Comprendre l'opposition parlementaire: le Parlement de Paris face aux réformes de Silhouette (1759)

The aim of this article is to reconsider the fiscal interpretation of opposition parlementaire to government policy. First, it suggests that the meaning of the remonstrances is blurred by specific constraints which make it very difficult to interpret these texts. Second, it analyses a variety of documents relating to Silhouette’s fiscal projects (1759) and shows that the real objective of the Parlement of Paris, which was never mentioned in its remonstrances, was to finance the Seven Years’ War by issuing paper-money. This reading reveals the influence of the British model of State finance, especially on the critical issue of credit, on both ministers and magistrates. In spite of this common reference, the government and the Parlement of Paris diverged in their reading of the fiscal crisis, and the political culture of the monarchy prevented the formation of a workable consensus.

Polysialic acid as a drug carrier: evaluation of a new polysialic acid–epirubicin conjugate and its comparison against established drug carriers

This paper explores the potential of polysialic acid (PSA) as a carrier for low molecular weight anticancer drugs. A PSA–epirubicin (Epi) conjugate was synthesized and compared against Epi conjugates containing established carriers, namely: N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers, poly(ethylene glycol) (PEG) and polyglutamic acid (PGA). Biological assessments in the breast cancer cell line MCF-7 and in the anthracycline resistant MCF-7/DX showed that the PSA–Epi conjugate had the highest activity (40% and 30% cell death in the two cell lines at 1 mM Epi equiv., respectively). FACS studies confirmed internalization of all conjugates by cholesterol-dependent endocytosis. PSA–Epi showed release of Epi (40% at 5 h) when incubated with lysosome extracts. In vivo evaluation showed that all conjugates had a significantly longer half-life compared to free Epi. This study also allowed an investigation on the effect of the polymeric carrier on the biological activity of a conjugate, with the biodegradability of the carrier emerging as an important feature.