Combinations of bright light, scheduled dark, sunglasses, and melatonin to facilitate circadian entrainment to night shift work

Various combinations of interventions were used to phase-delay circadian rhythms to correct their misalignment with night work and day sleep. Young participants (median age = 22, n = 67) participated in 5 consecutive simulated night shifts (2300 to 0700) and then slept at home (0830 to 1530) in darkened bedrooms. Participants wore sunglasses with normal or dark lenses (transmission 15% or 2%) when outside during the day. Participants took placebo or melatonin (1.8 mg sustained release) before daytime sleep. During the night shifts, participants were exposed to a moving (delaying) pattern of intermittent bright light (approximately 5000 lux, 20 min on, 40 min off, 4-5 light pulses/night) or remained in dim light (approximately 150 lux). There were 6 intervention groups ranging from the least complex (normal sunglasses) to the most complex (dark sunglasses + bright light + melatonin). The dim light melatonin onset (DLMO) was assessed before and after the night shifts (baseline and final), and 7 h was added to estimate the temperature minimum (Tmin). Participants were categorized by their amount of reentrainment based on their final Tmin: not re-entrained (Tmin before the daytime dark/sleep period), partially re-entrained (Tmin during the first half of dark/sleep), or completely re-entrained (Tmin during the second half of dark/ sleep). The sample was split into earlier participants (baseline Tmin < or = 0700, sunlight during the commute home fell after the Tmin) and later participants (baseline Tmin > 0700). The later participants were completely re-entrained regardless of intervention group, whereas the degree of re-entrainment for the earlier participants depended on the interventions. With bright light during the night shift, almost all of the earlier participants achieved complete re-entrainment, and the phase delay shift was so large that darker sunglasses and melatonin could not increase its magnitude. With only room light during the night shift, darker sunglasses helped earlier participants phase-delay more than normal sunglasses, but melatonin did not increase the phase delay. The authors recommend the combination of intermittent bright light during the night shift, sunglasses (as dark as possible) during the commute home, and a regular, early daytime dark/sleep period if the goal is complete circadian adaptation to night-shift work.     

Profile of 24-h light exposure and circadian phase of melatonin secretion in night workers.

Light exposure was measured in 30 permanent night nurses to determine if specific light/dark profiles could be associated with a better circadian adaptation. Circadian adaptation was defined as a significant shift in the timing of the episode of melatonin secretion into the daytime. Light exposure was continuously recorded with ambulatory wrist monitors for 56 h, including 3 consecutive nights of work. Participants were then admitted to the laboratory for 24 h where urine was collected every 2 h under dim light for the determination of 6-sulphatoxymelatonin concentration. Cosinor analysis was used to estimate the phase position of the episode of melatonin secretion. Five participants showed a circadian adaptation by phase delay ("delayed participants") and 3 participants showed a circadian adaptation by phase advance ("advanced participants"). The other 22 participants had a timing of melatonin secretion typical of day-oriented people ("nonshifters"). There was no significant difference between the 3 groups for total light exposure or for bright light exposure in the morning when traveling home. However, the 24-h profiles of light exposure were very distinctive. The timing of the main sleep episode was associated with the timing of light exposure. Delayed participants, however, slept in darker bedrooms, and this had a major impact on their profile of light/dark exposure. Delayed and advanced participants scored as evening and morning types, respectively, on a morningness-eveningness scale. This observation suggests that circadian phase prior to night work may contribute to the initial step toward circadian adaptation, later reinforced by specific patterns of light exposure.     

