A pilot study of copper supplementation effects on plasma F2alpha isoprostanes and urinary collagen crosslinks in young adult women.

Marginal copper deficiency has been proposed to occur frequently, but the benefits of correction remain largely uncharacterized. Two benefits could be reduced oxidant stress and better crosslinking of collagen in bone. Copper intake was increased in 8 female university students by supplementation with copper glycinate (2 mg copper/day) for 8 weeks. Supplementation improved copper status based on serum activity of two copper enzymes, ceruloplasmin and diamine oxidase (9% and 75% mean increase, respectively). No effect was seen for erythrocyte copper-zinc superoxide dismutase. Supplementation produced a 39% mean decrease in plasma for F(2alpha)-isoprostanes (a marker of oxidant stress), and gave a 62% increase in the urine ratio of collagen crosslinks to a measure of total collagen. None of the supplementation effects were duplicated for 8 women given placebo. In conclusion, this pilot study found that in young adult women, increased copper intake can alter biochemical parameters relevant to copper function.

Safety and antioxidant effects of a modest soy protein intervention in hemodialysis patients.

Antioxidant/anti-inflammatory effects of isoflavone-containing soy protein could partly explain why hemodialysis patients in Japan tend to outlive U.S. hemodialysis patients. However, a safety concern is that dialysis patients do not clear isoflavones well. A low-dose intervention with high isoflavone soy protein (25 g protein, four times a week for 4 weeks) was tested in 17 U.S. hemodialysis patients (eight given soy protein, nine given whey protein as a control). Soy protein intake produced no harmful effects based on a typical battery of blood safety tests. Post-treatment isoflavone levels, though high, were similar to those reported after a single 20-g soy protein intake by dialysis patients. In addition, intake of soy, but not whey, reduced plasma values for oxidized low-density lipoprotein, a risk factor for cardiovascular disease, which is a common mortality cause in hemodialysis patients. Three other measures of oxidant stress and/or inflammation were unchanged by the modest high isoflavone soy protein intervention. In conclusion, in hemodialysis patients, a fairly short, low intake level intervention with high isoflavone soy protein produced no obvious harm, and produced one potentially beneficial effect. This justifies tests of higher-dose, longer interventions with soy protein in hemodialysis patients.

Regulated expression and inhibitory function of Fcgamma RIIb in human monocytic cells.

Human monocytes/macrophages express three classes of receptors for IgG: FcgammaRI, FcgammaRII, and FcgammaRIII. The expression and function of these receptors has been extensively studied with the exception of one, FcgammaRIIb. While the mRNA for FcgammaRIIb has been detected in human monocytes, the protein has remained elusive. Studies in mouse models indicated that the macrophage FcgammaRIIb serves to down-regulate FcgammaR-mediated phagocytosis and immune complex-induced inflammation. FcgammaRIIb has also been shown to modulate the action of cytotoxic antibodies against tumors in mouse models. Hence, an understanding of how FcgammaRIIb expression is regulated is of great importance. Here we demonstrate for the first time FcgammaRIIb protein expression and function in human monocytes. We also report that the expression of FcgammaRIIb is highly up-regulated by interleukin-4, a Th2 cytokine, and that the up-regulation of FcgammaRIIb results in a decrease in the phagocytic efficiency of interleukin-4-treated THP-1 cells. Furthermore co-clustering FcgammaRIIb with FcgammaRIIa resulted in enhanced phosphorylation of the inositol phosphatase SHIP, association of SHIP with Shc, and phosphorylation of additional proteins around 120 and 60-65 kDa, with a concomitant attenuation of Akt activation. We, therefore, propose that FcgammaRIIb serves to inhibit FcgammaRI/IIa-mediated macrophage activation using SHIP as its effector.