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  • Keita, ÅsaLinköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten (author)

Gut barrier dysfunction : a primary defect in twins with Crohn's disease predominantly caused by genetic predisposition

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-04-12
  • Elsevier,2018
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:oru-66791
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-66791URI
  • https://doi.org/10.1093/ecco-jcc/jjy045DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-154129URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agency:Region Östergötland, ALF research funds of Linköping University 
  • Funding Agencies|Swedish Research Council-Medicine [VR-MH 2014-02537, 521-2011-2764]; Region Ostergotland, ALF research funds of Linkoping University
  • Background and aims: The aetiology of Crohn's disease is poorly understood. By investigating twin pairs discordant for Crohn's disease we aimed to assess if the dysregulated barrier represents a cause or a consequence of inflammation and to evaluate the impact of genetic predisposition on barrier function.Methods: Ileal biopsies from 15 twin pairs discordant for Crohn's disease (monozygotic n=9, dizygotic n=6) and 10 external controls were mounted in Ussing chambers to assess paracellular permeability to51Chromium (Cr)-EDTA and trancellular passage to non-pathogenic E. coli K-12. Experiments were performed with and without provocation with acetylsalicylic acid. Immunofluorescence and ELISA were used to quantify the expression level of tight junction proteins.Results: Healthy co-twins and affected twins displayed increased 51Cr-EDTA permeability at 120 min both with Acetylsalicylic acid (p<0.001) and without (p<0.001) when compared to controls. A significant increase in 51Cr-EDTA flux was seen already at 20 minutes in healthy monozygotic co-twins compared to controls (p≤0.05) when stratified by zygosity, but not in healthy dizygotic co-twins. No difference in E. coli passage was observed between groups. Immunofluorescence of the tight junction proteins claudin-5 and tricellulin showed lower levels in healthy co-twins (p<0.05) and affected twins (p<0.05) compared to external controls, while ELISA only showed lower tricellulin in Crohn's disease twins (p<0.05).Conclusion: Our results suggest that barrier dysfunction is a primary defect in Crohn's disease, since changes were predominantly seen in healthy monozygotic co-twins. Passage of E. coli seems to be a consequence of inflammation rather than representing a primary defect.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Lindqvist, Carl Mårten,1979-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medical Sciences,Örebro University, Örebro, Sweden(Swepub:oru)melt (author)
  • Öst, ÅkeDepartment of Pathology and Cytology, Aleris Medilab, Täby, Sweden (author)
  • Ley Magana, Carlos DanielLinköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten(Swepub:liu)carle20 (author)
  • Schoultz, Ida,1979-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medical Sciences,Örebro University, Örebro, Sweden(Swepub:oru)isz (author)
  • Halfvarson, Jonas,1970-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology,Örebro University, Örebro, Sweden(Swepub:oru)jshn (author)
  • Linköpings universitetAvdelningen för Kirurgi, Ortopedi och Onkologi (creator_code:org_t)

Related titles

  • In:Journal of Crohn's & Colitis: Elsevier12:10, s. 1200-12091873-99461876-4479

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