas-chromatography-mass-spectrometry-based-metabolomic-study-in-a-murine-model-of-irritable-bowel-syndrome
#10
Lei-Min Yu, Ke-Jia Zhao, Shuang-Shuang Wang, Xi Wang, Bin Lu
AIM: To study the role of microbial metabolites in the modulation of biochemical and physiological processes in irritable bowel syndrome (IBS). METHODS: In the current study, using a metabolomic approach, we analyzed the key metabolites differentially excreted in the feces of control mice and mice with IBS, with or without Clostridium butyricum (C. butyricum) treatment. C57BL/6 mice were divided into control, IBS, and IBS + C. butyricum groups. In the IBS and IBS + C...
February 28, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29428470/dsp-6952-a-novel-5-ht-4-receptor-partial-agonist-inhibits-visceral-hypersensitivity-and-ameliorates-gastrointestinal-dysfunction-in-experimental-animals
#11
Yukiko Mine, Tomohiro Itakura, Seiko Oku, Reiko Asada, Isao Shimizu
The pharmacological profile of DSP-6952, a novel 5-HT4 receptor partial agonist, was investigated to evaluate the potential use for GI disorders, and to compare its effects in some GI dysfunction models with those of clinically efficacious prokinetic agents. DSP-6952 enhanced gastric motility and caused colonic giant migrating contractions (GMCs) associated with defecation in conscious dogs, having ED50 value for inducing GMCs of 1.56 mg/kg. DSP-6952 (3-10 mg/kg, i.g.) significantly enhanced colonic transit rate in guinea pigs; this enhancement was antagonized by SB-207266, a selective 5-HT4 receptor antagonist...
May 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29416810/g-protein-beta-3-gn%C3%AE-3-c825t-polymorphism-and-irritable-bowel-syndrome-susceptibility-an-updated-meta-analysis-based-on-eleven-case-control-studies
#12
Dongbo Jiang, Dong Huang, Weiming Cai, Ting Li, Yan Wang, Huayan Chen, Tangming Guan, Xiaoli Ma
Several studies have reported an association between GNβ3 C825T polymorphism and irritable bowel syndrome (IBS). However, the results remain inconclusive and controversial, particularly for the data derived from different ethnicities and IBS subtypes. Therefore, we performed an updated meta-analysis to evaluate this association. All eligible case-control studies that met the search criteria were retrieved from multiple databases, and eleven case-control studies were included for detailed evaluation. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the strengths of the association between GNβ3 C825T polymorphism and susceptibility to IBS and its subtypes...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29380823/efficacy-and-tolerability-of-guanylate-cyclase-c-agonists-for-irritable-bowel-syndrome-with-constipation-and-chronic-idiopathic-constipation-a-systematic-review-and-meta-analysis
#13
REVIEW
Eric D Shah, Hyungjin Myra Kim, Philip Schoenfeld
OBJECTIVES: Linaclotide and plecanatide are guanylate cyclase-C (GCC) agonists for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Our objective is to evaluate the efficacy and tolerability of GCC agonists based on data from multiple randomized controlled trials (RCTs). METHODS: We searched PubMED, EMBASE, Cochrane databases, clinicaltrials.gov, major conference abstracts, Food and Drug Administration (FDA) websites, and United States Securities and Exchange Commission filings of drug sponsors to identify RCTs of CIC or IBS-C patients...
March 2018: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/29376436/efficacy-and-safety-of-plecanatide-in-treating-constipation-predominant-irritable-bowel-syndrome
#14
REVIEW
Philip B Miner
Uroguanylin interacting with intestinal Guanylate Cyclase C (GC-C) receptors plays an important role in gastrointestinal fluid and electrolyte homeostasis. Plecanatide is the first uroguanylin analog that stimulates GC-C receptors on gastrointestinal mucosa with pH-sensitive receptor binding. Binding to the GC-C receptor activates intracellular conversion of GTP to cGMP resulting in the stimulation of intestinal fluid secretion. Areas covered: Herein, all published research regarding the development of and clinical experience with plecanatide is reviewed...
February 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29345401/are-characteristics-of-abdominal-pain-helpful-to-identify-patients-with-visceral-hypersensitivity-in-irritable-bowel-syndrome-results-of-a-prospective-study
#15
C Melchior, L Bril, A-M Leroi, G Gourcerol, P Ducrotté
BACKGROUND: Some consider that patients with visceral hypersensitivity may represent a separate entity within the IBS population not only from a pathophysiological but also from a clinical perspective. The aim of this prospective exploratory study was to assess whether characteristics of abdominal pain in IBS patients could be suggestive of hypersensitivity. METHODS: This prospective study included consecutive IBS patients selected by Rome III criteria. Validated scores (IBS-SSS, Bristol stool scale, HADS) were used to phenotype patients who were also asked to describe the main location of their abdominal pain on a simple image (abdomen divided into 6 zones)...
