Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.4.6 (urease)
 7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Portacaval shunting in rats results in several metabolic alterations similar to those seen in patients with hepatic encephalopathy. The characteristic changes include: (a) diminution of cerebral function; (b) raised plasma ammonia and brain glutamine levels; (c) increased neutral amino acid transport across the blood-brain barrier; (d) altered brain and plasma amino acid levels; and (e) changes in brain neurotransmitter content. The aetiology of these abnormalities remains unknown. 2. To study the degree to which ammonia could be responsible, rats were made hyperammonaemic by administering 40 units of urease/kg body weight every 12 h and killing the rats 48 h after the first injection. 3. The changes observed in the urease-treated rats were: (a) whole-brain glucose use was significantly depressed, whereas the levels of high-energy phosphates remained unchanged; (b) the permeability of the blood-brain to barrier to two large neutral amino acids, tryptophan and leucine, was increased; (c) blood-brain barrier integrity was maintained, as indicated by the unchanged permeability-to-surface-area product for acetate; (d) plasma and brain amino acid concentrations were altered; and (e) dopamine, 5-hydroxytryptamine (serotonin) and noradrenaline levels in brain were unchanged, but 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of 5-hydroxytryptamine, was elevated. 4. The depressed brain glucose use, increased tryptophan permeability-to-surface-area product, elevated brain tryptophan content and rise in the level of cerebral 5-HIAA were closely correlated with the observed rise in brain glutamine content. 5. These results suggest that many of the metabolic alterations seen in rats with portacaval shunts could be due to elevated ammonia levels. Furthermore, the synthesis or accumulation of glutamine may be closely linked to cerebral dysfunction in hyperammonaemia.
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PMID:Hyperammonaemia causes many of the changes found after portacaval shunting. 170 23

Hyperammonemia is an important cause of cerebral dysfunction in liver failure. We used two well-established models to induce hyperammonemia in rats, injection of urease and injection of methionine sulfoximine (MSO). Urease gave a 10-fold increase in blood ammonia while MSO, a glutamine synthetase inhibitor, gave a 4-fold increase in blood ammonia with no increase in brain glutamine levels. We observed a 2-fold increase in 5-HT1A receptor (5-HT1A-R) expression ([3H] 8-OH-DPAT binding) in hippocampus, and little change elsewhere, including thalamus in both models, thus eliminating a role for increased glutamine in the receptor induction. In contrast, a 4 to 8-fold increase in 5-HT1A-R mRNA was observed both in hippocampus and thalamus, suggesting some post-transcriptional regulation. In the absence of glutamine, ammonium acetate treatment of a hippocampal cell line which had been engineered to stably express the 5-HT1A-R (HN2-5) gave a 1.5-fold increase in [3H] 8-OH-DPAT binding and a 4-fold increase in the mRNA levels for the 5-HT1A-R. We conclude that the cell line HN2-5 is a good model for studying some of the biochemical sequelae of hyperammonemia and that changes in brain function are not only at the metabolic level, as thought earlier, but can also occur at the transcriptional level.
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PMID:Hyperammonemia increases serotonin 1A receptor expression in both rat hippocampus and a transfected hippocampal cell line, HN2-5. 767 72

Minimal hepatic encephalopathy (MHE) describes patients with chronic liver disease or cirrhosis who have no clinical symptoms of brain dysfunction but perform worse on psychometric tests compared with healthy subjects. The pathogenesis of hepatic encephalopathy is controversial although ammonia has been found to induce cerebral dysfunction. Increased intestinal ammonia production is due to bacterial urease activity and the production of other toxin methabolities, such as mercaptans, thioles. This study assesses the clinical efficacy of Bifidobacterium longum plus fructo-oligosaccharides (FOS) in the treatment of MHE. A total of 60 cirrhotic patients were randomly and equally divided into two groups receiving Bifidobacterium+FOS (17 males, 13 females; mean age, 46+/-11 years) or placebo (16 males, 14 females; mean age, 45+/-12 years), respectively. All patients underwent clinical and laboratory assessment psychometric tests and automated EEG analysis: neurophysiological assessment, liver function assessment, amd neuropsychological assessment. After 90 days of treatment, fasting NH(4) serum levels were significantly decreased (P=0.003), performance on Trail Making Test-A was significantly decreased (P=0.000), performance on Trail Making Test-B was significantly decreased (P=0.000), performance on the symbol digit modalities test was significantly improved (P<0.05), performance on block design was significantly improved (P=0.000), and performance on the MMSE test was significantly improved (P=0.000). We conclude that the improvement in biochemical and neuropsychological tests of the group treated with Bifidobacterium longum+FOS are interesting and merit further, close examination.
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PMID:Bifidobacterium longum with fructo-oligosaccharide (FOS) treatment in minimal hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. 1739 30