Evidence map›Paper›PMID 23045481›Full record

ArticleInfection and immunity2012

Intrarectal instillation of Clostridium difficile toxin A triggers colonic inflammation and tissue damage: development of a novel and efficient mouse model of Clostridium difficile toxin exposure.

Simon A Hirota, Vadim Iablokov, Sarah E Tulk, L Patrick Schenck, Helen Becker, Jimmie Nguyen, Samir Al Bashir, Tanis C Dingle, Austin Laing, Jianrui Liu and 8 more

Open access · bronzeAbstract readEvaluation Study
In one paragraph

Article in Infection and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
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  4. Reviewing theMicroorganisms · 2024
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  6. Opportunities for Nanomedicine inAntibiotics (Basel, Switzerland) · 2021
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  9. A Palmitoylethanolamide ProducingFrontiers in pharmacology · 2021
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  10. Article
  11. Review
  12. RIPK3 PromotesJournal of immunology (Baltimore, Md. : 1950) · 2020
    Article
  13. Article
  14. The xenobiotic sensing pregnane X receptor regulates tissue damage and inflammation triggered by C difficile toxins.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  15. A new role for heat shock factor 27 in the pathophysiology ofAmerican journal of physiology. Gastrointestinal and liver physiology · 2020
    Article
  16. Clostridium difficile toxins A and B decrease intestinal SLC26A3 protein expression.American journal of physiology. Gastrointestinal and liver physiology · 2018
    Article
  17. Article
  18. Article
  19. Cysteine Protease-Mediated Autocleavage ofCellular and molecular gastroenterology and hepatology · 2018
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 1 institution in 1 country.

Simon A HirotaDepartment of Medicine, University of Calgary, Calgary, Canada. simon.hirota@ucalgary.ca
Vadim Iablokov
Sarah E Tulk
L Patrick Schenck
Helen Becker
Jimmie Nguyen
Samir Al Bashir
Tanis C Dingle
Austin Laing
Jianrui Liu
Yan Li
Jeff Bolstad
George L Mulvey
Glen D Armstrong
Wallace K MacNaughton
Daniel A Muruve
Justin A MacDonald
Paul L Beck
University of Calgary · CA

Funding

Canadian Institutes of Health Research ISO-106796Canadian Institutes of Health Research MOP-98004
6 · The paper itself

Abstract

Clostridium difficile, a major cause of hospital-acquired diarrhea, triggers disease through the release of two toxins, toxin A (TcdA) and toxin B (TcdB). These toxins disrupt the cytoskeleton of the intestinal epithelial cell, increasing intestinal permeability and triggering the release of inflammatory mediators resulting in intestinal injury and inflammation. The most prevalent animal model to study TcdA/TcdB-induced intestinal injury involves injecting toxin into the lumen of a surgically generated "ileal loop." This model is time-consuming and exhibits variability depending on the expertise of the surgeon. Furthermore, the target organ of C. difficile infection (CDI) in humans is the colon, not the ileum. In the current study, we describe a new model of CDI that involves intrarectal instillation of TcdA/TcdB into the mouse colon. The administration of TcdA/TcdB triggered colonic inflammation and neutrophil and macrophage infiltration as well as increased epithelial barrier permeability and intestinal epithelial cell death. The damage and inflammation triggered by TcdA/TcdB isolates from the VPI and 630 strains correlated with the concentration of TcdA and TcdB produced. TcdA/TcdB exposure increased the expression of a number of inflammatory mediators associated with human CDI, including interleukin-6 (IL-6), gamma interferon (IFN-γ), and IL-1β. Finally, we were able to demonstrate that TcdA was much more potent at inducing colonic injury than was TcdB but TcdB could act synergistically with TcdA to exacerbate injury. Taken together, our data indicate that the intrarectal murine model provides a robust and efficient system to examine the effects of TcdA/TcdB on the induction of inflammation and colonic tissue damage in the context of human CDI.

Indexed as

Disease Models, AnimalAdministration, RectalAnimalsBacterial ProteinsBacterial ToxinsClostridioides difficileColonDose-Response Relationship, DrugEnterocolitis, PseudomembranousEnterotoxinsFemaleHumansInflammationMiceMice, Inbred C57BLBacterial ProteinsBacterial ToxinsEnterotoxinstcdA protein, Clostridium difficiletoxB protein, Clostridium difficile

Identifiers

PMID23045481
PMCPMC3497439
OpenAlexW2105265651

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.