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Showing papers in "Chronobiology International in 2005"


Journal ArticleDOI
TL;DR: There is a wealth of information from both applied and experimental work, which, when considered together, suggests that sports performance is affected by time of day in normal entrained conditions and that the variation has at least some input from endogenous mechanisms.
Abstract: We discuss current knowledge on the description, impact, and underlying causes of circadian rhythmicity in sports performance. We argue that there is a wealth of information from both applied and experimental work, which, when considered together, suggests that sports performance is affected by time of day in normal entrained conditions and that the variation has at least some input from endogenous mechanisms. Nevertheless, precise information on the relative importance of endogenous and exogenous factors is lacking. No single study can answer both the applied and basic research questions that are relevant to this topic, but an appropriate mixture of real-world research on rhythm disturbances and tightly controlled experiments involving forced desynchronization protocols is needed. Important issues, which should be considered by any chronobiologist interested in sports and exercise, include how representative the study sample and the selected performance tests are, test-retest reliability, as well as overall design of the experiment.

518 citations


Journal ArticleDOI
TL;DR: The study shows that chronotype (based on MSF as measured by the MCTQ) strongly correlates with morningness‐eveningness (as measured with the MEQ), however, the M CTQ collects additional detailed information on sleep‐wake behavior under natural conditions.
Abstract: We report on results from an Internet survey of sleeping habits in a Dutch population using the Munich Chronotype Questionnaire (MCTQ), supplemented with the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ). The MCTQ was completed by 5,055 responders, of which 2,481 also completed the MEQ. MEQ score correlated well with the MCTQ assessment of time of mid-sleep on free days (MSF; r = - 0.73) and on workdays (MSW; r = - 0.61). MEQ was more strongly correlated with MSF (50% of sleep time) than with sleep onset (0%), rise time (100%), or with any other percentile (10 to 40, 60% to 90%) of sleep on free days. The study shows that chronotype (based on MSF as measured by the MCTQ) strongly correlates with morningness-eveningness (as measured by the MEQ). However, the MCTQ collects additional detailed information on sleep-wake behavior under natural conditions.

411 citations


Journal ArticleDOI
TL;DR: This review first examines reliable and convenient ways of measuring core temperature for studying the circadian rhythm, concluding that measurements of rectal and gut temperature fulfil these requirements, but that insulated axilla temperature does not.
Abstract: This review first examines reliable and convenient ways of measuring core temperature for studying the circadian rhythm, concluding that measurements of rectal and gut temperature fulfil these requirements, but that insulated axilla temperature does not. The origin of the circadian rhythm of core temperature is mainly due to circadian changes in the rate of loss of heat through the extremities, mediated by vasodilatation of the cutaneous vasculature. Difficulties arise when the rhythm of core temperature is used as a marker of the body clock, since it is also affected by the sleep-wake cycle. This masking effect can be overcome directly by constant routines and indirectly by "purification" methods, several of which are described. Evidence supports the value of purification methods to act as a substitute when constant routines cannot be performed. Since many of the mechanisms that rise to the circadian rhythm of core temperature are the same as those that occur during thermoregulation in exercise, there is an interaction between the two. This interaction is manifest in the initial response to spontaneous activity and to mild exercise, body temperature rising more quickly and thermoregulatory reflexes being recruited less quickly around the trough and rising phase of the resting temperature rhythm, in comparison with the peak and falling phase. There are also implications for athletes, who need to exercise maximally and with minimal risk of muscle injury or heat exhaustion in a variety of ambient temperatures and at different times of the day. Understanding the circadian rhythm of core temperature may reduce potential hazards due to the time of day when exercise is performed.

262 citations


Journal ArticleDOI
TL;DR: It is concluded that children with ADHD and chronic idiopathic sleep‐onset insomnia show a delayed sleep phase and delayed DLMO, compared with ADHD children without SOI.
Abstract: To investigate whether ADHD‐related sleep‐onset insomnia (SOI) is a circadian rhythm disorder, we compared actigraphic sleep estimates, the circadian rest‐activity rhythm, and dim light melatonin onset (DLMO) in ADHD children having chronic idiopathic SOI with that in ADHD children without sleep problems. Participants were 87 psychotropic-medication-naive children, aged 6 to 12 yrs, with rigorously diagnosed ADHD and SOI (ADHD‐SOI) and 33 children with ADHD without SOI (ADHD‐noSOI) referred from community mental health institutions and pediatric departments of non‐academic hospitals in The Netherlands. Measurements were 1 wk, 24 h actigraphy recordings and salivary DLMO. The mean (±SD) sleep onset time was 21:38±0:54 h in ADHD‐SOI, which was significantly (p<0.001) later than that of 20:49±0:49 h in ADHD‐noSOI. DLMO was significantly later in ADHD‐SOI (20:32±0:55 h), compared with ADHD‐noSOI (19:47±0:49 h; p<0.001). Wake‐up time in ADHD‐SOI was later than in ADHD‐noSOI (p=0.002). There were no significant...

