CIRCADIAN RHYTHMS AND SLEEP IN HUMAN AGING

This issue of Chronobiology International is dedicated to the age-related changes in circadian rhythms as they occur in humans. It seems timely to give an overview of the knowledge and hypotheses on these changes now that we enter a century in which the number and percentage of elderly in the population will be unprecedented. Although we should take care not to follow the current tendency to think of old age as a disease—ignoring the fine aspects of being old—there is definitely an age-related increase in the risk of a number of conditions that are at least uncomfortable.

Circadian rhythms have been attributed adaptive values that usually go unnoticed, but can surface painfully clear when derangements occur. Alterations in the regulation of circadian rhythms are thought to contribute to the symptoms of a number of conditions for which the risk is increased in old age (e.g., sleep disturbances, dementia, and depression). A multidisciplinary approach to investigate the mechanisms of age-related changes in circadian regulation eventually may result in treatment strategies that will improve the quality of life of the growing number of elderly.

Although diverse topics are addressed in this issue, the possible mechanisms by which a deranged circadian timing system may be involved in sleep disturbances receives the most attention. This seems appropriate in view of the numerous studies that have addressed this relation in the last decade and also because of the high frequency and strong impact of sleep disturbances in the elderly. This introduction to the special issue first briefly addresses the impact of disturbed sleep in the elderly to show that the development of therapeutic methods other than the currently available pharmacological treatments should be given high priority. I believe that chronobiological insights may play an important role in the development of rational therapeutical methods.(Chronobiology International, 17(3), 233–243, 2000)     

CIRCADIAN VARIABILITY OF BILIRUBIN IN HEALTHY MEN DURING NORMAL SLEEP AND AFTER AN ACUTE SHIFT OF SLEEP

Bilirubin is a laboratory test widely used for patient care, especially neonatal patients and patients with anemia or suspected liver disorders. Bilirubin has also been shown to be associated with sleep pattern and oxidative stress. The aim of this study was to investigate the variation of bilirubin in a group of healthy individuals with normal night sleep as well as during acutely displaced sleep, as sleep timing varies immensely between individuals while clinical samples are still mainly taken in the morning. We studied the diurnal variation of bilirubin during night-sleep and day-sleep conditions in seven healthy volunteers. Serum samples were collected every hour (50 samples/individual) to evaluate the effect of different sampling times and sleep displacement on the test results. The mean acrophases (peak time) occurred at 10.6?h during the night-sleep condition and at 18.4?h during the day-sleep condition. The diurnal intraindividual variation was high during both the night-sleep and day-sleep conditions, with coefficients of variation (CV) in the range of 12.8 to 42.5%. The diurnal variation was higher during the day compared to night-sleep condition. Thus, bilirubin sampling should be restricted to the morning, preferably after a normal night sleep, to minimize intraindividual variation. (Author correspondence: anders.larsson@akademiska.se)     

CIRCADIAN CHANGES OF HEART RATE IN WEST SYNDROME

Patterns of circadian and ultradian rhythms in the heart rate(HR) are described in a full-term baby with birth asphyxia and convulsions.A 24h HR recording was carried out at the age of 1, 15, 56, 289, and 295 days;West syndrome diagnosis was made when the patient was 3 months old. The HRshowed no circadian rhythm in the follow-up, whereas it is known that thecircadian rhythm appears in healthy infants at the age of 1 month and remainsthereafter. This observation may be an indirect indicator of the interferenceof West syndrome with centers of neurological maturity. (ChronobiologyInternational, 17(4), 591–595, 2000)     

CIRCADIAN VARIATION IN ONSET OF ACUTE CARDIOGENIC PULMONARY EDEMA IS INDEPENDENT OF PATIENTS' FEATURES AND UNDERLYING PATHOPHYSIOLOGICAL CAUSES

