Faculty Opinions recommendation of The tryptophan hydroxylase inhibitor LX1031 shows clinical benefit in patients with nonconstipating irritable bowel syndrome.

2011 ◽  
Author(s):  
Guido Basilisco
Keyword(s):  
Irritable Bowel Syndrome ◽  
Clinical Benefit ◽  
Tryptophan Hydroxylase ◽  
Irritable Bowel

scholarly journals The Tryptophan Hydroxylase Inhibitor LX1031 Shows Clinical Benefit in Patients With Nonconstipating Irritable Bowel Syndrome

2011 ◽  
Vol 141 (2) ◽  
pp. 507-516 ◽  
Author(s):  
Philip M. Brown ◽  
Douglas A. Drossman ◽  
Alastair J.J. Wood ◽  
Gary A. Cline ◽  
Kenny S. Frazier ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Clinical Benefit ◽  
Tryptophan Hydroxylase ◽  
Irritable Bowel

scholarly journals TPH Gene Polymorphisms Are Associated With Disease Perception and Quality of Life in Women With Irritable Bowel Syndrome

2012 ◽  
Vol 16 (1) ◽  
pp. 95-104 ◽  
Author(s):  
Sang-Eun Jun ◽  
Ruth Kohen ◽  
Kevin C. Cain ◽  
Monica E. Jarrett ◽  
Margaret M. Heitkemper
Keyword(s):  
Quality Of Life ◽  
Irritable Bowel Syndrome ◽  
Gene Polymorphisms ◽  
Tryptophan Hydroxylase ◽  
Univariate Analysis ◽  
Gastrointestinal Symptoms ◽  
Tph2 Gene ◽  
Irritable Bowel ◽  
The Impact

The aims of this exploratory study were to examine whether tryptophan hydroxylase ( TPH) gene polymorphisms are associated with psychosocial factors in women with irritable bowel syndrome (IBS). TPH is the rate-limiting enzyme in the biosynthesis of serotonin and has two isoforms, TPH1 and TPH2. Four single nucleotide polymorphisms (SNPs) in the TPH1 gene and one SNP in the TPH2 gene were selected based on previous studies investigating associations between these SNPs and psychiatric or behavioral disorders. One hundred ninety-nine Caucasian women with IBS were included. Results of univariate analysis showed no association between TPH1and TPH2 gene SNPs and current level of psychological distress or psychiatric illness. However, TPH1 gene SNPs were associated with IBS-related cognitions (rs4537731 and rs21105) and quality of life (rs684302 and rs1800532), in particular the mental health and energy subscales. These associations were independent of the subjects’ levels of gastrointestinal symptoms. These results suggest that patients’ perception of their illness, and of the impact it has on their lives, may be subject to genetic influences, in this case sequence variants in TPH1. However, caution should be used in interpreting these results given the large number of hypothesis tests performed in this exploratory hypothesis-generating study, and the results should be considered tentative until confirmed in an independent sample.

Effects of Electroacupuncture at St25 and Bl25 in a Sennae-induced rat model of diarrhoea-predominant irritable bowel syndrome

2017 ◽  
Vol 35 (3) ◽  
pp. 216-223 ◽  
Author(s):  
Xianwei Zhu ◽  
Zhibin Liu ◽  
Wenmin Niu ◽  
Yuan Wang ◽  
Aimin Zhang ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Small Intestine ◽  
Rat Model ◽  
Tryptophan Hydroxylase ◽  
Cell Number ◽  
Control Group ◽  
Loose Stool ◽  
Paracrine Signalling ◽  
Irritable Bowel ◽  
Small Intestine Transit

