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Biomedical subjects

A Clow

Publications and source records attributed to A Clow.

At least 37 records · Page 2Linked to original sources

Long-term administration of (-)-deprenyl increases mortality in male Wistar rats.

Long-term administration of the monoamine oxidase inhibitor (-)-deprenyl (0.5 mg/Kg) for up to 20 months significantly increased mortality in the male Wistar rat, whereas the dopamine agonist pergolide (0.4 mg/Kg) and the antioxidant diethyldithiocarbamate (400 mg/Kg) had no significant effect on mortality. The increased mortality was not related to dietary intake or body weight of the rats. This is of interest in the light of recent evidence that (-)-deprenyl increases mortality in humans.

Animals↗

Endogenous monoamine oxidase A inhibitory activity (tribulin), measured in saliva, is related to cardiovascular reactivity in normal individuals.

Salivary monoamine oxidase A inhibitory activity (MAO-AI), mean arterial blood pressure (MAP) and heart rate (HR) were determined simultaneously in healthy male students (n = 13) at rest, before a mild psychological stressor, twice during the task and 18 minutes after the end of the task. The sample as a whole showed significant differences in MAP and HR across occasions (respectively, p < 0.001 for both). Salivary MAO-AI could distinguish novice and experienced game players (p < 0.02) and was consistently positively correlated with MAP (r = 0.58, p < 0.05 on occasion 2). Pre-task measures of MAO-AI for an increased sample (n = 18) were associated with higher MAP (but not HR) throughout the experiment (p < 0.05). Those subject with falling MAO-AI profiles from task to recovery showed significantly greater simultaneous decline in HR than those with a rising MAO-AI profile (p < 0.05).

Adult↗

The relationship between circadian patterns of salivary cortisol and endogenous inhibitor of monoamine oxidase A.

The circadian pattern of free cortisol, measured in saliva, was monitored in normal healthy adults (N=41) for the first half hour immediately after awakening and in a smaller group (N=8) at timed intervals throughout the day. The endogenous inhibitor of monoamine oxidase A (MAO-AI) was measured in the same saliva samples in order to explore the relationship between circadian activation of the hypothalamic-pituitary-adrenocortical (HPA) axis and MAO-AI. A marked elevation of salivary cortisol was recorded in the first half hour immediately after awakening resulting in a two to three fold increase from the first awakening level. By contrast MAO-AI was highest immediately upon awakening and fell subsequently. Hence the cortisol response to awakening is preceded by heightened MAO-AI. Moreover those subjects who showed more persistently elevated MAO-AI were characterised by a more pronounced cortisol response. An association between MAO-AI and cortisol was also manifest in the diurnal pattern recorded at timed intervals throughout the day. The decline of salivary cortisol from the morning acrophase to the evening nadir was paralleled by MAO-AI. Both patterns of decline were significant (P< 0.01). Taken together with previously reported psychological stress studies these findings suggest a possible relationship between MAO-AI and HPA activity.

Adult↗

The relationship between salivary secretory immunoglobulin A and cortisol: neuroendocrine response to awakening and the diurnal cycle.

The level of secretory immunoglobulin A (sIgA) measured in saliva is downregulated during periods of chronic stress. In contrast, the response to an acute stress challenge is a transient increase. The process of awakening is associated with stress neuroendocrine activation characterised by increases in salivary cortisol. We therefore examined if this period of hypothalamic-pituitary-adrenal (HPA) activation was associated with changes in salivary sIgA. Associations of sIgA with the diurnal cortisol cycle were also investigated in a separate study. The awakening cortisol response was measured in 30 healthy day-active young adults. There was a marked elevation from the first awakening level over the succeeding 30 min. SIgA showed the opposite response with a marked fall from the highest first awakening concentration in the same samples over the same period. The cortisol rise was significantly correlated with the sIgA fall (r = 0.42). Salivary sIgA showed a similar diurnal cycle to cortisol in a study on eight healthy young adults. An early morning acrophase was followed by a decline to a stable base some 6 h after awakening. The physiological significance of these relationships and possible implications for vulnerability to infection are discussed.

Adult↗

Secretory immunoglobulin A and cardiovascular reactions to mental arithmetic and cold pressor.

