Dietary regulation of copper absorption and storage in rats: effects of sodium,zinc and histidine-zinc.

Zinc (Zn) and L-histidine (His) are known competitors of intestinal copper (Cu) uptake. Sodium (Na) appears to be an enhancer of the luminal phase of Cu absorption. We investigated whether dietary treatment with these modifiers would alter Cu absorption and tissue stores of Zn and Cu in rats. Juvenile male rats were fed semipurified diets with adequate amounts of Cu, Zn and Na (Ctl), or with the addition of either excess Na (Hi Na), Zn (Hi Zn), or Zn plus His (Hi Zn+His) for 3 weeks. The jejunum was perfused in situ with 0.1 mM Cu, 1 mM His to determine Cu and water absorption rates. The lowest Cu absorption rate was observed in the Hi Zn+His group, and both the Hi Zn and Hi Zn+His had greater Cu accumulation in the small intestine than did Ctl or Hi Na rats. Hi Na had no effect on Cu transport. There was excess Cu accumulation in the kidneys of Hi Zn+His rats, and hepatic and kidney metallothioneins were also elevated. These results indicate that while a high Na intake does not affect Cu absorption, excess dietary Zn and His have greater effect than does Zn only in the limitation of Cu uptake.     

An important risk factor in idiopathic generalized epilepsies

15q13.3 microdeletions increase risk of idiopathic generalized epilepsy
Helbig et al. (2009)
Nature Genetics 41(2):160–162     

Collagen induced MMP-2 activation in human breast cancer

Summary Matrix metalloproteinase-2 (MMP-2), a zymogen requiring proteolytic activation for catalytic activity, has been implicated broadly in the invasion and metastasis of many cancer model systems, including human breast cancer (HBC). MMP-2 has been immunolocalized to carcinomatous human breast, where the degree of activation of MMP-2 correlates well with tumor grade and patient prognosis. Using Matrigel assays, we have stratified HBC cell lines for invasivenessin vitro, and compared this to their potential for metastatic spread in nude mice. HBC cell lines expressing the mesenchymal marker protein vimentin were found to be highly invasivein vitro, and tended to form metastases in nude mice. We have further discovered that culture on collagen-I gels (Vitrogen^TM; Vg) induces MMP-2-activator in highly invasive but not poorly invasive HBC cell lines. As seen for other MMP-2-activator inducing regimens, this induction requires protein synthesis and an intact MMP-2 hemopexin-like domain, appears to be mediated by a cell surface activity, and can be inhibited by metalloproteinase inhibitors. The induction is highly specific to collagen I, and is not seen with thin coatings of collagen I, collagen IV, laminin, or fibronectin, or with 3-dimensional gels of laminin, Matrigel, or gelatin. This review focuses on collagen I and MMP-2, their localization and source in HBC, and their relationship(s) to MMP-2 activation and HBC metastasis. The relevance of collagen I in activation of MMP-2in vivo is discussed in terms of stromal cell: tumor cell interaction for collagen I deposition, MMP-2 production, and MMP-2-activation. Such cooperativity may existin vivo for MMP-2 participation in HBC dissemination. A more complete understanding of the regulation of MMP-2-activator by type I collagen may provide new avenues for improved diagnosis and prognosis of human breast cancer.     

Assessment of an abbreviated odorant identification task for children: a rapid screening device for schools and clinics

To validate the level of olfactory performance of children, we tested 825 volunteers, aged 4–17 years, with an abbreviated form of our pediatric odorant identification task. The test consisted of sniffing and identifying five odorants (baby powder, bubble gum, candy cane, licorice and peach). Mean olfactory scores increased as a function of age, reaching a plateau of about 94–95% correct at 8 years of age. In general, girls out–performed boys. Physicians require a test instrument such as the one we have devised to allow them to diagnose olfactory dysfunction in children. The present task is particularly applicable in screening large numbers of children in clinics or schools because it can be administered easily and rapidly. Adult subjects with olfactory dysfunction also performed poorly on this odorant identification task designed for children. Therefore, we expect that our odorant identification task will also detect children with severe olfactory dysfunction.