248 citations


Journal ArticleDOI
TL;DR: It was shown that younger BD1 patients, and those with rapid mood swings, were significantly more likely to have lower CS scores and to have later circadian phase, and CS scores were positively correlated with the age at onset and the duration of the most severe depressive episodes.
Abstract: Abnormalities in circadian rhythms are prominent features of bipolar I disorder (BD1). To investigate circadian variation in BD1, we evaluated morningness–eveningness (M/E), a stable trait reflecting circadian phase, using the composite scale (CS) among BD1 patients (DSM IV criteria; n=75), unscreened controls (n=349), and patients with schizophrenia (SZ) or schizoaffective disorder (SZA) (n=81). Our analyses showed that CS scores correlated significantly with age but did not differ by gender among the controls. BD1 patients differed significantly from controls and from SZ/SZA patients when age was considered. CS scores were distributed bi‐modally among BD1 cases. There are several possible reasons for the observed heterogeneity. Younger BD1 patients, and those with rapid mood swings, were significantly more likely to have lower CS scores (i.e., to score in the ‘evening’ range and to have later circadian phase). CS scores were also positively correlated with the age at onset and the duration of the most s...

195 citations


Journal ArticleDOI
TL;DR: Clinical medicine has been most concerned with the prevention of stroke in the morning, when population‐based studies show it is of greatest risk during the 24 h; however, improved protection of at‐risk patients against stroke inThe early evening, the second most vulnerable time of cerebrovascular accidents, has received relatively little attention.
Abstract: Stroke is the culmination of a heterogeneous group of cerebrovascular diseases that is manifested as ischemia or hemorrhage of one or more blood vessels of the brain. The occurrence of many acute cardiovascular events--such as myocardial infarction, sudden cardiac death, pulmonary embolism, critical limb ischemia, and aortic aneurysm rupture--exhibits prominent 24 h patterning, with a major morning peak and secondary early evening peak. The incidence of stroke exhibits the same 24 h pattern. Although ischemic and hemorrhagic strokes are different entities and are characterized by different pathophysiological mechanisms, they share an identical double-peak 24 h pattern. A constellation of endogenous circadian rhythms and exogenous cyclic factors are involved. The staging of the circadian rhythms in vascular tone, coagulative balance, and blood pressure plus temporal patterns in posture, physical activity, emotional stress, and medication effects play central and/or triggering roles. Features of the circadian rhythm of blood pressure, in terms of their chronic and acute effects on cerebral vessels, and of coagulation are especially important. Clinical medicine has been most concerned with the prevention of stroke in the morning, when population-based studies show it is of greatest risk during the 24 h; however, improved protection of at-risk patients against stroke in the early evening, the second most vulnerable time of cerebrovascular accidents, has received relatively little attention thus far.

168 citations


Journal ArticleDOI
TL;DR: The present results confirmed previous observations that muscle torque changes in a predictable manner during the 24 h period, and that the changes are linked to modifications prevailing at the muscular, rather than the neural, level.
Abstract: The study was conducted first, to determine the possibility of a dichotomy between circadian rhythm of maximal torque production of the knee extensors of the dominant and non-dominant legs, and second, to determine whether the possible dichotomy could be linked to a change in the downward drive of the central nervous system and/or to phenomena prevailing at the muscular level The dominant leg was defined as the one with which subjects spontaneously kick a football Tests were performed at 06:00, 10:00, 14:00, 18:00, and 22:00 h To distinguish the neural and muscular mechanisms that influence muscle strength, the electromyographic and mechanical muscle responses associated with electrically evoked and/or voluntary contractions of the human quadriceps and semi-tendinosus muscles for each leg were recorded and compared The main finding was an absence of interaction between time-of-day and dominance effects on the torque associated with maximal voluntary contraction (MVC) of both quadriceps A significant time-of-day effect on MVC torque of the knee extensors was observed for the dominant and non-dominant legs when the data were collapsed, with highest values occurring at 18:00 h (p < 001) From cosinor analysis, a circadian rhythm was documented (p < 0001) with the peak (acrophase) estimated at 18:18 +/- 00:12 h and amplitude (one-half the peak-to-trough variation) of 33 +/- 11% Independent of the leg tested, peripheral mechanisms demonstrated a significant time-of-day effect (p < 005) on the peak-torque of the single and doublet stimulations, with maximal levels attained at 18:00 h The central activation of the quadriceps muscle of each leg remained unchanged during the day The present results confirmed previous observations that muscle torque changes in a predictable manner during the 24 h period, and that the changes are linked to modifications prevailing at the muscular, rather than the neural, level The similar rhythmicity observed in this study between the dominant and non-dominant legs provides evidence that it is not essential to test both legs when simple motor tasks are investigated as a function of the time of day

