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O Van Reeth

Publications and source records attributed to O Van Reeth.

At least 37 records · Page 2Linked to original sources
PubMed1997

Comparative effects of a melatonin agonist on the circadian system in mice and Syrian hamsters.

S-20098 has potent and specific agonist properties on melatonin receptors both in vitro and in vivo. Behavioral studies on rodents already showed that repeated intraperitoneal administration of S-20098 could dose-dependently alter the functioning of the circadian clock. To determine whether single administration of S-20098 could alter the circadian rhythms of rodents, we first used the phase-response curve (PRC) approach in two different species: Syrian hamsters and mice (C3H/HeJ). Our results show that the shape, circadian times and extent of the PRC to S-20098 look very similar in mice and hamsters. In both species, the phase advance portion of the PRC to S-20098 is limited to a 3 h window preceding the onset of locomotor activity, but the magnitude of phase shifts is larger in mice. We also tested the phase shifting effects of increasing doses of S-20098 during the interval of maximal sensitivity to this compound. Treatment with S-20098 induces dose-dependent phase shifts, with maximal shifts observed after injections of 20 and 25 mg/kg S-20098 i.p., respectively, in mice and hamsters. Those results are in agreement with the limited distribution of melatonin-binding sites within the circadian clock of adult Syrian hamsters, as compared to other rodents.

Acetamides↗
PubMed1997

Sleepiness, performance, and neuroendocrine function during sleep deprivation: effects of exposure to bright light or exercise.

The temporal profiles of subjective fatigue (as assessed by the Stanford Sleepiness Scale), of cognitive performance (on a digit symbol substitution test and a symbol copying task), of body temperature, and of the peripheral concentrations of melatonin, thyroid-stimulating hormone (TSH), and cortisol were obtained simultaneously at frequent intervals in 17 normal young subjects submitted to a 43-h period of constant routine conditions involving continuous wakefulness at bed rest in dim indoor light. The subjects had knowledge of time of day. Caloric intake was exclusively in the form of an intravenous glucose infusion, and plasma glucose levels were monitored continuously in 8 of the 17 subjects. Under these conditions, fluctuations in plasma glucose reflect primarily changes in glucose use because endogenous glucose production is suppressed by the exogenous infusion. Following the completion of a baseline constant routine study, the volunteers participated in two subsequent studies using the same protocol to determine the immediate psychophysiological effects of exposure to a 3-h pulse of bright light or to a 3-h pulse of physical exercise. Sleepiness and performance varied in a mirror image, with significant negative correlations. Sleepiness scores were minimal around noon and then increased at a modest rate throughout the rest of the normal waking period. Staying awake during usual bedtime hours was associated with an acceleration in the rate of increase in sleepiness, which coincided with decreasing body temperature, rapidly rising cortisol concentrations, and maximal levels of melatonin and TSH. When body temperature reached its nadir, a further major increase in sleepiness occurred in parallel with a pronounced decrease in plasma glucose (reflecting increased glucose use). Recovery from maximal sleepiness started when blood glucose levels stopped falling and when significant decreases in cortisol and melatonin concentrations were initiated. Lower levels of subjective sleepiness resumed when glucose concentrations and body temperature had returned to levels similar to those observed prior to sleep deprivation and when melatonin and TSH concentrations had returned to daytime levels. The synchrony of behavioral, neuroendocrine, and metabolic changes suggests that circulating hormonal levels could exert modulatory influences on sleepiness and that metabolic alterations may underlie the sudden increase in fatigue consistently occurring at the end of a night of sleep deprivation. Effects of bright light or exercise exposure on subjective sleepiness appeared to be critically dependent on the timing of exposure.

Adult↗
PubMed1995

Alterations in the circadian system in advanced age.

