Maternal stress or anxiety in pregnancy and emotional development of the child.
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Biomedical subjects
Publications and source records attributed to V Glover.
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Isatin is an endogenous indole with a distinctive distribution in brain and tissues. In the brain, the highest levels have been found in the hippocampus (0.1 microgram/g), and an immunocytochemical stain has shown specific localization within particular cells. In vitro, its most potent known actions are as an inhibitor of monoamine oxidase B (IC50 approximately 3 microM), and of atrial natriuretic peptide (ANP) receptor binding and ANP-induced guanylate cyclase (both with an IC50 approximately 0.4 microM). In vivo, isatin administration (10-200 mg/kg) causes an increase of monoamine neurotransmitter levels in the brain. Isatin is anxiogenic in animal models at doses of 10-20 mg/kg and sedative at higher doses. Its anxiogenic effects are unlikely to be due to inhibition of monoamine oxidase, but may possibly stem from interaction with the ANP system. Isatin may mediate a link between monoamines and the natriuretic peptide system, and its analogues may provide new pharmacological tools.
Phenylethylamine and cortisol were measured in 24-h urine samples taken from women day 2/3 postpartum, and matched controls. They also completed self-rating blues and highs scales. There was no significant difference in phenylethylamine excretion in those who scored highly with blues or highs, and either postpartum or normal controls. The number of raised values for phenylethylamine output was significantly greater in the postpartum women, who had no psychopathology, than in normal controls. Cortisol levels were significantly raised in postpartum controls compared with normal controls; women with the highs excreted significantly less cortisol than other postpartum women.
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Rat atrial natriuretic peptide (ANP) was investigated for putative anxiolytic activity in rats, following intracerebroventricular (ICV) administration. ANP in doses of 200 and 500 ng/rat induced significant anxiolysis, comparable with that of lorazepam (0.5 mg/kg, i.p.) in a variety of anxiety models (open-field, elevated plus-maze, social interaction, and novelty-induced feeding suppression tests). Isatin, an endogenous anxiogenic indole, shown to be an antagonist of ANP in vitro, significantly inhibited the anxiolytic effect of ANP in the elevated plus-maze test in subanxiogenic doses. The anxiolytic action of ANP was unaffected by flumazenil, a benzodiazepine receptor antagonist. Conversely, the anxiolytic action of lorazepam was antagonized by flumazenil but not by isatin. The data indicate that ANP may function as an endogenous anxiomodulator, which may act in conjunction with isatin independently of benzodiazepine receptors. These results strengthen the evidence for links between physiological systems involved in anxiety and those in natriuresis.
Red wine-induced release of [14C]5-hydroxytryptamine (5HT) from platelets of red wine-sensitive migraine patients, migraine patients not sensitive to red wine and controls, was determined in vitro. No significant differences in platelet [14C]5HT release were found between any of the groups investigated.
There is considerable evidence that subjects vulnerable to endogenous depression excrete less tyramine sulphate after an oral dose of free tyramine than controls (the tyramine test). In this study, 26 psychiatric inpatients, exhibiting a wide range of responses to the test, and 10 normal controls were challenged with oral doses of paracetamol and tyramine on two separate occasions. Urinary output of paracetamol sulphate and paracetamol glucuronide in all subjects was monitored but there were no significant correlations with tyramine sulphate output. Thus, the output of these metabolites appears to be under complex control, and paracetamol cannot be substituted for tyramine in the "tyramine test". The basic deficit responsible for low values in the tyramine test is unlikely to stem from sulphate depletion or a generalised disturbance of the sulphation system, and remains obscure.
Anxiogenic agents, yohimbine, pentylenetetrazole (PTZ), quinine, bufotenine, flumazenil and isatin were administered (ip) to rats at doses known to induce anxiety in this species. All the drugs exhibited anxiogenic response on the elevated plus-maze and induced a parallel increase in endogenous brain monoamine oxidase (MAO) inhibitory (tribulin) activity. The intensity of the drug-induced anxiety was fairly well correlated with the magnitude of increase in the MAO A inhibitory component of tribulin but not so with its MAO B inhibitory component. Thus, in the doses used, the degree of anxiogenic activity was PTZ > yohimbine > bufotenine > quinine > isatin > flumazenil, in terms of % entries on the open arms of the maze, whereas the magnitude of endogenous MAO A inhibition was PTZ > yohimbine > bufotenine > quinine > flumazenil > isatin. The results indicate that the MAO A inhibitory component of tribulin, rather than its MAO B inhibitory component, may be responsible for the postulated function of tribulin as an endogenous marker of anxiety.
This study was designed to investigate tyramine sulfate conjugation in patients with migraine or tension-type headache, as defined by the newly introduced International Headache Society (IHS) criteria and to examine whether this relationship is mediated by major depression. A total of 62 subjects completed the study: 38 with migraine (22 with aura and 16 without aura), 12 with tension-type headache, and 12 controls. Patients with migraine had significantly lower urinary tyramine sulfate excretion following oral tyramine challenge than normal control. Tension-type headache was also associated with low tyramine conjugation, but only when comorbid with depression. Although mean tyramine sulfate output was lower among subjects with major depression within each of the subtypes of headache, no significant main effect emerged for depression or major subtype thereof. The lower tyramine sulfate excretion values among patients with both migraine and depression compared to those of migraine alone or depression alone in our data and those of others suggests that comorbid migraine with depression may represent a more severe form of migraine than migraine alone. The findings underscore the importance of comorbidity in clinical and epidemiological studies of migraine.
