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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma levels of different amino acids were observed in 10 patients with severe hepatitis, 9 viral in origin and 1 toxic, over the course of the disease. There would appear to be a close relationship between the onset of encephalopathy and the appearance of a particular pattern in plasma amino acid equilibrium, characterised by a significant fall in the molar ratio existing between ramified amino acids (valine, leucine, isoleucine) and aromatic amino acids (phenylalanine and tyrosine). The role of these disturbances in the physiopathology of the encephalopathy and their effects on the synthesis of normal neurotransmitters and the intracerebral accumulation of false neurotransmitters is discussed.
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PMID:[Variation of plasma amino acids in severe hepatitis with encephalopathy 10 cases]. 1 44

Sepsis is a major catabolic insult resulting in modifications in carbohydrate and fat energy metabolism, and leading to increased muscle breakdown and nitrogen loss. Insulin resistance, which develops in sepsis, decreases glucose utilization, but plasma insulin levels are sufficiently elevated to prevent lipolysis, resulting in a further energy deficit. The availability of fuels in sepsis is therefore limited, and the body resorts to muscle breakdown, gluconeogenesis, and amino acid oxidation for energy supply. Previous work has not defined, however, the exact alterations in amino acid metabolism. Therefore, the following studies were undertaken. Blood samples were drawn from fifteen patients in whom the diagnosis of sepsis was clinically established; the samples were analyzed for amino acid, beta-hydroxyphenylethanolamines, glucose, insulin and glucagon concentrations. The plasma amino acid pattern observed was characterized by an increase in total amino acid content, due mainly to high levels of the aromatic amino acids (phenylalanine and tyrosine) and the sulfur-containing amino acids (taurine, cystine and methionine). Alanine, aspartic acid, glutamic acid and proline were also elevated, but to a lesser degree. The branched chain amino acids (valine, leucine and isoleucine) were within normal limits, as were glycine, serine, threonine, lysine, histidine and tryptophan. Those patients who did not survive sepsis had higher levels of aromatic and sulfur-containing amino acids as compared to those patients surviving sepsis. On the other hand, those patients surviving sepsis had higher levels of alanine and the branched chain amino acids. In a second group of five patients with overwhelming sepsis accompanied by a state of metabolic encephalopathy, a parenteral nutrition solution consisting of 23% dextrose, and an amino acid formulation enriched with branched chain amino acids was administered. In these five patients, normalization of the plasma amino acid pattern and reversal of encephalopathy was observed. The following sequence of events may be postulated: The septic patient develops insulin resistance in the peripheral tissues, primarily muscle, while the adipose tissue is much less affected. The insulin resistance and the inability to utilize fat leads to increased muscle proteolysis. Muscle breakdown results in release into the blood of enormous amounts of various amino acids; the muscle itself is able to oxidize the branched chain amino acids, supplying the muscles' own energy requirements and alanine for gluconeogenesis. The extensive muscle proteolysis coupled with relative hepatic insufficiency occurring early in sepsis results in the appearance in the plasma of high levels of most of the amino acids present in muscle, particularly the aromatic and the sulfur-containing amino acids. The outcome of patients with sepsis might be positively affected by combined therapy with glucose, insulin and branched chain amino acids.
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PMID:Amino acid derangements in patients with sepsis: treatment with branched chain amino acid rich infusions. 9 98

Sepsis is a major catabolic insult resulting in a peripheral energy deficit which is made up in part by increased breakdown of lean body mass and oxidation of amino acids, principally the branched chain amino acids. The prognosis in any given case of sepsis is difficult to predict, but should theoretically be related to the degree of disturbance in peripheral energy deficit, which may in turn, be related to plasma amino acid pattern. In order to study whether this hypothesis was correct, plasma amino acids and some of their metabolic byproducts, the beta-hydroxyphenylethanolamines, were studied in 25 septic patients, and were used as discriminant variables in a series of computer performed discriminant analyses and multiple regressions. The two functions tested were the degree of metabolic septic encephalopathy as a determinant of the severity of sepsis and the final outcome in the septic patient. Plasma amino acid patterns exhibited elevated levels of the aromatic and sulfur containing amino acids, phenylalanine, tryosine, tryptophan, methionine, cysteine, and taurine, normal concentrations of alanine, and low normal concentrations of the branched chain amino acids, valine, leucine and isoleucine. Arginine levels, as previously noted, were very low. Patients not surviving the septic episode exhibited higher concentrations of aromatic and sulfur containing amino acids, while patients surviving sepsis had higher concentrations of the branched chain amino acids and arginine. When the degree of encephalopathy as a determinant of the severity of sepsis and step wise discriminant analysis with multiple crescent techniques were used, the best discriminant function between patients with and without encephalopathy was found to result from the interaction of cysteine, methionine, phenylalanine, isoleucine, leucine, and valine. These amino acids gave a correct classification in 82% of patients with no encephalopathy, and 80% of patients with septic encephalopathy. When the same amino acids were used for the discriminant analysis for patients dying of sepsis and patients surviving, the best discriminant function was achieved by using plasma concentrations of alanine, cysteine, methionine, isoleucine, arginine, tyrosine and phenylalanine resulting in 91% of the nonsurvivors, and 79% of the survivors correctly classified. The results suggest a close and significant relationship between the deranged energy metabolism and muscle protein breakdown in sepsis, and the outcome. This further suggests a central role for certain amino acids in perhaps predicting the severity of sepsis and its outcome.
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PMID:Plasma amino acids as predictors of the severity and outcome of sepsis. 38 83

