22 research outputs found
Efficiency review of Austria’s social insurance and healthcare system: volume 1 – international comparisons and policy options
In 2016, the London School of Economics and Political Science (LSE Health) was engaged by the Austrian Ministry of Labour, Social Affairs and Consumer Protection to undertake an efficiency review of the country’s social insurance system (see Appendix A for the original Concept Note). The review was specifically targeted at health competencies within the social insurance system; for this reason, consideration of accident and pension insurance, as well as other forms of care covered by Federal and Länder governments, were only examined where directly applicable
Combination Effects of (Tri)Azole Fungicides on Hormone Production and Xenobiotic Metabolism in a Human Placental Cell Line
Consumers are exposed to multiple residues of different pesticides via the diet. Therefore, EU legislation for pesticides requires the evaluation of single active substances as well as the consideration of combination effects. Hence the analysis of combined effects of substances in a broad dose range represents a key challenge to current experimental and regulatory toxicology. Here we report evidence for additive effects for (tri)azole fungicides, a widely used group of antifungal agents, in the human placental cell line Jeg-3. In addition to the triazoles cyproconazole, epoxiconazole, flusilazole and tebuconazole and the azole fungicide prochloraz also pesticides from other chemical classes assumed to act via different modes of action (i.e., the organophosphate chlorpyrifos and the triazinylsulfonylurea herbicide triflusulfuron-methyl) were investigated. Endpoints analysed include synthesis of steroid hormone production (progesterone and estradiol) and gene expression of steroidogenic and non-steroidogenic cytochrome-P-450 (CYP) enzymes. For the triazoles and prochloraz, a dose dependent inhibition of progesterone production was observed and additive effects could be confirmed for several combinations of these substances in vitro. The non-triazoles chlorpyrifos and triflusulfuron-methyl did not affect this endpoint and, in line with this finding, no additivity was observed when these substances were applied in mixtures with prochloraz. While prochloraz slightly increased aromatase expression and estradiol production and triflusulfuron-methyl decreased estradiol production, none of the other substances had effects on the expression levels of steroidogenic CYP-enzymes in Jeg-3 cells. For some triazoles, prochloraz and chlorpyrifos a significant induction of CYP1A1 mRNA expression and potential combination effects for this endpoint were observed. Inhibition of CYP1A1 mRNA induction by the AhR inhibitor CH223191 indicated AhR receptor dependence this effect
Science-based decision matrix for the identification of endocrine disruptors for regulatory purposes
Identification of Targeting Peptides for Mucosal Delivery in Sheep and Mice
In this study we identified and characterized
a novel cyclic peptide
that facilitates the rapid transportation of conjugated molecules
across the epithelial layer of the small intestine. The peptide was
initially selected from phage display libraries using a large animal
experimental model, which employed consecutive in vitro and in vivo
panning. The procedure was designed to enrich for peptides that facilitated
transcytosis across the intestinal epithelium into the intestinal
afferent lymphatic system. A small set of peptides was repeatedly
isolated using this selection method; however, the cyclic nonamer
CTANSSAQC, 13C, dominated. The activity of the putative targeting
peptide 13C was then verified using a mouse model. These experiments
showed that the 13C peptide as well as macromolecules conjugated to
it were rapidly transported across the intestinal mucosa into distinct
subsets of epithelial cells and CD11c+ cells located in the lamina
propria and Peyer’s Patches. Significant amounts of intact
protein could be delivered into the systemic circulation after rectal
and nasal application. Thus, peptide 13C is regarded as an attractive
carrier candidate for mucosal delivery of large molecules. The preferential
targeting to distinct intestinal cells may be utilized to deliver
active biological drugs for the effective control of diseases of the
gut