Chronobiological Aspects of Jejunum Function in Humans

This review is intended to present our knowledge on both chronomorphology and chronophysiology of jejunum mainly in humans, as well as on implications of chronobiologic principles in the practice of gastroenterology.     

The Nutritional Status and Eating Habits of Shift Workers: A Chronobiological Approach

The eating habits of workers may vary according to the season of the year and corresponding work schedule. A study aiming at verifying the changes in their diet in summer and winter, as well as the nutritional status of those who work fixed shifts, was conducted. The distribution during the 24 h in the quantity of calories and macronutrients ingested and the circadian rhythm of calories consumed were also analyzed. The study was conducted on 28 workers subject to three fixed work (morning, afternoon, and night) shifts at a transport company in the city of São Paulo, Brazil. The mean age of the workers was 32.8 (SD ± 5.3) yrs. Their food intake was ascertained by the use of a 3-day dietary record, and their nutritional status was evaluated by their body mass index (BMI), both in winter and summer. Two-way ANOVA (shift and season) showed food consumption—measured in calories/24 h—was significantly higher in winter than summer (F_(1.25) = 11.7; p < 0.001). No statistically significant differences were found among shifts (F_(2.25) = 0.85; p < 0.44), and the interaction effect between shift and season was also not significant (F_(2.25) = 0.15; p < 0.86). No seasonal difference in BMI was detected (Kruskal-Wallis test). Cosinor analyses showed circadian rhythmicity in calories consumed by morning (p < 0.01) as well as afternoon shift workers (p < 0.001), both in the winter and summer. Circadian rhythmicity in calories consumed by night workers was found only in summer (p < 0.01). The changes observed in the workers’ eating habits from one season to another and during the 24 h period show the need for further studies to help develop educational programs to improve the nutrition of shift employees taking into consideration shift schedule and season of the year when work is performed.     

The Relation of Shift Work Tolerance to the Circadian Adjustment

The amplitude and phasing of circadian rhythms are under discussion as possible predictors of tolerance to night work. In a field study, subjective sleepiness and oral temperature of 147 female nurses were measured at 2-hour intervals during a period with one morning shift and two consecutive night shifts. The nurses also filled out a questionnaire. Two types of tolerance indices were constructed: The “health index” was based on questions referring to general fatigue, gastrointestinal symptoms, and sleep disturbances, and the “sleepiness index” on the actual subjective ratings of sleepiness. According to the health index, the group with good tolerance had a larger circadian amplitude of the oral temperature rhythm on the day of the morning shift than the group with poor tolerance. However, with regard to the sleepiness index, the corresponding difference between the groups with good or poor tolerance was not significant. The data did not confirm the hypothesis that predicts a quick adjustment of the circadian rhythm when the circadian amplitude is small before the change to night work. The contradictory results found in this and in other studies do not yet permit prediction of tolerance to night work.     

The Relation of Shift Work Tolerance to the Circadian Adjustment

The amplitude and phasing of circadian rhythms are under discussion as possible predictors of tolerance to night work. In a field study, subjective sleepiness and oral temperature of 147 female nurses were measured at 2-hour intervals during a period with one morning shift and two consecutive night shifts. The nurses also filled out a questionnaire. Two types of tolerance indices were constructed: The “health index” was based on questions referring to general fatigue, gastrointestinal symptoms, and sleep disturbances, and the “sleepiness index” on the actual subjective ratings of sleepiness. According to the health index, the group with good tolerance had a larger circadian amplitude of the oral temperature rhythm on the day of the morning shift than the group with poor tolerance. However, with regard to the sleepiness index, the corresponding difference between the groups with good or poor tolerance was not significant. The data did not confirm the hypothesis that predicts a quick adjustment of the circadian rhythm when the circadian amplitude is small before the change to night work. The contradictory results found in this and in other studies do not yet permit prediction of tolerance to night work.     

