Background: The national programs for the harmonization of hemoglobin (Hb)A1c measurements in the US [National Glycohemoglobin Standardization Program (NGSP)], Japan [Japanese Diabetes Society (JDS)/Japanese Society of Clinical Chemistry (JSCC)], and Sweden are based on different designated comparison methods (DCMs). The future basis for international standardization will be the reference system developed by the IFCC Working Group on HbA1c Standardization. The aim of the present study was to determine the relationships between the IFCC Reference Method (RM) and the DCMs. Methods: Four method-comparison studies were performed in 2001–2003. In each study five to eight pooled blood samples were measured by 11 reference laboratories of the IFCC Network of Reference Laboratories, 9 Secondary Reference Laboratories of the NGSP, 3 reference laboratories of the JDS/JSCC program, and a Swedish reference laboratory. Regression equations were determined for the relationship between the IFCC RM and each of the DCMs. Results: Significant differences were observed between the HbA1c results of the IFCC RM and those of the DCMs. Significant differences were also demonstrated between the three DCMs. However, in all cases the relationship of the DCMs with the RM were linear. There were no statistically significant differences between the regression equations calculated for each of the four studies; therefore, the results could be combined. The relationship is described by the following regression equations: NGSP-HbA1c = 0.915(IFCC-HbA1c) + 2.15% (r2 = 0.998); JDS/JSCC-HbA1c = 0.927(IFCC-HbA1c) + 1.73% (r2 = 0.997); Swedish-HbA1c = 0.989(IFCC-HbA1c) + 0.88% (r2 = 0.996). Conclusion: There is a firm and reproducible link between the IFCC RM and DCM HbA1c values.
HbA1C is the stable glucose adduct to the N-terminal group of the beta-chain of HbA0. The measurement of HbA1c in human blood is most important for the long-term control of the glycaemic state in diabetic patients. Because there was no internationally agreed reference method the IFCC Working Group on HbA1c Standardization developed a reference method which is here described. In a first step haemoglobin is cleaved into peptides by the enzyme endoproteinase Glu-C, and in a second step the glycated and non-glycated N-terminal hexapeptides of the beta-chain obtained are separated and quantified by HPLC and electrospray ionisation mass spectrometry or in a two-dimensional approach using HPLC and capillary electrophoresis with UV-detection. Both principles give identical results. HbA1c is measured as ratio between the glycated and non-glycated hexapeptides. Calibrators consisting of mixtures of highly purified HbA1c and HbA0 are used. The analytical performance of the reference method has been evaluated by an international network of reference laboratories comprising laboratories from Europe, Japan and the USA. The intercomparison studies of the network showed excellent results with intra-laboratory CVs of 0.5 to 2% and inter-laboratory CVs of 1.4 to 2.3%. Possible interferences have been carefully investigated. Due to the higher specificity of the reference method the results are lower than those generated with most of the present commercial methods which currently are calibrated with unspecific designated comparison methods. The new reference method has been approved by the member societies of the International Federation of Clinical Chemistry and Laboratory Medicine and will be the basis for the future uniform standardization of HbA1c routine assays worldwide.
The Elecsys β-amyloid (1-42) assay has high analytical performance that may improve biomarker-based AD diagnosis.
Hepcidin levels in stable haemodialysis patients appear to reflect systemic iron load, but not inflammation. Due to the negative association between reticulocyte counts and hepcidin, the reduction of circulating hepcidin concentrations by dialysis and/or rhEpo treatment may positively affect erythropoiesis.
Liquid chromatography-mass spectrometry analysis of small molecules from biofluids requires sensitive and robust assays. Because of the very complex nature of many biological samples, efficient sample preparation protocols to remove unwanted components and to selectively extract the compounds of interest are an essential part of almost every bioanalytical workflow. This review describes the most common problems encountered during sample preparation, ways to optimize established sample preparation techniques and important recent developments to reduce or eliminate major interferents from biofluids.
