Gastric Acid Hypersecretion in Cystic Fibrosis

Cox, Kenneth L.; Isenberg, J. Nevin; Ament, Marvin E.

doi:10.1097/00005176-198212000-00019

Cited by 86 publications

(34 citation statements)

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“…The chloride channel required for acid production by gastric glands is debated, with reports citing CFTR, CLC2, or an unknown channel as its source (28). Enhanced gastric acid secretion in patients with CF has been previously observed (49)(50)(51); however, these findings differ from studies in DF508-CFTR mice that exhibit reduced gastric acid secretion in comparison to control mice (52). Duodenal pH in humans with CF (45,53) and CFTR-KO mice (46,47) has also been shown to be lower than in non-CF controls.…”

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confidence: 99%

Bioelectric Characterization of Epithelia from Neonatal CFTR Knockout Ferrets

Fisher¹,

Tyler

Zhang³

et al. 2013

Am J Respir Cell Mol Biol

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Cystic fibrosis (CF) is a life-shortening, recessive, multiorgan genetic disorder caused by the loss of CF transmembrane conductance regulator (CFTR) chloride channel function found in many types of epithelia. Animal models that recapitulate the human disease phenotype are critical to understanding pathophysiology in CF and developing therapies. CFTR knockout ferrets manifest many of the phenotypes observed in the human disease, including lung infections, pancreatic disease and diabetes, liver disease, malnutrition, and meconium ileus. In the present study, we have characterized abnormalities in the bioelectric properties of the trachea, stomach, intestine, and gallbladder of newborn CF ferrets. Short-circuit current (I SC ) analysis of CF and wild-type (WT) tracheas revealed the following similarities and differences: (1) amiloride-sensitive sodium currents were similar between genotypes; (2) responses to 4,49-diisothiocyano-2,29-stilbene disulphonic acid were 3.3-fold greater in CF animals, suggesting elevated baseline chloride transport through non-CFTR channels in a subset of CF animals; and (3) a lack of 3-isobutyl-1-methylxanthine (IBMX)/forskolin-stimulated and N-(2-Naphthalenyl)-((3,5-dibromo-2,4-dihydroxyphenyl)methylene) glycine hydrazide (GlyH-101)-inhibited currents in CF animals due to the lack of CFTR. CFTR mRNA was present throughout all levels of the WT ferret and IBMX/forskolin-inducible I SC was only observed in WT animals. However, despite the lack of CFTR function in the knockout ferret, the luminal pH of the CF ferret gallbladder, stomach, and intestines was not significantly changed relative to WT. The WT stomach and gallbladder exhibited significantly enhanced IBMX/ forskolin I SC responses and inhibition by GlyH-101 relative to CF samples. These findings demonstrate that multiple organs affected by disease in the CF ferret have bioelectric abnormalities consistent with the lack of cAMP-mediated chloride transport.

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confidence: 99%

Bioelectric Characterization of Epithelia from Neonatal CFTR Knockout Ferrets

Fisher¹,

Tyler

Zhang³

et al. 2013

Am J Respir Cell Mol Biol

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“…The provision of lipase from 2 and 4 Creon capsules used in this study might have been insufficient to provide any significant improvement in the digestive environment for CsA. In addition, duodenal hyperacidity is probably worse in CF due to the prevalance of acid hypersecretion [27] and the greater reduction in bicarbonate secretion [28]. However, no improvement in CsA bioavailability is found in the CF recipients studied when ranitidine is co-administered with pancreatic enzyme supplements.…”

Section: Discussionmentioning

confidence: 81%

Cyclosporin pharmacokinetics in heart-lung transplant recipients with cystic fibrosis

Tsang

Johnston

Héritier

et al. 1994

Eur J Clin Pharmacol

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Cyclosporin (CsA) is currently the main immunosuppressive agent used in organ transplantation with considerable improvement in graft survival. Oral CsA solution is highly lipophilic, and its bioavailability may be reduced in cystic fibrosis (CF) heart-lung transplant recipients with pancreatic, gastrointestinal, and hepatic insufficiency. The bioavailability of oral CsA solution in 7 CF transplant recipients (5 male and 2 female with a mean age of 27 years and a mean weight of 49 kg) and 3 non-CF heart-lung recipients (1 male and 2 female with a mean age of 41 years and a mean weight of 60 kg) was studied. Following intravenous CsA administration, the kinetic curves were similar with no significant difference in the volume of distribution and clearance of CsA demonstrated between the CF and non-CF groups. The mean daily dose of oral CsA in 7 CF subjects (23.3 mg.kg-1) was significantly higher than the 3 non-CF heart-lung recipients (4.8 mg.kg-1). The mean maximum blood concentration of CsA for the oral dose was 776 ng.ml-1 for the 7 CF subjects, which was comparable with the mean peak values of 789 ng.ml-1 for the 3 non-CF control subjects. Poor enteral absorption of CsA probably accounts for the significantly lower mean bioavailability in the 7 CF subjects (14.9%) compared with the 3 non-CF control subjects (39.4%). The effects on the bioavailability of oral CsA solution by pancreatic enzymes (Creon) and histamine-2 antagonist (ranitidine) were also evaluated in the 7 CF subjects. No significant difference was demonstrated.

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“…1 A) to that of 10 age-matched healthy subjects studied previously (1 1). Although it is not clear whether CF patients with pancreatic insufficiency have normal (52), hypo-(53) or hypersecretion (54) of gastric acid, the pH in the stomach of the CF patients studied was in the optimal range for lingual lipase activity (8,11,15). Seldom was the pH in the stomach <2.0 (Fig.…”

Section: Discussionmentioning

confidence: 98%