Key Points• Chemically modified nonanticoagulant heparins are strong inhibitors of hepcidin expression in normal and Bmp6 2/2 mice. • These heparins abolish hepcidin induction caused by LPS, a model of inflammation, and are candidates for treatment of inflammatory anemia.Hepcidin controls systemic iron availability, and its excess contributes to the anemia of chronic diseases, the most prevalent anemia in hospitalized patients. We previously reported that heparins are efficient hepcidin inhibitors both in vitro and in vivo, but their anticoagulant activity limits therapeutic use. We studied nonanticoagulant heparins produced by N-acetylation and oxidation/reduction (glycol-split) that lost antithrombinbinding affinity. Four nonanticoagulant heparins inhibited hepcidin expression in hepatic HepG2 cells and primary hepatocytes. The 2 most potent ones used in mice suppressed liver hepcidin expression and serum hepcidin in 6 hours, with a significant decrease of spleen iron. This occurred also in lipopolysaccharide (LPS)-treated animals that mimic inflammation, as well as after chronic 1-week treatments, without evident adverse effects on coagulation. Heparin injections increased iron mobilization and facilitated the recovery from the anemia induced by heat-killed Brucella abortus, a model of inflammatory anemia. The heparins were used also in Bmp6 2/2 mice. A single dose of heparin reduced the already low level of hepcidin of these mice and prevented its induction by LPS. These nonanticoagulant compounds impair bone morphogenetic protein /sons of mothers against decapentaplegic signaling with no evident adverse effect in vivo, even when administered chronically. They may offer a strategy for the treatment of diseases with high hepcidin levels. (Blood. 2014;123(10):1564-1573

The environmental interest of sulfonylurea herbicides was derived from the possibility of diffusion and penetration of these herbicides in the deepest layers of the ground, in particular in sandy or clay-poor soils, up to the ground waters; another interest of the study is their natural degradation pathway which leads to the formation of new species that are potentially more toxic and stable than the precursor herbicides. In this case, a lower persistence in the environment unfortunately does not correspond to a lower toxicity: hence, the importance of the identification of the species can be potentially formed. Here, nicosulfuron, a typical sulfonylurea herbicide, is considered in order to outline the environmental fate of the molecules generating from the simulation of one of the natural processes that can occur, i.e. photoinduced degradation. Aqueous nicosolfuron solutions underwent a simulated sun irradiation: the new species formed during the degradation process were identified by HPLC-DAD-MS/MS and a degradation pathway was proposed. The effect of temperature and the contribution of the hydrolysis were also evaluated. The use of ESI in both positive ion (PI) and negative ion (NI) mode and APCI in PI mode permits to obtain integrated information about the transformation products that can form; moreover, a study of the total ion chromatogram followed by the extraction of the SIM chromatograms of the most intense m/z signals made possible the identification of five possible photodegradation transformation products.

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Dedicated to Professor Jean-Claude Bünzli on the occasion of his 65th birthday Two new derivatives based on an s-triazine structural motif were synthesized by attaching two 2,2'-hydrazinylidenebis[acetic acid] moieties to the triazine ring to reach an overall heptadenticity for the complexation of lanthanide (III)