Circadian phase, sleepiness, and light exposure assessment in night workers with and without shift work disorder

Most night workers are unable to adjust their circadian rhythms to the atypical hours of sleep and wake. Between 10% and 30% of shiftworkers report symptoms of excessive sleepiness and/or insomnia consistent with a diagnosis of shift work disorder (SWD). Difficulties in attaining appropriate shifts in circadian phase, in response to night work, may explain why some individuals develop SWD. In the present study, it was hypothesized that disturbances of sleep and wakefulness in shiftworkers are related to the degree of mismatch between their endogenous circadian rhythms and the night-work schedule of sleep during the day and wake activities at night. Five asymptomatic night workers (ANWs) (3 females; [mean ± SD] age: 39.2 ± 12.5 yrs; mean yrs on shift = 9.3) and five night workers meeting diagnostic criteria (International Classification of Sleep Disorders [ICSD]-2) for SWD (3 females; age: 35.6 ± 8.6 yrs; mean years on shift = 8.4) participated. All participants were admitted to the sleep center at 16:00 h, where they stayed in a dim light (<10 lux) private room for the study period of 25 consecutive hours. Saliva samples for melatonin assessment were collected at 30-min intervals. Circadian phase was determined from circadian rhythms of salivary melatonin onset (dim light melatonin onset, DLMO) calculated for each individual melatonin profile. Objective sleepiness was assessed using the multiple sleep latency test (MSLT; 13 trials, 2-h intervals starting at 17:00 h). A Mann-Whitney U test was used for evaluation of differences between groups. The DLMO in ANW group was 04:42 ± 3.25 h, whereas in the SWD group it was 20:42 ± 2.21 h (z = 2.4; p 相似文献   

Amplitude reduction and phase shifts of melatonin, cortisol and other circadian rhythms after a gradual advance of sleep and light exposure in humans

Background

The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleep-wake cycle has not been fully characterized.

Methodology/Principal Findings

We assessed the phase and amplitude of the rhythms of melatonin, core body temperature, cortisol, alertness, performance and sleep after a perturbation of entrainment by a gradual advance of the sleep-wake schedule (10 h in 5 days) and associated light-dark cycle in 14 healthy men. The light-dark cycle consisted either of moderate intensity ‘room’ light (∼90–150 lux) or moderate light supplemented with bright light (∼10,000 lux) for 5 to 8 hours following sleep. After the advance of the sleep-wake schedule in moderate light, no significant advance of the melatonin rhythm was observed whereas, after bright light supplementation the phase advance was 8.1 h (SEM 0.7 h). Individual differences in phase shifts correlated across variables. The amplitude of the melatonin rhythm assessed under constant conditions was reduced after moderate light by 54% (17–94%) and after bright light by 52% (range 12–84%), as compared to the amplitude at baseline in the presence of a sleep-wake cycle. Individual differences in amplitude reduction of the melatonin rhythm correlated with the amplitude of body temperature, cortisol and alertness.

Conclusions/Significance

Alterations in the timing of the sleep-wake cycle and associated bright or moderate light exposure can lead to changes in phase and reduction of circadian amplitude which are consistent across multiple variables but differ between individuals. These data have implications for our understanding of circadian organization and the negative health outcomes associated with shift-work, jet-lag and exposure to artificial light.     

Controlled exposure to light and darkness realigns the salivary cortisol rhythm in night shift workers

The efficacy of a light/darkness intervention designed to promote circadian adaptation to night shift work was tested in this combined field and laboratory study. Six full-time night shift workers (mean age ± SD:37.1 ± 8.1 yrs) were provided an intervention consisting of an intermittent exposure to full-spectrum bright white light (∼2000 lux) in the first 6 h of their 8 h shift, shielding from morning light by tinted lenses (neutral gray density, 15% visual light transmission), and regular sleep/darkness episodes in darkened quarters beginning 2 h after the end of each shift. Five control group workers (41.1 ± 9.9 yrs) were observed in the presence of a regular sleep/darkness schedule only. Constant routines (CR) performed before and after a sequence of ∼12 night shifts over 3 weeks revealed that treatment group workers displayed significant shifts in the time of peak cortisol expression and realignment of the rhythm with the night-oriented schedule. Smaller phase shifts, suggesting an incomplete adaptation to the shift work schedule, were observed in the control group. Our observations support the careful control of the pattern of light and darkness exposure for the adaptation of physiological rhythms to night shift work.     

