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 181 records · Page 10Linked to original sources
PubMed1979

A new method for screening for hyperammonemia.

A new method for the detection of hyperammonemia, using a kit based on the principle of microdiffusion of ammonia, is described. The method requires only one drop of blood and takes only 15 min to complete. Experiments for recovery and reproducibility were satisfactory, and good correlation was obtained when compared with an enzymatic method for blood ammonia determination. The new method is considered to be useful for routine, low-cost mass-screening of newborn infants for hyperammonemia. It will also be useful for monitoring blood ammonia levels at the bedside in cases with hepatic disease or receiving parenteral nutrition.

Amino Acid Metabolism, Inborn Errors↗
PubMed1980

Diagnostic value of orotic acid excretion in heritable disorders of the urea cycle and in hyperammonemia due to organic acidurias.

Orotic acid excretion in urine in increased in ornithine transcarbamylase deficiency, citrullinemia and argininemia; it is barely increased in argininosuccinic aciduria and normal in carbamylphosphate synthetase deficiency and in hyperammonemia due to organic aciduria. The determination of orotic acid excretion is useful in differentiating the cases of hyperammonemia and reduces the need for enzymatic assays on tissue biopsies for decisions on therapy. The data indicate that orotic acid does not merely reflect ammonia concentration in plasma, but depends on carbamylphosphate concentration. Arginine could play a key role in the regulation of ammonia detoxication.

Amino Acid Metabolism, Inborn Errors↗
PubMed1982

Enteric coated polymyxin B in the treatment of hyperammonemia and endotoxemia in liver cirrhosis.

Effects of enteric coated polymyxin B capsules on hyperammonemia and endotoxemia in liver cirrhosis were investigated. Six million units of polymyxin B were orally administered daily to 21 patients with liver cirrhosis and 3 patients with hepatoma cum liver cirrhosis, whose plasma ammonia was higher than normal limit and/or whose plasma endotoxin was positive, for 5-32 days, and serum polymyxin B concentration (in 5 cases), changes of plasma ammonia level (in 19 cases) and plasma endotoxin (in all cases) were observed. Serum polymyxin B concentration was below the detectable limit (0.5 unit/ml) in all cases observed. In the patients with liver cirrhosis, plasma endotoxin and ammonia levels decreased rapidly after polymyxin B treatment, and the decreases in endotoxin levels were kept throughout the treatment. Twelve patients with liver cirrhosis (10 among them were treated with lactulose) were served as controls. All patients who were treated with lactulose alone showed rapid decrease in plasma ammonia, but the decrease in endotoxin in these patients was slower than that in those treated with polymyxin B. From these results, oral administration of polymyxin B is concluded to be useful in the treatment of hyperammonemia and endotoxemia in liver cirrhosis, as a poorly absorbed antibiotic and as an antiendotoxin agent.

Administration, Oral↗
PubMed1984

Effects of urease-induced hyperammonemia in mouse liver. Ultrastructural, stereologic and biochemical study.

Intraperitoneal injections of urease induced a marked and sustained hyperammonemia in mice. Ultrastructural and stereologic analysis of hepatocytes from urease-treated mice showed striking changes in the mitochondria, rough and smooth endoplasmic reticulum and lysosomes. Thus, mitochondria became larger and rounder, and contained a less electron-dense matrix although their volume density remained similar to that of control cells. In addition, increases in the smooth and rough reticulum and the lysosomal compartment, were observed. Biochemical analysis of the livers from urease-treated mice revealed a significant increase in the intracellular content of water and lipids. Although the mechanism by which ammonia induces these changes remains unclear, the possible relationship between these findings and those described in the liver of humans and experimental animals in conditions of sustained hyperammonemia is discussed.

Ammonia↗
PubMed1999

Hyperinsulinism-hyperammonemia syndrome caused by mutant glutamate dehydrogenase accompanied by novel enzyme kinetics.

Hyperinsulinism-hyperammonemia syndrome (HHS) is a recently identified genetic disorder characterized by hyperinsulinemic hypoglycemia with concomitant hyperammonemia. In patients with HHS, activating mutations in the glutamate dehydrogenase (GDH) gene have been identified. GDH is a key enzyme linking glutamate metabolism with the Krebs cycle and catalyzes the conversion of glutamate to alpha-ketoglutarate. The activity of GDH is controlled by allosteric inhibition by GTP and, so far, all the mutations of HHS patients have been located within the GTP-binding site. Characteristically, GDH from these individuals have therefore normal basal activity in conjunction with a loss of GTP inhibition. In this study, however, we have identified a novel variant GDH in a patient with a more severe form of HHS. The mutation is located outside the GTP-binding site and the patient's GDH shows consistently higher activity, even in the absence of allosteric effectors. These results further support the hypothesis that the activating mutation of GDH is the cause of HHS. The mechanism leading to the activation of GDH, however, is not always related to the loss of GTP inhibition as was originally suggested.

