High rate of intestinal absorption of the phospholipid analogue 1-dodecyl 2-(1-14C) octanamido-sn-2-deoxy-glycero-3-phosphocholine in the rat

International audienc

Dissociate arachidonic acid release from eicosanoid synthesis in rat peritoneal macrophages is possible using concomitantly eicosapentanoic acid and a phospholipid analogue

International audienc

Uptake of the phospholipase A2 inhibitor 1-dodecyl 2-(1-14C) octanamido-sn-2-deoxyglycero-3-phosphocholine by peritoneal macrophages

International audienc

Studies on lipidomimetic derivatives of α-difluoromethylornithine (DFMO) to enhance the bioavailability in a

DFMO, a trypanostatic drug, presents a satisfactory intestinal absorption but its elimination from the blood is rapid so that high doses are necessary to obtain a therapeutic effect. In this study, we propose a strategy to enhance the bioavailability of DFMO by using lipidomimetic derivatives. Three lipidomimetic DFMO derivatives called ODFMO, S-DFMO and Chol-DFMO were designed to reach easily the plasma and to be cleaved preferentially by plasma esterases progressively liberating free DFMO. Chol-DFMO only could be cleaved partially whereas the other compounds appeared to be stable in a reconstituted intestinal medium and mouse plasma. Nevertheless, the use of DFMO derivatives in T. b. brucei experimental chemotherapy appeared as an interesting approach. Thus, ODFMO was trypanocidal in vitro whereas DFMO, the active principle, was only trypanostatic. Nevertheless, this compound did not release DFMO in mouse blood as expected and acted therefore not as a prodrug. Oral treatment using low doses of compound O-DFMO was able to cure 40 % mice while the active principle (eflornithine) administered at 50 fold higher molarity failed to cure any mice. This indicates that compound ODFMO acts by a specific mechanism which remains to be investigated. S-DFMO was less active and Chol-DFMO had no in vitro activity but released small amounts of DFMO in mice, however, too slight to obtain a therapeutic effect

Calmness properties and contingent subgradients of integral functionals on Lebesgue spaces Lp, 1≤ p < ∞

International audienc

Discontinuation of first-line disease-modifying therapy in relapse onset multiple sclerosis

BACKGROUND: It is not known if and when first-line disease modifying therapy (DMT) can safely be discontinued in relapse onset multiple sclerosis (MS) patients. OBJECTIVES: To investigate the characteristics of patients who discontinued first-line DMT, and the occurrence of clinical and radiological inflammatory disease activity after discontinuation. METHODS: We collected clinical and MRI parameters from patients with relapse onset MS in the MS Center Amsterdam and Rijnstate Hospital Arnhem who discontinued first-line DMT with no intention of restarting or switching treatment. RESULTS: In total, 130 patients were included in the analyses. After discontinuation, 78 patients (60%) experienced disease activity. Sixty-three patients (48.5%) showed MRI activity after DMT discontinuation, 40 patients (30.8%) experienced relapse(s), and 29 patients (22.3%) restarted DMT. Higher age at DMT discontinuation was associated with a lower risk of MRI activity (45 -55 vs. 55 vs. 55 vs. <45 years: OR=0.081, p = 0.020). CONCLUSION: Higher age at first-line DMT discontinuation is associated with lower risk and severity of radiological disease activity in MS, and a lower risk of relapse(s) after discontinuation