Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “hyperammonemia”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2006

Ornithine restores ureagenesis capacity and mitigates hyperammonemia in Otc(spf-ash) mice.

We showed that Otc(spf-ash) mice, a model of ornithine transcarbamylase deficiency, were able to sustain ureagenesis at the same rate as control mice, despite reduced enzyme activity, when a complete mixture of amino acids was provided. An unbalanced amino acid mixture, however, resulted in reduced ureagenesis and hyperammonemia. To study the effect of ornithine supplementation [316 micromol/(kg.h)] on urea and glutamine kinetics in conscious Otc(spf-ash) mice under a glycine-alanine load [6.06 mmol/(kg.h)], a multiple tracer infusion protocol ([(13)C(18)O]urea, [5-(15)N]glutamine, [2,3,3,4,4 D(5)]glutamine and [ring-D(5)] phenylalanine) was conducted. Ornithine supplementation increased ureagenesis [3.18 +/- 0.88 vs. 4.56 +/- 0.51 mmol/(kg.h), P < 0.001], reduced plasma ammonia concentration (1125 +/- 621 vs. 193 +/- 94 micromol/L, P < 0.001), and prevented acute hepatic enlargement (P < 0.006) in Otc(spf-ash) mice. Ornithine supplementation also increased [96 +/- 20 vs. 120 +/- 16 micromol/(kg.h), P < 0.001] the transfer of (15)N from glutamine to urea, to values observed in the control mice [123 +/- 17 micromol/(kg.h)]. De novo amido-N glutamine flux was higher [1.57 +/- 0.37 vs. 3.04 +/- 0.86 mmol/(kg.h); P < 0.001] in Otc(spf-ash) mice, but ornithine supplementation had no effect (P < 0.56). The flux of glutamine carbon skeleton was affected by both genotype (P < 0.0001) and by ornithine (P 0. 036). In conclusion, ornithine supplementation restored ureagenesis, mitigated hyperammonemia, prevented liver enlargement, and normalized the transfer of (15)N from glutamine to urea. These data strongly suggest that ornithine has the potential for the biochemical correction of OTCD in Otc(spf-ash) mice.

Amino Acids↗
PubMed2001

Hyperammonemia and coma without hepatic dysfunction induced by valproate therapy.

The authors report a case of a 41-year-old mentally disabled man with bipolar disorder who presented to the emergency department with altered mental status. He was found to have a significantly elevated ammonia level (377 microM/L) with no signs of hepatic insufficiency. His coma and hyperammonemia were attributed to his chronic valproate therapy. This patient had the highest serum ammonia level ever reported with a therapeutic valproate level in the absence of any other anticonvulsant therapy, metabolic abnormality, or hepatic dysfunction. The authors discuss this case and review the current literature on hyperammonemia in valproic acid therapy and the use of L-carnitine in these patients.

Adult↗
PubMed2006

Clinical and functional characterization of a human ORNT1 mutation (T32R) in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome.

We studied two related families (HHH013 and HHH015) with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, a disorder of the urea cycle and ornithine degradation pathway, who have the same novel ornithine transporter (ORNT1) genotype (T32R) but a variable phenotype. Both HHH015 patients are doing well in school and are clinically stable; conversely, the three affected HHH013 siblings had academic difficulties and one suffered recurrent episodes of hyperammonemia and ultimately died. Overexpression studies revealed that the product of the ORNT1-T32R allele has residual function. Ornithine transport studies in HHH015 fibroblasts, however, showed basal activity similar to fibroblasts carrying nonfunctional ORNT1 alleles. We also examined two potential modifying factors, the ORNT2 gene and the mitochondrial DNA lineage (haplogroup). Haplogroups, associated with specific diseases, are hypothesized to influence mitochondrial function. Results demonstrated that both HHH015 patients are heterozygous for an ORNT2 gain of function polymorphism and belong to haplogroup A whereas the HHH013 siblings carry the wild-type ORNT2 and are haplogroup H. These observations suggest that the ORNT1 genotype cannot predict the phenotype of HHH patients. The reason for the phenotypic variability is unknown, but factors such as redundant transporters and mitochondrial lineage may contribute to the neuropathophysiology of HHH patients.

