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Biomedical subjects

S M Armstrong

Publications and source records attributed to S M Armstrong.

At least 37 records · Page 2Linked to original sources
PubMed1995

Dose dependent effects of S-20098, a melatonin agonist, on direction of re-entrainment of rat circadian activity rhythms.

The chronobiotic properties of melatonin are well documented. For example, following an 8-h phase advance of the light-dark cycle daily injections of melatonin administered at the pre-shift dark onset alter the direction of re-entrainment of rat activity rhythms. Using this 8-h phase advance paradigm, the effects of the melatonin agonist S-20098 (1 mg/kg and 3 mg/kg) on the rat circadian system were compared with those of melatonin. S-20098 altered the direction of re-entrainment in the same manner as melatonin. A study using lower doses of S-20098 showed that the effect on direction of re-entrainment was dose-dependent, with 100% of rats responding at a dose of 100 micrograms/kg. S-20098 may, therefore, have therapeutic potential as a chronobiotic in the treatment of circadian disorders in humans.

Acetamides↗
PubMed1994

Microbial degradation of phloroglucinol and other polyphenolic compounds.

Biodegradation of phloroglucinol (1,3,5-trihydroxybenzene) and other polyphenolic compounds by microbes may occur by aerobic and anaerobic metabolic pathways. Aerobic microbes may initiate the mineralization of phloroglucinol or other polyphenolics by either a reductive pathway, epoxide formation, or a specific hydroxylating mechanism. Cleavage of the various intermediates of phloroglucinol and polyphenolic degradation may occur by intradiol and extradiol mechanisms. The reductive pathway in contrast to other mechanisms utilized by aerobic microbes, seems both cumbersome and energy wasteful. The degradation of lignin and its associated phenolics follows an enzymatic combustion process which resembles a nonspecific enzyme-catalyzed burning. Anaerobic mineralization of phloroglucinol and its associated polyphenolics by several microbes seems to favour the reductive formation of a dihydrophloroglucinol (1,3-dioxo-5-hydroxycyclohexane), which is cleaved by a specific hydrolase. Mineralization of numerous other polyphenolic compounds by anaerobes seems to utilize phloroglucinol as a central metabolite.

Aerobiosis↗
PubMed1994

Circadian wheel running activity rhythms in two strains of domestic rabbit.

Results from experiments on two strains of domestic rabbit show that despite their hopping gait, circadian locomotor rhythms can be successfully measured using running wheels specially designed for large laboratory mammals. Three female rabbits of an English outbred strain were monitored in a 13:11 light:dark (LD) cycle and in constant light (LL), while 12 Dutch-Himalayan rabbits were monitored in a 14:10 LD cycle and constant dark (DD). Much stronger rhythms were observed in the latter strain, which under LD conditions showed individuals with patterns that varied from nocturnal (n = 5), diurnal (n = 4), crepuscular (n = 1), and predominantly arrhythmic (n = 2). In DD, 10 rabbits showed strong free-running rhythms, five with tau (tau) less than 24 h and five longer. The predominantly arrhythmic activity pattern in the remaining two made estimation of tau difficult. Differences in circadian patterns both under LD and DD were unrelated to sex. Results show that locomotor rhythms of the rabbit can be measured using the running wheel, the traditional apparatus of chronobiology. However, the experiments suggest also that the large-bodied breed of rabbits that tend towards obesity, such as the English outbred strain, are relatively inactive and that smaller, more active breeds such as the Dutch-Himalayan may be more suitable for studying circadian rhythmicity if the running wheel is employed.

Animals↗
PubMed1994

Seasonality in panic disorder.

Following a clinical observation of increased anxiety symptoms and mood changes during winter in panic disorder patients, the Seasonal Pattern Assessment Questionnaire (SPAQ) was completed by 133 patients. Global Seasonality Scores (GSS), and the prevalence of Seasonal Affective Disorder (SAD), were significantly higher than reported in general population studies. Seasonal changes were also found in anxiety and panic attacks. These findings suggest the possibility of a common aetiology for panic disorder and SAD, that seasonality may be a far more general phenomenon in psychopathology, and that light therapy may be a useful treatment for some panic disorder patients.