Blood pressure in night shift workers: circadian rhythms and levels and their seasonal differences

The average diurnal blood pressure profiles (DBPPs) were studied in subjects working at different hours of the day, including nighttime. The DBPPs and the curve levels in winter and in summer were compared. The study material included more than 497 000 prework blood pressure (BP) measurement points in 30 566 locomotive drivers. It was found that the average DBPP of the subjects working at different hours of the day is of a markedly nondipper type; i.e., despite night wakefulness, the BP was lower at night but not as low as that of those sleeping at night. In the cohort studied, the shapes of the DBPP curve did not differ in winter and in summer; however, the BP levels in winter were significantly higher.     

Serotonin increases the phase shift of the circadian locomotor activity rhythm in mice after dark pulses in constant light conditions

Investigations on the effects of the 5-HT agonists and antagonists on the phase of the circadian locomotor activity rhythm of animals kept in constant light conditions (LL) are rare. Therefore the influence of R-(+)-OH-DPAT (5-HT1A receptors agonist) and metergoline (5-HT1/2/7 receptors antagonist) on the phase shift of the locomotor-activity rhythm alone and when combined with dark pulses in mice kept in LL are examined. The results indicate that 8-OH-DPAT administered independently at 12.00CT (Circadian Time) shifted the phase of the circadian rhythm and reinforced the effect of dark pulses on this parameter. 12.00CT was defined arbitrarily as the onset of locomotor activity in constant conditions. Metergoline diminished the phase shifts after dark pulses compared to 8-OH-DPAT. The influence of the serotonin agonist showed that serotonin can reinforce the phase shifting effect of the locomotor activity rhythm after dark pulses in LL condition.     

Blood pressure in night shift workers: circadian rhythms and levels, and their seasonal variation

Average diurnal blood pressure (BP) profiles (DBPP) were studied in persons working at different hours of a day, including night workers. The results obtained in winter and summer seasons were compared. The study consisted of more than 497 000 pre-work BP measurement points for each of 30 566 locomotive drivers. It was found that average DBPP of persons working at different hours of a day is of the marked non-dipper type in spite of night wakefulness. BP was lower at night but not as low as that of night sleeping persons. In the cohort studied, the form of DBPP curve does not differ in winter and summer; however BP in winter is significantly higher.     

Differences in sleep, light, and circadian phase in offshore 18:00-06:00 h and 19:00-07:00 h shift workers

Complaints concerning sleep are high among those who work night shifts; this is in part due to the disturbed relationship between circadian phase and the timing of the sleep-wake cycle. Shift schedule, light exposure, and age are all known to affect adaptation to the night shift. This study investigated circadian phase, sleep, and light exposure in subjects working 18:00-06:00 h and 19:00-07:00 h schedules during summer (May-August). Ten men, aged 46+/-10 yrs (mean+/-SD), worked the 19:00-07:00 h shift schedule for two or three weeks offshore (58 degrees N). Seven men, mean age 41+/-12 yrs, worked the 18:00-06:00 h shift schedule for two weeks offshore (61 degrees N). Circadian phase was assessed by calculating the peak (acrophase) of the 6-sulphatoxymelatonin rhythm measured by radioimmunoassay of sequential urine samples collected for 72 h at the end of the night shift. Objective sleep and light exposure were assessed by actigraphy and subjective sleep diaries. Subjects working 18:00-06:00 h had a 6-sulphatoxymelatonin acrophase of 11.7+/-0.77 h (mean+/-SEM, decimal hours), whereas it was significantly later, 14.6+/-0.55 h (p=0.01), for adapted subjects working 19:00-07:00 h. Two subjects did not adapt to the 19:00-07:00 h night shift (6-sulphatoxymelatonin acrophases being 4.3+/-0.22 and 5.3+/-0.29 h). Actigraphy analysis of sleep duration showed significant differences (p=0.03), with a mean sleep duration for those working 19:00-07:00 h of 5.71+/-0.31 h compared to those working 18:00-06:00 h whose mean sleep duration was 6.64+/-0.33 h. There was a trend to higher morning light exposure (p=0.07) in the 19:00-07:00 h group. Circadian phase was later (delayed on average by 3 h) and objective sleep was shorter with the 19:00-07:00 h than the 18:00-06:00 h shift schedule. In these offshore conditions in summer, the earlier shift start and end time appears to favor daytime sleep.     