Measurement of,and Some Reasons for,Differences in Eating Habits Between Night and Day Workers

A questionnaire was designed to assess the following: why working people chose to eat or not to eat at a particular time of day; the factors that influenced the type of food eaten; and subjective responses to the meal (hunger before, enjoyment during, satiety afterward). Self-assessments were done every 3h during a typical week containing work and rest days, by one group of 50 day workers and another group of 43 night workers. During the night work hours compared to rest days, night workers evidenced a significantly altered food intake, with a greater frequency of cold rather than hot food (p < 0.001). The type and frequency of meals were influenced significantly more (p < 0.05) by habit and time availability and less by appetite. This pattern continued into the hours immediately after the night shift had ended. In day workers food intake during work hours, compared to rest days, was also influenced significantly more often (p < 0.05) by time availability than hunger, but less so than with night workers. Moreover, day workers were less dependent than night workers upon snacks (p = 0.01), and any significant differences from rest days did not continue beyond work hours. Not only did night workers change their eating habits during work days more than did day workers but also they looked forward to their meals significantly less (p < 0.001) and felt more bloated after consuming them (p < 0.05), such effects being present to some extent during their rest days also. These findings have clear implications for measures designed to ease eating problems that are commonly problematic in night workers.     

Methodological Aspects of Shift-Work Research

A major issue in shift-work research is to understand the possible ways in which shift work can impact performance and health. Nearly all body functions, from those of the cellular level to those of the entire body, are circadian rhythmic. Disturbances of these rhythms as well as the social consequences of odd work hours are of importance for the health and well-being of shift workers. This article reviews a number of common methodological issues which are of relevance to epidemiological studies in this area of research. It discusses conceptual problems regarding the use of the term “shift work,” and it underscores the need to develop models that explain the mechanisms of disease in shift workers.     

Impact of night-float rotation on sleep,mood, and alertness: the resident's perception

Night-float rotations were designed to alleviate the workload of residents on night call and thereby improve patient safety. However, the impact of the night float on residents is yet to be surveyed. We assessed the impact of the night-float rotation on pediatric residents using an anonymous questionnaire that covered topics, based on recall, about sleep, mood, alertness, adjustment, and others. The study was conducted in a major tertiary pediatric teaching hospital in the United States. Participants were pediatric residents who had completed one or two night-float rotations and were in active training at our teaching hospital at the time of the study. Fifty-two of 60 eligible residents (87%) responded. Sleep duration during the night-float rotation was shorter than during day-shift work in 24 residents (46%), longer in 20 (38%), and unchanged in eight (15%). A higher proportion of residents took longer to fall asleep, had more difficulty falling asleep, had more sleep interruptions, and felt less rested upon awakening. Twenty-four residents (46%) felt that their bodies never adjusted to the night shift. Also, 22 residents (43%) felt moody or depressed in contrast to seven (14%) who felt depressed during the daytime rotation (p=0.0001). Twenty-one residents (41%) felt they were slower in their thinking during the night float than daytime rotations. The results suggest that disturbances of sleep and mood and decreased alertness, typical of night shift, are present in the night-float rotation. Residency programs should monitor closely the impact of the night-float rotation on resident well being and patient safety. The impact of night-shift work should be considered in the design of night-float schedules, and teaching should be provided for residents to learn coping strategies for night-shift work.     

IMPACT OF NIGHT-FLOAT ROTATION ON SLEEP,MOOD, AND ALERTNESS: THE RESIDENT'S PERCEPTION

Night-float rotations were designed to alleviate the workload of residents on night call and thereby improve patient safety. However, the impact of the night float on residents is yet to be surveyed. We assessed the impact of the night-float rotation on pediatric residents using an anonymous questionnaire that covered topics, based on recall, about sleep, mood, alertness, adjustment, and others. The study was conducted in a major tertiary pediatric teaching hospital in the United States. Participants were pediatric residents who had completed one or two night-float rotations and were in active training at our teaching hospital at the time of the study. Fifty-two of 60 eligible residents (87%) responded. Sleep duration during the night-float rotation was shorter than during day-shift work in 24 residents (46%), longer in 20 (38%), and unchanged in eight (15%). A higher proportion of residents took longer to fall asleep, had more difficulty falling asleep, had more sleep interruptions, and felt less rested upon awakening. Twenty-four residents (46%) felt that their bodies never adjusted to the night shift. Also, 22 residents (43%) felt moody or depressed in contrast to seven (14%) who felt depressed during the daytime rotation (p=0.0001). Twenty-one residents (41%) felt they were slower in their thinking during the night float than daytime rotations. The results suggest that disturbances of sleep and mood and decreased alertness, typical of night shift, are present in the night-float rotation. Residency programs should monitor closely the impact of the night-float rotation on resident well being and patient safety. The impact of night-shift work should be considered in the design of night-float schedules, and teaching should be provided for residents to learn coping strategies for night-shift work.     