In addition to light, a variety of non-photic stimuli can induce phase shifts in the circadian clock of rodents. We have examined the effects of advanced age on the response of the circadian clock to both photic and non-photic stimuli in old hamsters (i.e., over 16 months of age). Among the age-related changes in the circadian rhythm of locomotor activity are: (1) alterations in the phase angle of entrainment to the light-dark cycle; (2) an altered response to the phase-shifting effects of light pulses; (3) changes in the time it takes to re-entrain to a new light-dark cycle; and (4) a loss of responsiveness to the phase-shifting or entraining effects of stimuli which induce an acute increase of activity. Many of the effects of ageing on the circadian clock system can be simulated in young animals by depleting brain monoamine levels, suggesting that ageing alters monoaminergic inputs to the clock. Some of the age-related changes in the response of the clock to an activity-inducing stimulus can be reversed by implanting old animals with fetal suprachiasmatic nuclear tissue. Determining the physiological basis of age-related changes in the responsiveness of the clock to both internal and external stimuli, and the mechanisms by which normal circadian functioning can be restored, should lead to new insight into the functioning of the circadian clock and may suggest new approaches to the normalization of disturbed circadian rhythms.

Aging↗
PubMed1994

Grafting fetal suprachiasmatic nuclei in the hypothalamus of old hamsters restores responsiveness of the circadian clock to a phase shifting stimulus.

In the present study, 18-25-month-old hamsters free-running in constant dim light were injected, both before and after receiving fetal grafts containing either cerebellar tissue or the suprachiasmatic nuclei (SCN), with a dose of triazolam given at a time known to reliably phase shift the rhythm of locomotor activity in young hamsters. SCN-grafted animals, but not control animals implanted with fetal cerebellar tissue, showed a significantly greater response to the phase shifting effects of triazolam, demonstrating that at least some age-related changes in the circadian system can be reversed by neuronal transplantation. These results raise the possibility that neuropharmacological interventions that can simulate the effects of fetal SCN grafts might be useful in the treatment of age-related disorders in circadian function.

Aging↗
PubMed1994

Demonstration of rapid light-induced advances and delays of the human circadian clock using hormonal phase markers.

To determine the magnitude and direction of phase shifts of human circadian rhythms occurring within 1 day after a single exposure to bright light, plasma thyrotropin, melatonin, and cortisol levels and body temperature were monitored for 38 h in 17 men who were each studied two times, once during continuous dim light conditions and once with light exposure. After a period of entrainment to a fixed sleep-wake cycle, a 3-h light pulse (5,000 lux) was presented under constant routine conditions, and the resultant phase shifts were measured, also under constant routine conditions, on the 1st day after pulse presentation. The phase shifts in response to light occurred within 24 h and were in the delaying direction for most of the nocturnal period, with the crossover to phase advances occurring approximately 1 h after the temperature minimum. Phase shifts averaged 1 h, with delays being larger than advances, and were achieved without significant changes in rhythm amplitude. The immediate response of the human circadian clock to a single 3-h light pulse is thus characteristic of "type 1" resetting.

Adult↗
PubMed1994

Nocturnal exercise phase delays circadian rhythms of melatonin and thyrotropin secretion in normal men.

To determine whether a single episode of physical activity is capable of inducing rapid phase shifts in human circadian rhythms, 17 subjects were studied two times under constant routine conditions, once in the absence of stimulus and once with a 3-h nighttime pulse of exercise interrupting the constant routine conditions. The profiles of plasma cortisol, thyrotropin (TSH), and melatonin and of body temperature were monitored continuously to derive estimations of circadian phase position. The phase shifts were measured on the 1st day after exercise exposure. The timing of the exercise period ranged from -5 h to +4 h around the time of the minimum body temperature rhythm. Nighttime exercise was associated with 1- to 2-h phase delays of both the melatonin and TSH rhythms, with the size of the delays tending to be smaller when the exercise was presented in the latter part of the nighttime period and in the early morning. These data demonstrate that nonphotic stimuli may exert phase-shifting effects on the human circadian pacemaker.

Adult↗
PubMed1994

Daily exposure to a nonphotic stimulus can alter photoperiodic response to short days in hamsters.

