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O.22 Glutaminase and glutamine-synthetase activity indicates advantages of enterally supplemented glutamate as compared with glutamine
O.19 Pro- or a n t i o x i d a n t activity of ascorbic acid in the p r e s e n c e of 'free' iron in p l a s m a of preterm infants? T. M. B e r g e r 1, C. Polidori2, P. J. Evans3, B. Halliwell 3, J. Morrow4 and B. Frei 2 1Joint Program in Neonatology, Harvard Medical School, Boston, MA, 2Boston University School of Medicine, Boston, MA, 3University of London King's College, London, UK, 4 Vanderbilt University School of Medicine, Nashville, TN, USA. Background: Ascorbic acid (AA) is a powerful antioxidant. In the presence of non-transferrin-bound iron (Fefree), however, AA can act as a prooxidant and contribute to the production of hydroxyl radicals, which in turn may initiate lipid peroxidation. Cord plasma concentrations of AA are high in preterm (PT) infants and Fefree can be detected in the plasma of many PT infants. Aim: To determine whether the combination of Fefree and high AA is associated with increased oxidation of endogenous AA and lipid peroxidation in the plasma of PT infants. Methods: Plama concentrations of AA (HPLC with electrochemical detection), Fefree (bleomycin assay), and F2-isoprostanes (F21P, markers of in vivo lipid peroxidation) were measured in 29 PT infants and 5 adult non-smokers. Pooled plasma samples of selected PT infants with high concentrations of Fefree (n = 4, group I), low concentrations of Fefree (n = 4, group II) and no Fefree (n = 3, group III, and n = 4, group IV) and 3 adults (group V) were incubated at 37°C and the time-concentration curves of AA and cholesterol ester hydroperoxides (CEOOH), as a marker of lipid peroxidation, were measured. Results: AA and F21P were significantly higher in the plasma of PT infants than adults (P < 0.01 and P < 0.002, respectively). F21P was positively correlated with both gestational age (P = 0.002) and AA (P = 0.02); however, there was no independent effect of Fefree on F21P levels. In the incubated plasma samples, the maximum rate of AA oxidation was similar in the five groups and not affected by the presence of Fefree (Table). In all samples, AA effectively protected against lipid peroxidation, with no CEOOH detectable (<10 nomol.I -~) during the initial 31 h of incubation. After AA consumption, CEOOH were formed in all samples irrespective of Fefree status.
Sample Group I Group II Group Ill Group IV Group V
Fefree
InitialAA
Rate of AA oxidation
(~mol.1-1) 1.83 0.22 Not detected Not detected Not detected
(t~mol.1-1) 154 174 194 162 116
(pmol-I-l-h -1) 2.78 2.90 3.49 2.83 1.92
Conclusion: AA prevents, rather than promotes, lipid peroxidation in plasma of PT infants in the presence of Fefree.
0.20 G l u t a m i n e - e n r i c h e d enteral diet e n h a n c e s bacterial c l e a r a n c e in protracted bacterial peritonitis S. F u r u k a w a , H. Saito, T. Inaba, M. T. Lin, T Inoue, K. Fukatsu, I. Han, T. Matsuda, Y, Hashiguichi and T. Mute Department of Surgery, University of Tokyo, Tokyo, Japan. The purpose of this study was to examine the effects of glutamine (Gin)enriched enteral diets on bacterial clearance in a rat protracted peritonitis model. Twenty-three rats underwent gastrostomy and osmotic pumps were implanted into the peritoneal cavity. The rats received a continuous intragastric infusion of three different diets: Gin-depleted (Gin 0), Ginenriched with free amino acid form (Gin F) or Gin-enriched with oligopeptide form (Gin P). The three formulas were isocaloric (200 kcal/kg/day) and isonitrogenous (1.36 gN/kg/day). Gin F and Gin P formulas contained Gin 23% w/w of amino acids. The pumps delivered a continuous infusion of E. coil (5 x 108 CFU/day) from 48 h after implantation over 24 h. Then, the animals were sacrificed. Numbers of peritoneal exudative cells (PEC), numbers of viable bacteria in the peritoneal lavage fluid (PLF), blood, liver, and spleen were determined. Plasma amino acid levels were measured. Tumour necrosis factor (TNF) and interleukin (IL)-8 levels in the PLF and plasma were determined with ELISA.
