Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity
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{"title"=>"Comparison of bile acids and acetaminophen protein adducts in children and adolescents with acetaminophen toxicity", "type"=>"journal", "authors"=>[{"first_name"=>"Laura", "last_name"=>"James", "scopus_author_id"=>"7201562936"}, {"first_name"=>"Ke", "last_name"=>"Yan", "scopus_author_id"=>"57196441166"}, {"first_name"=>"Lisa", "last_name"=>"Pence", "scopus_author_id"=>"8290192700"}, {"first_name"=>"Pippa", "last_name"=>"Simpson", "scopus_author_id"=>"7201907970"}, {"first_name"=>"Sudeepa", "last_name"=>"Bhattacharyya", "scopus_author_id"=>"7402157177"}, {"first_name"=>"Pritmohinder", "last_name"=>"Gill", "scopus_author_id"=>"56044032000"}, {"first_name"=>"Lynda", "last_name"=>"Letzig", "scopus_author_id"=>"6507565075"}, {"first_name"=>"Gregory", "last_name"=>"Kearns", "scopus_author_id"=>"7101725930"}, {"first_name"=>"Richard", "last_name"=>"Beger", "scopus_author_id"=>"7004106777"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84941662768", "pui"=>"605996921", "doi"=>"10.1371/journal.pone.0131010", "sgr"=>"84941662768", "pmid"=>"26208104"}, "id"=>"19733a1b-0d33-3742-bee4-440f909a3a77", "abstract"=>"Metabolomics approaches have enabled the study of new mechanisms of liver injury in experimental models of drug toxicity. Disruption of bile acid homeostasis is a known mechanism of drug induced liver injury. The relationship of individual bile acids to indicators of oxidative drug metabolism (acetaminophen protein adducts) and liver injury was examined in children with acetaminophen overdose, hospitalized children with low dose exposure to acetaminophen, and children with no recent exposure to acetaminophen. Nine bile acids were quantified through targeted metabolomic analysis in the serum samples of the three groups. Bile acids were compared to serum levels of acetaminophen protein adducts and alanine aminotransferase. Glycodeoxycholic acid, taurodeoxycholic acid, and glycochenodeoxycholic acid were significantly increased in children with acetaminophen overdose compared to healthy controls. Among patients with acetaminophen overdose, bile acids were higher in subjects with acetaminophen protein adduct values > 1.0 nmol/mL and modest correlations were noted for three bile acids and acetaminophen protein adducts as follows: taurodeoxycholic acid (R=0.604; p<0.001), glycodeoxycholic acid (R=0.581; p<0.001), and glycochenodeoxycholic acid (R=0.571; p<0.001). Variability in bile acids was greater among hospitalized children receiving low doses of acetaminophen than in healthy children with no recent acetaminophen exposure. Compared to bile acids, acetaminophen protein adducts more accurately discriminated among children with acetaminophen overdose, children with low dose exposure to acetaminophen, and healthy control subjects. In children with acetaminophen overdose, elevations of conjugated bile acids were associated with specific indicators of acetaminophen metabolism and non-specific indicators of liver injury.", "link"=>"http://www.mendeley.com/research/comparison-bile-acids-acetaminophen-protein-adducts-children-adolescents-acetaminophen-toxicity", "reader_count"=>10, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>3, "Student > Master"=>4, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>3, "Student > Master"=>4, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Medicine and Dentistry"=>5, "Agricultural and Biological Sciences"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>0}

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  • {"files"=>["https://ndownloader.figshare.com/files/2190200"], "description"=>"<p>*denotes > 2.0 times the 25–75<sup>th</sup> percentile; <sup>O</sup>denotes > 1.5 times the 25–75<sup>th</sup> percentile. GCA, Glycocholic acid; GDCA, Glycodeoxycholic acid; TDCA, Taurodeoxycholic acid.</p>", "links"=>[], "tags"=>["bile acid homeostasis", "acetaminophen protein adducts", "acetaminophen protein adduct values", "dose exposure", "Acetaminophen Toxicity Metabolomics approaches", "glycochenodeoxycholic acid", "oxidative drug metabolism", "acetaminophen overdose", "taurodeoxycholic acid", "liver injury", "bile acids"], "article_id"=>1494528, "categories"=>["Biological Sciences"], "users"=>["Laura James", "Ke Yan", "Lisa Pence", "Pippa Simpson", "Sudeepa Bhattacharyya", "Pritmohinder Gill", "Lynda Letzig", "Gregory Kearns", "Richard Beger"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131010.g001", "stats"=>{"downloads"=>0, "page_views"=>47, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_time_to_reach_peak_bile_acid_presented_as_a_function_of_peak_APAP_protein_adduct_lt_or_8805_1_0_nmol_mL_APAP_protein_adduct_/1494528", "title"=>"Comparison of time to reach peak bile acid, presented as a function of peak APAP protein adduct < or ≥ 1.0 nmol/mL APAP protein adduct.