Secretory immunoglobulin A (sIgA) in saliva and cardiovascular reactions to mental arithmetic and cold pressor tasks were recorded in 16 healthy young men on two sessions, 4 weeks apart. Both tasks elicited significant increases in sIgA secretion rate, reflecting increases in both salivary volume and sIgA concentration. Whereas mental arithmetic elicited a mixed pattern of alpha- and beta-adrenergic cardiovascular reactions, the pattern of reactions to cold pressor was predominantly alpha-adrenergic. Task levels of sIgA secretion rate, sIgA concentration, and saliva volume showed moderate to high test-retest reliability (r = .52-.83), although test-retest correlations were less impressive for change scores (r = -.19-.53). The pattern of correlations between change in sIgA secretion rate and cardiovascular reactivity variables was inconsistent.

Adult↗

The cortisol response to psychological challenge is preceded by a transient rise in endogenous inhibitor of monoamine oxidase.

The salivary cortisol response to an acute psychological stress challenge was investigated in normal male undergraduate students. A modified version of the Trier Social Stress Test (TSST) was used and saliva collected on 6 occasions before during and after the stress challenge. Control subjects were allowed to read quietly. As expected the cortisol response in experimental subjects was robust and peaked 12 minutes after the end of the stress. Endogenous monoamine oxidase A inhibitory activity (MAO-AI) was measured in the same saliva samples. MAO-AI also changed in response to the stress challenge, peaking in the saliva sample collected immediately after the stress challenge, 12 minutes prior to the cortisol peak sample. Furthermore the degree of increase in salivary MAO-AI was found to predict the degree of cortisol increase in the test subjects (r=0.76; n=14; p<0.001). These results are consistent with the hypothesis that elevated central monoamines, driven by inhibition of their main metabolic enzyme, can activate the hypothalamic-pituitary-adrenal (HPA) axis in the stress response. This finding lends further support to the notion that endogenous generation of MAO-AI is a normal homeostatic regulatory mechanism.

Adult↗

Isatin: a link between natriuretic peptides and monoamines?

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.

Animals↗

Urinary output of endogenous monoamine oxidase inhibitory activity is related to everyday stress.

The MAO A and B inhibitory components of urinary tribulin were investigated in normal individuals (11 males and 24 females, mean age +/- SD; 27.1 +/- 4.5 years) in relation to everyday stress. Volunteers collected a urine sample at the same time (late evening) on five days over a single week. On each occasion subjects also completed a mood adjective checklist which measured perceived stress levels over the day in question. For each subject all daily measures were aggregated. Mean individual urinary MAO A and B inhibitory activity was found to be positively correlated with stress scores both before (r = 0.38, p < 0.05 and r = 0.37, p < 0.05 respectively, n = 35) and after (r = 0.35, p < 0.05 and r = 0.33, p < 0.05 respectively, n = 35) correction for the effects of urinary volume. These results suggest that in normal healthy individuals high endogenous MAO inhibitory activity in the urine is indicative of a relatively enduring state of everyday stress.

Adult↗

Salivary monoamine oxidase A and B inhibitory activities correlate with stress.

MAO A and B inhibitory activities were determined, for the first time, in saliva samples. Saliva was collected on 4 occasions from 11 normal subjects (students) before and after delivering an important assessed oral presentation, a naturalistic stress inducing procedure. The first sample was collected 30 minutes before the presentation and 3 more within 40 minutes of finishing the presentation. At each collection a mood adjective checklist was completed. Mean MAO A inhibitory activity correlated with mean MAO B inhibitory activity (r = 0.872, p < 0.001, n = 11). Within subject analysis revealed a positive correlation between MAO A and B inhibitory activity and stress (r = 0.400, p < 0.01, n = 44 and r = 0.255, NS, n = 38 respectively). Mean MAO A and B inhibitory activity correlated with mean stress (r = 0.535, NS, n = 11 and r = 0.673, p < 0.05, n = 11 respectively). Peak MAO A and B inhibitory activities correlated with peak stress (r = 0.636, p < 0.05, n = 11 and r = 0.754, p < 0.01, n = 11, respectively). Salivary MAO A and B inhibitory activities were independent of salivary flow rate. We conclude that measurement of MAO A and B inhibitory activities in saliva is preferable to traditional urinary measures as sampling is less invasive and also supports a clear relationship to stress in normal individuals.

Female↗

Dysphoria and immune status in postpartum women.

This study investigated the relationship between psychological factors and circulating immune cell populations in postpartum women. The study group was 75 women who had vaginal deliveries and were free of psychotropic medication. Four days postpartum each subject completed three mood questionnaires, and a small blood sample was taken. All questionnaire scores were shown to be highly inter-correlated and principal component factor analysis revealed a single factor which we term dysphoria. This factor was significantly associated with lower total circulating lymphocyte counts. The effect was strongest for T cells (largely attributable to a reduction in CD4+ ve T helper cells) and weaker for NK cell counts. No evidence was found of a mediating role for serum cortisol although serum cortisol levels were weakly related to immune status. This study has thus demonstrated that changes in the distribution of the lymphocyte pool are associated with relatively minor differences in postpartum affect.