Adenosine Diphosphate↗
PubMed1999

Carnitine deficiency and hyperammonemia in children receiving valproic acid with and without other anticonvulsant drugs.

Plasma ammonia and total and free carnitine were measured in 84 children requiring anticonvulsant drugs: 32 patients (group A) on valproic acid alone, 28 children (group B) on polytherapy including valproic acid, and 24 patients (group C) on polytherapy without valproic acid. The other anticonvulsant drugs used in groups B and C were carbamazepine and phenobarbital. Plasma ammonia concentrations were elevated in both group A and B compared with controls. Group B patients showed significantly higher hyperammonemia than group A (59.9 +/- 16.3 micrograms/dl vs. 36.7 +/- 12.4 micrograms/dl; P < 0.05). Group C patients had plasma ammonia levels similar to those of controls (31.1 +/- 14.7 micrograms/dl vs. 29.7 +/- 12.1 micrograms/dl; NS). In both group A and group B patients, plasma ammonia levels were correlated with the valproic acid dosage (r = 0.32, P < 0.01) and with serum concentrations of valproic acid (r = 0.41, P < 0.001). Moreover, a significant correlation between plasma ammonia and duration of valproic acid therapy was found in the patients as a whole (r = 0.31, P < 0.01). Plasma total and free carnitine concentrations were significantly reduced in groups A and B (total carnitine 36.9 +/- 6.9 mumol/l vs. 32.9 +/- 9.7 mumol/l; free carnitine 28.9 +/- 5.1 mumol/l vs. 25.7 +/- 4.3 mumol/l, respectively) compared with group C patients who did not receive valproic acid and in whom values were similar to controls (total carnitine 46.1 +/- 9.0 mumol/l vs. 47.7 +/- 10.1 mumol/l; free carnitine 40.1 +/- 7.1 mumol/l vs. 42.9 +/- 8.0 mumol/l, respectively). Twenty-eight patients (18 of group A and 10 of group B) were re-evaluated and showed a complete normalization of plasma ammonia, and total and free carnitine levels which were similar to controls. Our data suggest that hyperammonemia is an important problem in patients receiving valproic acid, particularly in association with other anticonvulsant drugs. This increase of plasma ammonia and the concomitant reduction of carnitine seem to be transient and completely reversible.

Adolescent↗
PubMed1985

Neuron-specific mitochondrial degeneration induced by hyperammonemia and octanoic acidemia.

The neuropathological consequences of acute exposure to the neurotoxicants ammonia and octanoic acid were investigated with the isolated, perfused canine brain preparation. After 1 h of combined hyperammonemia and octanoic acidemia, ultrastructural changes were apparent in all brain regions examined. The cell bodies of neurons were the primary sites of these alterations. Neuronal mitochondria were distended, and the lamellae of the mitochondrial cristae were separated. In some cases the lamellae had completely dispersed, leaving only matrix remnants. Mitochondria of adjacent astrocytes appeared normal. Thus, a characteristic population of brain mitochondria is selectively vulnerable to a combination of hyperammonemia and octanoic acidemia and may be related to the biochemical mechanisms underlying encephalopathies of hepatic origin.

Ammonia↗
PubMed1993

Hyperammonemia and hepatic encephalopathy stimulate rat cerebral synaptic mitochondrial glutamate dehydrogenase activity specifically in the direction of glutamate oxidation.

The effects of hepatic encephalopathy (HE) due to thioacetamide (TAA)-induced liver failure and hyperammonemia (HA) produced by repeated i.p. administration of ammonium acetate on the activity of glutamate dehydrogenase (GlDH) in the direction of glutamate (Glu) synthesis from--(GlDH-NADH) or its oxidation to alpha-ketoglutarate (alpha-KG) (GlDH-NAD), respectively, were examined in non-synaptic and synaptic mitochondria from rat cerebral hemispheres. In non-synaptic mitochondria, HE and HA stimulated the GlDH-NADH activity by, respectively, 33% and 49%, but neither condition affected the GlDH-NAD activity. In synaptic mitochondria, HE and HA decreased the GlDH-NADH activity by, respectively, 31% and 28%, but stimulated the GlDH-NAD activity by as much as 90% (HE) and 100% (HA). Kinetic assays revealed that HA increased the Vmax of the synaptic mitochondrial GLDH-NAD by 105%, without affecting the Km for Glu. The stimulation of GlDH-NAD favors the oxidation of synaptic Glu to alpha-KG, and may represent an adaptive response serving to counteract hyperammonemia-induced decrease of cerebral alpha-KG production in other metabolic pathways.

