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The role of hepatic tissue in changes of protein metabolism after endotoxin treatment in rats
221
Nutrition, metnbolism, ulcolzolic liver discuses. pharnzrtcolog~~
CARBOHYDRATE DEFICIENT TRANSFERRIN AND KETOISOCAPROIC ACID TESTS FOR ALCOHOL ABUSE COMPARED WITH LIVER HISTOLOGY AND BIOCHEMICAL MARKERS A. Minzer, C. Jenni, P. Hildebrand, B. Meyer-Wyss, J. Drewe, C. Beglinger, CC Sieber. Division of Gastroenterology, University Hospital Basel,‘Basel, Switzerland. Laborchemical tests with a high sensitivity and specificity for moderate to heavy alcohol abuse are still lacking. Two markers, carbohydrate deficient transferrin (CDT) plasma levels and ketoisocaproic acid (KICA) metabolism claim to be both sensitive and specific. Aims. To compare these tests with laborchemical markers and liverhistology for exagerated alcohol consumption (>4Og/d for females, >6Og/d for males). Methods. 6i patients (38m, 23f, mean age 48~) with different gramer disease (Child class 52 A, 6 B and 3 C) were included into the study. CDT was tested by CDTect (Pharmacia) in all 61 patients and as %CDT of total transferrin (Axis) in 27 patients. KICA metabolism, galactose elimination capacity (GEK), biochemical and hematological parameters were tested in all patients. Results. Sensitivity and specificity were calculated in relation to alcoholintake. KICA gGT MCV . %CDT CDTect 1% Sensitivity 75 0 2 78; 84% 46% 100% 80% d KICA-test showed an inacceotable low sensitivit;. Besides a good sensitivity and high specificity for %CD?‘. significant correlations were found for bilirubin, transaminases, gGT, albumin, prothrombin time, platelet count, mean corpuscular volume, Child class, histology, GEK but not with KICA-test. Conclusion. Tests like %CDT with a high sensitivity and especially specificity are important, especially when used for forensic purposes. Patients history, clinical examination together with gGT and MCV already give a good estimate of chronic alcohol abuse.
NEUROLOGICAL TOXICITY OF ALPHA-INTERFERON IN HCV- OR HBVBELATED IMMUNOLOGICAL SYSTEMIC DISORDERS. C. Ferri’. L.La Civita’. M.Mont?. G.Lonnotnbardo’. P.Fadda’, G.Cereccia2, P.Gentilin?. G.Pesero’. AL.. Zieneeo2. ‘Depertment of Internal Medicine, University of Piss, Pisa, Italy ; %tstitnte of Internal Medicine, University of Florence, Florence, Italy.
A neurological toxicity of alpha-interferon (a-IFN) treatment has been anedoctally reported in different conditions, i.e. viral hepatitis, immunological diseases and malignances. We treated with a-IFN 75 pts with hepatotropic virus- related immunological systemic disorders, such as mixed ctyoglobulmemia. Here, we report a cohort of 6 pts (SHCV+, IHBV+) with severe neuropathy complicanting IFN treatment. Before a-IFN Pt no. 1 2 3 4 5 6
Age Sex 59 M 45 M 47 M 46 F 64 F 52 F
MC :mixed
After a-IFN
Clinical manifestations MC+CHtypeB
MU/wk
Dnrlwk
symptoms
21
4
severe smPN
MC+CHtypeC
14
3
severe smPN
Myositis+CH typeC
9
8
cranial N
UCTD,CH type C
18
12
SmpN
MC+CH ‘ype C
9
9
severe smPN
MC+CHtypeC
9
1
severe smPN
smPN
cryo.: CH rhronlc hepairs sensory-motor peripheral N :neuropalhy : UCTD unclawr~cable connecl,ve usue ; MU
:
: mego ~11,s.
neuropaty
In 2 cases (pts 3 and 4) the nenropathy appeared cx nova, while in the other 4 a mild sensory peripheral nenropathy severely worsened during a-IFN. It is difficult to explain the pathogenic mechanism responsible of this important side-effect, however, a wide preliminary clinical assesment and a careful monitoring of a-IFN therapy is recommendable especially in HCV+ or HBV+ pts with pre-existing, often subclinical, neuropathy and immunological disorders.