Results: Gin O(n = 7)
Gin F (n = 8)
Gin P (n = 8)
Bacterial no. in the PLF 4.16 -+0.20 2.33 ± 0.57* 1.52 ± 0.75** (log CFU/0.1 ml) Bacterial no. in the liver 3.19 _+0.34 1.86 _+0.29* 1.79 ± 0.47* (log CFU/1.0 gm) Means -+ SEM, *P < 0.05 vs Gin 0, **P < 0.01 vs Gin 0, ANOVA followed by Fisher PLSD.
Numbers of PEC were not different among the three groups. Numbers of bacteria in the PLF correlated significantly with the numbers of bacteria in the liver (r= 0.74, P < 0.01). There were no differences in numbers of bacteria in the blood or spleen. TNF and IL-8 levels in the PLF and plasma were not different among the three groups. Plasma levels of Gin, proline, alanine and citrulline were significantly higher in Gin F and Gin P groups than in Gin 0. Conclusions: These results suggest that antecedent Gin supplementation can enhance peritoneal and hepatic bacterial clearance, regardless of Gin form, in this model. The roles of TNF and IL-8 in enhancing bactericidal activity remain to be clarified. A Gin-enriched enteral diet may be more beneficial than a Gin-depleted enteral diet in peritonitis.
O.21 Effects of a short-term training program on hospitalized subjects suffering from protein-energy malnutrition S. B e r m o n , X. H6buterne, J. L. Peroux, P. Marconnet and P. Rampal Laboratoire de Biomecanique et Biologie de I'Exercice de I'Universite de Nice Sophia-Antipolis, France, and Service de Gastroenterologie et Nutrition, HSpital de I'Archet, CHU de Nice, France. Purpose: The aim of the present work is to study the effects of a shortterm aerobic training program on (1) nutritional status, (2) energy intake, (3) energy expenditure of hospitalized patients suffering from proteinenergy malnutrition. Methods: Fourteen malnourished subjects, 66.9 _+2.1 years old (mean _+SEM), treated with cyclic enteral nutrition (CyEN), were divided in to an active group (A) or control group (C), according to whether they took part or not in a 3-week aerobic training program (treadmill walking at 50% VO2max). At Day 0 (Do)-D1 and D2o-D21 subjects underwent the following tests: (1) calculation of the global nutritional deficiency (GND), a multiparametric assessment of nutritional status (H6buterne et al 1995), (2) measurement of energy intake (enteral intake + voluntary oral intake (VOI)), (3) evaluation of daily energy expenditure, without training session, a) with a 24-h heart rate (HR) recorder providing minimal HR (HRmin), average HR for 24-h (HR24_h), average HR between 07:00 h and 19:00 h (HR12_h), b) with an ankle secured pedometer. Results: Energy intakes were similar in both groups (mean value: 189.4 kJ.kg-l.d-1). GND showed a significant (P < 0.05) improvement in A compared to C (20.2 _+2.0% to 10.6 _+2.6% vs 21.8 _+ 1.7% to 18.6 _+ 2.4%). No significant changes in VOI were observed intra and inter groups. Reduction of HRm~n (P < 0.05) was observed in A (5 beats.min -~) whereas no significant changes in HR24_h and HR12. h were noted in both groups. A subjects showed a higher increase (P < 0.05) in pedometer readings compared to C. Discussions: A short-term aerobic training program, in old malnourished subjects, demonstrated positive effects on nutritional recovery. The lack of change in oral intake could be explained by a high energy intake provided by CyEN (mean value: 101.2kJ.kg-l.d-~). Possible reduction of maximal HR in A, as previously described by Rogers et al (1988), associated with HRmin reduction could evidence a reserve HR shift towards low HR values. Thus, the steady HR24. h and HR12_h observed in A could attest for an increased metabolic activity partly confirmed by the pedometer results.