Morphine (10 mg/kg), ethanol (8% w/v, 2 ml/kg), nicotine (0.1 mg/kg), cannabis extract (200 mg/kg), lorazepam (10 mg/kg) and ondansetron (0.1 mg/kg) were each administered to rats twice daily i.p. for 14 days and the anxiogenic response following their withdrawal was monitored by the elevated plus-maze test 24 h later. Brains were removed and endogenous monoamine oxidase (MAO) A and B inhibitory activity (tribulin) levels measured on day 14 and 24 h after drug withdrawal in different groups of animals. Morphine, ethanol, lorazepam and nicotine withdrawal was associated with significant anxiety and corresponding increase in brain tribulin activity, particularly its MAO A inhibitory component. Cannabis and ondansetron withdrawal were neither associated with anxiety or change in tribulin levels. The investigation supports the postulated role of tribulin as an endogenous correlate of anxiety, its MAO A inhibitory component accounting for a major part of this effect.
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We have confirmed our earlier finding that most red wines are able to bring about 5-hydroxytryptamine (5-HT, serotonin) release from platelets in vitro. Platelets from individual subjects manifested varying degrees of releasing ability but responded to different wines with a similar rank ordering. There was a high correlation (r = 0.87) between the effect of red wine and that of reserpine in different individuals. Some types of red wine caused a consistently higher release of 5-HT than others in all subjects; one red wine in particular resulted in negligible release. When several brands of this 'low-releasing' red wine were further examined, they all showed a lower activity than all the brands of a 'high-releasing' red wine type. This variation in releasing power was not related to intensity of red colour. Partial purification of red wine was achieved by column chromatography and showed releasing activity to be associated with a low molecular weight orange fraction. Preliminary studies, using solid phase extraction methods, showed that the active components lie mainly in a subgroup of the flavonoid fraction. If any of the adverse effects of red wine, such as headache induction, derive from this 5-HT releasing ability, then it may be possible to prepare red wines free from the chemical substances responsible.
The endogenous monoamine oxidase (MAO) inhibitory activity, termed tribulin, contains several components. We have previously identified one of them, isatin, which is a selective inhibitor of MAO B. In the present study we have purified several further components of human urinary tribulin which act as selective inhibitors of MAO A. They have been identified by gas chromatography-mass spectrometry (GC-MS) as ethyl indole-3-acetate (and/or methyl indole-3-propionate), methyl indole-3-acetate and ethyl 4-hydroxyphenylacetate. IC50 values for MAO A were found to be 44 microM (105 microM for methyl indole-3-propionate), 88 microM and 120 microM, respectively, whilst those for MAO B were each greater than 1 mM. The artificial formation of these esters was excluded by carrying the parent acids, from which they are presumably synthesized, through the purification procedure. As tribulin output is increased during stress or anxiety, these results point to a possible role for tryptamine and tyramine pathways in such disorders.
Isatin (indole-2,3-dione) is an endogenous compound with anxiogenic properties. In the brain, highest levels (0.1 microgram/g) have been found in the rat hippocampus. In the present study, we show that isatin has little effect on a wide range of neurotransmitter and hormonal receptors but that it acts as an inhibitor of atrial natriuretic peptide (ANP) binding, with an IC50 of 4x 10(-7) M. It also inhibits ANP-activated particulate guanylate cyclase from rat kidney, heart and brain membranes in dose-dependent fashion, varying also with ANP concentration. These findings suggest that isatin is a new endogenous regulator of mammalian ANP activity, with potential implications for the control of both anxiety and natriuresis.
The concept of dietary migraine as a clinical entity remains controversial. We review here such objective evidence that has been put forward for its existence. Red wine, in particular, is commonly alleged to initiate attacks in susceptible individuals. We discuss how some of its recently described pharmacological properties might trigger off the sequence of events leading to migrainous headache.
The endogenous monoamine oxidase inhibitor, tribulin, contains several components which selectively (or nonselectively) inhibit monoamine oxidases A and B. The pig brain tribulin component selectively inhibiting monoamine oxidase A was purified and identified as 4-hydroxyphenylethanol using gas chromatography-mass spectrometry. This compound was also found in the rabbit brain tribulin fraction which selectively inhibits monoamine oxidase A but has no influence on monoamine oxidase B. 4-Hydroxyphenylethanol inhibits monoamine oxidase A in an incompetitive manner with respect to the substrate, serotonin (Ki = 1.4 mM). Possible pathways of 4-hydroxyphenylethanol synthesis and its biological importance as the monoamine oxidase A inhibiting component of tribulin are discussed.
The purpose of this study was to investigate whether the fetus mounts a hormonal stress response to a potentially painful procedure, intrauterine needling. Cortisol and beta-endorphin concentrations in fetal plasma obtained during uncomplicated fetal blood sampling or intrauterine transfusions by needling the fetal intra-abdominal portion of the umbilical vein (intrahepatic vein) were compared to hormone concentrations in fetal plasma obtained by the conventional technique of needling the placental cord insertion, which is not innervated. Cortisol and beta-endorphin concentrations did not increase within 10 minutes of fetal abdominal needling (n = 15). However, more prolonged needling during transfusion at the intrahepatic vein was associated with an increase in fetal plasma cortisol (median increase 48 nmol/L; 95% Cl, 23-86) and beta-endorphin (207 pg/mL; 113-307) concentrations compared to transfusion at the placental cord insertion (p < 0.005 for both hormones). The magnitude of rise in hormone increased linearly with the duration of needling (cortisol, r = 0.80; beta-endorphin, r = 0.88, p < 0.05 for both). These data suggest that the fetus mounts a hormonal stress response to invasive procedures. They raise the possibility that the human fetus feels pain in utero, and may benefit from anaesthesia or analgesia for invasive procedures.