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)

Samples of ventricular CSF were taken from 52 consecutive patients admitted for psychosurgery for intractable depression. Concentrations of asparagine, aspartate, glutamine, glutamic acid, and serine were determined. Glutamate and aspartate concentrations, implicated in excitotoxic brain damage, were not affected by various types of psychotropic drug treatment. Serine, a modulator of glutamate responses, was significantly elevated in samples from subjects receiving antidepressants. These subjects responded poorly to the operation. Psychotropic drugs are unlikely to be neurotoxic. Nevertheless, antidepressants may influence excitatory neurotransmission.
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PMID:Effect of psychotropic drugs on excitatory amino acids in patients undergoing psychosurgery for depression. 135 Apr 94

It has been reported that the intraportal infusion of glutamine in Munich-Wistar rats will cause depression of renal perfusion and the urinary excretion of salt and water. We have attempted to reproduce these findings in anaesthetized dogs. L-Glutamine was infused at doses between 120 and 150 mumol/min into the portal vein and femoral vein of anaesthetized dogs. No effect was observed on portal venous pressure, blood pressure, or kidney function. Similar data were obtained with D-glutamine. Liver biopsy revealed no abnormalities. When 1.5-3 micrograms histamine (free base) was infused into the portal system, portal venous pressure rose from 15.2 +/- 0.33 to 24.8 +/- 0.40 cmH2O (p < 0.05) (1 cmH2O = 98.1 Pa). Glutamine infusions do not appear to initiate hepatorenal reflexes in dogs as they have been reported to do in rats.
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PMID:Portal venous infusions of L-glutamine in anaesthetized dogs do not influence renal function. 149 Feb 60

Acivicin (AT-125) is a glutamine antagonist with dose-limiting, schedule-dependent CNS toxicity and predictable CSF penetration after intravenous administration. Because of these properties, a trial in CNS malignancies was initiated. Thirty-two patients with recurrent or residual malignant astrocytomas were treated with AT-125. The majority of patients had glioblastoma multiforme (24) and had received prior nitrosoureas (21). The median age was 50 years, and Southwest Oncology Group (SWOG) performance status was 2. The major determinant of response was based upon radiologic criteria using computed tomographic (CT) scanning and/or magnetic resonance imaging (MRI) scans. The tumor mass was measured in two perpendicular planes, which yielded the largest cross-sectional area. Standard solid tumor criteria for response were used. All responding patients also had a stable or tapered dose of corticosteroids with stable or improved performance status and neurologic examination. There were four objective responses (12%): one complete remission (3 1/2+ years) and three partial remissions (57, 86, and 322 days). Two patients had improvement in disease that did not meet requirements for a partial remission. Toxicity was mild and primarily consisted of nausea, vomiting, and lethargy. Two patients were removed from study due to neurotoxicity (depression and hallucinations). The strict response criteria used in this trial were not those that have been used in testing other active agents such as carmustine (BCNU). We conclude that AT-125 has objective antitumor activity in malignant astrocytomas and warrants further study.
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PMID:Objective antitumor activity of acivicin in patients with recurrent CNS malignancies: a Southwest Oncology Group trial. 164 69

To see electrophysiological and neurochemical events during microdialysis with high [K+], direct current (DC) and excitatory postsynaptic field potentials (fEPSPs) due to perforant path stimulation were recorded in the granule cell layer of the fascia dentata, while 3, 25, 50 or 100 mM KCl was perfused through a microdialysis probe placed 1.5 mm from the recording electrode. Glutamate and glutamine content of the dialysate was measured by high performance liquid chromatography. Raising [K+] from 3 to 25 mM reduced the efflux of glutamine, without affecting that of glutamate or the electrical activity. In about 50% of experiments, 50 mM K+ induced large (20-30 mV) negative waves of spreading depression (SD), and a suppression of fEPSPs. In the other 50%, without SD, fEPSPs did not change. Glutamate efflux increased 3-fold in both groups. SD waves were produced in all experiments with 100 mM K+ which evoked a more than 10-fold increase in glutamate release. Glutamine efflux decreased equally, by about 50%, with the 3 concentrations of K+. Microdialysis with 20 mM fluoroacetate, a glial metabolic poison, decreased the spontaneous efflux of glutamine and glutamate and increased the incidence of SD waves. Results suggest that perfusion of 50 or 100 mM K+ through a microdialysis probe causes spreading depression which blocks surrounding electrical activity. The activity of glia partly protects against spreading depression caused by high [K+].
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PMID:Glutamate release and spreading depression in the fascia dentata in response to microdialysis with high K+: role of glia. 167 23

Application of a solution of 1-glutamine, 75 mM, to the pia-arachnoid surface of the dorsolateral neocortex of rabbits under dial-urethane anaesthesia was found to reversibly render the tissue insusceptible to spreading depression. It is suggested that this amide may play a part in the opposition normally offered by the tissue to undergo spreading depression. Some evidence is adduced which seems to support this suggestion.
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PMID:A note on the action of glutamine on cortical spreading depression. 174 76