0.22 G l u t a m i n a s e and g l u t a m i n e - s y n t h e t a s e activity indicates a d v a n t a g e s of enterally s u p p l e m e n t e d glutamate as c o m p a r e d with g l u t a m i n e M. H a s e b e , E. Mori, H. Suzuki, J. Furukawa, K. Kobayashi, T Akaike* and Y. Ueda* Trauma and Critical Care Center, Teikyo University School of Medicine, and * Terumo Corporation, Tokyo, Japan. Although glutamine (GLN) is a conditionally essential fuel source for the enterocyte, not all of the liquid enteral diets (EDs) contain this amino acid because of it being unstable in water. We have reported that glutamate (GLU), stable in water, can replace GLN with regard to benefit as an energy source for the enterocyte, under the hypothesis that both amino acids must be oxidized through the same pathway after GLN is converted to GLU. The purpose of this study was to elucidate the metabolic difference between enterally supplemented GLU and GLN by measuring enzyme activity. A 30% burn was applied in rats. The animals received an ED containing one of the following three amino acid formulas: 30% GLU (GLU-group: n =
8), 30% GLN (GLN-group: n - 7), and GLX-free (CTR-group: n = 6), for 60 h. Each ED was isocaloric and isonitrogenous. The small intestine and liver were obtained for the enzymatic study. Amino acid levels were measured in portal blood. Regarding the enzyme activity (nmol product/min/mg protein), glutaminase activity in the jejunal mucosa was significantly lower in GLU-group (40.2 + 8.1) than in GLN-group (58.4 _+10.9) and also than in CTR-group (60.4 +_ 13.8). Glutamine-synthetase activity in the liver tissue of GLUgroup (7.03 _+ 1.25) was higher than that of GLN-group (5.98 _+0.87) or CTR-group (5.00 + 1.21). Alanine level of the portal blood was significantly higher in GLU-group compared to the other two groups. The increase in portal atanine is considered to result from accelerated conversion of GLU to c~-ketoglutarate. The result of the enzymatic study supports that GLU is well oxidized in the enterocyte regardless of glutaminase activity and also its remnant may be converted to GLN in the liver. Qn the other hand, GLN may not be fully oxidized in situations in which glutaminase activity is suppressed, since GLN cannot affect glutaminase activity. We conclude that GLU is an advantageous fuel source for enterocytes as compared with GLN.
0.23 I n c r e a s e d liver protein s y n t h e s i s after a casein protein meal in c o m p a r i s o n to a soy protein meal M. J. B r u i n s , N. E. R Deutz and P. B. Soeters Dept Surgery, Univ. Limburg, Maastricht, The Netherlands. Soy has been claimed to provide protein of equal quality as milk protein, based on amino acid scoring patterns. In bio-assays, soy bean proteins, however, give consistently lower biological value. We showed that soy protein reduced amino acid retention in the gut wall during a meal [1]. As the role of liver still remains unknown, we investigated the response of the liver to soy and milk protein meals. Methods: Iso-nitrogenous enteral nutrition, consisting of maltodextrin (137g/I) with added casein (53g/I) or soy (68g/I) protein, was given to conscious, healthy female pigs (20-25 kg, n = 6) in which catheters were placed in the portal vein, the hepatic vein and the abdominal aorta, >1 week before. A primed-constant infusion protocol with L-[ring-2,63H]Phenylalanine (PHE) and L-[3,4-3H]Valine (VAL) was used to calculate liver PHE and VAL disposal, production and net balance (NB). VAL is used as an indicator for liver protein synthesis and PHE for liver PHE oxidation. Measurements were done postabsorptively and 2 h after initiation of enteral nutrition at a constant rate of 10 ml/kg body weight/h. Results: Both liver PHE production and disposal increased after soy, indicating an increase in PHE oxidation (not shown). However in casein, VAL production and disposal increased (Table). There was no difference between the two groups in the net balance of PHE and VAL.
