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A Clow

Publications and source records attributed to A Clow.

At least 19 recordsLinked to original sources
PubMed2006

Suspected non-adherence and weekend versus week day differences in the awakening cortisol response.

The pronounced rise in cortisol following awakening holds promise as a bio-marker of variables in the psychosocial domain, but its investigation also presents methodological challenges, which we attempted to address in this study. Forty-eight healthy, young students participated and were instructed to collect saliva 0, 15, 30 and 45 min post awakening on two consecutive normal weekdays and two consecutive weekend days (order counterbalanced). Participants' awakening cortisol response (ACR) profiles differed between the weekdays and weekend with trend analysis revealing a steeper rise on weekdays compared to the weekend. These differences were not accounted for by weekday/weekend differences in awakening time and state stress or by perceived stress over the previous month. Total salivary-free cortisol secretion (area under the cortisol curve (AUC)) over the 4 study days was negatively correlated with the measure of longer term stress and awakening time. The mean 4-day rise in cortisol (mean increase: MnInc) was also negatively correlated with awakening time. This awakening time effect was not mediated by stress or vice versa, since both were independent predictors of cortisol. In an attempt to address the ubiquitous problem of non-adherence to the requested saliva sampling regime, known to distort the shape of the ACR, suspected non-adherence (SNA) was examined by identifying instances of profiles showing no cortisol rise from the waking sample to either the 15 or 30 min sample post awakening. Analysis controlling for SNA status had no effect upon the observed associations with Perceived Stress Scale (PSS) and awakening time however it abolished the otherwise highly significant flatter profile at weekends.

Adolescent↗
PubMed2005

Post-awakening cortisol secretion during basic military training.

Salivary free cortisol concentrations in the first 30 min after awakening were assessed in 12 healthy army recruits at the beginning, middle and end of an 11-week intensive physical training course. To ensure strict adherence to protocol saliva collection was supervised and collected on each sampling day immediately on waking and again 15 and 30 min later. Self-rated psychological assessments of state levels of stress, arousal and fatigue were performed in the evening of each sampling day. A within-subjects repeated-measures analysis of participants who completed the course (12 of the original 20) showed a significant main effect of cortisol concentration across all three sampling points after awakening (F((2,22))=54.516, p<0.0001) and a significant main effect of weeks into the training course (F((3,33))=4.390, p=0.010). Further analysis of this effect of measurement-week revealed that at weeks 3 and 6 total cortisol secretion estimated by area under the curve was lower (F((3,33))=4.602, p=0.008) compared to the beginning and end of the course. Surprisingly self-reported stress, arousal and fatigue did not differ significantly across weeks, despite the large dropout rate (40%) and self-evident pressures of the course. We conclude that when controlling for many confounding variables, including participant adherence, post-awakening cortisol levels are sensitive to stressful challenge over a period of weeks.

Adolescent↗
PubMed2005

The diurnal patterns of the adrenal steroids cortisol and dehydroepiandrosterone (DHEA) in relation to awakening.

The steroid hormones, cortisol and dehydroepiandrosterone (DHEA) are the two main peripheral secretory products of the hypothalamic-pituitary-adrenal stress-neuroendocrine axis. The diurnal pattern of cortisol secretory activity has been well characterised. Various aspects of this pattern have been related to time of awakening, light exposure, psychological dimensions of affect, immune function and systemic health and well-being. DHEA is also an important adrenocortical steroid whose secretory activity has been related to immune function, psychological and health variables. The most pronounced feature of the diurnal cortisol cycle is a burst of secretory activity following awakening with a diurnal decline thereafter. We mapped DHEA secretory activity onto this cycle by measuring both steroids in saliva samples collected at distinct time points over the diurnal cycle, synchronised to awakening. Both steroids, particularly DHEA, showed stability across days of sample collection. A main distinction between cortisol and DHEA was that although DHEA was elevated in post-awakening samples compared with later in the day there was no evidence of an awakening stimulatory burst of DHEA secretory activity. Although DHEA in many respects paralleled cortisol secretory activity there was some dissociation; mean levels were positively but not tightly correlated. The secretory pattern of DHEA is very stable whereas cortisol secretory activity seems more sensitive to day-to-day variability.

Adolescent↗
PubMed2004

The effect of dawn simulation on the cortisol response to awakening in healthy participants.