Uptake of various amino acids was studied in slices from brain regions of rats four weeks after portocaval anastomosis. No differences of the inulin compartment were observed between control and experimental animals. After 60-minutes incubation, uptake showed an overall pattern of diminution. This was more evident for some amino acids: valine, methionine, and lysine exhibited a lowering of about 30%, which was fairly uniform in the four tested regions; others showed a regional decrease-- alanine in pons-medulla, phenylalanine in cerebellum, histidine and GABA in mesodiencephalon. This decrease did not seen to be related to transport classes. The restricted entry of amino acids into brain cells in portocaval encephalopathy is somewhat difficult to explain; a decreased rate of protein synthesis may be of some importance, but other factors, such as a "carrier" impairment, effects on release and on amino acid metabolism, may also be involved.
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PMID:Cerebral amino acid levels and uptake in rats after portocaval anastomosis: I. Regional studies in vitro. 46 64

Encephalopathic patients with cirrhosis of the liver consistently showed elevated levels of the aromatic amino acids, phenylalanine, tyrosine and free tryptophan as well as methionine in serum, whereas levels of the branched chain amino acids, valine, leucine and isoleucine, were depressed. Comatose patients with fulminant hepatitis had markedly elevated levels of all amino acids, the results being greatly different from those of cirrhotic patients. Molar ratios of (valine + leucine + isoleucine)/(phenylalanine + tyrosine) decreased both in cirrhotics with and without encephalopathy and in cases with fulminant hepatitis. Infusion of a commercially available L-amino acid solution in a cirrhotic patient induced a strikingly abnormal aminogram documented in hepatic encephalopathy. Therefore, effects of branched chain amino acid infusion on the deranged amino acid pattern were primarily studied for the purpose of improvement in hepatic encephalopathy by normalization of serum amino acid patterns. Elevated levels of the aromatic amino acids and methionine could be apparently depressed in a cirrhotic patient by this type of infusion but not in a case of fulminant hepatitis probably because of the poor utilization of these amino acids in severely impaired liver.
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PMID:Serum amino acids in hepatic encephalopathy--effects of branched chain amino acid infusion on serum aminogram. 52 13

The dog with an end-to-side portacaval shunt (PCS) has been extensively used as a model to investigate hepatic encephalopathy (HE) as it demonstrates a plasma amino acid pattern similar to patients with chronic liver disease. In adult mongrel dogs, the effect of PCS on plasma and CSF amino acids, octopamine (OCT), phenylethanolamine (PEA) and CSF 5-hydroxyindolacetic acid (5-HIAA), were studied. Moreover, the effect of correction of plasma amino acids by infusional techniques was investigated.Tyrosine, tryptophan and phenylalanine levels increased dramatically during the development of HE in plasma and CSF, while valine, leucine and isoleucine decreased in plasma only, but CSF levels remained stable. Plasma and CSF octopamine and phenylethanolamine and CSF 5-HIAA increased markedly as clinical features in the dogs' behavior, characteristic of hepatic encephalopathy occurred, including hypersalivation, ataxia, flapping tremor, somnolence and finally coma. Once in coma, the dogs were infused with an amino acid mixture (F080) calculated to normalize the plasma amino acid pattern. After one to eight hours, the dogs began to awake. Simultaneously, blood, and CSF aromatic amino acids returned to their control values, as did OCT, PEA and CSF 5-HIAA. If F080 infusion was stopped, biochemical alterations would appear within one week, again accompanied by clinical hepatic encephalopathy.The results indicate that the altered levels of aromatic and branched chain amino acids, octopamine and PEA in plasma and CSF correlate well with the development of HE and that correction of the plasma amino acid abnormalities improves encephalopathy simultaneously with correction of neurotransmitter derangements in CSF.
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PMID:Alterations in plasma and CSF amino acids, amines and metabolites in hepatic coma. 63 94