4th Session - CANCER,
0.25 Altered liver m e t a b o l i s m in weight-stable and w e i g h t - l o s i n g c a n c e r patients detected by Sip m a g n e t i c r e s o n a n c e s p e c t r o s c o p y in vitro P. C. D a g n e l i e , P. E, Sijens, J. W O. van den Berg, G. R. Swart, M. Oudkerk and J. H. P. Wilson Department of Diagnostic Radiology, Daniel den Hoed Cancer Center, Rotterdam, and Institute of Internal Medicine II, Erasmus University of Rotterdam, The Netherlands. Introduction: In animals with experimental tumours, marked reductions in hepatic phosphorylation status and intracellular levels of several intermediates of gluconeogenesis and lipid synthesis have been reported, using biochemical assays or 31p magnetic resonance spectroscopy (MRS) in vivo [1]. The purpose of this study was to determine whether similar abnormalities in liver metabolism are observed in human cancer patients with and without weight loss, using 31p whole-body MRS. Methods: Weight-stable (WS, n = 13) and weight-losing (WL, n = 10) cancer patients, without liver metastases or metabolic disease, and healthy control subjects (C, n = 12) were studied. Food intake was appraised by a 7-day food record. After an overnight fast, hepatic 31p MRS spectra were obtained using a Siemens Vision/Helicon MR system (2 Tesla, 16cm surface coil, repetition time 20 s).
Group
Production
Disposal
NB (+ = uptake)
Postabsorptive 771 _+280 736 _+221 -281 _+287 Casein 3953-+1174 a 3516+826 a 714+666 Soy 1779 _+853 659 +_283b 616 _+1367 Mean (nmol/kg bw/min) _+SEM. t-test: ap < 0.05 vs postabsorptive, bp < '0.05 VS casein.
Conclusion: These results indicate that casein stimulates liver amino acid synthesis and turnover while soy stimulates liver amino acid oxidation. These effects, however, did not result in changes in net uptake or release by the liver. Whether these effects influence liver urea production remains to be established.
Reference: [1] Clin Nutr 1995; 14 (suppl 2): 32.
0.24 C o n t i n u o u s jejunal application of s o l u b l e fibre on c h o l e c y s t o k i n i n and n e u r o t e n s i n release in surgical patients E. Kollig, M. Senkal, M. Kemen, B. Marpe, R. Meier1 and V. Zumtobel Dept of Surge~ Ruhr-University Bochum, Germany," 1Division of Gastroenterology, Kantonsspital Liestal, Switzerland. It has been shown that a liquid diet with soluble guar fibre, given as a bolus for 7 days, increases fasting cholecystokinin (CCK) concentrations. The aim of this study was to assess the effect of continuous feeding on plasma CCK and neurotensin (NT) release in patients who were operated for upper gastrointestinal cancer. Patients (n = 23), after upper gastrointestinal surgery (esophageal resection, gastrectomy), received continuously a liquid diet by jejunostomy. Two weeks after operation tube feeding and oral intake was discontinued for 24 h. Continuous jejunal tube feeding was then started and patients received either the standard enteral diet (SD) (n = 9) or the same diet with 2 0 g soluble guar fibre (Sunfiber ®, Sandoz Nutrition, Switzerland) (GD) (n = 14) at an infusion rate of 120 ml/h. Blood was drawn for basal CCK and NT levels and at regular intervals (30, 50, 70 and 70 min) after enteral feeding had started. CCK and NT concentrations were measured by specific radioimmunoassays. Basal CCK levels were 0.35 _+0.1 and increased to 2.6 +_ 1.0pg/ml after 90 min in the SD group. In the GD group, basal CCK levels were 1.3 + 0.4 and raised to 4.6 _+1.5 pg/ml at the same time. NT levels were 9.0 :~_2 and increased to 88 +_ 17 pg/ml after 90 min in the SD group. Similarly, basal NT levels were 6.4 _+ 1.3pg/ml and increased to 106 _+ 43pg/ml after 90 rain in the GD groups. No difference was seen for basal and postprandial concentrations between the two diets. Our data show a similar postprandial response for standard and guar fibre supplemented enteral diets in continuous jejunal feeding. In contrast to oral bolus feeding regimens, continuous feeding of a guar fibre containing liquid diet does not change basal CCK concentrations. This may explain the tolerability of jejunal feeding in pancreatitis patients.
