The chronic colitis developed by HLA-B27 transgenic rats is associated with altered in vivo mucin synthesis.

HLA-B27 transgenic rats spontaneously developing a chronic inflammation mainly involving the colon are recognized as a powerful animal model for IBD. We investigated the mucin production in 6-month-old HLA-B27 rats by measuring in vivo fractional synthesis rate (FSR) and expression of mucins. In the inflamed colon of HLA-B27 rats, the mucin FSR was stimulated by 75% compared to F-344 controls, while MUC2,3 mRNA expression was unchanged. A local depletion in mucus-containing goblet cells was observed, suggesting a rapid mucin production/release and/or a real global decrease in goblet cell number. In the noninflamed jejunum of HLA-B27 rats, the mucin FSR was reduced by 35% compared to controls, while MUC2,3 mRNA expression was unchanged. Different alterations in mucin metabolism and expression are observed between HLA-B27 rats and a model of chemically induced chronic colitis (DSS-treated rats), suggesting that mucin alterations may be dependent on the animal model and colitis underlying mechanism.

Mucin production and composition is altered in dextran sulfate sodium-induced colitis in rats.

We evaluated the small and large intestinal mucin production in a rat model of human ulcerative colitis by measuring the in vivo fractional synthesis rate (FSR) and the expression of mucins. A chronic colitis was induced by oral administration of 5% dextran sulfate sodium (DSS) for 9 days followed by 2% DSS for 18 days. DSS-treated rats showed increased colonic MUC2,3 mRNA levels compared pair-fed controls. The mucin FSR was unaffected while mucin-containing goblet cells were depleted in the vicinity of lesions. In the small intestine, no inflammatory lesions were observed but ileal MUC2 mRNA levels and mucin FSR were decreased by 46% and 21%, respectively. Finally, DSS-treated rats showed a marked decrease in mucin's threonine + serine content all along the gut, which may lead to a reduction of potential O-glycosylation sites. Our data indicate that the chronic colitis may impair the mucus layer protective function all along the gut.

Free and protein-bound glutamine have identical splanchnic extraction in healthy human volunteers.

The objectives of the present study were to determine the splanchnic extraction of glutamine after ingestion of glutamine-rich protein ((15)N-labeled oat proteins) and to compare it with that of free glutamine and to determine de novo glutamine synthesis before and after glutamine consumption. Eight healthy adults were infused intravenously in the postabsorptive state with L-[1-(13)C]glutamine (3 micromol x kg(-1) x h(-1)) and L-[1-(13)C]lysine (1.5 micromol x kg(-1) x h(-1)) for 8 h. Four hours after the beginning of the infusion, subjects consumed (every 20 min) a liquid formula providing either 2.5 g of protein from (15)N-labeled oat proteins or a mixture of free amino acids that mimicked the oat-amino acid profile and contained L-[2,5-(15)N(2)]glutamine and L-[2-(15)N]lysine. Splanchnic extraction of glutamine reached 62.5 +/- 5.0% and 66.7 +/- 3.9% after administration of (15)N-labeled oat proteins and the mixture of free amino acids, respectively. Lysine splanchnic extraction was also not different (40.9 +/- 11.9% and 34.9 +/- 10.6% for (15)N-labeled oat proteins and free amino acids, respectively). The main conclusion of the present study is that glutamine is equally bioavailable when given enterally as a free amino acid and when protein bound. Therefore, and taking into consideration the drawbacks of free glutamine supplementation of ready-to-use formulas for enteral nutrition, protein sources naturally rich in this amino acid are the best option for providing stable glutamine.

Effect of glutamine supplementation of the diet on tissue protein synthesis rate of glucocorticoid-treated rats.

