Intestinal permeability changes in response to acetylsalicylic acid in relatives of patients with Crohn's disease

1996 ◽  
Vol 110 (5) ◽  
pp. 1395-1403 ◽  
Author(s):  
RJ Hilsden ◽  
JB Meddings ◽  
LR Sutherland
1999 ◽  
Vol 13 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Samuel A Zamora ◽  
Robert J Hilsden ◽  
Jon B Meddings ◽  
J Decker Butzner ◽  
R Brent Scott ◽  
...  

BACKGROUND: Members of a subset of first-degree relatives of adults with Crohn’s disease have been shown to have an increased baseline intestinal permeability and/or an exaggerated increase in intestinal permeability after the administration of acetylsalicylic acid.PURPOSE: To determine intestinal permeability in unaffected first-degree relatives of children with Crohn’s disease before and after the administration of an ibuprofen challenge.METHODS: Lactulose-mannitol ratios, a measure of intestinal permeability, were determined in 14 healthy control families (41 subjects) and 14 families with a child with Crohn’s disease (36 relatives, 14 probands) before and after ingestion of ibuprofen. An upper reference limit was defined using the control group as mean ± 2 SD.RESULTS: The proportion of healthy, first-degree relatives with an exaggerated response to ibuprofen (20%, 95% CI 7% to 33%) was significantly higher than controls (P=0.003). The exaggerated response was more common among siblings than among parents of pediatric probands.CONCLUSIONS: Members of a subset of first-degree relatives of children with Crohn’s disease have an exaggerated increase in intestinal permeability after ibuprofen ingestion. These findings are compatible with there being a genetic link between abnormalities of intestinal permeability and Crohn’s disease.


1995 ◽  
Vol 9 (4) ◽  
pp. 203-212 ◽  
Author(s):  
Ingvar Bjarnason ◽  
Andrew Macpherson ◽  
Ian S Menzies

The authors review some of the more fundamental principles underlying the noninvasive assessment of intestinal permeability in humans, the choice of test markers and their analyses, and the practical aspects of test dose composition and how these can be changed to allow the specific assessment of regional permeability changes and other intestinal functions. The implications of increased intestinal permeability in the pathogenesis of human disease is discussed in relation to findings in patients with Crohn’s disease. A common feature of increased intestinal permeability is the development of a low grade enteropathy, and while quantitatively similar changes may be found in Crohn’s disease these seem to predict relapse of disease. Moreover, factors associated with relapse of Crohn’s disease have in common an action to increase intestinal permeability. While increased intestinal permeability does not seem to be important in the etiology of Crohn’s disease it may be a central mechanism in the clinical relapse of disease.


Gut ◽  
1999 ◽  
Vol 44 (1) ◽  
pp. 96-100 ◽  
Author(s):  
J D Söderholm ◽  
G Olaison ◽  
E Lindberg ◽  
U Hannestad ◽  
A Vindels ◽  
...  

BackgroundA familial defect in intestinal barrier function has been found in Crohn’s disease.AimTo investigate possible genetic and environmental influences on this barrier defect by studying intestinal permeability in both relatives and spouses of patients with Crohn’s disease.SubjectsThe study included 39 patients with Crohn’s disease, 34 healthy first degree relatives, and 22 spouses. Twenty nine healthy volunteers served as controls.MethodsIntestinal permeability was assessed as the lactulose:mannitol ratio in five hour urinary excretion after oral load, both before (baseline) and after ingestion of acetylsalicylic acid. The permeability response represents the difference between the two tests. A ratio above the 95th percentile for controls was classified as abnormal.ResultsBaseline permeability was higher in patients and spouses than in controls. An abnormal baseline permeability was seen in 36% of the patients, 23% of the spouses, 18% of the relatives, and 3% of the controls. After ingestion of acetylsalicylic acid, permeability increased significantly in all groups. Relatives were similar to patients with regard to permeability after exposure to acetylsalicylic acid, whereas spouses were similar to controls. The proportions with an abnormal permeability response to acetylsalicylic acid were 32% in patients, 14% in spouses, 41% in relatives, and 3% in controls.ConclusionThe findings suggest that baseline permeability is determined by environmental factors, whereas permeability provoked by acetylsalicylic acid is a function of the genetically determined state of the mucosal barrier, and support the notion that environmental and hereditary factors interact in the pathogenesis of Crohn’s disease.


2020 ◽  
Vol 159 (6) ◽  
pp. 2092-2100.e5 ◽  
Author(s):  
Williams Turpin ◽  
Sun-Ho Lee ◽  
Juan Antonio Raygoza Garay ◽  
Karen L. Madsen ◽  
Jonathan B. Meddings ◽  
...  

2001 ◽  
Vol 33 (8) ◽  
pp. 680-685 ◽  
Author(s):  
M. Secondulfo ◽  
L. de Magistris ◽  
R. Fiandra ◽  
L. Caserta ◽  
M. Belletta ◽  
...  

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0211973 ◽  
Author(s):  
Julius Z. H. von Martels ◽  
Arno R. Bourgonje ◽  
Hermie J. M. Harmsen ◽  
Klaas Nico Faber ◽  
Gerard Dijkstra

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