Neuro-endocrine correlations of hypothalamic-pituitary-thyroid axis in healthy humans

Neuro-endocrine hormone secretion is characterized by circadian rhythmicity. Melatonin, GRH and GH are secreted during the night, CRH and ACTH secretion peak in the morning, determining the circadian rhythm of cortisol secretion, TRH and TSH show circadian variations with higher levels at night. Thyroxine levels do not change with clear circadian rhythmicity. In this paper we have considered a possible influence of cortisol and melatonin on hypothalamic-pituitary-thyroid axis function in humans. Melatonin, cortisol, TRH, TSH and FT4 serum levels were determined in blood samples obtained every four hours for 24 hours from ten healthy males, aged 36-51 years. We correlated hormone serum levels at each sampling time and evaluated the presence of circadian rhythmicity of hormone secretion. In the activity phase (06:00 h-10:00 h-14:00 h) cortisol correlated negatively with FT4, TSH correlated positively with TRH, TRH correlated positively with FT4 and melatonin correlated positively with TSH. In the resting phase (18:00 h-22:00 h-02:00 h) TRH correlated positively with FT4, melatonin correlated negatively with FT4, TSH correlated negatively with FT4, cortisol correlated positively with FT4 and TSH correlated positively with TRH. A clear circadian rhythm was validated for the time-qualified changes of melatonin and TSH secretion (with acrophase during the night), for cortisol serum levels (with acrophase in the morning), but not for TRH and FT4 serum level changes. In conclusion, the hypothalamic-pituitary-thyroid axis function may be modulated by cortisol and melatonin serum levels and by their circadian rhythmicity of variation.     

Twenty-four-hour rhythm patterns of plasma melatonin in short-day and long-day breeders maintained under natural environmental conditions

ABSTRACT

Photoperiodic treatments have been of practical interest in controlling seasonal reproduction in sheep, goats and horses. Melatonin is the principal mediator of the environmental photoperiodic message. To investigate the intra- and inter-subject variability of melatonin 24 h rhythm, ten female Italian Saddle horses (8–10 yrs old, mean body weight 525 ± 30 kg), ten female Sarda breed sheep (2–3 yrs old, mean body weight 40.5 ± 2.8 kg) and ten female Sarda breed goats (3–4 yrs old, mean body weight 38.9 ± 4.1 kg), housed individually in a 4 × 4 m soundproof box equipped with 50 × 100 cm opening windows, were subjected to a natural photoperiod of the vernal equinox (sunrise 06:00 h; sunset 18:00 h). Blood samples were collected from each animal, every 3 h over a 48 h period starting at 00:00 h of day 1 and ending at 00:00 h of day 3. Plasma melatonin concentrations were determined by direct radioimmunoassay (MelatoninDirect RIA, Labor Diagnostika Nord GmbH, Nordhorn, Germany). The application of single cosinor method substantiated a circadian rhythm of melatonin with a nocturnal peak in all studied species. The application of two-way ANOVA on the rhythmic parameters indicated statistically significant differences between the three species in all of the cosinor analysis-derived parameters of MESOR, amplitude, acrophase and robustness of rhythm. Analyses of intra- and inter-subject variability indicate that organization of the melatonin 24 h rhythm is characterized by great accuracy of control within and between the individuals of a breed. In conclusion, features of the 24 h rhythm of melatonin among species; however, the 24 h rhythmicity of melatonin each species showed high stability within the various subjects and within the same subject. These findings must be taken into consideration when applying photoperiod and melatonin treatments for breeding purposes.     

Environmental stress of mobile phone EM radiation on locomotor activity and melatonin circadian rhythms of rats

Biological clocks are innate timing mechanisms that regulate many behavioral and physiological parameters in most organisms. In our modern life, heavy use of mobile phones (MPs) exerts a massive stress on organisms because their electromagnetic radiation usually results in varying degrees of damage to their biological systems including the biological rhythms. In the present study, the possible effects of exposure to radiofrequency–electromagnetic radiation (RF–EMR) from MPs on two characteristic circadian rhythms, locomotor activity and melatonin hormone rhythms, were investigated. Rats were exposed to RF–EMR from MPs at 900 MHz frequency (2-h/day for 2 weeks) during nighttime (20:00–22:00 h) followed by another two weeks without exposure for recovery. Locomotor activity rhythms of the control and treated groups (n = 5/group) were daily recorded using running wheels along the experimental period. For evaluating melatonin hormone rhythm, blood samples of control and treated groups (n = 12/group), were collected at the end of exposure and recovery periods, at 6-h time intervals per day (at 4:00, 10:00, 16:00, and 22:00 h). Rats exposed to RF–EMR exhibited phase shifting as well as a significant increased acrophase level in locomotor activity. Meanwhile, a significant decrease in serum melatonin levels with retaining lower amplitude rhythmicity was observed. Ceasing exposure for two weeks did not restore melatonin levels and circadian locomotor activity rhythms. It could be concluded that, under the current conditions, exposure to RF–EMR revealed disturbances in locomotor activity and melatonin level, although they maintained rhythmicity.     

