Evidence map›Paper›PMID 16368960›Full record

ArticleInfection and immunity2006

Caspase and bid involvement in Clostridium difficile toxin A-induced apoptosis and modulation of toxin A effects by glutamine and alanyl-glutamine in vivo and in vitro.

Benedito A Carneiro, Jun Fujii, Gerly A C Brito, Cirle Alcantara, Reinaldo B Oriá, Aldo A M Lima, Tom Obrig, Richard L Guerrant

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

49 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
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  3. Review
  4. Article
  5. Mechanisms ofFrontiers in cellular and infection microbiology · 2025
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  7. Review
  8. Review
  9. Article
  10. Article
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  13. Article
  14. Article
  15. Investigational Treatment Agents for RecurrentJournal of experimental pharmacology · 2020
    Review
  16. Article
  17. Article
  18. Effects ofOncology letters · 2018
    Article
  19. Review
  20. Review
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

8 authors at 3 institutions in 2 countries.

Benedito A CarneiroCenter for Global Health, Division of Infectious Diseases and International Health, University of Virginia, MR4, Lane Road, Room 3148, Charlottesville, VA 22908, USA.
Jun Fujii
Gerly A C Brito
Cirle Alcantara
Reinaldo B Oriá
Aldo A M Lima
Tom Obrig
Richard L Guerrant
Center for Global Health · USUniversity of Virginia · USUniversidade Federal do Ceará · BR

Funding

RECOGNITION &EXPRESSION OF TROPICAL INFECTIOUS DISEASESU01AI026512 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GUERRANT, RICHARD L · 1994 to 2014
$8.5M
ACTION FOR BUILDING CAPACITY (ABC) AT UVAD43TW001136 · FIC · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GUERRANT, RICHARD L · 1999 to 2004
$498k
Alanyl-glutamine as Oral Rehydration &Nutrition TherapyR43DK058419 · NIDDK · ALGLUTAMINE, LLC · PI BRITO, GERLY A · 2001 to 2001
$100k
FIC NIH HHS 5D43 TW 01136-04FIC NIH HHS D43 TW001136NIAID NIH HHS 5U01 AI 26512-14NIAID NIH HHS U01 AI026512NIDDK NIH HHS 1R43 DK 58419-01A1
6 · The paper itself

Abstract

Clostridium difficile is the leading cause of nosocomial bacterial diarrhea. Glutamine and its stable and highly soluble derivative alanyl-glutamine, have been beneficial in models of intestinal injury. In this study, we extend our work on the mechanisms of Clostridium difficile toxin A (TxA)-induced apoptosis in human intestinal epithelial T84 cells and evaluate the effects of glutamine and alanyl-glutamine on TxA-induced apoptosis in vitro and disruption of ileal mucosa in vivo. T84 cells were incubated with TxA (100 ng/ml) in medium with or without glutamine or alanyl-glutamine (3 to 100 mM). Apoptosis was evaluated by DNA fragmentation in vitro and the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling method in vivo. Caspase and Bid involvement were investigated by Western blotting. Ligated rabbit ileal loops were used for the evaluation of intestinal secretion, mucosal disruption, and apoptosis. TxA induced caspases 6, 8, and 9 prior to caspase 3 activation in T84 cells and induced Bid cleavage by a caspase-independent mechanism. Glutamine or alanyl-glutamine significantly reduced TxA-induced apoptosis of T84 cells by 47% and inhibited activation of caspase 8. Both glutamine and alanyl-glutamine reduced TxA-induced ileal mucosal disruption and secretion. Altogether, we further delineated the apoptosis-signaling cascade induced by TxA in T84 cells and demonstrated the protective effects of glutamine and alanyl-glutamine. Glutamine and alanyl-glutamine inhibited the apoptosis of T84 cells by preventing caspase 8 activation and reduced TxA-induced intestinal secretion and disruption.

Indexed as

AnimalsApoptosisBacterial ToxinsBH3 Interacting Domain Death Agonist ProteinCaspasesCell LineClostridioides difficileDipeptidesEnterotoxinsGlutamineHumansIleumIntestinal MucosaRabbitsalanylglutamineBacterial ToxinsBH3 Interacting Domain Death Agonist ProteinBID protein, humanCaspasesDipeptidesEnterotoxinsGlutaminetcdA protein, Clostridium difficile

Identifiers

PMID16368960
PMCPMC1346681
OpenAlexW2132910118

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.