The ability of mammals to measure seasonal changes in daylength depends upon a circadian clock and the phase-relationship between this clock and the light: dark cycle. Recently, a number of pharmacological and nonpharmacological stimuli have been shown to have pronounced effects on the phase of the circadian clock of rodents. The objective of the present study was to determine if a drug-induced change in the phase-relationship between a measurable circadian rhythm (i.e., wheel running behavior) and the light:dark cycle would alter the effects of the light cycle on the neuroendocrine-gonadal axis. Adult male hamsters with regressed testes due to exposure to an inhibitory 10:14-hr light:dark cycle were daily injected with vehicle or the short-acting benzodiazepine, triazolam, while remaining on short days, while a control group of hamsters was transferred to a photostimulatory 14:10-hr light:dark cycle. Two other groups of hamsters with regressed testes were blinded and daily injected with vehicle or triazolam. The injections were timed to occur about 4 hr before activity onset because previous studies had demonstrated that injections of triazolam at this time can lead to a phase advance in the activity rhythm. The circadian rhythm of wheel running behavior was measured in all the animals maintained on the 10:14-hr light:dark cycle in order to monitor circadian phase. While no testicular growth was observed after 25 days of vehicle injections, growth was observed in the triazolam-treated animals that was comparable to that observed in control animals transferred to long days. Testicular growth in triazolam-treated animals was associated with an earlier onset of locomotor activity, when compared with the vehicle-treated animals. Importantly, triazolam had no effect on the testicular size of blind animals. These results indicate that daily injections of triazolam can stimulate neuroendocrine-gonadal activity by altering the phase-relationship between the cycle and the circadian clock involved in photoperiodic time measurement, and that agents which can affect the clock may be useful in altering seasonal cycles.

Animals↗
PubMed1993

Fos protein expression in the circadian clock is not associated with phase shifts induced by a nonphotic stimulus, triazolam.

Recent studies have shown that light-induced phase shifts of the circadian rhythm of locomotor activity are associated with c-fos expression in the suprachiasmatic nucleus (SCN) and intergeniculate leaflet (IGL) of the lateral geniculate nucleus of rodents. In order to determine whether c-fos expression is necessary for the phase shifting effects of a non-photic stimulus, we assessed Fos-like immunoreactivity (Fos-lir) in the SCN and IGL at various times after an injection of the short-acting benzodiazepine, triazolam, at circadian time (CT) 6; i.e. at a time when triazolam induces an acute increase in locomotor activity and maximal phase advances in the circadian rhythm of locomotor activity. Specific Fos-lir staining was not observed in the SCN or IGL regions of any animals treated with triazolam or vehicle at any time point examined. These results indicate that exposure to an activity-inducing stimulus at circadian times when this stimulus induces phase shifts does not induce Fos protein synthesis in the SCN or IGL regions.

Amino Acid Sequence↗
PubMed1993

Aging alters the entraining effects of an activity-inducing stimulus on the circadian clock.

In young hamsters, a single injection of the short-acting benzodiazepine, triazolam, can induce permanent phase shifts in the circadian clock, while repeated injections of triazolam entrain the circadian clock to the period of the injections. Triazolam appears to act on the circadian clock by inducing an acute increase in the activity of the animals, which in turn phase-shifts the circadian clock. Surprisingly, single injections of benzodiazepines do not phase-shift the activity rhythm of old hamsters, despite the fact that such treatment induces similar acute changes in the activity state of young and old animals. We compared the entraining effects of repeated injections of triazolam on the circadian clock of young and old hamsters; while six out of seven young hamsters were entrained to the triazolam injections, only one out of seven old animals was entrained by this treatment. Three of the remaining six old hamsters showed a lengthening of the activity rhythm, while no consistent effect on the period of the activity rhythm was observed in the remaining three old animals. These results indicate that the circadian system of old hamsters becomes selectively unresponsive to synchronizing signals mediated by the activity-rest state, and suggest that aging is associated with a weakened coupling between the activity-rest cycle and the circadian clock.

Aging↗
PubMed1993

Preliminary studies on the immediate phase-shifting effects of light and exercise on the human circadian clock.

The aim of the present research was to determine the magnitude and direction of immediate phase shifts of human rhythms following a single exposure to a 3-hr pulse of bright light or physical activity. The pulse of light or activity was presented under "constant-routine" conditions, and measurements of the resultant phase shifts were performed under the same constant-routine conditions on the first day following pulse presentation. Four overt rhythms that are strongly dependent on circadian timing--namely, the rhythms of plasma cortisol, plasma thyroid-stimulating hormone (TSH), plasma melatonin, and body temperature--were monitored. The analysis of the TSH profiles indicated that exposure to light at about the time of the minimum of body temperature resulted in phase advances averaging less than 1 hr in magnitude. Exposure to light approximately 3 hr before the time of the minimum of body temperature resulted in phase delays of 1-2 hr. Preliminary analyses of the melatonin profiles have confirmed these observations. Our findings regarding the effects of exercise are still inconclusive.