Effects of 24-Hour Shift Work with Nighttin Napping on Circadian Rhythm Characteristi in Ambulance Personnel

Forty-two ambulance personnel engaged in a 24-h shift system participated in a chronobiological field study to study the effects of 24-h shift work on circadian rhythm characteristics. Autorhythmometry of circadian rhythms of oral temperature, right and left grip strengths, and heart rate plus subjective assessment of drowsiness, fatigue, and attention was performed every ～ 4 h except during sleep for 7 days. Cosinor and power spectral analyses were applied to the longitudinal data of each individual. Changes in circadian period different from 24 h of oral temperature, grip strengths, and heart rate plus subjective drowsiness, fatigue, and attention were observed in ambulance personnel. The incidence of circadian periodicity different from 24 h in oral temperature and right and left grip strength was 28.6%, 35.7%, and 47.6%, respectively. The incidence was relatively lower than that of shift workers engaged in a discontinuous 8-h shift system we reported on previously. Working conditions allowing ambulance personnel to nap when not called for emergency (for > 4 h) might contribute to a stabilization of circadian rhythms. Furthermore, long nighttime ambulance service amounting to >100 min was significantly associated with a high incidence of at least one prominent circadian period among oral temperature and right and left grip strength rhythms different from 24 h. In conclusion, 24-h shift work altered the characteristics of circadian rhythms of ambulance personnel; nighttime naps seemed to have a favorable effect on averting changes in circadian rhythms.     

Chronobiological Evaluation of the Active Biliary and Renal Secretion of Ampicillin

This study was carried out to determine the circadian rhythm of active renal and biliary excretion of ampicillin. Sprague-Dawley male rats, housed under a light-dark (12 h: 12 h) cycle, were used in these studies. Rats received an i.v. bolus of ampicillin (50 mg/kg) at 0800, 1200, 1600, 2000, 2400, and 0400. Plasma, bile, and urine were collected. There was a significant circadian rhythm in the renal and biliary clearances of ampicillin. Clearance was increased approximately twofold during the active cycle compared with the resting cycle. No change in volume of distribution was noted. Therefore, the mean residence time of ampicillin was significantly lower during the active cycle. Since the majority of ampicillin that is excreted into the urine and bile is actively secreted via the anion carrier-mediated pathway, the circadian rhythm of glomerular filtration cannot explain the variation observed in this study. Changes in renal/hepatic blood flow could explain, in part, the circadian rhythm observed in these studies; however, variability in either the capacity of the anionic carrier or the binding affinity of the drug for the carrier cannot be ruled out.     

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).     

Shift work and inter-individual differences in sleep and sleepiness

Inter-individual differences in tolerance for shift work have been studied primarily in terms of external factors affecting alertness on the job or the ability to rest and sleep while at home. However, there is increasing evidence that neurobiological factors play a role as well, particularly the major processes involved in the regulation of sleep and wakefulness. These include a sleep homeostatic process seeking to balance wakefulness and sleep and a circadian process seeking to promote wakefulness during the day and sleep during the night. Shift work is associated with a temporal misalignment of these two endogenous processes. During nightwork, this misalignment makes it difficult to stay awake during the nightshift and sleep during the day. However, inter-individual variability in the processes involved in sleep/wake regulation is substantial. Recent studies have demonstrated the existence of inter-individual differences in vulnerability to cognitive deficits from sleep loss. Moreover, these inter-individual differences were shown to constitute a trait. Interestingly, self-evaluations of sleepiness did not correspond well with the trait inter-individual variability in objective levels of performance impairment during sleep deprivation. Perhaps because of this discrepancy, in operational settings, the inter-individual differences in vulnerability to sleep loss do not appear to be limited due to self-selection mechanisms. Indeed, even among a highly select group of active-duty jet fighter pilots flying a series of simulated night missions, systematic inter-individual differences in performance impairment from sleep loss were still observed. There are significant personal and economic consequences to human error and accidents caused by performance deficits due to sleep loss. It is important, therefore, to study the inter-individual differences in the regulation of sleep and wakefulness in the work environment so that cognitive impairment during shift work may be better anticipated and prevented.     

