Melatonin treatment for circadian rhythm sleep disorders

We administered 1-3 mg melatonin to 11 patients (eight men, three women, aged 16-46 years) with circadian rhythm sleep disorders; nine with delayed sleep phase syndrome and two with non-24-hour sleep-wake syndrome. Sleep logs were recorded throughout the study periods and actigraph and rectal temperature were monitored during treatment periods. Melatonin was administered 1-2 h before the desirable bedtime for expected phase-shifting, or 0.5-1 h before habitual bedtime for gradual advance expecting an hypnotic effect of the melatonin. Melatonin treatments were successful in 6/11 patients. Timing and dose of melatonin administration, together with its pharmacological properties for circadian rhythm sleep disorders, should be further studied.     

Effects of corticotropin-releasing factor on circadian locomotor rhythm in the golden hamster

Stress produces a reduction in the amplitude of some circadian rhythms. The neurochemical mechanisms underlying stress-induced changes in circadian rhythms are not known. To investigate a possible role of corticotropin-releasing factor (CRF) in this phenomenon, three related experiments were carried out: activity rhythms of male golden hamsters (10/14 hours light/dark entrained, lights on at 0800 h) were measured 1) following the intracerebroventricular administration of CRF (0.5, 1.0, 2.0, or 4.0 microg) at two different times of day, 2) following social stress (30-min resident-intruder confrontation), 3) and following the administration of the CRF-antagonist alpha-helical CRF9-41 (2.0 microg) prior to a 15-min resident-intruder confrontation. CRF produced a significant, dose-related decrease in circadian rhythm amplitude following administration in the morning hours, but not in the afternoon. CRF also induced transient increases in activity post injection concomitant with an activation of the hypothalamic-pituitary-adrenocortical (HPA) system. Stress similarly reduced the amplitude of activity patterns and stimulated the HPA system. The stress-induced depression of circadian rhythm amplitude was significantly attenuated following alpha-helical CRF9-41. These data suggest a role for CRF in the stress-related modulation of circadian locomotor rhythm amplitude.     

Effects of ageing on modulation of hormonal secretions by sleep and circadian rhythmicity

Circadian rhythmicity persists in healthy elderly subjects but a number of 24 hour rhythms are dampened and/or advanced in old age. The tendency for earlier sleep onset, earlier morning awakening and a more fragmented and more shallow sleep period is representative of these alterations. Other overt rhythms which have been shown to be of lower amplitude and/or phase-advanced are those of body temperature and of the peripheral levels of hormones such as cortisol, melatonin, TSH, testosterone, prolactin and GH. Mean hormonal levels are generally decreased, but overall cortisol secretion is increased with ageing. These modifications are likely to be partially due to alterations of the circadian central nervous system processes controlling circadian rhythmicity and sleep.     

The effects of sleep on circulating catecholamines and aqueous flow in human subjects

OBJECTIVE: To compare the safety, efficacy and acceptability of a continuous low dose oestradiol releasing vaginal ring with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy. DESIGN: An open, parallel, comparative multicentre trial. SETTING: Sydney and Melbourne, Australia. PARTICIPANTS AND INTERVENTIONS: One hundred and ninety-four postmenopausal women with symptoms and signs of urogenital atrophy were randomised on a 2:1 basis to 12 weeks of treatment with an oestrogen vaginal ring versus an oestrogen cream. MAIN OUTCOME MEASURES AND RESULTS: Equivalence (95% CI) was demonstrated between the two treatments for relief of vaginal dryness and dyspareunia, resolution of atrophic signs, improvement in vaginal mucosal maturation indices and reduction in vaginal pH. No significant difference was demonstrated in endometrial response to a progestogen challenge test and equivalence was demonstrated in the incidence of intercurrent bleeding episodes. The vaginal ring was significantly more acceptable than the cream P < 0.0001), and was preferred to the cream (P < 0.001). CONCLUSION: With equivalent efficacy and safety and superior acceptability to vaginal cream, the low dose oestradiol vaginal ring is an advance in vaginal delivery systems for the treatment of urogenital atrophy.     

