UMLS:C0085584 - FACTA Search

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

Acute liver failure was induced in rats by successive administrations of thioacetamide over 3 days. At progressing stages of hepatic encephalopathy (HE), brains were fixed with microwave irradiation for analysis of metabolite levels or with formaldehyde for histopathological analysis. Metabolite levels were determined using 1H-nuclear magnetic resonance spectroscopy of perchloric acid extracts of the frontal cortex, parietal or occipital cortex, hippocampus, striatum, brain stem, and cerebellum. After thioacetamide treatment, thioacetamide and its metabolites were detected in the brains at levels that did not correlate with the stage of HE. No changes were observed in the levels of N-acetylaspartate, alanine, gamma-aminobutyric acid, aspartate, or inositol in any brain region after thioacetamide treatment. HE was accompanied by elevated glutamine, glucose, and lactate throughout the brain. At all stages of HE, taurine was decreased in the neocortex and hippocampus, and glutamate and choline compounds were decreased in the frontal cortex. None of the metabolite changes showed progression with the stage of HE. Progressing HE was accompanied by increasing neuronal injury in layer III of the neocortex, in the Purkinje cells of the cerebellum, and in the hippocampus, particularly in the CA4 sector. The similarity of this distribution of injury to that associated with excitotoxic injury suggests that metabolic abnormalities after acute hepatic failure may give rise to adverse effects at excitatory (glutamatergic) neuronal receptors, leading to neuronal injury and clinical symptoms of progressing encephalopathy in this model. However, neuronal injury and the presence of thioacetamide and its metabolites in the brain raise questions about the validity of thioacetamide-induced liver failure as a model for clinical HE.
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PMID:Cerebral metabolic and histological effects of thioacetamide-induced liver failure. 821 78

A three compartment mathematical model was used to analyse the urea response to an alanine infusion in six control subjects, and in 15 patients with liver cirrhosis and variable degree of hepatocellular failure. Model-derived coefficients were used to calculate two parameters (Ymax and Tmax), able to describe the theoretical response of the conversion of amino acid derived nitrogen into urea, in response to a unit impulse in alanine concentration. They correspond to the maximum rate of conversion of nitrogen from an intermediary pool into urea and to the time delay between the impulse and Ymax, respectively. In cirrhosis, the apparent volume of distribution of infused alanine was smaller than in controls, while the conversion of alanine nitrogen into an intermediary pool of nitrogen and finally into urea nitrogen were both reduced. Also Ymax was reduced by 50% in cirrhosis, whereas Tmax was increased by 50%, and both significantly correlated with galactose elimination capacity (GEC; R2 = 0.706 and R2 = 0.505, respectively) and with antipyrine clearance (Ap Cl; R2 = 0.823 and R2 = 0.576, respectively). Model-derived assessment of urea appearance in response to alanine infusion is able to quantify the functional liver cell mass, and may prove useful for the study of nitrogen metabolism in cirrhosis, mainly in relation to encephalopathy.
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PMID:Model-derived assessment of urea appearance in response to alanine infusion: a quantitative measure of liver function in cirrhosis. 828 Aug 43

Zinc deficiency is common in cirrhosis and has been involved in the altered nitrogen metabolism. In this study, we measured the effects of zinc supplementation on the dynamics of amino acid-derived urea synthesis in cirrhosis with mild or latent encephalopathy. The hepatic conversion of amino acids into urea was studied in eight patients with advanced cirrhosis under controlled conditions of substrate availability (continuous alanine infusion), before and after 3-month oral zinc sulfate supplementation (600 mg/d). Eight more patients, matched for hepatocellular failure and encephalopathy, served as controls. Plasma zinc levels were reduced in all patients and returned to normal after oral zinc. The alanine-stimulated urea nitrogen synthesis rate in relation to alpha-amino-N concentration--the functional hepatic nitrogen clearance--increased by 25% after zinc supplementation, i.e., more urea was produced at any alpha-amino-N concentration. Basal and alanine-induced glucagon decreased by 50%, and the ammonia response to alanine decreased by 30%. Psychometric tests improved, as did routine and dynamic liver function tests and the Child-Pugh score. Also, the plasma concentration of lipid peroxides was reduced by zinc. No significant changes were observed in the control group. Our data indicate that long-term oral zinc speeds up the kinetics of urea formation from amino acids and ammonia. Changes in the hormonal drive and/or the antioxidant activity of zinc might be involved in the general improvement in liver function, whereas the beneficial effects on encephalopathy might stem from decreased ammonia.
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PMID:Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis. 862 Nov 38

