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Biomedical subjects

William F Stenson

Publications and source records attributed to William F Stenson.

25 records · Page 2Linked to original sources
PubMed2003

Inhibition of cholesterol absorption by phytosterol-replete wheat germ compared with phytosterol-depleted wheat germ.

BACKGROUND: Low-fat vegetable foods contain phytosterols, but it is not known whether they are in biologically active forms or whether their concentrations are high enough to reduce cholesterol absorption and favorably affect lipid metabolism. OBJECTIVE: The objective was to establish whether the selective removal of phytosterols from wheat germ would increase the cholesterol absorption measured from test meals composed of wheat germ muffins. DESIGN: Wheat germ, which has a high content of phytosterols relative to total fat, was chosen as a low-fat test food. Cholesterol absorption was measured 3 times in 10 subjects. Each test meal was a muffin containing 30 mg heptadeuterated cholesterol tracer and, in random order, 80 g original wheat germ containing 328 mg phytosterols, wheat germ from which phytosterols had been selectively extracted, or extracted wheat germ reconstituted with purified phytosterols. Changes in cholesterol absorption were monitored by the measurement of tracer enrichment of plasma cholesterol 4 and 5 d after each meal with the use of negative ion mass spectrometry. RESULTS: Tracer enrichment of plasma cholesterol was 42.8% higher after consumption of phytosterol-free wheat germ than after that of the original wheat germ (0.415 +/- 0.035 compared with 0.291 +/- 0.024 micro mol tracer/mmol cholesterol; P < 0.01). Tracer enrichment of plasma cholesterol was not significantly different between the wheat germ with extracted-and-reconstituted phytosterol (0.305 +/- 0.022 micro mol tracer/mmol cholesterol) and the original wheat germ. CONCLUSION: The efficiency of cholesterol absorption from test meals was substantially lower after consumption of original wheat germ than after consumption of phytosterol-free wheat germ, which suggests that endogenous phytosterols in wheat germ and possibly in other low-fat vegetable foods may have important effects on cholesterol absorption and metabolism that are independent of major nutrients.

Absorption↗
PubMed2002

Prosurvival and antiapoptotic effects of PGE2 in radiation injury are mediated by EP2 receptor in intestine.

The biological activities of PGE(2) are mediated through EP receptors (EP(1)-EP(4)), plasma membrane G protein-coupled receptors that differ in ligand binding and signal-transduction pathways. We investigated gastrointestinal EP(2) receptor expression in adult mice before and after radiation injury and evaluated intestinal stem cell survival and crypt epithelial apoptosis after radiation injury in EP(2) null mice. EP(2) was expressed throughout the gut. Intestinal EP(2) mRNA increased fivefold after gamma-irradiation. Crypt survival was diminished in EP(2)-/- mice (4.06 crypts/cross section) compared with wild-type littermates (8.15 crypts/cross section). Radiation-induced apoptosis was significantly increased in EP(2)-/- mice compared with wild-type littermates. Apoptosis was 1.6-fold higher in EP(2) (-/-) mice (5.9 apoptotic cells/crypt) than in wild-type mice (3.5 apoptotic cells/crypt). The EP(2) receptor is expressed in mouse gastrointestinal epithelial cells and is upregulated following radiation injury. The effects of PGE(2) on both crypt epithelial apoptosis and intestinal crypt stem cell survival are mediated through the EP(2) receptor.

Animals↗
PubMed2002

Basic fibroblast growth factor upregulates cyclooxygenase-2 in I407 cells through p38 MAP kinase.

The intestinal cell line I407 responds to basic fibroblast growth factor (bFGF) by upregulating cyclooxygenase-2 (COX-2) mRNA and protein expression and increasing PGE(2) production. bFGF treatment of I407 cells results in phosphorylation of p38, and the p38 inhibitor SB-203580 abrogates bFGF-induced PGE(2) synthesis. Wild-type p38alpha (p38alphaWT) and dominant-negative p38alpha (p38alphaDN) stable transfectant clones of I407 cells were used to examine the role of the p38 MAP kinase pathway in the events controlling PGE(2) synthesis after treatment with bFGF. Treatment of p38alphaWT clones with bFGF resulted in increased COX-2 protein levels and PGE(2) synthesis similar to those seen in bFGF-treated control-transfected cells. In contrast, the p38alphaDN clones failed to upregulate COX-2 protein or increase PGE(2) synthesis when treated with bFGF. Exogenous arachidonate did not restore PGE(2) synthesis by p38alphaDN cells. bFGF treatment increased COX-2 mRNA stability, and the p38 inhibitor SB-203580 attenuated COX-2 mRNA stability in bFGF-treated I407 cells. These data demonstrate a crucial role for p38alpha in growth factor-induced PGE(2) synthesis by intestinal cells. Furthermore, they indicate that p38 activity is required at a step distal to arachidonate release, most likely COX-2 upregulation, because exogenous arachidonate did not restore PGE(2) synthesis.