151 citations


Journal ArticleDOI
TL;DR: It is found that significant heritable influences on human circadian phase and subjective sleep indices can be detected through family‐based studies.
Abstract: Individual variation in the phase and amplitude of human circadian rhythms is well known, but the impact of heritable factors on such variation is less clear. We estimated the narrow-sense heritability for selected circadian and sleep timing, quality, and duration measures among related members of the Hutterites, an endogamous, religious community (n=521 participants). "Morningness-eveningness" (M/E), a stable trait reflecting circadian phase, was evaluated using the Composite Scale (CS). Subjective sleep measures were assessed using the Sleep Timing Questionnaire. Initial analyses reconfirmed the impact of age on M/E. Previously reported correlations between M/E scores and the sleep measures were also noted, demonstrating the construct validity of the questionnaires among the participants. Following corrections for age, gender, and colony of residence, significant narrow-sense heritability was noted for M/E (23%). The heritability for subjective sleep measures (related to timing, duration, and quality) were statistically significant for all but one variable, and varied between 12.4% and 29.4%. Thus, significant heritable influences on human circadian phase and subjective sleep indices can be detected through family-based studies. In view of the impact of circadian malfunction on human health, it may be worthwhile to map genetic factors impacting circadian and sleep variation.

135 citations


Journal ArticleDOI
TL;DR: There are national differences in factorial structure and that cut‐off scores used to categorize participants as morning‐ and evening‐types should be established for different cultural and age groups.
Abstract: Morningness scales have been translated into several languages, but a lack of normative data and methodological differences make cross-cultural comparisons difficult. This study examines the psychometric properties and factor structure of the Composite Scale of Morningness (CSM) in samples from five countries: France (n = 627), Italy (n = 702), Spain (n = 391), Thailand (n = 503), and Australia (n = 654). Strong national differences are identified. A quadratic relationship between age and CSM total score was apparent in the Australian data with a downward trend after age 35 yrs. There was no age effect in any sample in the range from 18 to 29 yrs. Factor analysis identified a three-factor solution in all groups for both men and women. Tucker's congruence coefficients indicate that: (1) this solution is highly congruent between sexes in each culture, and (2) a morning affect factor is highly congruent between cultures. These results indicate there are national differences in factorial structure and that cut-off scores used to categorize participants as morning- and evening-types should be established for different cultural and age groups.

130 citations


Journal ArticleDOI
TL;DR: It is reported that lower (physiological) doses of up to 300 µg can entrain (synchronize) free‐running circadian rhythms of 10 totally blind subjects that would otherwise drift later each day.
Abstract: The specific circadian role proposed for endogenous melatonin production was based on a study of sighted people who took low pharmacological doses (500 microg) of this chemical signal for the "biological night": the magnitude and direction of the induced phase shifts were dependent on what time of day exogenous melatonin was administered and were described by a phase-response curve that turned out to be the opposite of that for light. We now report that lower (physiological) doses of up to 300 microg can entrain (synchronize) free-running circadian rhythms of 10 totally blind subjects that would otherwise drift later each day. The resulting log-linear dose-response curve in the physiological range adds support for a circadian function of endogenous melatonin in humans. Efficacy of exogenous doses in the physiological range are of clinical significance for totally blind people who will need to take melatonin daily over their entire lifetimes in order to remain entrained to the 24 h day. Left untreated, their free-running endocrine, metabolic, behavioral, and sleep/wake cycles can be almost as burdensome as not having vision.

125 citations


Journal ArticleDOI
TL;DR: Young adult healthy sleepers show robust gender differences in PSG sleep, like older populations, with better sleep quality in women than in men, which highlights the importance of gender in sleep and circadian rhythm research studies employing young subjects and has broader implications for women's health issues relating to these topics.
Abstract: Middle-aged and elderly populations exhibit gender differences in polysomnographic (PSG) sleep; however, whether young men and women also show such differences remains unclear. Thirty-one young healthy sleepers (16 men and 15 women, aged 18 to 30 yr, mean+/-SD, 20.5+/-2.4 yr) completed 3 consecutive overnight sessions in a sleep laboratory, after maintaining a stable sleep-wake cycle for 1 wk before study entry. Standard PSG sleep and self-rated sleepiness data were collected each night. Across nights, women showed better sleep quality than men: they fell asleep faster (shorter sleep onset latency) and had better sleep efficiency, with more time asleep and less time awake (all differences showed large effect sizes, d=0.98 to 1.12). By contrast, men were sleepier than women across nights. Both men and women demonstrated poorer overall sleep quality on the first night compared with the subsequent 2 nights of study. We conclude young adult healthy sleepers show robust gender differences in PSG sleep, like older populations, with better sleep quality in women than in men. These results highlight the importance of gender in sleep and circadian rhythm research studies employing young subjects and have broader implications for women's health issues relating to these topics.

