Evidence map›Paper›PMID 23781123›Full record

ArticleMediators of inflammation2013

Biphasic modulation of NOS expression, protein and nitrite products by hydroxocobalamin underlies its protective effect in endotoxemic shock: downstream regulation of COX-2, IL-1β, TNF-α, IL-6, and HMGB1 expression.

André L F Sampaio, Jesmond Dalli, Vincenzo Brancaleone, Fulvio D'Acquisto, Mauro Perretti, Carmen Wheatley

Open access · goldAbstract read
In one paragraph

Article in Mediators of inflammation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Case report of high-dose hydroxocobalamin in the treatment of vasoplegic syndrome during liver transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2018
    Article
  7. Article
  8. Article
  9. Article
  10. Glucocorticoid receptor agonist dexamethasone attenuates renal ischemia/reperfusion injury by up-regulating eNOS/iNOS.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2014
    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

6 authors at 4 institutions in 3 countries.

André L F SampaioThe William Harvey Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.
Jesmond Dalli
Vincenzo Brancaleone
Fulvio D'Acquisto
Mauro Perretti
Carmen Wheatley
Queen Mary University of London · GBScience Oxford · GBUniversity of Basilicata · ITWilliam Harvey Research Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNOS/•NO inhibitors are potential therapeutics for sepsis, yet they increase clinical mortality. However, there has been no in vivo investigation of the (in vitro) •NO scavenger, cobalamin's (Cbl) endogenous effects on NOS/•NO/inflammatory mediators during the immune response to sepsis.

methodsWe used quantitative polymerase chain reaction (qPCR), ELISA, Western blot, and NOS Griess assays, in a C57BL/6 mouse, acute endotoxaemia model.

resultsDuring the immune response, pro-inflammatory phase, parenteral hydroxocobalamin (HOCbl) treatment partially inhibits hepatic, but not lung, iNOS mRNA and promotes lung eNOS mRNA, but attenuates the LPS hepatic rise in eNOS mRNA, whilst paradoxically promoting high iNOS/eNOS protein translation, but relatively moderate •NO production. HOCbl/NOS/•NO regulation is reciprocally associated with lower 4 h expression of TNF-α, IL-1β, COX-2, and lower circulating TNF-α, but not IL-6. In resolution, 24 h after LPS, HOCbl completely abrogates a major late mediator of sepsis mortality, high mobility group box 1 (HMGB1) mRNA, inhibits iNOS mRNA, and attenuates LPS-induced hepatic inhibition of eNOS mRNA, whilst showing increased, but still moderate, NOS activity, relative to LPS only. experiments (LPS+D-Galactosamine) HOCbl afforded significant, dose-dependent protection in mice.

conclusionsHOCbl produces a complex, time- and organ-dependent, selective regulation of NOS/•NO during endotoxaemia, corollary regulation of downstream inflammatory mediators, and increased survival. This merits clinical evaluation.

Indexed as

AnimalsBlotting, WesternCyclooxygenase 2EndotoxemiaGalactosamineHMGB1 ProteinHydroxocobalaminInterleukin-1betaInterleukin-6LiverLungMaleMiceMice, Inbred C57BLNitric OxideNitric Oxide Synthase Type IICyclooxygenase 2GalactosamineHMGB1 ProteinHydroxocobalaminInterleukin-1betaInterleukin-6Nitric OxideNitric Oxide Synthase Type IINitric Oxide Synthase Type IIITumor Necrosis Factor-alpha

Identifiers

PMID23781123
PMCPMC3679756
OpenAlexW2068522925

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LicenceCC BY
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Registered trials

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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.