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Retinoid Expression in Onchocercal Skin Disease: Pilot Study

Based on the observation that the parasite Onchocerca volvulus selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic...

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Autores principales: Mawson, Anthony R, Makunde, Williams H, Penman, Alan D, Hernandez Morales, Veronica de Los Angeles, Kalinga, Akili K, Francis, Filbert, Rubinchik, Semyon, Kibweja, Addow
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755798/
https://www.ncbi.nlm.nih.gov/pubmed/29317828
http://dx.doi.org/10.1177/1178633617731741
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author Mawson, Anthony R
Makunde, Williams H
Penman, Alan D
Hernandez Morales, Veronica de Los Angeles
Kalinga, Akili K
Francis, Filbert
Rubinchik, Semyon
Kibweja, Addow
author_facet Mawson, Anthony R
Makunde, Williams H
Penman, Alan D
Hernandez Morales, Veronica de Los Angeles
Kalinga, Akili K
Francis, Filbert
Rubinchik, Semyon
Kibweja, Addow
author_sort Mawson, Anthony R
collection PubMed
description Based on the observation that the parasite Onchocerca volvulus selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic concentrations, inducing the signs and symptoms of onchocerciasis. We conducted a pilot study to test the hypothesis in Songea communities in Southern Tanzania, where mass drug administration with ivermectin had not been implemented by the time of the survey. The specific aim was to evaluate the correlation between the diagnosis of onchocerciasis and increased levels of retinoic acid at infection sites. The analysis was performed by determining copy numbers of a genome of O volvulus present in skin snip samples of persons with onchocerciacis, and correlating these numbers with expression levels of retinoic acid receptor-α (RAR-α), which is inducible by retinoic acid. Total DNA and RNA were extracted from each of 25 mf-positive and 25 mf-negative skin samples and evaluated using quantitative polymerase chain reaction with appropriate negative controls. Analysis of the samples, adjusted with glyceraldehyde 3-phosphate dehydrogenase gene levels, revealed that most samples with detectable RAR-α transcripts had higher levels of RAR-α expression than the assay control. However, the quality and number of samples were insufficient for statistical analysis. Fold data on the expression levels of both O volvulus DNA and RAR RNA suggested a possible trend toward higher relative RAR-α expression in samples with higher levels of O volvulus DNA (r(2) = 0.25, P = .079). Evidence of a contribution of vitamin A to the pathology of onchocerciasis thus remains elusive. Future studies on the role of retinoids in onchocerciasis will require larger groups of participants as well as careful monitoring of the cold chain and tissue storage procedures in view of the sensitivity of vitamin A to heat and light.
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spelling pubmed-57557982018-01-09 Retinoid Expression in Onchocercal Skin Disease: Pilot Study Mawson, Anthony R Makunde, Williams H Penman, Alan D Hernandez Morales, Veronica de Los Angeles Kalinga, Akili K Francis, Filbert Rubinchik, Semyon Kibweja, Addow Infect Dis (Auckl) Original Research Based on the observation that the parasite Onchocerca volvulus selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic concentrations, inducing the signs and symptoms of onchocerciasis. We conducted a pilot study to test the hypothesis in Songea communities in Southern Tanzania, where mass drug administration with ivermectin had not been implemented by the time of the survey. The specific aim was to evaluate the correlation between the diagnosis of onchocerciasis and increased levels of retinoic acid at infection sites. The analysis was performed by determining copy numbers of a genome of O volvulus present in skin snip samples of persons with onchocerciacis, and correlating these numbers with expression levels of retinoic acid receptor-α (RAR-α), which is inducible by retinoic acid. Total DNA and RNA were extracted from each of 25 mf-positive and 25 mf-negative skin samples and evaluated using quantitative polymerase chain reaction with appropriate negative controls. Analysis of the samples, adjusted with glyceraldehyde 3-phosphate dehydrogenase gene levels, revealed that most samples with detectable RAR-α transcripts had higher levels of RAR-α expression than the assay control. However, the quality and number of samples were insufficient for statistical analysis. Fold data on the expression levels of both O volvulus DNA and RAR RNA suggested a possible trend toward higher relative RAR-α expression in samples with higher levels of O volvulus DNA (r(2) = 0.25, P = .079). Evidence of a contribution of vitamin A to the pathology of onchocerciasis thus remains elusive. Future studies on the role of retinoids in onchocerciasis will require larger groups of participants as well as careful monitoring of the cold chain and tissue storage procedures in view of the sensitivity of vitamin A to heat and light. SAGE Publications 2017-09-20 /pmc/articles/PMC5755798/ /pubmed/29317828 http://dx.doi.org/10.1177/1178633617731741 Text en © The Author(s) 2017 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page(https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Mawson, Anthony R
Makunde, Williams H
Penman, Alan D
Hernandez Morales, Veronica de Los Angeles
Kalinga, Akili K
Francis, Filbert
Rubinchik, Semyon
Kibweja, Addow
Retinoid Expression in Onchocercal Skin Disease: Pilot Study
title Retinoid Expression in Onchocercal Skin Disease: Pilot Study
title_full Retinoid Expression in Onchocercal Skin Disease: Pilot Study
title_fullStr Retinoid Expression in Onchocercal Skin Disease: Pilot Study
title_full_unstemmed Retinoid Expression in Onchocercal Skin Disease: Pilot Study
title_short Retinoid Expression in Onchocercal Skin Disease: Pilot Study
title_sort retinoid expression in onchocercal skin disease: pilot study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755798/
https://www.ncbi.nlm.nih.gov/pubmed/29317828
http://dx.doi.org/10.1177/1178633617731741
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