A752 AGA ABSTRACTS GASTROENTEROLOGY, Vol. 108, No. 4

• EFFECT OF L-GLUTAMINE ON THE BARRIER FUNCTION OF RAT COLON. W. Scheppach, G. Dusel, C. Loges, T. Kulm, P. Bartram, F. Richter, S. Christi, H. Karch*, I-E Kasper. Depts. of Medicine & Mierebiology*, University of Wiirzburg, Germany.

L-Gtutamine(Gin) is an important nutrient for intestinal epithelia affecting both their stsu~xtre and function: We studied the effect of Gin on resealing of rat distal colon niter acid injury. Methods: Isolated colonic mucosa was mounted in Ussing chambers and exposed to Krebs-Ringer solution for 4 hours (37°C, Carbogen gas). Epithelial injury was induced by short-term exposure to luminal HC1 (10 mM, 5 rain) and resealing was studied with or without added Gin (2 raM, luminal+serosal). We measured potential difference (PD), conductance (C), permeability (mucosal to serosal side) of mannitol (Man) and lactulnse (Lac), and translocation of an enteropathogenic strain of E. coli (T-EPEC). Bromodeoxyuridine hnmtmohistochemistry was employed to assess mucosal proliferation (Lluc, upper crypt labeling index). Results: Gin (2 raM) Control 12 PD-AUC(%iv*h) 278.8+88.6 194.5+46.8 0.116 C-AUC(%iv*h) 420.4_+81.9 642.6_+101.5 0.028 Man-AUC(uM*h)~42.5+ 8.6 146.5_+ 33.2 0.028 Lac-AUC(uM*h) 35.8÷ 5.1 87.0+ 19.5 0.028 T.EPEC(u*103/m02.02-_+I.02 33.70~13103 0.028 Lluc 0~072+_0.008 0.040_+0.007 0.036 (Mean _+ SEM, AUC = area under curve/4 h, %iv per cent of initial value, Wilcoxon test). Conclusion: These data suggest that Gin stimulates repair mechanisms of rat colonic mucosa aider acid injury (electrical conductance, saceharide permeability and 'bacterial translocation diminished). This effect on the gut barrier may be due to a stimulation of crypt cell proliferation and/or migration. The addition of glutamine to parenteral solutions may be beneficial for patients under intensive care whose intestinal barrier may be weakened in the course of sepsis and trauma:

NASOENTERAL NUTRITION FOR HIV ASSOCIATED WASTING - PROMISE AND OUTCOME. A. Schulte-Bockholt, A. Schwenk , A. Fr iede l , M. Schrappe , B. Lembcke. Divis ion of Gastroenterology, Department of Medicine, Universities Frankfurt & Cologne, Germany.

The value of nasoenteral nutrition (NEN) in the treatment of the HIV associated Wasting Syndrom is unclear, up to now only 4 case reports (each involving one patient) have been published as abstracts. The purpose of this s tudy was to eva lua te acceptance , outcome and management strategies for enteral nutrition intervention in malnourished Aids patients. METHODS: 89 Aids patients (CDC stage C) with weight loss > 10% of their usual body weight underwent a medical work up for treatable disease and an intensified nutritional counseling. 23 Patients had no acute treatable opportunistic infection, tumor or contraindikation for enteral feeding and were offered NEN support. 12 patients declined NEN, 2 other patients did not finish the study due to cosmetic acceptance and compliance reasons. 9 Patients completed the 5 week NEN study. 2000 kcal/d O f a polymeric diet were given via a pump through a CH 8. polyurethan naso-gastric or duodenal feeding tube. Recently initiated AZT/DDI therapy was an exclusion criterium. RESULTS: 8 o u t o f 9 patients gainedweight (1-7.5 kg; Mean 3.1 kg) during the 5 week study. The 9th. pat ient who lost 1.8 kg, was rediagnosed and had CMV infection. After starting CMV therapy he gained 5 kg after NEN was restarted. In the 8 pat ients who gained weight , Body Cell Mass (BCM,measured by BIA) increased significantly (0.6-2.5 kg; Mean 1.2 kg). Albumin, Transferrin, Cholinesterase tended to be higher (not significant); CD 4 count and p24 Ag were unchanged after 5 weeks nu t r i t iona l therapy. No NEN induced compl ica t ions were seen. CONCLUSIONS: For patients not gaining weight with nutritional counseling (step 1), enteral nutrition (step 2) is indicated before initiation of more costly and risky parenteral nutrition (step 3). NEN is a less invasive and alternative procedure to PEG. NEN increased weight and BCM in all patients not having an active opportunistic infection. Although NEN was tolerated well , al l 4/9 patients who asked for continued nutritional support after completing the study, opted for PEG (due to psychosocial reasons) when offered as an alternative to NEN after completion of the study. We therefore recommend NEN in the initial phase of enteral nutrition therapy, to evaluate i f enteral therapy is effective, or if contraindications to PEG exists. For long term use of enteral nutrition a PEG is preferred by patients despite being an invasive procedure. - Supported by: Else Kr6ner-Fresenius Foundation.