Background. The present study aimed to confirm the existence of a circadian pattern in the onset of acute pulmonary edema (APE) and to verify whether sex, age, preexisting diseases, and clinical causes determining the event may influence it. Subjects and Methods. The study considered all consecutive cases of APE observed at the St. Anna General Hospital of Ferrara, Italy, during a 7-year period from January 1, 1992, to December 31, 1998. The sample population was divided into subgroups by sex, age (<75 and ≥75 years), presence or absence of diabetes and hypertension, clinical causes determining the event (i.e., acute myocardial infarction (AMI), pulmonary embolism, arrhythmias). The most important associated or concomitant diseases were also considered (i.e., coronary heart disease and angina, previous myocardial infarction, chronic cardiac failure, dilatative cardiopathy, chronic atrial fibrillation, valvular disease, chronic obstructive pulmonary disease, chronic cor pulmonale, malignancy, chronic renal failure). Time of symptom onset of each event was recorded accurately, then tabulated into 24 increments of 1h (e.g., 06:00 to 06:59 was reported as 6 A.M.). For statistical chronobiological analysis, partial Fourier series were used. Results. During the 7-year period, 1321 consecutive cases of APE in 1014 different subjects were observed. The majority of events occurred at night, and statistical analysis showed a 24h rhythmicity both in the total sample population and in all considered subgroups, with the only exception being patients with pulmonary embolism and arrhythmias, for which the small number of cases made the study of rhythms in APE impossible. Conclusions. The nighttime preference in the occurrence of APE appears to be quite independent of all demographic features or underlying pathophysiological causes. (Chronobiology International, 17(5), 705–715, 2000)     

MOOD AND THE CIRCADIAN SYSTEM: INVESTIGATION OF A CIRCADIAN COMPONENT IN POSITIVE AFFECT

The aim of this study was to test if the pattern of human mood variation across the day is consistent with the hypothesis that self-reports of positive affect (PA) have a circadian component, and self-reports of negative affect (NA) do not. Data were collected under two protocols: normal ambulatory conditions of activity and rest and during a 27h constant routine (CR) procedure. Mood data were collected every 3 h during the wake span of the ambulatory protocol and hourly during the 27h CR. In both protocols, rectal temperature data were continuously recorded. In the ambulatory protocol, activity data were also collected to enable estimation of the unmasked (purified) temperature rhythm. Participants were 14 healthy females aged 18–25 yr in the follicular phase of the menstrual cycle. Under both protocols, PA exhibited significant 24h temporal variation [CR: F(23,161)=2.12, p<0.01; ambulatory: F(5,55)=2.44, p<0.05] with a significant sinusoidal component [CR: F(2,21)=7.51, p<0.01; ambulatory: F(2,3)=20.49, p<.05] of the same form as the circadian temperature rhythm. In contrast, NA exhibited an increasing linear trend over time under the ambulatory protocol [F(1,11)=5.74, p<0.05] but nonsignificant temporal variation under the CR protocol. The findings support the hypothesis of a circadian component in PA variation.     

MODIFICATIONS TO WEEKEND RECOVERY SLEEP DELAY CIRCADIAN PHASE IN OLDER ADOLESCENTS

Adolescents often report shorter time in bed and earlier wake-up times on school days compared to weekend days. Extending sleep on weekend nights may reflect a “recovery” process as youngsters try to compensate for an accumulated school-week sleep debt. The authors examined whether the circadian timing system of adolescents shifted after keeping a common late weekend “recovery” sleep schedule; it was hypothesized that a circadian phase delay shift would follow this later and longer weekend sleep. The second aim of this study was to test whether modifying sleep timing or light exposure on weekends while still providing recovery sleep can stabilize the circadian system. Two experiments addressed these aims. Experiment 1 was a 4-wk, within-subjects counterbalanced design comparing two weekend sleep schedule conditions, “TYPICAL” and “NAP.” Compared to weeknights, participants retired 1.5?h later and woke 3?h later on TYPICAL weekends but 1?h later on NAP weekends, which also included a 2-h afternoon nap. Experiment 2 was a 2-wk, between-subjects design with two groups (“TYPICAL” or “LIGHT”) that differed by weekend morning light exposure. TYPICAL and LIGHT groups followed the TYPICAL weekend schedule of Experiment 1, and the LIGHT group received 1?h of light (454–484?nm) upon weekend wake-up. Weekend time in bed was 1.5?h longer/night than weeknights in both experimental protocols. Participants slept at home during the study. Dim light melatonin onset (DLMO) phase was assessed in the laboratory before (Friday) and after (Sunday) each weekend. Participants were ages 15 to 17 yrs. Twelve participants (4 boys) were included in Experiment 1, and 33 (10 boys) were included in Experiment 2. DLMO phase delayed over TYPICAL weekends in Experiment 1 by (mean?±?SD) 45?±?31?min and Experiment 2 by 46?±?34?min. DLMO phase also delayed over NAP weekends (41?±?34?min) and did not differ from the TYPICAL condition of Experiment 1. DLMO phase delayed over LIGHT weekends (38?±?28?min) and did not differ from the TYPICAL group of Experiment 2. In summary, adolescents phase delay after keeping a commonly observed weekend sleep schedule. Waking earlier or exposure to short-wavelength light on weekend mornings, however, did not stabilize circadian timing in this sample of youngsters. These data inform chronotherapy interventions and underscore the need to test circadian phase-shifting responses to light in this age group. (Author correspondence: Stephanie_J_Crowley@rush.edu)     

