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Parenteral use of L-alanyl-L-glutamine (Ala-Gln) and glycyl-L-tyrosine (Gly-Tyr) in postoperative patients
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PARENTEHAL USE UF L-ALANYL-L-GLUTAMINE (ALA-GLNJ A&d ~L~CYL-c-TYROSINE (GLY-1YR) IN POSTOPERATIVE PATIENTS. P. FDrst, S. Albers, P. Stehle, L. Pollack, N. Mertes*, C. Puchstein* (Inst.
Biol.
Chem.
& Nutr.,
Univ.
Hohenheim,
Stuttgart;
*Dept.
Anesth.
Miinster, FRG)
This is the first study investigating in vivo utilization of the synthetic dipeptides Ala-Gln and Gly-Tyr in postoperative trauma. 12 patients undergoing major uncomplicated ooerations were randomized in a control (C) group (n=6, 2F/4M, 51.8k5.6 years) and in a (40 kcal/kg peptide (P) group (3F/3M, 55.5i6.8 years). All patients received isoenergetic i3W.d. isonitroaenous (0.23 a N/kq BW.d) TPN over 5 davs. In the P-qroup part of the amino acids (AA) was-replaced by ila:Gin (286 mg/kg BW.d) and Gly-Tyr (56 mgjkg BW.d). Clinical biochemistry, daily N-balance and repeated measurements of plasma and muscle free (preop and 3/4th d postop.) AA and peptides were carried out throughout the study. The apparent corrected N-balance was calculated by considering the creatinine clearance and the changes of urea in the total body water. Ic/ec distribution of Hz0 and AA were calculated using the Cl-method. The day to day N-balance was significantly better in the P-group on each day of the study; the mean N-balance during the 5 postop. days being -1.5tO.4 (P) and -3.6tO.2 g N (C) (p
0.62
THE LEE OF Departments
SXOGENOUS of Surgery*
TO IMPROVE PROTEIN-SPARINS WRIHC EXPER-AL EFARVATIOW AJ Rich*, RFW Jacksonli and P Chambers* and Organic Chemistryli, University of Newcastle upon Tyne, England.
KETONES
Ketone bodies assume a key role during starvation when they “spare” muscle breakdown by replacing glucose as a principal brain fuel. Loss of nitrogen can be artificially reduced by the administration of exogenous B-hydroxybutyrate (BHB) during voluntary starvation in the obese, but this appears to be less effective following surgical injury. The form of BHB used has been the racemic mixture CD-DL-hydroxybutyrate) and since only the D-isomer is believed to be active in mammals, it seems possible that it might not be utilized efficiently. Accordingly a study was carried out to determine the effect on nitrogen balance in the semistarved rat of the D-isomer and an experimental polymer of the D-form of BHB in comparison with the racemic mixture. Four groups of rats were housed in metabolic cages and provided with one-third of their normal dally nutrient requirements for a five day period. ln addition, each was given 0.0658 of either normal saline (Ccntmlk), B-DL-hydroxybutyrate (group 1x3, 8-D-hydroxybutyrate (group m or B-D-hydroxybutyrate polymer (group Poiymer). 24-hour nitrogen balances were calculated. All groups lost weight, and mean nitrogen balances became Increasingly negative as the study progressed. Because of wide variations in voluntary nitrogen intake the mean percentage change in nitrogen balance on day 1 was compared with that for day 4 (%A,_,). This showed that in the Control group (%A,_. 13 f 220) and the Polymer group (%A,_., 17 f 38) there was an improvement in balance, whereas in group DL (%A,_, -179 2 78) and group D (%A,_, -783 r ‘-24) the change In balance became worse. The differences between the Polymer group and groups D (p = 0.002) and DL (p = 0.03) were significant or highly significant. These results demonstrate an effect of oral BHB polymer in reducing the magnitude of the negative nitrogen balance seen during semi-starvation in the rat. The effect is not seen with either 8-DL- or B-D-hydroxybutyrate where, under the conditions of oral feeding, ketones appear to result in excessive protein losses.
