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Dietary intake of selenium has been implicated in a wide range of health issues, including aging, heart disease and cancer. Selenium deficiency, which can reduce selenoprotein levels, has been associated with several striated muscle pathologies. To investigate the role of selenoproteins in skeletal muscle biology, we used a transgenic mouse (referred to as [i.sup.6][A.sup.-]) that has reduced levels of selenoproteins due to the introduction and expression of a dominantly acting mutant form of selenocysteine transfer RNA (tRN[A.sup.[Ser]sec]). As a consequence, each organ contains reduced levels of most selenoproteins, yet these mice are normal with regard to fertility, overall health, behavior and blood chemistries. In the present study, although skeletal muscles from [i.sup.6][A.sup.-] mice were phenotypically indistinguishable from those of wild-type mice, plantaris muscles were ~50% heavier after synergist ablation, a model of exercise overload. Like muscle in wild-type mice, the enhanced growth in the [i.sup.6][A.sup.-] mice was completely blocked by inhibition of the mammalian target of rapamycin (mTOR) pathway. Muscles of transgenic mice exhibited increased site-specific phosphorylation on both Akt and p70 ribosomal S6 kinase ([p70.sup.S6k]) (P- KEY WORDS: * selenium * Akt/PKB * transgenic * signaling * p70 ribosomal S6 kinase

Consumption of lycopene, the predominant carotenoid in tomatoes and tomato products, is associated with reduced prostate cancer risk. The purpose of this study was to measure the pharmacokinetics and tissue distribution of lycopene after oral administration to male dogs. After single doses of 10, 30 and 50 mg/kg body weight (BW) lycopene to 2 dogs/dose, the mean half-life was 36 h and the plasma systemic exposure levels (AU[C.sub.0-[infinity]], area under the curve) after the 30 and 50 mg/kg BW doses were similar. In a repeat dose study, 30 mg/(kg BW * d) administered orally to six dogs for 28 d resulted in steady-state plasma concentrations between 785 and 997 nmol/L lycopene. Apparent clearance, volume of distribution and apparent elimination half-life were 2.29 L/(h * kg), 96 L/kg and 30.5 h, respectively. Dogs were killed 1 or 5 d after the last dose and 23 tissues were collected for lycopene analysis. Lycopene concentrations were highest in liver, adrenals, spleen, lymph nodes and intestinal tissues. Liver lycopene concentrations were 66 and 91 nmol/g 1 and 5 d after cessation of treatment, respectively. Prostate lycopene concentrations were < 0.2 nmol/g both 1 and 5 d after dosing ceased ( KEY WORDS: * carotenoid * prostate * cancer * chemoprevention * canine

Serum concentrations of several nutrients were measured in 12 captive wild felid species including caracal (Felis caracal), cheetah (Acinonyx jubatus), cougar (Fells concolor), fishing cat (Fells viverrinus), leopard (Panthera pardus), lion (Panthera leo), ocelot (Fells pardalis), pallas cat (Fells manul), sand cat (Fells margarita), serval (Felis serval), snow leopard (Panthera uncia) and tiger (Panthera tigris). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens and North Carolina Zoological Park). The nutritional composition of the diets at each institution met the probable dietary requirements for each species except for the pallas cat. Blood samples were collected from each animal (n = 69) and analyzed for lipids (total cholesterol, triacylglycerides, HDL cholesterol and LDL cholesterol), vitamin D metabolites [25-hydroxycholecalciferol (25(OH)D) and 1,25-dihydroxycholecalciferol (1,25(OH)2D)], vitamin A (retinol, retinyl stearate and retinyl palmitate), vitamin E ([alpha]- and [gamma]-tocopherol) and selected carotenoids. Species differences were found for all except triacylglycerides and 1,25(OH)2D. Genus differences were found for retinol, retinyl palmitate, retinyl stearate, [gamma]-tocopherol and [beta]-carotene. Circulating nutrient concentrations for many of the species in this study have not been reported previously and most have not been compared with the animals' dietary intakes. The large number of animals analyzed provides a substantial base for comparing the serum nutrient concentrations of healthy animals, for both wild and captive exotic species. KEY WORDS: * Fells * lipids * vitamin A * vitamin D * vitamin E

Age-related macular degeneration (ARMD) is inversely associated with the accumulation of lutein + zeaxanthin in the macula, but higher lutein intakes are inconsistently related to reduced risk of ARMD in epidemiologic studies. Resolution of efficacy awaits clinical trials designed with knowledge of lutein supplement pharmacokinetics. Lutein bioavailability was determined for lutein diester and unesterified lutein formulations as they might be incorporated into dietary supplements. Healthy subjects (n = 18) consumed a single dose of each formulation (either 0.5 or 0.67 [micro]mol lutein/kg body, 10 and 8 subjects, respectively) in random order, and the appearance of free lutein + zeaxanthin was measured in serum from 0 to 408 h. Areas under the serum concentration x time curves (AUC), as a measure of bioavailability, were independent of gender, body mass index and lutein dose. The lutein diester formulation was 61.6% more bioavailable than the unesterified lutein formulation with higher mean AUC, maximum serum concentration and ascending slope (P < 0.05). The AUC was greater in 14 of 18 subjects when they consumed the lutein diester formulation. Comparison with data from previous studies suggested that dissolution was a greater limitation to bioavailability than lutein ester hydrolysis because an oil-solubilized unesterified lutein preparation, given at 0.5 [micro]mol/kg body, resulted in greater mean peak concentrations and AUC compared with either the unesterified or lutein diester formulations used in our study. In conclusion, the lutein diester formulation poses no impediment to lutein bioavailability at the doses tested, but formulation dissolution is an important factor in lutein bioavailability and should be evaluated before a supplement and dose are selected for use in clinical trials. J. Nutr. 132: 3668-3673, 2002. KEY WORDS: * lutein * lutein ester * bioavailability * humans

Assesses the oxidative DNA damage in prostate cancer patients consuming tomato sauce-based foods. Accumulation of lycopene in the prostate tissue; Analysis of lycopene concentration in tomato sauce; Method and design of the study.

The article focuses on the selection of surrogate endpoint biomarkers to evaluate the efficacy of lycopene/tomatoes for the prevention/progression of prostate cancer. The use of surrogate endpoint biomarkers (SEBs) is essential to the crafting of cost-effective clinical trials to evaluate not only the efficacy of lycopene/tomatoes but also combinations of bioactive compounds. The closer the SEB is in the pathway to prostate cancer expression or progression, the more likely its predictive value. High-grade prostate intraepithelial neoplasia, microvessel density, and prostate-specific antigen have been exploited for these purposes, and their sensitivity and specificity in predicting clinically relevant prostate cancer can be determined. The pathways modulated by tomato bioactive ingredients can be determined through tissue culture and animal studies. A number of possible bioactive compounds are contained in tomato. consumption. Lycopene and quercetin are the likeliest candidates for prostate cancer mediation. They are predominant compounds in tomato and have been shown in animal studies to reduce cancer.