Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic alcoholism results in thiamine deficiency as a consequence of inadequate dietary intake and of impaired absorption of the vitamin. In addition, there is evidence to suggest that alcohol reduces thiamine phosphorylation to thiamine pyrophosphate (TPP) in brain. TPP is a cofactor for the pyruvate dehydrogenase complex (PDHC), alpha-ketoglutarate dehydrogenase (alpha KGDH) and transketolase (TK), three enzymes involved in cerebral glucose and energy metabolism. Pyrithiamine-induced thiamine deficiency in the rat results in early, selective, reversible reductions of alpha KGDH in brain; PDHC activities are unaffected. Reductions of alpha KGDH are accompanied by decreased aspartate, glutamate and GABA and by concomitantly increased alanine in the brain of thiamine-deficient animals. It is suggested that decreased alpha KGDH, rather than decreased PDHC constitutes 'the biochemical lesion' in thiamine deficiency encephalopathy first enunciated by Peters in the 1930s. If sufficiently prolonged and severe, thiamine deficiency results in brain cell death. Possible mechanisms involved include compromised cerebral energy metabolism and focal accumulation of lactate, both of which could result from decreased activities of alpha KGDH. In addition, it is proposed that brain cell death in severe thiamine deficiency may result from excessive release of excitotoxic amino acids. Comparable mechanisms could be involved in the cell death and in the pathogenesis of the thiamine-unresponsive symptoms of the Wernicke-Korsakoff Syndrome in humans.
 ...
PMID:Effects of thiamine deficiency on brain metabolism: implications for the pathogenesis of the Wernicke-Korsakoff syndrome. 267 60

We have previously reported that chronic valproate administration reduced ketonemia in suckling mice and fasting epileptic children. The present study demonstrates that even a single dose of valproate in the therapeutic range for man caused a prolonged reduction of plasma beta-hydroxybutyrate levels in normal infant mice; the plasma glucose concentration was also significantly lowered. In the livers of these animals, there were extraordinary decreases in levels of free coenzyme A, acetyl CoA and free carnitine. Concomitantly concentrations of acid-soluble fatty acid (short-chain, non-acetyl) coenzyme A esters and of acid-insoluble (long-chain) fatty acid carnitine esters increased. There was evidence for inhibition of the metabolic flux through the Krebs citric acid cycle at those enzyme reactions which require coenzyme A. While valproate doubled liver alanine levels, concentrations of liver aspartate, glutamate and glutamine were reduced. All of the valproate-induced metabolite changes can be explained by the decrease of coenzyme A due to the accumulation of acid-soluble (non-acetyl) coenzyme A esters (presumably valproyl CoA and further metabolites). Decreased coenzyme A would limit the activities of one or more enzymes in the pathway of fatty acid oxidation and the Krebs citric acid cycle. Secondary decreases in acetyl CoA would limit both ketogenesis and gluconeogenesis. Decreased levels of selected hepatic amino acids could reflect their use as alternative fuels. The effect of clinical doses of valproate in infant mice may relate to the valproate-associated syndrome of hepatic failure and Reye-like encephalopathy in some infants and children and suggest a simple screen for those who may be at particular risk.
 ...
PMID:A single therapeutic dose of valproate affects liver carbohydrate, fat, adenylate, amino acid, coenzyme A, and carnitine metabolism in infant mice: possible clinical significance. 392 91

In systemic carnitine deficiency, an early phase of nonketotic hypoglycemia and liver dysfunction may precede a late phase of encephalopathy and myopathy. We studied two children with recurrent episodes of nonketotic hypoglycemia who were found to have systemic carnitine deficiency without myopathy or encephalopathy. Early institution of appropriate therapy prevented the onset of late debilitating complications in one patient, whereas therapeutic noncompliance in the other patient led to an episode of encephalopathy and myopathy. Metabolic studies indicated that decreased availability of alanine may be a factor in the genesis of hypoglycemia; concurrent depletion of cerebral glucose, ketones, and glycogen may be the cause of the encephalopathy.
 ...
PMID:Nonketotic hypoglycemia: an early indicator of systemic carnitine deficiency. 668 57

