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

The amino acids glutamate, aspartate, gamma-aminobutyric acid (GABA), and glutamine were measured as their dansyl derivatives in whole brain and specific brain regions by a sensitive double-labelling technique at various times during the development of hypoglycaemic encephalopathy. Hypoglycaemia was induced by administration of insulin (100 i.u./kg) to 24-h fasted rats. No significant changes in glutamate, GABA, or glutamine were detected in whole brain at any time up to and including the onset of hypoglycaemic convulsions. In cerebral cortex, however, GABA levels were reduced to 65% or normal prior to the appearance of neurological symptoms of hypoglycaemia. Onset of symptoms (severe catalepsy and loss of righting reflex, but before the onset of convulsions) was accompanied by marked decreases of glutamate and glutamine in striatum and hippocampus. These regions, in addition to cerebral cortex, show the greatest vulnerability to hypoglycaemic insult, according to previous anatomical studies. Aspartate levels were significantly increased (p less than 0.01) in the cerebral cortex of convulsing animals, confirming a previous report. No changes were detectable in any of the amino acids studied in medulla-pons at any time during the progression of hypoglycaemia. Cerebral cortex and striatum showed a selective net loss of amino acids (2.2 and 3.5 mumol/g. respectively) prior to the onset of insulin-hypoglycaemic convulsions.
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PMID:Regional amino acid distribution in relation to function in insulin hypoglycaemia. 612 Oct 12

Sustained hyperammonemia resulting from portocaval anastomosis (PCA) in the rat, is accompanied by neurological symptoms and reversible morphological changes in brain, the nature and distribution of which suggest selective vulnerability of certain brain structures. The present study was initiated to investigate the effects of increasing CNS ammonia on the distribution of amino acids in regions of the rat brain in relation to the degree of neurological impairment in PCA rats. Four weeks following PCA, rats were administered ammonium acetate (5.2 mmol/kg, i.p.) to precipitate neurological symptoms of encephalopathy which included diminished locomotor activity, loss of hindlimb extension and righting reflexes and ultimately coma. At various stages during the development of encephalopathy, rats were sacrificed and the amino acids glutamine, glutamate and aspartate measured simultaneously, using a sensitive double-isotope dansyl microassay. Homogenates of the following regions of the CNS were assayed: cerebral cortex, hippocampus, striatum, midbrain, hypothalamus, cerebellum, medulla-pons, spinal cord (gray matter) and spinal cord (white matter). Sustained hyperammonemia associated with PCA alone resulted in a non-uniform 2-4 fold increase of glutamine in all regions of the CNS. Glutamate, on the other hand, was selectively increased in striatum and cerebellum, two regions of brain shown to exhibit early morphologically-characterised astrocytic abnormalities in rats with PCA. Onset of severe neurological dysfunction was accompanied by significantly decreased glutamine and glutamate in striatum and cerebellum. Thus, sustained hyperammonemia in association with portocaval shunting results in region-selective effects with respect to glutamine-glutamate metabolism in the CNS.
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PMID:Amino acid changes in regions of the CNS in relation to function in experimental portal-systemic encephalopathy. 615 Apr 51

Ammonia intoxication decreases the hyperpolarizing action of postsynaptic inhibition. This study examines the metabolic state of the spinal cord during this effect of ammonia intoxication on spinal motoneurons. ATP, ADP, AMP, the adenylate energy charge, glucose, PCr, pyruvate, alpha-ketoglutarate and glutamate were unchanged during the effect of ammonia on the hyperpolarizing action of postsynaptic inhibition. NH4+, glutamine and lactate were increased. Ammonia intoxication affected postsynaptic inhibition without changes of the resting membrane potential, the neuron input resistance, the action potential and EPSPs. The encephalopathy caused by ammonia intoxication is known to occur without an alteration of the tissue energy state. The effect of ammonia intoxication on postsynaptic inhibition can be considered as a cause of the encephalopathy because postsynaptic inhibition is altered without a change of the tissue energy state, the resting membrane potential, the whole neuron resistance, the action potential and EPSPs.
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PMID:Ammonia, postsynaptic inhibition and CNS-energy state. 632 74

Hyperammonemic associated encephalopathy developed in an adult receiving essential amino acids. Evidence that her encephalopathy was related to her hyperammonemia included (1) elevated CSF glutamine and serum ammonia levels, (2) the absence of any other drug or metabolic cause of encephalopathy, and (3) resolution of her encephalopathy and abnormal ammonia levels with discontinuation of the hyperalimentation. The serum ammonia levels of patients receiving essential amino acid fluid should be monitored. If the levels remain elevated or if toxicity develops, consideration should be given to switching to an alternate fluid.
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PMID:Hyperammonemic encephalopathy due to essential amino acid hyperalimentation. 643 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