Adult↗
PubMed1994

Sleeping patterns during pregnancy in Japanese women.

Although sleep disturbance is commonly reported in pregnancy, there have been few studies on sleep characteristics in pregnancy. In this study, all women attending the antenatal clinic at Sapporo Medical College Hospital for 1 month during autumn and 3 months during winter were surveyed with a questionnaire and sleep log. Of the 192 patients, 169 (88.0%) stated that sleep was altered from their usual experience. A principal components analysis identified three sleep factors from the ten items in the measure of sleep used (Sleep Log). The three factors were: Sleep Duration and Quality, Insomnia and Daytime Alertness. Although no significant differences across trimesters were found on the three sleep factors, Sleep Duration and Quality, and Insomnia were worst during the first trimester. Sleep normalized in the second trimester, but the third trimester was characterized by increased Insomnia and decreased Daytime Alertness. The most frequent reasons cited by women for sleep alterations were urinary frequency, backache or ache in the hips and fetal movement. Contingency X2 analyses were used to investigate a relationship between the frequency of reporting the reasons and the trimester of pregnancy. Significant increases were found in reporting as the reasons for sleep difficulties, fetal movement in the third trimester, and heartburn, nausea and vomiting in the first trimester. The description of sleep patterns during pregnancy has clinical relevance as sleep alterations in pregnancy are common.

Adult↗
PubMed1993

Successful use of S20098 and melatonin in an animal model of delayed sleep-phase syndrome (DSPS).

In human delayed sleep-phase syndrome (DSPS), sleep onset and wake times occur far later than normal. In the population, DSPS may be an important contributor to complaints of sleep onset insomnia. We previously reported an animal model of DSPS in laboratory rats in which the onset of nocturnal activity is delayed by several hours [negative phase angle difference (PAD)]. The effect of melatonin 1 mg/kg SC and S20098 (Servier) 1 and 3 mg/kg on the negative PAD was investigated over 22 days of injections. In comparison to control injections of dimethylsulfoxide (DMSO), both melatonin and S20098 over approximately 9 days phase advanced the onset of activity toward the onset of darkness. At cessation of injections, activity onset delayed over approximately 11 days back toward, but as a group did not reach the original PAD. This effect of melatonin on the phase angle of entrained rats is consistent with its effects on delayed sleep in humans. It is likely, therefore, that S20098 may be of use to ameliorate DSPS in humans.

Acetamides↗
PubMed1993

Melatonin and hormonal changes in disturbed sleep during late pregnancy.

Although sleep disturbance is commonly reported in pregnancy, there have been surprisingly few studies on the etiology of this condition. Since most hormones show circadian rhythmicity and maintain specific phase relationships with that of the sleep-wake cycle, it was of interest to establish whether sleep disturbances covaried with endocrine changes. This overnight study of pregnant women compared melatonin, cortisol, and prolactin secretion rhythms in six good sleepers and six poor sleepers. The groups were compared by ratios of the areas under the various hormonal curves. Significant differences in the cortisol/melatonin ratio were found between the poor sleeper group (lower values) and the good sleeper group (higher values). Nonsignificant trends, which might be expected to become significant with larger sample sizes, were found for decreased amplitude in the cortisol rhythm and increased amplitude in the melatonin rhythm in poor sleepers. The decreased amplitude of the cortisol rhythm in poor sleepers appeared to be due to a suppression of the early morning (0500-0800) rise. Prolactin levels were high and showed no rhythmicity in both groups. These differences may reflect changes in the circadian pacemaker system of poor sleepers, with increases in melatonin release being a response to counteract poor sleep.

Adult↗
PubMed1993

Limited effect of three types of daily stress on rat free-running locomotor rhythms.

The effects of three types of stress/arousal on rat free-running circadian locomotor rhythms in constant darkness were investigated over a 93-day treatment period. Rats were subjected to 30-min daily immobilisation stress or 30-min novelty or to brief handling (n = 10/group). Seven of the 30 rats exhibited some changes in circadian parameters. Three rats (two immobilised, one handling) showed entrainment, three rats (one from each group) showed a change in tau, and one rat (novelty) showed a phase advance. Thus, in total, 30% immobilisation, 20% percent novelty, and 20% handled rats showed circadian changes. These group changes paralleled changes in faecal boli and body weight, which were taken as indirect indices of the level of stress. Five of the seven changes took place when the end of the active phase (alpha), i.e., subjective dawn, coincided with the time of treatment and the other two when the onset of sigma, i.e., subjective dusk, coincided. Rat circadian locomotor rhythms appear much less susceptible to stress/arousal than those reported for hamsters.