Adolescent↗
PubMed2004

Hyperammonemia, brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paracetamol intoxication.

AIM: To study the blood-brain barrier integrity, brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS: Adults male Wistar rats were divided into four groups. Group I: sham operation; II: Prehepatic portal hypertension, produced by partial portal vein ligation; III: Acetaminophen intoxication and IV: Prehepatic portal hypertension plus acetaminophen. Acetaminophen was administered to produce acute hepatic injury. Portal pressure, liver serum enzymes and ammonia plasma levels were determined. Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity. Reflexes and behavioral tests were recorded. RESULTS: Portal hypertension was significantly elevated in groups II and IV. Liver enzymes and ammonia plasma levels were increased in groups II, III and IV. Prehepatic portal hypertension (group II), acetaminophen intoxication (group III) and both (group IV) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia. Cortical edema was present in rats with acute hepatic injury in groups III and IV. Behavioral test (rota rod) was altered in group IV. CONCLUSION: These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (cytotoxic). Group IV, with behavioral altered test, can be considered as a model for study at an early stage of portal-systemic encephalopathy.

Acetaminophen↗
PubMed2000

[Clinical significance of a multiple myeloma cell line, derived from a case associated with hyperammonemia].

Recently, there have been several reports describing patients with multiple myeloma complicated by consciousness disturbance due to hyperammonemia. Here we report a patient with multiple myeloma and hyperammonemia, who died after rapid progression of the disease. A 71-year-old man who had been diagnosed as having Bence Jones protein (kappa)-type multiple myeloma in 1996 was readmitted to our hospital in February 1997 because of worsening bone pain, renal dysfunction, and hypercalcemia. Bone marrow aspiration yielded an almost dry tap, and the bone marrow was found to be completely occupied by immature plasma cells. Although liver dysfunction was slight, the serum ammonia level was high and increased gradually. Despite treatment, the patient died due to cerebral embolism and progression of plasmacytic leukemia in October 1997. Peripheral blood sampled at the time of death showed a serum ammonia level of 204 micrograms/dl, and the myeloma calls were cultured using monolayered bone marrow stromal cells as feeder cells. This led to the successful establishment of a cell line. The level of ammonia in the supernatant was high, indicating that the cultured myeloma cells produced and released ammonia.

Aged↗
PubMed2003

[Acute encephalopathy due to thiamine deficiency with hyperammonemia in a chronic hemodialysis patient: a case report].

Hemodialysis(HD) patients are at risk for thiamine deficiency because of low intake and accelerated loss of thiamine during HD. We report here an HD patient, an 82-year-old woman, who developed acute encephalopathy due to thiamine deficiency with hyperammonemia. She was admitted to Nishikawa Town Hospital due to pneumonia and was treated with ABPC/SBT for one week. While she was cured of pneumonia, she had a persistently poor appetite. On the twenty-fourth day after admission, HD with intradialytic parenteral nutrition(IDPN), which consisted of 10% glucose 500 ml, in order to correct her malnutrition, was started. She suddenly presented confusion, speech disturbance and ophthalmoplegia. HD with IDPN was stopped after two hours because of her symptoms. Laboratory studies disclosed plasma glucose of 186 mg/dl and serum ammonium of 155 micrograms/dl. Arterial blood gas analysis(inhaling 3 l/min O2) showed severe metabolic acidosis and respiratory acidosis (pH 7.138, pCO2 44.8 mmHg, pO2 108.9 mmHg, HCO3- 15.1 mmol/l). Her malnutrition, unexplained metabolic acidosis and neurological presentation raised the suspicion of acute encephalopathy due to thiamine deficiency. Fursultiamine 100 mg was administered intravenously. After two hours, metabolic acidosis disappeared (pH 7.437, pCO2 33.9 mmHg, pO2 161.0 mmHg, HCO3- 22.9 mmol/l), and she regained her clear consciousness and serum ammonium decreased at 16 micrograms/dl on the next morning. Serum lactate and thiamine level were shown later to be 57.5 mg/dl and 27 nmol/l, respectively. Her clinical course suggests that the glucose load including IDPN may have caused deterioration of the neurological disorder under the condition of thiamine deficiency. Furthermore, it is possible that a relationship exists between thiamine deficiency and hyperammonemia.

