Source:http://linkedlifedata.com/resource/pubmed/id/19437490
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2009-7-2
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pubmed:abstractText |
Treatment of hyperammonemia and hepatic encephalopathy in cirrhosis is an unmet clinical need. The aims of this study were to determine whether L-ornithine and phenylacetate/phenylbutyrate (administered as the pro-drug phenylbutyrate) (OP) combined are synergistic and produce sustained reduction in ammonia by L-ornithine acting as a substrate for glutamine synthesis, thereby detoxifying ammonia, and the phenylacetate excreting the ornithine-derived glutamine as phenylacetylglutamine in the urine. Sprague-Dawley rats were studied 4 weeks after bile duct ligation (BDL) or sham operation. Study 1: Three hours before termination, an internal carotid sampling catheter was inserted, and intraperitoneal saline (placebo), OP, phenylbutyrate, or L-ornithine were administered after randomization. BDL was associated with significantly higher arterial ammonia and brain water and lower brain myoinositol (P < 0.01, respectively), compared with sham-operated controls, which was significantly improved in the OP-treated animals; arterial ammonia (P < 0.001), brain water (P < 0.05), brain myoinositol (P < 0.001), and urinary phenylacetylglutamine (P < 0.01). Individually, L-ornithine or phenylbutyrate were similar to the BDL group. In study 2, BDL rats were randomized to saline or OP administered intraperitoneally for 6 hours or 3, 5, or 10 days and were sacrificed between 4.5 and 5 weeks. The results showed that the administration of OP was associated with sustained reduction in arterial ammonia (P < 0.01) and brain water (P < 0.01) and markedly increased arterial glutamine (P < 0.01) and urinary excretion of phenylacetylglutamine (P < 0.01) in each of the OP treated groups. Conclusion: The results of this study provide proof of the concept that L-ornithine and phenylbutyrate/phenylacetate act synergistically to produce sustained improvement in arterial ammonia, its brain metabolism, and brain water in cirrhotic rats.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1527-3350
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pubmed:author |
pubmed-author:DaviesD CeriDC,
pubmed-author:DaviesNathan ANA,
pubmed-author:FuskevågOle-MartinOM,
pubmed-author:HabtesionAbebaA,
pubmed-author:HodgesStephen JSJ,
pubmed-author:JalanRajivR,
pubmed-author:StadlbauerVanessaV,
pubmed-author:WrightGavinG,
pubmed-author:YtrebøLars MLM,
pubmed-author:ZwingmannClaudiaC
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pubmed:issnType |
Electronic
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
155-64
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pubmed:meshHeading |
pubmed-meshheading:19437490-Ammonia,
pubmed-meshheading:19437490-Animals,
pubmed-meshheading:19437490-Body Water,
pubmed-meshheading:19437490-Brain,
pubmed-meshheading:19437490-Drug Synergism,
pubmed-meshheading:19437490-Liver Cirrhosis,
pubmed-meshheading:19437490-Male,
pubmed-meshheading:19437490-Ornithine,
pubmed-meshheading:19437490-Phenylacetates,
pubmed-meshheading:19437490-Phenylbutyrates,
pubmed-meshheading:19437490-Rats,
pubmed-meshheading:19437490-Rats, Sprague-Dawley
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pubmed:year |
2009
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pubmed:articleTitle |
L-ornithine and phenylacetate synergistically produce sustained reduction in ammonia and brain water in cirrhotic rats.
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pubmed:affiliation |
Liver Failure Group, Institute of Hepatology, University College London, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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