According to literature, anabolism is present in the visceral organs also during stress and early poststress-periods. During early periods of fasting, those enzyme structures of the visceral organs which are of prime importance are being catabolized. Therefore, an adequate nutrition is not only reasonable, but obligatory especially in those patients severely ill. As for the parenteral management of protein nutrition, solutions of L-amino acids (a.a.) are the only types suitable. These solutions should contain at least proportionate quantities of the 8 essential a.a., histidine, arginine, proline, alanine, glutamic acid and glycine with each single a.a. being within the respective physiologic regulation range. Different pattern of the a.a. requirement of adults are being established for different metabolic conditions. These types of a.a. pattern are highly dependent on the alterations of the functional requirement of one or more a.a. For the clinical need of total parenteral nutrition (t.p.n.) of adults, at least 3 types of different compositions of L-a.a. solution should be available: a) a standard a.a. solution (adapted to the physiologic requirement of adults) for long-term t.p.m. b) an a.a. solution with a high E/T-ratio for the t.p.n. of uremic patients (this solution is the one also used for t.p.n. of infants), c) an a.a. solution with high concentrations of branched-chain a.a. for the therapy of portosystemic encephalopathy. The metabolic significant and clinical importance of other special a.a. solutions are discussed.
 ...
PMID:[Postoperative amino acid metabolism]. 680 88

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.
 ...
PMID:Free amino acid changes in the cerebral cortex of experimental uremic rat. 685 32

Plasma amino-acid concentrations were measured in 167 patients with liver disease of varying aetiology and severity, all free of encephalopathy, and the results compared with those in 57 control subjects matched for age and sex. In the four groups of patients with chronic liver disease (26 patients with chronic active hepatitis, 23 with primary biliary cirrhosis, 11 with cryptogenic cirrhosis, and 48 with alcoholic hepatitis +/- cirrhosis) plasma concentrations of methionine were significantly increased, while concentrations of the three branched chain amino-acids were significantly reduced. In the first three groups of patients plasma concentrations of aspartate, serine, and one or both of the aromatic amino-acids tyrosine and phenylalanine were also significantly increased, while in the patients with alcoholic hepatitis +/- cirrhosis plasma concentrations of glycine, alanine, and phenylalanine were significantly reduced. In the three groups of patients with minimal, potentially reversible liver disease (31 patients with alcoholic fatty liver, 10 with viral hepatitis, and 18 with biliary disease) plasma concentrations of proline and the three branched chain amino-acids were significantly reduced. Patients with alcoholic fatty liver also showed significantly reduced plasma phenylalanine values. Most changes in plasma amino-acid concentrations in patients with chronic liver disease may be explained on the basis of impaired hepatic function, portal-systemic shunting of blood, and hyperinsulinaemia and hyperglucagonaemia. The changes in patients with minimal liver disease are less easily explained.
 ...
PMID:Plasma amino-acid patterns in liver disease. 707 13

Femoral arterio-venous (A-V) differences of blood free amino acids and plasma ammonia (NH3) were simultaneously determined after an overnight fast in 16 patients with decompensated liver cirrhosis in the absence and presence of encephalopathy, as compared with those in 8 control subjects. In spite of increased releases of phenylalanine (Phe) and tyrosine (Tyr) from the peripheral tissue, releases of isoleucine (Ile) and leucine (Leu) as well as alanine (Ala) were found to be significantly reduced in decompensated liver cirrhosis, particularly in the presence of hepatic encephalopathy. Furthermore, NH3 was found to be significantly taken up by the skeletal muscle of these patients, and a positive correlation was observed between arterial NH3 level and the A-V differences of Leu, of Ile and of Ala. These findings strongly suggest that net degradation (or utilization) of branched-chain amino acids (in particular, Leu and Ile) is enhanced in the muscle for detoxication of ammonia (i.e., glutamine synthesis) by supplying the carbon skeleton and energy in cirrhosis of the liver.
 ...
PMID:Augmented utilization of branched-chain amino acids by skeletal muscle in decompensated liver cirrhosis in special relation to ammonia detoxication. 722 60

