Assessing the Accuracy of Sales Forecasts Submitted by Pharmaceutical Companies Applying for Reimbursement in Austria.

Reimbursement decisions on new medicines require an assessment of their value. In Austria, when applying for reimbursement of new medicines, pharmaceutical companies are also obliged to submit forecasts of future sales. We systematically examined the accuracy of these pharmaceutical sales forecasts and hence the usefulness of these forecasts for reimbursement evaluations.

Policies for biosimilar uptake in Europe: An overview.

Background: Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe.

Objectives: The aim of this article is to provide an overview of different initiatives and policies that may influence the uptake of biosimilars in different European countries. Recommendations will be formulated on how to create sustainable uptake.

[Polypharmacy--activities of the social insurance in Austria].

In Austria, about a quarter of the population older than 60 years receives more than five medicines per quarter at the expense of the statutory health insurance. Especially for older and multimorbid people the risk of adverse drug reactions increases by taking multiple drugs. The social insurance has initiated activities to direct the focus on the issue of polypharmacy and the associated problems.

Recruitment of a cytoplasmic chaperone relay by the A2A adenosine receptor.

The adenosine A2A receptor is a prototypical rhodopsin-like G protein-coupled receptor but has several unique structural features, in particular a long C terminus (of >120 residues) devoid of a palmitoylation site. It is known to interact with several accessory proteins other than those canonically involved in signaling. However, it is evident that many more proteins must interact with the A2A receptor, if the trafficking trajectory of the receptor is taken into account from its site of synthesis in the endoplasmic reticulum (ER) to its disposal by the lysosome.

Reengineering the collision coupling and diffusion mode of the A2A-adenosine receptor: palmitoylation in helix 8 relieves confinement.

The A(2A)-adenosine receptor undergoes restricted collision coupling with its cognate G protein G(s) and lacks a palmitoylation site at the end of helix 8 in its intracellular C terminus. We explored the hypothesis that there was a causal link between the absence of a palmitoyl moiety and restricted collision coupling by introducing a palmitoylation site. The resulting mutant A(2A)-R309C receptor underwent palmitoylation as verified by both mass spectrometry and metabolic labeling.

Expression of G protein-coupled receptor 19 in human lung cancer cells is triggered by entry into S-phase and supports G(2)-M cell-cycle progression.

It has long been known that G protein-coupled receptors (GPCR) are subject to illegitimate expression in tumor cells. Presumably, hijacking the normal physiologic functions of GPCRs contributes to all biologic capabilities acquired during tumorigenesis. Here, we searched for GPCRs that were expressed in lung cancer: the mRNA encoding orphan G protein-coupled receptor 19 (GPR19) was found frequently overexpressed in tissue samples obtained from patients with small cell lung cancer.

From cradle to twilight: the carboxyl terminus directs the fate of the A(2A)-adenosine receptor.

The extended carboxyl terminus of the A(2A)-adenosine receptor is known to engage several proteins other than those canonically involved in signalling by GPCRs (i.e., G proteins, G protein-coupled receptor kinases/GRKs, arrestins).

Restricted collision coupling of the A2A receptor revisited: evidence for physical separation of two signaling cascades.

The A(2A)-adenosine receptor is a prototypical G(s) protein-coupled receptor but stimulates MAPK/ERK in a G(s)-independent way. The A(2A) receptor has long been known to undergo restricted collision coupling with G(s); the mechanistic basis for this mode of coupling has remained elusive. Here we visualized agonist-induced changes in mobility of the yellow fluorescent protein-tagged receptor by fluorescence recovery after photobleaching microscopy.