L-carnitine administration prevents the neurological symptoms of acute ammonia toxicity. To further evaluate its efficacy in the prevention of hepatic encephalopathy in hyperammonemic conditions, L-carnitine (16 mmol/kg, intraperitoneally [i.p.] was administered 1 hour before ammonium acetate (NH4OAc) (8.5 mmol/kg, subcutaneously) to portacaval shunted (PCS) rats. Cerebrospinal fluid (CSF) ammonia, lactate, and amino acid levels were measured in relation to deteriorating neurological status in these animals. None of 35 L-carnitine-treated animals showed neurological deterioration after NH4OAC administration compared with saline-treated controls; the latter manifested severe encephalopathy progressing through loss of righting reflex to coma. Survival rate was 100% in the L-carnitine-treated group compared with 5% in saline-treated controls. Following NH4OAC administration to PCS rats, CSF ammonia increased to 0.93 +/- 0.15 mmol/L and 1.24 +/- 0.15 mmol/L at precoma and coma stages of encephalopathy (P < .01) respectively. Treatment with L-carnitine reduced CSF ammonia at both precoma and coma stages; the time-course of this protective effect paralleled blood and CSF L-carnitine accumulation. CSF alanine and lactate increases following NH4OAC administration to PCS rats were significantly attenuated following L-carnitine treatment. However, L-carnitine treatment did not lead to significant reductions in plasma ammonia nor CSF or brain glutamine in these animals. These findings show the therapeutic efficacy of L-carnitine in ammonia-precipitated coma in PCS rats and suggest that this protective effect is centrally mediated involving improved mitochondrial respiration. L-carnitine could be of therapeutic benefit in the prevention of hepatic encephalopathy precipitated by ammoniagenic conditions in humans with chronic liver disease.
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PMID:Protective effect of L-carnitine in ammonia-precipitated encephalopathy in the portacaval shunted rat. 904 97

The activity of glutamate decarboxylase, GABA-, aspartate-and alanine aminotransferases, the content of GABA, glutamate, aspartate and alanine were studied in the brain hemispheres and stem of rats that were undergoing the hypoglycemic coma as well as those rats had undergone 7-9 comas on the second day after the last coma. In hypoglycemia, the brain's content of glutamate, alanine and GABA decreased and content of aspartate increased; the activity of enzymes investigated did not change. On the second day after 7-9th hypoglycemic coma, the decrease of activity of glutamate decarboxylase in hemispheres and the decrease of GABA amount in brain stem were detected. This can be an evidence of decrease of GABA amount produced and secreted by nerve ends of the pathways leading from striata to substantia nigra. The detected changes result from multiple influence of hypoglycemia to the brain and may by important in the development of posthypoglycemic encephalopathy.
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PMID:[Enzyme activity and level of GABA-shunt substrates in rat brain during repeated exposure to hypoglycemic doses of insulin]. 925 15

Dengue viruses exist in nature as a collection of highly similar but not identical members (quasispecies). In order to correlate the presence of viral quasispecies with rare occurrence of unusual clinical manifestations in dengue-infected individuals, a dengue type 2 virus was isolated from the peripheral blood of a 12-year-old boy who presented with fever, headache, drowsiness and tonic seizure of the left arm, and subsequently manifested symptoms and signs of dengue hemorrhagic fever. Analysis of the envelope glycoprotein sequence of the encephalopathy-associated virus and two other dengue type 2 viruses from the same epidemic season in Chiang Mai, Thailand revealed that all three viruses belonged to the subtype IIIa of the five-subtype phylogenetic nomenclature system for dengue type 2 virus. The encephalopathy-associated dengue virus was more divergent from the others and was characterized by an Ala-->Val substitution at the position 173 of the envelope glycoprotein. This substitution mapped to the central domain 1 which was not known to be involved directly in envelope-receptor interaction.
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PMID:Primary sequence of the envelope glycoprotein of a dengue type 2 virus isolated from patient with dengue hemorrhagic fever and encephalopathy. 927 81

