Low hepcidin levels in severely anemic malawian children with high incidence of infectious diseases and bone marrow iron deficiency.

INTRODUCTION: A reliable diagnostic biomarker of iron status is required for severely anemic children living in malarious areas because presumptive treatment with iron may increase their infection risk if they are not iron deficient. Current biomarkers are limited because they are altered by host inflammation. In this study hepcidin concentrations were assessed in severely anemic children living in a highly malarious area of Malawi and evaluated against bone marrow iron in order to determine the usefulness of hepcidin as a point of care test. METHODS: 207 severely anemic children were assessed for levels of hepcidin, ferritin, serum transferrin receptor, erythropoietin, hematological indices, C-reactive protein, interleukin-6, malaria parasites and HIV infection. Deficiency of bone marrow iron stores was graded and erythroblast iron incorporation estimated. Interaction of covariates was assessed by structural-equation-modeling. RESULTS AND CONCLUSION: Hepcidin was a poor predictor of bone marrow iron deficiency (sensitivity 66.7%; specificity 48.5%), and of iron incorporation (sensitivity 54.2%; specificity 61.8%), and therefore would have limitations as a point of care test in this category of children. As upregulation of hepcidin by inflammation and iron status was blunted by erythropoietin in this population, enhanced iron absorption through the low hepcidin values may increase infection risk. Current recommendations to treat all severely anemic children living in malarious areas with iron should therefore be reconsidered.

Erythropoietin treatment in patients with combined heart and renal failure: objectives and design of the EPOCARES study.

BACKGROUND: Anemia is common in patients with the combination of chronic heart failure and chronic kidney disease and is associated with increased mortality. Recent clinical studies suggest that recombinant human erythropoietin (EPO) treatment has desirable as well as undesirable effects, related to its hematopoietic or nonhematopoietic effects. Therefore a translational study is needed to elucidate mechanistic aspects of EPO treatment. METHODS: In this open-label randomized 12-month trial (the Mechanisms of Erythropoietin Action in the Cardiorenal Syndrome [EPOCARES]), patients with the combination of chronic heart failure and chronic kidney disease (glomerular filtration rate 20-70 ml/min) and mild anemia (hemoglobin 10.3-12.6 g/dL in men, and 10.3-11.9 g/dL in women) are being randomized into 3 groups: 1 group (n=25) receives a fixed dose of 50 IU/kg per week EPO to increase hemoglobin level to a maximum of 13.7 g/dL for men and 13.4 g/dL for women; another group (n=25) is treated with 50 IU/kg per week EPO maintaining baseline hemoglobin levels for the first 6 months by phlebotomy. The control group (n=25) receives standard care without EPO. RESULTS: Cardiac and renal function as well as a panel of biomarkers and iron parameters are being assessed. Furthermore, the effects of EPO on monocyte gene expression profiles and on endothelial progenitor cells are being evaluated. CONCLUSION: This translational study is designed primarily to discern hematopoietic from nonhematopoietic effects of EPO in cardiorenal patients. The study will add insights into the mechanisms that could explain the fragile balance between desirable and undesirable effects of EPO (Trial registration: ClinicalTrials.gov identifier NCT00356733).

Benefits of the iQ200 automated urine microscopy analyser in routine urinalysis.

BACKGROUND: Urine microscopic analysis is hampered by its lack in standardisation and semi-quantitative reports, resulting in limited reliability. Automation of urinalysis could overcome these problems. METHODS: We compared the performance of the iQ200 with traditional microscopy and strip analysis in routine urinalysis. A total of 1482 routine samples, positive in dipstick testing, were evaluated for erythrocytes, leukocytes, casts, dysmorphic erythrocytes and bacteria using the iQ200 and traditional microscopy. The results of 320 of these samples were linked to underlying urological pathology as well as results from bacterial culturing. RESULTS: Analytically, the iQ200 surpasses traditional microscopy. The identification of casts and dysmorphic erythrocytes in routine samples improves when using the iQ200, although the sub-classification of casts required well-trained technicians. The auto-classification of particles was least reliable for yeast and bacterial cocci. The quantitative reports, and therefore the use of precise cut-off points allowed earlier and improved detection of urinary tract pathology. CONCLUSIONS: The performance of the iQ200 is equal to traditional microscopy, but it strongly improves the reliability of urinalysis by standardisation, quantitative reports and improved workflow. From a clinical point of view, renewed attention and improvement of routine urinalysis aids in the efficient detection of renal and urinary tract pathology.

Polyphenolic grape extract inhibits platelet activation through PECAM-1: an explanation for the French paradox.

BACKGROUND: Moderate and prolonged consumption of red wine is associated with decreased cardiovascular morbidity and mortality. Inhibition of platelet functions by ingredients in red wine is thought to be one of the causes. However, the molecular mechanism of this inhibition has remained unexplained. MATERIALS AND METHODS: We measured aggregation, changes in cytosolic Ca(2+) and tyrosine phosphorylation of the inhibitory receptor platelet endothelial cell adhesion molecule-1 (PECAM-1) in platelets stimulated with thrombin receptor (PAR-1) activating peptide (TRAP) and ADP and investigated the effects of alcohol-free polyphenolic grape extract (PGE), alcohol, and the polyphenols catechin, epi-catechin, resveratrol, trans-resveratrol, and gallic acid. RESULTS: Polyphenolic grape extract induced dose-dependent inhibition of TRAP-induced and ADP-induced platelet aggregation and Ca(2+) mobilization. Inhibition was accompanied by activation of PECAM-1. Apart from a slight inhibition by catechin, ethanol or other individual polyphenols failed to inhibit aggregation or activate PECAM-1. CONCLUSIONS: Red wine inhibits platelet functions through its PGE content, which stimulates the inhibitory receptor PECAM-1, thereby attenuating platelet activation.

Rapid intake of alcohol (binge drinking) inhibits platelet adhesion to fibrinogen under flow.

BACKGROUND: Moderate alcohol consumption is associated with decreased mortality from cardiovascular disease. Drinking large amounts in a short period (binge drinking) is associated with increased cardiovascular morbidity. We tested whether rapid consumption of a large dose of alcohol affects platelet aggregation and adhesion. METHODS: Healthy volunteers (n = 20) were asked to drink three glasses of alcohol or red wine in a 45-min period. Thereafter, another 45 min was allowed for absorption of alcohol. Ninety minutes after the start of the experiment, blood was collected. This entire cycle was repeated once, resulting in consumption of six alcohol-containing drinks in 3 hr. Adenosine-diphosphate (ADP)-induced aggregation was measured and platelet adhesion to fibrinogen and collagen was measured in a perfusion chamber at shear rates of 300/sec and 1600/sec. Platelet coverage and aggregate size were measured. RESULTS: Acute alcohol intake significantly increased platelet aggregation in suspension when stimulated with low concentrations of ADP (0.1 and 0.5 microg/ml). This effect was not observed when consuming red wine. In contrast, adhesion to fibrinogen was significantly inhibited by alcohol but not red wine at high shear rate after six drinks (p = 0.025). The inhibition was accompanied by a reduction in aggregate size at 90 and 180 min after the start of the experiment. Adhesion to collagen was not altered by either alcohol or red wine. CONCLUSIONS: Rapid intake of alcohol increases platelet aggregation, which might contribute to the increased mortality associated with binge drinking. Red wine does not show increased platelet aggregation, which might support the reduction of cardiovascular disease in red wine consumers. However, alcohol inhibits platelet adhesion to fibrinogen-coated surface under flow. The diminished adhesion might contribute to the cardioprotective effects of alcohol.