Macrogol 3350-Based Iso-Osmotic Laxative

2020 ◽  
Author(s):  
Life Sciences ◽  
2011 ◽  
Vol 88 (3-4) ◽  
pp. 194-200 ◽  
Author(s):  
Nobutomo Ikarashi ◽  
Toshihide Mochiduki ◽  
Ayaka Takasaki ◽  
Takashi Ushiki ◽  
Kohta Baba ◽  
...  

2004 ◽  
Vol 286 (6) ◽  
pp. G1050-G1058 ◽  
Author(s):  
Lane L. Clarke ◽  
Lara R. Gawenis ◽  
Emily M. Bradford ◽  
Louise M. Judd ◽  
Kathryn T. Boyle ◽  
...  

Paneth cells of intestinal crypts contribute to host defense by producing antimicrobial peptides that are packaged as granules for secretion into the crypt lumen. Here, we provide evidence using light and electron microscopy that postsecretory Paneth cell granules undergo limited dissolution and accumulate within the intestinal crypts of cystic fibrosis (CF) mice. On the basis of this finding, we evaluated bacterial colonization and expression of two major constituents of Paneth cells, i.e., α-defensins (cryptdins) and lysozyme, in CF murine intestine. Paneth cell granules accumulated in intestinal crypt lumens in both untreated CF mice with impending intestinal obstruction and in CF mice treated with an osmotic laxative that prevented overt clinical symptoms and mucus accretion. Ultrastructure studies indicated little change in granule morphology within mucus casts, whereas granules in laxative-treated mice appear to undergo limited dissolution. Protein extracts from CF intestine had increased levels of processed cryptdins compared with those from wild-type (WT) littermates. Nonetheless, colonization with aerobic bacteria species was not diminished in the CF intestine and oral challenge with a cryptdin-sensitive enteric pathogen, Salmonella typhimurium, resulted in greater colonization of CF compared with WT intestine. Modest downregulation of cryptdin and lysozyme mRNA in CF intestine was shown by microarray analysis, real-time quantitative PCR, and Northern blot analysis. Based on these findings, we conclude that antimicrobial peptide activity in CF mouse intestine is compromised by inadequate dissolution of Paneth cell granules within the crypt lumens.


2019 ◽  
Vol 316 (3) ◽  
pp. G404-G411 ◽  
Author(s):  
Anna Bertolini ◽  
Ivo P. van de Peppel ◽  
Marcela Doktorova-Demmin ◽  
Frank A. J. A. Bodewes ◽  
Hugo de Jonge ◽  
...  

The gastrointestinal phenotype of cystic fibrosis (CF) features intestinal bile acid (BA) malabsorption, impaired intestinal farnesoid X receptor (FXR) activation, and consequently reduced fibroblast growth factor 19 (FGF19, FGF15 in mice) production. The osmotic laxative polyethylene glycol (PEG) has been shown to decrease intestinal mucus accumulation in CF mice and could, by doing so, improve BA reabsorption. Here we determined the effect of PEG on BA excretion and FXR-FGF15 signaling in CF mice. Male Cftr−/−tm1Unc (CF) and wild-type (WT) littermates were administered PEG 4000 in drinking water and fed either chow or a semisynthetic diet. PEG was withdrawn for 3 days before termination. Fecal BA excretion was measured at PEG dosages of 37 g/l (100%) and 0 g/l (0%). Ileal FXR activation was assessed by gene expression of its downstream targets Fgf15 and small heterodimer partner ( Shp). In CF mice, PEG withdrawal increased fecal BA excretion on either diet compared with full PEG dosage (chow, 2-fold, P = 0.06; semisynthetic, 4.4-fold, P = 0.007). PEG withdrawal did not affect fecal BA excretion in WT mice on either diet. After PEG withdrawal, gene expression levels of intestinal FXR target genes Fgf15 and Shp were decreased in CF mice but unaffected in WT littermates. PEG did not affect the gene expression of the main intestinal BA transporter apical sodium-dependent bile acid transporter (ASBT). PEG treatment ameliorates intestinal BA malabsorption in CF mice and restores intestinal FXR-FGF15 signaling, independent from Asbt gene expression. These findings highlight the potential of PEG in the prevention and treatment of the gastrointestinal phenotype of CF. NEW & NOTEWORTHY A gastrointestinal feature of cystic fibrosis is bile acid malabsorption and consequent impairment of farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling. FXR-FGF15 signaling regulates various metabolic processes and could be implicated in metabolic and gastrointestinal complications of cystic fibrosis, such as diabetes and liver disease. In cystic fibrosis mice, treatment with the osmotic laxative polyethylene glycol is associated with decreased fecal bile acid loss and restoration of FXR-FGF15 signaling.


2017 ◽  
Vol 62 (11) ◽  
pp. 3156-3166 ◽  
Author(s):  
Jakob Lykke Poulsen ◽  
Christina Brock ◽  
Debbie Grønlund ◽  
Donghua Liao ◽  
Hans Gregersen ◽  
...  

JGH Open ◽  
2019 ◽  
Vol 3 (5) ◽  
pp. 374-380
Author(s):  
Dileep Mangira ◽  
Shara Ket ◽  
Jeremy Dwyer ◽  
Robyn Secomb ◽  
John Reynolds ◽  
...  

2012 ◽  
Vol 67 (6) ◽  
pp. 376-378 ◽  
Author(s):  
Alicia Borderé ◽  
Annelies Stockman ◽  
Barbara Boone ◽  
Ann-Sophie Franki ◽  
Marc J. Coppens ◽  
...  
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