IntroductionOur objective was to determine the interrelationships of interleukin (IL)-6 receptor inhibition with haemoglobin, acute-phase reactants and iron metabolism markers (including hepcidin) in patients with rheumatoid arthritis (RA).MethodsData of patients receiving tocilizumab or placebo in the MEASURE study were analysed. We investigated associations at baseline and during tocilizumab treatment among haemoglobin, parameters of haemoglobin and iron homeostasis [ferritin, total iron-binding capacity (TIBC), hepcidin, haptoglobin], IL-6 and acute-phase reactants [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] to identify statistical correlates of rise in haemoglobin level.ResultsAt baseline, CRP and haptoglobin were inversely correlated (modestly) with haemoglobin levels. After treatment with tocilizumab, CRP, hepcidin, ferritin and haptoglobin levels fell alongside increases in TIBC and haemoglobin. The falls in CRP, hepcidin and haptoglobin levels in the first 2 weeks correlated with a week 12 rise in TIBC and haemoglobin.ConclusionsInflammatory anaemia improves in patients with RA treated with tocilizumab. This improvement correlates with the degree of suppression of systemic inflammation, reduction in hepcidin and haptoglobin and increase in iron-binding capacity. These clinical data provide evidence of a role for IL-6 signalling in the inflammatory anaemia of RA.
Quantification of 25-hydroxyvitamin D 3 (25-hydroxycholecalciferol) in serum is the best-established indicator of vitamin D status (1 ). Vitamin D 3 (cholecalciferol) is absorbed from the diet, and, given sufficient ultraviolet irradiation, nutritionally adequate amounts of vitamin D 3 are formed in the skin from its precursor, 7-dehydrocholesterol. In the liver, vitamin D 3 undergoes hydroxylation to 25-hydroxyvitamin D 3 , which is further metabolized in the kidney to form the active metabolite 1,25-dihydroxyvitamin D 3 . Vitamin D 2 (ergocalciferol) is derived solely from plant sources; relevant serum concentrations of 25-hydroxyvitamin D 2 are observed only after ingestion of vitamin D 2 drug preparations, and biological equivalence to vitamin D 3 has never been demonstrated conclusively.The prevalence of hypovitaminosis D has been recognized as substantial (2, 3 ), even in regions with high sun exposure (4 ), contributing not only to osteoporosis (5, 6 ) but possibly to a loss of muscle strength in aging as well (7 ).Various assays are used for the quantification of circulating 25-hydroxyvitamin D 3 that incorporate either vitamin D-binding globulin or anti-vitamin D antibodies for analyte recognition (8 -10 ). Fully automated tests have become available during recent years (11 ). Several HPLC methods with ultraviolet detection have been described as well (12,13 ), but their routine use is limited by complex sample preparation requirements.A key problem for the quantification of circulating 25-hydroxyvitamin D 3 is the strong binding of the molecule to vitamin D-binding globulin. Precipitation of serum constituents by use of organic solvents or acids can lead to variable coprecipitation of the analyte. Release of 25-hydroxyvitamin D 3 from its bonds to the binding protein is technically challenging in automated assays in particular. In light of these analytical problems, a reference method for the quantification of 25-hydroxyvitamin D 3 is desired to permit validation of routine immunoassays. Gas chromatography-mass spectrometry methods were developed years ago (14 -17 ), but they are extremely complex and did not gain use for quality-control programs or routine assay validation. Liquid chromatography-tandem mass spectrometry (LC-TMS) requires substantially less time-consuming sample clean-up and offers far shorter analytical run times than gas chromatographymass spectrometry. The feasibility of vitamin D quantification by LC-TMS was demonstrated previously (18 ), but the procedure included derivatization, which is complex and labor-intensive. Reference systems based on LC-MS were accepted in clinical chemistry recently (19,20 ), and we decided to develop a convenient and specific isotopedilution LC-TMS method for the quantification of 25-hydroxyvitamin D 3 in serum as a candidate reference method.For use as an internal standard, stable-isotope-labeled 25-hydroxyvitamin D 3 was synthesized as described previously (14, 17 ); the molecule contained three deuterium atoms and one 13 C atom. 25-Hydroxyvitamin D...
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