FAILURE OF EXTRAOCULAR LIGHT TO FACILITATE CIRCADIAN RHYTHM REENTRAINMENT IN HUMANS

Although extraocular light can entrain the circadian rhythms of invertebrates and nonmammalian vertebrates, almost all studies show that the mammalian circadian system can only be affected by light to the eyes. The exception is a recent study by Campbell and Murphy that reported phase shifts in humans to bright light applied with fiber-optic pads behind the knees (popliteal region). We tested whether this extraocular light stimulus could accelerate the entrainment of circadian rhythms to a shift of the sleep schedule, as occurs in shift work or jet lag. In experiment 1, the sleep/dark episodes were delayed 8h from baseline for 2 days, and 3h light exposures were timed to occur before the temperature minimum to help delay circadian rhythms. There were three groups: (1) bright (about 13,000 lux) extraocular light from fiber-optic pads, (2) control (dim light, 10–20 lux), and (3) medium-intensity (about 1000 lux) ocular light from light boxes. In experiment 2, the sleep/dark episodes were inverted, and extraocular light was applied either before the temperature minimum to help delay circadian rhythms or after the temperature minimum to help advance rhythms. Circadian phase markers were the salivary dim light melatonin onset (DLMO) and the rectal temperature minimum. There was no evidence that the popliteal extraocular light had a phase-shifting effect in either experiment. Possible reasons for phase shifts in the Campbell and Murphy study and not the current study include the many differences between the protocols. In the current study, there was substantial sleep deprivation before the extraocular light was applied. There was a large shift in the sleep/dark schedule, rather than allowing subjects to sleep each day from midnight to noon, as in the Campbell and Murphy study. Also, when extraocular light was applied in the current protocol, subjects did not experience a change from sleeping to awake, a change in posture (from lying in bed to sitting in a chair), or a change in ocular light (from dark to dim light). Further research is necessary to determine the conditions under which extraocular light might produce phase shifts in human circadian rhythms. (Chronobiology International, 17(6), 807–826, 2000).     

SLEEP AND CIRCADIAN PHASE CHARACTERISTICS OF ADOLESCENT AND YOUNG ADULT MALES IN A NATURALISTIC SUMMERTIME CONDITION

Our aim was to compare the circadian phase characteristics of healthy adolescent and young adult males in a naturalistic summertime condition. A total of 19 adolescents (mean age 15.7 years) and 18 young adults (mean age 24.5 years) with no sleep problems took part in this study. Two-night polysomnographic (PSG) sleep recordings and 24h secretion patterns of urinary 6-sulfatoxymelatonin were monitored in all 37 subjects. Sleep-wake patterns were initially assessed at home using a standard sleep diary. Circadian assessment included the measure of dim light melatonin offset (DLMOff) and the morningness-eveningness (M/E) questionnaire. As expected, compared to young adults, adolescents habitually spent more nocturnal time in bed and spent more time (and percentage) in delta sleep. No difference was found between adolescents and young adults on multiple sleep latency test (MSLT) sleep onset latencies, M/E, melatonin secretion measures (24h total, nighttime, daytime, and night ratio), and DLMOff. For the subjects as a whole, correlational analyses revealed a significant association between the DLMOff and M/E and between both these phase markers and habitual bedtimes, habitual rising times, and melatonin secretion measures (daytime levels and the night ratio). No association was found between phase markers and daytime sleepiness or sleep consolidation parameters such as sleep efficiency or number of microarousals. These results together indicate that adolescents and young adults investigated during summertime showed similar circadian phase characteristics, and that, in these age groups, an evening phase preference is associated with a delayed melatonin secretion pattern and delayed habitual sleep patterns without a decrease in sleep consolidation or vigilance. (Chronobiology International, 17(4), 489–501, 2000)     