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-24 04:51:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/2190201"], "description"=>"<p>TDCA, Taurodeoxycholic acid; GCDA, Glycodeoxycholic acid.</p>", "links"=>[], "tags"=>["bile acid homeostasis", "acetaminophen protein adducts", "acetaminophen protein adduct values", "dose exposure", "Acetaminophen Toxicity Metabolomics approaches", "glycochenodeoxycholic acid", "oxidative drug metabolism", "acetaminophen overdose", "taurodeoxycholic acid", "liver injury", "bile acids"], "article_id"=>1494529, "categories"=>["Biological Sciences"], "users"=>["Laura James", "Ke Yan", "Lisa Pence", "Pippa Simpson", "Sudeepa Bhattacharyya", "Pritmohinder Gill", "Lynda Letzig", "Gregory Kearns", "Richard Beger"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131010.g002", "stats"=>{"downloads"=>0, "page_views"=>52, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Receiver_operator_curve_ROC_analysis_of_bile_acids_BA_that_best_distinguished_subjects_with_acetaminophen_protein_adducts_lt_1_versus_8805_1_0_nmol_mL_/1494529", "title"=>"Receiver operator curve (ROC) analysis of bile acids (BA) that best distinguished subjects with acetaminophen protein adducts < 1 versus ≥ 1.0 nmol/mL.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-24 04:51:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/2190202"], "description"=>"<p>Data are presented as median and range.</p><p>*p value for three way comparison and **p value for pairwise comparisons.</p><p>Demographic characteristics of study subjects by groups.</p>", "links"=>[], "tags"=>["bile acid homeostasis", "acetaminophen protein adducts", "acetaminophen protein adduct values", "dose exposure", "Acetaminophen Toxicity Metabolomics approaches", "glycochenodeoxycholic acid", "oxidative drug metabolism", "acetaminophen overdose", "taurodeoxycholic acid", "liver injury", "bile acids"], "article_id"=>1494530, "categories"=>["Biological Sciences"], "users"=>["Laura James", "Ke Yan", "Lisa Pence", "Pippa Simpson", "Sudeepa Bhattacharyya", "Pritmohinder Gill", "Lynda Letzig", "Gregory Kearns", "Richard Beger"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131010.t001", "stats"=>{"downloads"=>7, "page_views"=>54, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_characteristics_of_study_subjects_by_groups_/1494530", "title"=>"Demographic characteristics of study subjects by groups.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-07-24 04:51:19"}
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  • {"files"=>["https://ndownloader.figshare.com/files/2190204"], "description"=>"<p>*Log transformation of peak measurement of parameter.</p><p>Correlation analysis of peak biomarker versus time to treatment with N-acetylcysteine (NAC)<sup><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131010#t003fn001\" target=\"_blank\">*</a></sup>.</p>", "links"=>[], "tags"=>["bile acid homeostasis", "acetaminophen protein adducts", "acetaminophen protein adduct values", "dose exposure", "Acetaminophen Toxicity Metabolomics approaches", "glycochenodeoxycholic acid", "oxidative drug metabolism", "acetaminophen overdose", "taurodeoxycholic acid", "liver injury", "bile acids"], "article_id"=>1494532, "categories"=>["Biological Sciences"], "users"=>["Laura James", "Ke Yan", "Lisa Pence", "Pippa Simpson", "Sudeepa Bhattacharyya", "Pritmohinder Gill", "Lynda Letzig", "Gregory Kearns", "Richard Beger"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131010.t003", "stats"=>{"downloads"=>10, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlation_analysis_of_peak_biomarker_versus_time_to_treatment_with_N_acetylcysteine_NAC_/1494532", "title"=>"Correlation analysis of peak biomarker versus time to treatment with N-acetylcysteine (NAC)<sup>*</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-07-24 04:51:19"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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