Determination of the contamination by azole antimycotics in hospital and house sewage - a pilot project for the city of Dresden.

Medicininal compounds and their metabolites are known to end up in sewerage and may slip through the cleaning process. Azole antimycotics are frequently used in hospitals, in particular for patients with cancer or immunosuppression. The aim of the study was to determine whether measurable azole antimycotic concentrations were introducted in the sewarage drain of an acute care hospital with special interest in oncology and hematology and the extent of removal of antimycotics by the sewerage treatment plant. For this, the concentrations of three commonly used azole antimycotics were measured in the effluent of the sewerage drain at the University Hospital Dresden, as well as in the influent and effluent of the main sewerage treatment plant of the city. To extrapolate the theoretical influent to the sewerage treatment plant, prescription from the regio`s main health insurance the AOK Sachsen and the hospital consumption data were used. Measurable concentrations were obtained for fluconazole and ketoconazole in the influent and effluent of the sewerage treatment plant. Voriconazole's concentrations were under the lower limit of quantification. To determine the azole clearance of the treatment plant a sludge sample was investigated. Sufficient clearance was detected for ketoconazole but not for fluconazole. The consumption and prescription rates were collected and correlated with the measured concentrations. In result, only fluconazole's concentrations provided a good match with the prescription and consumption data.

GPR56 contributes to the development of acute myeloid leukemia in mice.

The G protein-coupled receptor 56 (GPR56) was identified as part of the molecular signature of functionally validated leukemic stem cells isolated from patients with acute myeloid leukemia (AML). This report now demonstrates particularly high expression of GPR56 in patients with mutant NPM1 and FLT3-length mutation and association of high GPR56 expression with inferior prognosis in a large patient cohort treated in two independent multicenter phase III trials. Functional relevance of GPR56 expression was validated in mice, in which co-expression of Gpr56 significantly accelerated HOXA9-induced leukemogenesis and vice versa knockdown of Gpr56 delayed onset of HOXA9/MEIS1-induced AML. Overexpression of Gpr56 grossly changed the molecular phenotype of Hoxa9-transduced cells affecting pathways involved in G protein-coupled receptors (GPRCs) and associated intracellular signaling. Blockage of surface GPR56 by an anti-GPR56 antibody successfully impaired engraftment of primary human AML cells. In summary, these data demonstrate that high expression of GPR56 is able to contribute to AML development and characterize the GPR56 as a potential novel target for antibody-mediated antileukemic strategies.