Search PubMed⌕ Search

Biomedical subjects

M Imler

Publications and source records attributed to M Imler.

At least 73 records · Page 4Linked to original sources
PubMed1983

Sodium valproate associated with phenobarbital: effects on ammonia metabolism in humans.

Treatment with sodium valproate (VPA) in association with phenobarbital (PB) is accompanied by a greater systemic hyperammonemia than treatment by VPA alone. The anatomical origins of this difference were studied by injecting a dose of 1,500 mg VPA i.v. into six unmedicated patients and six epileptics chronically treated with PB and measuring the ammonium (NH4+) concentration difference between arterial blood and renal, hepatic, internal jugular, and femoral venous blood. In unmedicated patients, arterial [NH4+] rose moderately, secondary to an increased amount of NH4+ released into the general circulation by the kidney; the hepatic metabolism of NH4+ remained normal. In epileptics treated with PB, arterial [NH4+] rose massively, partly as a result of the increased NH4+ release by the kidney and partly because of disturbance of the hepatic metabolism of NH4+. These results provide a clearer understanding of the potentiation of the secondary effects of VPA by PB.

Adult↗
PubMed1983

The renal origin of sodium valproate-induced hyperammonemia in fasting humans.

Acute administration of 1,500 mg of sodium valproate or chronic administration of 30 mg/kg/24 hours induced a more than twofold increase of renal ammoniagenesis in fasting subjects. Hyperammonemia was moderate, as normal hepatic ammonia detoxification persisted. Renal uptake of glutamine increased simultaneously.

Adult↗
PubMed1983

[Role of hyperammonemia in stuporous states induced by sodium valproate].

Stuporous states induced by sodium valproate (VPA) are accompanied by an isolated marked hyperammonemia. In reality, hyperammonemia occurs after administration of VPA even in the absence of neurological complications. The hyperammonemia is of purely renal origin and results from modifications in glutamine metabolism, this compound being the main precursor of amino acid neurotransmitters. Combined administration of VPA and phenobarbitone increases the level of hyperammonemia due to lack of detoxification by the liver of the excess of ammonia produced by the kidneys. The anatomical site of origin of the ammoniogenesis, and its intensity, were studied in two patients with a history of stuporous states during combined VPA-phenobarbitone treatment. A single injection of VPA at a later date when they were being treated by combined phenobarbitone-carbamazepine therapy, induced disturbances in ammonia metabolism which did not differ qualitatively from those observed when intolerance to VPA is lacking. It is therefore not possible to rely on simple biological tests to detect patients at risk. Correlation is also lacking between the degree of hyperammonemia and disorders of vigilance. Ammonia does not therefore appear to be the only factor responsible for neurological complications and the role of other factors must be investigated. These include: disturbances of metabolism of inhibitory and excitatory aminoacid neurotransmitters, the condition of the cerebral parenchyma, and the excitatory effect of sodium valproate which could act to varying degrees in synergy with the hyperammonemia to provoke a stuporous state.

Adult↗
PubMed1982

Neurotransmitter modifications in human cerebrospinal fluid and serum during hepatic encephalopathy.

The concentrations of catecholamines, serotonin, histamine and GABA as well as some of their precursors and metabolites were measured in the CSF and the serum of human patients at different grades of hepatic encephalopathy. In all grades the CSF concentrations of the neurotransmitters were much increased over control levels, while the amount of metabolites varied with the grade of coma. The data suggest modifications of the cerebral turnover of dopamine, norepinephrine and serotonin. The "false transmitters" also occurred in high concentration in all grades of hepatic coma and could play a role in the alterations of synaptic transmission. The present results suggest that the biochemical changes between grade 2 and grade 4 hepatic coma could be due to an inhibition of dopamine beta-hydroxylase. Moreover, the levels of neurotransmitter precursors, tyrosine and 5-hydroxytryptophan, showed enhancement in grades 2 and 3 followed by an important reduction in grade 4. Finally, it seems that the biogenic amines measured in the CSF are of central origin and that their quantification in human lumbar fluid gives new information on the central mechanisms involved in hepatic encephalopathy.

5-Hydroxytryptophan↗
PubMed1982

[Study of muscular metabolism of ammonia in the posterior limbs of the intact rat].

In order to evaluate the ammonia, glutamine, and alanine muscular uptake and/or release, we have studied the effects of ammonium acetate perfusions, in intact anaesthetized rat hindquarters, by simultaneous measure of blood flow and arterio-venous differences of ammonia, glutamine and alanine concentrations. Increasing doses of ammonium acetate perfusions (1.23-2.46-3.69 nmol/mm/100 g b.w.) result in an increase of ammonia rat hindquarters uptake which is correlated with the amount of ammonium infused and the arterial ammonia levels but without significant release or uptake of glutamine or alanine. However these perfusions induce an arterial hyperglutaminemia and hypoalaninemia likely due to extramuscular metabolic changes in these two amino-acids.

