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- Reims, Annika, 1962
(författare)
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Analysis of epithelial electrophysiological function in paediatric intestinal biopsies
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Intestinal biopsies are routinely taken from children under investigation of failure to thrive, diarrhoea, abdominal pain and/or malnutrition. These biopsies are usually only evaluated morphologically, i.e. no information is collected with regard to mucosal function. The aim of this work was to study electrogenic membrane transport, in particular electrogenic chloride secretion, in biopsies from the duodenum in children, and to evaluate the relation between morphological and functional disturbances. Intestinal biopsies from children with morphologically normal epithelia were obtained from different parts of the duodenum. A more pronounced reactivity of the prostaglandin E2 induced, cAMP mediated chloride secretion, was seen in the distal part of duodenum while the acetylcholine induced, Ca2+ mediated secretion, was expressed along the whole duodenum. Cysteinyl leukotrienes (LTC4 and LTD4) were shown to be secretagogues since they induced chloride secretion with similar pattern as the prostaglandins along the duodenum. The secretory response was also studied in children with coeliac disease in different stages. Biopsies with partial mucosal atrophy showed an enhanced response to most secretagogues, compared to controls. The magnitude of this electrogenic response was significantly related to serum levels of IgA gliadin antibodies. The response to leukotrienes was reduced, and this effect was reversed by pre-treatment with indomethacin, suggesting a complex interaction within the arachidonic acid cascade. The effects of prostaglandin E2 and acetylcholine on electrogenic chloride secretion was studied in biopsies from patients with cystic fibrosis. No response was seen in the ´F508 homozygotes. In other genotypes, secretion corresponded to the severity of the known mutations, the acetylcholine response being better preserved in mild phenotypes. A novel method to measure epithelial resistance, reflecting epithelial permeability, was used. The permeability was not affected by the secretagogues. Biopsies from children with coeliac disease or cystic fibrosis showed lower resistances, compared to controls, verifying earlier studies showing increased permeability in these diseases. The Ussing-technique can successfully be used in studies of secretion and permeability in duodenal biopsies in children. The technique offers possibilities to combine functional and morphological analysis of the same biopsy. Its role in practical gastroenterology remains to be determined, but our results encourage an introduction of this technique in at least tertiary care paediatric gastroenterological centres.
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- Reims, Annika, 1962, et al.
(författare)
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Cysteinyl leukotrienes are secretagogues in atrophic coeliac and in normal duodenal mucosa of children
- 2005
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Ingår i: Scand J Gastroenterol. - : Informa UK Limited. - 0036-5521. ; 40:2, s. 160-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The pathophysiology of intestinal inflammation and diarrhoea is complex and involves the arachidonic acid cascade. Prostaglandins induce chloride secretion in healthy subjects and in patients with coeliac disease. Leukotrienes (LTs) are also known inflammatory mediators which have been shown to stimulate ion secretion in ileum and colon of rats and rabbits. The aim of this study was to determine the effects of leukotrienes C(4) (LTC(4)) and D(4) (LTD(4)) in normal and atrophic intestinal mucosa in children. MATERIAL AND METHODS: Routine paediatric intestinal biopsies were obtained from 109 children. Sixty-seven control biopsies and 42 biopsies from children with different stages of coeliac disease were mounted in a modified Ussing chamber. Potential difference (Pd) was measured continuously and tissue resistance (R(t)) and the generated current (I(m)) were calculated. RESULTS: In morphologically normal mucosa of duodenum, LTC(4) and LTD(4) increased Pd and I(m) in a dose-dependent manner. The increase was more pronounced in the distal than in the proximal part, similar to the response to prostaglandin E(2). The induced current was chloride-mediated, since replacement of Cl(-) with SO(4)(2-) in the bathing solution eliminated the response to the LTs. The LTC(4)-induced secretion was significantly decreased in atrophic mucosa, but the response was partially restored after preincubation with the cyclooxygenase inhibitor indomethacin. CONCLUSIONS: The results showed that LTC(4) and LTD(4) are secretagogues in the duodenal mucosa from healthy children by inducing a net chloride secretion. Restoration of the response in coeliac disease by cyclooxygenase inhibition suggests interactions between the different pathways of the arachidonic cascade in the intestinal mucosa.
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| 4. |
- Reims, Annika, 1962, et al.
(författare)
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Epithelial electrical resistance as a measure of permeability changes in pediatric duodenal biopsies
- 2006
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Ingår i: J Pediatr Gastroenterol Nutr. - 1536-4801. ; 43:5, s. 619-23
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Intestinal permeability measured with medium-sized oral probes is increased in cystic fibrosis (CF) and celiac disease (CD), probably reflecting reduced tight junction resistance. The aim of this study was to evaluate whether square-pulse analysis of duodenal biopsies from children can be used to determine electrical tight junction resistance. METHODS: Intestinal biopsies from children with different stages of CD and from patients with CF were studied in a modified Ussing chamber. The epithelium was assumed to act as an electrical circuit consisting of a current generator parallel with a resistance and a capacitance. Subepithelial and epithelial resistances were determined by square-pulse analysis, and the generated current was calculated. RESULTS: Confirming data using permeability probes, reduced epithelial electrical resistance was found both in patients with CF and CD. Only the CF patients had reduced resting current as well. The secretagogues prostaglandin E2, cyclic adenosine monophosphate and acetylcholine increased the current in both control biopsies and biopsies with villous atrophy but had no significant effect on epithelial resistance. CONCLUSIONS: Measurement of electrical resistance in duodenal biopsies can be used as an alternative method of quantifying permeability in pediatric biopsies.
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