Chenodeoxycholic and Ursodeoxycholic Acids Alter Motility and Fluid Transit in the Canine Ileum

Kruis, Wolfgang; Haddad, Anne C.; Phillips, SM

doi:10.1159/000199328

Cited by 24 publications

(11 citation statements)

References 16 publications

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“…Perfusion of the mammalian or human colon with di‐ α ‐hydroxybile acids such as chenodeoxycholic acid or short‐chain fatty acids (SCFAs) results in high‐amplitude propagated contractions or rapid transit in healthy colon 161–165 . Studies have not been conducted in IBS patients.…”

Section: The Potential Role Of the Intraluminal Milieu And Genesmentioning

confidence: 99%

Mechanisms of hypersensitivity in IBS and functional disorders

Azpiroz

Bouin

Camilleri

et al. 2007

Neurogastroenterology Motil

313

251

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General introductionThe concept of visceral hypersensitivity is accepted as being germane to several functional gastrointestinal disorders (FGIDs). The causes or risk factors associated with this hypersensitivity are unclear. This article addresses the proposed mechanisms leading to hypersensitivity: from genetic to inflammatory disorders, from central to peripheral alterations of function. However, in order to place visceral hypersensitivity in a more global perspective as an aetiological factor for FGIDs, it also provides a review of recent evidence regarding the role of other peripheral mechanisms (the intraluminal milieu), as also genetic factors in the pathophysiology of these disorders. The article has been divided into five independent sections. The first three sections summarize the evidence of visceral hypersensitivity as a biological marker of functional gut disorders, the peripheral and central mechanisms involved, and the role of inflammation on hypersensitivity. In opposition to visceral hypersensitivity as an isolated phenomenon in functional gut disorders, the last two sections focus on the importance of peripheral mechanisms, like motor disturbances, specifically those resulting on altered transport of intestinal gas, and alterations of the intraluminal milieu and genetics.Keywords abdominal pain, functional gut disorders, irritable bowel syndrome, visceral hypersensitivity. VISCERAL HYPERSENSITIVITY: BIOLOGICAL MARKER, PERIPHERAL MECHANISMS AND HETEROGENEITY IntroductionVisceral hypersensitivity is currently the leading hypothesis to explain irritable bowel syndrome (IBS) and other functional gastrointestinal disorders (FGIDs). After years of disappointing research trying to establish a correlation between the increased motor activity of the gut and the painful cramps felt by IBS patients, the theory that pain could be related to enhanced visceral sensitivity was raised. Ritchie, 1 in 1973, first reported that IBS patients were more sensitive than normal subjects to balloon distension of the colon. This observation of increased visceral sensitivity in IBS patients was confirmed by many researchers including Whitehead et al. 2 , Mertz et al. 3 and others. In agreement with the hypersensitivity of the colon found in IBS patients, intolerance to gastric distension was also documented in patients with functional dyspepsia (FD). 4-6Visceral hypersensitivity: biological marker of FGID?Mertz et al. 3 proposed that Ôaltered rectal perception is a biological marker of patients with IBSÕ as it was identified in 94 of 100 IBS patients studied by a rectal distension by barostat. We collected rectal distension data by an electronic barostat in 164 patients (86 IBS, 26 painless constipation, 21 FD and 31 others with miscellaneous conditions), 7 as also in 25 normal controls evaluated. As expected ( thresholds to rectal distension were lower in patients with IBS when compared with control subjects; they were also lower than in patients with painless constipation, FD or other miscellaneous conditions. Assuming ...

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Section: The Potential Role Of the Intraluminal Milieu And Genesmentioning

confidence: 99%

Mechanisms of hypersensitivity in IBS and functional disorders

Azpiroz

Bouin

Camilleri

et al. 2007

Neurogastroenterology Motil

313

251

View full text Add to dashboard Cite

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“…As in other species, di‐αhydroxy bile acids induce fluid secretion in the human colon 15 . Bile acids also have been associated with increased colonic contractions; however, there is a wide range in the concentrations that induce propulsive contractions in canine (>20 mmol L −1 ) 16 and human (1 mmol L −1 ) 17 colon. In humans, a relationship was found between the faecal bile acid excretion and colonic motility; however, in those studies, 40% also had significant steatorrhoea, 18 a situation that is not typical for IBS.…”

Section: Introductionmentioning

confidence: 97%

Measurement of serum 7α‐hydroxy‐4‐cholesten‐3‐one (or 7αC4), a surrogate test for bile acid malabsorption in health, ileal disease and irritable bowel syndrome using liquid chromatography‐tandem mass spectrometry