• DISASSOCIATION OF FUNCTION AND MORPHOLOGY: A NEW MODEL OF INTESTINAL ADAPTATION USING BURMESE PYTHONS. S.M.Secor, E.E.Whang, S.W.Ashley, & J.Diamond. Depts. of Physiology & Surgery, UCLA School of Medicine, Los Angeles, CA

Burmese pythons exhibit an unprecedented adaptive response after ingestion of a meal, including as much as a 40-fold increase in intestinal nutrient uptake, a 45-fold increase in metabolic rate. and a more than 2-fold increase in intestinal mass. Because pythons possess cellular and molecular digestive processes similar to those of mammals and the magnitudes of their adaptive response is so remarkediy greater, we are using Burmese pythons to explore the mechanisms of intestinal adaptation. We have found that python small intestine up-regulates nutrient uptake and undergoes hypertrophy before the arrival of ingested nutrients into the small intestine Thus, we hypothesized that hormonal and/or neural signals, rather than luminal nutrients, were responsible for triggering intestinal adaptation. To test this hypothesis, we isolated from luminal continuity the.middle third of the small intestine while keeping its neurovascular supply intact (Thiry fistula). Continuity of the remaining intestine (main gut) was restored by reanastumosis. Following recovery from surgery one set of snakes were fed rat meals. We examined intestinal nutrient uptake (inverted-sleeve technique) and intestinal morphology (light and electron microscopy) m fasted snakes and snakes l and 3 days post-feeding. Within 24 hours after a meal, the main gut exhibited signs of adaptation: as much as a 10-fold increase in nutrient uptake, a 2-fold increase in mass. and a 5-fold increase in microvillus length. These changes persisted for at least 3 days following feeding. In contrast, the Thiry fistula exhibit no signs of either functional or morphological adaptation at 24 hours. However, at 3 days following a meal, the Thiry fistula exhibited significant increases in nutrient uptake, but morphological indices remained unchanged. From these results we propose: 1) the induction of morphological changes occurring during post- prandial intestinal adaptation reqmres a luminal signal; 2) initial functional adaptation of the main gut is triggered by a luminal signal; and, 3) neurohumoral signals alone can trigger a delayed functional response. Because the functional and morphological components of adaptation can be disassociated in this model, it holds promise for investigations of intestinal physiology.

BILE SALT-DEPENDENT CHOLESTERYL ESTER HYDROLASE AND CHOLESTEROL UPTAKE BY INTESTINAL CELLS. Raanan Shamir. William J. Johnson, Reza Zolfaghari, Edward A: Fisher. The Children's Hospital of Philadelphia and Medical College of Pennsylvania, Philadelphia, PA

Bile salt-stimulated eholesteryl ester hydrolase (CEH) has been implicated in t h e absorption of both free and esterified dietary cholesterol, but its role in the absorption and intracellular esterification of free cholesterol remains controversial.

To test the role of CEH in vitro, human intestinal CaCo2 cells transfected with rat CEH eDNA (Tr cells) or a control plasmid (NEO ceils) were incubated with mixed micelles that included taurocbolate, monoolein and various amounts of labeled cholesterol as free cholesterol or ester.

The % uptake of free cholesterolwas similar (P>0.5) between Tr and NEO cells, independent of final free cholesterol concentration (1 nM-50 #M), and averaged approximately 20% after 4h. The extent of esterification of the cholesterol taken up by both cell types was also similar. To demonstrate that these results were not due to insufficient expression of the eDNA, purified human or porcine CEH at a physiological concentration ( t00 nM) was added to the cultures and the % uptake actually decreased by approximately 25% (P <0.05). The use of different micelle stabilizers (monoolein vs. egg PC) demonstrated that a larger amount of free cholesterol (p < 0.0001) is taken by intestinal cells when monoolein is used, but still no difference in uptake was observed between Tr and NEO cells. In contrast to the effects on free cholesterol, the % uptake of cholesterol from micellar cholesteryl ester (eholesteryl-oleate, 5 or 10 #M) was increased 5-10X (Tr vs NEO, P <0.001), presumably as a result of ester hydrolysis by CEH in the medium and subsequent uptake of the liberated free cholesterol.

These results suggest that CEH promotes the absorption of dietary cholesterol only in the form of cholesteryl ester. In addition, in CaCo2 ceils, CEH does not play a significant role in the intracellular esterification of the free cholesterol derived from micelles.