Evidence map›Paper›PMID 29741098›Full record

ArticleAmerican journal of physiology. Renal physiology2018

Monophosphoryl lipid A prevents impairment of medullary thick ascending limb [Formula: see text] absorption and improves plasma [Formula: see text] concentration in septic mice.

Bruns A Watts, Thampi George, Edward R Sherwood, David W Good

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of physiology. Renal physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
  3. 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 1 country.

Bruns A WattsDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, Texas.
Thampi GeorgeDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, Texas.
Edward R SherwoodDepartment of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee.
David W GoodDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, Texas.
The University of Texas Medical Branch at Galveston · USVanderbilt University Medical Center · US

Funding

REGULATION OF THICK ASCENDING LIMB ACID-BASE TRANSPORTR01DK038217 · NIDDK · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI GOOD, DAVID WILLIAM · 1987 to 2019
$5.0M
NIDDK NIH HHS R01 DK038217
6 · The paper itself

Abstract

Metabolic acidosis is the most common acid-base disorder in septic patients and is associated with increased mortality. Previously, we demonstrated that sepsis induced by cecal ligation and puncture (CLP) impairs [Formula: see text] absorption in the medullary thick ascending limb (MTAL) by 1) decreasing the intrinsic [Formula: see text] absorptive capacity and 2) enhancing inhibition of [Formula: see text] absorption by LPS through upregulation of Toll-like receptor (TLR) 4 signaling. Both effects depend on ERK activation. Monophosphoryl lipid A (MPLA) is a detoxified TLR4 agonist that enhances innate antimicrobial immunity and improves survival following sepsis. Pretreatment of MTALs with MPLA in vitro prevents LPS inhibition of [Formula: see text] absorption. Here we examined whether pretreatment with MPLA would protect the MTAL against sepsis. Vehicle or MPLA was administered to mice 48 h before sham or CLP surgery, and MTALs were studied in vitro 18 h postsurgery. Pretreatment with MPLA prevented the effects of sepsis to decrease the basal [Formula: see text] absorption rate and enhance inhibition by LPS. These protective effects were mediated through MPLA stimulation of a Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β-(TRIF)-dependent phosphatidylinositol 3-kinase-Akt pathway that prevents sepsis- and LPS-induced ERK activation. The effects of MPLA to improve MTAL [Formula: see text] absorption were associated with marked improvement in plasma [Formula: see text] concentration, supporting a role for the kidneys in the pathogenesis of sepsis-induced metabolic acidosis. These studies support detoxified TLR4-based immunomodulators, such as MPLA, that enhance antimicrobial responses as a safe and effective approach to prevent or treat sepsis-induced renal tubule dysfunction and identify cell signaling pathways that can be targeted to preserve MTAL [Formula: see text] absorption and attenuate metabolic acidosis during sepsis.

Indexed as

Acid-Base EquilibriumAcidosisAdaptor Proteins, Vesicular TransportAnimalsBicarbonatesDisease Models, AnimalEnzyme ActivationExtracellular Signal-Regulated MAP KinasesLipid ALoop of HenleMaleMice, Inbred C57BLMice, KnockoutPhosphatidylinositol 3-KinaseProto-Oncogene Proteins c-aktRenal ReabsorptionAdaptor Proteins, Vesicular TransportBicarbonatesExtracellular Signal-Regulated MAP KinasesLipid Amonophosphoryl lipid APhosphatidylinositol 3-KinaseProto-Oncogene Proteins c-aktTicam1 protein, mouseTlr4 protein, mouseToll-Like Receptor 4kidneyLPSmetabolic acidosismonophosphoryl lipid Asepsis

Identifiers

PMID29741098
PMCPMC6172583
OpenAlexW2800507376

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.