Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration.

AIMS: To assess the incidence of intestinal inflammation in children with cystic fibrosis and to investigate whether probiotics decrease it. STUDY DESIGN: In this two-phase, controlled, prospective study, faecal calprotectin was measured by enzyme-linked immunosorbent assay in 30 children with cystic fibrosis, 30 healthy controls and 15 children with active inflammatory bowel disease. Ten children with cystic fibrosis received Lactobacillus GG, and faecal calprotectin was re-measured 4 weeks later. Rectal nitric oxide production was measured with the rectal dialysis bag technique in 20 children with cystic fibrosis, 20 healthy controls and 15 children with inflammatory bowel disease. Five children with cystic fibrosis received Lactobacillus GG and nitric oxide was re-measured 4 weeks later. RESULTS: Mean faecal calprotectin was significantly higher in the two groups of patients than in controls. Abnormal values were detected in 27 of 30 cystic fibrosis and in 15 of 15 inflammatory bowel disease children. Also mean nitric oxide production was increased in both group of patients, and abnormal values were detected in 19 of 20 cystic fibrosis and in 15 of 15 inflammatory bowel disease children. Calprotectin and nitric oxide concentrations were reduced after probiotics administration. CONCLUSIONS: Intestinal inflammation is a major feature of cystic fibrosis and is reduced by probiotics. The latter finding suggests that intestinal microflora play a major role in intestinal inflammation in cystic fibrosis children.

The functional effects of nutrients on enterocyte proliferation and intestinal ion transport in early infancy.

Nutrition has a key role in the modulation of the developing intestine in early infancy, and nutrients are able to modulate several intestinal functions including nutrient absorption, ion transport, cell growth and differentiation, motility and immunomodulation. Such modulation is exerted in part through a direct interaction between a single nutrient and the enterocyte. Two functions--ion transport and cell growth--are closely connected and appear to be modulated by nutrients. This is supported by the finding that a single nutrient (e.g. zinc) stimulates ion absorption and also promotes enterocyte growth. Interestingly, intracellular signalling for either effect is similar and involves mitogen-activated protein kinase. Other nutrients also modulate enterocyte function and there is evidence that their effect may depend on their side of action (apical or basolateral) and concentration. Knowledge of the interaction between nutrients and enterocytes may be exploited to obtain clinical effects using nutrition as a long-term treatment for intestinal and non-intestinal conditions.

Membrane localization of cAMP-dependent protein kinase amplifies cAMP signaling to the nucleus in PC12 cells.

The A126 cell line, in contrast to its PC12 parent, does not differentiate, accumulate nuclear cAMP-dependent protein kinase A (PKA) catalytic subunit, or transcribe cAMP-dependent promoters in response to cAMP. Total PKA is reduced by 50% and is partly resistant to cAMP-induced dissociation in vivo. Unlike PC12, where PKAII is membrane-associated, PKAII is exclusively cytosolic in A126. Cotransfection with the RII anchor protein (AKAP75) and the PKA catalytic subunit (C-PKA) restored cAMP-induced transcription to levels found in PC12. These data indicate that membrane-bound PKAII amplifies cAMP signaling to the nucleus and suggest that cAMP-mediated responses are specified by the type and cellular localization of the PKA isoform.