Bright light exposure after awakening has been shown to elevate cortisol levels in healthy participants. The present study examined the effect of dawn simulation (a treatment for seasonal affective disorder) on the cortisol response to awakening and mood. Twelve healthy participants were supplied with a dawn simulator (The Natural Alarm Clock, Outside In, Cambridge Ltd), a bedside light that increases in intensity prior to awakening to approximately 250 lux over 30 mins when an audible alarm sounds. A counterbalanced study was performed on 4 consecutive normal weekdays, two of which were control days (no dawn simulation) and two experimental (dawn simulation). Saliva samples were taken immediately on awakening then at 15, 30 and 45 minutes post awakening on all 4 study-days. Total cortisol production during the first 45 mins after awakening was found to be significantly higher in the experimental condition than in the control condition. Participants also reported greater arousal in the experimental condition and there was a trend for an association between increased arousal and increased cortisol secretory activity under dawn simulation. This study provides supportive evidence for the role of light and the suprachiasmatic nucleus in the awakening cortisol response.

Adult↗
PubMed2004

The awakening cortisol response: methodological issues and significance.

The awakening cortisol response (ACR) is a discrete and distinctive part of the cortisol circadian cycle. In healthy adults salivary free cortisol concentrations increase by between 50 and 160% in the first 30 min immediately post-awakening (approximate average increase of 9 nmol/l, range 4-15 nmol/l, estimated to be equivalent to about three secretory episodes). However there are no agreed norms for the absolute concentrations of free cortisol in saliva either immediately post-awakening (range of 4.7-18.5 nmol/l) or 30 min post-awakening (range of 8.6-21.9 nmol/l). This review explores reasons for these discrepancies in normative data including confounding factors such as gender, age, awakening time, light and participant adherence. Although the physiological role of the ACR has not been clearly defined evidence is discussed that suggests it is under a distinct regulatory influence, different from the rest of the diurnal cortisol secretory cycle. Despite the difficulties associated with its measurement a range of studies have demonstrated an association between the ACR and psychosocial variables, stress and health. However it remains unclear whether positive affect and good health are consistently associated with larger or smaller awakening responses. It is early days in the search for the role and significance of the ACR. Its putative role in the regulation of physiological function across the day (e.g. the immune system) and its sensitivity to psychosocial variables make it a prime candidate as an intermediary linking mind and health.

Adrenal Cortex↗
PubMed2002

The awakening cortisol response: no evidence for an influence of body posture.

It has recently been reported that the orthostatic challenge associated with postural change from sitting to an upright position is stimulatory to the hypothalamic-pituitary-adrenal axis as evidenced by increased salivary free cortisol. This stimulatory influence is potentially a confound for the many psychoneuroendocrine studies for which salivary free cortisol is the main dependent variable. This particularly relates to laboratory psychosocial stress procedures in which subjects are invited to stand in order to deliver public speech and the studies which have explored the cortisol response to awakening in which postural shift has not been controlled for. We therefore examined, in a balanced cross over design whether the awakening cortisol response was influenced by standing, shortly after awakening or remaining supine during the response study period. In addition and in the same subjects we measured the cardiovascular response and saliva cortisol response to the orthostatic challenge of shifting from a supine to a standing position later in the diurnal cortisol cycle. The expected cortisol response to awakening was demonstrated but there was no evidence that the postural shift, supine to standing, confounded the response. This same postural shift later in the day induced the expected increase in heart rate but cortisol simply followed the circadian decline. Under the conditions of the present study we found no evidence that the postural shift supine to standing could induce a cortisol secretory episode such as to contribute towards the awakening response.

Adult↗
PubMed2002

Ultrasound measures of bone and the diurnal free cortisol cycle: a positive association with the awakening cortisol response in healthy premenopausal women.

