Synchronisation of a Disturbed Sleep-Wake Cycle in a Blind Man by Melatonin Treatment

Arendt, Joséphine; Aldhous, M.; Wright, Jeremy

doi:10.1016/s0140-6736(88)91586-3

Cited by 187 publications

(78 citation statements)

References 6 publications

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“…Nonphotic stimuli have been reported to exert a small but significant synchronizing effect on the human circadian system in both sighted (32,33) and blind (34,35) subjects. Therefore, in our protocol, we cannot exclude that nonphotic cues, such as showers (pulses of temperature), meals, and sleep-wake schedule, exerted a weak synchronizing effect on the clock.…”

Section: Discussionmentioning

confidence: 99%

Entrainment of the human circadian pacemaker to longer-than-24-h days

Gronfier

Wright

Kronauer

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

185

143

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Entrainment of the circadian pacemaker to the light:dark cycle is necessary for rhythmic physiological functions to be appropriately timed over the 24-h day. Nonentrainment results in sleep, endocrine, and neurobehavioral impairments. Exposures to intermittent bright light pulses have been reported to phase shift the circadian pacemaker with great efficacy. Therefore, we tested the hypothesis that a modulated light exposure (MLE) with bright light pulses in the evening would entrain subjects to a light:dark cycle 1 h longer than their own circadian period ( ). Twelve subjects underwent a 65-day inpatient study. Individual subject's circadian period was determined in a forced desynchrony protocol. Subsequently, subjects were released into 30 longer-than-24-h days (daylength of ؉ 1 h) in one of three light:dark conditions: (i) Ϸ25 lux; (ii) Ϸ100 lux; and (iii) MLE: Ϸ25 lux followed by Ϸ100 lux, plus two 45-min bright light pulses of Ϸ9,500 lux near the end of scheduled wakefulness. We found that lighting levels of Ϸ25 lux were insufficient to entrain all subjects tested. Exposure to Ϸ100 lux was sufficient to entrain subjects, although at a significantly wider phase angle compared with baseline. Exposure to MLE was able to entrain the subjects to the imposed sleep-wake cycles but at a phase angle comparable to baseline. These results suggest that MLE can be used to entrain the circadian pacemaker to non-24-h days. The implications of these findings are important because they could be used to treat circadian misalignment associated with space flight and circadian rhythm sleep disorders such as shiftwork disorder.light ͉ melatonin ͉ phase angle of entrainment ͉ phase response curve ͉ sleep Entrainment of a circadian rhythm by a zeitgeber fulfills biological purpose in providing a very distinct phase relationship between the periodicity of the organism and that of the environment.J. Aschoff (1) T o be of functional significance for the organism, circadian rhythms must be entrained to the 24-h day. For nearly all species studied, the light:dark cycle is the most powerful circadian synchronizer. The resetting capacity of light depends on its intensity, timing, duration, temporal pattern, and spectral composition (2-7). In totally blind people, the circadian timekeeping system often loses synchrony with the earth's 24-h light:dark cycle (8). Well described in animals (9-11) and only recently confirmed in humans (12), entrainment of the circadian system depends on (i) its intrinsic period ( ), (ii) the light:dark cycle to which it is exposed (T; T-cycle), and (iii) the strength of the entraining stimulus (zeitgeber, from German for "time giver"). The generally accepted nonparametric model of circadian entrainment predicts immediate phase shifting in response to light, according to a phase response curve (PRC) (3, 9, 13). In humans, for whom the intrinsic period is on average Ϸ24.2 h (14), entrainment to the solar day of earth (T ϭ 24 h) requires that the biological clock be ''reset'' by on average of Ϸ0.2 h per day in th...

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Section: Discussionmentioning

confidence: 99%

Entrainment of the human circadian pacemaker to longer-than-24-h days

Gronfier

Wright

Kronauer

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

185

143

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“…Melatonin is widely used to treat various sleep disorders [119][120][121][122][123][124][125][126][127][128][129][130], including disorders associated with delayed phase sleep syndrome [119][120][121], periodic sleep disorders in blind patients [122][123][124][125] and sleep and behavioral disorders in children with severe brain damage [126][127][128][129]. In a randomized double-blind, placebo-controlled study [130], melatonin was shown to improve sleep efficiency and sleep latency [130] in cystic fibrosis (CF) patients, a chronic progressive disorder characterized by repeated episodes of respiratory distress and sleep disturbances [130].…”

Section: Role Of Melatonin In Maintaining and Restoring Human Healthmentioning

confidence: 99%

Melatonin: A pleiotropic molecule regulating inflammation

Radogna

Diederich

Ghibelli

2010

Biochemical Pharmacology

308

247

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Melatonin is a neurohormone produced by the pineal gland that regulates sleep and circadian functions. Melatonin also regulates inflammatory and immune processes acting as both an activator and inhibitor of these responses. Melatonin demonstrates endocrine, but also paracrine and autocrine effects in the leukocyte compartment: on one side, leukocytes respond to melatonin in a circadian fashion; on the other side, leukocytes are able to synthesize melatonin by themselves.With its endocrine and paracrine effects, melatonin differentially modulates pro-inflammatory enzymes, controls production of inflammatory mediators such as cytokines and leukotrienes and regulates the lifespan of leukocytes by interfering with apoptotic processes. Moreover, its potent anti-oxidant ability allows scavenging of oxidative stress in the inflamed tissues. The interesting timing of pro-and anti-inflammatory effects, such as those affecting lipoxygenase activity, suggests that melatonin might promote early phases of inflammation on one hand and contribute to its attenuation on the other hand, in order to avoid complications of chronic inflammation. This review aims at giving a comprehensive overview of the various inflammatory pathways regulated by this pleiotropic hormone.

