influence of ornithin-alphaketoglutarate on postoperative protein metabolism

1
P.41 INFLUENCE OF ORNITHIN-ALPHAKETOGLUTARATE ON POSTOPERATIVE PROTEIN METABOLISM: K.-W.Jauch.J.Mangold.P.FUrst jurgical Department,University of Munich F G and Institute biol.Chemistry.Univ.Hohenheim &&&&s Ornithin-Alphaketoglutarat(OKG) have been suggested to improve postoperative protein metabolism.by decreasing urea production in the liver and improving protein synthesis in muscle tissue.Therefore we studied 16 patients undergoing elective colon resection for colon cancer without previous weightloss.metabolic disorders and metastatic disease. Patients were randomised and received until the 4.th postop. day a isocaloric (127 kJ/kg BW/day) and isonitrogenous (0.2 gN/kgBW/d) parenteral nutrition.In the OKG-group 20% of N was given as OKG,whereas the control group reveived a commerciable available aminoacid solution (Aminofusin-Pfrimmer Co). The functional proteins.liver enzymes and daily excretion of NH-3 .Urea and creatinine were determined beside measurements of protein synthesis and breakdown in muscle speci- mens on day 0.1 and 4. Total plasma protein.albumin.cholinesterase.prealbuminand retinal-binding-protein were not different in the two groups during the study period.(RBP: day o:OKG-2.73+0.9 mg/dl vs 2.73t0.63 day 1:2.00+0.51 vs 2.05tO.51 day 4:2.84+0.97 vs 3.02+1.31). - Also the liver enzymes a? well as blocd cells plasma urea .creatinTne and hematocrit revealed no differences. Daily excretion of creatinine was within the normal range on the first three postopera- t7ve days in both groups. Nitrogen balance neither showed any difference between the two groups.Considering non- urinary nitrogen losses and n-losses by drainage the daily nitrogen balances were betweerj -3.lt3.0 on the third day in the OKG-group and to.8t1.7 in the control group on the third day. _ From these datas we cannot conclude a beneficial effect of OKG in postoperative state. The differences to earlier studies may be due to different patients selection and to the different amino acid pattern of the control solution as may be concluded from the determination of plasma amino acids. p.42 W'lINO ACID MEIAbalSM OF CULTURED TUMOR CtLi_S, USING GLN-DIPEPTIDES AS WTRIENT SUBSTRATES. ;.Ollenschl~ger, A.Simmel', B.Biirger, G.Hamilton', E-Roth' Dep.of Internal Medicine II, lJniv.of Cologne, FRG, and of Surgery I', Univ.of Vienna; Austria The growth behaviour of cultured tumor cells is highly dependent on a sufficient supply of GLN. The aim of our study WIE to evaluate whether differences of cell proliferation, as a consequence of incubation media with and without GLN-compounds, are reflected by the amino acid (AA) con- centration changes of cell supernatants. Methods: A human hematopoietic tumor cell line !K 562) was. incubated at a density of 0.2 mill/ml in RPM1 1640 (19 AA = 4_5mM/l) + 2 mM/l GLN, re- apect. acetyl-,glycyl-GLN, and without. After 1,2,4 days,, cells were counted,and AA were analyzed in the filtered supernatant, using HPLC. Results: On days 1 and 2, the AA pattern of the supernatants were unchan- ged with the exception of ORN, well as of GLN, which increased 1QO fold in all media, as 1, and of GLY/ ALA for GLY-/AC-GLN containing media. At GLN was 1,38 mM/l in GLN-media, 0.56 in AC-GLN, 0.25 in GLV-GLN, 0 day without GLN. AC-GLN was 0.84, GLY-GLN 1.6. Cell proliferation correlated with the GLN concentr. - 0 GLN: 48% of +GLN, AC-GLN: al%, GLY-GLN: 70%. On day 5, r Y: 0.12 the AA patterns of all media were entirely assimilated, with mM/l also in the GLN-lacking medzum. Total AA cont. xere de- cr~eased from 6.5 to about 5.0 mM/l at the cost of all,except GLCl !Cl_!55~, GLY (0.2) , ALA CO.%), F’RCI (0.33) , ORN (O.Z4). Conclusion: The AA pattern of the culture medium of the GLN-dependently growing cell line K 562 is only characterized by the bioavailability of the GLN-compounds during the first 2 days of incubation. After that,a AA pattern is formated, 5peciflc, which is independent of the GLN supply, but cell- as we de+~rre from similar results in other cell lines. 71

