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Niles SE, Blazy P, Cheuvront SN, Kenefick RW, Vidyasagar S, Smith AB, Fawkes N, Denman W. Effectiveness of an amino acid beverage formulation in diarrhea-predominant irritable bowel syndrome: A pragmatic real-world study. World J Gastrointest Pharmacol Ther 2023; 14:39-49. [PMID: 38174291 PMCID: PMC10758599 DOI: 10.4292/wjgpt.v14.i5.39] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 10/16/2023] [Accepted: 11/15/2023] [Indexed: 12/12/2023] Open
Abstract
BACKGROUND Amino-acid based medical foods have shown promise in alleviating symptoms of drug induced gastrointestinal side effects; particularly, diarrhea-predominant symptoms. Irritable bowel syndrome (IBS) is a gastrointestinal disorder that affects up to 9% of people globally, with diarrhea predominant IBS (IBS-D) being the most prevalent subtype. Further trials are needed to explore potential added benefits when integrated into standard care for IBS-D. AIM To assess the effectiveness of an amino acid-based medical food as an adjunct to standard of care for adults with IBS-D. METHODS This is a pragmatic, real world, open label, single arm study comparing a 2-week baseline assessment to a 2-week intervention period. One hundred adults, aged 18 to 65 years, with IBS-D, according to Rome IV criteria, were enrolled after completing a 2-week baseline assessment period and received a 2-week supply of an amino acid based medical food which was consumed at home twice daily on top of their standard of care. The primary outcome was an assessment of tolerability after 2-weeks of consumption, while secondary outcomes included changes in stool consistency (Bristol Stool Form Scale), severity of abdominal pain & discomfort, symptoms of urgency, Global Improvement Survey (GIS), and the IBS severity scoring system (IBS-SSS). RESULTS The test product was well-tolerated as each participant successfully completed the full 14-day trial, and there were no instances of dropouts or discontinuation of the study product reported. Forty percent of participants achieved a 50% or more reduction in the number of days with type 6-7 bowel movements (IBS-D stool consistency responders). Fifty-three percent of participants achieved a clinically meaningful reduction of 30% in mean weekly pain scores, and 55% experienced the same for mean weekly discomfort scores (IBS-D pain and discomfort responders). Participants experienced a mean -109.4 (95% confidence interval: -130.1, -88.8) point reduction on the IBS-SSS and 52% experienced a minimally clinically important difference of > 95 points. An IBS-SSS category shift from severe to moderate or mild occurred in 69% of participants. For functional symptoms, 76% of participants reported symptom relief on the GIS. CONCLUSION The amino acid-based medical food was well-tolerated, when added to the standard of care, and demonstrated improvements in both overall IBS symptom severity and IBS-D symptoms within just 2 wk.
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Affiliation(s)
- Samantha E Niles
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
| | - Phil Blazy
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
| | - Samuel N Cheuvront
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
| | - Robert W Kenefick
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
| | - Sadasivan Vidyasagar
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
- Department of Radiation Oncology, University of Florida, Gainesville, FL 32611, United States
| | - Adam B Smith
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
| | - Neil Fawkes
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
| | - William Denman
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
- Department of Anesthesiology, Massachusetts General Hospital, Boston, MA 02114, United States
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Suzuki H. To establish a treatment for GI symptoms of cystic fibrosis, it is necessary to develop a symptom evaluation tool. United European Gastroenterol J 2019; 7:873-874. [PMID: 31428410 PMCID: PMC6683642 DOI: 10.1177/2050640619856188] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Affiliation(s)
- Hidekazu Suzuki
- Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Japan
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Ranjbar S, Seyednejad SA, Nikfar S, Rahimi R, Abdollahi M. How can we develop better antispasmodics for irritable bowel syndrome? Expert Opin Drug Discov 2019; 14:549-562. [DOI: 10.1080/17460441.2019.1593369] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Sheyda Ranjbar