Ornithine transcarbamylase (OTC) deficiency is an X-linked disorder of urea synthesis. Among females who carry a mutant OTC allele, there is a wide range of phenotypic variability, ranging from apparent normality to a severe onset and the resulting profound neurologic impairment observed in hemizygous males. This study was designed to define the phenotypic variability of OTC deficiency in ostensibly healthy carrier females and to compare them to noncarrier females from their own and other families. One hundred seventy-five women from 89 families participated in this study. Each completed a mailed questionnaire, allopurinol testing, and fasting plasma amino acid determinations. OTC carrier status was determined by pedigree analysis, allopurinol test results, and/or DNA mutation analysis. Overall, 79 women were identified as carriers of a mutant OTC allele (60 proband mothers, 19 relatives), and 96 women (32 proband mothers, 64 female relatives) were determined to be noncarriers. Comparison of biochemical phenotypes indicated that carriers and noncarriers do not differ in daily urinary creatinine excretion, but that carriers excrete significantly less urea nitrogen and total nitrogen, reflecting their significantly lower historically reported daily protein intake. Carriers had significantly higher levels of fasting plasma glutamine and alanine, and significantly lower levels of citrulline and arginine compared with noncarriers. Carriers and noncarriers reported similar demographic characteristics, anthropometric measurements, level of education, and medical and pregnancy histories. There was no indication of increased incidence of migraine headaches among carriers. Thus, we found no evidence that asymptomatic adult female OTC heterozygotes are at increased risk for previously unidentified health problems apart from an unknown risk for hyperammonemic encephalopathy as occurred in 3 of the carriers in this study. Because these episodes appear to be related to physiologic stress (fracture, parturition), it would seem medically prudent for carriers to be aware of this risk.
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PMID:The phenotype of ostensibly healthy women who are carriers for ornithine transcarbamylase deficiency. 985 2

Carbohydrate-deficient glycoprotein syndrome (CDGS) represents a class of genetic diseases characterized by abnormal N-linked glycosylation. CDGS patients show a large number of glycoprotein abnormalities resulting in dysmorphy, encephalopathy, and other organ disorders. The majority of CDGSs described to date are related to an impaired biosynthesis of dolichyl pyrophosphate-linked Glc3Man9GlcNAc2 in the endoplasmic reticulum. Recently, we identified in four related patients a novel type of CDGS characterized by an accumulation of dolichyl pyrophosphate-linked Man9GlcNAc2. Elaborating on the analogy of this finding with the phenotype of alg5 and alg6 Saccharomyces cerevisiae strains, we have cloned and analyzed the human orthologs to the ALG5 dolichyl phosphate glucosyltransferase and ALG6 dolichyl pyrophosphate Man9GlcNAc2 alpha1,3-glucosyltransferase in four novel CDGS patients. Although ALG5 was not altered in the patients, a C-->T transition was detected in ALG6 cDNA of all four CDGS patients. The mutation cosegregated with the disease in a Mendelian recessive manner. Expression of the human ALG5 and ALG6 cDNA could partially complement the respective S. cerevisiae alg5 and alg6 deficiency. By contrast, the mutant ALG6 cDNA of CDGS patients failed to revert the hypoglycosylation observed in alg6 yeasts, thereby proving a functional relationship between the alanine to valine substitution introduced by the C-->T transition and the CDGS phenotype. The mutation in the ALG6 alpha1,3-glucosyltransferase gene defines an additional type of CDGS, which we propose to refer to as CDGS type-Ic.
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PMID:A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic. 1035 25

