Feed a cold, starve a fever?

within the first eight amino acid residues of its N-terminal region. This motif has not been reported to be present in serum derived amyloid proteins synthesized by the liver. Various milk and colostrum-associated bioactive peptides have been described that act directly or indirectly in muocsal development and innate protection. Intestinal mucins such as the major small intestinal mucin, MUG3,are large molecular weight glycoproteins produced and secreted to cover mucosal epithelial cells. The modulation of MUC3 expression is an important feature of innate mucosal protection. Objective. To evaluate whether MAA peptidas containing the conserved TFLK-motif upregulate MUC3 expression and to determine the specificity of the TFLK-motif in this response. Methods. HT29 cells were grown to enhance MUC3 expression. Synthetic 1B-met peptides were incubated with cells for 30 minutes. Following incubation, total RNAwas isolated using the guanidine isothldcyanate-ceeiumchloride cushion ultracentrifugation technique. Probe hybridizations of Northern blots were performed using cONA probes to the tandem repeat region of MUC3 mucins. Signals were detected by Phosphor screen autoradiography with levels expressed relative to 28s RNA loaded onto gels. Results. The 10mer peptide containing the TFLK-motif flanked on either side by three amino acid residues of native MAP,increased MUC3 mRNA expression (175±9% of control, mean_+SE)compared to incubating the cells with a lO-mer peptide of the carboxyl region of M M (111±18% of control, p-O.05). Similarly, MUC3 expression following incubation with a 10mer peptide with the entire 10 amino acid residue sequencescrambled was similar to control (109_+23% of control, p>-O.O5).Conclusion. The TFLK-motif of M M is capable of modulation of MUC3 mRNA expression. Colostrum and milk-derived bioactive pepticles from MAA may be important in the development of innate protection of the developing small intestine.

3645 A PPAR~ Agonist Improved Diabetic State Via Decreasing TNF-a Witilmet Any Change including Obesity In Genetically Obese Diabetie Rats. Akihiro Funakoshi, National Kyushu Cancer Ctr, Fukuoka Japan; Mineko Ichihawa, Yuko Sato, Setsuko Kanai, Minoru Ohta, Tokyo Metropolitan institute of Gerontology, Tokyo Japan; Atsuo Jimi, Kurume Univ, Kurume Japan; Kyoko Mlyasaka, Tokyo Metropolitan Institute of Gerontology, Tokyo Japan Background and Objectives: OLETFrats were developed as a model of non-insulin-dependent diabetes mellitus (onset of NIDDM at 18 weeks old) with mild obesity. Prevention of obesity postponed the manifestation of NIDDM in this strain. It has been reported that TNF-ar is involved in the condition of insulin resistance and that administration of a PPAR.y agonist reduced TNF-~ bioactivity. In the present study, we examinedthe effects of oral administration of a PPAR'yagonist piloglitazone hydrochloride (PIO). Methods: Standard diet and PIO (0.5m9/ kg/day)-containing diet were fed from 6 weeks of age in OLETF rats. The changes in body weight were recorded, and the energy metabolism was determined at 8 and 24 weeks of age. The 02 consumption and C02 production in expired air were measured continuously. Energy expenditure/day and the basal metabolic rate (BMR) were calculated. After the oral glucose tolerance test (oGTT) at 23 weeks of age, the animals were sacrificed at 25 weeks of age. The levels of blood glucose, HbAlc, plasma triglyceride (TG), cholesterol, le~n, TNF-~, and insulin were measured. Results: The changes in body weights, daily food intake, energy expenditure, and 8MR were similar to both treatments. The wet weight of visceral fat, plasma levels of leptin, TG, cholesterol, and insulin were not different between PIO and controls. The fasting blood glucose and HbAlc were significantly lower in PIO than in controls, although blood glucose levels after glucose ingestion of o613 were not influenced. The plasma levels of TNF-~ were significantly lower in PIO (165.1 pg/ml for controls vs 64.2 pg/ml for PIO). Conclusions: Treatment with a PPAR~,agonist improved the diabetic condition in OLETFrats without any effect including obesity or lipid metabolism. One of the mechanisms of PIO is considered to be a decrease in TNF-~.

derived from metastasis. We hypothesise that cells that have metastasised adapt to their new environment and have a reduced ability to metabolise butyrate.