Journal ArticleDOI
TL;DR: Lavender serves as a mild sedative and has practical applications as a novel, nonphotic method for promoting deep sleep in young men and women and for producing gender‐dependent sleep effects.
Abstract: Aromatherapy is an anecdotal method for modifying sleep and mood. However, whether olfactory exposure to essential oils affects night‐time objective sleep remains untested. Previous studies also de...

Journal ArticleDOI
TL;DR: The beneficial effect of time‐of‐day may be limited to a single expression of muscular power and fails to advantage performance during repeated sprints.
Abstract: We investigated the effect of time-of-day on both maximal sprint power and repeated-sprint ability (RSA). Nine volunteers (22+/-4 yrs) performed a RSA test both in the morning (07:00 to 09:00 h) and evening (17:00 to 19:00 h) on different days in a random order. The RSA cycle test consisted of five, 6 sec maximal sprints interspersed by 24 sec of passive recovery. Both blood lactate concentration and heart rate were higher in the evening than morning RSA (lactate values post exercise: 13+/-3 versus 11+/-3 mmol/L(-1), p<0.05). The peak power developed during the first sprint was higher in the evening than morning (958+/-112 vs. 915+/-133 W, p<0.05), but this difference was not apparent in subsequent sprints, leading to a higher power decrement across the 5x6 sec test in the evening (11+/-2 vs. 7+/-3%, p<0.05). Both the total work during the RSA cycle test and the power developed during bouts 2 to 5 failed to be influenced by time-of-day. This suggests that the beneficial effect of time-of-day may be limited to a single expression of muscular power and fails to advantage performance during repeated sprints.

Journal ArticleDOI
TL;DR: The diurnal variation of the muscle fatigue observed during a maximal and prolonged isokinetic exercise seems to reflect on the muscle, with a greater contractile capacity but a higher fatigability in the evening compared to the morning.
Abstract: The aim of this study was to examine the time-of-day (TOD) effects in myoelectric and mechanical properties of muscle during a maximal and prolonged isokinetic exercise. Twelve male subjects were asked to perform 50 maximal voluntary contractions (MVC) of the knee extensor muscles at a constant angular velocity of 2.09 rad . sec(-1), at 06 : 00 and 18 : 00 h. Torque and electromyographic (EMG) parameters were recorded for each contraction, and the ratio between these values was calculated to evaluate variations of the neuromuscular efficiency (NME) with fatigue and with TOD. The results indicated that maximal torque values (T(45)Max) was significantly higher (7.73%) in the evening than in the morning (p<0.003). The diurnal variation in torque decrease was used to define two phases. During the first phase (1st to the 26th repetition), torque values decreased fast and values were higher in the evening than in the morning, and during the second phase (27th to the 50th repetition), torque decreased slightly and reached a floor value that appeared constant with TOD. The EMG parameters (Root Mean Square; RMS) were modified with fatigue, but were not TOD dependent. The NME decrease-significantly with fatigue, showing that peripheral factors were mainly involved in the torque decrease. Furthermore, NME decrease was greater at 18 : 00 than at 06 : 00 h for the vastus medialis (p<0.05) and the vastus lateralis muscles (p<0.002), and this occurred during the first fatigue phase of the exercise. In conclusion, the diurnal variation of the muscle fatigue observed during a maximal and prolonged isokinetic exercise seems to reflect on the muscle, with a greater contractile capacity but a higher fatigability in the evening compared to the morning.

Journal ArticleDOI
TL;DR: This review summarizes the current knowledge about the ontogenetic development of the circadian system in mammals and reveals that, at prenatal and early postnatal stages, non‐photic cues deriving from the mother are effective and light‐dark entrainment develops later.
Abstract: This review summarizes the current knowledge about the ontogenetic development of the circadian system in mammals. The developmental changes of overt rhythms are discussed, although the main focus of the review is the underlying neuronal and molecular mechanisms. In addition, the review describes ontogenetic development, not only as a process of morpho‐functional maturation. The need of repeated adaptations and readaptations due to changing developmental stage and environmental conditions is also considered. The review analyzes mainly rodent data, obtained from the literature and from the author's own studies. Results from other species, including humans, are presented to demonstrate common features and species‐dependent differences. The review first describes the development of the suprachiasmatic nuclei as the central pacemaker system and shows that intrinsic circadian rhythms are already generated in the mammalian fetus. As in adult organisms, the period length is different from 24 h and needs continuo...