CIRCADIAN VARIATION OF SERUM LEPTIN IN HEALTHY AND DIABETIC MEN

Leptin, from the Greek leptos, meaning thin (in reference to its ability to reduce body fat stores), is a hormone secreted primarily by adipocytes. At one time, leptin was portrayed as a potential means of combating obesity. Recently, leptin has been identified as a potent inhibitor of bone formation, acting through the central nervous system. Since numerous studies clearly show that bone remodeling is circadian rhythmic with peak activity during sleep, it is of interest to explore circadian variability in serum leptin. Accordingly, circadian characteristics of serum leptin were examined in 7 clinically healthy men and 4 obese men with type II diabetes. Blood samples were collected for 24h at 3h intervals beginning at 19:00. The dark (sleep) phase of the light-dark cycle extended from 22:30 to 06:30, with brief awakening for sampling at 01:00 and 04:00. Subjects consumed general hospital meals (2400 calories) at 16:30, 07:30, and 13:30. Serum leptin levels were determined by a R&D Systems enzyme immunoassay technique. Data were analyzed by linear least-squares estimation using the population multiple components method. A statistically significant (P <. 018) circadian rhythm modeled by a single 24h cosine curve characterized the data of each group. The 24h mean leptin level was statistically greater (P <. 001) in the obese diabetic men than in the healthy men (9.47 ± 0.66 ng/mL vs. 24.07 ± 1.71 ng/mL, respectively). Higher leptin levels occurred between midnight and roughly 02:30, and lowest leptin levels occurred between noon and the early afternoon. The phasing of this rhythm is similar to the circadian rhythm in bone remodeling previously described. Our results suggest the findings from a single morning blood sampling for leptin may be misleading since it may underestimate the mean 24h and peak concentrations of the hormone. (Chronobiology International, 18(2), 273–283, 2001)     

CIRCADIAN STUDY OF DECOMPRESSION SICKNESS SYMPTOMS AND RESPONSE-ASSOCIATED VARIABLES IN RATS

In order to study circadian rhythms and decompression sickness (DCS), we determined: 1) the baseline circadian time structure in noncompressed rats of potential response variables to compression/decompression (C/D), and 2) whether rats subjected to C/D display a circadian time-dependent difference in inflammatory response intensity and biological tolerance. Subgroups of male rats, standardized to a 12?h light/12?h dark schedule, were evaluated every 4?h over 24?h after they were either compressed to 683?kPa (group E) or remained at sea level (group C). During 60?min recovery, evaluation included gross DCS symptoms and pulmonary edema in all E rats, and cell counts, nitric oxide, protein, thromboxane B_2, and leukotriene E₄ levels in survivors. Chi-square, ANOVA, and 24?h cosinor analyses were used to test for time-of-day effects. C/D exposures near the end of dark/activity or during light/resting were generally better tolerated, with lowest signs of DCS symptoms and lowest responses by most of the variables monitored. More deaths were observed in the first half of the dark/activity span. Of the 16 subsets of inflammatory-associated variables, overall increases were observed in 13 and decreases in 2. Significant or borderline significant circadian time effects were found in 14 variables in group C, 12 variables in group E, and 13 variables in response (E%C). Thus, nearly all baseline indices of DCS demonstrated circadian time-dependencies in the sea-level exposed control rats (group C), and nearly all were modified by the circadian time of C/D. Such time-of-day effects of DCS are potentially relevant to the operational concerns of occupations involving decompression exposures and the investigation of prevention and treatment intervention strategies of DCS. (Author correspondence: Bruce.D.Butler@uth.tmc.edu).     

树■排尿的昼夜节律及其在视交叉上核损毁后的变化

为探讨树视交叉上核是否参与泌尿昼夜节律的调控,对正常树及视交叉上核损毁后的树排尿的昼夜时间规律进行了观测分析。结果表明,正常树排尿呈现明显的昼夜节律———白天尿量为全天尿量的（８８５２±１５４０）％;视交叉上核损毁后,树排尿的昼夜节律明显改变———白天尿量仅为全天尿量的（６２８６±１８１８）％,同时树的尿量（特别是夜间的尿量）明显憎多。以上结果说明视交叉上核在树体内也参与了泌尿昼夜节律的调节。     

