Angiotensin receptor blockers shift the circadian rhythm of blood pressure by suppressing tubular sodium reabsorption

Recently, we found that an angiotensin II receptor blocker (ARB) restored the circadian rhythm of the blood pressure (BP) from a nondipper to a dipper pattern, similar to that achieved with sodium intake restriction and diuretics (Fukuda M, Yamanaka T, Mizuno M, Motokawa M, Shirasawa Y, Miyagi S, Nishio T, Yoshida A, Kimura G. J Hypertens 26: 583-588, 2008). ARB enhanced natriuresis during the day, while BP was markedly lower during the night, resulting in the dipper pattern. In the present study, we examined whether the suppression of tubular sodium reabsorption, similar to the action of diuretics, was the mechanism by which ARB normalized the circadian BP rhythm. BP and glomerulotubular balance were compared in 41 patients with chronic kidney disease before and during ARB treatment with olmesartan once a day in the morning for 8 wk. ARB increased natriuresis (sodium excretion rate; U(Na)V) during the day (4.5 ± 2.2 to 5.5 ± 2.1 mmol/h, P = 0.002), while it had no effect during the night (4.3 ± 2.0 to 3.8 ± 1.6 mmol/h, P = 0.1). The night/day ratios of both BP and U(Na)V were decreased. The decrease in the night/day ratio of BP correlated with the increase in the daytime U(Na)V (r = 0.42, P = 0.006). Throughout the whole day, the glomerular filtration rate (P = 0.0006) and tubular sodium reabsorption (P = 0.0005) were both reduced significantly by ARB, although U(Na)V remained constant (107 ± 45 vs. 118 ± 36 mmol/day, P = 0.07). These findings indicate that the suppression of tubular sodium reabsorption, showing a resemblance to the action of diuretics, is the primary mechanism by which ARB can shift the circadian BP rhythm into a dipper pattern.     

Sleep deprivation induces excess diuresis and natriuresis in healthy children

Urine production is reduced at night, allowing undisturbed sleep. This study was undertaken to show the effect of sleep deprivation (SD) on urine production in healthy children. Special focus was on gender and children at an age where enuresis is still prominent. Twenty healthy children (10 girls) underwent two 24-h studies, randomly assigned to either sleep or SD on the first study night. Diet and fluid intake were standardized. Blood samples were drawn every 4 h during daytime and every 2 h at night. Urine was fractionally collected. Blood pressure and heart rate were noninvasively monitored. Blood was analyzed for plasma antidiuretic hormone (AVP), atrial natriuretic peptide (ANP), angiotensin II, aldosterone, and renin. Urine was analyzed for aquaporin-2 and PGE(2). Successful SD was achieved in all participants with a minimum of 4 h 50 min, and full-night SD was obtained in 50% of the participants. During SD, both boys and girls produced markedly larger amounts of urine than during normal sleep (477 ± 145 vs. 291 ± 86 ml, P < 0.01). SD increased urinary excretion of sodium (0.17 ± 0.05 vs. 0.10 ± 0.03 mmol·kg(-1)·h(-1)) whereas solute-free water reabsorption remained unchanged. SD induced a significant fall in nighttime plasma AVP (P < 0.01), renin (P < 0.05), angiotensin II (P < 0.001), and aldosterone (P < 0.05) whereas plasma ANP levels remained uninfluenced (P = 0.807). Nighttime blood pressure and heart rate were significantly higher during SD (mean arterial pressure: 78.5 ± 8.0 vs. 74.7 ± 8.7 mmHg, P < 0.001). SD leads to natriuresis and excess diuresis in healthy children. The underlying mechanism could be a reduced nighttime dip in blood pressure and a decrease in renin-angiotensin-aldosterone system levels during sleep deprivation.     

Circadian coupling between pancreatic secretion and intestinal motility in humans

