European journal of clinical investigation
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Eur. J. Clin. Invest. · Aug 2006
ReviewEmerging role of a phosphatonin in mineral homeostasis and its derangements.
The study of a distinct group of renal phosphate wasting disorders with bone disease which comprise X-linked hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets (ADHR) and tumour-induced osteomalacia (TIO) gave rise to the identification of different hormone-like peptides, also known as phosphatonins. These factors are responsible for the major disease features that characterize XLH, ADHR and TIO. Recent reports on one of these phosphatonins, fibroblast growth factor-23 (FGF-23), point to a general role of this factor in mineral ion metabolism. ⋯ The FGF-23 has been shown to increase urinary phosphate excretion, inhibit bone mineralization and suppress 1,25-dihydroxy vitamin D(3)[1,25(OH)(2)D(3)], the main characteristics that XLH, ADHR and TIO have in common. Apart from its role in these phosphate wasting disorders serum FGF-23 is elevated in hypoparathyroidism and humoral hypercalcaemia of malignancy and responds to altered dietary phosphate and calcium supply in healthy subjects. The FGF-23 is also variably elevated in chronic kidney disease and associated secondary hyperparathyroidism where it correlates positively with serum phosphate and parathyroid hormone and negatively with 1,25(OH)(2)D(3). Such relationships, along with data from experimental studies, raise the question of whether FGF-23 contributes to the pathophysiology of chronic kidney disease.
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Eur. J. Clin. Invest. · Jul 2006
Cardiac troponin I and ventricular arrhythmia in patients with chronic heart failure.
Both detectable serum cardiac troponin I (cTnI) and ventricular dysrhythmias are common in patients with chronic heart failure (CHF) and are paralleled with the severity of the CHF. However, the relationship between serum cTnI and ventricular arrhythmia severity in patients with CHF remains unknown; the mechanism of the ventricular arrhythmia in the CHF patients also remains unclear. ⋯ In patients with CHF, serum cTnI is closely related to increased occurrence of ventricular dysrhythmias and could identify a subgroup of patients with ventricular tachycardia. The minimal myocardial injury detected by serum cTnI might be the abnormal substrate for ventricular dysrhythmias.
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Eur. J. Clin. Invest. · May 2006
CREB transcription factor modulates Bcl2 transcription in response to C5a in HL-60-derived neutrophils.
Complement fragment C5a and neutrophils have been implicated in the pathogenesis of renal disease and C5a has also been shown to delay apoptosis of human neutrophils via a transcription-independent pathway. However, transcription-dependent pathways have not been well described. The present study examined whether activation of HL-60-derived neutrophils by C5a modulates the transcription of two members of the Bcl2 family, Bax (pro-apoptotic) and Bcl2 (anti-apoptotic) molecules, and whether the cAMP-response element-binding protein (CREB) transcription factor mediates these effects through the phosphatidylinositol 3-kinase (PI3K)/Akt and extra-cellular signal-regulated kinase (ERK) signalling pathways. ⋯ This study demonstrates that C5a induces Bcl2 mRNA transcription in HL-60-derived neutrophils, which is mediated in part by CREB through the convergence of the PI3K/Akt and ERK-signalling pathways.
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Eur. J. Clin. Invest. · May 2006
Exhaled markers of oxidative stress in idiopathic pulmonary fibrosis.
Expired breath condensate (EBC) has never been used to explore the level of oxidative stress in idiopathic pulmonary fibrosis (IPF). Therefore, the aim of this study was to measure the levels of H2O2 and 8-isoprostane, as biomarkers of oxidative stress, in the EBC of patients with IPF. ⋯ Our data suggest that H2O2 and 8-isoprostane are increased in the EBC of patients with IPF. H2O2 may be correlated with the severity of the disease in IPF.
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When analyzing human cellular immune responses, most focus is placed on the peripheral blood (PB) and, to a lesser extent, the lymph nodes. To date the spleen has not been analyzed with regard to its role in adaptive cellular immunity and more notably not with respect to T-cell immune responses. ⋯ Our findings show that the distribution of the different lymphocyte subsets is markedly different between the spleen and the PB, thus inferring an important and distinct role for the spleen in CD4(+) and CD8(+) T-cell activation.