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Biomedical subjects

M H Joseph

Publications and source records attributed to M H Joseph.

At least 55 records · Page 3Linked to original sources
PubMed1983

Corticosteroid response to stress depends upon increased tryptophan availability.

Prior administration of valine to rats has been shown previously to prevent restraint stress-induced increases in brain tryptophan and 5HT turnover. The present study demonstrates that the accompanying attenuation of the corticosteroid response to this stress is substantially reversed by administration of tryptophan with the valine. Tyrosine is not effective in reversing this attenuation, and in fact itself attenuates the corticosteroid response to the stress when given alone. It is concluded that at least part of the corticosteroid response to restraint stress is mediated by an increase in serotonergic activity that is dependent on increased supply of the precursor, tryptophan, and that this can be antagonised by either of two amino acids which compete with tryptophan for access to the brain. Implications for stress-associated human disorders are discussed.

Adrenal Cortex Hormones↗
PubMed1983

Studies on kynurenine in human cerebrospinal fluid: lowered levels in epilepsy.

Kynurenine, tryptophan and 5-hydroxyindoleacetic acid were measured in human lumbar and cisternal cerebrospinal fluid (CSF) taken during pneumoencephalography. The results do not support the hypothesis that any substantial part of the CSF kynurenine is of central origin. However, the results suggest that CSF kynurenine is reduced in some epileptic subjects and this seems to be due to the disease rather than anticonvulsants. This finding is of interest in view of the reported convulsant effect of kynurenine in experimental animals.

Adolescent↗
PubMed1982

Does in vivo voltammetry in the hippocampus measure 5-HT release?

In vivo voltammetry enables catecholamine and 5-hydroxytryptamine (5-HT) release to be directly determined in the brains of conscious unrestrained animals. This study concerned the validation of the measurement of 5-HT release using scanning voltammetry at chronically implanted carbon paste/epoxy resin glass microelectrodes in the rat hippocampus. Automated recordings of the current produced by applying a ramp (100 mV/s) potential (0-1 V) to the electrode at 5 min intervals were made over a period of several hours. A current peak at 0.35-0.4 V corresponded to that produced by solutions of 5-HT in vitro. The effect of a number of drug known to affect 5-HT synthesis and release was then studied in vivo. p-Chloroamphetamine (PCA) caused an increase in the peak which correlated with a '5-HT behavioural syndrome'. p-Chlorophenylalanine caused a reduction in the peak and prevented both the increase seen with PCA and the PCA induced behavior. Fluoxetine and L-tryptophan also led to increases in signal; all these results were consistent with the signal reflecting extraneuronal 5-HT. However 5-hydroxyindoleacetic acid (5HIAA) also oxidizes at 0.35-0.4 V in vitro. Probenecid, which blocks 5HIAA egress from the brain caused a large increase in the hippocampal signal. The monoamine oxidase inhibitors pargyline and nialamide, which increases 5-HT and reduce 5HIAA levels, had no significant effect on the signal. These results, together with the greater increase in signal following probenecid than tryptophan and the delayed increase after tryptophan, and interpreted as implying that extraneuronal 5HIAA and 5-HT contribute approximately equally to the hippocampal signal. We conclude that this method gives information distinct from and complementary to biochemical estimations, and offers great scope for the investigation of the role of 5-hydroxyindole release in drug and environmental effects on behaviour.

Animals↗
PubMed1981

Simple high-performance liquid chromatographic method for the concurrent determination of the amine metabolites vanillylmandelic acid, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, dihydroxyphenylacetic acid and homovanillic acid in urine using electrochemical detection.

A simple method for the concurrent analysis of the noradrenaline metabolites vanillylmandelic acid and 3-methoxy-4-hydroxyphenylglycol, the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid, and the serotonin metabolite 5-hydroxyindoleacetic acid in human urine is described. Following organic extraction of the metabolites from acidified urine, they are separated by single-step gradient elution high-performance liquid chromatography on a reversed-phase column. Detection and quantification are achieved with an electrochemical detector using a carbon-paste electrode; samples can be injected at 40-min intervals. Optimisation of analytical parameters is described, and examples of the application of the method in the fields of clinical chemistry and clinical neuroscience are given. This provides a convenient method for the concurrent study of the metabolism of three major biogenic amines, and is readily adaptable for studies on cerebrospinal fluid and brain tissue.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1979

3-Methoxy-4-hydroxyphenylglycol excretion in acutely schizophrenic patients during a controlled clinical trial of the isomers of flupenthixol.