Journal ArticleDOI
TL;DR: There was no evidence for circadian desynchronization associated with aging, but there was evidence of some rearrangement of the internal phase‐angles among the studied circadian rhythms.
Abstract: There is evidence that aging may impair phase-shifting responses to light synchronizers, which could lead to disturbed or malsynchronized circadian rhythms. To explore this hypothesis, 62 elder participants (age, 58 to 84 years) and 25 young adults (age, 19 to 40 years) were studied, first with baseline 1-wk wrist actigraphy at home and then by 72 h in-laboratory study using an ultra-short sleep-wake cycle. Subjects were awake for 60 minutes in 50 lux followed by 30 minutes of darkness for sleep. Saliva samples were collected for melatonin, and urine samples were collected for aMT6s (a urinary metabolite of melatonin) and free cortisol every 90 minutes. Oral temperatures were also measured every 90 minutes. The timing of the circadian rhythms was not significantly more variable among the elders. The times of lights-out and wake-up at home and urinary free cortisol occurred earlier among elders, but the acrophases (cosinor analysis-derived peak time) of the circadian rhythm of salivary melatonin, urinary aMT6s, and oral temperature were not significantly phase-advanced among elders. The estimated duration of melatonin secretion was 9.9 h among elders and 8.4 h among young adults (p < 0.025), though the estimated half-life of blood melatonin was shorter among elders (p < 0.025), and young adults had higher saliva melatonin and urinary aMT6s levels. In summary, there was no evidence for circadian desynchronization associated with aging, but there was evidence of some rearrangement of the internal phase-angles among the studied circadian rhythms.

Journal ArticleDOI
TL;DR: The changes in the secretory pattern of hormones hereby reported may be part of the neuroendocrine and metabolic mechanisms evolved to maximize survival during periods of food shortage.
Abstract: Calorie restriction of young male rats increases plasma prolactin, decreases luteinizing hormone (LH) and testosterone, and disrupts their 24 h secretory pattern. To study whether this could be the consequence of stress, we examined the 24 h variations of plasma adrenocorticotropic hormone (ACTH) corticosterone, growth hormone (GH), leptin, and adrenal corticosterone. Rats were submitted to a calorie restriction equivalent to a 66% of usual intake for 4 weeks, starting on day 35 of life. Controls were kept in individual cages and allowed to eat a normal calorie regimen. Significantly lower ACTH levels were detected in calorie-restricted rats. Plasma corticosterone levels during the light phase of the daily cycle were significantly higher in calorie-restricted rats. Time-of-day variation in plasma ACTH and corticosterone levels attained significance in calorie-restricted rats only, with a maximum toward the end of the resting phase. The daily pattern of adrenal gland corticosterone mirrored that of circulating corticosterone; however, calorie restriction reduced its levels. Plasma ACTH and corticosterone correlated significantly in controls only. Calorie restriction decreased plasma GH and leptin, and it distorted 24h rhythmicity. In a second study, plasma ACTH and corticosterone levels were measured in group-caged rats, isolated control rats, and calorie-restricted rats during the light phase of the daily cycle. Plasma ACTH of calorie-restricted rats was lower, and plasma corticosterone was higher, compared with isolated or group-caged controls. The changes in the secretory pattern of hormones hereby reported may be part of the neuroendocrine and metabolic mechanisms evolved to maximize survival during periods of food shortage.

Journal ArticleDOI
TL;DR: Inferential chronobiological (Cosinor) analysis identified a significant annual pattern in AMI in those ≥65 yrs of age, with a peak between December and February—January for the total sample and December for non‐fatal infarctions (p=0.014).
Abstract: Like many other serious acute cardiovascular and cerebrovascular events, acute myocardial infarction (AMI) shows seasonal variation, being most frequent in the winter. We sought to investigate whether age, gender, and hypertension influence this pattern. We studied 4014 (2259 male and 1755 female) consecutive patients with AMI presenting to St. Anna Hospital of Ferrara, Italy between January 1998 and December 2004. Some 1131 (28.2%) of the AMI occurred in persons <65 yrs of age, and 2883 (71.8%) in those ≥65 yrs of age. AMI was over‐represented in males (82% in the <65 yr group vs. 56.6% in the ≥65 yr group (χ2=13.99; p<0.001). Hypertension had been previously documented in 964 (24%) of the cases. There were 691 (17.2%) fatal case outcomes; fatal outcomes were significantly higher among the 3054 normotensive (n=614 or 20.1%) than the 964 hypertensive cases (n=77 or 8%; χ2=74.94, p<0.001). AMIs were most frequent in the winter (n=1076 or 26.8% of all the events) and least in the summer (n=924 or 23.0% of a...