Animal Husbandry↗
PubMed1993

Alterations to plasma melatonin and cortisol after evening alprazolam administration in humans.

Six healthy volunteers were given a 2-mg dose of alprazolam at 21:00 h and hourly blood samples were collected until 08:00 h the following morning. A control night of hourly blood sampling was undertaken 7 days before Plasma was analyzed for melatonin, cortisol, and alprazolam concentrations. Melatonin concentrations were significantly suppressed by alprazolam at 23:00, midnight, 01:00, 06:00, and 07:00 h. A trend toward suppression was evident from 02:00 to 05:00 h. Cortisol concentrations were also suppressed by alprazolam at several times throughout the night (01:00-04:00 h). Plasma alprazolam levels showed a peak at 3 h and remained relatively high 19-20 h after the dose. The significance of melatonin suppression by alprazolam is discussed in terms of benzodiazepine binding sites and GABA minergic transmission in the human pineal gland, suprachiasmatic nuclei, and retina. Plasma cortisol suppression has been reported for other benzodiazepine drugs, but conflicting data exist for alprazolam. The present results do not support the proposed inhibitory effect of melatonin on the hypothalamic-pituitary-adrenal (HPA)-axis. It is suggested that there is no simple direct relationship between melatonin and the HPA axis in humans.

Adult↗
PubMed1991

Melatonin: a chronobiotic with anti-aging properties?

Recently, it has been reported that melatonin administration extends the lifespan of mice, a finding which supports previous research on the effects of pinealectomy and pineal extract administration. The prolongation of lifespan by melatonin has been interpreted in favour of an upregulation of the immune system as well as due to anti-stress properties of melatonin acting via the brain opioid system. In this paper we offer an alternative explanation of melatonin's anti-aging effect: the circadian pacemaker system has a diminished amplitude with age as indexed by a decrease in circulating melatonin levels. Stability of the circadian system correlates with its amplitude and loss of circadian amplitude produces lability which, in turn, leads to internal temporal disorder. Internal temporal disorder may be a precursor of disease states. Exogenous melatonin increases the amplitude of the circadian pacemaker system by feedback onto that system. The hypothalamic suprachiasmatic nuclei are thought to be the mammalian biological clock in the brain and have high concentrations of melatonin receptors. Therefore, melatonin administration in pharmacological doses may prevent aging symptoms by acting at the level of the circadian pacemaker's amplitude.

Aging↗
PubMed1991

Restricted feeding entrains circadian wheel-running activity rhythms of the kowari.

The effect of daily restricted feeding (RF) on the circadian wheel-running rhythms of the kowari, Dasyuroides byrnei, was examined in two experiments. Kowaris were presented with a preferred food (determined in a pilot study) during a daily 2-h meal in the light period of a 14:10 light-dark (LD) cycle (expts 1 and 2), during constant dark (DD) immediately after termination of the LD cycle (expt 1), and during DD when kowaris were free running (expt 1). Results showed that 1) RF elicited anticipatory activity similar in duration and phasing to that observed in the rat; 2) cycles of meal-associated activity free ran for up to 6 days after the termination of RF; 3) activity persists at a phase near that of the former mealtime during periods of food deprivation; and 4) activity indicative of beating between two pacemakers occurred when feeding was restricted to the L period of LD cycles. Together these observations suggest that the activity rhythms of the kowari may be controlled by separate, but possibly coupled, light-entrainable and food-entrainable pacemakers, as are those of the rat.

Activity Cycles↗
PubMed1990

A portable light source for bright light treatment.

A novel, portable, inexpensive bright light source is described. This unit, which has been demonstrated to exhibit physiological effects similar to those of the more conventional light boxes, offers a less restrictive home treatment for patients with seasonal affective disorder and sleep disorders.

Adult↗
PubMed1990

Plasma concentrations of melatonin in panic disorder.

