Quantification and isotopic analysis of bulk and of exchangeable and ultrafiltrable serum copper in healthy and alcoholic cirrhosis subjects

Lauwens, Sara; Costas‐Rodríguez, Marta; Delanghe, Joris; Vlierberghe, Hans Van; Vanhaecke, Frank

doi:10.1016/j.talanta.2018.07.011

Cited by 20 publications

(23 citation statements)

References 52 publications

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“…Lauwens et al 36 carried out isotopic analysis of the bulk serum Cu and of its exchangeable and ultrafiltrable (EXCH+UF) versus nonexchangeable and nonultrafiltrable (NEXCH+NUF) fractions in healthy and alcoholic cirrhosis subjects. The NEXCH+NUF fraction corresponds to Cu firmly bound to ceruloplasmin, while the EXCH+UF fraction contains Cu loosely bound to proteins, such as albumin, alpha‐2 macroglobulin, and other low‐molecular‐weight compounds, and is therefore also referred to as the labile Cu pool.…”

Section: Liver Diseasementioning

confidence: 99%

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High‐precision isotopic analysis of essential mineral elements: capabilities as a diagnostic/prognostic tool

Vanhaecke

Costas‐Rodríguez

2020

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All elements with two or more isotopes show natural variation in their isotopic composition as a result of the isotope fractionation that accompanies (bio)chemical reactions and (bio)physical processes. Multicollector inductively coupled plasma‐mass spectrometry (MC‐ICP‐MS) offers the precision required to reveal and quantify the differences in isotope ratios thus caused, although they are often of sub‐permil magnitude only. Using MC‐ICP‐MS, it has been shown that (a) in different body compartments, essential mineral elements may display different isotopic compositions, and (b) disease conditions may alter the isotopic composition of an essential mineral element in a biofluid and/or tissue. As a result, high‐precision isotopic analysis of these elements is a powerful way to unravel the actual role these essential mineral elements play in specific biochemical processes. Moreover, isotope ratio shifts also show promise as a diagnostic or prognostic tool. Despite the intensive sample pretreatment preceding MC‐ICP‐MS isotopic analysis and the high purchase and running costs of the instrumentation, this approach may be valuable, especially for diseases that can otherwise only be established at a later stage and/or via a more invasive approach. This review paper describes the basics of “biomedical isotopic analysis” and uses selected cases from the literature to sketch the state‐of‐art and illustrate in which context isotope ratio markers could be exploited in a clinical context.

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Section: Liver Diseasementioning

confidence: 99%

“…Right panel: isotopic composition of Cu in the EXCH+UF fraction and that of bulk serum versus Δ 65 Cu as defined higher. Reproduced with permission from Elsevier 36 …”

Section: Liver Diseasementioning

confidence: 99%

High‐precision isotopic analysis of essential mineral elements: capabilities as a diagnostic/prognostic tool

Vanhaecke

Costas‐Rodríguez

2020

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“…A larger patient cohort could have also allowed to evaluate assay reproducibility and sensitivity. Nevertheless, serum δ 65 Cu values have previously been shown to be reproducible in healthy controls [11][12][13], so that these results seem highly reliable.…”

Section: Limitationsmentioning

confidence: 93%

Lighter serum copper isotopic composition in patients with early non-alcoholic fatty liver disease

et al. 2020

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Objective: The occurrence of non-alcoholic fatty liver disease (NAFLD) is globally increasing. To challenge the current incidence of NAFLD, non-invasive markers that could identify patients at risk or monitor disease progression are an important need. Copper intake and organ copper concentrations have earlier been linked to NAFLD progression, but serum copper does not adequately represent the disease state. Cu atoms occur under the form of two stable isotopes, 63 Cu and 65 Cu, and the ratio of both (expressed as δ 65 Cu, in ‰) in blood serum has been shown to be altered in chronic liver disease. To assess whether the Cu isotope ratio might predict disease occurrence and progression of NAFLD, the serum Cu isotopic composition of patients with different stages of NAFLD was determined. Results: Our results showed that serum δ 65 Cu values were lower in NAFLD patients, already at the level of simple steatosis, and remained stable during further disease progression. ROC analysis shows an almost perfect diagnostic ability of serum δ 65 Cu values for NAFLD, but no discrimination between different severity degrees could be made. Therefore, the serum Cu isotopic composition might show potential for early diagnosis of NAFLD patients.

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“…Nevertheless, in a recent study, 14 patients with alcoholic cirrhosis subjects have REC value ≤19% except two patients with REC at 21 and 25%. There is no information concerning ATP7B genetic testing for these patients (39).…”

Section: Rec: a Specific And Sensitive Non-invasive Tool For Wd Diagnmentioning

confidence: 99%

New tools for Wilson’s disease diagnosis: exchangeable copper fraction

Djebrani‐Oussedik

Poujois

2019

Ann. Transl. Med

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Wilson's disease (WD) biochemical markers continue to evolve. Classical tests [serum copper, serum ceruloplasmin (Cp), urinary copper] have their own limits, and they are often insufficient to diagnose or exclude WD. So, calculated estimation of copper that is not bound to Cp has been proposed, but it is flawed. Therefore, we focused our research on a direct measurement of serum copper labile fraction. Exchangeable copper (CuEXC) offers a correct view of the free copper overload. It provides information on the spread and severity of WD. Relative exchangeable copper (REC) (percentage of exchangeable to total serum copper) that appreciates the toxic fraction of copper in blood is an excellent biomarker for WD diagnosis. These two tests are reliable and non-invasive. They give rapid answers for an appropriate diagnosis and make possible to start the treatment quickly without waiting for the result of the genetic tests.

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Quantification and isotopic analysis of bulk and of exchangeable and ultrafiltrable serum copper in healthy and alcoholic cirrhosis subjects

Cited by 20 publications

References 52 publications

High‐precision isotopic analysis of essential mineral elements: capabilities as a diagnostic/prognostic tool

High‐precision isotopic analysis of essential mineral elements: capabilities as a diagnostic/prognostic tool

Lighter serum copper isotopic composition in patients with early non-alcoholic fatty liver disease

New tools for Wilson’s disease diagnosis: exchangeable copper fraction

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