کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11005746 | 1494806 | 2018 | 23 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Evaluation of the accuracy of exchangeable copper and relative exchangeable copper (REC) in a mouse model of Wilson's disease
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کلمات کلیدی
CuSExchangeable copperLong-Evans CinnamonLECALTrecserum aspartate aminotransferase - آسپارتات آمینوترانسفراز سرمAST - آسپارتات ترانس آمینازserum alanine aminotransferase - آلانین آمینوترانسفراز سرمstandard deviation - انحراف معیارWilson’s disease - بیماری ویلسونDiagnostic test - تست تشخیصیCirrhosis - سیروزLod - لودlower limit of detection - محدودیت پایین تشخیصwild type - نوع وحشیquality control - کنترل کیفیت
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Wilson's disease (WD) is caused by mutations in the ATP7B gene responsible for a toxic copper overload mainly in the liver and the central nervous system. Phenotypic heterogeneity may challenge the diagnostic confirmation. Exchangeable copper (CuEXC) has recently been proposed as a new marker of WD, and its ratio to the total serum copper (Cus), Relative Exchangeable Copper (RECâ¯=â¯CuEXC/Cus), as a diagnostic marker. This study aimed to investigate whether this could be confirmed in Atp7b-/- mice, an engineered WD animal model. Atp7b-/- (nâ¯=â¯137) and wild type (WT; nâ¯=â¯101) mice were investigated under the same conditions at 6-8, 20, 39, or 50 weeks of age. Twenty-four Atp7bâ/â mice received D-penicillamine treatment from 39 to 50 weeks of age. Serum and liver [histology and intrahepatic copper (IHCu)] data were evaluated. In the WT group, all serum and liver data were normal. Atp7bâ/â livers developed a chronic injury from isolated moderate inflammation (6-8 weeks: 16/33â¯=â¯48%) to inflammatory fibrosis with cirrhosis (50 weeks: 25/25â¯=â¯100% and 16/25â¯=â¯64% respectively). Cus and CuEXC increased until week 39, whereas IHCu and REC were stable with increasing age and much higher than in WT mice (meanâ¯Â±â¯SD: 669â¯Â±â¯269 vs. 13â¯Â±â¯3â¯Î¼g/g dry liver and 39â¯Â±â¯12 vs. 11â¯Â±â¯3%, respectively). A threshold value of 20% for REC provided a diagnostic sensitivity and specificity of 100%, regardless of sex, age, or the use of D-penicillamine. Eleven weeks of 100â¯mg/kg D-penicillamine reduced liver fibrosis (pâ¯=â¯0.001), IHCu (pâ¯=â¯0.026) and CuEXC (pâ¯=â¯0.175). In conclusion, this study confirms REC as a WD diagnostic marker in a mouse model of chronic liver disease caused by copper overload. Further studies are needed to assess the usefulness of CuEXC to monitor the evolution of WD, particularly during treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Trace Elements in Medicine and Biology - Volume 50, December 2018, Pages 652-657
Journal: Journal of Trace Elements in Medicine and Biology - Volume 50, December 2018, Pages 652-657
نویسندگان
Sophie Heissat, Amélie Harel, Khémary Um, Anne-Sophie Brunet, Valérie Hervieu, Olivier Guillaud, Jerome Dumortier, Alain Lachaux, Elisabeth Mintz, Muriel Bost,