Nocturnal plasma melatonin concentrations were measured in seven patients with panic disorder and eight healthy control subjects. The five patients who had never received psychotropic medication had significantly greater melatonin concentrations from 4:00 a.m. to 7:00 a.m. than the control subjects. In addition it is possible that a phase delay occurred in these unmedicated patients. The findings are discussed in terms of previous studies showing increased melatonin in manic patients and the effect of intense stress on melatonin synthesis. The two patients who had been medication free for only 1 week showed a decreased melatonin rhythm, which is consistent with previous findings in medicated patients.

Adult↗
PubMed1989

Melatonin and circadian control in mammals.

Although pinealectomy has little influence on the circadian locomotor rhythms of laboratory rats, administration of the pineal hormone melatonin has profound effects. Evidence for this comes from studies in which pharmacological doses of melatonin are administered under conditions of external desynchronization, internal desynchronization, steady state light-dark conditions, and phase shifts of the zeitgeber. Taken together with recent findings on melatonin receptor concentration in the rat hypothalamus, particularly at the level of the suprachiasmatic nuclei, these results suggest that melatonin is a potent synchronizer of rat circadian rhythms and has a direct action on the circadian pacemaker. It is possible, therefore, that the natural role of endogenous melatonin is to act as an internal zeitgeber for the total circadian structure of mammals at the level of cell, tissue, organ, whole organism and interaction of that organism with environmental photoperiod changes.

Animals↗
PubMed1989

Quantal melatonin suppression by exposure to low intensity light in man.

Plasma melatonin concentrations were examined following three relatively low intensities of artificial light. Six normal, healthy control subjects were all exposed to (a) 200 lux, (b) 400 lux and (c) 600 lux for a three hour duration from midnight to 0300 h. Blood was also collected on a control night where light intensity was less than 10 lux throughout. Significant suppression of melatonin was observed following light of 400 lux and 600 lux intensity when compared to the control night (p less than 0.05; Mann-Whitney U-test). 200 lux light did not produce a statistically significant melatonin suppression when compared with control samples. Each light intensity produced its own individual maximal melatonin suppression by one hour of exposure. Increased duration of exposure to the light had no further influence on melatonin plasma concentrations. These data confirm a dose response relationship between light and melatonin suppression, and indicate that there is no reciprocal relationship between the effects of light intensity and the duration of exposure on maximal melatonin suppression in man.

Adult↗
PubMed1989

Phase-response curve to 1-hour light pulses for the marsupial, Dasyuroides byrnei.

Most Australian marsupials are nocturnal and consequently it might be expected that the circadian system of this group may be similar to the circadian system of nocturnal rodents. Ten male kowaris (Dasyuroides byrnei) were allowed to free-run in constant darkness and were subsequently administered 1-hour light pulses (1000 lux) at known circadian times in their cycles at intervals of greater than 2 weeks. Changes in the phase of the kowari's circadian rhythm of wheel-running were measured when their rhythms reached a new steady-state after each light pulse and these data were used to construct a phase-response curve to light for the species. The kowari PRC exhibited essentially the same characteristics as those reported for the nocturnal rodents and the marsupial species Sminthopsis macroura. It appears that the kowari entrains its circadian rhythms to light/dark cycles via the discrete phase shifting mechanism as described in nocturnal rodents.

Animals↗
PubMed1989

Human melatonin response to light at different times of the night.

Normal control subjects were examined on three separate occasions with light of sufficient intensity to suppress nocturnal plasma melatonin concentrations. One hour of light was given at each of the following times: (a) 2100-2200h; (b) midnight to 0100h; (c) 0400-0500h. Melatonin synthesis was just becoming apparent at 2100h. There was significant suppression of melatonin by light when given at midnight-0100h and 0400-0500h, but not when light was given at 2100-2200h. In each case following light, melatonin synthesis was shown to resume, even after light applied in the second half of the dark period (0400-0500h). A second experiment was undertaken to examine a possible "rebound" in melatonin levels following light given at 2100-2200h. Six further control subjects were exposed to light at this time, and plasma melatonin levels were measured until 0400h. No rebound in melatonin concentrations was observed. These results are compared with other studies of melatonin response to evening light exposure.

Adult↗