CIRCADIAN CHARACTERISTICS OF CORTICOSTERONE SECRETION IN REDBACKED VOLES (CLETHRIONOMYS GAPPERI)

To provide necessary background for study of stress response in redbacked voles (Clethrionomys gapperi), the circadian and ultradian rhythm in corticosterone release was characterized. Animals were maintained under a 16h light, 8h dark cycle. A total of 55 males and 46 females provided 101 independent blood samples over a 6-month span. Samples were obtained at 1h to 2h intervals during the light and at 2h intervals during the dark. Using edited data (5 values beyond the upper 95% limit were removed), a significant time effect was found by analysis of variance (ANOVA) for both sexes at P <. 001. The composite single cosine best describing the circadian waveform for each sex consisted of three components (24h, 12h, and 6h), each significant at P <. 05 (overall model P <. 001). The 24h mean (mesor) was about 60% higher in females than males (646 ng/mL vs. 412 ng/mL, P =. 01), with amplitudes of 429 and 298 ng/mL being proportional (66% vs. 72%) to the respective mesor. The predictable range of change within a 24h span (determined by the double amplitude of a 24h + 12h + 6h cosine model) was large: It was more than 1600 ng/mL for females and more than 900 ng/mL for males. Highest values were found during the dark phase, with the 24h acrophase located at 2h into the dark span for both sexes. With the caveat of fewer samples obtained during dark than during light, the actual peak values for females occurred at 2h and for males at 6h into the 8h dark span. These results provide baseline information about the circadian time structure for serum corticosterone in red-backed voles under normal light-dark, lowstress conditions. (Chronobiology International 18(6) 933–945, 2001)     

BRAIN PHOTORECEPTOR PATHWAYS CONTRIBUTING TO CIRCADIAN RHYTHMICITY IN CRAYFISH

Freshwater crayfish have three known photoreceptive systems: the compound eyes, extraretinal brain photoreceptors, and caudal photoreceptors. The primary goal of the work described here was to explore the contribution of the brain photoreceptors to circadian locomotory activity and define some of the underlying neural pathways. Immunocytochemical studies of the brain photoreceptors in the parastacid (southern hemisphere) crayfish Cherax destructor reveal their expression of the blue light-sensitive photopigment cryptochrome and the neurotransmitter histamine. The brain photoreceptors project to two small protocerebral neuropils, the brain photoreceptor neuropils (BPNs), where they terminate among fibers expressing the neuropeptide pigment-dispersing hormone (PDH), a signaling molecule in arthropod circadian systems. Comparable pathways are also described in the astacid (northern hemisphere) crayfish Procambarus clarkii. Despite exhibiting markedly different diurnal locomotor activity rhythms, removal of the compound eyes and caudal photoreceptors in both C. destructor and P. clarkii (leaving the brain photoreceptors intact) does not abolish the normal light/dark activity cycle in either species, nor prevent the entrainment of their activity cycles to phase shifts of the light/dark period. These results suggest, therefore, that crayfish brain photoreceptors are sufficient for the entrainment of locomotor activity rhythms to photic stimuli, and that they can act in the absence of the compound eyes and caudal photoreceptors. We also demonstrate that the intensity of PDH expression in the BPNs varies in phase with the locomotor activity rhythm of both crayfish species. Together, these findings suggest that the brain photoreceptor cells can function as extraretinal circadian photoreceptors and that the BPN represents part of an entrainment pathway synchronizing locomotor activity to environmental light/dark cycles, and implicating the neuropeptide PDH in these functions. (Author correspondence: bbeltz@wellesley.edu)     

pH HOMEOSTASIS OF THE CIRCADIAN SPORULATION RHYTHM IN CLOCK MUTANTS OF NEUROSPORA CRASSA

The influence of environmental (extracellular) pH on the sporulation rhythm in Neurospora crassa was investigated for wild-type (frq⁺) and the mutants chr, frq¹, frq⁷, and frq⁸. In all mutants, including wild type, the growth rate was found to be influenced strongly by extracellular pH in the range 4–9. On the other hand, for the same pH range, the period length of the sporulation rhythm is little influenced in wild type, chr, and frq¹. A loss of pH homeostasis of the period, however, was observed in the mutants frq⁷ and frq⁸, which also are known to have lost temperature compensation. Concerning the influence of extracellular pH on growth rates, a clear correspondence between growth rates and the concentration of available H₂PO₄^? ion has been found, indicating that the uptake of H₂PO₄^? may be a limiting factor for growth under our experimental conditions. The loss of pH compensation in the frq⁷ and frq⁸ mutants may be related to less easily degradable FRQ^7,8 proteins when compared with wild-type FRQ. Results from recent model considerations and experimental results predict that, with increasing extra-and intracellular pH, the FRQ⁷ protein degradation increases and should lead to shorter period lengths. (Chronobiology International, 17(6), 733–750, 2000)     