) CO8/012 1 THE ROLE OF HEPATIC TISSUE IN CHANGES OF PROTEIN METABOLISM AFTER ENDOTOXIN TREATMENT IN RATS.
M. HoleEek and L. Sprongl*. Charles University School of Medicine, Hradec Krdlovt and *University Hospital Motol, Prague, Czech Republic.
, --
Linivenity if Pavia, Ito&. . BACKGROUND. An autooanio impniit
may be documented in patients with chronic
liver diseases, as well as in Human immuo&Iiciency Virus (HIV)-positive patients. In these patieots a reduced respnwe to oxidative sbns has been desclibed baause of B systemic d&tial of reduced glut&icme (GSH).Aim of the study has been IO detect both &mtional altmtims of the cardiac vu@ nervous system in p&m with CHC who were either HIV positive or ne@ive and the possible pathogemtic role of GSH depletion in iodwii these &X&XlS. PATIENTS AND METHODS. Electrccardicgmphic R-R interwl wnatmn were assessed in 125 ptients with chronic hqmtitis C (CHC) (65 HIV-positive and 60 HIV-negative) and 61 healthy contmls. The ratio of the coefficient of variatim to standard prediction value was wed as an index (CVc). H-GSH conantratl~n was determined by High Performance Liquid Chromatography ( HPLC) on liver spcimens obtained by ultmsamdguided bwpies acarding to the method desoribed by Reed et al. Blood samplesfor simubmeous
mtiom of GSF in peripheral blood monmuclear cells (LGSH) and in platelet-poor pIam (P-GSH) were obtained for each sub+ according to the methods described by soam et al. and by L3ri&ius et al. Erytrocyte GSH (E-GSH) cmcentretions were determined according to the methcd described by Ellmm and Lysko. Erythwqe malooydial&hyde ( MJ3A)levels, which were determined by HPLC accadmg to the m&h& detibed by Es~erbauer et al., repruented a marker of lipqxroxi&tion. RESULTS. H-GSH_PGSH,LGSH and EGSH were significantly reduced in ptientr; af&ted by CHC campwed with healthy wntrols @<0,OOl).HUSH and, ~oulruly, LGSH were more s~pificantly reduced m HIV-positive patients compared with HIV-negmw ones
(p
Endotoxin treatment induces a marked production of cytokines which are the principal cause of a life threatening muscle wasting often observed in liver cirrhosis, sepsis, trauma, bum injuries and cancer. The effect of cytokines on the metabolism of proteins and amino acids in hepatic tissue is not clear. Methods: Male rats (n = 34) were injected with endotoxin of S. enteritidis (5 mg/kg) or saline (control). Four hours later, the parameters of leucine utilization were determined in isolated perfused liver using the single-pass perfusion technique with [l“C]leucine and a-keto[ 1-‘?]isocaproate (KIC) as tracers. Results: Endotoxin treatment resulted in increased flux of leucine through branched-chain amino acid aminotransferase, and in a decreased flux of KIC through branched-chain keto acid dehydrogenase. Leucine incorporation in liver proteins was lower in endotoxin treated rats. We did not find a measurable incorporation of labeled carbon of KIC in liver proteins in either group of animals. The sum of individual amino acid levels in the effluent perfusate was higher in endotoxin treated animals. Conclusion: Our results demonstrate the important reaction of the hepatic tissue that enables the resynthesis of essential branchedchain amino acids, leucine, isoleucine, and valine from their ketoanalogues delivered into the liver from peripheral tissues, particularly from muscle. This response may inhibit the development of negative nitrogen balance and muscle wasting in systemic inflammatory response syndrome.
