Nanocapsules, as a delivery system, are able to target drugs and other biologically sensitive molecules to specific cells or organs. This system has been intensively investigated as a way to protect bioactives drugs from inactivation upon interaction with the body and to ensure the release to the target. However, the mechanism of improved activity of the nanoencapsulated molecules is far from being understood at the cellular and subcellular levels. Epidemiological studies suggest that dietary polyunsaturated fatty acids (PUFA) can reduce the morbidity and mortality from breast cancer. This influence could be modulated by the oxidative status of the diet and it has been suggested that the anti-proliferative properties of docosahexaenoic acid (DHA) are enhanced by pro-oxidant agents. The effect of encapsulation of PUFA on breast cancer cell proliferation in different oxidative medium was evaluated in vitro. We compared the proliferation of the human breast cancer cell line MDA-MB-231 and of the non-cancer human mammary epithelial cell line MCF-10A in different experimental conditions. DHA possessed anti-proliferative properties that were prevented by alpha-tocopherol (an antioxidant) and enhanced by the pro-oxidant hydrogen peroxide that confirms that DHA has to be oxidized to exert its anti-proliferative properties. We also evaluated the anti-proliferative effects of the 4(RS)-4-F4t-neuroprostane, a bioactive, non-enzymatic oxygenated metabolite of DHA known to play a major role in the prevention of cardiovascular diseases. DHA-loaded nanocapsules was less potent than non-encapsulated DHA while co-encapsulation of DHA with H2O2 maintained the inhibition of proliferation. The nanocapsules slightly improves the anti-proliferative effect in the case of 4(RS)-4-F4t-neuroprostane that is more hydrophilic than DHA. Overall, our findings suggest that the sensitivity of tumor cell lines to DHA involves oxidized metabolites. They also indicate that neuroprostane is a metabolite participating in the growth reducing effect of DHA, but it is not the sole. These results also suggest that NC seek to enhance the stability against degradation, enhance cellular availability, and control the release of bioactive fatty acids following their lipophilicities.
Syntheses of the enantiomerically pure phytoprostanes B(1) type I and II are described starting from furfural and n-propylfuran. Key steps include the preparation of the Freimanis (+/-)-hydroxycyclopentenone and Wittig coupling using chiral phosphonium salts.
Pre-eclampsia is a complex disorder of pregnancy that adversely affects the mother and baby. Arachidonic acid and docosahexaenoic acid are essential for fetal development and can undergo free radical oxidation to F(2)-isoprostanes (F(2)-IsoPs) and isofurans (IsoFs); and F(4)-neuroprostanes (F(4)-NeuroPs), respectively. These metabolites may be relevant to pre-eclampsia and fetal development. We examined IsoFs, F(4)-NeuroPs, and F(2)-IsoPs in maternal plasma and cord blood plasma of 23 women with pre-eclampsia and 21 normal pregnancies. Women with pre-eclampsia had significantly elevated maternal IsoFs and F(4)-NeuroPs, but not F(2)-IsoPs. Cord blood F(4)-NeuroPs were elevated among neonates of women with pre-eclampsia. In women with pre-eclampsia, birth weight was predicted by gestation at delivery. The latter was also true in normal pregnancy, but birth weight was negatively related to maternal F(2)-IsoPs, IsoFs, and F(4)-NeuroPs. We have shown that in women with pre-eclampsia, IsoFs and F(4)-NeuroPs are elevated, and cord blood F(4)-NeuroPs are increased. The inverse relationship between maternal F(2)-IsoPs, IsoFs, and F(4)-NeuroPs and birth weight may be relevant as predictors of low birth weight in normal pregnancy. Future studies should examine whether these markers in maternal blood at early stages of pregnancy relate to subsequent maternal, fetal, and neonatal complications.
/? a science et ses prolongements dans le domaine de la technologie ne cessent de J*~> mettre l'homme d'aujourd'hui en demeure de repondre a des questions qu'il n'a pas encore eu le temps d'examiner dans toute leur complexite (on pense aux possibilites ouvertes par le sequencage du genome, a certaines manipulations genetiques, au clonage par exemple) et qui, le forcant a une redefinition de l'humain, mettent sa morale a rude epreuve. Notre monde accueille aujourd'hui sans enthousiasme, et parfois meme avec une mefiance agressive, un avenir rendu plus perilleux par la science et dont la conception n'a d'autre justification, en dernier lieu, que les diktats du marche. L'homme contemporain ressemble au marcheur qui, s'il sait tres bien ce qu'il laisse derriere lui, progresse en revanche sans horizon et sans carte. Il se decouvre a la fois une creation de la nature et une donnee statistique jusque dans son intelligence, sa morale et son organisation sociale1. Dans le contexte d'un questionnement inquiet qui touche a la definition de la communaute (ethnique ou mondialeles evenements derniers de Seattle lies a l'OMC [decembre 1999], les protestations a Washington [avril 2000] contre la Banque Mondiale et le FMI, celles, plus recentes, de Montreal [avril 2001] et la constitution, en France, d'un mouvement de defense, Attac,2 en 1998, montrent a quel point l'inquietude est reelle), voila un portrait un peu caricatural sans doute, mais que l'on se trouve neanmoins justifie a faire du Zeitgeist de notre epoque qui, justement, semble parfois ne plus en avoir (de Geist) ! Gilles Quinsat exprime bien cette inquietude : « Le temps propre a ce « nouveau monde » desorbite et par essence conflictuel est peut-etre ce qui est le plus difficile a penser » (991). A partir du passage, inquietant mais bien reel, du concept de citoyen et d'heritier culturel a celui de consommateur mondial (avec le changement concomitant des organismes decisionnaires), se posent ainsi de facon urgente la question de la place et de l'importance de la souverainete, mais aussi, force ne faisant pas loi, celle du principe unificateur de la mondialisation, c'est-a-dire de la conception qui preside a son developpement et qui decide de la valeur qu'il faut lui attribuer. Car si le materialisme de notre epoque jette un discredit certain sur ce qu'il en est de l'autonomie de l'homme par rapport a la matiere, et si les phagocytages culturels3, frequents dans un monde ou tout est commercialisable, le depouille de ce qu'il considerait apparemment a tort comme sa seule identite et le pousse a vouloir la