- Evidence-based Evaluation of Cost-Effectiveness and Clinical Outcomes, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Afshin Seyednejad
- Evidence-based Evaluation of Cost-Effectiveness and Clinical Outcomes, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
| | - Shekoufeh Nikfar
- Evidence-based Evaluation of Cost-Effectiveness and Clinical Outcomes, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Roja Rahimi
- Evidence-based Evaluation of Cost-Effectiveness and Clinical Outcomes, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
- Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Abdollahi
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
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4
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Simrén M, Tack J. New treatments and therapeutic targets for IBS and other functional bowel disorders. Nat Rev Gastroenterol Hepatol 2018; 15:589-605. [PMID: 29930260 DOI: 10.1038/s41575-018-0034-5] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Functional bowel disorders (FBDs) are a spectrum of disorders characterized by combinations of symptoms attributable to the lower gastrointestinal tract. Most current first-line therapies for IBS and other FBDs target the predominant symptom and mainly affect one symptom in the symptom complex. Additional broadly effective treatment alternatives targeting the entire symptom complex are needed. New drugs for FBDs (such as lubiprostone, linaclotide, plecanatide, prucalopride, eluxadoline and rifaximin) target key mechanisms in the pathophysiology of these disorders and improve both the abnormal bowel habit and other key symptoms, such as abdominal pain and bloating. The current development of new treatment alternatives is focusing on different aspects of the complex pathophysiology of IBS and other FBDs: gut microenvironment (via diet and modulation of gut microbiota), enterohepatic circulation of bile acids, gastrointestinal secretion, motility and sensation, gut-brain interactions, gut barrier function and the immune system within the gastrointestinal tract. Studies also suggest that personalized treatment of IBS and other FBDs is possible using various diagnostic markers.
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Affiliation(s)
- Magnus Simrén
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA.
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium
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Sinagra E, Morreale GC, Mohammadian G, Fusco G, Guarnotta V, Tomasello G, Cappello F, Rossi F, Amvrosiadis G, Raimondo D. New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond. World J Gastroenterol 2017; 23:6593-6627. [PMID: 29085207 PMCID: PMC5643283 DOI: 10.3748/wjg.v23.i36.6593] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 04/15/2017] [Accepted: 07/04/2017] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic, recurring, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, distention, and changes in bowel habits. Although there are several drugs for IBS, effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed. Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS. With regards to therapies for restoring intestinal permeability, multiple studies with prebiotics and probiotics are ongoing, even if to date their efficacy has been limited. In parallel, much progress has been made in targeting low-grade inflammation, especially through the introduction of drugs such as mesalazine and rifaximin, even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs. This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS, most recently developed in preclinical as well as Phase 1 and Phase 2 clinical studies.
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Affiliation(s)
- Emanuele Sinagra
- Gastroenterology and Endoscopy Unit, Fondazione Istituto Giuseppe Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy
- Euro-Mediterranean Institute of Science and Technology, 90100 Palermo, Italy
- Department of Experimental Biomedicine and Clinical Neuroscience, Section of Human Anatomy, University of Palermo, 90100 Palermo, Italy
| | | | - Ghazaleh Mohammadian
- Department of Medicine, Division of Gastroenterology and Hepatology, Karolinska Institutet, Karolinska University Hospital, Huddinge, 17176 Stockholm, Sweden
| | - Giorgio Fusco
- Unit of Internal Medicine, Ospedali Riuniti Villa Sofia-Vincenzo Cervello, 90100 Palermo, Italy
| | - Valentina Guarnotta
- Section of Cardio-Respiratory and Endocrine-Metabolic Diseases, Biomedical Department of Internal and Specialist Medicine, University of Palermo, Palermo 90127, Italy
