16 research outputs found

    The natural organosulfur compound dipropyltetrasulfide prevents HOCL-induced systemic sclerosis in the mouse

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    PublishedArticleIntroduction: The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS) found in plants, which has antibiotic and anti-cancer properties, as a treatment of HOCl-induced systemic sclerosis in the mouse. Methods: The pro-oxidative, anti-proliferative and cytotoxic effects of DPTTS were evaluated ex vivo on fibroblasts from normal and HOCl-mice. In vivo, the anti-fibrotic and immunomodulating properties of DPTTS were evaluated in the skin and lungs of HOCl-mice. Results: H2O2 production was higher in fibroblasts derived from HOCl-mice than in normal fibroblasts (P<0.05). DPTTS did not increase H2O2 production in normal fibroblasts, but DPTTS dose-dependently increased H2O2 production in HOCl-fibroblasts (P<0.001 with 40μM DPTTS). Because H2O2 reached a lethal threshold in cells from HOCl-mice, the anti-proliferative, cytotoxic and pro-apoptotic effects of DPTTS were significantly higher in HOCl-fibroblasts than for normal fibroblasts. In vivo, DPTTS decreased dermal thickness (P<0.001), collagen content in skin (P<0.01) and lungs (P<0.05), SMA (P<0.01) and pSMAD2/3 (P<0.01) expression in skin, formation of advanced oxidation protein products and anti-DNA topoisomerase-1 antibodies in serum (P<0.05) versus untreated HOCl- mice. Moreover, in HOCl-mice, DPTTS reduced splenic B cell counts (P<0.01), the proliferative rates of B-splenocytes stimulated by lipopolysaccharide (P<0.05) and T-splenocytes stimulated by anti-CD3/CD28 mAb (P<0.001). Ex vivo, it also reduced the production of IL-4 and IL-13 by activated T cells (P<0.05 in both cases). Conclusions: The natural organosulfur compound DPTTS prevents skin and lung fibrosis in the mouse through the selective killing of diseased fibroblasts and its immunomodulating properties. DPTTS may be a potential treatment of Systemic sclerosis.This work was supported by European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement 215009 RedCat for financial support. The authors are grateful to Ms Agnes for her excellent typing of the manuscript

    The Influence of Amino Group Position on Aryl Moiety of SarAr on Metal Complexation and Protein Labelling

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    International audienceNew hexaazamacrobicyclic cage bi-functional chelators (BFCs), 1-N-(3-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (m-SarAr) and 1-N-(2-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (o-SarAr), were synthesised. Their complexation with selected transitions metal ions i.e. CuII, CoII, and CdII was investigated over a range of pH at micromolar concentrations. CuII was complexed by m-SarAr and o-SarAr rapidly within 5 min in pH range of 5–9 at ambient temperature. In contrast, the complexation of CoII and CdII by these ligands was slower. The conjugation efficiencies of p-SarAr, m-SarAr, and o-SarAr to bovine serum albumin (BSA) were compared under various reactions. Conditions were optimised to a molar ratio of BSA/N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC)/BFC of 1 : 250 : 50 in pH 5 buffer for 30 min at ambient temperature. Under these conditions, the average number of p-SarAr, m-SarAr, or o-SarAr attached to BSA were determined to be 2.21 ± 0.16, 4.90 × 10–1 ± 2.48 × 10–2, and 2.67 × 10–2 ± 2.67 × 10–3, respectively. This fundamental study clearly demonstrates that the position of the amine on the phenyl ring has a significant effect on the metal complexation and conjugation reactions with BSA

    Spectrally shaped light from supercontinuum fiber light sources

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    International audienceSupercontinuumfiberlightsources with their extremely wide wavelength spectrum can provide new options for achieving specific wavelength distributions in a very flexible way. Two concepts for the combination of such supercontinuumlightsources with a spectrally dispersive optical system and an interactive filter for modulating the light spectrum are discussed. These concepts provide the possibility to achieve laser-like lightsources with an almost arbitrary shape of the spectrum, great flexibility in interactive tuning of the spectral properties and covering wavelengths from UV to the infrared range
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