Brain edema sufficient to cause intracranial hypertension and brain herniation remains a major cause of mortality in acute liver failure (ALF). Studies in experimental animal models of ALF suggest a role for ammonia in the pathogenesis of both encephalopathy and brain edema in this condition. As part of a series of studies to evaluate the therapeutic efficacy of ammonia-lowering agents, groups of rats with ALF caused by hepatic devascularization were treated with L-ornithine-L-aspartate (OA), an agent shown previously to be effective in reducing blood ammonia concentrations in both experimental and human chronic liver failure. Treatment of rats in ALF with infusions of OA (0.33 g/kg/h, intravenously) resulted in normalization of plasma ammonia concentrations and in a significant delay in onset of severe encephalopathy. More importantly, brain water content was significantly reduced in OA-treated rats with ALF. These protective effects of OA were accompanied by increased plasma concentrations of several amino acids including glutamate, gamma-aminobutyric acid (GABA), taurine, and alanine, as well as the branched-chain amino acids, leucine, isoleucine, and valine. Increased availability of glutamate following OA treatment provides the substrate for the major ammonia-removal mechanism (glutamine synthetase). Plasma (but not cerebrospinal fluid) glutamine concentrations were increased 2-fold (P <.02) in OA-treated rats, consistent with increased muscle glutamine synthesis. Direct measurement of glutamine synthetase activities revealed a 2-fold increase following OA treatment. These findings demonstrate a significant ammonia-lowering effect of OA together with a protective effect on the development of encephalopathy and brain edema in this model of ALF.
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PMID:L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. 1046 68

Changes in plasma amino acid concentrations were measured in patients with hepatic failure during extracorporeal hemodiabsorption (using the Liver Dialysis Unit, "the Unit") or hemodiabsorption plus sorbent-based pheresis treatment (using the Liver Dialysis Plasmafilter Unit, "the PF-Unit") Systems. Eight patients with hepatic failure, grade 3 or 4 encephalopathy, elevated bilirubin and/or creatinine levels and respiratory or renal failure were treated for 1-3 days with the Unit alone. Three of these were also treated with the Unit containing 10 g of BCAA in the sorbent suspension. Four patients with hepatic failure treated with the PF Unit also had 10 g of branched chain amino acid (BCAA) added to the sorbents of the Unit portion of this device. Pre- and post-plasma samples were drawn and high performance liquid chromatography (HPLC) was used to separate and detect amino acids in the plasma. Both the Unit and the PF-Unit have the capability to selectively remove various amino acids, especially aromatic amino acids (AAA). The pre-treatment amino acid profiles of plasma were typical for hepatic failure, with abnormally high levels of phenylalanine, tyrosine, tryptophan, and methionine and decreased levels of valine, leucine and isbolucine. The average pre-treatment Fischer ratio (BCAA/AAA) for both Unit and PF-Unit patients was 1.43 (+/- 0.58). Treatments by both systems resulted in an increase of BCAA levels in blood and concomitant decrease of AAA levels, with an average Fischer ratio improvement of 30-38% for the Unit and PF-Unit without BCAA. The Fischer ratio improved by 90% (average) for the Unit with BCAA. Levels of many other amino acids (such as alanine, glycine, proline or lysine) increased during both Unit and PF-Unit treatments. The removal of strongly protein-bound toxin and amino acids such as tryptophan and sulphydryl amino acids was more effective by the PF-Unit. Both the Unit and the PF-Unit have the unique capability to remove toxic aromatic amino acids while increasing BCAA levels in patient. The increase in many amino acid levels may be related to the removal of toxins that interfere with normal amino acid metabolism. The addition of the PF module improves the removal of bilirubin and similarly protein-bound chemicals. Changes in amino acid profiles by the Unit and the PF-Unit contrast markedly with other extracorporeal devices.
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PMID:Effect of hemodiabsorption and sorbent-based pheresis on amino acid levels in hepatic failure. 1091 55

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