Differences in Sleep,Light, and Circadian Phase in Offshore 18:00–06:00 h and 19:00–07:00 h Shift Workers

Complaints concerning sleep are high among those who work night shifts; this is in part due to the disturbed relationship between circadian phase and the timing of the sleep‐wake cycle. Shift schedule, light exposure, and age are all known to affect adaptation to the night shift. This study investigated circadian phase, sleep, and light exposure in subjects working 18:00–06:00 h and 19:00–07:00 h schedules during summer (May–August). Ten men, aged 46±10 yrs (mean±SD), worked the 19:00–07:00 h shift schedule for two or three weeks offshore (58°N). Seven men, mean age 41±12 yrs, worked the 18:00–06:00 h shift schedule for two weeks offshore (61°N). Circadian phase was assessed by calculating the peak (acrophase) of the 6‐sulphatoxymelatonin rhythm measured by radioimmunoassay of sequential urine samples collected for 72 h at the end of the night shift. Objective sleep and light exposure were assessed by actigraphy and subjective sleep diaries. Subjects working 18:00–06:00 h had a 6‐sulphatoxymelatonin acrophase of 11.7±0.77 h (mean±SEM, decimal hours), whereas it was significantly later, 14.6±0.55 h (p=0.01), for adapted subjects working 19:00–07:00 h. Two subjects did not adapt to the 19:00–07:00 h night shift (6‐sulphatoxymelatonin acrophases being 4.3±0.22 and 5.3±0.29 h). Actigraphy analysis of sleep duration showed significant differences (p=0.03), with a mean sleep duration for those working 19:00–07:00 h of 5.71±0.31 h compared to those working 18:00–06:00 h whose mean sleep duration was 6.64±0.33 h. There was a trend to higher morning light exposure (p=0.07) in the 19:00–07:00 h group. Circadian phase was later (delayed on average by 3 h) and objective sleep was shorter with the 19:00–07:00 h than the 18:00–06:00 h shift schedule. In these offshore conditions in summer, the earlier shift start and end time appears to favor daytime sleep.     

Circadian rhythm of airways caliber and its autonomic modulation

ABSTRACT

The autonomic nervous system (ANS) is one of the effector pathways for circadian variation of many physiological parameters. Autonomic tone and airways caliber have been reported to exhibit circadian variation in separate studies. A simultaneous investigation of heart rate variability (HRV) and airway caliber might ascertain how airway caliber is modulated by autonomic tone. This study was planned to identify the variations in airway caliber and autonomic function tone during a 24-hour span. A total of 56 healthy male subjects with almost similar daily routines were studied. Time domain, frequency domain and nonlinear analysis of R-R interval from 5 min electrocardiogram (ECG) was done seven times during the daytime wake span at 3-hour intervals starting at 05:00 h in the morning until 23:00 h in the night. Simultaneously peak expiratory flow rate (PEFR) was determined using a mini Wright’s peak flow meter. Rhythmometric analysis was done for PEFR and HRV parameters. Significant circadian variation in low frequency (LF) and high frequency (HF) variance was identified in this group of healthy subjects. The circadian rhythm of LF variance was characterized by a gradual increase and corresponding reciprocal change in HF variance from morning until night. The LF/HF ratio and SD2/SD1 ratio reflecting sympatho-vagal balance showed low to high values from morning to evening. The acrophase of the PEFR temporal pattern is similar to that of LF power and almost opposite in phase to that of HF power. PEFR is positively correlated with LF power. The circadian rhythm of airway caliber co-varies with cardiac autonomic tone. It appears that the temporal pattern of cardiac autonomic tone precedes in time that of airways caliber, thereby suggesting the latter operates under the modulatory effect of the 24-hour pattern in sympatho-vagal balance.     