In this study we examined the relationship between characteristics of the diurnal pattern of salivary free cortisol concentration and ultrasound (US) measures of bone in premenopausal women. Subjects were 36 healthy, eumenorrhoeic, nonsmoking women mean age (SE) 30.9 (1.3) years. Saliva samples were collected on awakening and 10, 20, 30, 120, 240, and 600 minutes thereafter. Calcaneal broadband ultrasonic attenuation (BUA) and speed of sound (SOS) were determined. Mean (SE) salivary cortisol concentration was 4.7 (0.5) nmol/l on awakening, peaked at 8.6 (0.9) nmol/l 30 min later, and declined to a trough of 2.3 (0.2) nmol/l 600 min after awakening. BUA and SOS were significantly associated with cortisol 0 and 30 min after awakening (r = 0.40 and 0.40 for BUA and 0.33 and 0.37 for SOS, respectively, with body mass included as covariate). Cortisol levels 240 and 600 min after awakening were not significantly associated with bone variables. Women above the median for peak (30 min after awakening) cortisol had significantly higher BUA and SOS than those below the median [BUA 51.8 (1.0) vs 47.4 (1.5) dB/MHz, P = 0.017; SOS 1554.0 (2.5) vs 1546.4 (1.5) m/sec, P = 0.008]. A high peak in cortisol following awakening was associated with higher US measures of bone in healthy premenopausal women. This finding suggests the possibility that diurnal variation in cortisol may have a role in bone metabolism.

Adult↗
PubMed2001

Exploration of the awakening cortisol response in relation to diurnal cortisol secretory activity.

Adrenocortical activity can be assessed by measurement of free cortisol in saliva. Cortisol status has important health implications in both physical and psychological terms. Assessment of cortisol status is complicated by the marked diurnal cortisol cycle. This cycle is characterised by an increase in secretory activity following awakening to achieve the morning acrophase. Thereafter it falls with a declining trend over the remainder of the day. For between subject studies the timing of sampling in relation to this cycle is an important consideration. We report a comprehensive study of the diurnal free cortisol cycle designed to analyse its components and to investigate their reliability and inter-relatedness. We instructed 42 healthy volunteers to collect saliva samples at home on two consecutive days. On each day the first sample was collected immediately upon awakening, followed by a further three samples at 15-minute intervals which collectively comprised the "awakening samples". A further four sample's were collected through the day at 3-hour intervals, all synchronized to awakening time. The cortisol response to awakening was calculated in two ways. Overall cortisol production in the first 45 minutes after awakening was calculated as area under the cortisol curve with reference to zero (AUC). The dynamic of the cortisol response to awakening was calculated as area under the cortisol response curve (AURC) with reference to the first awakening sample. In addition the underlying cortisol secretory activity was assessed based upon the diurnal three-hourly samples. All three parameters of adrenocortical activity showed reasonable stability across the two sampling days indicating all were reliable indexes of trait characteristic. AUC was representative of underlying diurnal activity but AURC was not. Measurement at any time point, 3, 6, 9 or 12 hours post-awakening was representative of the underlying 12-hour diurnal activity.

Adrenal Cortex↗
PubMed2001

Association between time of awakening and diurnal cortisol secretory activity.

A 12-hour diurnal profile of salivary free cortisol was measured in healthy adults (n=40) on two consecutive days. Samples were collected at timed intervals synchronised to awakening. The mean profile is characterised by a marked increase in cortisol concentration following awakening, peaking after about 30 min, and a subsequent decline over the remainder of the day. Thus two components of the diurnal cycle were examined: a) the first 45 min post-awakening (the awakening cortisol response) and b) the underlying 12 h profile from immediately until 12 h post awakening (but without the awakening response). Both of these components were analysed in two ways such as to provide an indication of overall cortisol concentration and the degree of change in cortisol concentration, i.e. the rise for the awakening response and the diurnal decline. Both components of the cortisol diurnal profile were negatively correlated with awakening time. Thus, those subjects who awoke earliest had higher levels of cortisol over the 45 min following awakening as well as throughout the rest of the day. They also displayed a more marked diurnal decline to be convergent with late awakeners at the end of diurnal measurement, 12 h following awakening. Hence the diurnal cortisol cycle, which is synchronised to awakening, is significantly related to awakening time. These findings support the notion of a close association between suprachiasmatic nucleus (SCN) control of both awakening and cortisol secretory activity.

Adult↗
PubMed2001

The impact of psychological stress on immune function in the athletic population.

In many ways, the physiological and immune consequences of acute bursts of physical exercise parallel the effect of an acute psychological stressor. Similarly, the net effects of endurance training resemble chronic psychological stress, whereas the physiological milieu associated with overtraining resembles that of melancholic depression. We suggest that the prolonged psychological stress often associated with athletic training and competition may make athletes more vulnerable to the negative health effects of training. Furthermore, a relationship between anxiety and life events on susceptibility to injury is well documented. Individual differences in self-confidence and self-esteem are also known to relate to the occurrence of injury as well as recovery from injury. We suggest that these two observations may be linked. It is the purpose of this paper to review the most recent evidence that psychological stress does impact upon the balance of the immune system in such a way as to be relevant to health outcomes and that the athletic population, in particular those with low self-esteem, may be especially vulnerable due to the probable synergistic effects of both physical and psychological stress.