Acidosis, Lactic↗
PubMed2004

Hyperammonemia with citrullinemia.

Two cases of hyperammonemia with elevated citrulline are reported, one resulting from a deficiency of pyruvate carboxylase and the other from a partial deficiency of argininosuccinate synthetase. Diagnosis was based on clinical, biochemical and amino acid profiles. The utility of amino acid determinations in hyperammonemia suspected to underlie an inborn error of metabolism is emphasized.

Adolescent↗
PubMed2005

Hyperammonemia: an unusual presenting feature of multiple myeloma.

A 76 year old lady presented with altered sensorium and was found to have hyperammonemia on evaluation. She had no evidence of liver disease. For her symptomatology of backache, evaluation by bone marrow study showed evidence of multiple myeloma. She was given chemotherapy for multiple myeloma, which resulted in improvement in her sensorium, along with this there was also a rapid decline in serum ammonia levels. Hyperviscosity and hypercalcemia are common causes of altered sensorium in a patient with myeloma but in this case hyperammonemia was the likely cause.

Aged↗
PubMed1982

Asymptomatic hyperammonemia in patients receiving valproic acid.

To determine the frequency of hyperammonemia in asymptomatic patients receiving valproic acid, plasma ammonia concentrations were measured in 55 patients receiving this drug and in 12 patients receiving other anticonvulsants. Twenty-nine of the 55 patients receiving valproic acid and none of the control patients had plasma NH3 levels above the normal range. Ten of the 11 patients receiving both valproic acid and phenytoin sodium in combination had elevated NH3 levels, as did five of six patients receiving both valproic acid and phenobarbital sodium. Elevations in plasma NH3 levels, as high as 140 mumole/L, were well tolerated, and valproic acid dose reductions were not necessary. Based on our findings, hyperammonemia is not an indication for reducing or eliminating valproic acid therapy.

Adolescent↗
PubMed1991

Hyperammonemia following allogeneic bone marrow transplantation.

Hyperammonemia is a rare and serious complication of intensive cytotoxic chemotherapy. We report the case of a patient who developed profound idiopathic hyperammonemia following bone marrow transplantation for chronic myelogenous leukemia. Despite rapid institution of hemodialysis, sodium benzoate, and the experimental agent sodium phenylacetate, the patient ultimately succumbed to complications of this metabolic derangement. The literature is reviewed, and recommendations for an approach to this complication of marrow transplantation are proposed.

Ammonia↗
PubMed1985

Partial pyruvate decarboxylase deficiency with profound lactic acidosis and hyperammonemia: responses to dichloroacetate and benzoate.

We describe the successful use of sodium benzoate in a neonate with hyperammonemia associated with congenital lactic acidosis caused by a partial deficiency of the E1 component of pyruvate dehydrogenase (PDH); of note, this biochemical disturbance has not been previously described in PDH deficiency. The pyruvate dehydrogenase complex in skin fibroblasts had 48% of normal activity with a deficiency of the E1 component. The infant presented with rapid onset of a severe metabolic lactic acidosis, hyperventilation, hyperammonemia, and coma. At 30 hours of age continuous peritoneal dialysis was started; however, plasma NH3 concentrations remained in the 300-400 micrograms/dl range over the next 12 hours. Sodium benzoate, 250 mg/kg, was infused intravenously with a decrease in plasma ammonia of 25 micrograms/dl/hr. Hippurate was documented in the urine and peritoneal fluid after benzoate therapy. At 10.5 months of age, 50 mg/kg dichloroacetate was administered orally under fasting conditions, which resulted in a 56 and 62% reduction in the serum lactate and pyruvate levels, respectively; after 2 weeks on dichloroacetate his fasting levels were significantly decreased. Fibroblast PDH activity responded similarly to this drug. In our patient sodium benzoate was rapidly effective in producing a decline in plasma ammonia that was associated with clinical improvement. We feel that its use in organic acidemias deserves further evaluation and, furthermore, that any child with suspected PDH deficiency requires a clinical trial of dichloroacetate.