Peripheral clock system circadian abnormalities in Cushing’s disease

ABSTRACT

In Cushing’s syndrome, the cortisol rhythm is impaired and can be associated with the disruption in the rhythmic expression of clock genes. In this study, we evaluated the expression of CLOCK, BMAL1, CRY1, CRY2, PER1, PER2, PER3 genes in peripheral blood leukocytes of healthy individuals (n = 13) and Cushing’s disease (CD) patients (n = 12). Participants underwent salivary cortisol measurement at 0900 h and 2300 h. Peripheral blood samples were obtained at 0900 h, 1300 h, 1700 h, and 2300 h for assessing clock gene expression by qPCR. Gene expression circadian variations were evaluated by the Cosinor method. In healthy controls, a circadian variation in the expression of CLOCK, BMAL1, CRY1, PER2, and PER3 was observed, whereas the expression of PER1 and CRY2 followed no specific pattern. The expression of PER2 and PER3 in healthy leukocytes presented a late afternoon acrophase, similarly to CLOCK, whereas CRY1 showed night acrophase, similarly to BMAL1. In CD patients, the circadian variation in the expression of clock genes was lost, along with the abolition of cortisol circadian rhythm. However, CRY2 exhibited a circadian variation with acrophase during the dark phase in patients. In conclusion, our data suggest that Cushing’s disease, which is characterized by hypercortisolism, is associated with abnormalities in the circadian pattern of clock genes. Higher expression of CRY2 at night outlines its putative role in the cortisol circadian rhythm disruption.     

Preoperative circadian physical activity rhythm and postoperative delirium in cardiovascular surgery patients

ABSTRACT

Postoperative delirium, a common perioperative complication, is frequently observed in elderly surgical patients. Few studies have investigated the life rhythm of preoperative patients, and whether or not the preoperative life rhythm is associated with the development of postoperative delirium. The purpose of this study was to investigate the relationship between the preoperative circadian physical activity rhythm and postoperative delirium in cardiovascular surgery patients. A total of 43 patients who underwent cardiovascular surgery were included in this prospective study between July 2016 and September 2017 at Kobe University Hospital. All subjects used a “Life Microscope” wristband (a wristwatch-type terminal incorporating a 3-axis accelerometer monitoring) for 3–7 days at home before the planned surgery. Hourly mean values were calculated for the metabolic equivalents from the obtained activity amounts, and subsequently evaluated using cosine periodic regression analysis. The circadian rhythm parameters of mesor (24 h time series mean), amplitude (half the peak-trough variation), and acrophase (peak time) for the metabolic equivalents were obtained. The intensive care delirium screening checklist was used to assess for postoperative delirium. The acrophase significantly advanced in the postoperative delirium group (median, 11:55 h [interquartile range, 11:06–12:27 h]) compared to the group without postoperative delirium (median, 13:25 h [interquartile range, 12:52–14:13 h]) (p < .001). Furthermore, binary logistic regression analysis showed that advances in the physical activity phase remained independently associated with postoperative delirium (odds ratio, 0.003 [95% confidence interval, 0–0.63]). These results suggest that misalignment between advanced life rhythm before hospitalization and life rhythm after hospitalization might be associated with risk for developing postoperative delirium. Our results led us to speculate that adequate consideration of the patient’s life rhythm before hospitalization is needed to prevent postoperative delirium.     