Nutrition, metnbolism, ulcolzolic liver discuses. pharnzrtcolog~~
CARBOHYDRATE DEFICIENT TRANSFERRIN AND KETOISOCAPROIC ACID TESTS FOR ALCOHOL ABUSE COMPARED WITH LIVER HISTOLOGY AND BIOCHEMICAL MARKERS A. Minzer, C. Jenni, P. Hildebrand, B. Meyer-Wyss, J. Drewe, C. Beglinger, CC Sieber. Division of Gastroenterology, University Hospital Basel,‘Basel, Switzerland. Laborchemical tests with a high sensitivity and specificity for moderate to heavy alcohol abuse are still lacking. Two markers, carbohydrate deficient transferrin (CDT) plasma levels and ketoisocaproic acid (KICA) metabolism claim to be both sensitive and specific. Aims. To compare these tests with laborchemical markers and liverhistology for exagerated alcohol consumption (>4Og/d for females, >6Og/d for males). Methods. 6i patients (38m, 23f, mean age 48~) with different gramer disease (Child class 52 A, 6 B and 3 C) were included into the study. CDT was tested by CDTect (Pharmacia) in all 61 patients and as %CDT of total transferrin (Axis) in 27 patients. KICA metabolism, galactose elimination capacity (GEK), biochemical and hematological parameters were tested in all patients. Results. Sensitivity and specificity were calculated in relation to alcoholintake. KICA gGT MCV . %CDT CDTect 1% Sensitivity 75 0 2 78; 84% 46% 100% 80% d KICA-test showed an inacceotable low sensitivit;. Besides a good sensitivity and high specificity for %CD?‘. significant correlations were found for bilirubin, transaminases, gGT, albumin, prothrombin time, platelet count, mean corpuscular volume, Child class, histology, GEK but not with KICA-test. Conclusion. Tests like %CDT with a high sensitivity and especially specificity are important, especially when used for forensic purposes. Patients history, clinical examination together with gGT and MCV already give a good estimate of chronic alcohol abuse.
NEUROLOGICAL TOXICITY OF ALPHA-INTERFERON IN HCV- OR HBVBELATED IMMUNOLOGICAL SYSTEMIC DISORDERS. C. Ferri’. L.La Civita’. M.Mont?. G.Lonnotnbardo’. P.Fadda’, G.Cereccia2, P.Gentilin?. G.Pesero’. AL.. Zieneeo2. ‘Depertment of Internal Medicine, University of Piss, Pisa, Italy ; %tstitnte of Internal Medicine, University of Florence, Florence, Italy.
A neurological toxicity of alpha-interferon (a-IFN) treatment has been anedoctally reported in different conditions, i.e. viral hepatitis, immunological diseases and malignances. We treated with a-IFN 75 pts with hepatotropic virus- related immunological systemic disorders, such as mixed ctyoglobulmemia. Here, we report a cohort of 6 pts (SHCV+, IHBV+) with severe neuropathy complicanting IFN treatment. Before a-IFN Pt no. 1 2 3 4 5 6
Age Sex 59 M 45 M 47 M 46 F 64 F 52 F
MC :mixed
After a-IFN
Clinical manifestations MC+CHtypeB
MU/wk
Dnrlwk
symptoms
21
4
severe smPN
MC+CHtypeC
14
3
severe smPN
Myositis+CH typeC
9
8
cranial N
UCTD,CH type C
18
12
SmpN
MC+CH ‘ype C
9
9
severe smPN
MC+CHtypeC
9
1
severe smPN
smPN
cryo.: CH rhronlc hepairs sensory-motor peripheral N :neuropalhy : UCTD unclawr~cable connecl,ve usue ; MU
:
: mego ~11,s.
neuropaty
In 2 cases (pts 3 and 4) the nenropathy appeared cx nova, while in the other 4 a mild sensory peripheral nenropathy severely worsened during a-IFN. It is difficult to explain the pathogenic mechanism responsible of this important side-effect, however, a wide preliminary clinical assesment and a careful monitoring of a-IFN therapy is recommendable especially in HCV+ or HBV+ pts with pre-existing, often subclinical, neuropathy and immunological disorders.