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Page 1: Influence of ornithin-alphaketoglutarate on postoperative protein metabolism

P.41 INFLUENCE OF ORNITHIN-ALPHAKETOGLUTARATE ON POSTOPERATIVE PROTEIN METABOLISM:

K.-W.Jauch.J.Mangold.P.FUrst

jurgical Department,University of Munich F G and Institute biol.Chemistry.Univ.Hohenheim &&&&s

Ornithin-Alphaketoglutarat(OKG) have been suggested to improve postoperative protein metabolism.by decreasing urea production in the liver and improving protein synthesis in muscle tissue.Therefore we studied 16 patients undergoing elective colon resection for colon cancer without previous weightloss.metabolic disorders and metastatic disease. Patients were randomised and received until the 4.th postop. day a isocaloric (127 kJ/kg BW/day) and isonitrogenous (0.2 gN/kgBW/d) parenteral nutrition.In the OKG-group 20% of N was given as OKG,whereas the control group reveived a commerciable available aminoacid solution (Aminofusin-Pfrimmer Co). The functional proteins.liver enzymes and daily excretion of NH-3 .Urea and creatinine were determined beside measurements of protein synthesis and breakdown in muscle speci- mens on day 0.1 and 4. Total plasma protein.albumin.cholinesterase.prealbuminand retinal-binding-protein were not different in the two groups during the study period.(RBP: day o:OKG-2.73+0.9 mg/dl vs 2.73t0.63 day 1:2.00+0.51 vs 2.05tO.51 day 4:2.84+0.97 vs 3.02+1.31). - Also the liver enzymes a? well as blocd cells plasma urea .creatinTne and hematocrit revealed no differences. Daily excretion of creatinine was within the normal range on the first three postopera- t7ve days in both groups. Nitrogen balance neither showed any difference between the two groups.Considering non- urinary nitrogen losses and n-losses by drainage the daily nitrogen balances were betweerj -3.lt3.0 on the third day in the OKG-group and to.8t1.7 in the control group on the third day.

_

From these datas we cannot conclude a beneficial effect of OKG in postoperative state. The differences to earlier studies may be due to different patients selection and to the different amino acid pattern of the control solution as may be concluded from the determination of plasma amino acids.

p.42 W'lINO ACID MEIAbalSM OF CULTURED TUMOR CtLi_S, USING GLN-DIPEPTIDES AS

WTRIENT SUBSTRATES.

;.Ollenschl~ger, A.Simmel', B.Biirger, G.Hamilton', E-Roth'

Dep.of Internal Medicine II, lJniv.of Cologne, FRG, and of Surgery I', Univ.of Vienna; Austria

The growth behaviour of cultured tumor cells is highly dependent on a

sufficient supply of GLN. The aim of our study WIE to evaluate whether differences of cell proliferation, as a consequence of incubation media with and without GLN-compounds, are reflected by the amino acid (AA) con- centration changes of cell supernatants.

Methods: A human hematopoietic tumor cell line !K 562) was. incubated at a

density of 0.2 mill/ml in RPM1 1640 (19 AA = 4_5mM/l) + 2 mM/l GLN, re- apect. acetyl-,glycyl-GLN, and without. After 1,2,4 days,, cells were

counted,and AA were analyzed in the filtered supernatant, using HPLC. Results: On days 1 and 2, the AA pattern of the supernatants were unchan- ged with the exception of ORN, well as of GLN,

which increased 1QO fold in all media, as

1,

and of GLY/ ALA for GLY-/AC-GLN containing media. At GLN was 1,38 mM/l in GLN-media, 0.56 in AC-GLN, 0.25 in GLV-GLN, 0

day

without GLN. AC-GLN was 0.84, GLY-GLN 1.6. Cell proliferation correlated with the GLN concentr. - 0 GLN: 48% of +GLN, AC-GLN: al%, GLY-GLN: 70%. On day 5, r Y: 0.12

the AA patterns of all media were entirely assimilated, with mM/l also in the GLN-lacking medzum. Total AA cont. xere de-

cr~eased from 6.5 to about 5.0 mM/l at the cost of all,except GLCl !Cl_!55~,

GLY (0.2) , ALA CO.%), F’RCI (0.33) , ORN (O.Z4).

Conclusion: The AA pattern of the culture medium of the GLN-dependently growing cell line K 562 is only characterized by the bioavailability of the GLN-compounds during the first 2 days of incubation. After that,a AA pattern is formated, 5peciflc,

which is independent of the GLN supply, but cell- as we de+~rre from similar results in other cell lines.

71