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Whole blood acetaldehyde concentrations in alcoholic cirrhosis and non alcoholic liver disease
WHOLE BLOOD AC~fAT,nRwY]]E CONCENTRATIONS NON ALCOHOLIC LIVER DISEASE
IN ALCOHOLIC CIRRHOSIS AND
H A1 Mardini~ K Matthewson~ C 0 Record Gastroenterology Unit, Royal Victoria Infirmary and University of Newcastle upon Tyne
Abstract Acetaldehyde concentrations following ingestion of an alcohol load are increased in patients with alcoholic liver disease and it has been suggested that this reactive metabolite is responsible for alcohol related liver injury. Increased blood acetaldehyde concentrations may be due to a aecrease in the activity of hepatic cytosolic aldehyde dehydrogenase and it has been suggested that this is a primary metabolic defect. These abnormalities could however be a non specific result of liver damage from a variety of causes. In order to test their specificity, we have determined blood acet~dehyde concentrations and hepatic cytosolic aldehyde dehydrogenase activity in 14 patients with alcoholic cirrhosis, 15 patients with non alcoholic liver disease and 7 control subjects. Blood acetaldehyde concentrations were significantly increased 30-180 minutes after ethanol loading in patients with alcoholic cirrhosis when compared to controls but were also significantly increased 30, 120, 150 and 180 minutes after ethanol in patients with non alcoholic liver disease. Cytosolic aldehyde dehydrogenase activity was significantly decreased both in cirrhosis due to alcohol and in patients with active chronic hepatitis and paracetamol overdose, while activities in patients with primary biliary cirrhosis fell within normal limits. These results do not support an import~=nt role for scetaldehyde in the pathogenesis of alcohol related liver damage.
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VALIDATION OF A NEW CHROMOGENICASSAY'FOR ENDOTOXAEMIAIN LIVER DISEASE. E.M.Alstead, F.J.Khan, A.I.Morris, I.T.Gilmore and J.,Ware. Department of Medicine, University of Liverpool, P.O.Box 147, Liverpool L69 3BX, U.K.
The measurement of endotoxaemia in live~ disease has been d i f f i c u l t , u n r e l i a b l e and only semiquantitative. With the development of a commercially available chromogenic substrate based limulus lysate k i t (Byk Mallinckrodt),we have evaluated i t s quantitative use in patients with l i v e r disease. Using this method normal plasma containing known amounts of endotoxin produce linear results (mean gradient 0.60 ± 0.062 S.D.),similar to but with a gradient s i g n i f i c a n t l y different from that obtained from crystalloid fluids (mean gradient 0.88 ± D.083 S.D.); p < O.Ol. As the assay relies on a yellow chromogen ( p - n i t r o a n i l i n e ) , i t was important to validate its use in jaundiced plasma. Using plasma from 15 jaundiced patients, similar linear results were obtained (mean gradient 0.77 ± 0.061S.D.). The .gradient was s i g n i f i c a n t l y d i f f e r e n t from those for normal plasma (p < O.Ol) and different from that of crystalloids (p < O.Ol) using linear regression analysis. Because of the influence of b i l i r u b i n on the assay i t is important to perform a standard curve for each patient's plasma. Studies of patients with diverse l i v e r disease have shown that this is a simple repeatable and sensitive test ( s e n s i t i v i t y ~/O.IEu/ml) to determine the presence of endotoxaemia in normal and jaundiced plasma.
$4
IN ALCOHOLIC CIRRHOSIS AND
H A1 Mardini~ K Matthewson~ C 0 Record Gastroenterology Unit, Royal Victoria Infirmary and University of Newcastle upon Tyne
Abstract Acetaldehyde concentrations following ingestion of an alcohol load are increased in patients with alcoholic liver disease and it has been suggested that this reactive metabolite is responsible for alcohol related liver injury. Increased blood acetaldehyde concentrations may be due to a aecrease in the activity of hepatic cytosolic aldehyde dehydrogenase and it has been suggested that this is a primary metabolic defect. These abnormalities could however be a non specific result of liver damage from a variety of causes. In order to test their specificity, we have determined blood acet~dehyde concentrations and hepatic cytosolic aldehyde dehydrogenase activity in 14 patients with alcoholic cirrhosis, 15 patients with non alcoholic liver disease and 7 control subjects. Blood acetaldehyde concentrations were significantly increased 30-180 minutes after ethanol loading in patients with alcoholic cirrhosis when compared to controls but were also significantly increased 30, 120, 150 and 180 minutes after ethanol in patients with non alcoholic liver disease. Cytosolic aldehyde dehydrogenase activity was significantly decreased both in cirrhosis due to alcohol and in patients with active chronic hepatitis and paracetamol overdose, while activities in patients with primary biliary cirrhosis fell within normal limits. These results do not support an import~=nt role for scetaldehyde in the pathogenesis of alcohol related liver damage.
8
VALIDATION OF A NEW CHROMOGENICASSAY'FOR ENDOTOXAEMIAIN LIVER DISEASE. E.M.Alstead, F.J.Khan, A.I.Morris, I.T.Gilmore and J.,Ware. Department of Medicine, University of Liverpool, P.O.Box 147, Liverpool L69 3BX, U.K.
The measurement of endotoxaemia in live~ disease has been d i f f i c u l t , u n r e l i a b l e and only semiquantitative. With the development of a commercially available chromogenic substrate based limulus lysate k i t (Byk Mallinckrodt),we have evaluated i t s quantitative use in patients with l i v e r disease. Using this method normal plasma containing known amounts of endotoxin produce linear results (mean gradient 0.60 ± 0.062 S.D.),similar to but with a gradient s i g n i f i c a n t l y different from that obtained from crystalloid fluids (mean gradient 0.88 ± D.083 S.D.); p < O.Ol. As the assay relies on a yellow chromogen ( p - n i t r o a n i l i n e ) , i t was important to validate its use in jaundiced plasma. Using plasma from 15 jaundiced patients, similar linear results were obtained (mean gradient 0.77 ± 0.061S.D.). The .gradient was s i g n i f i c a n t l y d i f f e r e n t from those for normal plasma (p < O.Ol) and different from that of crystalloids (p < O.Ol) using linear regression analysis. Because of the influence of b i l i r u b i n on the assay i t is important to perform a standard curve for each patient's plasma. Studies of patients with diverse l i v e r disease have shown that this is a simple repeatable and sensitive test ( s e n s i t i v i t y ~/O.IEu/ml) to determine the presence of endotoxaemia in normal and jaundiced plasma.
$4