Wrist activity rhythm and sleep diary of delayed sleep phase syndrome

PURPOSE: To describe the complication of retained intraocular recipient corneal button after penetrating keratoplasty. METHOD: Case report. A 27-year-old man was referred to us because of complications after penetrating keratoplasty on the right eye. Slit-lamp examination disclosed a clear graft with a second clear corneal button behind. RESULTS: A second penetrating keratoplasty was performed successfully on the right eye. Histologic examination showed an intact epithelium and stroma vascularization of the recipient corneal button. Immunochemistry of the recipient corneal button and the first donor corneal button was performed. CONCLUSION: Although the recipient corneal button remained inside the anterior chamber for 5 months, no epithelial ingrowth occurred.     

The effect of calcium supplementation on the circadian rhythm of bone resorption

Bone resorption shows a circadian rhythm in human subjects, but the physiological mechanisms underlying this rhythm are unknown. We compared the circadian rhythm of bone collagen degradation in 18 premenopausal women before and after oral calcium supplementation (1000 mg calcium for 14 days). Subjects were randomized to receive calcium at either 0800 h or 2300 h. Continuous 48-h urine collections and 1 day of 4-h urine collections were obtained before and after the 14-day supplementation period. We measured urinary deoxypyridinoline (Dpd) and the cross-linked N-telopeptide of type I collagen (NTx) as biochemical markers of bone resorption. There was a significant effect of time of day on excretion of Dpd and NTx (analysis of variance, P < 0.001) with peak excretion between 0300-0700 h and a nadir between 1500-1900 h. The mean amplitude (peak to trough) was similar for Dpd and NTx (70.3% and 63.3%, respectively). Evening calcium supplementation resulted in marked suppression of the nocturnal increase in Dpd and NTx and reversed the usual nocturnal increase in the level of parathyroid hormone. In contrast, morning calcium supplementation had no significant effect on the circadian rhythm of Dpd or NTx. Evening calcium supplementation suppressed overall daily excretion of Dpd by 20.1% (P = 0.03) and NTx by 18.1% (P = 0.03). Morning calcium supplementation had no significant effect on overall daily excretion of either Dpd or NTx. We conclude that evening calcium supplementation suppresses the circadian rhythm of bone resorption. The daily rhythm of PTH secretion or calcium intake is likely to be an important determinant of this rhythm. Experimental protocols designed to investigate the effect of calcium supplementation on bone mineral density should take the timing of supplementation into account.     

Effects of organophosphates on rabbit pyramidal cells firing pattern and hippocampal theta rhythm

The effects of the irreversible acetylcholinesterase (AChE) antagonist paraoxon (Px) on hippocampal neurophysiology were investigated and compared to those of physostigmine in urethane-anaesthetized rabbits. Hippocampal CA1 EEG signals were analyzed by power spectra. Following intracarotid administration, the two drugs induced a similar fundamental low-frequency theta power peak while the appearance of a second theta harmonic was commonly found under Px. Again, inhibition of CA1 pyramidal cells firing was significantly more pronounced after Px injection than after physostigmine. A potent inhibitory action was also described following local Px iontophoretic application. However, a discrepancy appeared between the effects of Px and the classical cholinergic drugs (acetylcholine, physostigmine). The results indicate that Px and physostigmine have a rather similar influence on the septo-hippocampal pathway and support suggestions that Px could act within local hippocampal circuitry through other systems than the cholinergic system exclusively.     

Recognition memory, sleep and circadian rhythms.