Rhythms in human bone marrow and blood cells

In 24h studies of bone marrow (BM), circadian stage-dependent variations were demonstrated in the proliferative activity of BM cells from subsets of 35 healthy diurnally active men. On an average, the percentage of total BM cells in deoxyribonucleic acid (DNA) synthesis phase was 188% greater at midday than at midnight (circadian rhythm: p = 0.018; acrophase or peak time of 13: 16h). Patients with malignant disease (n = 15) and a normal cortisol circadian rhythm showed higher fractions of BM cells in S-phase at midday. Colony-forming units--granulocyte/macrophage (CFU-GM), an indicator of myeloid progenitor cells, showed the same circadian variation as DNA S-phase (average range of change or ROC = 136%; circadian rhythm: p < 0.001; acrophase of 12:09h). Deoxyribonucleic acid S-phase and CFU-GM in BM both showed a circannual rhythm (p = 0.015 and 0.008) with an identical acrophase of August 12. The daily peak in BM glutathione content, a tripeptide involved in cellular defense against cytotoxic damage, preceded BM proliferative peaks by 4-5 h (ROC = 31-90%; circadian rhythm: p = 0.05; acrophase of 08:30h). Myeloid (ROC = 57%; circadian rhythm: p = 0.056; acrophase at 08:40h) and erythroid (ROC = 26%; circadian rhythm: p = 0.01; acrophase of 13:01h) precursor cells were positively correlated (r = 0.41; p < 0.001), indicating a circadian temporal relationship and equal influence on S-phase of total BM cells. Yield of positive selected CD34+ progenitor stem cells also showed significant circadian variation (ROC = 595%; circadian rhythm: p = 0.02; acrophase of 12:40h). Thus, the temporal synchrony in cell cycling renders BM cells more sensitive at specific times to hematopoietic growth factors and cell cycle-specific cytotoxic drugs. Moreover, proper timing of BM harvesting may improve progenitor cell yield. When using marker rhythms in the blood to allow for individualized timing of BM procedures, the times of low values in white blood corpuscles, neutrophils, and lymphocytes and high values in cortisol were predictive of the times of highest BM erythroid, myeloid, and total S-phase numbers occurring in the following 12 h.     

Comparison of rectal and vaginal temperature daily rhythm in dogs (Canis familiaris) under different photoperiod

To investigate the daily rhythm of rectal and vaginal temperature, we used six mongrel dogs with a mean body weight of 15±3 kg, aged between 2 and 3 years old. Rectal and vaginal temperatures were recorded every 3 h over 48-h period during three different lighting regimes: natural light/dark (L/D) cycle (sunrise 06:25, sunset 17:05), constant light (L/L) and constant darkness (D/D). A daily rhythm of rectal temperature was observed in both days of monitoring in all experimental conditions. Vaginal temperature showed a daily rhythmicity in L/D and D/D cycle. During the L/L cycle, daily rhythm was disrupted. Rhythmic parameters (MESOR, amplitude, acrophase and robustness) did not change between the different photoperiod and the site of temperature collection. In conclusion, the monitoring of vaginal temperature can be considered a valid alternative to the monitoring of body temperature as well as rectal temperature under natural lighting conditions in canine medicine.     

The Circadian Body Temperature Rhythm in the Elderly: Effect of Single Daily Melatonin Dosing

The present study is part of a more extensive investigation dedicated to the study and treatment of age‐dependent changes/disturbances in the circadian system in humans. It was performed in the Tyumen Elderly Veteran House and included 97 subjects of both genders, ranging from 63 to 91 yrs of age. They lived a self‐chosen sleep‐wake regimen to suit their personal convenience. The experiment lasted 3 wks. After 1 control week, part of the group (n=63) received 1.5 mg melatonin (Melaxen?) daily at 22:30 h for 2 wks. The other 34 subjects were given placebo. Axillary temperature was measured using calibrated mercury thermometers at 03:00, 08:00, 11:00, 14:00, 17:00, and 23:00 h each of the first and third week. Specially trained personnel took the measurements, avoiding disturbing the sleep of the subjects. To evaluate age‐dependent changes, data obtained under similar conditions on 58 young adults (both genders, 17 to 39 yrs of age) were used. Rhythm characteristics were estimated by means of cosinor analyses, and intra‐ and inter‐individual variability by analysis of variance (ANOVA). In both age groups, the body temperature underwent daily changes. The MESOR (36.38±0.19°C vs. 36.17±0.21°C) and circadian amplitude (0.33±0.01°C vs. 0.26±0.01°C) were slightly decreased in the elderly compared to the young adult subjects (p<0.001). The mean circadian acrophase was similar in both age groups (17.19±1.66 vs. 16.93±3.08 h). However, the inter‐individual differences were higher in the older group, with individual values varying between 10:00 and 23:00 h. It was mainly this phase variability that caused a decrease in the inter‐daily rhythm stability and lower group amplitude. With melatonin treatment, the MESOR was lower by 0.1°C and the amplitude increased to 0.34±0.01°C, a similar value to that found in young adults. This was probably due to the increase of the inter‐daily rhythm stability. The mean acrophase did not change (16.93 vs. 16.75 h), although the inter‐individual variability decreased considerably. The corresponding standard deviations (SD) of the group acrophases were 3.08 and 1.51 h (p<0.01). A highly significant correlation between the acrophase before treatment and the phase change under melatonin treatment indicates that this is due to a synchronizing effect of melatonin. Apart from the difference in MESOR, the body temperature rhythm in the elderly subjects undergoing melatonin treatment was not significantly different from that of young adults. The data clearly show that age‐dependent changes mainly concern rhythm stability and synchronization with the 24 h day. A single daily melatonin dose stabilizes/synchronizes the body temperature rhythm, most probably via hypothermic and sleep‐improving effects.     

