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Biomedical subjects

G Curzon

Publications and source records attributed to G Curzon.

At least 145 records · Page 8Linked to original sources
PubMed1979

Study of disturbed tryptophan metabolism in depressive illness.

The evidence for disturbances of tryptophan and 5-hydroxytryptamine in depression and for various mechanisms by which such disturbances could occur is discussed. Two recent relevant studies in the author's laboratory are described: a) non-esterified fatty acid and total and free tryptophan were determined in plasmas of psychiatric patients unselected with respect to psychiatric diagnosis before and after a stress situation. Retarded patients had significantly low total and free tryptophan values which correlated negatively with agitation. Total tryptophan fell significantly after stress in the non-retarded subjects. The only biochemical abnormality significantly associated with a diagnosis of primary depression was the rise of plasma non-esterified fatty acid after stress. Thus tryptophan abnormalities were associated more with psychiatric rating scores than with diagnoses. b) Determinations on plasma and lumbar and ventricular CSF from psychiatric patients undergoing psychosurgery indicate that low plasma free tryptophan concentrations are associated with decreased 5HT turnover in the central nervous system.

Depression↗
PubMed1978

Effect of d-amphetamine on tryptophan and other aromatic amino acids in brain.

The investigation examined the mechanism of the increase in brain tryptophan concentration of rats treated with d-amphetamine. Certain well recognised influences upon brain tryptophan have been excluded as responsible. Thus, the effect is not associated with changes in the plasma concentrations of NEFA or free tryptophan. It is probably not due to a tryptophan-specific mechanism, because amphetamine increases the ratio of brain/plasma concentrations not only of tryptophan but also of tyrosine and phenylalanine. The concentration ratios for liver/plasma also rose, as did the liver tryptophan concentration, but these changes were less striking than for brain. Both alpha- and beta-adrenergic blocking drugs opposed the changes in brain, but in different ways. Thus, after treatment of rats with phentolamine, amphetamine decreased the plasma concentrations of the three aromatic amino acids; however, as the brain concentrations were little altered, the brain/plasma concentration ratios rose. Propranolol (and the dopamine blocker pimozide) opposed the increases of the ratios, so that the brain concentrations again altered little. The increased brain/plasma ratios resulting from the administration of amphetamine were associated with hyperthermia. Propranolol, pimozide and the diabetogenic drug streptozotocin opposed the changes in both plasma and brain; phentolamine affected neither. Despite the increase in brain tryptophan caused by amphetamine this drug had relatively little concurrent effect on 5HT synthesis. Experiments with adrenergic blockers suggest that the small rise of plasma insulin after the injection of amphetamine into rats did not cause the brain changes; these are probably a consequence of hyperthermia. The findings with streptozotocin suggest that the hyperthermic effect of amphetamine is manifested only in states of normal insulin secretion.

Amino Acids↗
PubMed1978

Effects of chronic experimental liver dysfunction and L-tryptophan on behaviour in the rat.

Rats with chronic experimental portocaval anastomosis were hypoactive as indicated by diminished activity in the home cage, during habituation in red light to an observation box and during exposure in white light to an open-field. Food intake and responsiveness to electric shock were also decreased. However, there was an abnormally high frequency of social activity when anastomosed rats were paired together after having been caged singly for 3 weeks. Also, sham-operated rats interacted more with anastomosed rats than they did with other sham-operated animals. Anastomosis also raised brain concentrations of tryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Administration of tryptophan to sham-operated rats increased shock threshold and decreased ambulation in an open-field. Thus, while anastomosed rats are not comatose they do have considerable behavioural abnormalities for which brain tryptophan changes may be in part responsible.

Animals↗
PubMed1978

5-Hydroxytryptamine: the effects of impaired synthesis on its metabolism and release in rat.

1 Control rats given L-tryptophan (100 mg/kg) showed a smaller increase of brain 5-hydroxytryptamine (5-HT) than its metabolite 5-hydroxyindoleacetic acid (5-HIAA). However, when brain 5-HT concentrations were depleted by 40-50% after treatment with the synthesis inhibitor p-chlorophenylalanine (PCPA) (150 mg/kg) L-tryptophan caused a considerable increase in 5-HT but no change in 5-HIAA. Similar results were obtained following depletion of brain 5-HT by pretreatment with p-chloroamphetamine (10 mg/kg).2 Electrical stimulation of the median raphe nucleus of control rats significantly increased 5-HIAA in the hypothalamus, hippocampus and striatum. However, stimulation of PCPA (200 mg/kg) pretreated animals did not significantly increase 5-H1AA either 24 or 72 h after administration of the drug.3 Pretreatment of rats with PCPA (200 mg/kg) increased striatal synaptosomal uptake of [(3)H]-5HT by 30% and reduced 5-HT concentration in the rest of the brain by 62%.4 PCPA (150 mg/kg) markedly reduced the acute behavioural response (-76%) to p-chloroamphetamine (10 mg/kg) although brain 5-HT was only moderately reduced (-36%). L-Tryptophan (100 mg/kg) given 15 min before p-chloroamphetamine restored both brain 5-HT and the behavioural effects of p-chloroamphetamine in PCPA pretreated rats and enhanced the behavioural response to p-chloroamphetamine in control rats.5 The results suggest that newly synthesized 5-HT is less rapidly metabolized in rats with low brain 5-HT. The possible reasons for this and the relevance of the results to the use of L-tryptophan in the treatment of depressive illness are discussed.