TRANSPLANTATION
Results: In contrast with tumour-bearing animals, liver phosphorylation status (indicated by Pi/ATP) was unchanged (Table 1). However, despite similar energy intake in all groups, phosphomonoester (PME) to ATP ratios and pH values increased significantly (P < 0.05) in the order control < WS < WL (Table 1), and were significantly con'elated with the degree of weight loss in the previous 6 months. Phosphodiesters (PDE) were elevated in WS and WL cancer patients alike. Raised PME levels in cancer patients were combined with a significant downfield shift of the PME peak position, suggesting that elevated PME was caused by raised hepatic levels of gluconeogenic intermediates. Hepatic concentrations of metabolites relative to ATP concentration (mean _+SEM). Cancer, Cancer, Parameter Controlsubjects weight-stable weight-lo.c~ing 2PME/ATP PDE/ATP Pi/ATP pH
0.58 ± 0.04 1.84 -+0.08 0.56 -+0.03 7.40 -+0.04
0.72 -+0.07 2.27 ± 0.15 0.61 -+0.05 7.53 -+0.07
090 -+0.12 2.08 -+0.16 0.56 -+0.08 7.70 -+0.07
Conclusions: The MRS changes observed in cancer patients, despite normal food intake, suggest fundamental alterations within the hepatic
Sample Group I Group II Group Ill Group IV Group V
Fefree
InitialAA
Rate of AA oxidation
(~mol.1-1) 1.83 0.22 Not detected Not detected Not detected
(t~mol.1-1) 154 174 194 162 116
(pmol-I-l-h -1) 2.78 2.90 3.49 2.83 1.92
Conclusion: AA prevents, rather than promotes, lipid peroxidation in plasma of PT infants in the presence of Fefree.
0.20 G l u t a m i n e - e n r i c h e d enteral diet e n h a n c e s bacterial c l e a r a n c e in protracted bacterial peritonitis S. F u r u k a w a , H. Saito, T. Inaba, M. T. Lin, T Inoue, K. Fukatsu, I. Han, T. Matsuda, Y, Hashiguichi and T. Mute Department of Surgery, University of Tokyo, Tokyo, Japan. The purpose of this study was to examine the effects of glutamine (Gin)enriched enteral diets on bacterial clearance in a rat protracted peritonitis model. Twenty-three rats underwent gastrostomy and osmotic pumps were implanted into the peritoneal cavity. The rats received a continuous intragastric infusion of three different diets: Gin-depleted (Gin 0), Ginenriched with free amino acid form (Gin F) or Gin-enriched with oligopeptide form (Gin P). The three formulas were isocaloric (200 kcal/kg/day) and isonitrogenous (1.36 gN/kg/day). Gin F and Gin P formulas contained Gin 23% w/w of amino acids. The pumps delivered a continuous infusion of E. coil (5 x 108 CFU/day) from 48 h after implantation over 24 h. Then, the animals were sacrificed. Numbers of peritoneal exudative cells (PEC), numbers of viable bacteria in the peritoneal lavage fluid (PLF), blood, liver, and spleen were determined. Plasma amino acid levels were measured. Tumour necrosis factor (TNF) and interleukin (IL)-8 levels in the PLF and plasma were determined with ELISA.
Results: Gin O(n = 7)
Gin F (n = 8)
Gin P (n = 8)
Bacterial no. in the PLF 4.16 -+0.20 2.33 ± 0.57* 1.52 ± 0.75** (log CFU/0.1 ml) Bacterial no. in the liver 3.19 _+0.34 1.86 _+0.29* 1.79 ± 0.47* (log CFU/1.0 gm) Means -+ SEM, *P < 0.05 vs Gin 0, **P < 0.01 vs Gin 0, ANOVA followed by Fisher PLSD.
Numbers of PEC were not different among the three groups. Numbers of bacteria in the PLF correlated significantly with the numbers of bacteria in the liver (r= 0.74, P < 0.01). There were no differences in numbers of bacteria in the blood or spleen. TNF and IL-8 levels in the PLF and plasma were not different among the three groups. Plasma levels of Gin, proline, alanine and citrulline were significantly higher in Gin F and Gin P groups than in Gin 0. Conclusions: These results suggest that antecedent Gin supplementation can enhance peritoneal and hepatic bacterial clearance, regardless of Gin form, in this model. The roles of TNF and IL-8 in enhancing bactericidal activity remain to be clarified. A Gin-enriched enteral diet may be more beneficial than a Gin-depleted enteral diet in peritonitis.