Recent studies showed that hyperammonaemia caused many of the metabolic changes in portacaval-shunted rats, a model of hepatic encephalopathy. These changes included a depression in the cerebral metabolic rate of glucose (CMRGlc), an indication of decreased brain function. 2. The purpose of the present experiments was to determine whether the depression of CMRGlc caused by ammonia is confined to certain brain structures, or whether the depression is an overall decrease in all structures, such as occurs in portacaval-shunted rats. To accomplish this objective, rats were made hyperammonaemic by giving them intraperitoneal injections of 40 units of urease/kg body wt. every 12 h; control rats received 0.154 m-NaCl. CMRGlc was measured 48 h after the first injection, by using quantitative autoradiography with [6-14C]glucose as a tracer. 3. The experimental rats had high plasma ammonia concentrations (control 70 nmol/ml, experimental 610 nmol/ml) and brain glutamine levels (control 5.4 mumol/ml). Hyperammonaemia decreased CMRGlc throughout the brain by an average of 19%. CMRGlc showed an inverse correlation with plasma ammonia, but a stronger correlation with the brain glutamine content. 4. Hyperammonaemia led to a decrease in CMRGlc throughout the brain that was indistinguishable from the pattern seen in portacaval-shunted rats. This is taken as further evidence that the cerebral depression found in portacaval-shunted rats is a consequence of hyperammonaemia. The observation that depression of CMRGlc correlated more closely with brain glutamine content than with plasma ammonia suggests that metabolism of ammonia is an important step in the pathological sequence.
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PMID:Hyperammonaemia depresses glucose consumption throughout the brain. 187 5

1. It has been established that chronic hyperammonaemia, whether caused by portacaval shunting or other means, leads to a variety of metabolic changes, including a depression in the cerebral metabolic rate of glucose (CMRGlc) increased permeability of the blood-brain barrier to neutral amino acids, and an increase in the brain content of aromatic amino acids. The preceding paper [Jessy, DeJoseph & Hawkins (1991) Biochem. J. 277, 693-696] showed that the depression in CMRGlc caused by hyperammonaemia correlated more closely with glutamine, a metabolite of ammonia, than with ammonia itself. This suggested that ammonia (NH3 and NH4+) was without effect. The present experiments address the question whether ammonia, in the absence of net glutamine synthesis, induces any of the metabolic symptoms of cerebral dysfunction associated with hyperammonaemia. 2. Small doses of methionine sulphoximine, an inhibitor of glutamine synthetase, were used to raise the plasma ammonia levels of normal rats without increasing the brain glutamine content. These hyperammonaemic rats, with plasma and brain ammonia levels equivalent to those known to depress brain function, behaved normally over 48 h. There was no depression of cerebral energy metabolism (i.e. the rate of glucose consumption). Contents of key intermediary metabolites and high-energy phosphates were normal. Neutral amino acid transport (tryptophan and leucine) and the brain contents of aromatic amino acids were unchanged. 3. The data suggest that ammonia is without effect at concentrations less than 1 mumol/ml if it is not converted into glutamine. The deleterious effect of chronic hyperammonaemia seems to begin with the synthesis of glutamine.
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PMID:Hyperammonaemia does not impair brain function in the absence of net glutamine synthesis. 187 6

The purpose of this study was to evaluate whether heart glucose metabolism can account for elevated heart oxygen consumption in a tumor-bearing host. This is the first report of altered metabolism in perfused hearts from tumor-bearing animals. Glucose, glycerol, lactate, and amino acid metabolism was examined under steady-state conditions in isolated perfused hearts from sarcoma-bearing rats and compared to the metabolism in hearts from starved (96 hr) and fed control rats. Heart dry weight was reduced by 10% in tumor-bearing rats and by 30% in starved rats when compared to freely fed control animals. Cardiac glucose uptake was decreased in tumor-bearing rats (206 +/- 33 mumoles/hr/g dry wt) compared to both starved (298 +/- 18) and fed control rats (293 +/- 25). Hearts from both fed and starved controls released lactate and glycerol at significant rates during perfusion which was not evident in hearts from tumor-bearing rats. The release of individual amino acids from working hearts during perfusion was different among the animal groups with a severe depression of both glutamine and alanine release in tumor-bearing rats. In starved rats alanine release was normal although glutamine release was depressed by more than 50%. The net release of all amino acids was lowest in hearts from tumor-bearing rats, intermediate in the starved animals, and highest in the control animals, while the nonmetabolized amino acids (phenylalanine, tyrosine, methionine) were released at increased rates only from tumor-host hearts, indicating an increased net breakdown of some cardiac proteins in tumor-bearing animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose uptake and amino acid metabolism in perfused hearts from tumor-bearing rats. 235 96

Twenty-four acutely ill schizophrenic patients (DSM-III-R), 18-42 years old, were treated for 6 weeks with sulpiride. Sulpiride was administered in three different daily dosages (400, 800 or 1200 mg) according to a double dummy blind randomized administration schedule. The psychopathology of the patients was rated by the Comprehensive Psychopathological Rating Scale (CPRS) and the Nurse's Observation Scale for Inpatient Evaluation (NOSIE). The monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA), 4-hydroxy-3-methoxy-phenylglycol (HMPG) and the amino acids tyrosine, tryptophan, glutamate and glutamine were measured in serum before and once a week during sulpiride treatment. There were no significant correlations between the CPRS or the NOSIE morbidity scores and the biochemical measures before drug treatment. HVA levels were not correlated to rating scores during treatment, but after 6 weeks HVA had decreased significantly in the patients with a good response but not in the patients with a poor response. A negative relationship between 5-HIAA levels and depressive and negative symptoms was found. Non-responders according to the subscale for depression had low 5-HIAA levels throughout the treatment. An increase of tryptophan was correlated to improvement in the early part of treatment. High levels of glutamate or glutamine were found in non-responders before treatment. During treatment an increase of the glutamate level was correlated to improvement. Low levels of glutamine were related to improvement according to global and NOSIE (total) rating scores. Peripheral biochemical measures may be a valuable tool in the study of pathophysiological mechanisms and treatment effects in patients with schizophrenia.
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PMID:Relationships between clinical effects and monoamine metabolites and amino acids in sulpiride-treated schizophrenic patients. 236 52

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


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