Arachidonic Acid↗
PubMed2002

Phytosterols that are naturally present in commercial corn oil significantly reduce cholesterol absorption in humans.

BACKGROUND: Although supplementing the diet with large quantities of phytosterols reduces cholesterol absorption and LDL-cholesterol concentrations, very little is known about the smaller amounts of phytosterols present naturally in food. Vegetable oils are the richest dietary source of phytosterols; corn oil contains 0.77% phytosterols by weight. OBJECTIVE: We tested the hypothesis that removing phytosterols from corn oil would increase cholesterol absorption when measured in single-meal tests containing corn oil as a source of fat. DESIGN: Free and esterified phytosterols were removed from corn oil on a kilogram scale by a new technique of competitive saturation adsorption to silica. Healthy subjects with a mean (+/-SEM) serum cholesterol concentration of 5.10 +/- 0.18 mmol/L received an otherwise sterol-free test breakfast on 2 occasions 2 wk apart that contained 35 mg hexadeuterated cholesterol and 30-35 g of a corn oil preparation. The plasma enrichment of tracer was measured by negative ion mass spectrometry. RESULTS: Cholesterol absorption was 38.0 +/- 10.2% higher after consumption of the sterol-free corn oil than after consumption of commercial corn oil with an identical fatty acid content (P = 0.005; n = 10). When corn oil phytosterols were added back to sterol-free corn oil at a concentration of 150 mg/test meal, cholesterol absorption was reduced by 12.1 +/- 3.7% (P = 0.03; n = 5) and by 27.9 +/- 9.1% (P = 0.01; n = 10) after inclusion of 300 mg phytosterols. CONCLUSIONS: Phytosterols comprising < 1% of commercial corn oil substantially reduced cholesterol absorption and may account for part of the cholesterol-lowering activity of corn oil previously attributed solely to unsaturated fatty acids.

Absorption↗
PubMed2002

Gastrointestinal absorption and plasma kinetics of soy Delta(5)-phytosterols and phytostanols in humans.

Our objective was to measure the systemic absorption of lecithin-emulsified Delta(5)-phytosterols and phytostanols during test meals by use of dual stable isotopic tracers. Ten healthy subjects underwent two single-meal absorption tests in random order 2 wk apart, one with intravenous dideuterated Delta(5)-phytosterols and oral pentadeuterated Delta(5)-phytosterols and the other with the corresponding labeled stanols. The oral-to-intravenous tracer ratio in plasma, a reflection of absorption, was measured by a sensitive negative ion mass spectroscopic technique and became constant after 2 days. Absorption from 600 mg of Delta(5)-soy sterols given with a standard test breakfast was 0.512 +/- 0.038% for sitosterol and 1.89 +/- 0.27% for campesterol. The absorption from 600 mg of soy stanols was 0.0441 +/- 0.004% for sitostanol and 0.155 +/- 0.017% for campestanol. Reduction of the double bond at position 5 decreased absorption by 90%. Plasma t(1/2) for stanols was significantly shorter than that for Delta(5)-sterols. We conclude that the efficiency of phytosterol absorption is lower than what was reported previously and is critically dependent on the structure of both sterol nucleus and side chain.

Adult↗
PubMed2002

Effects of trace components of dietary fat on cholesterol metabolism: phytosterols, oxysterols, and squalene.

The effect of dietary fats on serum cholesterol is widely assumed to be due solely to the fatty acids and cholesterol they contain. Phytosterols, sterol oxidation products, and sterol precursors such as squalene, however, are often present in dietary fats. Little is known of the physiology of these substances in natural foods and most published diet studies do not consider them at all. Supplementation of the diet with high-dose phytosterols is now recommended for prevention of heart disease, but both recent and old data strongly suggest that the lower levels of phytosterols naturally present in vegetable fats may also reduce cholesterol absorption and serum cholesterol substantially. Moreover, unmeasured phytosterols may confound otherwise well-controlled diet studies because there is an inverse correlation between phytosterol and saturated fatty acid content of vegetable fats. Sterol oxidation products, many of which are found in foods, are potent regulators of lipoprotein and cholesterol transport pathways in vitro. Squalene is a phytosterol precursor abundant in olive oil that is at least partly absorbed and then quantitatively converted to cholesterol. The effects of dietary triglyceride-derived fatty acids have not been experimentally separated from the effects of trace fat components in most clinical studies. A better understanding of the activity of sterol-related dietary components is needed to reduce variability in diet studies, accurately assess the effects of dietary fatty acids and to maximize the effectiveness of dietary treatment for hypercholesterolemia.

Cholesterol↗