3647 hdluuces of Exefetse th BCAAand AM Balances of Vadous Tissues in Liver Cirdmets Model Rat Teruo Miyazaki, Yasushi Matsuzaki, Masaaki Karube, Masato Abel, Junichi Shoda, Naomi Tanaka, Univ of Tsukuba, Tsukuba Japan [BACKGROUNDS and AIMS] It is well known that the amino acids imbalance i.e., decrease of BCAA (branched-chain amino acids) and increase of AAA (aromatic amino acids) in plasma, and the decreased plasma albumin concentration occur in the liver cirrhosis (LC) patients. Recently, in exercise nutrition fields, the effectiveness of BCAA for energy metabolism has been shed light on the modus operandi. The aim of this study was to clarity the influences of exercise to BCM and AAA balances of various tissues in LC model. [METHODS]SD rats were divided into CTL group iN=7) and LC groups, which were administrated olive oil or CCI, for 10 weeks, respectively. After administration of CCI,, rats in LC groups were divided into LC group iN=7) and LC plus exercise (LC- EX: N=7) group. Rats in LC+EX group were loaded a transient treadmill running for 90 min, 10 m/rain. We examined BCAA and A,4A concentrations of plasma, liver, brain, heart and lower leg skeletal muscles (soleus, gastrocnemius, plantaris and EDL) in three groups. [RESULTS] As result of CCI4administration for 10 weeks,1): Blood biochemical and histological findings, rats of LC groups were regarded as completed LC. 2): Fischer ratios (8CANAAA) of all samples except for liver in LC groups were significantly decreased compared to those in CTL group. Among Fischer ratios of all samples in LC groups, there were no significant differences. Fischer ratios were decreased due to the balancesas follows. In plasma, brain and heart, BCAAconcentration was decreased and AAA concentration increased in LC group compared to CTL group. Decreased8CAA and increased AAA concentrations were accelerated significantly by exercise. In skeletal muscles, both 8CAA and AAA concentrations were increased in LC group compared to CTL group, whereasthe increasedAAA concentrations were more than the increased BCAAconcentrations. In LC + EX group, BCM and AAA concentrations in skeletal muscles significantly increased more than LC group. 3): In liver, Fischer ratios were not differenced among three groups. Both BCAA and AAA concentrations in LC groups were decreased compared to CTL group. We found BCAA and AAA concentrations in liver had a close positive correlation relationship (r2= 0.973). [CONCLUSION] It was observed each tissue in LC had its own amino acids imbalance. Moreover, the amino acids imbalances were accelerated by exercise load. In conclusion, the maintenance of the amino acids good balances in whole body has to be considered important points in nutrition and exercise therapy for LC patients. 3lS,m "Feed a cold, starve a lever"? Gi]s R. Van Den Brink, Danielle E. Van Den Boogaardt, Sander J.H. Van Deventer, Maikel P. Peppelenbosch,AMC, Amsterdam Netherlands Backgmuod: Although the English old wives-tale 'leed a cold, starve a fever" advises us to eat well when having a cold and refrain from calorie ingestion when having a fever, this popular wisdom has to date not been addressed by science. CD4 expressing T helper (Th) cells produce cytokines which skew the adaptive immune response either toward cell-mediated immunity by producing IFN-~, or toward humoral immunity by production of IL4. We followed the immune response after eating and fasting. Methods: Six non-smoking healthy male volunteers (mean age 28, range 26-33, mean BMI 23.8, range 21.5-26.3) were studied on two occasions. After overnight starvation the participants received a liquid meal on one occasion (1200 kcal), and an equal volume of water on the other. Heparinized blood was obtained at the start of the experiment at 9:00 am and every hour for six hours hereafter. Blood was diluted 1:1 in pyrogen-frse RPMI 1640 (Big Whittaker, Verviers, Belgium) and cultured in triplicate for 24 hr in the presence or absence of the T cell receptor activating antibodies anti Oz)-CD3/o-CD28 (CLB, Amsterdam). IFN--yand IL4 were measured by ELISA (CL8). Results: Six hour after the meal, six out of six volunteers showed strongly increased IFN--y production averaging 450% of baseline (range: 117-867%). Upon fasting, however, IFN-~ production decreased to an average 83% of baseline (range: 47-116%). Both food intake and fasting increased IL4 production. The increase was significantly higher however in fastened volunteers, the most marked difference being noted five hours after meal intake. Whereas in fastened volunteers IL4 levels reached an average 398% of baseline (range: 671114%), after food intake IL-4 production reachedonly an averageof 142% of baseline (range: 80-243%). Statistical analysis was performed using atwo-factor repeated-measurementdesign on absolute measurements relative to baseline (t = O). The food/time interaction was significant for both cytokines, p
3646 Nutrient Metabolism In Colonic Mucoea And Cancer Pavan Aujla, Margaret Eggo, Michael Langman, Sukhdev Singh, Univ of Birmingham, Birmingham United Kingdom BACKGROUNDColonic epithelium derives energy from glucose present in the circulation and from short chain fatty acids (acetate, butyrate and propionate) frOm the colonic lumen. Previous studies of rat colonocytes and human biopsies have d e m o n s t ~ a metabolic dependenceon butyrate, however, the nutritional requirements of normal colonocytes, colon carcinomas and colonic cell lines are not known. Since butyrate also regulates colonocyte cell cycle by inducing apoptosis, the ability to metabolice butyrate may be important to cell survival. OBJECTIVE To determine and compare the ability of normal human colonocytes, carcinomas and colonic cell lines to metabolise the nutrients but/rate, glucose and glutamine. METHODColonocytes were isolated by mechanical disruption and collagenaseaction, washed and incubated with either [~4C(U)]-glucose,n-[1-'4C]-butyrate or ['4C(U)]-glutamine. Oxidation of coldnocytes and cell lines was measured by trapping I'CO2released on sodium hydroxidesaturated filter paper and counted. HT29 and CaCO-2established from primary tumors and COLD-205, LoVo and SW620 established from metastatis were used. RESULTSA reduction in the metabolism particularly of butyrate but also glucose and glutaroine was seen in the colon cancer specimens (n=22 patients) when compared to their normal counterparts. At 3mM butyrate, glucose and glutamine the normal human colonocytes yielded 89.9 -+ 2.5, 23.2 ± 4.8 and 19.1 ± 0.4 nmol CO2/mg protein respectively. The human malignant colonocytes showed a similar order but with a reduced metabolism of butyrate, glucose and glutamine 23.7 +_ 1.2, 17.5 _+ 0.8 and 10.9 -+ 0.7 nmol C02/mg protein respectively. In cancer cell lines a similar trend to the primary cultures was observed (butyrate>glucose>glutamine). However, those cell lines derived from a primary tumour origin showed a 2-fold increase in butyrate oxidation compared to those cell lines derived from metastases. CONCLUSIONTo our knowledge, this is the first report of nutrient utilisation in colonic cell lines, colonic tumors and their normal counterparts using a short-term primary culture micro-assay. There was an overall reduction in the metabolism of the nutrients butyrate, glucose and glutamine in malignant carcinomas when compared to their normal counterparts. Colon cancer cell lines from a primary tumor source showed a greater capacity to metabolise butyrate than those

~9 Elemental Diet MoOletes the Inflammatory Response of Enterocytes Eric J. Kelly, Sandhia Naik, lan R. Sanderson, Nick M. Croft, St Bartholomew's Hosp, London United Kingdom Nutitional therapy is recognized as a useful therapeutic modality in IBD. It is at least as successful as corticosterolds at decreasing inflammation and leading to clinical remission (Sanderson et al Archives of Disease in Childhood 1987). However, little is known about the way diets achieve their response. The aim of this study is to determine, in vitro, whether diets can modulate the inflammatory respose of stimulated intestinal epithelial cells. Caco2 cells were grown in serum free media. The cells were stimulated with iL1/~ (1 no/mL) with or without pre-incubation with different diets (5%). The diets used were Breast Milk, Modulin (Nestle), Boost (Mead Johnson) and Ensure Plus (Ross). After 24 hours the cell-free culture

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