| | - Giovanni Tomasello
- Euro-Mediterranean Institute of Science and Technology, 90100 Palermo, Italy
- Department of Experimental Biomedicine and Clinical Neuroscience, Section of Human Anatomy, University of Palermo, 90100 Palermo, Italy
| | - Francesco Cappello
- Euro-Mediterranean Institute of Science and Technology, 90100 Palermo, Italy
- Department of Experimental Biomedicine and Clinical Neuroscience, Section of Human Anatomy, University of Palermo, 90100 Palermo, Italy
| | - Francesca Rossi
- Gastroenterology and Endoscopy Unit, Fondazione Istituto Giuseppe Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy
| | - Georgios Amvrosiadis
- Unit of Gastroenterology, Ospedali Riuniti Villa Sofia-Vincenzo Cervello, 90100 Palermo, Italy
| | - Dario Raimondo
- Gastroenterology and Endoscopy Unit, Fondazione Istituto Giuseppe Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy
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Kim KS, Kim HJ, Lee SH, Cho ST, Moon HS. Association Between Irritable Bowel Syndrome and Overactive Bladder: A Research Survey. Urology 2017; 109:88-93. [PMID: 28803902 DOI: 10.1016/j.urology.2017.06.038] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 06/22/2017] [Accepted: 06/26/2017] [Indexed: 12/28/2022]
Abstract
OBJECTIVE To investigate the relationship between irritable bowel syndrome (IBS) and overactive bladder (OAB) in men and women using questionnaires. MATERIALS AND METHODS This research survey was based on multicenter data (men and women older than 20 years). The Korean version of the Rome III criteria was used for the diagnosis of IBS, Overactive Bladder Symptom Score (OABSS) was used for screening OAB, Self-Rating Depression Scale was used for depressive symptoms, and International Prostate Symptom Score and Quality of Life were used to determine the degrees of lower urinary tract symptoms. RESULTS A total of 609 (men: 257, women: 352) people answered the questionnaire. The prevalence of IBS and OAB was 31.9% (men vs women: 27.3% vs 39.2%) and 19.2% (men vs women: 25.3% vs 18.5%), respectively. The OABSS values of patients with IBS and non-IBS patients were 1.70 ± 2.48 and 2.48 ± 2.79 (P <.001). On the Self-Rating Depression Scale, individuals with IBS had a higher score than non-IBS individuals (n = 201) (44.92 ± 13.71 vs 39.19 ± 10.39, P <.001). In men, non-IBS (n = 56) had higher OABSS and OABSS question number 3 responses than patients with IBS (OABSS: 2.56 ± 2.69 vs 1.57 ± 2.43, P = .01, OABSS Q3: 0.92 ± 1.26 vs 0.66 ± 1.13, P = .17). Also, in women, non-IBS (n = 214) had higher OABSS and OABSS question number 3 responses than patients with IBS (n = 138) (OABSS: 2.40 ± 2.87 vs 1.76 ± 2.52, P = .03, OABSS Q3: 0.83 ± 1.25 vs 0.70 ± 1.18, P = .32). CONCLUSION IBS in adults had no relationship with OAB in our study. These data suggest that more studies are needed to determine the relationship between IBS and OAB.
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Affiliation(s)
- Kyu Shik Kim
- Department of Urology, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Hyung-Jee Kim
- Department of Urology, Dankook University College of Medicine, Cheonan, Republic of Korea
| | - Seong Ho Lee
- Department of Urology, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Sung Tae Cho
- Department of Urology, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Hong Sang Moon
- Department of Urology, Hanyang University College of Medicine, Seoul, Republic of Korea.
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Camilleri M, Bueno L, Andresen V, De Ponti F, Choi MG, Lembo A. Pharmacological, Pharmacokinetic, and Pharmacogenomic Aspects of Functional Gastrointestinal Disorders. Gastroenterology 2016; 150:S0016-5085(16)00220-1. [PMID: 27144621 DOI: 10.1053/j.gastro.2016.02.029] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 02/09/2016] [Indexed: 02/08/2023]
Abstract
This article reviews medications commonly used for the treatment of patients with functional gastrointestinal disorders. Specifically, we review the animal models that have been validated for the study of drug effects on sensation and motility; the preclinical pharmacology, pharmacokinetics, and toxicology usually required for introduction of new drugs; the biomarkers that are validated for studies of sensation and motility endpoints with experimental medications in humans; the pharmacogenomics applied to these medications and their relevance to the FGIDs; and the pharmacology of agents that are applied or have potential for the treatment of FGIDs, including psychopharmacologic drugs.