O.21 Effects of a short-term training program on hospitalized subjects suffering from protein-energy malnutrition S. B e r m o n , X. H6buterne, J. L. Peroux, P. Marconnet and P. Rampal Laboratoire de Biomecanique et Biologie de I'Exercice de I'Universite de Nice Sophia-Antipolis, France, and Service de Gastroenterologie et Nutrition, HSpital de I'Archet, CHU de Nice, France. Purpose: The aim of the present work is to study the effects of a shortterm aerobic training program on (1) nutritional status, (2) energy intake, (3) energy expenditure of hospitalized patients suffering from proteinenergy malnutrition. Methods: Fourteen malnourished subjects, 66.9 _+2.1 years old (mean _+SEM), treated with cyclic enteral nutrition (CyEN), were divided in to an active group (A) or control group (C), according to whether they took part or not in a 3-week aerobic training program (treadmill walking at 50% VO2max). At Day 0 (Do)-D1 and D2o-D21 subjects underwent the following tests: (1) calculation of the global nutritional deficiency (GND), a multiparametric assessment of nutritional status (H6buterne et al 1995), (2) measurement of energy intake (enteral intake + voluntary oral intake (VOI)), (3) evaluation of daily energy expenditure, without training session, a) with a 24-h heart rate (HR) recorder providing minimal HR (HRmin), average HR for 24-h (HR24_h), average HR between 07:00 h and 19:00 h (HR12_h), b) with an ankle secured pedometer. Results: Energy intakes were similar in both groups (mean value: 189.4 kJ.kg-l.d-1). GND showed a significant (P < 0.05) improvement in A compared to C (20.2 _+2.0% to 10.6 _+2.6% vs 21.8 _+ 1.7% to 18.6 _+ 2.4%). No significant changes in VOI were observed intra and inter groups. Reduction of HRm~n (P < 0.05) was observed in A (5 beats.min -~) whereas no significant changes in HR24_h and HR12. h were noted in both groups. A subjects showed a higher increase (P < 0.05) in pedometer readings compared to C. Discussions: A short-term aerobic training program, in old malnourished subjects, demonstrated positive effects on nutritional recovery. The lack of change in oral intake could be explained by a high energy intake provided by CyEN (mean value: 101.2kJ.kg-l.d-~). Possible reduction of maximal HR in A, as previously described by Rogers et al (1988), associated with HRmin reduction could evidence a reserve HR shift towards low HR values. Thus, the steady HR24. h and HR12_h observed in A could attest for an increased metabolic activity partly confirmed by the pedometer results.
0.22 G l u t a m i n a s e and g l u t a m i n e - s y n t h e t a s e activity indicates a d v a n t a g e s of enterally s u p p l e m e n t e d glutamate as c o m p a r e d with g l u t a m i n e M. H a s e b e , E. Mori, H. Suzuki, J. Furukawa, K. Kobayashi, T Akaike* and Y. Ueda* Trauma and Critical Care Center, Teikyo University School of Medicine, and * Terumo Corporation, Tokyo, Japan. Although glutamine (GLN) is a conditionally essential fuel source for the enterocyte, not all of the liquid enteral diets (EDs) contain this amino acid because of it being unstable in water. We have reported that glutamate (GLU), stable in water, can replace GLN with regard to benefit as an energy source for the enterocyte, under the hypothesis that both amino acids must be oxidized through the same pathway after GLN is converted to GLU. The purpose of this study was to elucidate the metabolic difference between enterally supplemented GLU and GLN by measuring enzyme activity. A 30% burn was applied in rats. The animals received an ED containing one of the following three amino acid formulas: 30% GLU (GLU-group: n =
8), 30% GLN (GLN-group: n - 7), and GLX-free (CTR-group: n = 6), for 60 h. Each ED was isocaloric and isonitrogenous. The small intestine and liver were obtained for the enzymatic study. Amino acid levels were measured in portal blood. Regarding the enzyme activity (nmol product/min/mg protein), glutaminase activity in the jejunal mucosa was significantly lower in GLU-group (40.2 + 8.1) than in GLN-group (58.4 _+10.9) and also than in CTR-group (60.4 +_ 13.8). Glutamine-synthetase activity in the liver tissue of GLUgroup (7.03 _+ 1.25) was higher than that of GLN-group (5.98 _+0.87) or CTR-group (5.00 + 1.21). Alanine level of the portal blood was significantly higher in GLU-group compared to the other two groups. The increase in portal atanine is considered to result from accelerated conversion of GLU to c~-ketoglutarate. The result of the enzymatic study supports that GLU is well oxidized in the enterocyte regardless of glutaminase activity and also its remnant may be converted to GLN in the liver. Qn the other hand, GLN may not be fully oxidized in situations in which glutaminase activity is suppressed, since GLN cannot affect glutaminase activity. We conclude that GLU is an advantageous fuel source for enterocytes as compared with GLN.
