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Summary: The diagnosis and management of hyponatremia can be intimidating, for both trainees and clinicians alike. We present five clinical scenarios of patients with hyponatremia. These discussions reinforce concepts reviewed elsewhere in this issue of Seminars in Nephrology and/or emphasize specific causes and management issues. [ABSTRACT FROM AUTHOR]

Selectin-mediated leukocyte adhesion to endothelia, the crucial first step initiating the pathogenic cascade of inflammation, is an attractive target for specific therapies. The small-molecule macrolide, efomycine M, inhibits selectin-mediated leukocyte adhesion in vitro and in vivo, and effectively alleviates inflammatory disorders in vivo. To define the molecular basis of the therapeutically relevant antiadhesive properties of efomycines, several new species of this family were purified and/or synthesized. Efomycines E and G were isolated from Steptomyces BS1261. Efomycine O was synthesized by Lewis acid-catalyzed acetalization and efomycine M was generated by base-catalyzed deglycosylation. Efomycine S resulted from ester cleavage of the macrolide ring system, and efomycine T represents the peracetylated form of efomycine M. When the functional activity of efomycines on adhesion of leukocytes to vascular endothelium was studied, some remarkable differences between the compounds became apparent, inasmuch as efomycines E, G, M, and O significantly inhibited adhesion of both human and porcine leukocytes to the vascular endothelium, whereas efomycines S and T did not show any biological activity. A novel docking engine (ProPose), generating an improved, fully configurable protein–ligand interaction model, demonstrated that biological activities of efomycines can be predicted in silico, thus highlighting the utility of such combinatorial approaches.Journal of Investigative Dermatology (2006) 126, 882–889. doi:10.1038/sj.jid.5700159; published online 26 January 2006 [ABSTRACT FROM AUTHOR]

Liquid biopsy holds great promise to complement traditional analysis on cancerous tissue during clinical management of cancer: screening of patients, (early) disease diagnosis, prognosis, therapy selection as well as early response to treatment and disease monitoring. Among emerging circulating biomarkers, cell-free miRNA (cfmiRNA) may have potential in detecting lung cancer and following the course of the disease. Furthermore, several studies highlighted the possibility to utilize these regulatory RNAs to obtain prognostic information as well as to verify patient's response towards treatment. However, despite these findings, cfmiRNA is not used in the clinical practice as biomarkers to date, since their clinical utility and validity has not been confirmed in prospective clinical studies yet. In addition, there is no consensus on standardized (pre)analytical procedures. In this review, we present an overview of cfmiRNA biomarker candidates for clinical management of lung cancer and we discuss the issue of assay standardization. [ABSTRACT FROM AUTHOR]

Background: In this study we analyzed putative biomarkers for myocardial remodeling in plasma from 55 endstage heart failure patients with the need for mechanical circulatory support (MCS). We compared our data to 40 healthy controls and examined if MCS by either ventricular assist devices or total artificial hearts has an impact on plasma concentrations of remodeling biomarkers. Methods & Results: Plasma biomarkers were analysed pre and 30 days post implantation of a MCS device using commercially available enzyme linked immunosorbent assays (ELISA). We observed that the plasma concentrations of remodeling biomarkers: tissue inhibitor of metalloproteinase 1 (TIMP1), tenascin C (TNC), galectin 3 (LGALS3), osteopontin (OPN) and of neurohumoral biomarker brain natriuretic peptide (BNP), are significantly elevated in patients with terminal heart failure compared to healthy controls. We did not find elevated plasma concentrations for matrix metalloproteinase 2 (MMP2) and procollagen I C-terminal peptide (PCIP). However, only BNP plasma levels were reduced by MCS, whereas the concentrations of remodeling biomarkers remained elevated or even increased further 30 days after MCS. LGALS3 plasma concentrations at device implantation were significantly higher in patients who did not survive MCS due to multi organ failure (MOF). Conclusions: Our findings indicate that mechanical unloading in endstage heart failure is not reflected by a rapid reduction of remodeling plasma biomarkers. [Copyright &y& Elsevier]