Ammonia↗
PubMed1978

The effect of glucose oral administration on hyperammonemia in cirrhotics.

In order to investigate the controverted effect of glucose on hyperammonemia the diet of eight advanced cirrhotics was supplemented hourly, between 9 a.m. and 5 p.m., with 20 g of glucose orally. Plasma insulin and arterial and median cubital venous ammonia levels were measured hourly and the results were compared to those of a control test performed in the same patients without glucose supplementation. In the control test the lunch (protein meal) induced an identical rise in arterial and venous ammonia levels (+40 +/- 3 and +36 +/- 5 microgram/100 ml, respectively). With glucose supplementation plasma insulin rose significantly and the arterial ammonia increase produced by lunch (+42 +/- 3 microgram/100 ml) did not differ from that observed in the control test; but the rise in venous ammonemia was lower (+12 +/- 4 microgram/100 ml; p less than 0.01) with a significant increase in arterio-venous ammonia difference. These results suggest that oral glucose administration increases the peripheral muscular ammonia uptake through a mechanism which remains to be elucidated but which is inefficient for arterial hyperammonemia.

Ammonia↗
PubMed1983

Sodium valproate-induced hyperammonemia in the rat: role of the kidney.

The intravenous injection of sodium valproate (VPA) 200 mg/kg provoked in fasting rats a 100% increase in the arterial NH+4 concentration by the 10th min. The increase persisted at this level for at least 100 min. Simultaneous measurements of NH+4 and glutamine concentrations in the carotid artery, renal vein and suprahepatic vein showed that there were increases in the release of NH+4 and the uptake of glutamine by the kidney while the [NH+4] of suprahepatic venous blood remained stable. In binephrectomized rats injected with VPA, NH+4 levels did not change. These results suggest that the VPA-induced arterial hyperammonemia depended on the accelerated catabolism or possibly the reduced synthesis of glutamine by the kidneys. The liver of fasting rats does not seem to play a preponderant role in the VPA-induced hyperammonemia.

Ammonia↗
PubMed1984

Protective effect of L-carnitine on hyperammonemia.

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.

Acetates↗
PubMed1989

Hyperammonemia decreases body fat content in rat.

We have developed an animal model of hyperammonemia consisting of feeding rats a diet containing 20% (w/w) ammonium acetate. Ingestion of this diet markedly affects carcass composition, with a 46% reduction in lipid content. The ammonium diet alters levels of several key compounds involved in lipid metabolism. Long-chain acylcarnitine is increased in liver by approx. 60% while free carnitine and acetylcarnitine are unaffected. The hepatic content of acetyl-CoA increases by approx. 50%. The level of ketone bodies in blood increases by 32% but remains unchanged in liver. Our data indicate that hyperammonemia alters lipid metabolism and results in a significant decrease in body lipid content.

Acetates↗
PubMed1983

Increased tryptophan uptake into the brain in hyperammonemia.

Hyperammonemia was provoked in rats by urease injection over three days. Tryptophan transport into the forebrain measured by the bolus injection technique was increased in hyperammonemic rats in comparison with pairfed controls. The concentration of the large neutral aminoacids, of tryptophan and of 5-hydroxyindole acetic acid were increased in the forebrain and brainstem. Probenecid administration led to a significantly higher accumulation of 5-hydroxyindole acetic acid in the forebrain of hyperammonemic rats. Since liver function was not impaired the data indicate that hyperammonemia in absence of hepatic insufficiency alters the carrier function for large neutral aminoacids at the blood brain barrier.

Amino Acids↗
PubMed1984

Hyperammonemia.

A symptomatic elevation in plasma ammonium concentration, termed hyperammonemia, is associated with numerous congenital and acquired conditions (Table 11). In some cases, such as urea cycle disorders, ammonia is the principal toxin. In other instances, such as portal systemic encephalopathy, it is but one of a number of metabolic disturbances, However, in either case hyperammonemic episodes should be treated aggressively to prevent coma, subsequent brain damage, or death. This involves restricting protein intake, providing adequate calories, and giving agents that remove accumulated nitrogen. Long-term therapy relies on diagnosing the specific disease rate. This rarely requires invasive procedures such as liver biopsy. In most cases measurement of plasma amino acids and urinary organic acids will identify the defect. Treatment involving restriction of nitrogen intake, vitamin supplementation, or stimulation of alternative pathways of waste nitrogen excretion can then be instituted. Early therapy, especially in patients with neonatal-onset hyperammonemia, is imperative to avoid severe brain damage. On this basis, the plasma ammonium level should be determined in virtually every newborn with lethargy, hypotonia, poor feeding, seizures, and/or respiratory distress of unclear origin (Table 12).