Examined the effects of sleep on memory. In Exp 1, 43 Ss learned a list of words and were tested for recognition 24 hrs later. For the delayed sleep group, learning was followed by a period of wakefulness; for the immediate sleep group, it was followed by a period of sleep. Retention was significantly better for the immediate sleep group. In Exp 2, 69 Ss were tested approximately 8 hrs after learning. The normal waking group learned and was tested after a period of daytime wakefulness; the normal sleep group learned and was tested after a period of nighttime sleep; and the sleep deprivation group learned and was tested after a period of nighttime wakefulness. In agreement with previous work (e.g., J. G. Jenkins and K. M. Dallenbach, 1924), retention for the normal sleep group was superior to that of the normal waking group; however, retention was not better for the normal sleep group than for the sleep deprivation group. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of sleep deprivation and other stressors on the immune and inflammatory responses of influenza-infected mice

Many stressors have well-documented effects on host immune competence. However, two important stressors that have not been extensively characterized in terms of their immune-modulatory properties are sleep deprivation and alterations in light:dark cycles. We therefore evaluated the effects of these stressors on the immune and inflammatory responses of mice inoculated intranasally with influenza virus. In contrast to a previous report, sleep deprivation did not significantly alter viral clearance or antibody titers of either virus-naive or immunized mice. Exposure to constant light also failed to affect these variables. However, repeated overnight restraint, a well-characterized stressor, reduced the pulmonary inflammatory response elicited by influenza virus, as previously reported. The data indicate that sleep deprivation and altered light cycles do not markedly influence selected host defense responses to influenza infection under the conditions tested.     

A circadian rhythm of locomotor activity in newly emerged Ceratophyllus sciurorum

An amended version of the Short Form 36 health survey questionnaire (SF-36), which has been suggested as being more suitable for self-completion in older adults, was evaluated among a group of elderly subjects with Parkinson's disease (PD). In the subjects who were able to fully complete the modified SF-36 unaided, the severity of PD was broadly reflected by low reported levels of functioning and well-being with this measure. However, the modified questionnaire still did not overcome the problem of missing responses from elderly subjects. A total of 24% of respondents missed one or more of the 36 statements and 80% of missing responses were concentrated in the three statements which had been modified. The SF-36 in its original form would need to be combined with a disease-specific measure to adequately evaluate the health status of older adults with PD.     

Effect of chronic tryptophan depletion on the circadian rhythm of wheel-running activity in rats

The effect of chronic treatment with a tryptophan (TRP)-free diet on the free-running circadian wheel-running rhythm and the central serotonergic system was investigated in blinded male rats. The long-term TRP-free diet did not change periods of activity, but disordered their patterns. This seemed to be due to masking, entrainment, enhancement of the morning activity, and obscuring of the activity onset as well as appearance of some periodic activities within the subjective night. A long-term TRP-fre diet decreased the concentration of TRP, 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in all brain regions tested: frontal cortex, hippocampus, thalamus, hypothalamus, midbrain, and pons. Density of 5-HT1A receptor binding was significantly decreased in the frontal cortex and hypothalamus, whereas no significant change was observed in the density of 5-HT2 receptor binding in all regions. These results suggest that the period of primary circadian pacemaker is not affected, but its oscillation, as well as the coupling strength between the primary and secondary pacemakers, is weakened by the dysfunction of the serotonergic system caused by chronic TRP depletion.     

Changes in circadian rhythm of blood pressure in on-call pediatric residents

To provide an objective measure of the effects of on-call stress on the blood pressure (BP) of a group of pediatric residents, we used a SpaceLabs Ambulatory Blood Pressure Monitor (ABPM) to compare 37 pediatric residents' on- and off-call BPs. Residents wore the ABPM for 24 h (once on call and again off call) to assess systolic and diastolic BPs every 30 min during the day and hourly overnight. We found significantly higher MESOR (an acronym for midline estimating statistic of rhythm, which yields a mean value more representative of the true mean than an average of a series of measurements) BPs and BP loads (%BP readings > 135 mm Hg for systolic and/or 85 mm Hg diastolic) during the on-call period. Some residents became hypertensive on call, and the normal 24-h pattern of lower nighttime blood pressures was altered during this period. ABPM monitoring may prove useful in evaluating the effectiveness of interventions to reduce the stress of residency training.     