Athletic Injuries↗
PubMed2000

CuZn-superoxide dismutase transgenic mice: no effect on longevity, locomotor activity and 3H-mazindol and 3H-spiperone binding over 19 months.

This study was designed to determine whether CuZn-superoxide dismutase (SOD) is neuroprotective against aging in the nigrostriatal tract. Twenty-four male mice transgenic for human CuZnSOD, resulting in overexpression of the cytosolic enzyme, were compared with 11 matched controls over 19 months. There was no difference in longevity, locomotor activity, or 3H-mazindol or 3H-spiperone binding in the nigrostriatal tract in the two groups. Thus there was no evidence that increased CuZnSOD was neuroprotective in this model.

Animals↗
PubMed2000

Endogenous monoamine oxidase inhibitory activity and HPA activation in the pig.

Previously we have shown that an increase in endogenous monoamine oxidase A inhibitory activity (MAO-AI), measured in human saliva, both precedes and predicts psychological stress-induced activation of the hypothalamic pituitary adrenal (HPA) axis, as determined by the cortisol response. We now report the relationship between endogenous MAO-AI and the cortisol response in the plasma of prepubertal pigs (n=5 or 6) under two experimental paradigms of HPA activation. In the first condition, pigs were physically restrained (snaring) for 15 minutes. Blood samples were taken from indwelling catheters at intervals before and after snaring (a sampling period of about 1 hour), and at the same time intervals on a separate day to provide baseline measures. Both cortisol concentration and percentage MAO-AI were determined in each plasma sample. There was a pronounced cortisol response on the snaring day (cortisol peaked 30 minutes after the start of the snaring). There was also a significant MAO-AI response to snaring which peaked 15 minutes after the start of the stress challenge. In the second experimental paradigm, bacterial endotoxin (LPS: 20microg/pig) was used to induce HPA activation and plasma cortisol and MAO-AI were determined. This time, however, the cortisol response was not preceded by any change in MAO-AI. We conclude that generation of MAO-AI, which is associated with HPA activation induced by psychological stress, is not a component of the pathways involved in immunological stimulation of the HPA axis.

Animals↗
PubMed2000

Modulation of secretory immunoglobulin A in saliva; response to manipulation of mood.

Secretory immunoglobulin A (sIgA) measured in saliva, an index of mucosal immunity, has repeatedly been shown to be sensitive to psychological variables. Chronic stress is downregulatory whereas an acute psychological challenge induces mobilisation. We examined whether an acute manipulation of mood to induce negative hedonic tone would be downregulatory, as in the chronic stress paradigm and further, whether induction of positive mood might have opposite effects. Two separate experiments were conducted. In the first, mood manipulation was by mental recall and in the second by music. For both sIgA concentration and sIgA secretion rate there was a significant elevation in response to the mood manipulation by recall regardless of hedonic tone. There was some evidence that for sIgA secretion rate the response was more pronounced for positive mood. Mood induction by music also resulted in significant elevations in sIgA concentration and secretion rate and responses were not distinguished by mood valence. None of the mood induction procedures was associated with changes in free cortisol. In these studies, we found no evidence that transient lowering of mood was downregulatory for salivary sIgA. The predominant finding was of sIgA mobilisation.

Adult↗
PubMed1999

The awakening cortisol response and blood glucose levels.

The hypothalamic-pituitary-adrenal axis is characterized by a marked circadian cycle with heightened activity in the morning. This is synchronized to awakening such that free cortisol increases two to three fold in the first thirty to forty five minutes following awakening -- the awakening cortisol response. It has been suggested that this activity, by mobilizing energy reserves prepares the body for the metabolic demands of the day. Similar arguments are applied to the cortisol response to psychological challenge. Paradoxically the cortisol response to a psychosocial stressor is abrogated in fasted individuals with low blood glucose. Also cortisol response to a psychosocial stressor is positively correlated to blood glucose levels after glucose load. We examined if the same relationship applies to the awakening cortisol response. There was no correlation between the cortisol response and awakening blood glucose levels. Moreover a group with mean blood glucose at the bottom of the euglycemic range, identified by split at the median for glucose level upon awakening, showed no deficit in cortisol response. Hence the physiology of the awakening response differs to that of a psychological stress response. These data challenge the view that an oxidisable substrate for energy metabolism is permissive for cortisol responses. In addition the present findings do not support a predominantly gluconeogenic role for morning cortisol activation.