Journal ArticleDOI
TL;DR: Abcb1a P‐glycoprotein expression, and apparently its function, are 24 h rhythmic at least in mouse intestine tissue, and this circadian variation might be involved in various chronopharmacological phenomena.
Abstract: Recent studies have shown the gene expression of several transporters to be circadian rhythmic. However, it remains to be elucidated whether the expression of P-glycoprotein, which is involved in the transport of many medications, undergoes 24 h rhythmicity. To address this issue, we investigated daily profiles of P-glycoprotein mRNA and protein levels in peripheral mouse tissues. In the liver and intestine, but not in the kidney, Abcb1a mRNA expression showed clear 24 h rhythmicity. On the other hand, Abcb1b and Abcb4, the other P-glycoprotein genes, did not exhibit significant rhythmic expression in the studied tissues. In the intestine, levels of whole P-glycoprotein also exhibited a daily rhythm, with a peak occurring in the latter half of the light phase and a trough at the onset of the light phase. Consistent with the day-night change of P-glycoprotein level, the ex vivo accumulation of digoxin, an Abcb1a P-glycoprotein substrate, into the intestinal segments at the onset of dark phase was significantly lower than it was at the onset of the light phase. Thus, Abcb1a P-glycoprotein expression, and apparently its function, are 24 h rhythmic at least in mouse intestine tissue. This circadian variation might be involved in various chronopharmacological phenomena.

Journal ArticleDOI
TL;DR: In elderly hypertensive patients, mainly characterized by a diminished nocturnal decline in BP, bed‐time valsartan dosing is better than morning dosing since it improves efficacy during the nighttime sleep span, with the potential reduction in cardiovascular risk that has been associated with a normalized diurnal/nocturnal BP ratio.
Abstract: Previous results have indicated that valsartan administration at bed-time, as opposed to upon wakening, improves the diurnal/nocturnal ratio of blood pressure (BP) toward a normal dipping pattern, without loss of 24 h efficacy. This ratio is characterized by a progressive decrease with aging. Accordingly, we investigated the administration time-dependent antihypertensive efficacy of valsartan, an angiotensin blocking agent, in elderly hypertensive patients. We studied 100 elderly patients with grade 1-2 essential hypertension (34 men and 66 women), 68.2+/-4.9 years of age, randomly assigned to receive valsartan (160 mg/d) as a monotherapy either upon awakening or at bed-time. BP was measured for 48 h by ambulatory monitoring, at 20 min intervals between 07:00 to 23:00 h and at 30 min intervals at night, before and after 3 months of therapy. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately determine the duration of sleep and wake spans to enable the accurate calculation of the diurnal and nocturnal means of BP for each subject. There was a highly significant BP reduction after 3 months of valsartan treatment (p 0.195). This ratio was significantly increased (6.6 and 5.4 for systolic and diastolic BP; p < 0.001) when valsartan was ingested at bed-time. The reduction of the nocturnal mean was doubled in the group ingesting valsartan at bed-time, as compared to the group ingesting it in the morning (p < 0.001). In elderly hypertensive patients, mainly characterized by a diminished nocturnal decline in BP, bed-time valsartan dosing is better than morning dosing since it improves efficacy during the nighttime sleep span, with the potential reduction in cardiovascular risk that has been associated with a normalized diurnal/nocturnal BP ratio.

Journal ArticleDOI
TL;DR: There is a significant difference in the number of AAD events occurring during the different seasons of the year, with highest incidence in winter and lowest incidence in summer, suggesting that the relative change in temperature, rather than absolute temperature, and/or endogenous annual rhythms are critical mechanistic factors.
Abstract: We recently reported the existence of a higher risk of acute aortic dissection (AAD) during the winter months. However, it is not known whether this winter peak is affected by climate. To address this issue, we evaluated data from 969 AAD patients who were enrolled at various sites around the globe and who were participating in the International Registry of Acute Aortic Dissection (IRAD). We found a significant (p = 0.001; chi2 test) difference in the number of AAD events occurring during the different seasons of the year, with highest incidence in winter (28.4%) and lowest incidence in summer (19.9%). Furthermore, the winter peak was evident in both cold and temperate climate settings, suggesting that the relative change in temperature, rather than absolute temperature, and/or endogenous annual rhythms are critical mechanistic factors.