Camilleri

Nadeau

Tremaine

et al. 2009

Neurogastroenterology Motil

146

117

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Background Bile acid malabsorption (BAM) is reported in up to 50% of patients with functional diarrhea and irritable bowel syndrome with diarrhea (IBS-D). Serum 7α-hydroxy-4-cholesten-3-one (7αHCO, or 7αC4), an indirect measurement of hepatic bile acid synthesis, has been validated as a measurement of BAM relative to the 75SeHCAT retention test. Aim To develop a serum 7αC4 assay, normal values, and compare results from healthy controls, patients with ileal Crohn’s disease or resection, and patients with IBS-D or IBS with constipation (IBS-C). Methods Stored serum samples were used from adult men and women in the following groups: 111 normal healthy controls, 15 IBS-D, 15 IBS-C, 24 with distal ileal Crohn’s disease, and 20 with distal ileal resection for Crohn’s disease. We adapted a published high pressure liquid chromatography, tandem mass spectrometry (HPLC-MS/MS) assay. Results The HPLC-MS/MS assay showed good linearity in concentration range 0–200 ng/mL, sensitivity (lowest limit of detection 0.04 ng/mL), and high analytical recovery (average 99%, range 93–107%). The 5th to 95th percentile for 111 normal healthy controls was 6–60.7 ng/mL. There were significant overall group differences (ANOVA on ranks p<0.001), with significantly higher values for terminal ileal disease or resection. There were significant differences between health and IBS (ANOVA p=0.043) with higher mean values in IBS-D relative to controls (rank sum test, p=0.027). Conclusions We have established a sensitive non-isotopic assay based on HPLC-MS/MS, determined normal 7αC4 values, and identified increased 7αC4 in IBS-D and in distal ileal resection and disease. This assay has potential as a noninvasive test for BAM in IBS.

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“…Diarrhea is also a well-known potential side effect of orlistat and UDCA treatment (35,36). Orlistat has been shown to accelerate gastric emptying (22), whereas UDCA treatment accelerated the gastrointestinal transit in dogs and can improve gastrointestinal motility defects in bile stone patients (20,37). Theoretically, phototherapy or oral treatments could thus well exert (part of) their hypobilirubinemic effect by acceleration of the gastrointestinal transit.…”

Section: Discussionmentioning

confidence: 99%

Combined Treatment Strategies for Unconjugated Hyperbilirubinemia in Gunn Rats

2011

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ABSTRACT:We recently demonstrated that acceleration of the gastrointestinal transit by polyethylene glycol (PEG) treats unconjugated hyperbilirubinemia in jaundiced Gunn rats. It is unclear whether acceleration of gastrointestinal transit also (partly) underlies the therapeutic effects of established hypobilirubinemic treatments or whether PEG cotreatment might enhance these effects. We treated Gunn rats with phototherapy (17 W/cm 2 /nm), orlistat (200 mg/kg chow), ursodeoxycholate (5 g/kg chow), or calcium phosphate (CaP) (20 g/kg chow) either as single treatment or in combination with PEG. Three weeks of phototherapy, orlistat, ursodeoxycholic acid, or CaP treatment decreased plasma unconjugated bilirubin (UCB) levels by 47, 27, 28, and 45%, respectively (each p Ͻ 0.001), without a significant impact on gastrointestinal transit time. PEG cotreatment accelerated the gastrointestinal transit in all treatment groups, which resulted in an additive hypobilirubinemic effect of Ϫ20% and Ϫ26% (final plasma UCB Ϫ67 and Ϫ53%, respectively) in phototherapyand orlistat-treated animals. PEG cotreatment did not enhance the hypobilirubinemic effect of ursodeoxycholic acid or CaP. We conclude that phototherapy, orlistat, ursodoxycholic acid, and CaP do not exert their hypobilirubinemic effect via acceleration of the gastrointestinal transit. PEG cotreatment enhanced the hypobilirubinemic effects of phototherapy and of orlistat treatment. Current results support a clinical trial to evaluate PEG cotreatment during phototherapy. (Pediatr Res 70: 560-565, 2011)

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Chenodeoxycholic and Ursodeoxycholic Acids Alter Motility and Fluid Transit in the Canine Ileum

Cited by 24 publications

References 16 publications

Mechanisms of hypersensitivity in IBS and functional disorders

Mechanisms of hypersensitivity in IBS and functional disorders

Measurement of serum 7α‐hydroxy‐4‐cholesten‐3‐one (or 7αC4), a surrogate test for bile acid malabsorption in health, ileal disease and irritable bowel syndrome using liquid chromatography‐tandem mass spectrometry

Combined Treatment Strategies for Unconjugated Hyperbilirubinemia in Gunn Rats

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