Because much data have accrued to support the concept that oxidatively modified LDL (Ox-LDL) can promote atherogenesis, the role of antioxidants in decreasing LDL oxidation has assumed great importance. High-dose alpha-tocopherol supplementation in humans decreases the susceptibility of LDL to oxidation. Hence, the aim of the present study was to ascertain the minimum dose of alpha-tocopherol that would decrease the susceptibility of LDL to oxidation. The effect of alpha-tocopherol in doses of 60, 200, 400, 800, and 1200 IU/d on copper-catalyzed LDL oxidation was tested in a randomized placebo-controlled study over 8 weeks. There were eight subjects in each group. Oxidation of LDL was monitored by measuring the formation of conjugated dienes and lipid peroxides by the thiobarbituric acid-reacting substances (TBARS) assay over an 8-hour time course at baseline and after 8 weeks of supplementation. Neither placebo nor any of the doses of alpha-tocopherol resulted in any side effects or exerted an adverse effect on the plasma lipoprotein profile. However, there was a dose-dependent increase in plasma and lipid-standardized alpha-tocopherol levels with increasing doses of alpha-tocopherol supplementation. LDL alpha-tocopherol appeared to follow a similar trend. When the time-course curves of LDL oxidation and the kinetics of LDL oxidation were examined, there was no significant effect at 8 weeks compared with baseline in the groups that received placebo or alpha-tocopherol 60 or 200 IU/d.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVEThe metabolic syndrome (MetS) is highly prevalent and confers an increased risk for diabetes and cardiovascular disease (CVD). While MetS is a proinflammatory state, there is a paucity of data on cellular inflammation in MetS. Toll-like receptors (TLRs) are classical pattern recognition receptors of the innate immune response.RESEARCH DESIGN AND METHODSThe aim of this study was to examine monocyte TLR2 and TLR4 in MetS patients without diabetes or CVD and control subjects since both of the receptors have been implicated in atherosclerosis and insulin resistance. Fasting blood was obtained for TLR expression and activity.RESULTSCirculating levels of high-sensitivity C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, and soluble tumor necrosis factor receptor 1 (sTNFR1) were significantly increased in MetS versus control subjects following adjustment for waist circumference. There was a significant increase in both TLR2 and TLR4 surface expression and mRNA on monocytes after adjustment for waist circumference. In addition to increased nuclear factor-κB nuclear binding, there was significantly increased release of IL-1β, IL-6, and IL-8 in MetS versus control subjects following priming of the monocytes with lipopolysaccharides. While both plasma free fatty acids and endotoxin were increased in MetS, they correlated significantly with TLR4 only.CONCLUSIONSIn conclusion, we make the novel observation that both TLR2 and TLR4 expression and activity are increased in the monocytes of patients with MetS and could contribute to increased risk for diabetes and CVD.

Ingestion of 2 gm AA daily results in no change in urinary pH but a moderate though statistically significant increase in urinary oxalate in NS (20%) and SF (33%). Stone formers respond no differently to AA than normal subjects. We recommend limiting AA use to less than 2 gm daily in CaOx stone formers.

Objective Metabolic syndrome (MetS) is characterized by low-grade inflammation and confers an increased risk for cardiovascular disease. Endothelial progenitor cells (EPCs) are a measure of vascular health and are decreased in patients with various risk factors for cardiovascular disease (CVD). There is a paucity of data examining the EPC status especially in terms of their functionality in MetS subjects without diabetes or cardiovascular disease. We aimed to enumerate and functionally characterize EPCs in subjects with MetS in comparison to healthy controls. Methods The study was performed at the University of California Davis Medical Center. Healthy controls (n=31) and MetS (n=46) subjects were included in the study. EPCs were ennumerated in fasting blood by KDR/CD34 dual positivity. Functionality was assessed by the colony forming units (CFU) assay, migration and tubule formation. Results Subjects with MetS had significantly decreased number of EPCs compared to control subjects. Furthermore, EPCs from MetS subjects depicted significantly impaired clonogenic capacity i.e., decreased colony forming units, and impaired capacity to incorporate into tubular structures suggesting functional impairment of EPCs from MetS subjects. Conclusions We make the novel observation that MetS subjects without diabetes or CVD have decreased EPC number and impaired functionality as compared to control subjects. These findings could contribute to the increased CV risk in this population.

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