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

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

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

Blood substrate and hormone concentration were determined in 16 children with Reye syndrome prior to and following administration of hypertonic glucose. Baseline concentrations of lactate, pyruvate, alanine, glutamine, glutamate, proline, hydroxyproline, lysine, and aspartate were elevated (p less than 0.01), whereas citrulline and arginine were low. All substrate concentrations were below or within the normal range following 36 hours of therapy except those of lactate, pyruvate, and aspartate. Urea nitrogen excretion was reduced (p less than 0.05) on the second day of therapy. Plasma concentrations of insulin and growth hormone increased and glucagon decreased during the first day. Cortisol remained elevated throughout the study period. We conclude that the high circulating concentrations of substrates are the result of both increased mobilization and decreased clearance and that hypertonic glucose infusion suppresses substrate mobilization. A primary abnormality of the mitochondria could explain the metabolic perturbations that occurred. A possible relationship between the encephalopathy in this disorder and an insult to both brain and brain capillary mitochondria is discussed.
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PMID:Metabolic response to hypertonic glucose administration in Reye syndrome. 66 61

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

Defects in mitochondrial DNA (mtDNA) are associated with several different human diseases, including the mitochondrial encephalomyopathies. The mutations include deletions but also duplications and point mutations. Individuals with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) carry a common A-to-G substitution in a highly conserved portion of the gene for transfer RNA(Leu(UUR)). Although the MELAS mutation may be comparable to the defect in the tRNA(Lys) gene associated with MERRF (myoclonus epilepsy associated with ragged-red fibres), it is also embedded in the middle of a tridecamer sequence necessary for the formation of the 3' ends of 16S ribosomal RNA in vitro. We found that the MELAS mutation results in severe impairment of 16S rRNA transcription termination, which correlates with a reduced affinity of the partially purified termination protein for the MELAS template. This suggests that the molecular defect in MELAS is the inability to produce the correct type and quantity of rRNA relative to other mitochondrial gene products.
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PMID:Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mitochondrial encephalomyopathies. 175 69

Sera from 40 patients with a clinical diagnosis of halothane-associated hepatitis were tested for the presence of antibodies to the trifluoroacetate (TFA) halothane metabolite hapten using an ELISA assay, with TFA-albumin as the antigen. Positive results were obtained in 30% of cases of which 3/4 with encephalopathy were positive and 9/36 non-fulminant cases were positive. Antibody specificity to the TFA hapten was confirmed in each positive result by a 'hapten inhibition' experiment in which TFA albumin binding was blocked by preincubation of serum with TFA-lysine. Most probably this assay detects a relatively low affinity cross-reaction with the TFA hapten of antibodies in the patients' sera which are directed against specific TFA-labelled liver proteins. Anti-TFA-albumin antibodies were not detected in 28 normal subjects, 5 subjects with fulminant hepatic failure secondary to other causes, 6 subjects with a history of 2 or more exposures to halothane but with no evidence of liver disease and 28 patients with a variety of chronic liver diseases. It is concluded that ELISA testing using trifluoroacetylated rabbit serum albumin (TFA-RSA) as antigen is a quick and convenient assay for the confirmation of halothane-associated hepatitis in fulminant hepatic failure secondary to halothane, but is less sensitive when the illness follows a milder course.
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PMID:Detection of antibodies to a halothane metabolite hapten in sera from patients with halothane-associated hepatitis. 260 25

The uremic syndrome is multifactorial, and affects most tissues and organs. Disturbances in protein and amino acid metabolism may play important roles, especially in chronic uremia, either directly or by production of toxic metabolites, with resultant negative nitrogen (N) balance, muscle wasting, reduced protein synthesis, and characteristically abnormal intracellular free amino acid concentrations. There are also grossly abnormal amino acid levels in the plasma of uremic patients, e.g., increases in conjugated amino acids, high levels of several nonessential and low levels of essential amino acids. The ratios of tyrosine/phenylalanine and of valine/glycine are decreased. The low tryptophan levels may contribute to encephalopathy as a result of an imbalance in neurotransmitter synthesis. Citrulline is found in excess; the explanation is unresolved. There are elevated concentrations of the sulfur-containing amino acids: cystine, taurine, cystathionine, and homocysteine. Excess of the latter is implicated in the atherogenesis of renal failure. Disturbed metabolism and interorgan exchange of amino acids in the uremic state explains some of the abnormalities in tissue and plasma concentrations of individual amino acids. Enzymatic defects are involved in the disturbed metabolism of branched chain amino acids (BCAA), with possible antagonism among them, which impairs growth and amino acid utilization. Carbohydrate intolerance, associated with insensitivity of peripheral tissues to insulin and hyperinsulinemia, elicits decreased plasma BCAA. Protein synthesis rates in normal and pathological conditions are more closely related to the intracellular amino acid pool than to plasma amino acid levels. Concentrations of individual amino acids in the plasma pool are poor indicators of their intracellular concentrations. Muscle contains the largest pool of protein and free amino acids in the body. In chronic renal failure patients, the intracellular concentrations of valine, threonine, lysine, and carnosine are low. With low protein diets and in hemodialysis, serine, tyrosine, and taurine often are also low. The low taurine may be related to fatigue and to uremic cardiomyopathies. The commonly used amino acid supplements generally fail to correct the intracellular amino acid deficits. A "New Formula" has been developed to correct these intracellular amino acid abnormalities, and to supplement a low protein diet. It provides more valine than leucine, increased tyrosine and threonine, and less histidine, leucine, isoleucine, lysine, methionine, and phenylalanine than in formulas customarily used for patients with chronic renal failure. It is uncertain whether other ap
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PMID:Amino acid metabolism in uremia. 267 58