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“…In particular, this drug delays circadian rhythms when administered in the morning and advances them when administered in the afternoon or early evening according to a phase response curve (PRC), which is nearly opposite in phase to the PRC's for light exposure (Lewy et al 1992). Melatonin has proven to exert a chronobiotic mode of action (Dawson and Armstrong 1996) by its ability to facilitate the post-flight adaptation to jet-lag (Arendt et al 1986), to phase advance the sleep of patients suffering from a phase-delay syndrome (Dahlitz et al 1991;Tzischinsky et al 1993), and to re-entrain the sleep-wake cycle of patients with a non-24-hour rhythm, such as in the blind, to the environmental light-dark cycle (Arendt et al 1988;Lapierre and Dumont 1995;McArthur et al 1996).However, in only one of the clinical studies (Haimov et al 1995), in which exogenous melatonin proved usefulness, did low endogenous melatonin excretion predict response (Garfinkel et al 1995;Hughes et al 1998 Lushington et al 1998;Youngstedt et al 1998). Furthermore, normative data as to the amount of melatonin secretion demonstrate a huge inter-individual variability in humans (Dawson et al 1992;Bergiannaki et al 1995;Smith et al 1997).…”

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confidence: 99%

mentioning

confidence: 99%

A New Concept for Melatonin Deficit On Pineal Calcification and Melatonin Excretion

Kunz

1999

Neuropsychopharmacology

139

102

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Even though exogenous melatonin has proven to influence sleep and circadian parameters, low endogenous melatonin is not related to sleep disturbances, nor does it predict response to melatonin replacement therapy. In this manuscript, we present a new concept towards a definition of a melatonin deficit. The purpose of the study was to introduce a marker for an intra-individual decrease in melatonin production. Therefore, we developed a method to quantify the degree of pineal calcification (DOC) usingIn mammals, the circadian timing system has proven to be involved in the daily variation of almost any physiological and psychological variable evaluated so far (Weitzman et al. 1978;Wirz-Justice 1987;Johnson et al. 1992;Dijk and Czeisler 1995;Boivin et al. 1997). The rhythm of the circadian pacemaker comprised in the nuclei suprachiasmatici (SCN) becomes entrained to the environmental 24-hour rhythm, predominantly by two zeitgebers, light and melatonin (Dawson and Armstrong 1996).Melatonin influences the circadian phase in humans inversely compared to light. In particular, this drug delays circadian rhythms when administered in the morning and advances them when administered in the afternoon or early evening according to a phase response curve (PRC), which is nearly opposite in phase to the PRC's for light exposure (Lewy et al. 1992). Melatonin has proven to exert a chronobiotic mode of action (Dawson and Armstrong 1996) by its ability to facilitate the post-flight adaptation to jet-lag (Arendt et al. 1986), to phase advance the sleep of patients suffering from a phase-delay syndrome (Dahlitz et al. 1991;Tzischinsky et al. 1993), and to re-entrain the sleep-wake cycle of patients with a non-24-hour rhythm, such as in the blind, to the environmental light-dark cycle (Arendt et al. 1988;Lapierre and Dumont 1995;McArthur et al. 1996).However, in only one of the clinical studies (Haimov et al. 1995), in which exogenous melatonin proved usefulness, did low endogenous melatonin excretion predict response (Garfinkel et al. 1995;Hughes et al. 1998 Lushington et al. 1998;Youngstedt et al. 1998). Furthermore, normative data as to the amount of melatonin secretion demonstrate a huge inter-individual variability in humans (Dawson et al. 1992;Bergiannaki et al. 1995;Smith et al. 1997). Thus, existing normative data on melatonin excretion in a "healthy population" might only be considered normal in the sense that they are representative for the normal scatter. But since there is yet no pathology that can be attributed to either high or low melatonin levels, "normative" in this context may not necessarily indicate being healthy. The question arises, does a melatonin deficit or a hypopinealism exist at all?In a previously reported pilot-study we showed that the degree of pineal calcification (DOC) correlated positively to the incidence of chronic daytime tiredness as well as the subjective perception of sleep disturbances (Kunz et al. 1998). The basic assumption in that study was the hypothesis that an increasing degree of pineal c...

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Synchronisation of a Disturbed Sleep-Wake Cycle in a Blind Man by Melatonin Treatment

Cited by 187 publications

References 6 publications

Entrainment of the human circadian pacemaker to longer-than-24-h days

Entrainment of the human circadian pacemaker to longer-than-24-h days

Melatonin: A pleiotropic molecule regulating inflammation

A New Concept for Melatonin Deficit On Pineal Calcification and Melatonin Excretion

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