258 Poster Sessions gradient in cirrhosis. The increase in whole-body oxygen uptake after a meal is reduced by propranolol in normal subjects, however, the effect in cirrhotic patients is unknown. Methods: Twelve patients with biopsy proven alcoholic cirrhosis were ran- domised to a standard liquid meal of 700 kcal alone or in combination with an IV infusion of propranolol (bolus injection of 0.1 mg/kg followed by 1 microgram/min/kg). Whole-body oxygen uptake and energy expenditure (EE) were measured by an open-circuit ventilated hood system before and for 2 hrs after the meal. Oxygen, haemoglobin and lactate were determined in arterial and hepatic venous blood. HBF was measured by constant in- fusion of indocyanine green. Splanchnic oxygen uptake and lactate flux in splanchnic blood drained by the liver were calculated by Fick's principle. Results" Meal-induced whole-body oxygen uptake was significantly lower in patients given propranolol: 135.7 q- 61.0 vs. 19.2 4- 38.0 mmol/120 min (mean -4- SD, P < 0.01), comparing to a reduction of EE in these patients from 67.0 -4- 26.1 to 15.0 ± 18.9 kJ/min (P < 0.01). The meal-induced increase in splanchnic oxygen uptake was obliterated by propranolol treat- ment: 0.92 ± 0.29 vs. -0.11 ± 0.29 mmol/min (P = 0.04). Splanchnic lactate flux was not affected by propranolol. Conclusion: Propranolol reduces meal-induced whole-body oxygen up- take and energy expenditure as well as splanchnic oxygen uptake. The splanchnic reduction in oxygen consumption can explain almost the entire reduction in whole-body oxygen consumption. ~'~A 'CROSS-TALK' BETWEEN POLYAMINE CATABOLISM AND PROTECTIVE CAPTOPRIL EFFECTS IN PARACETAMOL-HEPATOTOXlCITY D. Pavlovic, G. Bjelakovic, I. Stojanovic, G. Kocic, T. Cvetkovic, T. Jevtovic, V. Djordjevic. Institute of Biochemistry, Faculty of Medicine, University of Nis, Yugoslavia We have already demonstrated that captopril (SH-containing ACE in- hibitor) and putrescine may reverse depletion of hepatic GSH level in paracetamol treated rats (J Hepatol, 30, suppl, 1999: 148; J Hepatol, 32, supp2, 2000: 209). Although the cellular mechanism of paracetamol- induced hepatotoxicity remains controversial, the results of several studies suggest that the ability of paracetamol to inhibit passage of cell through both GI and S phases might suppress liver regeneration and repair. Know- ing that metabolism of polyamines is closely related to growth and regen- eration, that polyamines inhibit PKC and MAP kinases and can modulate redox cell signalization (all of which are proposed as a new precise mech- anism in paracetamol toxicity), our aim was to examine a possible relation between polyamine catabolism (PAO and DAO activities) and captopril (CP) beneficial effect in paracetamol-induced liver failure. Methods: For in vivo investigation, rats were divided into following groups: I-control, II-treated with a single paracetamol dose (800 mg/kg BM ip), III-given captopril orally for 5 days before paracetamol treatment at 7.5 mg/kg/daily dose, IV-treated with captopril only in the aforemen- tioned dose. Rats were killed 3 h after paracetamol administration. The results are as follows: Variable Control Paracetamol Paracetamil + CP Captopril Liver GSH ixM/mgp 24.16-1-4.5 14.414-2.5'** 28.63 ± 3.7 *+* 33.64-4.2** DAO U/rng p 1.54-0.09 2.64-0.1"** 1.74-0.18 "H" 1.4-4-0.07 PAO U/mgp 0.89 4- 0.06 1.25 4- 0.07* 0.92 4- 0.03 + 0.81 4- 0.02 XO nmol/mgp 3.78 4- 0.6 4.8 4- 0.46** 2.44 4- 0.394 +4 3.8 4- 0.7 Serum (U/I) AST 121.4 4- 20 535.34- 78*** 148.48 4- 48* + ++ 139.8 4- 15.3 ALT 48.2 4- 2.5 100.88 4- 14.1"** 60.18 4- 18.1 ++ 51.6 4- 3.0 *p < 0.05; **p < 0.01; ***p < 0.001 vs control; ÷ p < 0.01; ~ p < 0.00l vs paraceta- mol. This is the first study to demonstrate that paracetamol treatment can sig- nificantly increase polyamine catabolism. The obtained data permit the following