Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of ammonia infusion on monoamine metabolism was studied in the rat brain. Seven days after portocaval shunt (PCS) or sham operation animals were infused with ammonia or saline. Brain metabolism of serotonin and norepinephrine was studied after injection of a decarboxylase inhibitor (m-hydroxybenzylhydrazine, NSD 1015) which blocks the conversion of 5-hydroxytryptophan to serotonin and dihydroxyphenylalanine to dopamine. Neurologic testing was conducted before killing. Plasma and brain amino acids were measured. PCS animals infused with ammonia were in deep coma after 6 h infusion, whereas sham-operated animals were virtually unaffected. Brain amino acid analyses demonstrated increased concentrations of the aromatic amino acids and a tenfold increase in glutamine. Serotonin metabolism was diminished after 6 h. Dopamine synthesis was normal, but norepinephrine levels were low after 6h. The study suggests that hyperammonemia in PCS rats results in a depression of the serotonin synthesis rate in accordance with two previous studies but in contrast to previous hypotheses on the regulation of serotonin metabolism.
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PMID:The effect of ammonia infusion on brain monoamine metabolism in portacaval-shunted rats. 247 Dec 38

Metadoxine is an active drug for treatment of acute and chronic alcohol intoxication, affecting both liver and brain function. The authors reviewed the international pharmacological and clinical literature on the drug which shows the potential usefulness of metadoxine in the treatment of alcohol-induced diseases. The case report concerns the results in 20 chronic alcoholics, admitted to the hospital for acute alcohol intake treated with metadoxine (one 500 mg tablet twice daily). Biohumoral hepatopathy parameters and clinical parameters of neuropsychic behaviour were examined simultaneously. Compared with a control group of patients undergoing traditional therapy (sedative and multi-vitamin drugs), metadoxine showed a significant improvement of the values of gamma-GT, GPT, blood ammonia, blood alcohol and of neuropsychic and behavioural parameters such as agitation, tremor, asterixis, sopor and depression. No side-effects or unfavourable reactions occurred during metadoxine treatment, which confirms the safety of this molecule.
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PMID:[Metadoxine in alcohol-related pathology]. 252 84

The neurochemical and receptor theories relate depression to deficient neurotransmission at critical sites in the brain. While this concept has generated a number of theories of depression over the years, the research findings do not fully support any single theory in its entirety. Several issues thus remain controversial or inconclusive. For instance, the monoamine deficit theory is supported by low urinary MHPG in some forms of bipolar, but not unipolar depression. Cerebrospinal fluid MHPG and 5-HIAA studies are inconclusive. Amine metabolite research is also limited in scope because the information derived pertains to pre-synaptic and synaptic events and ignores post-synaptic events. Receptor research, which includes study of both pre-and post-synaptic sites, suggests supersensitivity of Beta-adrenergic receptors in depression. But this research is criticized because it is mostly animal based. Also, the findings of low melatonin in depression contradict the supersensitivity-hypothesis. Abnormally low post-synaptic alpha-2 adrenoceptors is indicated by findings of an attenuated GH response to clonidine. But abnormality of pre-synaptic alpha-2 adrenoceptor functions has not been demonstrated conclusively. Recent findings in depression suggest a dysregulation in the dynamic and interactive relationship between neurotransmitters and receptors. Accordingly, a comprehensive view of the abnormalities of the various neurotransmitter systems in depression requires studies which investigate pre- and post-synaptic events simultaneously, preferably during illness and remission.
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PMID:Neurochemical and receptor theories of depression. 256 46