Late circadian phase in adults and children is correlated with use of high color temperature light at home at night

Light is the strongest synchronizer of human circadian rhythms, and exposure to residential light at night reportedly causes a delay of circadian rhythms. The present study was conducted to investigate the association between color temperature of light at home and circadian phase of salivary melatonin in adults and children. Twenty healthy children (mean age: 9.7 year) and 17 of their parents (mean age: 41.9 years) participated in the experiment. Circadian phase assessments were made with dim light melatonin onset (DLMO). There were large individual variations in DLMO both in adults and children. The average DLMO in adults and in children were 21:50 ± 1:12 and 20:55 ± 0:44, respectively. The average illuminance and color temperature of light at eye level were 139.6 ± 82.7 lx and 3862.0 ± 965.6 K, respectively. There were significant correlations between color temperature of light and DLMO in adults (r = 0.735, p < 0.01) and children (r = 0.479, p < 0.05), although no significant correlations were found between illuminance level and DLMO. The results suggest that high color temperature light at home might be a cause of the delay of circadian phase in adults and children.     

A randomized controlled trial with bright light and melatonin for delayed sleep phase disorder: Effects on subjective and objective sleep

Delayed sleep phase disorder (DSPD) is assumed to be common amongst adolescents, with potentially severe consequences in terms of school attendance and daytime functioning. The most common treatment approaches for DSPD are based on the administration of bright light and/or exogenous melatonin with or without adjunct behavioural instructions. Much is generally known about the chronobiological effects of light and melatonin. However, placebo-controlled treatment studies for DSPD are scarce, in particular in adolescents and young adults, and no standardized guidelines exist regarding treatment. The aim of the present study was, therefore, to investigate the short- and long-term effects on sleep of a DSPD treatment protocol involving administration of timed bright light and melatonin alongside gradual advancement of rise time in adolescents and young adults with DSPD in a randomized controlled trial and an open label follow-up study. A total of 40 adolescents and young adults (age range 16–25 years) diagnosed with DSPD were recruited to participate in the study. The participants were randomized to receive treatment for two weeks in one of four treatment conditions: dim light and placebo capsules, bright light and placebo capsules, dim light and melatonin capsules or bright light and melatonin capsules. In a follow-up study, participants were re-randomized to either receive treatment with the combination of bright light and melatonin or no treatment in an open label trial for approximately three months. Light and capsules were administered alongside gradual advancement of rise times. The main end points were sleep as assessed by sleep diaries and actigraphy recordings and circadian phase as assessed by salivary dim light melatonin onset (DLMO). During the two-week intervention, the timing of sleep and DLMO was advanced in all treatment conditions as seen by about 1?h advance of bed time, 2?h advance of rise time and 2?h advance of DLMO in all four groups. Sleep duration was reduced with approximately 1?h. At three-month follow-up, only the treatment group had maintained an advanced sleep phase. Sleep duration had returned to baseline levels in both groups. In conclusion, gradual advancement of rise time produced a phase advance during the two-week intervention, irrespective of treatment condition. Termination of treatment caused relapse into delayed sleep times, whereas long-term treatment with bright light and melatonin (three months) allowed maintenance of the advanced sleep phase.     