Background Electroacupuncture (EA) may have a role in the treatment of diarrhoea symptoms. Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter and paracrine signalling molecule in the gastrointestinal (GI) tract, which initiates peristaltic, secretory, vasodilatory, vagal and nociceptive reflexes. In addition, according to the results of our previous report, EA stimulation mediates GI peristalsis by increasing expression of 5-HT and tryptophan hydroxylase (TPH). Aim To investigate the effect of EA at acupuncture points ST25 and BL25 in a rat model of diarrhoea. Methods A diarrhoea-predominant irritable bowel syndrome (IBS-D) model was induced by Folium Sennae in 24 rats, which remained untreated (n=6) or received EA at ST25 (n=6), BL25 (n=6) or the combination of ST25 and BL25 (n=6). A control group of healthy rats was also included (n=6). After treatment, changes in loose stool and small intestine transit rates, enterochromaffin (EC) cell number, expression of TPH, and faecal/colonic 5-HT contents were measured. Results Loose stool and small intestine transit rates, EC cell numbers, colonic TPH expression and faecal/colonic 5-HT content of IBS-D rats were significantly increased relative to controls (p<0.05) and all these parameters were improved by EA at ST25, BL25, or ST25 and BL25 in combination (all p<0.05 vs untreated IBS-D rats). Conclusions EA at ST25 and/or BL25 had a positive effect on objective markers of diarrhoea in a IBS-D rat model and induced changes in EC cell number, colonic TPH and 5-HT contents. The effects of EA stimulation at ST25/BL25 on IBS-D rats may be mediated by excitation of sympathetic nerves.

Process Development of Tryptophan Hydroxylase Inhibitor LX1031, a Drug Candidate for the Treatment of Irritable Bowel Syndrome

2020 ◽  
Vol 24 (2) ◽  
pp. 261-273
Author(s):  
Matthew M. Zhao ◽  
Haiming Zhang ◽  
Shinya Iimura ◽  
Mark S. Bednarz ◽  
Ramanaiah C. Kanamarlapudi ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Tryptophan Hydroxylase ◽  
Process Development ◽  
Drug Candidate ◽  
Irritable Bowel

scholarly journals Involvement of Mucosal Flora and Enterochromaffin Cell of Cecum and Descending Colon in Diarrhea-Predominant Irritable Bowel Syndrome

2020 ◽  
Author(s):  
Jingze Yang ◽  
Peng Wang ◽  
Tong Liu ◽  
Lin Lin ◽  
Lixiang Li ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Abdominal Pain ◽  
Colonic Mucosa ◽  
Tryptophan Hydroxylase ◽  
Cell Number ◽  
Enterochromaffin Cell ◽  
Ec Cells ◽  
Descending Colon ◽  
Irritable Bowel ◽  
The Relationship

Abstract Background: The comparison between microbiota of cecal and colonic mucosa in irritable bowel syndrome (IBS) was rarely studied. In addition, enterochromaffin (EC) cell had interaction with IBS. The aim of this study was to investigate the relationship among gut microbiota, EC cell and diarrhea-predominant IBS (IBS-D) symptoms in cecum and descending colon. Methods: Biopsies from cecum and descending colon were taken during endoscopy withdrawal. We assessed EC cell numbers, expression of tryptophan hydroxylase 1 (TPH1) and microbial diversity.Results: Total of 22 IBS-D patients and 22 health controls (HCs) were enrolled. The relative abundance of Ruminococcus_torques_group (4.91% vs. 2.20%, P = 0.04763) of cecum increased in IBS-D, while Raoultella (1.58% vs. 1.76%, P = 0.03117) and Fusobacterium (0.12% vs. 1.66%, P = 0.01892) were less abundant. In descending colon, the relative abundances of Ruminococcus_torques_group (5.94% vs. 2.29%, P = 0.04183) and Dorea (2.68% vs. 1.14%, P = 0.04962) of IBS-D increased but Fusobacterium (1.52% vs. 1.89%, P = 0.0345) decreased. EC cells number in cecum of IBS-D was higher than that in HCs and TPH1 level of IBS-D was higher than that of HCs in cecum and descending colon. Correlation analysis showed that Ruminococcus_torques_group were positively associated with HAM-A (r= 0.66, P = 0.004), HAM-D (r= 0.61, P = 0.009), EC cell number (r= 0.49, P = 0.047), IBS-SSS (r= 0.65, P = 0.004), Degree of Abdominal Pain (r = 0.63, P = 0.007), Frequency of Abdominal Pain (r = 0.63, P = 0.007), Frequency of Defecation (r = 0.60, P = 0.011). The abundance of Dorea were positively associated with EC cell number (r = 0.57, P = 0.018), IBS-SSS (r = 0.52, P = 0.034), HAM-A (r = 0.72, P = 0.001), HAM-D (r = 0.59, P = 0.012), Frequency of Abdominal Pain (r = 0.67, P = 0.003).Conclusions: EC cells number increased in IBS-D patients and the expression of TPH1 was higher than HCs. In addition, our results suggested Ruminococcus_torques_group and Dorea may be targets for treatment of IBS-D but still need further studies.