Human interdigestive intestinal motility follows a circadian rhythm with reduced nocturnal activity, but circadian pancreatic exocrine secretion is unknown. To determine whether circadian changes in interdigestive pancreatic secretion occur and are associated with motor events, pancreatic enzyme outputs, proximal jejunal motility, and plasma pancreatic polypeptide concentrations were measured during consecutive daytime and nighttime periods (12 h each) in seven healthy volunteers using orojejunal multilumen intubation. Studies were randomly started in the morning or evening. Nocturnally, motility decreased (motor quiescence: 67 +/- 22 vs. 146 +/- 37 min; motility index: 3.59 +/- 0.33 vs. 2.78 +/- 0.40 mmHg/min; both P < 0.05) but amylase output increased (273 +/- 78 vs. 384 +/- 100 U/min; P < 0.05) and protease output remained unchanged (P > 0.05); consequently, enzyme/motility ratio increased. Amylase outputs were always lowest during phase I. Motor but not pancreatic circadian activities were associated with sleep. Pancreatic polypeptide plasma concentrations were unchanged. Consequently, intestinal motor and pancreatic exocrine functions may have different circadian rhythms, i.e., decreased motor and stable secretory activity during the night. However, the association between individual phases of interdigestive motor and secretory activity is preserved. The nocturnal increase in enzyme/motility ratio is probably not caused by increased cholinergic tone.     

A compromise phase position for permanent night shift workers: circadian phase after two night shifts with scheduled sleep and light/dark exposure

Night shift work is associated with a myriad of health and safety risks. Phase-shifting the circadian clock such that it is more aligned with night work and day sleep is one way to attenuate these risks. However, workers will not be satisfied with complete adaptation to night work if it leaves them misaligned during days off. Therefore, the goal of this set of studies is to produce a compromise phase position in which individuals working night shifts delay their circadian clocks to a position that is more compatible with nighttime work and daytime sleep yet is not incompatible with late nighttime sleep on days off. This is the first in the set of studies describing the magnitude of circadian phase delays that occurs on progressively later days within a series of night shifts interspersed with days off. The series will be ended on various days in order to take a "snapshot" of circadian phase. In this set of studies, subjects sleep from 23:00 to 7:00 h for three weeks. Following this baseline period, there is a series of night shifts (23:00 to 07:00 h) and days off. Experimental subjects receive five 15 min intermittent bright light pulses (approximately 3500 lux; approximately 1100 microW/cm2) once per hour during the night shifts, wear sunglasses that attenuate all visible wavelengths--especially short wavelengths ("blue-blockers")--while traveling home after the shifts, and sleep in the dark (08:30-15:30 h) after each night shift. Control subjects remain in typical dim room light (<50 lux) throughout the night shift, wear sunglasses that do not attenuate as much light, and sleep whenever they want after the night shifts. Circadian phase is determined from the circadian rhythm of melatonin collected during a dim light phase assessment at the beginning and end of each study. The sleepiest time of day, approximated by the body temperature minimum (Tmin), is estimated by adding 7 h to the dim light melatonin onset. In this first study, circadian phase was measured after two night shifts and day sleep periods. The Tmin of the experimental subjects (n=11) was 04:24+/-0.8 h (mean+/-SD) at baseline and 7:36+/-1.4 h after the night shifts. Thus, after two night shifts, the Tmin had not yet delayed into the daytime sleep period, which began at 08:30 h. The Tmin of the control subjects (n=12) was 04:00+/-1.2 h at baseline and drifted to 4:36+/-1.4 h after the night shifts. Thus, two night shifts with a practical pattern of intermittent bright light, the wearing of sunglasses on the way home from night shifts, and a regular sleep period early in the daytime, phase delayed the circadian clock toward the desired compromise phase position for permanent night shift workers. Additional night shifts with bright light pulses and daytime sleep in the dark are expected to displace the sleepiest time of day into the daytime sleep period, improving both nighttime alertness and daytime sleep but not precluding adequate sleep on days off.     

Chronobiological evidence for an uncoupling of the Na,K-ATPase to aldosterone in normal renin hypertension

The Na,K-ATPase activity of erythrocyte membranes is markedly increased in normal-renin essential hypertensives. A temporal shift of the chronobiology of the erythrocyte-membrane-bound Na,K-ATPase in these patients is described. The disorder causes a loss of synchronism between the circadian rhythms of aldosterone and Na,K-ATPase. Such uncoupling phenomenon may explain the inversion of the day/night sodium excretion ratio and other disturbances of sodium metabolism found in essential hypertensives.     

