Advanced glycosylation end-products (AGEs) are believed to play a significant role in the development of vascular complications in diabetic patients. One such product, AGE-LDL, has been shown to be immunogenic. In this report, we describe the isolation and characterization of human AGE-LDL antibodies from the sera of seven patients with Type 1 diabetes by affinity chomatography using an immobilized AGE-LDL preparation that contained primarily the AGE N (carboxymethyl)lysine (CML, 14.6 mmol/mol lysine), and smaller amounts of N (carboxyethyl)lysine (CEL, 2.7 mmol/mol lysine). The isolated antibodies were predominantly IgG of subclasses 1 and 3, and considered proinflammatory because of their ability to promote Fc ␥ R-mediated phagocytosis and to activate complement. We determined dissociation constants

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Exemestane is an aromatase inhibitor drug used for the treatment of hormone-dependent breast cancer. 17-hydroexemestane, the major and biologically active metabolite of exemestane in humans is eliminated via glucuronidation by the polymorphic UGT2B17 phase II drug metabolizing enzyme. Previous microsomal studies have shown that UGT2B17 gene deletion affects the intrinsic hepatic clearances of 17-hydroexemestane in vitro. In this open-label study, we set out to assess the effect of UGT2B17 gene deletion on the pharmacokinetics of 17-hydroexemestane in healthy female volunteers with and without UGT2B17. To achieve this goal, 14 healthy postmenopausal women (eight carriers of the homozygous UGT2B17 wild-type allele and six carriers of the homozygous UGT2B17 gene deletion allele) were enrolled and invited to receive a single 25 mg oral dose of exemestane. Pharmacokinetics was assessed over 72 hours post-dosing. Our results showed that there were statistically significant differences in plasma 17-hydroexemestane AUC0-∞ (p = 0.0007) and urine 17-hydroexemestane C24hr (p = 0.001) between UGT2B17 genotype groups. Our data suggest that UGT2B17 gene deletion influences 17-hydroexemestane pharmacokinetics in humans.