) CO8/012 1 THE ROLE OF HEPATIC TISSUE IN CHANGES OF PROTEIN METABOLISM AFTER ENDOTOXIN TREATMENT IN RATS.
M. HoleEek and L. Sprongl*. Charles University School of Medicine, Hradec Krdlovt and *University Hospital Motol, Prague, Czech Republic.
, --
Linivenity if Pavia, Ito&. . BACKGROUND. An autooanio impniit
may be documented in patients with chronic
liver diseases, as well as in Human immuo&Iiciency Virus (HIV)-positive patients. In these patieots a reduced respnwe to oxidative sbns has been desclibed baause of B systemic d&tial of reduced glut&icme (GSH).Aim of the study has been IO detect both &mtional altmtims of the cardiac vu@ nervous system in p&m with CHC who were either HIV positive or ne@ive and the possible pathogemtic role of GSH depletion in iodwii these &X&XlS. PATIENTS AND METHODS. Electrccardicgmphic R-R interwl wnatmn were assessed in 125 ptients with chronic hqmtitis C (CHC) (65 HIV-positive and 60 HIV-negative) and 61 healthy contmls. The ratio of the coefficient of variatim to standard prediction value was wed as an index (CVc). H-GSH conantratl~n was determined by High Performance Liquid Chromatography ( HPLC) on liver spcimens obtained by ultmsamdguided bwpies acarding to the method desoribed by Reed et al. Blood samplesfor simubmeous
mtiom of GSF in peripheral blood monmuclear cells (LGSH) and in platelet-poor pIam (P-GSH) were obtained for each sub+ according to the methods described by soam et al. and by L3ri&ius et al. Erytrocyte GSH (E-GSH) cmcentretions were determined according to the methcd described by Ellmm and Lysko. Erythwqe malooydial&hyde ( MJ3A)levels, which were determined by HPLC accadmg to the m&h& detibed by Es~erbauer et al., repruented a marker of lipqxroxi&tion. RESULTS. H-GSH_PGSH,LGSH and EGSH were significantly reduced in ptientr; af&ted by CHC campwed with healthy wntrols @<0,OOl).HUSH and, ~oulruly, LGSH were more s~pificantly reduced m HIV-positive patients compared with HIV-negmw ones
(p
Endotoxin treatment induces a marked production of cytokines which are the principal cause of a life threatening muscle wasting often observed in liver cirrhosis, sepsis, trauma, bum injuries and cancer. The effect of cytokines on the metabolism of proteins and amino acids in hepatic tissue is not clear. Methods: Male rats (n = 34) were injected with endotoxin of S. enteritidis (5 mg/kg) or saline (control). Four hours later, the parameters of leucine utilization were determined in isolated perfused liver using the single-pass perfusion technique with [l“C]leucine and a-keto[ 1-‘?]isocaproate (KIC) as tracers. Results: Endotoxin treatment resulted in increased flux of leucine through branched-chain amino acid aminotransferase, and in a decreased flux of KIC through branched-chain keto acid dehydrogenase. Leucine incorporation in liver proteins was lower in endotoxin treated rats. We did not find a measurable incorporation of labeled carbon of KIC in liver proteins in either group of animals. The sum of individual amino acid levels in the effluent perfusate was higher in endotoxin treated animals. Conclusion: Our results demonstrate the important reaction of the hepatic tissue that enables the resynthesis of essential branchedchain amino acids, leucine, isoleucine, and valine from their ketoanalogues delivered into the liver from peripheral tissues, particularly from muscle. This response may inhibit the development of negative nitrogen balance and muscle wasting in systemic inflammatory response syndrome.