The ability of B6 vitamers to prevent the lymphopenic effects of ammonia caramel fed to rats has been evaluated. Diets containing 10 ppm pyridoxine or pyridoxal prevented the lymphopenia produced in rats consuming an 8% (w/v) solution of ammonia caramel, whereas the dietary content of pyridoxamine needed to be increased to 20 ppm to have the same effect. In contrast to the results of the enteral administration of the individual B6 vitamers, pyridoxamine was found to be the most effective vitamer in preventing the ammonia caramel-induced lymphopenia when administered parenterally. However, all the nutritionally active forms of vitamin B6 were able to prevent the depression of the peripheral blood lymphocyte count, which resulted from ingestion of ammonia caramel by rats. The proposal that oral administration of pyridoxine may prevent the intestinal absorption of the lymphopenic constituent of ammonia caramel, 2-acetyl-4(5)-(1,2,3,4-tetrahydroxy)butylimidazole (THI), is discredited, since THI was found to reduce the lymphocyte count after parenteral administration in rats fed 0.04 ppm pyridoxone in the diet and that increased amounts of dietary pyridoxine (10 ppm) could still prevent this effect. These findings further emphasise the important relationship between dietary vitamin B6 content and the lymphopenic effects of ammonia caramel/THI in the rat.
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PMID:Effect of oral and parenteral administration of B6 vitamers on the lymphopenia produced by feeding ammonia caramel or 2-acetyl-4(5)-(1,2,3,4-tetrahydroxy)butylimidazole to rats. 260 99

A 30 day exposure of C. punctatus to sublethal levels of phenol, ammonia, mercuric chloride, cadmium chloride and a mixture of the four resulted in an overall activation of guaiacol peroxidase and depression of iodide peroxidase (IPOD) activity and blood T4 titre. Interestingly enough, in case of 15 day ammonia and 1 day mercury exposures, an increase of IPOD activity was accompanied by a decrease in T4 titre. In general, phenol, mercury, cadmium and the mixture of pollutants were found to inhibit LP activity by 56% to 85% while ammonia inhibited lysosomal protease (LP) activity by 70%. Alterations in acid phosphatase (AP) activity indicate changes in the lysosomal membrane characteristics caused by these toxicants. Considering the concomitant alterations in IPOD, T4, LP and AP it is surmised that thyroid function in C. punctatus is influenced by the pollutants by two pathways, one via IPOD pathway affecting T4 synthesis and the other via lysosomal pathway affecting T4 release.
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PMID:Influence of industrial pollutants on thyroid function in Channa punctatus (Bloch). 260 23

It has been proposed that administration of non-nitrogenous precursors to glycine is necessary to realize the full potential of benzoate metabolism as a pathway for disposal of waste nitrogen during ammonia intoxication (Coude et al., Clin Chim Acta 136: 211-217, 1984). However, when glyoxylate, a keto acid precursor to glycine, was administered with benzoate 1 hr prior to a challenge of ammonia, protection against ammonia toxicity was less successful than with benzoate alone. At the cellular and subcellular levels, glyoxylate and benzoate each inhibited the urea cycle in isolated hepatocytes and pyruvate carboxylase in isolated mitochondria. The action of each drug was associated with depletion of aspartate content in isolated hepatocytes and reduction of pyruvate-dependent incorporation of CO2 into aspartate in assays with isolated mitochondria. Depression of aspartate regeneration by inhibition of pyruvate carboxylase is a likely mechanism for impairment of urea cycle activity by both drugs. In whole animals, inhibition of pyruvate carboxylase may contribute to benzoate toxicity and the adverse influence of glyoxylate on benzoate therapy.
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PMID:Potentiation of benzoate toxicity by glyoxylate. Inhibition of pyruvate carboxylase and the urea cycle. 277 12

Effects of ammonia on excitatory synaptic transmission were studied in the rat hippocampal slice preparation. Population spikes, elicited by orthodromic or antidromic stimulation, were recorded in the cell body layer of the CA1, CA3 and dentate regions. Perfusion with 5 mM ammonium chloride induced a profound and reversible depression of orthodromically evoked population spikes in all three regions. Antidromic population spikes were not depressed in any of the regions, indicating that neither axonal conduction nor electrical excitability were affected by ammonia. The paired-pulse test revealed a transient disinhibition during the early phase of perfusion. Iontophoretic application of glutamate evoked unit firing even when the synaptically evoked responses were reduced by ammonia, indicating that the postsynaptic sensitivity to the putative transmitter was not depressed. Depression of release of the excitatory transmitter, probably because of depletion following the block of transmitter synthesis, is the likely explanation of these findings. It is suggested that ammonia-induced depression of excitatory transmission may account for coma and other symptoms of central nervous system depression encountered in hyperammonemic states.
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PMID:Effects of ammonium chloride on synaptic transmission in the rat hippocampal slice. 285 52