Acetyltransferases↗
PubMed1988

Biochemical analysis of decreased ornithine transport activity in the liver mitochondria from patients with hyperornithinemia, hyperammonemia and homocitrullinuria.

Hyperornithinemia, hyperammonemia and homocitrullinuria (HHH disorder) is an inherited metabolic disorder which shows peculiar amino acid changes in the serum and urine. The primary defect is considered to be the transport of ornithine across the mitochondrial membrane, but there is no direct evidence for this so far. We have analyzed ornithine transport activities in the liver mitochondria from three patients with HHH disorder. In coupled liver mitochondria we demonstrated low activities of citrulline synthesis and low rates of ornithine uptake. However, there were no abnormalities in carbamoyl-phosphate synthetase activity, ornithine carbamoyltransferase activity, N-acetylglutamate levels or O2 uptake with succinate. We also performed a kinetic study of citrulline synthesis as a function of ornithine concentration. We found increased Km values for ornithine and varied Vmax values of citrulline synthesis, which suggested the presence of a mutant transport protein. From these results we conclude that the defect of hyperornithinemia, hyperammonemia and homocitrullinuria lies in the transport of ornithine across the mitochondrial membrane.

Amino Acid Metabolism, Inborn Errors↗
PubMed1991

Effect of ammonium acetate-induced hyperammonemia on metabolism of guanidino compounds.

Guanidino compounds are synthesized from arginine in various tissues such as liver, kidney, brain, and skeletal muscle. Guanidino compounds such as arginine and creatine play an important role in nitrogen metabolism, whereas other guanidino compounds such as guanidinosuccinic acid and alpha-N-acetylarginine are known toxins. In order to understand the changes in the metabolism of guanidino compounds during ammonia toxicity, we investigated the effect of hyperammonemia induced by an ammonium acetate injection on the levels of guanidino compounds in plasma, liver, kidney, and brain of rats. Control animals were injected with an equal volume of saline. Blood and tissues were removed 1 h following ammonium acetate or saline injection and guanidino compounds were analyzed by high-performance liquid chromatography. Plasma and kidney levels of guanidinosuccinic acid were significantly elevated in rats challenged with ammonium acetate. Brain alpha-N-acetylarginine levels were also significantly higher in rats injected with ammonium acetate as compared to those in controls. Our results suggest that guanidinosuccinic acid and alpha-N-acetylarginine may play an important role in hyperammonemia.

Acetates↗
PubMed1995

Serum amino acid disturbance in multiple myeloma with hyperammonemia.

From October 1987 to November 1993 we evaluated the serum levels of ammonia and amino acids in 85 patients with multiple myeloma. Six of the 85 cases of multiple myeloma demonstrated hyperammonemia and none of the known causes of hyperammonemia, such as liver failure, could be identified in these patients. All six patients also showed serum amino acid disturbances and conscious disorders in various degrees. In this study we compared these abnormalities in multiple myeloma with those in chronic liver failure (n = 14), the basic diseases of which were liver cirrhosis in six cases and liver cirrhosis complicated hepatocellular carcinoma in eight cases. There was a marked difference in the levels of individual serum amino acids between these two groups. The level of glycine was significantly higher in the multiple myeloma group (P < 0.001); on the other hand, that of tyrosine was significantly higher in the liver failure group (P < 0.005). The histidine (P < 0.005) and arginine (P < 0.005) levels were lower in the myeloma group. The ratio of glycine to tyrosine (Gly/Tyr) was 16.7 +/- 4.85 in the myeloma group and 1.7 +/- 0.12 in the liver failure group. The ratio of glycine to tyrosine was an important criterion for differential diagnosis.

Adult↗
PubMed1992

Symptomatic hyperammonemia caused by a congenital portosystemic shunt.

A child with trisomy 21 had altered mental status and hyperammonemia at presentation and was found to have a congenital portosystemic shunt as a result of a congenital abnormality of the portal venous system. Anomalies of the portal venous system leading to portosystemic shunting, although they are infrequent, should be considered in the differential diagnosis of hyperammonemia.

Amino Acids↗