41
PARENTEHAL USE UF L-ALANYL-L-GLUTAMINE (ALA-GLNJ A&d ~L~CYL-c-TYROSINE (GLY-1YR) IN POSTOPERATIVE PATIENTS. P. FDrst, S. Albers, P. Stehle, L. Pollack, N. Mertes*, C. Puchstein* (Inst.
Biol.
Chem.
& Nutr.,
Univ.
Hohenheim,
Stuttgart;
*Dept.
Anesth.
Miinster, FRG)
This is the first study investigating in vivo utilization of the synthetic dipeptides Ala-Gln and Gly-Tyr in postoperative trauma. 12 patients undergoing major uncomplicated ooerations were randomized in a control (C) group (n=6, 2F/4M, 51.8k5.6 years) and in a (40 kcal/kg peptide (P) group (3F/3M, 55.5i6.8 years). All patients received isoenergetic i3W.d. isonitroaenous (0.23 a N/kq BW.d) TPN over 5 davs. In the P-qroup part of the amino acids (AA) was-replaced by ila:Gin (286 mg/kg BW.d) and Gly-Tyr (56 mgjkg BW.d). Clinical biochemistry, daily N-balance and repeated measurements of plasma and muscle free (preop and 3/4th d postop.) AA and peptides were carried out throughout the study. The apparent corrected N-balance was calculated by considering the creatinine clearance and the changes of urea in the total body water. Ic/ec distribution of Hz0 and AA were calculated using the Cl-method. The day to day N-balance was significantly better in the P-group on each day of the study; the mean N-balance during the 5 postop. days being -1.5tO.4 (P) and -3.6tO.2 g N (C) (p
0.62
THE LEE OF Departments
SXOGENOUS of Surgery*
TO IMPROVE PROTEIN-SPARINS WRIHC EXPER-AL EFARVATIOW AJ Rich*, RFW Jacksonli and P Chambers* and Organic Chemistryli, University of Newcastle upon Tyne, England.
KETONES
Ketone bodies assume a key role during starvation when they “spare” muscle breakdown by replacing glucose as a principal brain fuel. Loss of nitrogen can be artificially reduced by the administration of exogenous B-hydroxybutyrate (BHB) during voluntary starvation in the obese, but this appears to be less effective following surgical injury. The form of BHB used has been the racemic mixture CD-DL-hydroxybutyrate) and since only the D-isomer is believed to be active in mammals, it seems possible that it might not be utilized efficiently. Accordingly a study was carried out to determine the effect on nitrogen balance in the semistarved rat of the D-isomer and an experimental polymer of the D-form of BHB in comparison with the racemic mixture. Four groups of rats were housed in metabolic cages and provided with one-third of their normal dally nutrient requirements for a five day period. ln addition, each was given 0.0658 of either normal saline (Ccntmlk), B-DL-hydroxybutyrate (group 1x3, 8-D-hydroxybutyrate (group m or B-D-hydroxybutyrate polymer (group Poiymer). 24-hour nitrogen balances were calculated. All groups lost weight, and mean nitrogen balances became Increasingly negative as the study progressed. Because of wide variations in voluntary nitrogen intake the mean percentage change in nitrogen balance on day 1 was compared with that for day 4 (%A,_,). This showed that in the Control group (%A,_. 13 f 220) and the Polymer group (%A,_., 17 f 38) there was an improvement in balance, whereas in group DL (%A,_, -179 2 78) and group D (%A,_, -783 r ‘-24) the change In balance became worse. The differences between the Polymer group and groups D (p = 0.002) and DL (p = 0.03) were significant or highly significant. These results demonstrate an effect of oral BHB polymer in reducing the magnitude of the negative nitrogen balance seen during semi-starvation in the rat. The effect is not seen with either 8-DL- or B-D-hydroxybutyrate where, under the conditions of oral feeding, ketones appear to result in excessive protein losses.
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