Time-of-day effect on the torque and neuromuscular properties of dominant and non-dominant quadriceps femoris

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 < 0.01). From cosinor analysis, a circadian rhythm was documented (p < 0.001) with the peak (acrophase) estimated at 18:18 +/- 00:12 h and amplitude (one-half the peak-to-trough variation) of 3.3 +/- 1.1%. Independent of the leg tested, peripheral mechanisms demonstrated a significant time-of-day effect (p < 0.05) 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.     

Orcadian Rhythm in the Torque Developed by Elbow Flexors During Isometric Contraction Effect of Sampling Schedules

Time-dependent changes in elbow flexion torque have been documented according to two different sampling schedules. Seven physical education students took part in the first series of experiments, and 7 other similar subjects in the second. In both sets of experiments, the subjects performed isometric contractions: maximal and submaximal at 90° in the first experiments and maximal at different angular positions in the second. After a 30-minute rest period, the torque developed was measured at 00:00, 06:00, 09:00, 12:00, 15:00, 18:00, and 21:00h on the day of the experiment. These subjects remained in the laboratory for 24h. In the second series of experiments, the torque developed was measured at 01:00, 05:00, 09:00, 13:00, 17:00, and 21:00h over the subsequent 6 days with only one test session per day. In this case, there was an interval of 20h between two successive test sessions. In the first experiment, a significant time-of-day effect was observed for the torque of the elbow flexors under isometric conditions with an acrophase at 17:58h. The 24h normalized mean score was 92.85% with an amplitude of 7.63% of the daily mean. In the second series of experiments, there was evidence of a circadian rhythm in the torque developed by the elbow flexors at every angle position, especially at 90°, the angle investigated in the first set of experiments. The peak torque was calculated to have occurred at 17:55h. The amplitude of the rhythm was equal to 6.99% of the daily mean. There were no statistically significant differences in the characteristics of the circadian rhythm observed between the two experimental designs. We concluded that an experiment extending over several days could be employed to evaluate circadian rhythms in muscular activity reliably. (Chronobiology International, 14(3), 287–294, 1997)     

Diurnal variations of heart rate,urine flow and catecholamine excretion in subjects wearing clothing that provides different thermal insulation

This study investigated the effects of clothing providing different Clo values upon the circadian rhythm of sympathetic nervous activity, as inferred from urinary catecholamine excretion and heart rate, in a thermoneutral environment. Seven health female subjects were studied for 37.5 h, from 21:00 h on the first day to 10:30 h on the third day, in an isolated climatic chamber controlled at 23.8?±?0.2 °C and 60?±?5% RH. Light intensity was 500 lux from 06:30 to 19:30 h, 100 lux from 19:30 to 22:30 h and 0 lux from 22:30 to 06:30 h. Subjects were tested while wearing two different types of clothing: Type L, offering 1.048 Clo of thermal insulation and with the subjects’ extremities covered; and Type H, 0.744 Clo of thermal insulation and the subjects’ extremities exposed. Urine samples were collected every 4 h, their volumes were measured and they were later assayed for their contents of adrenaline and noradrenaline; the mean heart rate for each of these 4-h periods was also calculated. The daily profiles of the variables were assessed by ANOVA, which indicated that the amplitudes and phases of the daily rhythms differed between the clothing types. This result was examined in more detail by assessing the profiles by single and group cosinor analysis (period = 24 h). All four physiological variables showed clear and statistically significant group cosinor rhythms with both types of clothing. The mean amplitudes of urine flow, the excretion rate of urinary adrenaline and heart rate were greater when wearing Type H rather than Type L clothing (p = 0.01 for urine flow and heart rate; p = 0.072 for rate of excretion of adrenaline). Also, the acrophase of the rate of urinary adrenaline excretion was earlier in all subjects wearing Type H rather than Type L clothing (p = 0.048), and the acrophases of urine flow and urinary noradrenaline excretion rate were earlier in six and five of the subjects, respectively. These results show that clothing which is worn in an environment of moderate temperature (23.8 °C) and which offers a lower Clo value (especially if the distal extremities are exposed) might induce an increase in amplitude and/or an advance of acrophase in circadian rhythms of urine flow, excretion of urinary catecholamines and heart rate. It is suggested that these rhythmic changes, which imply changes in the daily profile of sympathetic nervous system activity, might be important when daily thermoregulation and comfort in response to the type of clothing being worn in daily life are considered.     

