Because T-cells play an important role in the pathological process of inflammatory diseases we investigated the effect of an aqueous Viola extract on lymphocyte functions and explored the ‘active’ principle of the extract using bioactivity-guided fractionation. Material Erastin inhibitor and Methods: An aqueous Viola extract was prepared by C-18 solid-phase extraction. Effects on proliferation of activated lymphocytes (using the cell membrane permeable fluorescein dye

CFSE), apoptosis and necrosis (using annexin V and propidium iodide staining), interleukin-2 (IL-2) receptor expression (using fluorochrome-conjugated antibodies) and IL-2 cytokine secretion (using an ELISA-based bead array system) were measured by flow cytometry. Influence on lymphocyte polyfunctionality was characterized by Viola extract-induced production of IFN-gamma and TNF-alpha, as well as its influence PD98059 solubility dmso on lymphocyte degranulation activity. Fractionation and phytochemical analysis of the extract were performed by RP-HPLC and mass spectrometry. Results: The aqueous Viola extract inhibited proliferation of activated lymphocytes by reducing IL-2 cytokine secretion without affecting IL-2 receptor expression. Similarly, effector functions were affected as indicated by the reduction of IFN-gamma and TNF-alpha production; degranulation capacity of activated lymphocytes

remained unaffected. Bioassay-guided fractionation and phytochemical analysis of the extract led to identification

of circular plant peptides, so called cyclotides, as bioactive components. Conclusion: An aqueous Viola extract contains bioactive cyclotides, which inhibit proliferation of activated lymphocytes in an IL-2 dependent manner. The findings provide a rationale for use of herbal Viola preparations in the therapy of disorders related to an overactive immune system. However, further studies to evaluate its clinical potency and potential risks have to be performed. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“In order to establish the environmental impact of an active pharmaceutical ingredient (API), good information on the level of exposure in surface waters is needed. Exposure concentrations are typically estimated BI 6727 using information on the usage of an API as well as removal rates in the patient, the wastewater system and in surface waters. These input data are often highly variable and difficult to obtain, so model estimates often do not agree with measurements made in the field. In this paper we present an approach which uses inverse modelling to estimate overall removal rates of pharmaceuticals at the catchment scale using a hydrological model as well as prescription and monitoring data for a few representative sites for a country or region. These overall removal rates are then used to model exposure across the broader landscape.