Acetates↗
PubMed1981

Effect of colectomy upon ammonemia and glutaminemia in rats with stricture of the portal vein.

Current theories on the pathogenesis of hepatic encephalopathy indicate that intestinal bacteria produce cerebral toxins, such as ammonia; colectomy has been proposed in the treatment of chronic portal systemic encephalopathy. This study was undertaken to evaluate the evolution of ammonemia and glutaminemia during a four month period in rats after a colectomy, with and without portal vein stricture. Groups of nine rats were studied: group 1 served as control study, total colectomy was performed on the rats in groups 2 and 3, but a gradual stricture of the portal vein was produced in the rats of group 3 and group 4 that had not had a colectomy. The ammonia levels were stable in groups 1 and 2, 48 +/- 2 milligrams per 100 milliliters; in group 3, ammonia levels rose significantly one week after portal vein stricture, 136 +/- 10, and decreased progressively until the end of the first month, 70 +/- 10, although in group 4 of the ammonia level always remained higher than in this one. The levels of glutamine decreased after colectomy in group 2 and rose markedly in both groups 3 and 4 during the first week but persisted at the same level only in group 4. These data confirm the importance of hepatic clearing of portal blood in ammonia and glutamine metabolism and underline the importance of the colon as the main, but not exclusive, site of splanchnic ammonia and glutamine production. The improvement in hepatic encephalopathy observed after removal of the colon may be due to the reduced output of these two substances.

Ammonia↗
PubMed1980

[Effects of experimental hyperammonemia on the secretion of insulin and glucagon in the rat].

In order to investigate the controverted effect of ammonia on insulin and glucagon secretion 3 groups of 55 rats were perfused either by Na+ acetate (controls), either by NH4+ acetate: in the first group plasma insulin (IRI) and glucagon (IRG) levels were compared before and after perfusion; the second group was supplemented by glucose perfusion (1 g/100 g/hour); in the last group an arginine perfusion (1 g/kg/min) was started 15 min after the beginning of NH4+ or Na acetate and IRI and IRG levels were determined in the portal blood. Hyperammonemia, which reached about 500 microgram/dl, reduced significantly the IRI portal level and the IRI secretion induced by glucose or arginine, whereas basal or stimulated IRG levels are not modified. The ratio IRI:IRG is diminished in each group perfused with NH4+ acetate. Our results show that ammonia inhibits insulin without modifications in the glucagon secretion; hyperglucagonemia and hyperinsulinism reported in hepatic encephalopathy with chronic hyperammonemia may not be attributed to an effect of ammonia.

Ammonia↗
PubMed1980

Variations in blood ammonia and glutamine levels after hepatectomy and/or abdominal evisceration in the rat.

In order to specify the role of peripheral muscular tissue in ammonia metabolism, we studied, in rats, the variations of ammonia and glutamine levels in arterial and femoral venous blood after hepatectomy and abdominal evisceration with nephrectomy. In non-fasting rats this operation was immediately followed by an important hyperammonemia which was due to ammonia muscular release; glutamine blood levels increased only slightly without any modification in their arterio-femoral venous differences. The hyperammonemia induced by hepatectomy-evisceration was greatly reduced in animals which had been fasting for 48 hours but was not modified by a 72hrs preoperative sucrose feeding. These nutritional conditions did not change the blood glutamine variations which were first related to the abdominal evisceration. Indeed, in abdominal eviscerated rats without hepatectomy there was an important hyperglutaminemia with only a slight increase in blood ammonia. These results indicate that in rat 1) the liver plays an important part in skeletal muscle ammonia metabolism, 2) this metabolism is related to food ingestion, 3) the gastrointestinal tissue intervenes in glutamine metabolism.

Ammonia↗
PubMed1979

Semiautomated enzymic microassay for plasma L-alanine.

Plasma L-alanine is deaminated by bacterial alanine-dehydrogenase; the resulting ammonia is dialyzed out and measured by use of a continuous flow phenol-hypochlorite colorimetric microassay. Concentrations in the range of 10-1,000 mumol alanine/l can be determined in a 50-microliter sample. The optimal conditions for the assay are specified. Study of the analytical qualities of the technique shows high specificity, good reproducibility , and a detection limit of 6 mumol/l. Usual values in human plasma from arterial or venous blood are respectively 296 +/- 166 and 376 +/- 214 mumol alanine/l (x +/- 2 SD). The usual values in rats are close to those found in man.

Alanine↗