Animals↗
PubMed1978

Cerebral transmitter precursors and metabolites in advanced renal disease.

Patients with chronic renal disease had low plasma total tryptophan but an abnormally high proportion of this was in the free state. The subjects with encephalopathy had raised plasma free tryptophan, CSF tryptophan, and CSF 5-hydroxyindoleacetic acid. CSF tryptophan correlated better with plasma free than with plasma total tryptophan. Plasma and CSF tyrosine concentrations were normal but CSF homovanillic acid was raised especially in subjects with encephalopathy. The possible significance of these changes in advanced renal disease is discussed.

Adult↗
PubMed1978

Effects of portocaval anastomosis on behaviour and brain tryptophan metabolism.

The rat with portocaval anastomosis represents a convenient took for the investigation of (a) factors determining the availability of tryptophan to the brain and (b) the role, if any, that altered tryptophan metabolism may have in the development of hepatic encephalopathy. It was found that increases in brain tryptophan following anastomosis paralleled plasma free tryptophan rather than plasma total tryptophan regardless of whether or not correction for inhibition from amino acids competing with tryptophan for uptake into brain was applied. Nevertheless, while plasma free tryptophan exerts a major influence on brain tryptophan in both sham-operated and anastomosed rats, in the latter group brain tryptophan is raised further by some other mechanism. The anastomosed rat was also found to be behaviourally abnormal in a number of test situations. Thus, they were hypoactive during chronic exposure to an open-field and were less responsive to electric shock. Following the administration of tryptophan, sham-operated rats were also less active in an open-field and less responsive to electric shock when compared with saline-treated rats. Thus, anastomosed rats have behavioural abnormalities for which altered tryptophan metabolism might, to some extent, be responsible.

Animals↗
PubMed1977

Fluorimetric determination of plasma unesterified fatty acid.

A reliable and simple method is described for the determination of plasma unesterified fatty acid. The method involves extraction by Dole's reagent, washing with dilute sulphuric acid and determination by the decrease of fluorescence of a dilute solution of 7-hydroxy-4-methylcoumarin. Results on rat and human plasma are in good agreement with those obtained by titration.

Animals↗
PubMed1977

Fatty acid and tryptophan changes on disturbing groups of rats and caging them singly.

The effects of disturbing groups of 24 hr fasted rats on plasma unesterified fatty acid (UFA) and tryptophan concentrations and brain tryptophan concentrations were investigated. Removing rats from cages rapidly increased plasma UFA and corticosterone and decreased plasma and whole blood tryptophan of cage mates. The disturbance also appeared to influence biochemical values of rats in other cages within the same chamber. Effects specific to individual cages were also suggested. In subsequent experiments 24 fasting rats caged together were rapidly transferred to 24 separate cages and killed at intervals. Plasma UFA rose to a maximum by 12 min and then fell toward initial values. Plasma total tryptophan concurrently fell then rose. Its percentage in the free (ultrafilterable) state, and in some experiments the absolute values of free tryptophan rose then fell. When the latter rise was marked then brain tryptophan and the 5-HT metabolite 5-hydroxyindoleacetic acid rose. Tyrosine changes were negligible. Thus altered brain tryptophan level and 5-HT metabolism may be associated with plasma tryptophan changes caused by brief environmental disturbance.

Animals↗
PubMed1977

Effects of adrenaline injection on human plasma tryptophan and non-esterified fatty acids.

1. Subcutaneous injection of adrenaline into normal male volunteer subjects caused large increases of plasma non-esterified fatty acids and free tryptophan, but plasma total tryptophan fell considerably. Therefore increases of the percentage of plasma tryptophan in the free state were more marked than absolute increases of free tryptophan. 2. Plasma tyrosine fell slightly and plasma phenylalanine and cortisol were unaffected. 3. It is suggested that catecholamine release could lead to abnormalities of tryptophan disposition in stress and psychiatric illness.

Epinephrine↗
PubMed1977

Drugs altering insulin secretion: effects on plasma and brain concentrations of aromatic amino acids and on brain 5-hydroxytryptamine turnover.

1 An investigation was made into the effects of drugs which alter insulin secretion on the concentrations of tryptophan and other aromatic amino acids in plasma and brain and on 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in brain. Drugs used were streptozotocin, propranolol, tolbutamide and phentolamine. 2 Tolbutamide and phentolamine increased the plasma insulin concentrations by 100% and 300% respectively but with little effect on the brain/plasma ratios for the aromatic amino acids. Previously propranolol was found to decrease plasma insulin by 50% without altering the above ratios. The ratios were decreased by streptozotocin but only when plasma insulin fell by more than 50%. 3 Phentolamine and propranolol did not alter the brain/plasma ratios for the aromatic amino acids in streptozotocin-treated rats. 4 The results suggest that only large changes of insulin secretion e.g. those associated with food intake or aminophylline injection are likely to alter appreciably the brain/plasma ratios for the aromatic amino acids. 5 Tolbutamide displaced tryptophan from its binding to plasma albumin and increased brain 5-HIAA probably by inhibiting 5-HIAA efflux from brain. The other drugs did not alter brain 5-HT or 5-HIAA concentrations.

Amino Acids↗