Correlations of serotonin and its metabolites in individual rat pineal glands over light:dark cycles and after acute light exposure

Profiles of pineal indolealkylamines were estimated by high performance liquid chromatography and were correlated in individual glands of male rats sacrificed over several light:dark cycles and after acute exposure to light at night. A significant and positive correlation of 5HIAA vs 5HT in individual glands over both normal and experimental lighting conditions suggested that oxidative deamination is not a major factor in photic regulation of pineal 5HT levels and that the formation of 5HIAA is dependent on substrate availability. Regression analysis of other indole constituents revealed that there was a positive and significant correlation between 5HT vs N-acetylserotonin, but not between 5HT vs melatonin and N-acetylserotonin vs melatonin in individual glands during the dark phase of a light:dark cycle. We propose that this effect may be related to a pulsatile release of melatonin into the blood stream and is the result of sampling glands at different stages in the storage/release of melatonin.     

A model for penicillin production with and without temperature shift after the growth phase

Summary A strain of Penicillium chrysogenum producting about 8 g/l of penicillin V, was cultivated in a 10-1 bioreactor. Under carbon (C)-limitation during the production phase a glucose/ammonium sulphate mixture was fed using microprocessor control. When the temperature was shifted from 25° C to 30° C at the end of the active growth phase, the specific penicillin production rate was increased by 30%, while the yield remained constant. Maximal productivity without sporulation was obtained when the net growth rate of the active (respiring and producing) biomass, estimated by measuring the respiration rate under defined conditions, was equal to or higher than 0.004 h^–1. A model was developed for penicillin fermentation during C-limitation possessing the following properties: (1) the model is based on ordinary differential equations; (2) the influence of different nutrients is considered; (3) the model recognizes two cell types (active and inactive); (4) the model describes the influence of a temperature shift at the end of the vigorous growth phase. Offprint requests to: D. Siegmund     

Modeling circadian rhythm generation in the suprachiasmatic nucleus with locally coupled self-sustained oscillators: phase shifts and phase response curves

Circadian rhythm generation in the suprachiasmatic nucleus was modeled by locally coupled self-sustained oscillators. The model is composed of 10,000 oscillators, arranged in a square array. Coupling between oscillators and standard deviation of (randomly determined) intrinsic oscillator periods were varied. A stable overall rhythm emerged. The model behavior was investigated for phase shifts of a 24-h zeitgeber cycle. Prolongation of either the dark or the light phase resulted in a lengthening of the period, whereas shortening of the dark or the light phase shortened the period. The model's response to shifts in the light-dark cycle was dependent only on the extent of the shift and was insensitive to changes in parameters. Phase response curves (PRC) and amplitude response curves were determined for single and triple 5-h light pulses (1000 lux). Single pulses lead to type 1 PRCs with larger phase shifts for weak coupling. Triple pulses generally evoked type 1 PRCs with the exception of weak coupling, where a type 0 PRC was observed.     

Changes of the diurnal and circadian (endogenous) mRNA oscillations of the chlorophyll a/b binding protein in tomato leaves during altered day/night (light/dark) regimes

Characteristic steady-state mRNA level oscillations were monitored for the chlorophyll a/b-binding (cab) protein in tomato plants grown under the natural day/night (light/dark) regime as well as under constant environmental conditions. This typical expression pattern was altered when plants were transferred to different light/dark regimes. For example, by shifting the light phase by six hours, a change of the time points of maximum and minimum of expression level was monitored, while the principal oscillation pattern remained the same. It appeared that the transition from dark to light is involved in determining the time points of minima and maxima of mRNA accumulation.After exposing tomato plants to an abnormal light/dark periodicity (e.g. six hours of alternating light/dark) an altered oscillation pattern was determined: within 24 hours two maxima of cab mRNA levels were detected. However, this entrained abnormal rhythm was not manifested at the molecular level and the circadian pattern reappeared under constant environmental conditions (e.g. darkness). This result favours the hypothesis that the oscillation pattern of the cab mRNA in tomato plants is not only endogenous but also hereditary.     