0.23 I n c r e a s e d liver protein s y n t h e s i s after a casein protein meal in c o m p a r i s o n to a soy protein meal M. J. B r u i n s , N. E. R Deutz and P. B. Soeters Dept Surgery, Univ. Limburg, Maastricht, The Netherlands. Soy has been claimed to provide protein of equal quality as milk protein, based on amino acid scoring patterns. In bio-assays, soy bean proteins, however, give consistently lower biological value. We showed that soy protein reduced amino acid retention in the gut wall during a meal [1]. As the role of liver still remains unknown, we investigated the response of the liver to soy and milk protein meals. Methods: Iso-nitrogenous enteral nutrition, consisting of maltodextrin (137g/I) with added casein (53g/I) or soy (68g/I) protein, was given to conscious, healthy female pigs (20-25 kg, n = 6) in which catheters were placed in the portal vein, the hepatic vein and the abdominal aorta, >1 week before. A primed-constant infusion protocol with L-[ring-2,63H]Phenylalanine (PHE) and L-[3,4-3H]Valine (VAL) was used to calculate liver PHE and VAL disposal, production and net balance (NB). VAL is used as an indicator for liver protein synthesis and PHE for liver PHE oxidation. Measurements were done postabsorptively and 2 h after initiation of enteral nutrition at a constant rate of 10 ml/kg body weight/h. Results: Both liver PHE production and disposal increased after soy, indicating an increase in PHE oxidation (not shown). However in casein, VAL production and disposal increased (Table). There was no difference between the two groups in the net balance of PHE and VAL.
4th Session - CANCER,
0.25 Altered liver m e t a b o l i s m in weight-stable and w e i g h t - l o s i n g c a n c e r patients detected by Sip m a g n e t i c r e s o n a n c e s p e c t r o s c o p y in vitro P. C. D a g n e l i e , P. E, Sijens, J. W O. van den Berg, G. R. Swart, M. Oudkerk and J. H. P. Wilson Department of Diagnostic Radiology, Daniel den Hoed Cancer Center, Rotterdam, and Institute of Internal Medicine II, Erasmus University of Rotterdam, The Netherlands. Introduction: In animals with experimental tumours, marked reductions in hepatic phosphorylation status and intracellular levels of several intermediates of gluconeogenesis and lipid synthesis have been reported, using biochemical assays or 31p magnetic resonance spectroscopy (MRS) in vivo [1]. The purpose of this study was to determine whether similar abnormalities in liver metabolism are observed in human cancer patients with and without weight loss, using 31p whole-body MRS. Methods: Weight-stable (WS, n = 13) and weight-losing (WL, n = 10) cancer patients, without liver metastases or metabolic disease, and healthy control subjects (C, n = 12) were studied. Food intake was appraised by a 7-day food record. After an overnight fast, hepatic 31p MRS spectra were obtained using a Siemens Vision/Helicon MR system (2 Tesla, 16cm surface coil, repetition time 20 s).