Journal ArticleDOI
TL;DR: Establishing the presence of clock proteins in human colonic crypts is the first step toward the study of the regulation of the intestinal circadian clock by nutrients and feeding rhythms.
Abstract: Biological clock components have been detected in many epithelial tissues of the digestive tract of mammals (oral mucosa, pancreas, and liver), suggesting the existence of peripheral circadian clocks that may be entrainable by food. Our aim was to investigate the expression of main peripheral clock genes in colonocytes of healthy humans and in human colon carcinoma cell lines. The presence of clock components was investigated in single intact colonic crypts isolated by chelation from the biopsies of 25 patients (free of any sign of colonic lesions) undergoing routine colonoscopy and in cell lines of human colon carcinoma (Caco2 and HT29 clone 19A). Per-1, per-2, and clock mRNA were detected by real-time RT-PCR. The three-dimensional distributions of PER-1, PER-2, CLOCK, and BMAL1 proteins were recorded along colonic crypts by immunofluorescent confocal imaging. We demonstrate the presence of per-1, per-2, and clock mRNA in samples prepared from colonic crypts of 5 patients and in all cell lines. We also demonstrate the presence of two circadian clock proteins, PER-1 and CLOCK, in human colonocytes on crypts isolated from 20 patients (15 patients for PER-1 and 6 for CLOCK) and in colon carcinoma cells. Establishing the presence of clock proteins in human colonic crypts is the first step toward the study of the regulation of the intestinal circadian clock by nutrients and feeding rhythms.

Journal ArticleDOI
TL;DR: It was observed that light pulses applied at MD affected plasma melatonin content and locomotor activity, which suggests that the melatonin system is capable of transducing light even under dim conditions, which may be used by this nocturnal fish to synchronize to weak night light signals.
Abstract: Melatonin production by the pineal organ is influenced by light intensity, as has been described in most vertebrate species, in which melatonin is considered a synchronizer of circadian rhythms. In...

Journal ArticleDOI
TL;DR: The data show that TOD affects K and θ and that these two important factors involved in in‐vivo muscle torque generation capacity are associated, and shows that peak torque Extcorr still shows a significant upward shift in the evening relative to the morning.
Abstract: The aim of the current study was to examine the relationships between quadriceps torque, vastus lateralis pennation angle (theta), and patella tendon stiffness (K) at 07:45 and 17:45 h. Using short-duration static contractions, simultaneous recordings were made of vastus lateralis (VL) electromyograph (EMG), theta and patella tendon K. Peak isometric extension torque (Peak torque Ext(corr)) increased by 29.4+/-6.5% at a knee angle of 70 degrees (p=0.03) in the evening compared to the morning. In the contracted muscle, a 35.0+/-11.0% (p=0.02) time-of-day (TOD)-related change in theta (to a greater evening compared to morning theta) was observed. Morning and evening measures of theta were also made, both at rest and at a standardized force level (250 N), to separate architecture change effects from increased torque capacity effects. Significant increments in theta in both the resting muscle (13.0+/-5.1%, p=0.046) and during the standardized exertions (8.0+/-3.1%, p=0.04) were observed in the evening versus the morning. Increases in theta with TOD were significantly correlated with the 40% (p=0.018) decrease in K both during the standardized contractions (r=0.788, p<0.001) and at rest (r=0.77, p=0.026). These data show that TOD affects K and theta and that these two important factors involved in in-vivo muscle torque generation capacity are associated. The data also show that despite the potentially deleterious effects of the direction of the changes in both K and theta with TOD, peak torque Ext(corr) still shows a significant upward shift in the evening relative to the morning.

Journal ArticleDOI
TL;DR: While highest incidence of AAD occurred in the morning and winter, clinical events were similar during the four different periods of the 24 h periods, and the χ2 test for goodness of fit was used to evaluate non‐uniformity of the time of day and time of year for critical in‐hospital clinical events, including death.
Abstract: The risk of acute aortic dissection (AAD) exhibits chronobiological variations with peak onset in the morning and in winter. However, it is not known whether the time of day or season of the year of the AAD affects clinical outcomes. We studied 1,032 patients enrolled in the International Registry of Acute Aortic Dissection from January 1997 to December 2001. For circadian and seasonal analysis, the time and date of symptom onset were available for 741 and 1,007 patients, respectively, and were grouped into four 6 h periods (morning, afternoon, evening, and night) and four seasons (winter, spring, summer, and autumn). The χ2 test for goodness of fit was used to evaluate non‐uniformity of the time of day and time of year for critical in‐hospital clinical events, including death. While highest incidence of AAD occurred in the morning and winter, clinical events (including mortality) were similar during the four different periods of the 24 h (χ2=1.9, p=0.60) and seasonal (χ2=1.2, p=0.75) periods.

