Ageing and the circadian and homeostatic regulation of human sleep during forced desynchrony of rest, melatonin and temperature rhythms.
(9/4912)
1. The circadian timing system has been implicated in age-related changes in sleep structure, timing and consolidation in humans. 2. We investigated the circadian regulation of sleep in 13 older men and women and 11 young men by forced desynchrony of polysomnographically recorded sleep episodes (total, 482; 9 h 20 min each) and the circadian rhythms of plasma melatonin and core body temperature. 3. Stage 4 sleep was reduced in older people. Overall levels of rapid eye movement (REM) sleep were not significantly affected by age. The latencies to REM sleep were shorter in older people when sleep coincided with the melatonin rhythm. REM sleep was increased in the first quarter of the sleep episode and the increase of REM sleep in the course of sleep was diminished in older people. 4. Sleep propensity co-varied with the circadian rhythms of body temperature and plasma melatonin in both age groups. Sleep latencies were longest just before the onset of melatonin secretion and short sleep latencies were observed close to the temperature nadir. In older people sleep latencies were longer close to the crest of the melatonin rhythm. 5. In older people sleep duration was reduced at all circadian phases and sleep consolidation deteriorated more rapidly during the course of sleep, especially when the second half of the sleep episode occurred after the crest of the melatonin rhythm. 6. The data demonstrate age-related decrements in sleep consolidation and increased susceptibility to circadian phase misalignment in older people. These changes, and the associated internal phase advance of the propensity to awaken from sleep, appear to be related to the interaction between a reduction in the homeostatic drive for sleep and a reduced strength of the circadian signal promoting sleep in the early morning. (+info)
Prevalence of insomnia: a survey of the enrollees at five managed care organizations.
(10/4912)
The purpose of the study was to assess the prevalence of and factors associated with insomnia among enrollees of managed care organizations (MCOs). A survey was distributed either by mail or during a clinic visit to 7,500 enrollees of five MCOs in the United States. The survey included a sleep questionnaire, demographic questions, and questions about medical encounters and prescription drug use. Three levels of insomnia (none; level I--difficulty initiating or maintaining sleep; level II--insomnia with daytime dysfunction) were defined from the responses. Comorbidities were determined by proxy from prescription drug use reported by respondents. A total of 3,447 survey responses were received, yielding a response rate of 46%. Level I and level II insomnia was reported by 13.5% and 32.5% of the respondents, respectively. Level II insomnia increased with decreasing education, income, and age and was more prevalent in women and non-Caucasians. Insomnia was significantly correlated with all daytime sleepiness and most nighttime disturbances factors. Fifty-two percent of all respondents reported at least one comorbid condition. Respondents with multiple comorbidities reported level II insomnia more frequently than those with no comorbidities. Only 0.9% of clinic visitors were seeing a physician specifically for sleep problems. Of those with level I and level II insomnia, only 5.5% and 11.6%, respectively, were taking prescription medications specifically for sleep problems; 11.2% and 21.4%, respectively, were taking over-the-counter medications for sleep. Insomnia occurs in MCO enrollees at rates comparable to those found in the general population. However, few patients with insomnia are actually being treated for their condition. Proper evaluation, diagnosis, and treatment of insomnia are warranted. (+info)
Eastward long distance flights, sleep and wake patterns in air crews in connection with a two-day layover.
(11/4912)
The present study describes the spontaneous sleep/wake pattern in connection with an eastward (Stockholm to Tokyo, +8 h) transmeridian flight and short (51 h) layovers. To describe all sleep episodes and the recovery process across 4 days, and to relate adjustment to individual differences, 49 Scandinavian Airlines System (SAS) air crew were monitored for 9 days with activity monitors and sleep/wake diary before-during-after flight. The outbound flight involved a period of wakefulness extended to 21 h, frequently (87% of air crew) terminated by a long nap in Tokyo which was calm but difficult to wake up from. Then followed two night oriented sleep periods of normal length but of reduced efficiency, containing many and long awakenings. Napping was common during the extended periods of wakefulness, particularly during flights. During the recovery days, ease of rising from sleep in the mornings was difficult throughout, and feelings of not being refreshed returned to baseline levels on the third recovery sleep. Elevated daytime sleepiness (24% of the day) was observed on the first recovery day. No individual differences related to gender, age or position (cabin/pilot) was found in sleep strategy. Poor adjusters, subjects with a perceived lowered capacity on recovery days, showed more premature awakenings abroad and less refreshing sleep during the last 12 months, suggesting a decreased ability to cope with air crew scheduling. Comparisons with a westbound flight showed the eastbound flight layover sleep to be more problematic and containing more napping. (+info)
Evaluation of the effect on heart rate variability of a beta2-adrenoceptor agonist and antagonist using non-linear scatterplot and sequence methods.
