Evidence map›Paper›PMID 18575598›Full record

ArticlePloS one2008

On the action of cyclosporine A, rapamycin and tacrolimus on M. avium including subspecies paratuberculosis.

Robert J Greenstein, Liya Su, Ramon A Juste, Sheldon T Brown

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.6field-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

26 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Translational gastroenterology and hepatology · 2023
    Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Anaerobic adaptation ofGut pathogens · 2017
    Article
  13. Pathogenesis, Molecular Genetics, and Genomics ofFrontiers in veterinary science · 2017
    Review
  14. Pathogenesis of Crohn's disease: Bug or no bug.World journal of gastrointestinal pathophysiology · 2015
    Review
  15. Article
  16. Mycobacterium paratuberculosis as a cause of Crohn's disease.Expert review of gastroenterology & hepatology · 2015
    Review
  17. Review
  18. Article
  19. 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

4 authors at 2 institutions in 2 countries.

Robert J GreensteinDepartment of Surgery, Veterans Affairs Medical Center, Bronx, New York, United States of America. BGAxis@aol.com
Liya Su
Ramon A Juste
Sheldon T Brown
NEIKER, the Basque Institute for Agricultural Research and Development · ESVeterans Health Administration · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMycobacterium avium subspecies paratuberculosis (MAP) may be zoonotic. Recently the "immuno-modulators" methotrexate, azathioprine and 6-MP and the "anti-inflammatory" 5-ASA have been shown to inhibit MAP growth in vitro. We concluded that their most plausible mechanism of action is as antiMAP antibiotics. The "immunosuppressants" Cyclosporine A, Rapamycin and Tacrolimus (FK 506) treat a variety of "autoimmune" and "inflammatory" diseases. Rapamycin and Tacrolimus are macrolides. We hypothesized that their mode of action may simply be to inhibit MAP growth. METHODOLOGY: The effect on radiometric MAP (14)CO(2) growth kinetics of Cyclosporine A, Rapamycin and Tacrolimus on MAP cultured from humans (Dominic & UCF 4) or ruminants (ATCC 19698 & 303) and M. avium subspecies avium (ATCC 25291 & 101) are presented as "percent decrease in cumulative GI" (%-DeltacGI.) PRINCIPAL

findingsThe positive control clofazimine has 99%-DeltacGI at 0.5 microg/ml (Dominic). Phthalimide, a negative control has no dose dependent inhibition on any strain. Against MAP there is dose dependent inhibition by the immunosuppressants. Cyclosporine has 97%-DeltacGI by 32 microg/ml (Dominic), Rapamycin has 74%-DeltacGI by 64 microg/ml (UCF 4) and Tacrolimus 43%-DeltacGI by 64 microg/ml (UCF 4)

conclusionsWe show heretofore-undescribed inhibition of MAP growth in vitro by "immunosuppressants;" the cyclic undecapeptide Cyclosporine A, and the macrolides Rapamycin and Tacrolimus. These data are compatible with our thesis that, unknowingly, the medical profession has been treating MAP infections since 1942 when 5-ASA and subsequently azathioprine, 6-MP and methotrexate were introduced in the therapy of some "autoimmune" and "inflammatory" diseases.

Indexed as

CyclosporineHumansImmunosuppressive AgentsMycobacterium aviumSirolimusSpecies SpecificityTacrolimusCyclosporineImmunosuppressive AgentsSirolimusTacrolimus

Identifiers

PMID18575598
PMCPMC2427180
OpenAlexW2152773856

What OpenQuestion holds

Textmetadata
LicenceCC0
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.