Evidence map›Paper›PMID 19586414›Full record

ArticleThe Journal of infectious diseases2009

Disruption of tight junctions by cellulose sulfate facilitates HIV infection: model of microbicide safety.

Pedro M M Mesquita, Natalia Cheshenko, Sarah S Wilson, Mohak Mhatre, Esmeralda Guzman, Esra Fakioglu, Marla J Keller, Betsy C Herold

Open access · greenAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 1 pooled it
6.2field-weighted citation impact, top 2% 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

71 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.

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11 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Pedro M M MesquitaDepartment of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Natalia Cheshenko
Sarah S Wilson
Mohak Mhatre
Esmeralda Guzman
Esra Fakioglu
Marla J Keller
Betsy C Herold
Albert Einstein College of Medicine · US

Funding

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025750 · NCRR · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI SHAMOON, HARRY · 2008 to 2011
$20.5M
Impact of HSV-2 on Female Genital Tract Mucosal Immunity & HIV InfectionR01AI065309 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI HEROLD, BETSY C. · 2005 to 2014
$5.1M
Novel Mucosal Models Predictive of Microbicide SafetyR33AI079763 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI HEROLD, BETSY C., KELLER, MARLA J · 2010 to 2012
$1.4M
Novel Mucosal Models Predictive of Microbicide SafetyR21AI079763 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI HEROLD, BETSY C., KELLER, MARLA J · 2008 to 2009
$457k
NCRR NIH HHS UL1 RR025750NCRR NIH HHS UL1RR025750NIAID NIH HHS AI065309NIAID NIH HHS AI079763NIAID NIH HHS R01 AI065309NIAID NIH HHS R21 AI079763NIAID NIH HHS R33 AI079763
6 · The paper itself

Abstract

backgroundThe lack of biomarkers that are predictive of safety is a critical gap in the development of microbicides. The present experiments were designed to evaluate the predictive value of in vitro models of microbicide safety.

methodsChanges in the epithelial barrier were evaluated by measuring transepithelial electrical resistance (TER) after exposure of human epithelial cells to candidate microbicides in a dual-chamber system. The significance of observed changes was addressed by challenging cultures with human immunodeficiency virus (HIV) and measuring the ability of virus to cross the epithelium and infect target T cells cultured in the lower chamber.

resultsExposure to nonoxynol-9 (N-9) or cellulose sulfate (CS), but not 9-[2-(phosphonomethoxy)propyl]adenine (also referred to as tenofovir) or PRO2000, resulted in a rapid and sustained reduction in TER and a marked increase in HIV infection of T cells cultured in the lower chamber. Moreover, CS triggered nuclear factor kappaB activation in peripheral blood mononuclear cells and increased HIV replication in chronically infected U1 cells.

conclusionsEpithelial barrier disruption and enhanced viral replication may have contributed to the increased risk of HIV acquisition observed in phase 3 trials of N-9 and CS. Expansion of in vitro safety testing to include these models would provide a more stringent preclinical assessment of microbicide safety and may prove to be more predictive of clinical outcomes.

Indexed as

AdenineAnti-HIV AgentsAnti-Infective AgentsCell LineCelluloseElectric ImpedanceEpithelial CellsHIVHumansInflammationNaphthalenesulfonatesNF-kappa BOrganophosphonatesPolymersTenofovirTight JunctionsAdenineAnti-HIV AgentsAnti-Infective AgentsCellulosecellulose sulfateNaphthalenesulfonatesNF-kappa BOrganophosphonatesPolymersPRO 2000Tenofovir

Identifiers

PMID19586414
PMCPMC2877491
OpenAlexW2150550553

What OpenQuestion holds

Textmetadata
LicenceTDM
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.