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Affiliation(s)
- Michael Camilleri
- Professor of Medicine, Pharmacology, and Physiology, Mayo Clinic College of Medicine, Consultant in Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Viola Andresen
- Israelitic Hospital, University of Hamburg, Orchideenstieg 14, Hamburg, Germany
| | - Fabrizio De Ponti
- Professor of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Myung-Gyu Choi
- Professor of Gastroenterology, The Catholic University of Korea College of Medicine Internal Medicine , President, Korean Society of Neurogastroenterology and Motility , Seoul, Korea
| | - Anthony Lembo
- Associate Professor, Harvard Medical School, Director of the GI Motility Laboratory at the Beth Israel Deaconess Medical Center's (BIDMC) Division of Gastroenterology, Boston, MA, USA
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Abstract
Irritable bowel syndrome (IBS) affects about 15 % of the US population and results in significant morbidity and health care costs. There remains a significant unmet need for effective treatments particularly for the pain component of IBS and other functional gastrointestinal disorders (FGIDs). Progress made in our understanding of pathophysiological mechanisms such as the role of altered bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and secretory properties of the gut has led to advancements in therapeutic armamentarium for IBS. This review discusses the new drugs for constipation and diarrhea-predominant IBS subtypes that have been tested or have been under investigation over the last 3-4 years. Overall, there is a promising pipeline of investigational drugs for the future treatment of IBS and related FGIDs.
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Affiliation(s)
- Akhilesh Wadhwa
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
| | - Madhusudan Grover
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
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Lazaraki G, Chatzimavroudis G, Katsinelos P. Recent advances in pharmacological treatment of irritable bowel syndrome. World J Gastroenterol 2014; 20:8867-8885. [PMID: 25083060 PMCID: PMC4112893 DOI: 10.3748/wjg.v20.i27.8867] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 03/13/2014] [Accepted: 06/23/2014] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a highly prevalent functional disorder that reduces patients’ quality of life. It is a chronic disorder characterized by abdominal pain or discomfort associated with disordered defecation in the absence of identifiable structural or biochemical abnormalities. IBS imposes a significant economic burden to the healthcare system. Alteration in neurohumoral mechanisms and psychological factors, bacterial overgrowth, genetic factors, gut motility, visceral hypersensitivity, and immune system factors are currently believed to influence the pathogenesis of IBS. It is possible that there is an interaction of one or more of these etiologic factors leading to heterogeneous symptoms of IBS. IBS treatment is predicated upon the patient’s most bothersome symptoms. Despite the wide range of medications and the high prevalence of the disease, to date no completely effective remedy is available. This article reviews the literature from January 2008 to July 2013 on the subject of IBS peripherally acting pharmacological treatment. Drugs are categorized according to their administration for IBS-C, IBS-D or abdominal pain predominant IBS.
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10
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Yueh TP, Chen FY, Lin TE, Chuang MT. Diarrhea after laparoscopic cholecystectomy: associated factors and predictors. Asian J Surg 2014; 37:171-7. [PMID: 24647139 DOI: 10.1016/j.asjsur.2014.01.008] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Revised: 01/13/2014] [Accepted: 01/14/2014] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Diarrhea is part of the postlaparoscopic cholecystectomy syndrome, but is not well defined. Published reports have ignored possible associated factors such as the preoperative excretion pattern, gastrointestinal disorders, personality disorders, the effect of drugs, unsanitary food, and high-fat diets. PURPOSE The aim of this study was to define the associated factors and predictors of postlaparoscopic cholecystectomy diarrhea (PLCD) at different time intervals after the operation and to identify the possible associated factors and predictors of PLCD. We also aimed to determine the effectiveness of a low-fat diet in these patients and to educate the patients about their diet after the operation. METHODS Data were obtained from clinical records and preoperative interviews with patients, who were also interviewed or contacted by telephone 1 week after the operation, and then surveyed by telephone 3 months later using standardized questionnaires. A total of 125 consecutive patients who were adequately informed and who had assented to accepting a prescription of a low-fat diet after undergoing laparoscopic cholecystectomy participated in this prospective study. RESULTS Thirty-eight patients (25.2%) had diarrhea 1 week after laparoscopic cholecystectomy and seven patients (5.7%) had diarrhea 3 months after laparoscopic cholecystectomy. The important predictors of PLCD at 1 week were a low-fat diet (B = -0.177, p = 0.000) and a high score on a preoperative diarrhea scale (B = 0.311, p = 0.031). There was no predictor for PLCD 3 months after laparoscopic cholecystectomy. CONCLUSION We advise patients who have undergone laparoscopic cholecystectomy to follow a low-fat diet for at least 1 week to reduce the possibility of diarrhea, especially when they are ≤45 years of age, of male sex, and had a high preoperative tendency for diarrhea.