Adult↗
PubMed1999

Investigation of bax-induced release of cytochrome c from yeast mitochondria permeability of mitochondrial membranes, role of VDAC and ATP requirement.

Recent studies that attempt to explore the action of pro- and anti-apoptotic proteins of the bcl2 family demonstrate the crucial role of relocalization of cytochrome c from the mitochondrial intermembrane space to the cytosol. This early event of apoptosis can be mimicked in the yeast Saccharomyces cerevisiae following expression of bax. In mammalian mitochondria, the mechanism of relocalization is thought to involve the opening of the so-called permeability transition pore. We show in this paper: (a) that bax-induced release of cytochrome c in yeast does not involve any permeability transition of the inner mitochondrial membrane but involves a general alteration of the permeability of the outer mitochondrial membrane to macromolecules. This suggests that a permeability transition of the inner mitochondrial membrane is not an event required for the relocalization of cytochrome c in yeast. (b) The outer-membrane voltage-dependent anion channel (VDAC), a putative component of the permeability transition pore, is not involved in bax-induced release of cytochrome c or in the prevention of this release by bcl-xL. (c) Bax devoid of its C-terminal putative hydrophobic alpha-helix is as efficient as full-length bax to allow the relocalization of cytochrome c, demonstrating this segment of the protein is not required for membrane-targeting. (d) We finally observe that the action of bax on the outer mitochondrial membrane requires the presence of ATP both in vitro and in vivo, and it is shown that ATP directly increases the amount of bax inserted to mitochondria.

Adenosine Triphosphate↗
PubMed1998

Under respiratory growth conditions, Bcl-x(L) and Bcl-2 are unable to overcome yeast cell death triggered by a mutant Bax protein lacking the membrane anchor.

We have reported earlier that cytosolic expression of the full-length human apoptosis inducer Bax-alpha (Bax) in the yeast Saccharomyces cerevisiae suppresses growth and induces mortality in cells containing functional mitochondria. Human Bcl-x(L) overcomes this toxicity. Here we describe that a mutant Bax protein, with a missing membrane anchor region (Bax delta), also inhibits growth and causes cell death in yeast. However, the death inhibitory proteins Bcl-x(L) and Bcl-2 fail to rescue Bax delta-mediated growth inhibition under conditions promoting respiration, although they bind Bax delta in the cell. Results in Jurkat T-cells corroborate that Bcl-x(L) is much less efficient at rescuing mammalian cells from the effect of Bax delta than from full length Bax. We have also inquired if the respiration-dependent toxicity of Bax and Bax delta in yeast is nullified by Bcl-x(L)delta and Bcl-2delta, molecules which lack membrane anchors but bind Bax in the yeast two-hybrid system. It appears that, under conditions which facilitate respiration in yeast, Bcl-x(L)delta and Bcl-2delta are incapable of rescuing both Bax-containing and Bax delta-containing cells. Our results open up the interesting possibility that there might exist proteins, unrelated to the Bcl-2 family, which could negate death induced by a membrane anchor-free form of Bax.

Amino Acid Sequence↗
PubMed1998

Regional and molecular separation of the four bioactivities of 'tribulin'.

The endocoid tribulin has four known bioactivities: monoamine oxidase A and B inhibitory activities (MAO-AI and MAO-BI) and peripheral and central benzodiazepine receptor binding inhibitory activities (PBR-I and CBR-I). Analysis of the four bioactivities in rat tissue reveals regional dissociation. Most notably liver was particularly rich in PBR-I yet contained no detectable MAO-AI. In addition we have succeeded in separating the four activities from human urine. MAO-AI and MAO-BI have greater retention on charcoal than PBR-I and CBR-I when eluted step-wise with aqueous methanol. MAO-AI can be separated from MAO-BI and in addition PBR-I can be separated from CBR-I by step aqueous methanol elution from Amberlite XAD-4. Hence we present two lines of evidence that, contrary to the original view, tribulin is composed of a number of distinct molecular components.

Adrenal Glands↗