Overnight heart rate variability and next day cortisol response during simulated on-call conditions.

OBJECTIVE: This study had two specific objectives, 1) to investigate the impact of being on-call on overnight heart rate variability during sleep and; 2) to examine whether being on-call overnight impacted next-day salivary cortisol concentrations. METHODS: Data are reported from three within-subject laboratory studies (n = 24 in each study) that assessed varying on-call conditions. Healthy male participants (n = 72 total) completed a four-night laboratory protocol, comprising an adaptation night, a control night, and two counterbalanced on-call nights with varying on-call conditions. These on-call conditions were designed to determine the impact of, Study 1: the likelihood of receiving a call (definitely, maybe), Study 2: task stress (high-stress, low-stress), and Study 3: chance of missing the alarm (high-chance, low-chance), on measures of physiological stress. Overnight heart rate variability (HRV) (during sleep) was measured using two-lead electrocardiography, and time- and frequency-domain variables were analysed. Saliva samples were collected at 15-min time intervals from 0700-0800 h to determine cortisol awakening response outcomes and at four daily time points (0930 h, 1230 h, 1430 h, and 1730 h) to assess diurnal cortisol profiles. RESULTS: There were few differences in HRV measures during sleep across all three studies. The only exception was in Study 1 where the standard deviation of the time interval between consecutive heartbeats and the root mean square of consecutive differences between heartbeats were lower across all sleep stages in the definitely condition, when compared to control. Across all three studies, being on-call overnight also had little impact on next-day cortisol awakening response (CAR), with the exception of Study 2 where the 1) CAR area under the curve with respect to increase was blunted in the high-stress condition, compared to the control and low-stress conditions and, 2) CAR reactivity was higher in low-stress condition, compared with the high-stress condition. In Study 1, diurnal cortisol area under the curve with respect to ground was lower in the on-call conditions (definitely and maybe) when compared to control. There were no differences in diurnal cortisol measures in Study 3. CONCLUSION: This is the first study to investigate how different aspects of being on-call affect physiological stress responses. Overall, relatively little differences in measures of overnight heart rate variability and next-day cortisol response were recorded in all three studies. Further research utilising real on-call work tasks, not just on-call expectations (as in the current study) will help determine the impact of on-call work on the physiological stress response.

Circadian Melatonin and Temperature Taus in Delayed Sleep-wake Phase Disorder and Non-24-hour Sleep-wake Rhythm Disorder Patients: An Ultradian Constant Routine Study.

Our objectives were to investigate the period lengths (i.e., taus) of the endogenous core body temperature rhythm and melatonin rhythm in delayed sleep-wake phase disorder patients (DSWPD) and non-24-h sleep-wake rhythm disorder patients (N24SWD) compared with normally entrained individuals. Circadian rhythms were measured during an 80-h ultradian modified constant routine consisting of 80 ultrashort 1-h "days" in which participants had 20-min sleep opportunities alternating with 40 min of enforced wakefulness. We recruited a community-based sample of 26 DSWPD patients who met diagnostic criteria (17 males, 9 females; age, 21.85 ± 4.97 years) and 18 healthy controls (10 males, 8 females; age, 23.72 ± 5.10 years). Additionally, 4 full-sighted patients (3 males, 1 female; age, 25.75 ± 4.99 years) were diagnosed with N24SWD and included as a discrete study group. Ingestible core temperature capsules were used to record minute temperatures that were averaged to obtain 80 hourly data points. Salivary melatonin concentration was assessed every half-hour to determine time of dim light melatonin onset at the beginning and end of the 80-h protocol. DSWPD patients had significantly longer melatonin rhythm taus (24 h 34 min ± 17 min) than controls (24 h 22 min ± 15 min, p = 0.03, d = 0.70). These results were further supported by longer temperature rhythm taus in DSWPD patients (24 h 34 min ± 26 min) relative to controls (24 h 13 min ± 15 min, p = 0.01, d = 0.80). N24SWD patients had even longer melatonin (25 h ± 19 min) and temperature (24 h 52 min ± 17 min) taus than both DSWPD (p = 0.007, p = 0.06) and control participants (p < 0.001, p = 0.02, respectively). Between 12% and 19% of the variance in DSWPD patients' sleep timing could be explained by longer taus. This indicates that longer taus of circadian rhythms may contribute to the DSWPD patients' persistent tendency to delay, their frequent failure to respond to treatment, and their relapse following treatment. Additionally, other factors can contribute to misalignments in DSWPD and N24SWD disorders.

Cholestyramine feeding lowers number of colonic apoptotic cells in rat.