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Affiliation(s)
- Tuan-Pin Yueh
- Surgical Department, Saint Martin de Porres Hospital, Chiayi, Taiwan; Department of Nursing, College of Medicine & Nursing, Hung Kuang University, Taichung, Taiwan; Nursing Department, Saint Martin de Porres Hospital, Chiayi, Taiwan
| | - Fong-Ying Chen
- Department of Nursing, College of Medicine & Nursing, Hung Kuang University, Taichung, Taiwan
| | - Tsyr-En Lin
- Nursing Department, Saint Martin de Porres Hospital, Chiayi, Taiwan; Department of Nursing, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi, Taiwan
| | - Mao-Te Chuang
- Surgical Department, Saint Martin de Porres Hospital, Chiayi, Taiwan.
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Kimoto M, Zeredo JL, Ota MS, Nihei Z, Toda K. Comparison of stress-induced modulation of smooth-muscle activity between ileum and colon in male rats. Auton Neurosci 2014; 183:8-11. [PMID: 24530114 DOI: 10.1016/j.autneu.2014.01.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Revised: 01/22/2014] [Accepted: 01/24/2014] [Indexed: 12/13/2022]
Abstract
Stress is a well-known cause of numerous digestive conditions, including gastrointestinal-function disorders. The autonomic nervous system regulates intestinal movements via cholinergic and adrenergic efferent fibers; however it is not clear how stress could affect these control mechanisms and in particular whether in a site-dependent manner. In this study we tested in vitro the effects of topical application of acetylcholine (Ach) and adrenalin (Adr) on smooth-muscle contractions of intestinal segments isolated from stress-conditioned rats. Stress was loaded by hypergravity stimulation (10min/day) for periods of 1, 6 or 30days. As a result, stress-conditioning affected intestinal sensitivity to Ach and Adr differently at sections of the ileum and colon. In the ileum no significant differences were found between control and stress-conditioned rats, whereas in the colon, samples from 6- and 30-day stress-conditioned rats showed larger amplitudes of Ach-induced contraction, as well as greater antagonization by Adr application. These results suggest that stress conditioning can modify autonomic control of intestinal movements by altering smooth-muscle sensitivity to Ach and Adr.
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Affiliation(s)
- Mari Kimoto
- Physiological Laboratories, Japan Women's University, Tokyo, Japan
| | - Jorge L Zeredo
- University of Brasilia, Brasilia, Brazil; Integrative Sensory Physiology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Masato S Ota
- Laboratory of Biochemistry and Food Biology, Japan Women's University, Tokyo, Japan
| | - Zenro Nihei
- Integrative Sensory Physiology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Kazuo Toda
- Physiological Laboratories, Japan Women's University, Tokyo, Japan; Integrative Sensory Physiology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
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12
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Camilleri M. Pharmacological agents currently in clinical trials for disorders in neurogastroenterology. J Clin Invest 2013; 123:4111-20. [PMID: 24084743 DOI: 10.1172/jci70837] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Esophageal, gastrointestinal, and colonic diseases resulting from disorders of the motor and sensory functions represent almost half the patients presenting to gastroenterologists. There have been significant advances in understanding the mechanisms of these disorders, through basic and translational research, and in targeting the receptors or mediators involved, through clinical trials involving biomarkers and patient responses. These advances have led to relief of patients' symptoms and improved quality of life, although there are still significant unmet needs. This article reviews the pipeline of medications in development for esophageal sensorimotor disorders, gastroparesis, chronic diarrhea, chronic constipation (including opioid-induced constipation), and visceral pain.
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13
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Affiliation(s)
- Full-Young Chang
- Environmental Heath and Safety Office, Division of Gastroenterology, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, Taipei, Taiwan
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Suzuki H, Matsuzaki J. Are Solifenacin and Ramosetron Really Ideal to Treat Irritable Bowel Syndrome?: Author's Reply. J Neurogastroenterol Motil 2012; 18:459. [PMID: 23106012 PMCID: PMC3479265 DOI: 10.5056/jnm.2012.18.4.459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Hidekazu Suzuki
- Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
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