Abstract
Plasma and cerebrospinal fluid amino acid levels were measured in 12 cirrhotic patients in grade 0 hepatic encephalopathy and 17 in grade 3–4 hepatic encephalopathy. In 5 of these patients amino acid determinations were performed during the evolution of the encephalopathy. No correlation was found between the degree of hepatic encephalopathy and the plasma amino acid imbalance. In the CSF of cirrhotic patients without encephalopathy, a significant increase was found in nearly all amino acids, including those known to not easily cross the blood-brain barrier; this suggests the presence of a nonspecific modification of the blood-brain barrier permeability. In patients with severe hepatic encephalopathy, the further increase only in cerebrospinal fluid aromatic amino acids and methionine levels suggests the presence of a selective stimulation of the neutral amino acid transport system across the blood-brain barrier. Finally, the good correlation between glutamine and the sum of neutral amino acids found in the cerebrospinal fluid only in the presence of encephalopathy supports the hypothesis that brain glutamine may stimulate neutral amino acid transport across the blood-brain barrier.
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Fischer JE, Baldessarini RJ: False neurotransmitters and hepatic failure. Lancet 2:75–79, 1971
Fischer JE, Rosen HM, Ebeid AM: The effect of normalization of plasma amino acids on hepatic encephalopathy. Surgery 80:77–91, 1976
Cascino A, Cangiano C, Calcaterra V, Rossi Fanelli F, Capocaccia L: Plasma amino acid imbalance in patients with liver disease. Am J Dig Dis 23:591–598, 1978
Morgan MP, Hilsom JP, Sherlock S: Plasma ratio of valine, leucine and isoleucine to phenylalanine and tyrosine in liver disease. Gut 19:1068–1073, 1978
Hutson DG, Ono J, Dombro RS, Levi VJ, Livingstone A, Zeppa R: A longitudinal study of tryptophan involvement in hepatic coma. Am J Surg 137:235–239, 1979
Marchesini G, Zoli M, Dondi C, Cecchini L, Bianchi FP, Pisi E: Prevalence of subclinical hepatic encephalopathy in cirrhotics and relationship to plasma amino acid imbalance. Dig Dis Sci 25:763–768, 1980
Smith AR, Rossi Fanelli F, Ziparo V, James JH, Perelle BA, Fischer JE: Alterations in plasma and CSF amino acids, amines and metabolites in hepatic coma. Ann Surg 187:343–350, 1978
James JH, Hodgman JM, Funovics JM, Yashimura N, Fisher JE: Brain tryptophan, plasma free tryptophan and distribution of plasma neutral amino acids. Metabolism 25:471–474, 1976
Moskowitz MA, Wurtman RJ: Catecholamines and neurological diseases. N Engl J Med 293:274–280, 1975
Knell AJ, Davidson RR, Williams R, Kantamanemi BP, Curzon G: Dopamine and serotonine metabolism in hepatic encephalopathy. Br Med J 268:549–551, 1974
Ono J, Hutson DJ, Dombro RS, Levi JV, Livingstone A, Zeppa R: Tryptophan and hepatic coma. Gastroenterology 74:196–200, 1978
Duggan DE, Undenfriend S: Spectrofluorimetric determination of tryptophan in plasma and of tyrosine and tryptophan in protein hydrolysates. J Biol Chem 223:313–329, 1956
Cangiano C, Calcaterra V, Cascino A, Rossi Fanelli F, Capocaccia L: Bound and free tryptophan plasma levels in hepatic encephalopathy. Rendic Gastroenterol 8:186–189, 1976
Capocaccia L, Rossi Fanelli F, Calcaterra V, Cascino A, Cangiano C: Tryptophan plasma levels in hepatic encephalopathy. Clin Res 24(5):A628, 1976
Fischer JE, Funovics JM, Aguirre A, James JH, Keane JM, Wesdorp RIC, Yoshimura N, Westman T: The role of plasma amino acids in hepatic encephalopathy. Surgery 78:276–290, 1975
Striebel JP, Holm E, Lutz H, Storz LW: Parenteral nutrition and coma therapy with amino acids in hepatic failure. Journal Parenteral and Enterol Nutrition 3:240–246, 1979