conclusions. Condusious: first, paracetamot alters polyamine homeostatis; second, paracetamol possesses proantioxidant activity; third, during CP co- administration with paracetamol, the hepatotoxic effect, produced by paracetamol, was diminished. The results confirm the function of capto- pril as an antioxidant and hepatoprotector and establish a novel 'cross-talk' mechanism that allows signal integration. However, the precise role of polyamines in the signaling cascade in paracetamol-induced liver damage has not been investigated. These findings represent an interesting area for further research and therapeutic manipulation in fulminant liver diseases. -] THREE DAYS NON-INVASIVE 13C-METHACETIN LIVER FUNCTION BREATH TEST IN HEALTHY SUBJECTS Norbert Pixner, Kurt Lenz, Thomas Mueller, Xiuquin Zhu. Barmh Brueder A-4020 Linz Seilerstaette 2, Austria Purpose: Aim of the study was to evaluate, whether a non-invasive 13C- methacetin liver function breath test shows similar results when repeating the test for three days running. This could be clinically important, since liver function might be tested in short intervals under different therapeutic conditions. Methods: Seven healthy subjects (6 males, 1 females) were fasted overnight. Breath samples were collected at 10, 20, 30, 40, 50, 60, 80, 100 and 120 minutes after ingestion of 75 mg of 13C-methacetin dissolved into 100 ml of tea. The subjects repeated the test procedures for three days under the same conditions. Maximal 13CO2 values after 40 minutes and cumulative 13CO2 doses at 40 and 120 minutes were observed for three days, results were compared with the non-parametric Friedman-Test. Results: There was no statistically significant difference among the median maximal 13CO2 values after 40 minutes (31.2% vs 31.2% vs 33.0%, p = 0.192) the three days cumulative 13CO2 doses at 40 minutes (14.8%, 15.1% and 15.5% (p = 0.502)) and at 120 minutes (32.7%, 35.6% and 38.2%, p = 0.085) Conclusion: Our data demonstrate that the results of hepatic mitochondrial function measurement by a non-invasive 13C-methacetin breath test does not significantly change when repeating the test for three days running. Thus, this test may be repeated in short intervals when indicated, without falsification of the results by stimulating mitochondrial oxidation due to 13C-methacetin load. ~-I NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IN MORBID OBESE PATIENTS: CLINICAL AND LABORATORY FEATURES AND IMMUNOHISTOCHEMICAL INVESTIGATION OF HEPATIC STELLATE CELL ACTIVATION 2 2 3 Amoldo Riquelme 1, Camilo Boza , Carolina Gomez , Ignacio Duarte , 1 1 Sergio Guzman 2, Marco Arrese . Department of Gastroenterology, Catholic University of Chile School of Medicine, Santiago; 2Department of Digestive Surgery, Catholic University of Chile School of Medicine, Santiago; 3Department of Pathology, Catholic University of Chile School of Medicine, Santiago, Chile Baekgrounfl/Ainm: NAFLD is common in morbid obese patients and can progress to cirrhosis and liver failure. Hepatic stellate cell (HSC) activa- tion has a major role in hepatic fibrosis. Recently it has been reported that HSC activation may occur in NAFLD. This study evaluates liver pathol- ogy in morbid obese patients and assesses HSC activation in this selected population. Methods: Liver biopsies were taken at the time of bariatric surgery in 28 consecutive patients. Variables analyzed included body mass index (BMI), presence of diabetes mellitus and arterial hypertension, lipid profile, liver function tests, plasma glucose levels, insufinemia and insulin resistance by the homeostasis model assessment (HOMA). These variables were evalu- ated for correlation with specific histologic features. Activated HSC were identified immunohistochemically using a monoclonal antibody against alpha-actin, and semiquantitatively graded using a scoring method.