Group
Production
Disposal
NB (+ = uptake)
Postabsorptive 771 _+280 736 _+221 -281 _+287 Casein 3953-+1174 a 3516+826 a 714+666 Soy 1779 _+853 659 +_283b 616 _+1367 Mean (nmol/kg bw/min) _+SEM. t-test: ap < 0.05 vs postabsorptive, bp < '0.05 VS casein.
Conclusion: These results indicate that casein stimulates liver amino acid synthesis and turnover while soy stimulates liver amino acid oxidation. These effects, however, did not result in changes in net uptake or release by the liver. Whether these effects influence liver urea production remains to be established.
Reference: [1] Clin Nutr 1995; 14 (suppl 2): 32.
0.24 C o n t i n u o u s jejunal application of s o l u b l e fibre on c h o l e c y s t o k i n i n and n e u r o t e n s i n release in surgical patients E. Kollig, M. Senkal, M. Kemen, B. Marpe, R. Meier1 and V. Zumtobel Dept of Surge~ Ruhr-University Bochum, Germany," 1Division of Gastroenterology, Kantonsspital Liestal, Switzerland. It has been shown that a liquid diet with soluble guar fibre, given as a bolus for 7 days, increases fasting cholecystokinin (CCK) concentrations. The aim of this study was to assess the effect of continuous feeding on plasma CCK and neurotensin (NT) release in patients who were operated for upper gastrointestinal cancer. Patients (n = 23), after upper gastrointestinal surgery (esophageal resection, gastrectomy), received continuously a liquid diet by jejunostomy. Two weeks after operation tube feeding and oral intake was discontinued for 24 h. Continuous jejunal tube feeding was then started and patients received either the standard enteral diet (SD) (n = 9) or the same diet with 2 0 g soluble guar fibre (Sunfiber ®, Sandoz Nutrition, Switzerland) (GD) (n = 14) at an infusion rate of 120 ml/h. Blood was drawn for basal CCK and NT levels and at regular intervals (30, 50, 70 and 70 min) after enteral feeding had started. CCK and NT concentrations were measured by specific radioimmunoassays. Basal CCK levels were 0.35 _+0.1 and increased to 2.6 +_ 1.0pg/ml after 90 min in the SD group. In the GD group, basal CCK levels were 1.3 + 0.4 and raised to 4.6 _+1.5 pg/ml at the same time. NT levels were 9.0 :~_2 and increased to 88 +_ 17 pg/ml after 90 min in the SD group. Similarly, basal NT levels were 6.4 _+ 1.3pg/ml and increased to 106 _+ 43pg/ml after 90 rain in the GD groups. No difference was seen for basal and postprandial concentrations between the two diets. Our data show a similar postprandial response for standard and guar fibre supplemented enteral diets in continuous jejunal feeding. In contrast to oral bolus feeding regimens, continuous feeding of a guar fibre containing liquid diet does not change basal CCK concentrations. This may explain the tolerability of jejunal feeding in pancreatitis patients.
TRANSPLANTATION
Results: In contrast with tumour-bearing animals, liver phosphorylation status (indicated by Pi/ATP) was unchanged (Table 1). However, despite similar energy intake in all groups, phosphomonoester (PME) to ATP ratios and pH values increased significantly (P < 0.05) in the order control < WS < WL (Table 1), and were significantly con'elated with the degree of weight loss in the previous 6 months. Phosphodiesters (PDE) were elevated in WS and WL cancer patients alike. Raised PME levels in cancer patients were combined with a significant downfield shift of the PME peak position, suggesting that elevated PME was caused by raised hepatic levels of gluconeogenic intermediates. Hepatic concentrations of metabolites relative to ATP concentration (mean _+SEM). Cancer, Cancer, Parameter Controlsubjects weight-stable weight-lo.c~ing 2PME/ATP PDE/ATP Pi/ATP pH
0.58 ± 0.04 1.84 -+0.08 0.56 -+0.03 7.40 -+0.04
0.72 -+0.07 2.27 ± 0.15 0.61 -+0.05 7.53 -+0.07
090 -+0.12 2.08 -+0.16 0.56 -+0.08 7.70 -+0.07
Conclusions: The MRS changes observed in cancer patients, despite normal food intake, suggest fundamental alterations within the hepatic