Fiaccadori F, Ghinelli F, Pelosi G, Sacchini D, Vaona GL, Zeneroli ML, Rocchi E, Santunione V, Gibertini P, Ventura E: Selective Amino acid solutions in hepatic encephalopathy treatment. La Ricerca 10:411–422, 1980
Capocaccia L, Calcaterra V, Cangiano C, Cascino A, Fiaccadori F, Ghinelli F, Pelosi G, Riggio O, Rossi Fanelli F, Sacchini D, Giunchi G: Therapeutic effect of branched chain amino acids in hepatic encephalopathy. A preliminary study.In Medical and Surgical Problems of Portal Hypertension. MJ Orloff, S Stipa, V Ziparo (eds). London, Academic Press, 1980, pp 239–249
Rossi Fanelli F, Riggio O, Cangiano C, Cascino A, De Conciliis D, Merli M, Capocaccia L: Intravenous branchedchain amino acids (BCAA) infusions vs lactulose (L) in the treatment of hepatic encephalopathy (HE). A controlled study. Clin Res 29(2):305 A, 1981
Smith AR, Rossi Fanelli F, Freund H, Fischer JE: Induction of a coma like state in normal dogs by intracarotid infusion of amino acids. Gastroenterology 173:49A, 1977
Livingston A, Hinchey EJ, Goresky CA: Changes in the blood-brain barrier in acute hepatic coma. Surg Forum 25:351–352, 1974
James JH, Escourrou J, Fischer JE: Blood-brain neutral amino acid transport activity is increased after porta-caval anastomosis. Science 200:1395–1397, 1978
Cangiano C, Cascino A, Fiaccadori F, Riggio O, Rossi Fanelli F, Capocaccia L: Is the blood-brain barrier really intact in portal-systemic encephalopathy? Lancet 1:1367, 1981
Oldendorf WH, Szabo J: Amino acid assignment to one of three blood-brain barrier amino acid carriers. Am J Physiol 230:94–98, 1976
Marshall JP, Parker TH, Roberts RK, Schenker S: Biochemistry of hepatic coma in alcohol-induced liver disease and other types of hepatic dysfunction.In Biochemistry and Pharmacology of Ethanol. E Majchrowicz, EP Noble (eds). New York, Plenum Press, 1979, pp 479–502
Higashi T, Watanabe A, Hayashi S, Obata T, Takei N, Nagashima H: Effect of branched-chain amino acid infusion on alterations in CSF neutral amino acids and their transport across the blood-brain barrier in hepatic encephalopathy.In Metabolism and Clinical Implications of Branched Chain Amino and Keto-Acids. M Walter, JR Williamson (eds). New York, Elsevier North Holland, 1981, pp. 465–470
James JH, Ziparo V, Jeppsson B, Fischer JE: Hyperammonemia, plasma amino acid imbalance and blood brain amino acid transport: A unified theory of portal-systemic encephalopathy. Lancet 2:772–775, 1979
Pardridge WM: Regulation of amino acid availability to the brain.In Nutrition and the Brain, Vol 1, RJ Wurtman, JJ Wurtman (eds). New York, Raven Press, 1979, pp 141–182
Cardelli Cangiano P, Cangiano C, James JH, Jeppsson B, Brenner W, Fischer JE: Uptake of amino acids by brain microvessels isolated from rats after portacaval anastomosis. J Neurochem 36:627–632, 1981
Cangiano C, Cardelli Cangiano P, James JH, Fischer JE: Ammonia stimulates amino acid uptake by bovine isolated brain microvessels. Gastroenterology 78:1302, 1980
James JH, Cangiano C, Cardelli Cangiano P, Fischer JE: Glutamine links hyperammonemia and neurotransmitter derangements in portal systemic shunting. Gastroenterology 78:1308, 1980
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This work was supported by grant 500.6/Contr. 70/1743 Ministry of Health, Rome, Italy.
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Cascino, A., Cangiano, C., Fiaccadori, F. et al. Plasma and cerebrospinal fluid amino acid patterns in hepatic encephalopathy. Digest Dis Sci 27, 828–832 (1982). https://doi.org/10.1007/BF01391377
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DOI: https://doi.org/10.1007/BF01391377