(12/4912)
AIMS: To examine the impact on heart rate variability (HRV), of agonism or antagonism at the cardiac beta2-adrenoceptor in healthy volunteers, using standard time-domain summary statistics and non-linear methods (scatterplot and quadrant analysis). METHODS: Under double-blind and randomised conditions (Latin square design), 17 normal volunteers received placebo, salbutamol (beta2-adrenoceptor partial agonist), ICI 118,551 (specific beta2-adrenoceptor antagonist), or salbutamol plus ICI 118,551. Single oral doses of medication (at weekly intervals) were administered at 22.30 h, with HRV assessed from the sleeping heart rates. RESULTS: Salbutamol reduced the long-term (SDNN: 135 ms [120, 156], SDANN: 107 ms [89, 124]) time-domain indicators of HRV compared with placebo (SDNN: 39 [24, 55], SDANN 42 [29, 56], [mean difference [95% confidence intervals of difference]]). Alone, ICI 118,551 did not effect HRV, but in combination blocked the actions of salbutamol. Scatterplot length (944 ms [869, 1019]) and area (222*10(3) ms2 [191, 253]) were reduced by salbutamol compared with placebo; (length difference (164 [98, 230]) and area difference 59 [36, 83]). Scatterplot width (dispersion) was lower at both low (width RR-1 25% salbutamol 277 ms [261, 293]: salbutamol minus placebo 14 ms [0, 28]) and high (width 75% salbutamol 417 [391, 443]: salbutamol minus placebo 41 [20, 62]) heart rates. ICI 118,551 alone did not alter scatterplot parameters but in combination blocked the effect of salbutamol. Cardiac acceleration episodes (i.e. consecutive deltaRR and deltaRRn+1 shorten) were increased following salbutamol 7288 [6089, 8486] compared with placebo -1890 [-2600, -1179]; the beat-to beat difference (deltaRRn+1) was reduced after salbutamol compared with the other treatments. ICI 118,551 did not effect acceleration episodes but reduced the effect of salbutamol when used in combination. CONCLUSIONS: Agonism at the cardiac beta2-adrenoceptor in healthy volunteers with salbutamol altered autonomic balance towards sympathetic dominance; this re-balancing was blocked by ICI 118,551 given in combination with salbutamol. However antagonism at the beta2-adrenoceptor with ICI 118,551 alone did not significantly alter the HRV. The beta2-adrenoceptor modulates HRV in healthy volunteers; the implications of agonism and antagonism at the beta2-adrenoceptor in cardiovascular disease states warrants further investigation. (+info)
Intracerebroventricular injection of TNF-alpha promotes sleep and is recovered in cervical lymph.
(13/4912)
Recent studies have shown that the central nervous system (CNS) communicates with the periphery by the drainage of cerebrospinal fluid and brain interstitial fluid into blood and lymph. We hypothesized that tumor necrosis factor (TNF)-alpha would not only influence the CNS by promoting sleep but also would be directly transmitted into the peripheral immune system. Five hundred nanograms of 125I-labeled TNF-alpha were injected into the lateral ventricles of the brain of six sheep and sampled in venous blood and cervical and prescapular lymph every 30 min for 6 h. 125I-TNF-alpha was measured in lymph nodes and control fat, skin, and muscle tissues 6 h postinjection. 125I-TNF-alpha was detected in the cervical lymphatics within the first 30 min and peaked within 2-3 h. 125I-TNF-alpha counts were elevated in the nodes of the head and neck region. Polysomnographic recordings of four animals showed that TNF-alpha induced a significant increase in slow-wave sleep at postinjection hours 4 and 5. CNS TNF-alpha and its direct drainage into the lymphatic system may influence both the sleeping/waking brain and peripheral immune functions. (+info)
Somnogenic relationships between tumor necrosis factor and interleukin-1.