Journal ArticleDOI
TL;DR: It is concluded that the amount of jet lag varies during the course of the day and that it can be predicted from contemporaneous assessments of alertness and motivation—but not from assessments made at other times of theday, nor from other variables that are symptoms ofJet lag, even though these other variables are significantly increased.
Abstract: The disruption of circadian rhythms following time-zone transitions gives rise to the syndrome of jet lag. The power of some of the symptoms of jet lag to predict the amount of jet lag measured at the same and at different times of the day has been investigated. Eleven healthy subjects were studied in an Isolation Unit for two days after a simulated flight from the UK to Beijing (8 time zones to the east). At six time-points (08:30, 11:00, 14:00, 17:00, 20:00, and 23:00 h), the subjects recorded their jet lag, and the differences from "normal" (that is, from days in which there is no jet lag) of alertness, hunger, indigestion, concentration, motivation, and irritability. They recorded at 08:30 h the type of food they had eaten since rising at 08:00h and, at the other times, the type of food eaten in the last three hours. Assessments were made by visual analogue scales or, in the case of type of food, by a nominal scale. Following the time-zone transition, the adjustment of meals appeared to be complete almost immediately. Jet lag and its symptoms were present during both experimental days. Jet lag tended to rise during the course of the daytime, accompanied by falls in alertness, motivation, and concentration. Correlation matrices between jet lag and each of the other variables were produced, using lags between the variable (from up to 5 time-points before the assessment of jet lag to 5 time-points afterwards) and pooling the results from both days. These matrices indicated that significant correlations existed only between jet lag and alertness, concentration, and motivation, and then only when these other variables were assessed at the same time as jet lag or 1 or 2 time-points earlier. Jet lag was then treated as the dependent variable and the symptoms as covariates in analysis of covariances (ANCOVAs), with the days treated as a random effect. This analysis enabled the significance of potential predictors of jet lag, together with their beta-coefficients (the relationship between a unit change of each significant predictor and the change in jet lag), to be calculated. Falls in alertness and motivation were significant predictors of increased jet lag, provided that they were measured at the same time, when they accounted for about 50% of the jet lag; when measured at other time-points, they did not act as significant predictors. It is concluded that the amount of jet lag varies during the course of the day and that it can be predicted from contemporaneous assessments of alertness and motivation-but not from assessments made at other times of the day, nor from other variables that are symptoms of jet lag, even though these other variables are significantly increased. In considering the results of this and our previous study, we reiterate the view that the exact meaning of "jet lag" is complex and that the particular combination of factors that contribute to it might vary with the time of day that the assessment is made. Inferences about any decrements due to time-zone transitions cannot be made reliably at times of the day that differ from the time when jet lag is assessed.

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TL;DR: No evidence is provided that circadian phase advance mediates the therapeutic mechanism in patients with SAD, and pre‐ and post‐treatment comparisons found that the degree of symptom change did not correlate with the level of phase change associated with treatment.
Abstract: In the context of Lewy's phase delay hypothesis, the present study tested whether effective treatment of winter Seasonal Affective Disorder (SAD) is mediated by advancing of circadian phase. Following a baseline week, 78 outpatients with SAD were randomized into 8 weeks of treatment with either fluoxetine and placebo light treatment or light treatment and placebo pill. Depression levels were measured on the Ham17+7 and the BDI-II, and circadian phase was estimated on the basis of daily sleep logs and self-reported morningness-eveningness. Among the 61 outpatients with complete data, both treatments were associated with significant antidepressant effect and phase advance. However, pre- and post-treatment comparisons found that the degree of symptom change did not correlate with the degree of phase change associated with treatment. The study therefore provides no evidence that circadian phase advance mediates the therapeutic mechanism in patients with SAD. Findings are discussed in terms of the limitations of the circadian measures employed.

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TL;DR: Human PBMCs may be a useful surrogate marker for the investigation of drug effects on clock genes by studying their mRNA expressions in human bronchial epithelium and following stimulation by the glucocorticoid homologue dexamethasone in vitro.
Abstract: We determined whether human peripheral blood mononuclear cells (PBMCs) could be used to analyze clock genes by studying their mRNA expressions in human bronchial epithelium (BEAS-2B) and PBMCs following stimulation by the glucocorticoid homologue dexamethasone (DEX) in vitro. PBMCs were obtained at 10:00 h from two diurnally active (approximately 07:00 to 23:00 h) healthy volunteers and were evaluated for hPer1 mRNA expression following DEX stimulation in vitro using real time-PCR analysis. DEX stimulation of human BEAS-2B cells and PBMCs in vitro led to a remarkable increase of hPer1 mRNA. The glucocorticoid rapidly affected the expression of hPer1 mRNA in PBMCs, suggesting that human PBMCs may be a useful surrogate marker for the investigation of drug effects on clock genes.

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TL;DR: It is concluded that circadian dysfunction is deleterious, and proper functioning of circadian clocks is essential for the physiological well being of D. melanogaster.
Abstract: Circadian clocks regulate physiological and behavioral processes in a wide variety of organisms, and any malfunction in these clocks can cause significant health problems. In this paper, we report ...

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TL;DR: Results can at least partly explain why LI‐voles died during the winter under field conditions, through eliminating winter acclimatization of the thermoregulatory system, or what is considered as “seasons out of time.”
Abstract: The change in photoperiod is the main environmental cue for seasonal function of the reproductive, thermoregulatory, and immune systems in rodents existing outside of the tropics. In Israel, the so...