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Novel biomarkers in amniotic fluid for early assessment of intraamniotic infection
Institution:1. Neonatal Research Unit, Health Research Institute La Fe, Valencia, Avenida Fernando Abril Martorell 106; 46026 Valencia; Spain;2. Department of Obstetrics and Gynecology, Fetomaternal Medical Center, Helsinki University Central Hospital and University of Helsinki, Haartmaninkatu 2, 00029, Helsinki, Finland;3. Children’s Hospital, University of Helsinki and Helsinki University Hospital, Stenbäckinkatu 11, PO Box 281, 00029, Helsinki, Finland;4. Division of Neonatology, University & Polytechnic Hospital La Fe, Avenida Fernando Abril Martorell 106; 46026 Valencia, Spain;1. Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 West Walnut Street, R4-W116, Indianapolis, IN 46202, USA;2. Pediatrics, E Doisy Research Center, Saint Louis University School of Medicine, 1100 South Grand Boulevard, St Louis, MO 63104, USA;3. Molecular Microbiology & Immunology, E Doisy Research Center, Saint Louis University School of Medicine, 1100 South Grand Boulevard, St Louis, MO 63106, USA;1. Institut Montpellierain Alexander Grothendieck, CNRS, University of Montpellier, Montpellier, France;2. Medical Oncology, Dana-Farber Cancer, Institute Harvard Medical School, Boston, MA;3. Department of Biostatistics and Computational Biology, Dana-Farber Cancer, Institute Harvard Medical School, Boston, MA;4. Hematology Department, University Hospital, Nancy, France;5. Unit for Genomics in Myeloma, Institut Universitaire du Cancer-Oncopole, Toulouse, France;6. Centre de Reserches en Cancérologie de Toulouse, INSERM U1037, Toulouse, France;7. VA Boston Healthcare System, West Roxbury, MA;1. National Cancer Institute;2. University of Tübingen
Abstract:Intra-amniotic infection/inflammation (IAI) is associated with preterm birth, short and long-term adverse clinical outcomes and oxidative stress. The diagnosis of IAI is based on histological and clinical findings; however, often these results are unspecific. Therefore, efforts have been directed towards validating reliable methods for patients lacking overt clinical symptoms. In this study, amniotic fluid (AF) samples were prospectively collected from 23 women grouped into two categories (with or without IAI) following clinical, microbiological and histological criteria. AFs were analyzed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the determination of the following biomarkers: oxidized and nitrated tyrosines (Tyr), 8-hydroxy-2'-deoxyguanosine (8OHdG), oxidized glutathione (GSSG) and glutathione sulfonamide (GSA). 3-NO2-Tyrosine (3NO2-Tyr) and GSSG concentrations in AF were not identified as significantly relevant biomarkers in the presence of IAI. However, inflammatory biomarkers such as GSA (p=0.002) and 3-Chloro-Tyrosine 3Cl-Tyr (p=0.049)], and oxidative stress biomarker 8OHdG (p=0.021) were significantly increased in AF with IAI as compared to normal controls. Biomarkers of inflammation and oxidative stress determined in AF samples could represent a new approach towards an early diagnosis of IAI and subsequent chorioamnionitis in the clinical setting.
Keywords:Biomarkers  Chorioamnionitis  Intra-amniotic inflammation/infection  Oxidative stress  Liquid chromatography – tandem mass spectrometry (LC-MS/MS)
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