(14/4912)
Both tumor necrosis factor (TNF) and interleukin (IL)-1 are somnogenic cytokines. They also induce each other's production and both induce nuclear factor kappa B activation, which in turn enhances IL-1 and TNF transcription. We hypothesized that TNF and IL-1 could influence each other's somnogenic actions. To test this hypothesis, we determined the effects of blocking both endogenous TNF and IL-1 on spontaneous sleep and on sleep rebound after sleep deprivation in rabbits. Furthermore, the effects of inhibition of TNF on IL-1-induced sleep and the effects of blocking IL-1 on TNF-induced sleep were determined. A TNF receptor fragment (TNFRF), as a TNF inhibitor, and an IL-1 receptor fragment (IL-1RF), as an IL-1 inhibitor, were used. Intracerebroventricular injection of a combination of the TNFRF plus the IL-1RF significantly reduced spontaneous non-rapid eye movement sleep by 87 min over a 22-h recording period. Pretreatment of rabbits with the combination of TNFRF and IL-1RF also significantly attenuated sleep rebound after sleep deprivation. Furthermore, the TNFRF significantly attenuated IL-1-induced sleep but not fever. Finally, the IL-1RF blocked TNF-induced sleep responses but not fever. Results indicate that TNF and IL-1 cooperate to regulate physiological sleep. (+info)
Effects of granulocyte colony-stimulating factor on night sleep in humans.
(15/4912)
Numerous animal studies suggest that cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) mediate increased sleep amount and intensity observed during infection and are, moreover, involved in physiological sleep regulation. In humans the role of cytokines in sleep-wake regulation is largely unknown. In a single-blind, placebo-controlled study, we investigated the effects of granulocyte colony-stimulating factor (G-CSF, 300 microgram sc) on the plasma levels of cytokines, soluble cytokine receptors, and hormones as well as on night sleep. G-CSF did not affect rectal temperature or the plasma levels of cortisol and growth hormone but did induce increases in the plasma levels of IL-1 receptor antagonist and both soluble TNF receptors within 2 h after injection. In parallel, the amount of slow-wave sleep and electroencephalographic delta power were reduced, indicating a lowered sleep intensity. We conclude that G-CSF suppresses sleep intensity via increased circulating amounts of endogenous antagonists of IL-1beta and TNF-alpha activity, suggesting that these cytokines are involved in human sleep regulation. (+info)
Normal electrophysiological and behavioral responses to ethanol in mice lacking the long splice variant of the gamma2 subunit of the gamma-aminobutyrate type A receptor.
(16/4912)
The gamma subunit of the gamma-aminobutyric acid type A receptor (GABA(A)-R) is essential for bestowing both normal single channel conductance and sensitivity to benzodiazepines on native GABA(A)-Rs. The long splice variant of the gamma2 subunit (gamma2L) has been postulated to be essential in mediating the modulatory actions of ethanol at the GABA(A)-R. In order to evaluate this hypothesis, gene targeting was used to delete the 24bp exon which distinguishes gamma2L from the short splice variant (gamma2S). Mice homozygous for this exon deletion (gamma2L-/-) are viable and indistinguishable from wild-type (gamma2L+/+) mice. No gamma2L mRNA was detected in these mice, nor could gamma2L-containing GABA(A)-R protein be detected by specific antibodies. Radioligand binding studies showed the total amount of gamma2 subunit protein to be not significantly changed, suggesting that gamma2S replaces gamma2L in the brains of the knockout animals. Electrophysiological recordings from dorsal root ganglion neurons revealed a normal complement of functional receptors. There was no difference in the potentiation of GABA currents by ethanol (20-200 mM) observed in neurons from gamma2L+/+ or gamma2L-/- mice. Several behavioral effects of ethanol, such as sleep time, anxiolysis, acute functional tolerance, chronic withdrawal hyperexcitability and hyperlocomotor activity were also unaffected by genotype. It is concluded that gamma2L is not required for ethanol's modulatory action at the GABA(A)-R or whole animal behavioral effects. (+info)