scholarly journals A Functional Promoter Variant in the Tryptophan Hydroxylase 1 Gene is Associated With a Bowel Habit Phenotype in Patients With Irritable Bowel Syndrome (IBS)

2011 ◽  
Vol 140 (5) ◽  
pp. S-111
Author(s):  
Helmut Grasberger ◽  
Lin Chang ◽  
Wendy Shih ◽  
Angela P. Presson ◽  
Emeran A. Mayer ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Tryptophan Hydroxylase ◽  
Bowel Habit ◽  
Irritable Bowel

scholarly journals JCM-16021, a Chinese Herbal Formula, Attenuated Visceral Hyperalgesia in TNBS-Induced Postinflammatory Irritable Bowel Syndrome through Reducing Colonic EC Cell Hyperplasia and Serotonin Availability in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Hong-Yan Qin ◽  
Hai-Tao Xiao ◽  
Fung-Ping Leung ◽  
Zhi-Jun Yang ◽  
Justin C. Y. Wu ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Analgesic Effect ◽  
Tryptophan Hydroxylase ◽  
Herbal Formula ◽  
Mechanical Stimuli ◽  
Visceral Hyperalgesia ◽  
Cell Hyperplasia ◽  
Chinese Herbal Formula ◽  
Chinese Herbal ◽  
Irritable Bowel

The present study aimed to investigate the analgesic effect of JCM-16021, a revised traditional Chinese herbal formula, on postinflammatory irritable bowel syndrome (PI-IBS) in rats. The trinitrobenzene sulfonic (TNBS) acid-induced PI-IBS model rats were orally administrated with different doses of JCM-16021 (1.2, 2.4, and 4.8 g/kg/d) for 14 consecutive days. The results showed that JCM-16021 treatment dose-dependently attenuated visceral hyperalgesia in PI-IBS rats. Further, the colonic enterochromaffin (EC) cell number, serotonin (5-HT) content, tryptophan hydroxylase expression, and mechanical-stimuli-induced 5-HT release were significantly ameliorated. Moreover, the decreased levels of mucosal cytokines in PI-IBS, especially the helper T-cell type 1- (Th1-) related cytokine TNF-α, were also elevated after JCM-16021 treatment. These data demonstrate that the analgesic effect of JCM-16021 on TNBS-induced PI-IBS rats may be medicated via reducing colonic EC cell hyperplasia and 5-HT availability.

Analgesic Effects of Electroacupuncture at St25 and Cv12 in a Rat Model of Postinflammatory Irritable Bowel Syndrome Visceral Pain

2018 ◽  
Vol 36 (4) ◽  
pp. 240-246 ◽  
Author(s):  
Xianwei Zhu ◽  
Zhibin Liu ◽  
Yifei Qin ◽  
Wenmin Niu ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Analgesic Effect ◽  
Tryptophan Hydroxylase ◽  
Visceral Pain ◽  
Cell Number ◽  
Trinitrobenzene Sulfonic Acid ◽  
Visceral Hyperalgesia ◽  
Cell Numbers ◽  
Analgesic Effects ◽  
Irritable Bowel

Background Treatment with electroacupuncture (EA) at ST25 and CV12 has a significant analgesic effect on postinflammatory irritable bowel syndrome (PI-IBS) visceral pain. Enterochromaffin (EC) cells and serotonin (5-hydroxytryptamine (5-HT)) are important in the development of visceral hyperalgesia. Objective To investigate the analgesic effect and underlying mechanisms of EA at ST25 and CV12 on the treatment of trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS visceral hyperalgesia in rats. Methods After EA at ST25 and CV12, changes in abdominal withdrawal reflex (AWR), electromyography (EMG) recordings, colonic EC cell numbers, and expression of tryptophan hydroxylase (TPH), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) of TNBS-induced PI-IBS visceral hyperalgesia in rats were examined. Results The results of AWR tests and EMG recordings indicated a significant analgesic effect of EA stimulation at ST25 and CV12on PI-IBS visceral hyperalgesia (p<0.05). In addition, the increased EC cell numbers and colonic expression of TPH and 5-HT in rats with TNBS-induced PI-IBS visceral hyperalgesia were significantly reduced by EA (p<0.05). Conclusions EA stimulation at ST25 and CV12 can attenuate visceral hyperalgesia. This analgesic effect may be mediated via reduction of both colonic EC cell number and 5-HT concentration.

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