Acidosis↗
PubMed1982

Valproate-induced hyperammonemia.

A patient with carbamyl phosphate synthetase deficiency had four episodes of hyperammonemia, up to 226 microM, associated with valproate (VPA) treatment. These were accompanied by vomiting, lethargy, and coma. A group of epileptic patients receiving VPA remained asymptomatic but had significantly higher mean plasma ammonium levels when compared to epileptic patients receiving other anticonvulsants: 33.6 +/- 1.9 (SEM) versus 23.6 +/- 1.5 microM. Thus, VPA caused symptomatic hyperammonemia in a patient with an impairment in urea synthesis and resulted in mildly elevated ammonium levels in epileptic patients. These data suggest that ammonium levels should be monitored in patients receiving VPA who exhibit signs of vomiting or lethargy.

Adolescent↗
PubMedDate not supplied

Changes in glutamate receptors on synaptic membranes associated with hepatic encephalopathy or hyperammonemia in the rabbit.

The status of the excitatory glutamatergic neurotransmitter system in hepatic encephalopathy has been studied. Synaptic membranes (SM) were prepared from the brains of normal rabbits, hyperammonemic normal rabbits, and rabbits with fulminant hepatic failure. Data on the specific binding of glutamate to SM indicated that fulminant hepatic failure was associated with a decrease in the number of glutamate receptors on SM from cerebral cortex, cerebellum, and particularly the hippocampus, without any associated change in the affinity of these receptors. In contrast, hyperammonemia was associated with an increase in the affinity and no decrease in the number of glutamate receptors on SM from the hippocampus. These findings indicate that the effects of hyperammonemia and fulminant hepatic failure on cerebral glutamate receptors are fundamentally different. The decreased number of glutamate receptors in hepatic encephalopathy might reflect a decreased sensitivity of glutamatergic neurons to glutamate-mediated neural excitation, a phenomenon that could contribute to the neural inhibition of hepatic encephalopathy.

Ammonia↗
PubMed1993

Metabolic adaptation of the kidney to hyperammonemia during chronic liver insufficiency in the rat.

The aim of this study was to evaluate the role of renal ammonia and glutamine metabolism in the metabolic adaptation to chronic liver insufficiency-induced hyperammonemia in the rat. To this purpose, urinary excretion, renal net exchange and tissue concentrations of ammonia and amino acids were measured in anesthetized, normal control rats that did not undergo surgery, in control rats that underwent sham surgery, in rats that underwent portacaval shunting and in rats that underwent both portacaval shunting and bile duct ligation. Rats that underwent sham surgery and portacaval shunting were pair-fed with rats that underwent portacaval shunting and biliary obstruction, to correct for anorexia in that group, and all rats that were operated on were studied 7 and 14 days after surgery. Arterial ammonia and glutamine levels were elevated in groups that underwent portacaval shunting and portacaval shunting plus biliary obstruction at all time points. At days 7 and 14, total renal ammonia production decreased in rats that underwent portacaval shunting and in rats that underwent portacaval shunting plus biliary obstruction, associated with a 50% decrease in net renal glutamine uptake and strongly diminished net ammonia release into the renal vein, which was most prominent in the group that underwent portacaval shunting plus biliary obstruction. Urinary ammonia excretion was similar in rats that underwent portacaval shunting and in those that underwent sham surgery but was increased more than 200% at days 7 and 14 in rats that underwent portacaval shunting plus biliary obstruction. In this group, in contrast to portacaval-shunted rats, the kidney appeared to be an organ of net ammonia disposal from the body. In separate experiments in unanesthetized, unrestrained rats, similar changes in urinary ammonia excretion were observed without changes in arterial pH, excluding an effect of anesthesia or pH on the obtained results. These results indicate that the kidney plays an important role in the metabolic adaptation to hyperammonemia during chronic liver insufficiency in the rat.

Adaptation, Physiological↗
PubMed1997

Memantine, a noncompetitive NMDA receptor antagonist improves hyperammonemia-induced encephalopathy and acute hepatic encephalopathy in rats.

