Factors influencing the concentrations of the large neutral amino acids in the brain and in the CSF of dogs after portacaval anastomosis.

Portal-systemic shunting of blood is associated with hyperammonemia, an increased glutamine concentration in brain, an altered plasma neutral amino acid pattern, and high levels of several of the large neutral amino acids in brain. Since some of these amino acids are precursors for neurotransmitters and for other potentially neuroactive substances, high CNS levels of these amino acids may contribute to the development of encephalopathy. In order to determine the relative importance of changes in brain glutamine levels and changes in competition among the neutral amino acids for blood-brain transport, we measured the concentrations of the large neutral amino acids in plasma, cisternal cerebrospinal fluid and in brain tissue from various regions of dogs after end-to-side portacaval shunt. Although the changes in CSF amino acid levels correlated partially with altered amino acid plasma competitor ratios, better correlations were observed with the elevation of CSF glutamine. These results suggest a model of blood-brain amino acid transport in which a high level of glutamine in brain extracellular fluid competes with other neutral amino acids for efflux from brain, thus raising brain amino acid levels after portal-systemic shunting.

The effect of prostaglandins, branched-chain amino acids and other drugs on the outcome of experimental acute porcine hepatic failure.

Prostaglandins, N-acetyl-cysteine, cholestyramine and essential phospholipids have all been shown to protect experimental animals from severe hepatic damage in various models when used prophylactically. Silibinin has been used in the treatment of Amanita phalloides poisoning. Branched-chain amino acids have been recommended in acute hepatic failure. We have used all these forms of therapy at the time of initiation of hepatic failure in a reliable pig model. Of the above, only prostaglandins have been shown to reverse the effects of the hepatic insult in terms of prolonged survival and histological changes. Although conventional liver function tests and plasma amino acids in prostaglandin-treated animals are not improved, cerebrospinal fluid amino acids remain normal, in contrast to the other groups of untreated and treated hepatic failure animals.

Concentrations of plasma and cerebrospinal fluid-free amino acids in hypercapnic coma and acute respiratory failure.

A comparison between the concentrations of free amino acids in the plasma and cerebrospinal fluid (CSF) in cases of hypercapnic coma and acute respiratory failure has been made. Hypotheses are formulated to interpret the observed changes in the cerebral metabolism of amino acids in these pathological conditions.

Changes in free amino acids of cerebrospinal fluid and plasma in various neurological diseases.

By means of liquid chromatography we investigated free amino acids in cerebrospinal fluid (CSF) (161 subjects) and in plasma (138 subjects) in various neurological diseases and in controls. A general increase in CSF amino acids was found in Group C (samples exhibiting both pleocytosis and increasing CSF protein concentration) and in "spinal canal block" and "neuro-Behçet's syndrome". Also, some abnormalities were detected in these groups with regard to changes in CSF cells, protein or IgG%. In the case of "Guillain-Barré syndrome" we noted an increase in CSF alanine, glycine, methionine, arginine and the branched-chain group. In "multiple sclerosis" an increase was evident in CSF alanine, in plasma alanine and arginine, and in the plasma: CSF ratio of tyrosine. In patients of "motor neuron diseases (MND)" CSF glutamic acid, alanine, histidine and arginine all indicated an increase, along with the plasma: CSF ratio of tyrosine. In Group C and in "neuro-Behçet's syndrome" glycine, methionine and lysine were lowered in the plasma: CSF ratio. Also, the ratio of valine in the former and histidine in the latter indicated a decrease. These results can be supposed to reflect either biochemical abnormalities of plasma and/or the CNS, or changes in the transport systems of the blood-brain barrier.

Concentrations of free amino acids in plasma, erythrocytes and cerebrospinal fluid in coma.

The concentrations of free amino acids were measured in plasma and erythrocytes in 15 patients, and in cerebrospinal fluid in eight patients, who were in coma. Although there was a variety of causes of coma, there seemed to be a characteristic pattern of the concentrations of amino acids for coma, and the plasma/cerebrospinal fluid ratios also showed constant patterns.