Melatonin suppression during a simulated night shift in medium intensity light is increased by 10-minute breaks in dim light and decreased by 10-minute breaks in bright light

ABSTRACT

Exposure to light at night results in disruption of endogenous circadian rhythmicity and/or suppression of pineal melatonin, which can consequently lead to acute or chronic adverse health problems. In the present study, we investigated whether exposure to very dim light or very bright light for a short duration influences melatonin suppression, subjective sleepiness, and performance during exposure to constant moderately bright light. Twenty-four healthy male university students were divided into two experimental groups: Half of them (mean age: 20.0 ± 0.9 years) participated in an experiment for short-duration (10 min) light conditions of medium intensity light (430 lx, medium breaks) vs. very dim light (< 1 lx, dim breaks) and the other half (mean age: 21.3 ± 2.5 years) participated in an experiment for short-duration light conditions of medium intensity light (430 lx, medium breaks) vs. very bright light (4700 lx, bright breaks). Each simulated night shift consisting of 5 sets (each including 50-minute night work and 10-minute break) was performed from 01:00 to 06:00 h. The subjects were exposed to medium intensity light (550 lx) during the night work. Each 10-minute break was conducted every hour from 02:00 to 06:00 h. Salivary melatonin concentrations were measured, subjective sleepiness was assessed, the psychomotor vigilance task was performed at hourly intervals from 21:00 h until the end of the experiment. Compared to melatonin suppression between 04:00 and 06:00 h in the condition of medium breaks, the condition of dim breaks significantly promoted melatonin suppression and the condition of bright breaks significantly diminished melatonin suppression. However, there was no remarkable effect of either dim breaks or bright breaks on subjective sleepiness and performance of the psychomotor vigilance task. Our findings suggest that periodic exposure to light for short durations during exposure to a constant light environment affects the sensitivity of pineal melatonin to constant light depending on the difference between light intensities in the two light conditions (i.e., short light exposure vs. constant light exposure). Also, our findings indicate that exposure to light of various intensities at night could be a factor influencing the light-induced melatonin suppression in real night work settings.     

Circadian variations in self-monitoring,a component of executive functions

The objective of this study was to identify circadian rhythms in self-monitoring, a component of executive functions. Participants were 10 undergraduate students, age: 18.5 ± 2.68 years, two male and eight female. They were recorded on a 30-h constant routine protocol; rectal temperature was recorded every minute and performance on a tracking task was assessed every 100 min. Self-monitoring indicators were adjustments of responses to random changes of speed and trajectory of a circle moving on the computer screen. Participants showed better accuracy during the afternoon, with decreases in the morning (06:20 and 08:00 h). These variations showed a phase delay of 2:29 ± 2:19 h with respect to the circadian rhythm of body temperature. In conclusion, there are circadian variations in self-monitoring. The decline in this component of executive functions could cause serious accidents among people working or studying during a morning shift, as well as commuting to and from work or school.     

Circadian rhythmicity in leukocytes immune responses in the freshwater snake,Natrix piscator

Circadian rhythm is observed in most of the physiological functions including immune response. The use of animal models other than mammals is useful in understanding how the vertebrate circadian system is organized and how this biological clock has changed throughout the vertebrate evolution. The present study was aimed to examine the circadian variability in the innate immune responses of leukocytes in the freshwater snake, Natrix piscator. Leukocytes were isolated and processed for total and differential leukocyte count, leukocyte phagocytosis, NBT reduction, nitrite production, and lymphocyte proliferation. Experiments were conducted for seven time points at 24, 4, 8, 12, 16, 20, and 24 h in three seasons – summer, winter, and spring. Cosinor analysis revealed that among leukocytes, only lymphocyte count showed circadian variation in summer. Percent phagocytosis and phagocytic index had significant rhythm of 24 h in winter and summer season, respectively. The acrophase of NBT reduction and nitrite release were coming during the evening hours in summer and during morning hours in winter and had circadian rhythmicity. A significant phase shift in nitrite release was observed with a trend of delayed phase shift from winter to summer. Circadian rhythm was also observed in lymphocyte proliferation (basal and concanavalin A stimulated). It is evident from the present study that animals synchronize their immune activity according to the time of the day and season. Enhancement of immune function helps the individual cope with seasonal stressors that would otherwise jeopardize the survival of animal.     