The effects of ammonium acetate or chloride, perfused through the lateral ventricle, were studied on the hippocampal formation of the rat. During perfusion with ammonia, the population spikes, evoked by stimuli delivered to the fimbria, were first increased and then reduced. On the other hand, the late positive wave gradually decreased throughout the application of ammonia. The inhibition, studied by the paired-pulse test, was found to be reduced when the population spike was transiently enhanced, indicating that disinhibition could be responsible for the enhancement of synaptically evoked responses. Neither antidromically evoked population spikes nor the typical effects of iontophoretically applied glutamate, aspartate or gamma-aminobutyrate were changed by ammonia. These findings can be accounted for by a single action of ammonia, a depression of excitatory synaptic transmission, the excitatory synapses on inhibitory interneurons being more readily depressed than those on the pyramidal cells. Both effects, early hyperexcitability and late depression, are probably due to a reduction in the release of the excitatory neurotransmitter, glutamate and/or aspartate. We tentatively suggest that these mechanisms are responsible for some of the symptoms observed during the development of hyperammonemic encephalopathies.
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PMID:Effects of ammonium salts on synaptic transmission to hippocampal CA1 and CA3 pyramidal cells in vivo. 285 53

The effect of intravenous glutamic acid infusion (3 mg/kg/min) was studied during myocardial ischemia and reperfusion in anesthetized dogs. Left ventricular ischemia was induced by underperfusion of the anterior descending and circumflex coronary arteries. Glutamic acid reduced the ischemic contractile depression 2 min after a 60%-reduction of the coronary blood flow. The left ventricular systolic pressure was decreased by 9% versus 22%, dP/dt by 16% versus 29%, left ventricular systolic pressure heart rate product by 16% versus 31%. Reperfusion with glutamic acid improved the recovery of cardiac performance without any increase in myocardial oxygen consumption. Glutamic acid infusion resulted in a 2-fold augmentation of glutamate uptake by the ischemic myocardium. It led to cessation of ammonia release by the heart due to activation of glutamine synthesis, enhancement of alanine formation coupled with pyruvate utilization and did not change lactate production. The mechanisms of the protective action of glutamic acid are discussed.
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PMID:[Correction of contractile function and metabolism in canine ischemic myocardium due to exogenous glutamic acid]. 286 92

In vivo studies were performed in the dog to verify if sodium lactate had an important effect on the metabolism of glutamine by the kidney. The animals were infused with 0.6 M sodium lactate to induce acute metabolic alkalosis with plasma bicarbonate of 29.7 mM. During these experiments, it was demonstrated that the renal uptake of glutamine increased by 46%, while the renal production of ammonia was unchanged. The renal production of alanine rose from 6.0 to 16.8 mumol/min. Plasma concentration of lactate increased from 1.3 to 19.2 mM, while that of pyruvate increased from 0.075 to 0.454 mM. In the renal tissue, alpha-ketoglutarate, malate, oxaloacetate, lactate, pyruvate, citrate, and alanine increased significantly. Similar changes were found in the liver and skeletal muscle. The observed changes are best described by transamination of pyruvate and glutamate under the influence of alanine aminotransferase (GPT). It can be calculated that this reaction was responsible for 76% of the production of ammonia from glutamine, the latter being necessary to provide glutamate for the synthesis of alanine. Dogs infused with 0.3 M sodium bicarbonate instead of sodium lactate with the same degree of acute metabolic alkalosis, showed a depression of 40% in the renal uptake of glutamine with a 38% decrease in renal ammoniagenesis and a 20% fall in the production of alanine. The present studies demonstrate that the production of ammonia from glutamine is not necessarily related to changes in acid-base balance, but may be associated with biochemical alterations related to the synthesis of alanine by the kidney.
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PMID:The metabolic response of the kidney to acute sodium lactate alkalosis. 286 25


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