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

Reports indicate that L-carnitine administration before 100% lethal dose of ammonium acetate suppresses the symptoms of ammonia toxicity and prevents death in mice. However, we have been unable to confirm this observation. The cause of discrepancy between our results and the results of others was investigated with two models of hyperammonemia in mice: 1) that induced by intraperitoneal injection of urease and 2) that induced by intraperitoneal injection of ammonium acetate. L-Carnitine administration failed to protect mice against ammonia toxicity induced by intraperitoneal injection of urease. Mortality in mice treated with L-carnitine 30 min before injection of ammonium acetate was similar to that of controls pretreated with saline. Ammonia and urea levels in plasma, liver, and brain were also similar in both groups. However, the values were significantly lower than those in mice denied either pretreatment before the ammonium acetate challenge. These results indicate that pretreatment acts to reduce blood and tissue ammonia simply by diminishing the rate of absorption of the challenge, owing to the dilution of ammonium acetate upon mixing with the contents of the peritoneal cavity. Thus, any protocol that does not compare results of a putative protective agent with those obtained with an equal volume of solvents or saline runs the risk of ascribing protective property to the agent when the protection may, in fact, have been afforded by the solvent.
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PMID:Failure of L-carnitine to protect mice against hyperammonemia induced by ammonium acetate or urease injection. 223 23

Inborn errors of the urea cycle, liver malfunction and drug-induced hepatotoxicity are causes of life-threatening encephalopathies arising from hyperammonemia. L-Carnitine prevented entirely ammonia toxicity in mice when injected intraperitoneally 30 min before a lethal dose of ammonium acetate. Survival depends on the dose of L-carnitine injected, e.g., 0, 60, 70, 80 and 100% with 0, 1, 2, 8 and 16 mmol L-carnitine/kg, respectively. At the highest doses L-carnitine abolishes the convulsions that accompany acute ammonia intoxication. At lower doses it delayed their onset. The protective effect was associated with a marked decrease of blood ammonia, while in unprotected mice ammonemia was lethal in less than 15 min. When sustained hyperammonemia was induced by urease injections, protection was also obtained. The mechanism of protection is under investigation, however, since L-carnitine facilitates fatty acid entry into mitochondria, possibly ATP or reducing equivalents are increased.
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PMID:Protective effect of L-carnitine on hyperammonemia. 669 30

A 51-year-old female presented with acute confusion associated with a non-specific headache and lethargy. The patient's history included bipolar disorder on valproate and recent travel to northern Vietnam. The patient was subsequently found to have hyperammonaemia as well as a urinary tract infection and bacteraemia with Klebsiellapneumoniae The patient was presumed to have a multifactorial non-cirrhotic hyperammonaemic encephalopathy due to a combination of a urinary tract infection and bacteraemia with K. pneumoniae, a urease-producing bacteria, and also valproate use, a medication known to interfere with ammonia elimination. The patient's treatment included supportive care, ceasing valproate, empiric then rationalised antibiotics, N-acetylcysteine and L-carnitine. We present a case of non-cirrhotic hyperammonaemic encephalopathy and explain why it is multifactorial in origin.
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PMID:Multifactorial non-cirrhotic hyperammonaemic encephalopathy. 2952 11