Central adaptation models of the vestibulo-ocular and optokinetic systems

A theoretical analysis of two models of the vestibulo-ocular and optokinetic systems was performed. Each model contains a filter element in the vestibular periphery to account for peripheral adaptation, and a filter element in the central vestibulooptokinetic circuit to account for central adaptation. Both models account for1 adaptation, i.e. a response decay to a constant angular acceleration input, in both peripheral vestibular afferent and vestibulo-ocular reflex (VOR) responses and2 the reversal phases of optokinetic after-nystagmus (OKAN) and the VOR and3 oscillatory behavior such as periodic alternating nystagmus. The two models differ regarding the order of their VOR transfer function. Also, they predict different OKAN patterns following a prolonged optokinetic stimulus. These models have behavioral implications and suggest future experiments.     

Development of model based on clock gene expression of human hair follicle cells to estimate circadian time

ABSTRACT

Considering the effects of circadian misalignment on human pathophysiology and behavior, it is important to be able to detect an individual’s endogenous circadian time. We developed an endogenous Clock Estimation Model (eCEM) based on a machine learning process using the expression of 10 circadian genes. Hair follicle cells were collected from 18 healthy subjects at 08:00, 11:00, 15:00, 19:00, and 23:00 h for two consecutive days, and the expression patterns of 10 circadian genes were obtained. The eCEM was designed using the inverse form of the circadian gene rhythm function (i.e., Circadian Time = F(gene)), and the accuracy of eCEM was evaluated by leave-one-out cross-validation (LOOCV). As a result, six genes (PER1, PER3, CLOCK, CRY2, NPAS2, and NR1D2) were selected as the best model, and the error range between actual and predicted time was 3.24 h. The eCEM is simple and applicable in that a single time-point sampling of hair follicle cells at any time of the day is sufficient to estimate the endogenous circadian time.     

Differences in sleep, light, and circadian phase in offshore 18:00-06:00 h and 19:00-07:00 h shift workers

Complaints concerning sleep are high among those who work night shifts; this is in part due to the disturbed relationship between circadian phase and the timing of the sleep-wake cycle. Shift schedule, light exposure, and age are all known to affect adaptation to the night shift. This study investigated circadian phase, sleep, and light exposure in subjects working 18:00-06:00 h and 19:00-07:00 h schedules during summer (May-August). Ten men, aged 46+/-10 yrs (mean+/-SD), worked the 19:00-07:00 h shift schedule for two or three weeks offshore (58 degrees N). Seven men, mean age 41+/-12 yrs, worked the 18:00-06:00 h shift schedule for two weeks offshore (61 degrees N). Circadian phase was assessed by calculating the peak (acrophase) of the 6-sulphatoxymelatonin rhythm measured by radioimmunoassay of sequential urine samples collected for 72 h at the end of the night shift. Objective sleep and light exposure were assessed by actigraphy and subjective sleep diaries. Subjects working 18:00-06:00 h had a 6-sulphatoxymelatonin acrophase of 11.7+/-0.77 h (mean+/-SEM, decimal hours), whereas it was significantly later, 14.6+/-0.55 h (p=0.01), for adapted subjects working 19:00-07:00 h. Two subjects did not adapt to the 19:00-07:00 h night shift (6-sulphatoxymelatonin acrophases being 4.3+/-0.22 and 5.3+/-0.29 h). Actigraphy analysis of sleep duration showed significant differences (p=0.03), with a mean sleep duration for those working 19:00-07:00 h of 5.71+/-0.31 h compared to those working 18:00-06:00 h whose mean sleep duration was 6.64+/-0.33 h. There was a trend to higher morning light exposure (p=0.07) in the 19:00-07:00 h group. Circadian phase was later (delayed on average by 3 h) and objective sleep was shorter with the 19:00-07:00 h than the 18:00-06:00 h shift schedule. In these offshore conditions in summer, the earlier shift start and end time appears to favor daytime sleep.