The Shape of the Endogenous Circadian Rhythm of Rectal Temperature in Humans

Fourteen healthy subjects have been studied in an isolation unit while living on a 30h “day” (20h awake, 10h asleep) for 14 (solar) days but while aware of real time. Waking activities were sedentary and included reading, watching television, and so forth. Throughout, regular recordings of rectal temperature were made, and in a subgroup of 6 subjects, activity was measured by a wrist accelerometer. Temperature data have been subjected to cosinor analysis after “purification,” a method that enables the endogenous (clock-driven) and exogenous (activity-driven) components of the circadian rhythm to be assessed. Moreover, the protocol enables effects due to the circadian rhythm and time-since-waking to be separated. Results showed that activity was slightly affected by the endogenous temperature rhythm. Also, the masking effects on body temperature exerted by the exogenous factors appeared to be less than average in the hours before and just after the peak of the endogenous temperature rhythm. This has the effect of producing a temperature plateau rather than a peak during the daytime. The implications of this for mental performance and sleep initiation are discussed. (Chronobiology International, 13(4), 261-271, 1996)     

A Chronobiological Approach to Circulating Levels of Renin, Angiotensin-Converting Enzyme, Aldosterone, ACTH, and Cortisol in Addison's Disease

This study deals with a chronobiological approach to the circadian rhythm of the renin-angiotensin-aldosterone system (RAAS) and the ACTH-cor-tisol axis (ACA) in patients with Addison's disease (PAD). The aim is to explore the mechanism(s) for which the circadian rhythmicity of the RAAS and ACA takes place. The study has shown that both the RAAS and ACA are devoid of a circadian rhythm in PAD. The lack of rhythmicity for renin and ACTH provides indirect evidence that their rhythmic secretion is in some way related to the circadian oscillation of aldosterone and cortisol. This implies a new concept: a positive feedback may be included among the mechanisms which chronoregulate the RAAS and ACA.     

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).     

Contrast in the circadian behaviors of an electrodermal activity and bioimpedance spectroscopy

ABSTRACT

Probing the electrical response of the human body is minimally invasive and a promising area of investigation for future health care. The electrical responses of individuals may vary depending on daily physiological rhythms or environmental changes, which may hamper their prediction for pathological status. In this study, we observed circadian expressions via both alternating current (AC) and direct current (DC) electrical responses of the human body using bioelectrical impedance analysis (BIA) and electrodermal activity (EDA). In total, 14 healthy adults (9 males and 5 females) participated and were hospitalized for 2 nights with controlled caloric intake, sleep hours and residential conditions. The EDA data showed a significant circadian rhythm, but the BIA data did not show significant modulations during the measurement period. No difference was found between circadian changes in male and female participants. The acrophase of the EDA voltage response showed similar behavior with variations in the heart rate variability, with a resistance minimum occurring at approximately 4 pm, implying that the behavior of the EDA is probably affected by the sympathetic nerve response. Moreover, the resistance of the EDA varied by up to 15% from its mean value, which suggests that circadian variations cannot be neglected for the correct diagnosis of pathological conditions. In contrast, the BIA method did not show this circadian variation but showed independent results over the measurement period. This difference in performance implies that the DC and AC responses of the human body contain different electrophysiological information.     

Estimating the circadian rhythm in the risk of occupational injuries and accidents

The authors recently published a prototypic Risk Index (RI) to estimate the risk of critical errors associated with shift systems. This RI was based on published trends in the relative risk of injuries and accidents, and a simple additive model was proposed to estimate the risk for a given shift system. However, extending the RI to irregular work schedules requires an estimation of the phase and amplitude of the circadian rhythm in risk. This paper integrates the published evidence on three independent sources of data that allow such estimations to be made: the trend in risk over a 24 h day, over the course of the night shift, and across the three different (8 h) shifts. Despite potential confounders, maximum risk (i.e., acrophase=peak time) estimates across these three trends showed a remarkable consistency, with all three estimates occurring at about midnight, although the amplitude estimates varied considerably. The best estimate of the amplitude of the circadian rhythm in risk would appear to be that based on trend over the three (8 h) shifts, as this trend is the least confounded. The estimated acrophase (peak time) in risk appeared earlier than would be predicted from consideration of the circadian rhythm in alertness, fatigue, or performance on simple interpolated tasks, such as reaction time or performance on the Psychomotor Vigilance Test.     