The etiology of uremic encephalopathy remains largely unknown. In order to elucidate the role of amino acid changes in uremic encephalopathy, the free amino acids in serum and cerebral cortex were measured in the experimental uremic models. The rats weighing 200 g underwent bilateral ureteral ligation for 48 hours (acute uremia), while the other animals were kept for 4 months after unilateral nephrectomy followed by partial 2/3 nephrectomy of the remaining kidney (chronic uremia). They were confirmed to develop chemical changes compatible with uremia showing markedly elevated serum levels of BUN, creatinine and K+, and were compared with the sham-operated controls. The amino acid patterns, obtained from serum and cerebral cortex, were essentially identical in both acute and chronic uremia. In serum, aspartic acid, glycine and 3-methylhistidine were significantly elevated, and in addition citrulline, alpha-aminoadipic acid, cystine and gamma-aminobutyric acid specifically appeared in uremia. On the contrary, glutamic acid, leucine, lysine, tryptophan, tyrosine and valine were significantly reduced. Tyrosine/phenylalanine ratio, valine/glycine ratio, essential amino acids/non essential amino acids ratio were also apparently reduced in uremia. In cerebral cortex, aspartic acid, glutamine, glycine, histidine, ornithine, phenylalanine, phosphoethanolamine and taurine were significantly elevated, whereas 1-methylhistidine and 3-methylhistidine were specifically detected. Carnocine, glutamic acid and ornithine disclosed a significant reduction in uremia. The above complicated changes in cerebral cortex could not be explained simply by the enhanced permeability of the blood-brain barrier, or by the accelerated ammonia fixation. Therefore, it was suggested that the amino acid levels in cerebral cortex vary under the control of the sophisticated mechanism.
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PMID:[A comparative study of free amino acid levels in serum and cerebral cortex in uremic rat]. 650 56

The influx of phenylalanine, tryptophan, leucine, and lysine across the blood-brain barrier of individual brain structures was studied in rats 7--8 weeks after a portacaval shunt or sham operation. The method involved a brief infusion of labeled amino acid in tracer quantity and quantitative autoradiography. The clearance rates of phenylalanine, tryptophan, and leucine were increased in proportion to each other in every region examined, but not by the same factor. Tryptophan clearance increased the most (about 200%) and leucine the least (about 30%), compared with phenylalanine (about 80%). This was unexpected, as all three amino acids are believed to be transported by the same mechanism. The changes were most marked in several limbic structures and the reticular formation, whereas the hypothalamus was least affected. Plasma clearance of lysine was decreased in all areas by about 70%. Since the circulating lysine concentration was decreased by 13%, the actual rate of lysine influx was even more reduced. The results demonstrate specific alterations in two different amino acid transport systems. The resulting excess brain neutral amino acids, some of which are neurotransmitter precursors, as well as reduced basic amino acid availability, may be of etiological significance in heptic encephalopathy.
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PMID:Regional blood-brain barrier permeability to amino acids after portacaval anastomosis. 705 89

Patients with sepsis often manifest disorientation, somnolence, asterixis and coma, symptoms also seen in portasystemic encephalopathy. Altered plasma concentrations of the neutral amino acids and in creased blood-brain transport of these acids may play a role in portasystemic encephalopathy. Plasma amino acids and blood-brain barrier transport of neutral amino acids were investigated in a rat model of abdominal sepsis, cecal ligation and puncture. The blood-brain transport was studied by the technique of Oldendorf with carbon-14-amino acids 12 and 24 hours after the induction of sepsis. In similar groups of animals, isolation of brain capillaries was carried out by the technique of Hjelle and the capillaries were incubated with carbon-14-amino acids to study transport activity. Plasma and brain amino acids were deranged in a fashion similar to the derangements seen in portasystemic encephalopathy, with a decrease in plasma branched chain amino acids and an increase in most neutral amino acids in brain. The changes were most pronounced after 24 hours. The brain uptake of several neutral amino acids was increased in the septic rats, while the uptake of lysine, a basic amino acid, was normal. In the brain capillaries isolated from septic rats, tyrosine and leucine transport was also greater than in sham-operated animals. Elevated neutral amino acids may play a role in the encephalopathy encountered in septic patients similar to its role in patients with portasystemic encephalopathy, as similar mechanisms appear to be operating.
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PMID:Blood-brain barrier derangement in sepsis: cause of septic encephalopathy? 745 18


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