January 18, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29333891/therapeutic-potential-of-zataria-multiflora-boiss-in-treatment-of-irritable-bowel-syndrome-ibs
#16
Mohaddese Mahboubi
Irritable Bowel syndrome (IBS), the most common chronic functional gastrointestinal disorder, is categorized as IBS-C and IBS-D, which are equivalent to Ghoolenj Rihi and Maghs Rihi in Iranian traditional medicine. One of the main applications of Zataria multiflora Boiss in traditional medicine is its efficacy in the gastrointestinal tract with symptoms such as IBS. The aim of this study was to evaluate the efficacy of Zataria multiflora essential oil in management of IBS. We used all the accessible references (electronic and published books, theses, and reports) to write this article...
January 15, 2018: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/29327820/gastroenterology-today-between-certainties-and-news-a-meeting-held-in-turin-on-may-27-2017
#17
Rinaldo Pellicano, Davide G Ribaldone, Marco Astegiano, Luca Dughera, Edda Battaglia, Anna Morgando, Arrigo Arrigoni, Mauro Spandre, Mario Grassini, Giorgio M Saracco, Francis Mégraud
This special article reports on two crucial issues discussed during a meeting. The first was the updated management of Helicobacter pylori infection. This was approached taking into account the recent European Guidelines, with a focus on novelties in treatment. In particular, considering the increasing H. pylori antibiotic resistance to clarithromycin, in countries with a high clarithromycin resistance rate the bismuth-containing quadruple therapies should be preferred. The new formulation, with bismuth, metronidazole, and tetracycline contained in a single capsule (three-in-one), has shown exciting results both in naive and in non-responder patients...
January 10, 2018: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/29319191/linaclotide-in-irritable-bowel-syndrome-with-constipation-a-phase-3-randomized-trial-in-china-and-other-regions
#18
Yunsheng Yang, Jingyuan Fang, Xiaozhong Guo, Ning Dai, Xizhong Shen, Youlin Yang, Jing Sun, Bal Raj Bhandari, David S Reasner, Jacquelyn A Cronin, Mark G Currie, Jeffrey M Johnston, Peter Zeng, Niwat Montreewasuwat, George Zhijian Chen, Sam Lim
BACKGROUND AND AIM: Linaclotide is a guanylate cyclase-C agonist approved in multiple countries to treat irritable bowel syndrome with constipation (IBS-C). China has unmet need for well-tolerated therapy that is effective in treating both bowel and abdominal symptoms of IBS-C. This trial evaluated linaclotide's efficacy and safety in IBS-C patients in China and other regions. METHODS: This Phase 3, double-blind trial randomized IBS-C patients to once-daily oral 290-μg linaclotide or placebo at centers in China, North America, and Oceania...
January 10, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29284389/efficacy-and-safety-of-serotonin-receptor-ligands-in-the-treatment-of-irritable-bowel-syndrome-a-review
#19
Agata Binienda, Martin Storr, Jakub Fichna, Maciej Salaga
Irritable bowel syndrome (IBS) is a chronic, recurrent bowel disorder with an unknown etiology, which is most likely multifactorial. Increased mucosal permeability, visceral hypersensitivity and activation status of intestinal mucosal immune cells cause changes in gastrointestinal (GI) motility, secretion and sensation observed in the course of IBS. Permanent, cumbersome symptoms, such as diarrhea, constipation and abdominal pain greatly lower quality of life of IBS patients. On this basis, according to the Rome IV criteria, different forms of IBS can be distinguished...
December 27, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/29278278/determining-an-optimal-dose-of-linaclotide-for-use-in-japanese-patients-with-irritable-bowel-syndrome-with-constipation-a-phase-ii-randomized-double-blind-placebo-controlled-study
#20
S Fukudo, A Nakajima, Y Fujiyama, M Kosako, A Nakagawa, H Akiho, Y Nakashima, J M Johnston, H Miwa
BACKGROUND: Clinical testing to determine a suitable dose of linaclotide for Japanese patients with irritable bowel syndrome with constipation (IBS-C) was needed. METHODS: This was a randomized, double-blind, placebo-controlled, dose-finding trial. Japanese patients with IBS-C diagnosed using Rome III criteria (n = 559, men/women: 49/510) were randomly assigned to 1 of 4 linaclotide doses (0.0625, 0.125, 0.25, or 0.5 mg) or placebo for the 12-week treatment period...
December 26, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
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