The role of vasopressin in modulating circadian rhythm responses to phase shifts

Telemetered body temperature (BT), heart rate (HR), and motor activity (AC) data were collected in vasopressin-containing, Long-Evans (LE) and vasopressin-deficient, Brattleboro (DI) rats. In Experiment 1, the rats were initially exposed to a 12 h/12 h light/dark cycle under ad-libitum feeding and were then subjected to either a phase-advance or phase-delay shift of 6 h. After the phase-advance shift, neither strain adapted; however, after the phase-delay shift, both strains adapted rapidly. In Experiment 2, the animals were subjected to either a nocturnal or a diurnal restricted-feeding paradigm and were then exposed to either a phase-advance or phase-delay shift with synchronized feeding. In the nocturnal restricted-feeding paradigms, both strains rapidly adapted to both shifts. Concerning diurnal restricted-feeding, DI animals readily entrained to the presentation of food in both shifts; whereas, LE animals exhibited a confused rhythmicity. In Experiment 3, animals were subjected to a phase-advance shift, while the time of feeding was held constant. Following the shift, LE animals responded to the onset of the dark at the new time; yet, were still influenced by the presentation of food. The DI animals maintained the preshift circadian pattern and continued to be dominated by the presentation of food. These experiments indicate that circadian rhythms of LE animals are dominated by the light entrainable oscillator (LEO) in ad-libitum feeding and by both the LEO and food entrainable oscillator (FEO) in restricted-feeding. On the other hand, the circadian rhythms of DI animals are dominated by the FEO unless food is provided ad-libitum. The demonstrated role of vasopressin in synchronizing circadian rhythms to the LEO may be of significance in understanding human circadian rhythm disturbances, such as jet lag.     

Effects of dexamethasone on sleep

OBJECTIVE: To explore the morphological feature, its pathogenesis and clinical significance of hypoxic-ischemic encephalopathy (HIE) through pathological examinations. METHODS: In addition to the routine pathologic examination, the brain tissues, including frontal lobus, temporal lobus, occipital lobus, hippocampus, capsula interna, cerebellum and medullary bulb, were sectioned and examined respectively. RESULTS: (1) 93.5% of cases had a history of direct or indirect asphyxia. (2) The main pathological alterations were edema, congestion, hyaline thrombosis, haemorrhage, degeneration and necrosis of nerve cells. Softening, calcification, cavity formation and fibrosis were also seen in some cases. CONCLUSIONS: The study suggested that congestion and edema of cerebral tissue were essential changes for the pathogenesis of HIE. Hemorrhage and necrosis were common pathological alterations. Fibrosis and cavitation were changes of convalescence. It is of primary importance to treat asphyxia during perinatal period for the prevention of HIE.     

Effects of hormones on sleep

Administration of hormones to humans and animals results in specific effects on the sleep electroencephalogram (EEG) and nocturnal hormone secretion. Studies with pulsatile administration of various neuropeptides in young and old normal controls and in patients with depression suggest they play a key role in sleep-endocrine regulation. Growth hormone (GH)-releasing hormone (GHRH) stimulates GH and slow wave sleep (SWS) and inhibits cortisol, whereas corticotropin-releasing hormone (CRH) exerts opposite effects. Changes in the GHRH:CRH ratio contribute to sleep-endocrine aberrations during normal ageing and acute depression. In addition, galanin and neuropeptide Y promote sleep, whereas, in the elderly, somatostatin impairs sleep. The rapid eye movement (REM)-nonREM cycle is modulated by vasoactive intestinal polypeptide. Cortisol stimulates SWS and GH, probably by feedback inhibition of CRH. Neuroactive steroids exert specific effects on the sleep EEG, which can be explained by gamma-aminobutyric acid(A) receptor modulation.