In order to define further the therapeutic role of hemodialytic procedures in acute hepatic failure, 20 pigs with ischemic hepatic necrosis underwent randomized hemodialysis against an electrolyte solution (n = 6), hemofiltration with re-infusion of an electrolyte solution (n = 5), control hemofiltration with re-infusion of autologous ultrafiltrate (n = 4) or no extracorporeal procedure at all (n = 5). Pigs on hemodialytic procedures survived significantly longer (51 +/- 11 hrs) than controls (36 +/- 8 hrs). There were no differences in the duration of survival between hemodialysis and hemofiltration, nor between controls undergoing and those not undergoing an extracorporeal procedure. Electroencephalograms showed more rapid (p less than 0.05) deterioration in control animals than in the treatment group. Putative toxins such as ammonia, glutamine, tyrosine, tryptophan, and methionine all decreased transiently in the treatment group; in the control group a continuous increase in the levels of the putative toxins was observed. Comparison of all pigs surviving 35 hrs or less (n = 6) and animals surviving more than 45 hrs (n = 7) showed that long-term survival was significantly associated with lower plasma ammonia and methionine concentrations and fewer abnormalities on the electroencephalogram 10 hrs after the start of extracorporeal procedures; moreover six of the 7 long-term survivors underwent hemodialysis or hemofiltration procedures. We conclude that hemodialytic procedures prolong survival in pigs with ischemic hepatic necrosis by slowing the development of encephalopathy; this effect of hemodialytic procedures may be mediated by the lowering of plasma ammonia and methionine levels.
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PMID:Large-pore hemodialytic procedures in pigs with ischemic hepatic necrosis; a randomized study. 651 36

Arterial and internal jugular venous levels of false neurotransmitters (FNTs: octopamine, OCT, and phenylethanolamine, PEA), aromatic and branched-chain amino acids, glutamine, ammonia, and pH were measured in patients with portal-systemic encephalopathy (PSE) and in appropriate controls to define the role of these parameters in the pathogenesis of hepatic coma. The typical plasma patterns reported in the literature were observed: hyperammonaemia (59 +/- 8 mumol/l v. controls 30 +/- 4, P less than 0.005), elevated OCT (19 +/- 3 nmol/l v. 6 +/- 1, P less than 0.001) and PEA (64 +/- 8 nmol/l v. 27 +/-3, P less than 0.001), high ratio of aromatic to branched-chain amino acids (0.92 +/- 0.12 v. 0.32 +/- 0.04, P less than 0.005), and variable glutamine levels 216-734 mumol/l). No consistent net flux into or out of the brain could be demonstrated for any of these substances. The degree of encephalopathy correlated with the level of respiratory alkalosis (r=0.325, P less than 0.05) which, in turn, correlated with the degree of elevation of plasma OCT (r=0.439, P less than 0.05) and PEA (r=0.489, P less than 0.05) as well as with the excess of glutamine efflux from the brain (r=0.927, P less than 0.05). These findings support current views that hyperammonaemia, plasma amino acid imbalance, and elevated production of FNTs are interrelated disturbances which contribute to the pathogenesis of PSE. In addition, the data suggest that alkalosis accentuates the altered metabolism of these substances within the brain.
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PMID:Plasma levels of false neurotransmitters across the brain in portal-systemic encephalopathy. 680 48

The levels of free amino acids in the cerebral cortex of acute and chronic uremic rats were examined. Amino acids significantly elevated were aspartate, glutamine, glycine, histidine, ornithine, phenylalanine, phosphoethanolamine and taurine, whereas 1-methyl histidine and 3-methyl histidine were specifically detected in uremic rats. Glutamate, arginine and carnosine disclosed a significant reduction. There was no change in the concentrations of gamma-aminobutyrate and alanine. The above findings were essentially identical in both acute and chronic uremia. It was conjectured that these changes of amino acid levels in the brain might participate in the progress of uremic encephalopathy.
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PMID:Free amino acid changes in the cerebral cortex of experimental uremic rat. 685 32

We treated 13 adult patients with acute leukemia or chronic myelocytic leukemia (CML) in blast phase using succinylated Acinetobacter glutaminase-asparaginase (SAGA) administered on a daily dose schedule. SAGA reduced the peripheral blast count in two patients with acute lymphoblastic leukemia and two with blastic CML; however, no patient achieved either complete or partial remission. Marked central nervous system toxic effects (encephalopathy and coma) were observed, limiting treatment in patients whose disease appeared responsive; this effect finally prompted early discontinuance of the trial. Other toxic effects observed included nausea, hyperglycemia, and respiratory alkalosis. Hypersensitivity reactions to the enzyme were not seen. Pharmacologic analyses showed that prolonged blood glutamine depletion was achieved only by daily enzyme administration; however, we noted the importance of performing amino acid analysis on blood which was deproteinized immediately following phlebotomy. Our results demonstrate excessive central nervous system toxicity when glutaminase-asparaginase is administered on a daily schedule. Because of this effect, we propose that future trials of similar enzymes be limited to short courses of enzyme therapy, possibly with the addition of antimetabolites or amino acid analogs, which could enhance the antitumor effect without increasing toxicity.
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PMID:Clinical evaluation of succinylated Acinetobacter glutaminase-asparaginase in adult leukemia. 704 29

Plasma and cerebrospinal fluid amino acid levels wee 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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PMID:Plasma and cerebrospinal fluid amino acid patterns in hepatic encephalopathy. 710 54


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