Comparison of gastrointestinal pH in cystic fibrosis and healthy subjects

The primary objective of this study was to define the pH conditions under which supplemental pancreatic enzyme preparations must function in the upper gastrointestinal tract. The hypothesis was that normal or greater gastric acid output in patients with cystic fibrosis (CF), combined with low pancreatic bicarbonate output, results in an acidic duodenal pH, compromising both dosage-form performance and enzyme activity. Gastrointestinal pH profiles were obtained in 10 CF and 10 healthy volunteers under fasting and postprandial conditions. A radiotelemetric monitoring method, the Heidelberg capsule, was used to continuously monitor pH. Postprandial duodenal pH was lower in CF than in healthy subjects, especially in the first postprandial hour (mean time greater than pH 6 was 5 min in CF, 11 min in healthy subjects, P <0.05). Based on the dissolution pH profiles of current enteric-coated pancreatic enzyme products, the duodenal postprandial pH in CF subjects may be too acidic to permit rapid dissolution of current enteric-coated dosage forms. However, the pH was above 4 more than 90% of the time on the average, suggesting that irreversible lipase inactivation in the duodenum is not likely to be a significant limitation to enzyme efficacy. Overall results suggest that slow dissolution of pH-sensitive coatings, rather than enzyme inactivation, may contribute to the failure of enteric-coated enzyme supplements to normalize fat absorption.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44403/1/10620_2005_Article_BF01296029.pd

Identification and Characterisation of <i>Pseudomonas</i> 16S Ribosomal DNA from Ileal Biopsies of Children with Crohn's Disease

Molecular analysis of bacterial 16S rRNA genes has made a significant contribution to the identification and characterisation of bacterial flora in the human gut. In particular, this methodology has helped characterise bacterial families implicated in the aetiology of inflammatory bowel disease (IBD). In this study we have used a genus specific bacterial 16S PCR to investigate the prevalence and diversity of Pseudomonas species derived from the ileum of children with Crohn's disease (CD), and from control children with non-inflammatory bowel disease (non-IBD) undergoing their initial endoscopic examination. Fifty eight percent of CD patients (18/32) were positive using the Pseudomonas PCR, while significantly fewer children in the non-IBD group, 33% (12/36), were PCR positive for Pseudomonas (p<0.05, Fischer's exact test). Pseudomonas specific 16S PCR products from 13 CD and 12 non-IBD children were cloned and sequenced. Five hundred and eighty one sequences were generated and used for the comparative analysis of Pseudomonas diversity between CD and non-IBD patients. Pseudomonas species were less diverse in CD patients compared with non-IBD patients. In particular P.aeruginosa was only identified in non-IBD patients

<i>TLR4</i>, <i>IL10RA</i>, and <i>NOD2</i> mutation in paediatric Crohn's disease patients: an association with <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> and TLR4 and IL10RA expression

Mycobacterium avium subspecies paratuberculosis (MAP) has been implicated in the pathogenesis of Crohn's disease (CD). The role of CD susceptibility genes in association with these microbes is not known. Sixty-two early onset paediatric CD patients and 46 controls with known MAP status were analysed for an association with 34 single nucleotide polymorphisms (SNPs) from 18 CD susceptibility genes. Functional studies on peripheral blood mononuclear cells (PBMCs) were conducted on 17 CD patients with known CD mutations to assess IL-6, IL-10, and TNF-α expression upon stimulation with MAP precipitated protein derivative (PPD) and lipopolysaccharide (LPS). In addition, surface expression of IL10R and TLR4 on resting B cells, NK cells, T cells, and monocytes was assessed. A mutation in TLR4 (rs4986790) and IL10RA (rs22291130) was significantly associated with MAP-positive CD patients compared to MAP-negative CD patients (27.6 vs. 6.1 %, p = 0.021, and 62.1 vs. 33.3 %, p = 0.024, respectively). PPD and LPS significantly increased IL-6, IL-10, and TNF-α production in PBMCs. IL-10 and TNF-α production were significantly lower in a subgroup of CD patients (5/12) with a known NOD2 mutation. Receptor for IL-10 was significantly higher expressed on NK cells (CD56low) and on NK T cells harbouring a NOD2 mutations compared to wildtype cells (p = 0.031 and 0.005, respectively). TLR4 was significantly higher expressed on NK cells (CD56high) harbouring a NOD2 mutations compared to wildtype cells (p = 0.038)