CHRONOTYPE,SLEEP LENGTH,AND SCHOOL ACHIEVEMENT OF 11- TO 23-YEAR-OLD STUDENTS IN NORTHERN EUROPEAN RUSSIA

Residing at northern latitudes for long periods of time is associated with sleep disturbances and internal desynchronization, which are considered to be causes of chronic diseases in old age. In children and teenagers, they result in a poor school achievement, psychological problems, and increase in consumption of stimulants. In this paper, we analyze the relationship between both chronotype and sleep length and the variables of age, sex, place of residence, type of settlement (village/city), latitude and longitude of residence, and school achievement of young inhabitants of northern European Russia. We surveyed 1101 children and teenagers between 11 to 23 yrs of age living in four settlements located between 59° and 67° North latitude and 33° and 60° East longitude. The Munich chronotype questionnaire (MCTQ) was used in the study, and all participants were also required to answer a question about their school achievements. An analysis of covariance (ANCOVA) was used to assess the influence of the analyzed factors on sleep length and chronotype. Self-reported sleep length of teenagers depended moderately on age, whereas the place of residence, latitude, and type of settlement only had a weak effect. Chronotype strongly depended on place of residence and longitude; it moderately depended on latitude and age; and it weakly depended on sex and type of settlement. The sleep length of village teenagers was 46?min longer than that of urban teenagers. The authors found a 1?h and 18?min phase delay of the sleep-wake rhythm (as a marker of chronotype) in teenagers moving in the East-West direction and a 16-min delay moving in the South-North direction within one time zone. There was a weak, but significant, positive correlation between chronotype and time of sunrise. There was about a 2-fold stronger influence of chronotype than sleep length on achievement of school children and college students. We conclude that socioeconomic factors exert a significant influence on sleep length and that climatic conditions exert a significant influence on the chronotype of teenagers in the northern latitudes. (Author correspondence: borisenkov@physiol.komisc.ru)     

CIRCADIAN PATTERN OF AMBULATORY BLOOD PRESSURE IN UNTREATED HYPERTENSIVE PATIENTS WITH AND WITHOUT METABOLIC SYNDROME

There is a strong association between metabolic syndrome (MS) and increased risk of end-organ damage, cardiovascular disease, stroke, and cardiovascular mortality. Moreover, non-dipping (<?10% decline in the asleep relative to the awake blood pressure [BP] mean) and elevated ambulatory pulse pressure (PP), among other factors related to the circadian BP pattern, have also been associated with increased cardiovascular morbidity and mortality. This cross-sectional study investigated the circadian BP pattern in 2,045 non-diabetic untreated patients with uncomplicated essential hypertension (941 men/1,099 women), 48.7?±?11.9 yrs of age, classified by the presence or absence of MS. BP was measured by ambulatory monitoring for 48 consecutive hours to substantiate reproducibility of the dipping pattern. Physical activity was simultaneously monitored every min by wrist actigraphy to accurately calculate mean BP when awake and asleep for each subject. MS was present in 40.7% of the patients. Patients with MS were characterized by a significantly higher 24?h mean of systolic BP and a lower diastolic BP compared to patients without MS. Accordingly, ambulatory PP was significantly elevated the entire 24?h in MS patients. The prevalence of an altered non-dipper BP profile was significantly higher in MS patients (48.4 vs. 36.1% in patients without MS, p?<?0.001). MS patients were characterized, among other risk factors, by significantly higher uric acid, fibrinogen, leukocyte count, hemoglobin and globular sedimentation velocity, plus lower estimated glomerular filtration rate. Apart from corroborating the significant increased prevalence of a blunted nocturnal BP decline in MS, this study documents ambulatory PP is higher in MS, without differences between groups in mean arterial pressure. This elevated PP might reflect increased arterial stiffness in MS. MS patients were also characterized by elevated values of relevant markers of cardiovascular risk, including fibrinogen and globular sedimentation velocity. These collective findings indicate that MS should be included among the clinical situations in which ambulatory BP monitoring is recommended. (Author correspondence: rhermida@uvigo.es)     

