Blood platelet glutathione peroxidase: some properties and partial purification.
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Biomedical subjects
Publications and source records attributed to C Dreux.
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Some studies suggested a role for histamine in the pathogenesis of the migraine. So we decided to investigate the histamine-release in two groups of patients: 8 common migraine patients, 8 healthy subjects. Plasma from either controls or migraineurs were mixed with the same control whole blood and histamine release was measured using a radio-enzymatic assay. Migraine plasma induced an histamine release significantly more important than control plasma (p less than 0.01). The nature of an "histamine releasing factor" in the plasma of migraine patient is discussed. This work is an argument for a possible immuno-allergic process in migraine.
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In infantile autism, the serotoninergic (5-HT) hypothesis is corroborated by biological dosages and therapeutic effects of fenfluramine which decrease blood serotonin. However other drugs, such as dopaminergic agonists or antagonists, have therapeutic effects. Therefore, we tested the hypothesis that two dopaminergic (DA) drugs have a similar 5-HT effect underlying the therapeutic efficiency. We evaluated in a randomized, double-blind and cross-over study, the effects of a DA agonist (bromocriptine) and a DA antagonist (amisulpride) on platelet 5-HT in infantile autism. The prolactinemia, reflecting the DA action, has been also measured. Nine children, aged from 4 to 13 years, according to the DSM III for infantile autism, received either drug in a random order during four weeks with an in-between placebo period of six weeks. The dosages of platelet 5-HT and serum prolactin were carried out at the beginning and at the end of every phase of treatment (active or placebo) with radioenzymology and radioimmunoassay methods respectively. The principal results on serum prolactin show neither order x treatment interaction, nor order effect but a significant treatment effect (p < 0.01): amisulpride increases serum prolactin whereas bromocriptine decreases according to the usual data. About platelet 5-HT, there is neither order x treatment interaction, nor treatment effect but a significant order effect (p < 0.01). Both drugs increase platelet 5-HT in the first phase of treatment. This order effect could be explained by a remanent effect of amisulpride after 6 wash-out weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
All along clinical studies of a new drug, during the second, third, or fourth phase, the hospital laboratory occurs in the biological tolerance supervision. Therefore, it calls on a number of quality controls, either voluntary or obligatory: patient identity control, analytical quality controls: between and within laboratory, regional and national controls, biological quality control. Beside these quality controls, that are necessary at the same time for clinical studies and for routine analysis, biological laboratories are submitted on norms of material, area, and employees qualification (Law of July 11th 1975).
In post-partum depressive illness ("post-partum blue") we measured urinary MHPG, VMA, 5-HIAA and free and total Trp. VMA and especially MHPG reflect the brain noradrenaline metabolism. Trp is the precursor of 5-HT synthesis and 5-HIAA is the main urinary catabolite of 5-HT. The clinical evaluation consisted in self-evaluation scales: Pitt scale 1, 3 and 5 days after delivery, CESD scale of NIMH (depression) and BONIS scale (anxiety) at 6th day. Moreover a psychiatrist measured depression intensity on the MADRS scale and DSM III data. First results seem to indicate a decrease of free MHPG and VMA, an increase of 5-HIAA and no alteration of free and total Trp. These modifications could involve adrenergic and serotoninergic alterations in brain.
In a group of 22 autistic children aged 5 to 16 y., and a group of normal controls matched for age and sex, catecholamines metabolism has been investigated in plasma, platelets and urine. This investigation was part of a research project in which several biological parameters (including serotonin) were simultaneously explored in the same children. In the autistic group, epinephrine and norepinephrine and dopamine were significantly lower in isolated platelets, and no significant difference was found between the two groups for the urinary excretion of epinephrine, norepinephrine, dopamine, DOPAC and MHPG. Other differences between the two groups in the statistical correlations of several biochemical parameters (plasma norepinephrine and dopamine with platelet MAO activity, platelet norepinephrine with platelet dopamine, platelet dopamine, platelet dopamine with platelet serotonin) also suggest abnormalities of bioamine metabolism in the platelets of autistic children.
There are some evidences to propose blood platelets as a model of bioaminergic neurons. Similarities between platelets and neurons are particularly important with respect to serotonin metabolism but now it is possible to extend this model to other neurotransmitters such as dopamine, GABA, glutamate... The reason for these similarities may be due to the common embryonic origin of these two very different cell types. Some changes of platelet functions are observed in psychiatric syndromes. For example: serotonin uptake, bioamine storage, enzymatic activities are modified in different types of depression and schizophrenia, infantile autism, neurologic diseases (migraine, chorea, Down syndrom). Furthermore, psychotropic drugs also alter the platelet functions. Recently, the discovery of neuro-endocrine disorders in psychiatric diseases has led to the proposal of platelets as a model in neuro-endocrinology. Some arguments can be developed to support this hypothesis. In biological psychiatry, the platelet model seems actually useful essentially in the classification of psychiatric diseases, the management of treatments and the study of new psychotropic drugs. However methodologic difficulties still presently limit the development of this model.
Several arguments suggest that dopamine (DA) plays a role in the physiopathology of migraine. Conjugated and unconjugated plasma and platelet DA, as well as platelet phenolsulfotransferase M activity (responsible for DA sulfatation) were measured in 30 control subjects, 27 common migraine patients between attacks and 9 migraineurs during an attack. No modification of any of the parameters tested was detected in attack-free periods. During the attack no change of conjugated DA was observed; in contrast, a significant decrease of unconjugated platelet DA and a significant and correlated increase of plasma unconjugated DA were demonstrated. This corresponds to a release of unconjugated DA by the very dense bodies in platelets of migraine patients during the attack.
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In this controlled study of 22 autistic children and 22 normal controls matched for age and sex, the frequency of hyperserotonemia in infantile autism was confirmed. Platelet serotonin was elevated in patients. Comparative to controls, serotonin was also high in urine of autistic patients, while, on the contrary there was no difference for the urinary excretion of 5-HIAA. No difference was observed either for serotonin uptake and efflux or for MAO activity, in isolated platelets. The elevation of plasma free tryptophan - significant only with the Kolmogorov Smirnov test - suggests that 5-HT biosynthesis might be enhanced. In the group of patient reported in this study, disorders of serotonin metabolism are associated with disturbances of platelet catecholamines, and also with elevated immunoglobulins and enhanced cellular immunity reactions.
In sixteen autistic children high values of IgG and a high level of lymphocyte stimulation with PHA were observed. Principal component analysis showed: 1) a significant correlation between basic lymphocyte mitogenic activity and the clinical symptoms opposition and hyperactivity, 2) a significant correlation between high Ig levels, high PHA stimulation responses and the main autistic symptoms (withdrawal, inaffectivity, hypoactivity, mannerism, stereotypy and negatively echolalia), 3) a significant correlation with serotonin uptake by platelets and high immunological responses. Such correlations are strongly in favor of an immunologic component in autistic disease.
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