The effects of exposure to night shift work on liver function: A cross-sectional study with emphasis of alkaline phosphatase enzyme

ABSTRACT

Background: Previous studies have demonstrated that shift work can be significantly associated with adverse effects on liver function. However, the association between shift work and alkaline phosphatase (ALP) enzyme as a well-known biomarker of liver disease has been undefined. Methods: This cross-sectional study was conducted on a total number of 6,475 eligible oil refinery workers. According to shift work schedules, the participants divided to the following groups: 12-hr rotating night (n = 2,630) and 12-hr fixed day (n = 3845). The Spearman’s correlation and logistic regression were applied to assess the association between shift work and ALP. Results: We found significantly higher levels of ALP in 12-hr rotating night compared to 12-hr fixed-day shift work groups (196.2 ± 52.1 versus 191.5 ± 53.4). According to quartile (Q) logistic regression adjusted by significant variables between study group (age, body mass index, fasting blood sugar, and total cholesterol), the odds ratio and 95% confidence interval of high (Q2–<Q3 versus <Q1) and severe (≥Q3 versus <Q1) levels of ALP in 12-hr rotating night group in comparison to 12-hr fixed-day group were estimated as 1.26 (1.08–1.45) and 1.26 (1.09–1.45), respectively. Conclusions: This study indicated that 12-hr rotating night shift work may be associated with higher levels of ALP. More studies are needed to confirm our findings.     

Birds after dark: an efficient and inexpensive system for making long‐range observations at night

ABSTRACT The ability of investigators to study the behavior of animals at night is often limited by the difficulties of making observations in the dark, particularly at a distance. Indirect techniques, such as radio tracking, generally produce limited behavioral data, and most night‐viewing equipment tends to be both inefficient for making long‐range observations and expensive. We describe a long‐range night‐vision system consisting of a camcorder and infrared laser illuminators. We tested the performance of this system by comparing our ability to quantify the foraging behavior of shorebirds during the day and at night. Distance thresholds for detecting ingestion of prey and for identifying them were similar during the day and night for all species. At night, we were able to quantify all foraging parameters for all species at distances up to 59 m, and to count pecks and steps at distances greater than 200 m for some species. The observation system we describe can be further improved by using camcorders with higher optical zooms or more powerful infrared laser illuminators. Because of its efficiency and relatively low cost, this system has the potential for being useful in many other applications that require long‐range observations of animals at night.     

Regulation of L1 expression and retrotransposition by melatonin and its receptor: implications for cancer risk associated with light exposure at night

Expression of long interspersed element-1 (L1) is upregulated in many human malignancies. L1 can introduce genomic instability via insertional mutagenesis and DNA double-strand breaks, both of which may promote cancer. Light exposure at night, a recently recognized carcinogen, is associated with an increased risk of cancer in shift workers. We report that melatonin receptor 1 inhibits mobilization of L1 in cultured cells through downregulation of L1 mRNA and ORF1 protein. The addition of melatonin receptor antagonists abolishes the MT1 effect on retrotransposition in a dose-dependent manner. Furthermore, melatonin-rich, but not melatonin-poor, human blood collected at different times during the circadian cycle suppresses endogenous L1 mRNA during in situ perfusion of tissue-isolated xenografts of human cancer. Supplementation of human blood with exogenous melatonin or melatonin receptor antagonist during the in situ perfusion establishes a receptor-mediated action of melatonin on L1 expression. Combined tissue culture and in vivo data support that environmental light exposure of the host regulates expression of L1 elements in tumors. Our data imply that light-induced suppression of melatonin production in shift workers may increase L1-induced genomic instability in their genomes and suggest a possible connection between L1 activity and increased incidence of cancer associated with circadian disruption.     

A comparison of light and temperature entrainment: evidence for a multioscillator circadian system

ABSTRACT. Both photoperiodic and thermoperiodic cycles synchronize circadian calling activity of male crickets, Teleogryllus commodus (Walker). Because the phase relationships between these cycles and the entrained singing activity are clearly distinguishable, we studied the relative power of these factors in affecting the circadian clock. Upon resumption of constant conditions after exposure to a thermoperiodic cycle, singing activity sometimes splits into two daily bouts, each with a distinctive period. This observation, together with results derived from simultaneous fluctuation of both factors in and out of phase, suggests that the system integrating environmental input is composed of multiple oscillators.