Adult↗
PubMed1992

Aging alters feedback effects of the activity-rest cycle on the circadian clock.

Two different stimuli (i.e., benzodiazepines and dark pulses) inducing phase shifts in the circadian clock of young hamsters through changes in the level of activity do not induce phase shifts in old hamsters, despite the fact that these stimuli induce a similar acute change in locomotor activity in young and old animals. In contrast, old hamsters remain sensitive to the phase-shifting effects of stimuli clearly not associated with any change in locomotor activity (i.e., protein synthesis inhibitors or light). Thus the circadian system of old animals becomes selectively unresponsive to synchronizing signals mediated by the activity-rest state of the animals. Previous age-related changes in circadian rhythmicity that have been observed in mammals, including humans, may be related to a weakened coupling between the activity-rest cycle and the circadian clock.

Activity Cycles↗
PubMed1992

Changes in the phase response curve of the circadian clock to a phase-shifting stimulus.

Experiments were conducted in hamsters to determine whether the phase response curve (PRC) to injections of the short-acting benzodiazepine triazolam is a fixed or a labile property of the circadian clock. The results indicated that (1) both the shape and the amplitude of the PRC to triazolam generated on the first day of transfer from a light-dark cycle (LD 14:10) to constant darkness (DD) (i.e., PRCLD) were different from those of the PRC generated after many days in DD (PRCDD); and (2) the phase-shifting effects of triazolam on the activity rhythms of hamsters transferred from LD 14:10 or 12:12 to DD changed dramatically within the first 8-9 days spent in DD. In an attempt to accelerate the resynchronization of the circadian clock of hamsters subjected to an 8-hr advance in the LD cycle, triazolam was given to the animals at a time selected on the basis of the characteristics of PRCLD. The activity rhythms of five of eight triazolam-treated animals were resynchronized to the new LD cycle within 2-4 days after the shift, whereas those of most of the control animals were resynchronized 21-29 days after the shift. These findings suggest that attempts to use pharmacological or nonpharmacological tools to phase-shift circadian clocks under entrained conditions should take into account information derived from PRCs generated at the time of transition from entrained to free-running conditions.

Animals↗
PubMed1991

The effects of short periods of immobilization on the hamster circadian clock.

Recent findings indicate that stimuli which induce an acute increase in locomotor activity can induce phase shifts in the circadian clock of hamsters. Support for the actual role of the acute increase in activity in the mediation of these phase shifts is provided by the observation that immobilization can totally block phase shifts in the activity rhythm that are normally induced in response to exposure to two of these stimuli, either a pulse of darkness or an injection of a benzodiazepine. In order to further examine the effects of immobilization on the circadian system of hamsters, 3 studies were carried out. In a first study, the effects of a 3-h period of immobilization procedure on the phase of the free running circadian rhythm of locomotor activity were tested at 8 different circadian times. Immobilization during the highly active part of the animal's activity cycle resulted in phase delays in the activity rhythm, while immobilization at other circadian times had little or no effect on the circadian time-keeping system. In two other studies, we reported that immobilization had no effect on phase shifts normally induced by 3-h pulses of light or injections of the protein synthesis inhibitor, cycloheximide, two stimuli that are clearly not associated with an increase in locomotor activity in hamsters. Thus, the ability of immobilization to block stimulus-induced phase shifts in the circadian clock appears to be specific to those stimuli that induce an acute increase in locomotor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of amiodarone on serum T3 and T4 concentrations in hyperthyroid patients treated with propylthiouracil.