EXOGENOUS CORTICOSTEROID AND SHIFTS OF CIRCADIAN RHYTHMS IN HAMSTERS

We tested the hypothesis that glucocorticoid stimulation mediates the effect of exercise on circadian clock resetting in hamsters. We injected animals with 1 and 5 mg dexamethasone—a potent glucocorticoid agonist—at zeitgeber time (ZT) 4 and ZT6, circadian phases at which vigorous exercise induces maximal phase advances of about 3h. Neither dose of dexamethasone induced phase shifts that were significantly larger than those induced by injections of saline vehicle at either of the phases tested. Some animals, however, showed quite large and consistent phase shifts to repeated injections whether with saline or dexamethasone, such that there was a statistically significant correlation between individuals' responses to the two treatments. The data indicate no role for increased glucocorticoid activity in mediating the effects of exercise on circadian phase shifting, but suggest a modest role for nonspecific stimulation, independent of exercise, in inducing phase shifts at ZT4–ZT6. (Chronobiology International, 18(2), 203–213, 2001)     

THERMOCYCLIC AND PHOTOCYCLIC ENTRAINMENT OF CIRCADIAN LOCOMOTOR ACTIVITY RHYTHMS IN SLEEPY LIZARDS,TILIQUA RUGOSA

Australian sleepy lizards (Tiliqua rugosa) exhibit marked locomotor activity rhythms in the field and laboratory. Light-dark (LD) and temperature cycles (TCs) are considered important for the entrainment of circadian locomotor activity rhythms and for mediating seasonal adjustments in aspects of these rhythms, such as phase, amplitude, and activity pattern. The relative importance of 24 h LD and TCs in entraining the circadian locomotor activity rhythm in T. rugosa was examined in three experiments. In the first experiment, lizards were held under LD 12:12 and subjected to either a TC of 33:15?°?C in phase with the LD cycle or a reversed TC positioned in antiphase to the LD cycle. Following LD 12:12, lizards were maintained under the same TCs but were subjected to DD. Activity was restricted to the thermophase in LD, irrespective of the lighting regime and during the period of DD that followed, suggesting entrainment by the TC. The amplitude of the TC was lowered by 8?°?C to reduce the intensity and possible masking effect of the TC zeitgeber in subsequent experiments. In the second experiment, lizards were held under LD 12.5:11.5 and subjected to one of three treatments: constant 30?°?C, normal TC (30:20?°?C) in phase with the LD cycle, or reversed TC. Following LD, all lizards were subjected to DD and constant 30?°?C. Post-entrainment free-run records revealed that LD cycles and TCs could both entrain the locomotor rhythms of T. rugosa. In LD, mean activity duration (α) of lizards in the normal TC group was considerably less than that in the constant 30?°?C group. Mean α also increased between LD and DD in lizards in the normal TC group. Although there was large variation in the phasing of the rhythm in relation to the LD cycle in reversed TC lizards, TCs presented in phase with the LD cycle most accurately synchronized the rhythm to the photocycle. In the third experiment, lizards were held in DD at constant 30?°?C before being subjected to a further period of DD and one of four treatments: normal TC (06:00 to 18:00 h thermophase), delayed TC (12:00 to 00:00 h thermophase), advanced TC (00:00 to 12:00 h thermophase), or control (no TC, constant 30?°?C). While control lizards continued to free-run in DD at constant temperature, the locomotor activity rhythms of lizards subjected to TCs rapidly entrained to TCs, whether or not the TC was phase advanced or delayed by 6 h. There was no difference in the phase relationships of lizard activity rhythms to the onset of the thermophase among the normal, delayed, and advanced TC groups, suggesting equally strong entrainment to the TC in each group. The results of this experiment excluded the possibility that masking effects were responsible for the locomotor activity responses of lizards to TCs. The three experiments demonstrated that TCs are important for entraining circadian locomotor activity rhythms of T. rugosa, even when photic cues are conflicting or absent, and that an interaction between LD cycles and TCs most accurately synchronizes this rhythm. (Author correspondence: david.j.ellis@adelaide.edu.au)