Adolescent↗

The effect of pergolide and MDL 72974 on rat brain CuZn superoxide dismutase.

It has previously been shown that both the dopamine receptor agonist, pergolide, and the monoamine oxidase inhibitor, (-)-deprenyl, can cause induction of CuZn superoxide dismutase in the rat striatum. We have now confirmed this effect of pergolide (0.04 mg/kg i.p.) as being localised to the striatum, but not the cerebellum, and shown it to take 3 weeks to develop. Furthermore, we have found that MDL 72974, a more specific monoamine oxidase inhibitor than (-)-deprenyl, failed to bring about such an induction either at a low selective monoamine oxidase B inhibitory dose, or at a higher non-selective dose.

Allyl Compounds↗

The relationship between secretory immunity, mood and life-events.

Twelve subjects volunteered to take part in a short trial involving daily life-event and mood recording over a period of up to two weeks. On each day subjects also provided timed saliva samples. Aggregated data across the trial period revealed that unstimulated secretion rate of secretory immunoglobulin A from whole saliva correlated strongly and significantly with net desirable event reporting, defined as a subject's tendency to report relatively frequent desirable events and relatively infrequent undesirable events. Correlations with positive and negative mood were insignificant, although the pattern of results was in line with hypotheses. Within-subject analyses revealed a totally contrary pattern of results. In particular, negative mood was significantly associated with higher sIgA secretion rate. Analyses involving total sIgA concentration paralleled those using secretion rate. Results are discussed in relation to psychoneuroimmunological models of illness vulnerability, particularly upper respiratory infection, and previous findings in regard to secretory immunity.

Adult↗

Changes in plasma cortisol and catecholamine concentrations in response to massage in preterm infants.

The biochemical and clinical response to massage in preterm infants was assessed. Eleven stable infants, of 29 weeks' median gestational age, median birth weight 980 g, and median postnatal age 20 days, were studied. Blood samples were obtained for the determination of adrenaline, noradrenaline, and cortisol 45 minutes before the start of massage and approximately one hour after completion of massage. Cortisol, but not catecholamine, concentrations decreased consistently after massage (median difference -35.8 nmol/l; 95% confidence interval -0.5 to -94.0, Wilcoxon matched pairs). There was a slight decrease in skin temperature (median difference -0.36 degrees C, 95% confidence interval -0.09 to -0.65) but there was no change in oxygenation or oxygen requirement. This study has shown that it is possible to detect an objective hormonal change following a supposedly 'non-therapeutic' intervention in preterm infants. The development of such methods of assessment are likely to be of particular relevance in the extremely immature or ill neonate in whom behavioural evaluation cannot play more than a limited part.

Birth Weight↗

Effects of dopaminergic drugs on superoxide dismutase: implications for senescence.

Both (-)-deprenyl and pergolide have been found to induce superoxide dismutase (SOD) in rat striata. There are several reports showing that strains or species with higher levels of SOD live longer. Other studies indicate that (-)-deprenyl can increase life expectancy in rats and that both (-)-deprenyl and pergolide may retard nigrostriatal degeneration. This present paper suggests that all these findings are linked, and that (-)-deprenyl and pergolide possess neuroprotective properties by virtue of an activated removal of toxic oxygen radicals.

Aging↗

Inhibitory potency of some isatin analogues on human monoamine oxidase A and B.

Isatin is an endogenous compound which acts as a selective inhibitor of monoamine oxidase (MAO) B. In this study a range of isatin analogues were tested for their in vitro inhibition of human MAO A and B. Most of the analogues were less potent than isatin. Hydroxylation of the aromatic ring changed the inhibitory potency in favour of MAO A, with 5-hydroxyisatin being a potent and selective MAO A inhibitor (IC50 8 microM). Isatinic acid, which is formed reversibly from isatin at alkaline pH, showed no inhibition.

Blood Platelets↗

Pergolide can induce soluble superoxide dismutase in rat striata.

Pergolide, a dopamine receptor agonist, given daily i.p. for three weeks at 0.04 mg/kg and 0.4 mg/kg, significantly induced soluble (Cu-Zn) superoxide dismutase in the rat striatum, while having no effect on the mitochondrial (Mn) form of the enzyme. Such induction, which can also be effected by (-)-deprenyl, may help to protect against nigrostriatal degeneration.

Animals↗