Klinische chemie voor iedereen: het Wikipedia-project

Public relations (PR) and information to patients are key goals of the Dutch Society of Clinical Chemistry (NVKC). In this paper several initiatives will be discussed that have been undertaken to meet this statement. The Wikipedia project is one of those initiatives in which information concerning clinical chemistry is added or revised to the Dutch version of the online encyclopaedia Wikipedia. Over 100 tests and items of clinical chemistry have been added or revised and are recognized as a separate category within this online encyclopaedia. Statistical analysis showed an increase in the number of visitors to these articles of Wikipedia. Furthermore, by adding and improving the available information, the quality of the information provided online is enhanced. In conclusion: the attribution of health care professionals to this public domain leads to enhanced access of high quality information for the main public to clinical chemistry in general and to specific laboratory blood tests

Hepcidin: analysis, regulation and clinical perspectives.

Contains fulltext : 71215.pdf (publisher's version ) (Open Access)The major aim of this thesis was the development of a high through-put assay for hepcidin in order to study the regulation of this peptide, and to gain knowledge on the role of hepcidin in iron metabolism. Chapter 2 presents a novel urinary hepcidin assay exploiting surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). This assay showed to have a strong correlation with the only pre-existing antibody-based dotblot assay. As described in chapter 3, further analytical improvement of this assay expanded the usability of hepcidin analysis also for serum samples and made it possible to determine associations with other iron related parameters, especially in patients with distorted iron metabolism. By using this serum hepcidin assay chapter 4 shows that insights on hepcidin regulation, foremost gained form in vitro cell culture and mice studies, can indeed be translated to the human in vivo model. Besides this, chapter 4 also describes an algorithm, based on biochemical serum parameters reflecting the main hepcidin regulators, which is capable to predict highly accurate the measured serum hepcidin levels. Chapter 5, shows a time-course analysis of urinary hepcidin, serum iron and plasma cytokine levels in a human endotoxemia experiment that defines the temporal associations between Interleukin 6, hepcidin and iron during inflammation. Using this endotoxemia model, next to hepcidin the contribution of nitric oxide (NO) in the development of hypoferremia was assessed with the use of aminoguanidine as specific inducible NO synthase (iNOS) inhibitor during acute inflammation, as described in chapter 6. Finally, the clinical use of hepcidin in the pre-screening of non-HFE hemochromatosis patients is described in chapter 7. These results indicate a potential role for hepcidin measurements in clinical practice which has to be explored more intensively in the near future.RU Radboud Universiteit Nijmegen, 7 maart 2008Promotor : Willems, J.L. Co-promotores : Swinkels, D.W., Tjalsma, H.127 p

Hepcidinemetingen in serum en urine met behulp van massaspectrometrie: analytische aspecten en klinische implicaties.

Contains fulltext : 53662.pdf (publisher's version ) (Open Access

Hepcidine: een ijzersterke biomarker?

Contains fulltext : 70063.pdf (publisher's version ) (Open Access

Reply to: [Comment to: Hepcidin: from discovery to differential diagnosis.]

Contains fulltext : 71180.pdf (publisher's version ) (Open Access

Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications.

Contains fulltext : 52294.pdf (publisher's version ) (Open Access)BACKGROUND: Discovery of the central role of hepcidin in body iron regulation has shed new light on the pathophysiology of iron disorders. Information is lacking on newer analytical approaches to measure hepcidin in serum and urine. Recent reports on the measurement of urine and serum hepcidin by surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) necessitate analytical and clinical evaluation of MS-based methodologies. METHODS: We used SELDI-TOF MS, immunocapture, and tandem MS to identify and characterize hepcidin in serum and urine. In addition to diagnostic application, we investigated analytical reproducibility and biological and preanalytical variation for both serum and urine on Normal Phase 20 and Immobilized Metal Affinity Capture 30 ProteinChip arrays. We obtained samples from healthy controls and patients with documented iron-deficiency anemia, inflammation-induced anemia, thalassemia major, and hereditary hemochromatosis. RESULTS: Proteomic techniques showed that hepcidin-20, -22, and -25 isoforms are present in urine. Hepcidin-25 in serum had the same amino acid sequence as hepcidin-25 in urine, whereas hepcidin-22 was not detected in serum. The interarray CV was 15% to 27%, and interspot CV was 11% to 13%. Preliminary studies showed that hepcidin-25 differentiated disorders of iron metabolism. Urine hepcidin is more affected by multiple freeze-thaw cycles and storage conditions, but less influenced by diurnal variation, than is serum hepcidin. CONCLUSION: SELDI-TOF MS can be used to measure hepcidin in both serum and urine, but serum requires a standardized sampling protocol

Hepcidin: from discovery to differential diagnosis.

Contains fulltext : 70062.pdf (publisher's version ) (Open Access)Although iron is essential for living organisms to survive, its reactive properties require strict regulation in order to prevent toxic effects. Hepcidin, a liver produced peptide hormone, is thought to be the central regulator of body iron metabolism. Its production is mainly controlled by the erythropoietic activity of the bone-marrow, the amount of circulating and stored body iron, and inflammation. Recent reports, however, provide new hypotheses on how hepcidin might exert its regulatory function. Although hepcidin was first discovered in human urine and serum, most of our understanding of hepcidin regulation and action comes from in vitro and mice studies that often use hepcidin mRNA expression as a read out. The difficulties in carrying out studies in humans have mostly been due to the lack of suitable hepcidin assay. The recent development of assays to measure hepcidin in serum and urine has offered new opportunities to study hepcidin regulation in humans. However, for the moment, only a small number of laboratories are able to perform these assays. The aim of this review is to discuss insights into hepcidin regulation obtained from recent clinical studies in the light of findings from in vitro and mice studies. Ongoing studies in humans should provide us with more information on the etiology of iron metabolism disorders in order to create new therapeutic strategies and improve differential diagnosis protocols for these diseases

Nitric oxide does not contribute to inflammation-induced hypoferremia in humans.

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Measuring serum hepcidin concentrations

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Regulation of hepcidin: insights from biochemical analyses on human serum samples.

Contains fulltext : 71205.pdf (publisher's version ) (Closed access)Knowledge of hepcidin regulation is foremost gained by in vitro studies. We aimed to translate this knowledge into the human in vivo situation. Therefore, we measured serum markers as transferrin saturation (TS), soluble transferrin receptor (sTfR), and C-reactive protein (CRP) in parallel with hepcidin and prohepcidin in patients with iron metabolism disorders and controls. To assess sTfR as erythropoietic activity-associated factor in hepcidin regulation, we studied its influence on hepcidin expression in HepG2 cells. Results showed that sTfR highly associates with erythropoietic activity that strongly interfered with the iron store regulation of hepcidin. HepG2 expression results display an inverse association between hepcidin and sTfR. Inflammation was strongly related to increased hepcidin levels regardless of the iron store and erythropoietic activity status. In contrast, prohepcidin failed to correlate to any other parameter. In conclusion, these studies verify that previous conclusions based on in vitro studies on hepcidin regulation are also likely to apply to human patients. This is underscored by a simple algorithm, based on parameters reflecting the main regulating pathways, that accurately predict the actual measured hepcidin levels. Future studies are needed to validate the combined utility of this predictive algorithm together with actual measured hepcidin levels in clinical diagnosis