Ammonia production by eight groups of intestinal bacteria was measured, and the effect on ammonia production of lowered pH and ambient ammonia concentration was determined. Endogenous ammonia production from bacterial protoplasm was also examined. To examine the mechanisms by which fermentable substrates reduce ammonia formation in a faecal incubation system, the effect of lactose, lactulose or glucose on ammonia release by pure cultures of intestinal bacteria was studied. The largest amounts of ammonia were generated by gram-negative anaerobes, clostridia, enterobacteria, and Bacillus spp. Gram-positive non-sporing anaerobes, streptococci and micrococci formed modest amounts, and lactobacilli and yeasts formed very little ammonia. All groups of bacteria formed less ammonia at pH 5.0 than at pH 7.0 and production of ammonia was not inhibited when 30 mmol ammonia/litre was included in the medium. Small amounts of ammonia were formed due to endogenous metabolism of bacterial cells. Washed cell suspensions of four isolates of Bacteroides, one clostridial isolate and two streptococcal isolates formed less ammonia from alanine, methionine or histidine after growth in the presence of either lactose or lactulose. In contrast, the Bacteroides isolates formed more ammonia from aspartate than from either lactose or lactulose. Also, cultures of gram-negative anaerobes and enterobacteria, and to a lesser extent clostridia and streptococci, formed significantly less ammonia in nutrient broth when lactose, lactulose or glucose was included in the medium. This decrease in ammonia formation was not due to a fall in pH of the medium. Ammonia production by gram-positive non-sporing anaerobes was not affected by carbohydrate fermentation. These results suggest that gram-negative anaerobic bacteria make a major contribution to ammonia generated from peptides and amino acids in vivo, and that ammonia may be formed from bacterial cells in the colon. Fermentation of lactose and lactulose may repress the formation and inhibit the activity of enzymes responsible for ammonia release. In the human colon these substrate effects may decrease the amount of ammonia available to exert a toxic effect on the host, and thus contribute to the beneficial effects of lactulose when it is used in the treatment of portosystemic encephalopathy.
 ...
PMID:Ammonia production by intestinal bacteria: the effects of lactose, lactulose and glucose. 738 15

Acute hepatic failure is associated with many biochemical abnormalities in plasma and brain. Changes that correlate well with the degree of behavioral impairment may be important factors in the development of encephalopathy. We measured the concentrations of intermediary metabolites, ammonia, and amino acids in brain and plasma and the rate of whole-brain glucose utilization in rats with an acutely devascularized liver. In all rats an estimate of the grade of encephalopathy (reflected by behavioral impairment) was made. Rats underwent portacaval shunting and hepatic artery ligation (or sham operation) and were kept normoglycemic and normothermic thereafter. We sampled blood and whole brain (by near-instantaneous freeze-blowing) 2, 4, or 6 h later. There were no alterations in levels of high-energy phosphate metabolites in the brain or in metabolites associated with the glycolytic pathway and Krebs cycle, except lactate and pyruvate. Brain glucose use was decreased similarly at all times after surgery. Levels of ammonia and many amino acids were increased in brain and plasma; brain aspartate, glutamate, and arginine levels were decreased. The increases in content of plasma ammonia and brain glutamine, proline, alanine, and aromatic amino acids and the decreases in brain aspartate and glutamate were most strongly correlated with behavioral impairment.
 ...
PMID:Metabolic abnormalities and grade of encephalopathy in acute hepatic failure. 793 39

Eight cases of liver failure and encephalopathy were observed among twenty cases of grade 3 and grade 4 dengue hemorrhagic fever/dengue shock syndrome admitted to the Department of Pediatrics, University Hospital, Kuala Lumpur from January 1990 to December 1991. All patients with deterioriation in mental status showed a marked increase in liver enzymes (aspartate and alanine aminotransaminases) and severe coagulopathy. Six patients needed cerebral protection, including ventilation, intravenous sedation and muscle relaxants. There was one death during the period of study and one case of residual hemiparesis in a boy who had, in addition, intracerebral hemorrhage. All other survivors had complete recovery of liver and neurological function.
 ...
PMID:Fulminant hepatitis in dengue infection. 816 54


<< Previous 1 2 3 4 5 Next >>