The aim of this study was to investigate the possible role of N-methyl-D-aspartate (NMDA)-receptor overactivity in two different experimental rat models of encephalopathy: subacute encephalopathy caused by severe hyperammonemia in portacaval-shunted rats (AI-PCS rats) and acute hepatic encephalopathy caused by complete liver ischemia (LIS rats). The effect of the noncompetitive NMDA-receptor antagonist memantine (intraperitoneal [i.p.] 10-20 mg/kg bw or intravenous [i.v.] 5 mg/kg bw) was studied on the severity of encephalopathy by assessment of clinical grading and electroencephalogram (EEG) spectral analysis, on plasma ammonia concentrations, amino acid concentrations in cerebrospinal fluid (CSF), intracranial pressure (ICP), and brain water content. Both rat models developed encephalopathy within 3 to 6 hours, associated with increased CSF glutamate and aspartate concentrations and increased ICP and brain water content. Memantine administration in AI-PCS and LIS rats resulted in a significant improvement in clinical grading and less slowing of EEG activity (P < .05), and smaller increases in CSF glutamate (P < .05) concentrations. Moreover, ICP and brain water content were significantly lower in memantine-treated AI-PCS rats than in untreated AI-PCS rats (P < .05). Memantine had no significant effect on ICP and brain water content in LIS rats, and on ammonia concentrations in both models. These results indicate that NMDA-receptor activation might be involved in the pathogenesis of hyperammonemia-induced encephalopathy and of acute hepatic encephalopathy caused by LIS.

Ammonia↗
PubMed1991

The use of in vivo proton NMR to study the effects of hyperammonemia in the rat cerebral cortex.

Using in vivo 1H NMR spectroscopy (1H MRS) and biochemical analysis, the effects of hyperammonemia on cerebral function were studied in three rat models: acute liver ischemia (LIS), administration of urease (UREASE) and administration of methionine sulfoximine (MSO). By means of localization in three dimensions signals were obtained exclusively from the cerebral cortex. Specially developed lineshape correction and fitting methods were used to quantitate the MRS signals. The following concentration changes were observed; a decrease in glutamate and (phospho)choline for all the models; an increase in glutamine in the LIS and UREASE model but a decrease in the MSO model; a marked increase in lactate in the LIS and UREASE group; a tendency to a decrease in N-acetylaspartate in all the models. These changes agree well with the changes in the post-mortem biochemically determined cerebral cortex glutamine and glutamate concentrations. Estimated absolute 1H MRS metabolite concentrations agree well with those obtained by other techniques; cerebral cortex glutamate, however, is underestimated by about 35% by NMR. The present data support the hypothesis that hyperammonemia is associated with a decreased availability of glutamate for neurotransmission.

Ammonia↗
PubMed1990

Glutamine synthetase inhibition prevents cerebral oedema during hyperammonemia.

The relationship between cerebral oedema and cerebral glutamine accumulation was investigated during acute hyperammonemia in anesthetized rats. Six hours of ammonium acetate infusion resulted in an increase in cortical glutamine concentration and a decrease in specific gravity. Pretreatment with methionine sulfoximine inhibited glutamine synthetase, prevented the increase in glutamine during hyperammonemia, and prevented the decrease in specific gravity. We conclude that the increase in brain water content is linked to the glutamine accumulation derived from the detoxification of ammonia by glutamine synthetase.

Acetates↗
PubMed1985

Intestinal obstruction due to peritoneal adhesions as a complication of peritoneal dialysis for neonatal hyperammonemia.

A male infant with ornithine transcarbamylase deficiency developed massive neonatal hyperammonemia and was treated with peritoneal dialysis. He later developed intestinal obstruction due to peritoneal bands which originated at the site of the previous peritoneal catheter. In this infant the blood concentration of ammonia could not be lowered below 1000 micrograms/dl using peritoneal dialysis, while treatment with sodium benzoate led to control within 24 h. In view of the possibility of this and other complications of peritoneal dialysis, pharmacologic therapy of neonatal hyperammonemia should be considered as an initial modality of treatment.

Ammonia↗