Amiodarone (Cordarone) has been proven to be useful in the management of atrial fibrillation. However, because of a large iodine content, this drug is not used in this complication of thyrotoxicosis. We previously have observed a greater fall in serum T3 and T4 concentrations in hyperthyroid patients treated with amiodarone and methimazole than with methimazole alone. In the present study, we determined whether the addition of amiodarone to propylthiouracil (PTU) could improve the levels of circulating thyroid hormones in hyperthyroid patients, and we assessed the release of iodide from amiodarone by measuring the 24 h urinary iodine excretion. Twelve hyperthyroid patients were treated either with PTU, 600 mg daily for 10 days (group PTU), or with amiodarone (A), 1200 mg daily for 3 days in addition to PTU (group A-PTU). Basal serum T4, T3, and rT3 concentrations (mean +/- SEM) were respectively 206 +/- 13 nmol/L, 5.13 +/- 0.8 nmol/L, and 81 +/- 7 ng/dL for group PTU and 238 +/- 39 nmol/L, 4.73 +/- 1.06 nmol/L, and 84 +/- 12 ng/dL for group A-PTU (NS). In group A-PTU, plasma amiodarone peaked on day 3 (mean +/- SEM: 0.48 +/- 0.11 mg/L), and urinary iodine reached 5.27 +/- 1.28 mg/day on day 5. The fall in serum T3 and the increase in serum rT3 concentrations were significantly greater in group A-PTU than in group PTU (ANOVA, p less than 0.05). In group A-PTU, the minimal serum T3 concentration was observed on day 5 of treatment (28 +/- 6% of the pretreatment values).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Daily injections of triazolam induce long-term changes in hamster circadian period.

Previous experiments in hamsters indicate that daily injections of the short-acting benzodiazepine, triazolam, can entrain the free-running circadian activity rhythm to the period of the injections and that, after discontinuation of triazolam injections, the period of the free-running activity rhythm remains close to that of the previous injection schedule for 20-50 cycles. In this paper, we extend these findings and demonstrate that 1) long-term treatment with triazolam can induce aftereffects on the period of the circadian clock underlying the activity rhythm that can last for up to 100 days, 2) triazolam-induced changes in period can lead to a loss of effect of daily injections of triazolam which can be restored if the time of injection is altered, and 3) chronic treatment with triazolam also alters the period of the circadian clock in animals entrained to a light-dark cycle, and such changes in period alter the phase relationship between the circadian clock and the entraining light-dark cycle.

Activity Cycles↗
PubMed1989

Stimulated activity mediates phase shifts in the hamster circadian clock induced by dark pulses or benzodiazepines.

A number of environmental and pharmacological stimuli capable of inducing phase shifts and/or period changes in the circadian clock of mammals have now been identified. Agents that can alter circadian clocks provide a means for investigating the cellular and neural mechanisms responsible for their generation, regulation and entrainment. Two stimuli that have been used to probe the basis of circadian rhythmicity are pulses of darkness on a background of constant light and injections of short-acting benzodiazepines, such as triazolam. Surprisingly, these two very different stimuli have remarkably similar phase-shifting effects on the circadian clock of hamsters. The observation that a short-term increase in locomotor activity occurs when the circadian activity rhythm of hamsters is shifted by dark pulses or triazolam injections, coupled with the finding that activity bouts themselves are capable of shifting this rhythm, raises the possibility that dark pulses or triazolam alter the circadian clock by inducing acute hyperactivity. Here we demonstrate that the phase-advancing and phase-delaying effects of dark pulses or triazolam on the circadian activity rhythm can be totally suppressed by immobilization of the animals during treatment. These results indicate that behavioural events mediate the phase-shifting effects of both dark pulses and triazolam on the circadian activity rhythm and question present hypotheses regarding the pathways by which light-dark information and pharmacological agents influence circadian pacemakers.

Activity Cycles↗
PubMed1989

Rapid correction of hyponatraemia with urea may protect against brain damage in rats.

1. Rapid correction of hyponatraemia in humans has been reported to be associated with central pontine myelinolysis (CPM). In patients with hyponatraemia related to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) we have rapidly corrected hyponatraemia by using urea, without observing clinical CPM. This led us to analyse the brain damage induced by hypertonic saline and by urea when used for the correction of hyponatraemia in a rat model of SIADH. 2. Severe hyponatraemia (serum Na+ less than 115 mmol/l) was produced in 28 rats. Seven rats were excluded from statistical analysis because they died during the correction of hyponatraemia, or because they were under- or over-corrected. Normalization of serum Na+ (135-146 mmol/l) was obtained in 48 h by hypertonic saline (group I, n = 7) or urea (group II, n = 8). 3. Despite similar correction of serum Na+ at 24 h and 48 h, all the rats treated with hypertonic saline presented severe brain damage, whereas those treated with urea were free of any brain damage. A third group of rats (n = 6) who spontaneously corrected their serum sodium level and presented mild hyponatraemia at 48 h (129 +/- 5.2 mmol/l) were also free of any brain damage.

Animals↗