Urinary MHPG excretion in patients with acute schizophrenia was studied before and during a trial of the isomers of flupenthixol and placebo. Pretrial MHPG excretion was not related to severity of illness before the trial or to other pretrial clinical variables. In male subjects higher pretrial MHPG excretion was associated with a better outcome 1 year post-trial. However in females no relationship between MHPG excretion and outcome was established. During the trial there was a reduction in MHPG excretion in patients treated with beta-flupenthixol but no decrease in the group treated with alpha-flupenthixol or chlorpromazine. In patients on placebo there was a reduction in MHPG excretion in those who did well clinically, but not in those who did poorly. Thus low MHPG excretion may be a predictor of poor outcome in schizophrenia, but MHPG excretion also changes both as a function of clinical state and of neuroleptic drug administration.

Adult↗
PubMed1979

Dopaminergic mechanisms and cognitive deficit in schizophrenia. A neurobiological model.

A hypothesis is briefly discussed proposing that schizophrenic symptoms are due to a breakdown in a mechanism by which conscious attention is limited and directed. It is shown that this mechanism can be modelled in terms of a simple nerve network in which every channel inhibits all the others. Failure of this inhibition would cause the defect hypothesised to occur in schizophrenia. It is shown that if dopamine is given a central role as transmitter in such a network then the various predictions about the biochemistry of schizophrenia that follow are not only consistent with the evidence for the 'dopamine theory' of schizophrenia, but also with much of the evidence held to be contrary to that theory. While not purporting to be an experimentally validated description of schizophrenia, this model goes beyond the single amine theories of schizophrenia and links dysfunctions in amine systems with specific behavioural control mechanisms. Given the current state of knowledge, such models can make only limited predictions about the biochemistry of schizophrenia. However, an attempt to link behavioural and biochemical systems in this way will be crucial for the development of viable animal models of schizophrenia.

Animals↗
PubMed1979

Monoamine mechanisms in chronic schizophrenia: post-mortem neurochemical findings.

Dopamine and its metabolites homovanillic acid and dihydroxyphenylacetic acid, noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid, and tryptophan and its metabolite kynurenine have been assayed in 9 schizophrenic and 10 control brains, together with the monoamine-related enzymes tyrosine hydroxylase monoamine oxidase, dopamine-beta-hydroxylase, and catechol-o-methyl-transferase. In schizophrenic brains dopamine, noradrenaline and serotonin were significantly increased in some areas of corpus striatum, but there were no significant changes in enzyme activity or monoamine metabolite concentrations in any of the brain areas examined. The findings are not consistent with theories that serotonin or noradrenaline stores are grossly depleted or noradrenaline neurones have degenerated, or that monoamine oxidase activity is abnormal, in schizophrenia, and provide no direct support for the hypothesis that dopamine neurones are overactive.

Aged↗
PubMed1978

Determination of kynurenine by a simple gas-liquid chromatographic method applicable to urine, plasma, brain and cerebrospinal fluid.

A simple, sensitive and specific method for the determination of kynurenine is described. This is based on alkaline cleavage of kynurenine, followed by solvent extraction, trifluoroacetylation and gas--liquid chromatography with electron capture detection. Using this method kynurenine has been determined in urine and plasma, and for the first time in brain and cerebrospinal fluid. Increases in kynurenine in brain, plasma and urine are demonstrated following tryptophan administration to man and rat.

Animals↗
PubMed1978

Brain tryptophan metabolism on the 5-hydroxytryptamine and kynurenine pathways in a strain of rats with a deficiency in platelet 5-HT.

1 Brain 5-hydroxytryptamine (5-HT) metabolism has been compared in albino (Sprague-Dawley; SD) and in Fawn-Hooded (FH) rats, which have an inherited platelet 5-HT deficiency. 2 It was confirmed that blood 5-HT levels in the FH rats were about one quarter of those in the SD rats. 3 Brain 5-HT and 5-HIAA were however higher in FH rats on a per gram basis; there was no difference between the strains on a per brain basis, because of the smaller brain weights of the FH rats. 4 Brain and plasma tryptophan were not significantly different in the two strains. Plasma kynurenine was higher in the FH rats, and brain kynurenine was also higher either on a per gram or on a per brain basis. 5 The reserpine-releasable brain 5-HT was the same proportion of total brain 5-HT in the two strains. 6 Experiments with pargyline suggested that the turnover of 5-HT was somewhat higher in the FH rats on a per gram basis, but not significantly so on a per brain basis. 7 It is concluded that although brain tryptophan metabolism may be somewhat accelerated along both the 5-HT and kynurenine pathways in the FH rats there is no gross deficiency in the binding of 5-HT in their brains analogous to that found in their platelets.

Animals↗