The traditional Mediterranean diet is thought to represent a healthy lifestyle; especially given the incidence of several cancers including colorectal cancer is lower in Mediterranean countries compared to Northern Europe. Olive oil, a central component of the Mediterranean diet, is believed to beneficially affect numerous biological processes. We used phenols extracted from virgin olive oil on a series of in vitro systems that model important stages of colon carcinogenesis. The effect the extract on DNA damage induced by hydrogen peroxide was measured in HT29 cells using single cell microgel-electrophoresis. A significant anti-genotoxic linear trend (p 5 0.011) was observed when HT29 cells were preincubated with olive oil phenols (0,5,10,25,50, 75, 100 lg/ml) for 24 hr, then challenged with hydrogen peroxide. The olive oil phenols (50, 100 lg/ml) significantly (p 5 0.004, p 5 0.002) improved barrier function of CACO2 cells after 48 hr as measured by transepithelial resistance. Significant inhibition of HT115 invasion (p < 0.01) was observed at olive oil phenols concentrations of 25, 50, 75, 100 lg/ml using the matrigel invasion assay. No effect was observed on HT115 viability over the concentration range 0, 25, 50 75, 100 lg/ml after 24 hr, although 75 and 100 lg/ml olive oil phenols significantly inhibited HT115 cell attachment (p 5 0.011, p 5 0.006). Olive oil phenols had no significant effect on metastasis-related gene expression in HT115 cells. We have demonstrated that phenols extracted from virgin olive oil are capable of inhibiting several stages in colon carcinogenesis in vitro. ' 2005 Wiley-Liss, Inc.
Objectives To evaluate the feasibility of an RCT of a pedometer driven walking program and education/advice to remain active compared with education/advice only for treatment of chronic low back pain (CLBP). Methods Fifty-seven participants with CLBP recruited from primary care were randomly allocated to either: (1) education/advice (E, n=17) or (2) education/advice plus an 8-week pedometer driven walking program (EWP, n=40). Step targets, actual daily step counts, and adverse events were recorded in a walking diary over the 8 weeks of intervention for the EWP group only. All other outcomes (eg, functional disability using the Oswestry Disability Questionnaire (ODQ), pain scores, physical activity (PA) measurement etc.) were recorded at baseline, week 9 (immediately post intervention), and 6 months in both groups. Results The recruitment rate was 22% and the dropout rate was lower than anticipated (13% to 18% at 6 mo). Adherence with the EWP was high, 93% (n=37/40) walked for ≥6 weeks, and increased their steps/day (mean absolute increase in steps/d, 2776, 95% confidence interval [CI], 1996–3557) by 59% (95% CI, 40.73%–76.25%) from baseline. Mean percentage adherence with weekly step targets was 70% (95% CI, 62%–77%). Eight (20%) minor-related adverse events were observed in 13% (5/40) of the participants. The EWP group participants demonstrated an 8.2% point improvement (95% CI, −13 to −3.4) on the ODQ at 6 months compared with 1.6% points (95% CI, –9.3 to 6.1) for the E group (between group d=0.44). There was also a larger mean improvement in pain (d=0.4) and a larger increase in PA (d=0.59) at 6 months in EWP. Discussion This preliminary study demonstrated that a main RCT is feasible. EWP was safe and produced a real increase in walking; CLBP function and pain improved, and participants perceived a greater improvement in their PA levels. These improvements require confirmation in a fully powered RCT.
. Measurement of glycated insulin in plasma of type 2 diabetic subjects by specific RIA gave circulating levels of 10.1 ؎ 2.3 pmol/l, corresponding to ϳ9% total insulin. Biological activity of pure synthetic monoglycated insulin (insulin B-chain Phe 1 -glucitol adduct) was evaluated in seven overnight-fasted healthy nonobese male volunteers using two-step euglycemichyperinsulinemic clamps (2 h at 16.6 g ⅐ kg ؊1 ⅐ min ؊1 , followed by 2 h at 83.0 g ⅐ kg ؊1 ⅐ min ؊1 ; corresponding to 0.4 and 2.0 mU ⅐ kg ؊1 ⅐ min ؊1 ). At the lower dose, the exogenous glucose infusion rates required to maintain euglycemia during steady state were significantly lower with glycated insulin (P < 0.01) and ϳ70% more glycated insulin was required to induce a similar rate of insulin-mediated glucose uptake. Maximal responses at the higher rates of infusion were similar for glycated and control insulin. Inhibitory effects on endogenous glucose production, insulin secretion, and lipolysis, as indicated by measurements of C-peptide, nonesterified free fatty acids, and glycerol, were also similar. Receptor binding to CHO-T cells transfected with human insulin receptor and in vivo metabolic clearance revealed no differences between glycated and native insulin, suggesting that impaired biological activity is due to a postreceptor effect. The present demonstration of glycated insulin in human plasma and related impairment of physiological insulin-mediated glucose uptake suggests a role for glycated insulin in glucose toxicity and impaired insulin action in type 2 diabetes. Diabetes 52:492-498, 2003
Physaria fendleri (syn. Lesquerella) is a Brassicaceae producing lesquerolic acid, a highly valued hydroxy fatty acid that could be used for several industrial applications, such as cosmetics, lubricating greases, paints, plastics and biofuels. Free of toxins, Physaria oil is an attractive alternative to imported castor (Ricinus communis) oil, and is hence on the verge of commercialization. Gas chromatography-mass spectrometry analysis of fatty acid methyl esters revealed that lesquerolic acid was synthesized and accumulated in the embryos, reaching 60% (w/w) of the total fatty acids. The sequential extraction and characterization of biomass compounds revealed that Physaria embryo metabolism switched from protein to fatty acid biosynthesis between 18 and 24 days post-anthesis (DPA). In order to unravel the metabolic pathways involved in fatty acid synthesis, a targeted metabolomics study was conducted on Physaria embryos at different stages of development. For this purpose, two novel high-throughput liquid chromatography-tandem mass spectrometry methods were developed and validated to quantify sugars, sugar alcohols and amino acids. Specificity was achieved using multiple reaction monitoring, and the limits of quantification were in the pmole-fmole range. The comparative metabolomic study underlined that: (i) the majority of the metabolites accumulate in Physaria embryos between 18 and 27 DPA; (ii) the oxidative pentose phosphate pathway, glycolysis, the tricarboxilic acid cycle and the anaplerotic pathway drain a substantial amount of carbon; and (iii) ribulose-1,5-bisphosphate is present, which specifically indicates that the Calvin cycle is occurring. The importance and the relevance of these findings regarding fatty acid synthesis were discussed.
The phenolic compositions of fecal water samples from ten free-living human subjects without marked dietary restrictions were monitored before and after intake of raspberry puree (200 g/day, 4 days) using gas chromatography-mass spectrometry. No single phenolic component was increased in all subjects after intake, but a majority of subjects had significant elevations in phenylacetic acid (7/10), 4-hydroxyphenylacetic acid (6/10), 3-hydroxyphenylacetic acid (5/10), 3-phenylpropionic acid and 3-(4-hydroxyphenyl)propionic acid. The levels of 3,4-dihydroxbenzoic acid were elevated in 8/10 subjects, significantly for 6 subjects (p < 0.05), and not significantly reduced in the other 2 subjects. In addition, unlike most other fecal metabolites, the increase was always >2-fold. This metabolite may be representative of the increased colonic dose of cyanidin anthocyanins. The colonic microbiota varied greatly between individuals, and supplementation with raspberries did not produce any statistically significant alterations in the profile of colonic bacteria, nor was a common pattern revealed to account for the interindividual variations observed in the fecal water phenolic profiles.
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