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      Vaginal lipidomics of women with vulvovaginal candidiasis and cytolytic vaginosis: A non-targeted LC-MS pilot study

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          Abstract

          Objective

          To characterize the lipid profile in vaginal discharge of women with vulvovaginal candidiasis, cytolytic vaginosis, or no vaginal infection or dysbiosis.

          Design

          Cross-sectional study.

          Setting

          Genital Infections Ambulatory, Department of Tocogynecology, University of Campinas, Campinas, São Paulo–Brazil.

          Sample

          Twenty-four women were included in this study: eight with vulvovaginal candidiasis, eight with cytolytic vaginosis and eight with no vaginal infections or dysbiosis (control group).

          Methods

          The lipid profile in vaginal discharge of the different study groups was determined by liquid chromatography-mass spectrometry and further analyzed with MetaboAnalyst 3.0 platform.

          Main outcome measures

          Vaginal lipids concentration and its correlation with vulvovaginal candidiasis and cytolytic vaginosis.

          Results

          PCA, PLS-DA and hierarchical clustering analyses indicated 38 potential lipid biomarkers for the different groups, correlating with oxidative stress, inflammation, apoptosis and integrity of the vaginal epithelial tissue. Among these, greater concentrations were found for Glycochenodeoxycholic acid-7-sulfate, O-adipoylcarnitine, 1-eicosyl-2-heptadecanoyl-glycero-3-phosphoserine, undecanoic acid, formyl dodecanoate and lipoic acid in the vulvovaginal candidiasis group; N–(tetradecanoyl)-sphinganine, DL-PPMP, 1-oleoyl-cyclic phosphatidic, palmitic acid and 5-aminopentanoic acid in the cytolytic vaginosis group; and 1-nonadecanoyl-glycero-3-phosphate, eicosadienoic acid, 1-stearoyl-cyclic-phosphatidic acid, 1-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphate, formyl 9Z-tetradecenoate and 7Z,10Z-hexadecadienoic acid in the control group.

          Conclusions

          Lipids related to oxidative stress and apoptosis were found in higher concentrations in women with vulvovaginal candidiasis and cytolytic vaginosis, while lipids related to epithelial tissue integrity were more pronounced in the control group. Furthermore, in women with cytolytic vaginosis, we observed higher concentrations of lipids related to bacterial overgrowth.

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          Most cited references50

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          XCMS Online: a web-based platform to process untargeted metabolomic data.

          Recently, interest in untargeted metabolomics has become prevalent in the general scientific community among an increasing number of investigators. The majority of these investigators, however, do not have the bioinformatic expertise that has been required to process metabolomic data by using command-line driven software programs. Here we introduce a novel platform to process untargeted metabolomic data that uses an intuitive graphical interface and does not require installation or technical expertise. This platform, called XCMS Online, is a web-based version of the widely used XCMS software that allows users to easily upload and process liquid chromatography/mass spectrometry data with only a few mouse clicks. XCMS Online provides a solution for the complete untargeted metabolomic workflow including feature detection, retention time correction, alignment, annotation, statistical analysis, and data visualization. Results can be browsed online in an interactive, customizable table showing statistics, chromatograms, and putative METLIN identities for each metabolite. Additionally, all results and images can be downloaded as zip files for offline analysis and publication. XCMS Online is available at https://xcmsonline.scripps.edu.
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            Vulvovaginal candidosis.

            Despite therapeutic advances, vulvovaginal candidosis remains a common problem worldwide, affecting all strata of society. Understanding of anti-candida host defence mechanisms in the vagina has developed slowly and, despite a growing list of recognised risk factors, a fundamental grasp of pathogenic mechanisms continues to elude us. The absence of rapid, simple, and inexpensive diagnostic tests continues to result in both overdiagnosis and underdiagnosis of vulvovaginal candidosis. I review the epidemiology and pathogenesis of this infection, and also discuss management strategies.
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              Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations.

              Numerous previous studies of nonspecific vaginitis have yielded contradictory results regarding its cause and clinical manifestations, due to a lack of uniform case definition and laboratory methods. We studied 397 consecutive unselected female university students and applied sets of well defined criteria to distinguish nonspecific vaginitis from other forms of vaginitis and from normal findings. Using such criteria, we diagnosed nonspecific vaginitis in up to 25 percent of our study population; asymptomatic disease was recognized in more than 50 percent of those with nonspecific vaginitis. A clinical diagnosis of nonspecific vaginitis, based on simple office procedures, was correlated with both the presence and the concentration of Gardnerella vaginalis (Hemophilus vaginalis) in vaginal discharge, and with characteristic biochemical findings in vaginal discharge. Nonspecific vaginitis was also correlated with a history of sexual activity, a history of previous trichomoniasis, current use of nonbarrier contraceptive methods, and, particularly, use of an intrauterine device. G. vaginalis was isolated from 51.3 percent of the total population using a highly selective medium that detected the organism in lower concentration in vaginal discharge than did previously used media. Practical diagnostic criteria for standard clinical use are proposed. Application of such criteria should assist in clinical management of nonspecific vaginitis and in further study of the microbiologic and biochemical correlates and the pathogenesis of this mild but quite prevalent disease.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: Funding acquisitionRole: Methodology
                Role: Funding acquisitionRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: Supervision
                Role: MethodologyRole: Writing – review & editing
                Role: Methodology
                Role: Data curationRole: Formal analysisRole: Software
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 August 2018
                2018
                : 13
                : 8
                : e0202401
                Affiliations
                [1 ] Campinas State University, Department of Tocoginecology, Campinas, São Paulo, Brazil
                [2 ] Campinas State University, Institute of Chemistry, Campinas, São Paulo, Brazil
                [3 ] University of São Paulo, Polytechnic School, São Paulo, São Paulo, Brazil
                [4 ] University of São Paulo, School of Pharmaceutical Sciences, São Paulo, São Paulo, Brazil
                Universitat de Lleida-IRBLLEIDA, SPAIN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-7025-7421
                Article
                PONE-D-17-40070
                10.1371/journal.pone.0202401
                6105002
                30133508
                cbe337ee-9389-4866-adab-189390bc7b41
                © 2018 Sanches et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 November 2017
                : 2 August 2018
                Page count
                Figures: 4, Tables: 0, Pages: 13
                Funding
                Funded by: Research Support Foundation of Sao Paulo (FAPESP)
                Award ID: 2016/18850-9
                Award Recipient :
                This study was supported by the Research Support Foundation of Sao Paulo (FAPESP) (2016/18850-9 to Mr. José Marcos Sanches). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Lipids
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Biology and Life Sciences
                Cell Biology
                Oxidative Stress
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Multivariate Analysis
                Principal Component Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Multivariate Analysis
                Principal Component Analysis
                Biology and Life Sciences
                Molecular Biology
                Macromolecular Structure Analysis
                Lipid Analysis
                Biology and Life Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Inflammation
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Inflammation
                Medicine and Health Sciences
                Urology
                Genitourinary Infections
                Candidiasis
                Medicine and Health Sciences
                Infectious Diseases
                Sexually Transmitted Diseases
                Candidiasis
                Biology and Life Sciences
                Biochemistry
                Lipids
                Fatty Acids
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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