Evaluation of the circadian profile of peripheral plasma galanin concentrations in normal subjects

Galanin administration can influence pituitary function principally resulting in an increase in GH secretion. However, the role of circulating GAL levels in human endocrine function is still unknown. In the present study we simultaneously measured the circadian profiles of GAL, ACTH and GH in peripheral blood of ten adult subjects. Plasma samples were collected through an intravenous catheter at 0800, 1200, 1600, 2000, 2200, 2400, 0200, 0400 hours. The results were statistically evaluated by the cosinor analysis technique. A significant circadian rhythm of both plasma ACTH (p < 0.001) and GH levels (p < 0.03) was found with acrophases occurring at 0753 hrs and 0131 hrs for ACTH and GH, respectively. On the contrary, no significant rhythm was found in plasma GAL levels, indicating that no correlations exist between GAL and either GH or ACTH circadian profiles. Furthermore, the simultaneous assay of both GAL and GH plasma levels during a nocturnal frequent sampling performed in four volunteers showed the presence of peaks in GAL levels which, however, were not concomitant to the peaks in GH levels. These data demonstrate the lack of rhythmicity in the circadian profile of plasma GAL levels in healthy human subjects. The role of GAL in human endocrine function remains unknown and these results suggest that, in spite of the well documented increase in plasma GH concentrations following the intravenous administration of GAL, physiologically circulating levels of GAL are likely not involved in the regulation of GH secretion.     

The Effect of Activity on the Waking Temperature Rhythm in Humans

Nine healthy female subjects were studied when exposed to the natural light-dark cycle, but living for 17 “days” on a 27h day (9h sleep, 18h wake). Since the circadian endogenous oscillator cannot entrain to this imposed period, forced desynchronization between the sleep/activity cycle and the endogenous circadian temperature rhythm took place. This enabled the effects of activity on core temperature to be assessed at different endogenous circadian phases and at different stages of the sleep/activity cycle. Rectal temperature was measured at 6-minute intervals, and the activity of the nondominant wrist was summed at 1-minute intervals. Each waking span was divided into overlapping 3h sections, and each section was submitted to linear regression analysis between the rectal temperatures and the total activity in the previous 30 minutes. From this analysis were obtained the gradient (of the change in rectal temperature produced by a unit change in activity) and the intercept (the rectal temperature predicted when activity was zero). The gradients were subjected to a two-factor analysis of variance (ANOVA) (circadian phase/ time awake). There was no significant effect of time awake, but circadian phase was highly significant statistically. Post hoc tests (Newman-Keuls) indicated that gradients around the temperature peak were significantly less than those around its trough. The intercepts formed a sinusoid that, for the group, showed a mesor (±SE) of 36.97 (±0.12) and amplitude (95% confidence interval) of 0.22°C (0.12°C, 0.32°C). We conclude that this is a further method for removing masking effects from circadian temperature rhythm data in order to assess its endogenous component, a method that can be used when subjects are able to live normally. We suggest also that the decreased effect of activity on temperature when the endogenous circadian rhythm and activity are at their peak will reduce the possibility of hyperthermia.     

Circadian Rhythm of Blood Pressure: Internal and External Time Triggers

Diurnal blood pressure (BP) fluctuations are superimposed by a 24-h rhythm with usually lower levels during the night and higher levels during the day. In contrast to other rhythmic bioparameters, the diurnal BP rhythm is largely dependent on activity and sleep rather than on clock time. This has been demonstrated by the BP characteristics after shifted sleeping and working phases, during transition from sleep to wakefulness, and by the influence of sleep and activities on the 24-h BP curve during normal daily routines. Whereas the circadian rhythm of BP is predominantly governed by external time triggers, endogenous rhythmic-ity can only be detected by time microscopic analysis or in conditions where effects of external time triggers are almost excluded.