Secondary bile acids that are formed in the colon by bacterial action have the potential property of eliciting pathological conditions. Apoptosis of mucosal epithelial cells is recognized as an adaptation that may counteract such pathologies. Cholestyramine, an anion exchange resin that sequesters bile salts in the gut, could decrease levels of secondary bile salt stress and thus conserve the potency of the protective action. Two groups of rats were studied: those fed 4% cholestyramine and those fed regular rat food. Rats were fed cholestyramine for 7, 14, 21, or 28 d. All animals were evaluated for cell death (apoptosis) using in situ TUNEL staining, and confirmed with single-stranded DNA (ssDNA). The effect of cholestyramine on the proliferating cell nuclear antigen (PCNA) in colonic crypt cells was also examined. Our data shows that animals fed cholestyramine for 28 d show evidence of a significant decrease in the levels of apoptotic cells in their large intestines, particularly goblet cells, when compared with the control animals and no change in cell proliferation. Thus, cholestyramine may serve as an alternative in attenuating apoptosis associated with inflammatory disorders that can result in significant enterocyte and goblet-cell death.

Nocturnal Melatonin Profiles in Patients with Delayed Sleep-Wake Phase Disorder and Control Sleepers.

A significant delay in the timing of endogenous circadian rhythms has been associated with delayed sleep phase disorder (DSPD). More recently, other mechanisms have also been proposed to account for this disorder. To further explore the etiology of DSPD, the present study compared nocturnal melatonin profiles of 26 DSPD patients (18 males, 8 females; age, 21.73 ± 4.98 years) and 17 normally timed good sleepers (10 males, 7 females; age, 23.82 ± 5.23 years) in a time-free, dim-light (<10 lux) laboratory environment. A 30-h modified constant routine with alternating 20-min sleep opportunities and 40 min of enforced wakefulness was used to measure the endogenous melatonin circadian rhythm. Salivary melatonin was sampled half-hourly from 1820 h to 0020 h and then hourly from 0120 h to 1620 h. DSPD patients had significantly later timed melatonin profiles that were delayed by approximately 3 h compared to normal sleepers, and there were no notable differences in the relative duration of secretion between groups. However, melatonin secretion between dim-light melatonin onset (DLMO) and acrophase was less prominent in DSPD patients compared to good sleepers, who showed a more acute initial surge of melatonin following the DLMO. Although the regulatory role of melatonin is unknown, abnormal melatonin profiles have been linked to psychiatric and neurological disorders (e.g., major depression, obsessive compulsive disorder, Parkinson disease). These results therefore suggest that in addition to a delayed endogenous circadian rhythm, a diminished initial surge of melatonin secretion following DLMO may contribute to the etiology of DSPD.

The maintenance of wakefulness test in normal healthy subjects.

STUDY OBJECTIVES: The Maintenance of Wakefulness Test (MWT) examines an individual's ability to stay awake in an environment of decreased sensory stimulation. Only 1 previous study has systematically examined the MWT in normal healthy subjects. SETTING: Sleep disorders unit laboratory PARTICIPANTS AND DESIGN: 31 subjects (mean age 48.5 years, SD 9.6; 8 women) were randomly selected via the telephone directory within a 30-km radius of the test centers. They answered a general screen for health complaints (respiratory, cardiovascular, and psychiatric disorders) and sleep difficulties (snoring). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Overnight polysomnography and a 40-minute MWT the following day were performed on all subjects. Mean sleep latency to the first epoch of unequivocal sleep during the 40-minute trial MWT was 36.9 +/- 5.4 (SD) minutes. The lower normal limit, defined as 2 SD below the mean, was therefore 26.1 minutes. Mean sleep latency for the first 20 minutes of the trial (with sleep latency defined as time to the first appearance of 1 epoch of stage 1 sleep or a 10-second microsleep) was 18.6 +/- 2.3 minutes, with a lower normal limit of 14.0 minutes. CONCLUSIONS: The mean results are consistent with previously published normative data. However, the SDs found in this study are smaller, and, thus, the lower normal limit suggested here is 4 to 6 minutes longer. The subjects in this study were randomly selected from the general population and may, therefore, be a truer representation of the normal population than in the previous study in which subjects were recruited via hospital advertisements and word of mouth.

Differential effects of light wavelength in phase advancing the melatonin rhythm.

Shorter wavelength light has been shown to be more effective than longer wavelengths in suppressing nocturnal melatonin and phase delaying the melatonin rhythm. In the present study, different wavelengths of light were evaluated for their capacity to phase advance the saliva melatonin rhythm. Two long wavelengths, 595 nm (amber) and 660 nm (red) and three shorter wavelengths, 470 nm (blue), 497 nm (blue/green), and 525 nm (green) were compared with a no-light control condition. Light was administered via a portable light source comprising two light-emitting diodes per eye, with the irradiance of each diode set at 65 microW/cm(2). Forty-two volunteers participated in up to six conditions resulting in 15 per condition. For the active light conditions, a 2-hr light pulse was administered from 06:00 hr on two consecutive mornings. Half-hourly saliva samples were collected on the evening prior to the first light pulse and the evening following the second light pulse. The time of melatonin onset was calculated for each night and the difference was calculated as a measure of phase advance. The shorter wavelengths of 470, 495 and 525 nm showed the greatest melatonin onset advances ranging from approximately 40-65 min while the longer wavelengths produced no significant phase advance. These results strengthen earlier findings that the human circadian system is more sensitive to the short wavelengths of light than the longer wavelengths.