Evidence map›Paper›PMID 26405813›Full record

ArticlePLoS neglected tropical diseases2015

Electrophysiological Studies into the Safety of the Anti-diarrheal Drug Clotrimazole during Oral Rehydration Therapy.

Willem S Lexmond, Paul A Rufo, Edda Fiebiger, Wayne I Lencer

Open access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 44% 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

1 citing paper in PubMed, 5 citations in OpenAlex.

  1. 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.

Willem S LexmondDivision of Gastroenterology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Paul A RufoDivision of Gastroenterology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Edda FiebigerDivision of Gastroenterology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Wayne I LencerDivision of Gastroenterology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Harvard University · USBoston Children's Hospital · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
Mechanism of action for the epithelial-specific ER stress sensor IRE1β in regulating intestinal homeostasis and host defenseR01DK048106 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI WAYNE I LENCER · 1993 to 2026
$9.6M
Intestinal Disease-enterocyte toxin interactionR37DK048106 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI LENCER, WAYNE I · 2011 to 2020
$7.0M
Studies of Fc-epsilon-RI as an antigen presentation structure at mucosal surfacesR01AI075037 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI FIEBIGER, ELISABETH EDDA · 2009 to 2013
$2.0M
FcRn-dependent sorting of IgG and IgG-opsinized antigens by epithelial cellsR01DK084424 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI LENCER, WAYNE I · 2009 to 2013
$1.9M
Unsaturated glycoceramide as novel platform for mucosal vaccine and drug deliveryR21DK090603 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI LENCER, WAYNE I · 2010 to 2011
$473k
NIAID NIH HHS R01 AI075037NIAID NIH HHS R01AI075037NIDDK NIH HHS DK034854NIDDK NIH HHS DK084424NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R01 DK048106NIDDK NIH HHS R01 DK084424NIDDK NIH HHS R01 DK48106NIDDK NIH HHS R21 DK090603NIDDK NIH HHS R21DK090603NIDDK NIH HHS R37 DK048106
6 · The paper itself

Abstract

BACKGROUND AND

aimsMorbidity and mortality from acute diarrheal disease remains high, particularly in developing countries and in cases of natural or man-made disasters. Previous work has shown that the small molecule clotrimazole inhibits intestinal Cl- secretion by blocking both cyclic nucleotide- and Ca(2+)-gated K(+) channels, implicating its use in the treatment of diarrhea of diverse etiologies. Clotrimazole, however, might also inhibit transporters that mediate the inwardly directed electrochemical potential for Na(+)-dependent solute absorption, which would undermine its clinical application. Here we test this possibility by examining the effects of clotrimazole on Na(+)-coupled glucose uptake. MATERIALS AND

methodsShort-circuit currents (Isc) following administration of glucose and secretagogues were studied in clotrimazole-treated jejunal sections of mouse intestine mounted in Ussing chambers.

resultsTreatment of small intestinal tissue with clotrimazole inhibited the Cl- secretory currents that resulted from challenge with the cAMP-agonist vasoactive intestinal peptide (VIP) or Ca(2+)-agonist carbachol in a dose-dependent fashion. A dose of 30 μM was effective in significantly reducing the Isc response to VIP and carbachol by 50% and 72%, respectively. At this dose, uptake of glucose was only marginally affected (decreased by 14%, p = 0.37). There was no measurable effect on SGLT1-mediated sugar transport, as uptake of SGLT1-restricted 3-O-methyl glucose was equivalent between clotrimazole-treated and untreated tissue (98% vs. 100%, p = 0.90).

conclusionTreatment of intestinal tissue with clotrimazole significantly reduced secretory responses caused by both cAMP- and Ca(2+)-dependent agonists as expected, but did not affect Na(+)-coupled glucose absorption. Clotrimazole could thus be used in conjunction with oral rehydration solution as a low-cost, auxiliary treatment of acute secretory diarrheas.

Indexed as

AnimalsAntidiarrhealsBiological TransportClotrimazoleDiagnostic Techniques, Digestive SystemDiarrheaElectrochemical TechniquesElectrophysiological PhenomenaEnterocytesFluid TherapyJejunumMiceMice, Inbred BALB CModels, AnimalSymportersAntidiarrhealsClotrimazoleSymporters

Identifiers

PMID26405813
PMCPMC4583490
OpenAlexW1882077706

What OpenQuestion holds

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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.