In hepatic coma as well as diabetic coma severe disturbances occur in the amino acid metabolism. The defect lies in completely different levels which result two different plasma aminograms (PAG). In 24 patients with hepatic encephalopathy stage III-IV (7 patients with acute and 17 with chronic liver failure) the PAG were evaluated. The determination of the plasma amino acids (PAA) was carried out on Multichrom B (Beckmann, Munich). In hepatic coma high concentrations of Met, Tyr, Ala, Lys and Arg are found. The deviations of PAA from normal controls show between acute and chronic hepatic failure no qualitative but only quantitative differences. In diabetic coma the three branches chain AA (Val, Leu and Ile) were elevated upon 3--5 times of normal. Near normal concentrations are found for the AA Thr, Ser, Gly, Ala, Met and the aromatic AA (Phe and Tyr). The quotient between the branched chain and aromatic AA lies for hepatic coma at a mean of 1.18 and by diabetic coma at 7.18 (p less than 0.001). In hepatic coma a correlation exists between the level of the AA-quotient improvement and the decrease with a deterioriation of the metabolic encephalopathy. The high level of the AA-quotient in the patients of diabetic "coma" gives therefore a good explanation for the rare unconscious state of these patients.
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PMID:[Differences in plasma aminograms in hepatic and diabetic coma]. 74 45

Previous work from this laboratory has suggested that the plasma amino acid pattern, known to be deranged in hepatic encephalopathy, may be related causally. In order to test this hypothesis, 23% dextrose and a special amino acid solution whose components were calculated to normalize the plasma amino acid pattern were infused in 11 patients, eight with chronic cirrhosis and acute exacerbation (Group 1) and three patients with fulminant hepatitis (Group 2), in amounts of up to 120 Gm. of protein equivalent per 24 hours. Plasma amino acids were abnormal but different in both groups. In Group 1 (cirrhosis) changes in plasma amino acid pattern including elevated phenylalanine, tyrosine, glutamate, aspartate, and methionine and decreased valine, leucine, and isoleucine. In Group 2 all amino acids were elevated, with the exception of the branched chains which were normal. Hepatic encephalopathy improved in all patients in Group 1 and in one of three patients in Group 2 following the infusion. The ratio (see article) showed an excellent correlation with a grade of encephalopathy. When this ratio, previously 1.0 in the presence of encephalopathy, returned to the normal value near 3.0 to 3.5, encephalopathy improved. An excellent correlation was obtained between the ratio and the grade of encephalopathy and was dose related as well. The results suggest that different amino acid patterns in hepatic encephalopathy of differing etiologies require treatment modalities which may differ for the two types of encephalopathy. Whereas amino acid infusion appears to be a valuable, efficacious way of providing nutrition in treating hepatic encephalopathy in patients with cirrhosis and acute deterioration and coma, other means of therapy such as plasms "laundering" appear to be necessary in patients with fulminant hepatitis.
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PMID:The effect of normalization of plasma amino acids on hepatic encephalopathy in man. 81 29

To study the effect of ammonia administration on amino acids and indoleamines in cerebrospinal fluid (CSF) and on amino acids, insulin, and glucagon in plasma in humans with liver cirrhosis, we performed seven ammonia tolerance tests on six patients with stable liver cirrhosis. The grade of encephalopathy was determined by psychometric tests. Only one of the patients had pronounced encephalopathy. The other patients had no or only slight encephalopathy. The plasma concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, and methionine decreased after the ammonia load, whereas no changes were found in the plasma concentrations of glucagon and insulin. In CSF the concentrations of glutamine, aromatic amino acids, and indoleamines increased only in the patient who had pronounced encephalopathy, whereas no changes were found in the other patients. The effect of an ammonia load on the concentrations of neutral amino acids in CSF in patients with pronounced encephalopathy remains to be demonstrated.
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PMID:The effects of ammonia tolerance tests on the cerebrospinal fluid concentrations of amino acids and indoleamines in patients with liver cirrhosis. 169 97

Using an indwelling cisterna magna catheter technique, serial CSF samples were analyzed for amino acid content in rats at various stages of portal-systemic encephalopathy resulting from ammonium acetate administration following portacaval anastomosis. Anastomosis alone resulted in increased CSF concentrations of glutamine, tyrosine, phenylalanine, glutamate and alanine. GABA levels, on the other hand were not significantly changed. Onset of severe neurological symptoms following ammonium acetate administration resulted in selectively increased CSF alanine. Other amino acids were not further increased at severe stages of encephalopathy. Increased CSF alanine probably results from increased glutamine transamination in the brains of portacaval shunted rats.
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PMID:Cerebrospinal fluid amino acids in relation to neurological status in experimental portal-systemic encephalopathy. 174 65


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