Although glutamine status in the critically ill patient can be improved by nutritional means, the most effective way of effecting such supplementation has received little attention. We evaluated two different ways of supplementing clinical nutrition products with glutamine, either with free glutamine or by providing a glutamine-rich protein source, in acute glucocorticoid-treated (intraperitoneal dexamethasone, 120 mg/kg) rats. During the recovery period, the animals received isonitrogenous and isoenergetic diets containing either casein, mixed whey proteins with or without glutamine, or carob protein plus essential amino acids. Plasma and tissue amino acids and glutathione as well as tissue protein synthesis were measured. Dexamethasone treatment lowered weight gain, muscle glutamine, and muscle and jejunal protein synthetic rate. Muscle protein synthesis was increased (from 15.9% to 24.2%/d) only when glutamine was included in the diet as a free amino acid. This increase paralleled a rise in plasma glutamine. We speculate that glutamine provided in dietary protein is extensively metabolized by the splanchnic tissues and does not influence peripheral glutamine status to the same extent as glutamine provided in a free amino acid form. However, both forms of glutamine supplementation were equally effective in increasing protein synthesis in the jejunum (by 25%). This is likely the main benefit of glutamine supplementation of enteral nutrition formulas.

Evaluation of taurine metabolism in cats by dual stable isotope analysis.

Taurine kinetics in cats was investigated using a bolus dose of [15N]- and [1,2-13C2]taurine. The comparison of [15N]- and [13C2]taurine kinetics permitted an evaluation of the extent of taurine transamination. A methodology which involves N-pentafluorobenzoyl di-n-butylamine derivatization of taurine and GC/MS measurements of the 15N- and 13C-enrichments in cat urine was developed. Accuracy of the measurements was determined using pure standard compounds and the results showed that [13C2]taurine does not interfere with [15N]taurine. In cats, no differences were observed between both tracers. Therefore, we conclude that taurine reversible transamination does not occur at a significant level in cats.

Energy, protein, and substrate metabolism in simulated microgravity.

Whole body protein turnover and energy expenditure before and during an oral glucose tolerance test (1 g/kg body wt) were studied on separate occasions in six healthy young men before and during 3 days of simulated microgravity using the 6 degrees head-down tilt (HDT) method. After 42-47 h of HDT, basal insulin concentrations increased significantly from 9.4 +/- 1.9 to 13.1 +/- 0.1 microU/ml (P < 0.002). No significant differences in glycemia, insulinemia, or free fatty acid concentrations were observed in response to the oral glucose load. With HDT, increases were observed in basal postabsorptive resting metabolic rate (8%; P < 0.05), lipid oxidation (33 +/- 2 to 51 +/- 5 mg/min; P < 0.02), and the thermic effect of glucose (7.7 +/- 1 to 10.7 +/- 0.6%; not significant). Protein turnover (arithmetic mean of ammonia and urea flux rates) was unchanged by HDT, but a significant increase was seen when calculated from ammonia alone (P < 0.02). The present data show that HDT results in an increased energy requirement through elevations in both the basal metabolic rate and the thermic response to food ingestion. These changes may have been brought about by a cephalic shift of body fluids similar to that experienced in microgravity.

Fecal bile acid excretion and taurine status in cats fed canned and dry diets.

Cats conjugate their bile acids with taurine but are unable to synthesize sufficient quantities of this amino acid to meet their needs. To maintain the same blood taurine level, canned foods must contain more taurine than dry foods. In the present study we examined the effect of soluble fiber on fecal bile acid excretion and taurine status and compared the quantity and profile of fecal bile acids in cats fed canned and dry diets. In a cross-over design, 10 adult cats were fed a typical canned diet containing 0.25% kappa carrageenan with or without the addition of 0.5% guar gum (2.5% on a dry matter basis) for 6 wk. All cats were then transferred to a dry diet. The addition of guar gum to the canned diet had no significant effect on taurine status, but the dry diet, which contained less taurine than the canned diet, resulted in an increase in plasma taurine. With the dry diet, total bile acid excretion was reduced by approximately 65%. The profile of bile acids in feces was also radically different with a marked decrease in secondary bile acids. This work suggests that when canned rather than dry diets are fed, the conversion of primary to secondary bile acids is greater and is indicative of an alteration in the activity of the gut flora that may lead to an increase in taurine degradation.