Wearing Blue-Blockers in the Morning Could Improve Sleep of Workers on a Permanent Night Schedule: A Pilot Study

Night shiftworkers often complain of disturbed sleep during the day. This could be partly caused by morning sunlight exposure during the commute home, which tends to maintain the circadian clock on a daytime rhythm. The circadian clock is most sensitive to the blue portion of the visible spectrum, so our aim was to determine if blocking short wavelengths of light below 540 nm could improve daytime sleep quality and nighttime vigilance of night shiftworkers. Eight permanent night shiftworkers (32–56 yrs of age) of Quebec City's Canada Post distribution center were evaluated during summertime, and twenty others (24–55 yrs of age) during fall and winter. Timing, efficacy, and fragmentation of daytime sleep were analyzed over four weeks by a wrist activity monitor, and subjective vigilance was additionally assessed at the end of the night shift in the fall–winter group. The first two weeks served as baseline and the remaining two as experimental weeks when workers had to wear blue-blockers glasses, either just before leaving the workplace at the end of their shift (summer group) or 2 h before the end of the night shift (fall–winter group). They all had to wear the glasses when outside during the day until 16:00 h. When wearing the glasses, workers slept, on average ±SD, 32±29 and 34±60 more min/day, increased their sleep efficacy by 1.95±2.17% and 4.56±6.1%, and lowered their sleep fragmentation by 1.74±1.36% and 4.22±9.16% in the summer and fall–winter group, respectively. Subjective vigilance also generally improved on Fridays in the fall–winter group. Blue-blockers seem to improve daytime sleep of permanent night-shift workers.     

Physiological effects of shift work on hospital nurses

OBJECTIVE: The purpose of this study was to assess the physiological effects of shift work on the urinary excretion rates of norepinephrine, 6-sulfatoxymelatonin and estriol in hospital nurses. METHOD: Twenty-four hour urine specimens were examined on a daytime/nighttime basis for each work shift of pregnant and non-pregnant subjects. The urinary norepinephrine and 6-sulfatoxymelatonin were measured by enzyme-linked immunosorbent assay and estriol by radio-immunoassay. RESULTS: Urinary norepinephrine level during the night work was higher than the night levels of the days off and the day shift. Urinary 6-sulfatoxymelatonin level during the night work was lower than the night levels of the days off and the day shift. Urinary estriol level of pregnant subjects showed no differences among work shift and also between daytime and nighttime. CONCLUSIONS: Urinary excretion rates of norepinephrine and 6-sulfatoxymelatonin were affected by shift work both for non-pregnant and pregnant subjects. It was unlikely that urinary estriol levels in the pregnant subjects were significantly affected by shift work.     

Proteomic analysis of day-night variations in protein levels in the rat pineal gland

The pineal gland secretes the hormone melatonin. This secretion exhibits a circadian rhythm with a zenith during night and a nadir during day. We have performed proteome analysis of the superficial pineal gland in rats during daytime and nighttime. The proteins were extracted and subjected to 2-DE. Of 1747 protein spots revealed by electrophoresis, densitometric analysis showed the up-regulation of 25 proteins during nighttime and of 35 proteins during daytime. Thirty-seven of the proteins were identified by MALDI-TOF MS. The proteins up-regulated during the night are involved in the Krebs cycle, energy transduction, calcium binding, and intracellular transport. During the daytime, enzymes involved in glycolysis, electron transport, and also the Krebs cycle were up-regulated as well as proteins taking part in RNA binding and RNA processing. Our data show a prominent day-night variation of the protein levels in the rat pineal gland. Some proteins are up-regulated during the night concomitant with the melatonin secretion of the gland. Other proteins are up-regulated during the day indicating a pineal metabolism not related to the melatonin synthesis.     

A Compromise Phase Position for Permanent Night Shift Workers: Circadian Phase after Two Night Shifts with Scheduled Sleep and Light/Dark Exposure

Night shift work is associated with a myriad of health and safety risks. Phase‐shifting the circadian clock such that it is more aligned with night work and day sleep is one way to attenuate these risks. However, workers will not be satisfied with complete adaptation to night work if it leaves them misaligned during days off. Therefore, the goal of this set of studies is to produce a compromise phase position in which individuals working night shifts delay their circadian clocks to a position that is more compatible with nighttime work and daytime sleep yet is not incompatible with late nighttime sleep on days off. This is the first in the set of studies describing the magnitude of circadian phase delays that occurs on progressively later days within a series of night shifts interspersed with days off. The series will be ended on various days in order to take a “snapshot” of circadian phase. In this set of studies, subjects sleep from 23:00 to 7:00 h for three weeks. Following this baseline period, there is a series of night shifts (23:00 to 07:00 h) and days off. Experimental subjects receive five 15 min intermittent bright light pulses (～3500 lux; ～1100 µW/cm²) once per hour during the night shifts, wear sunglasses that attenuate all visible wavelengths—especially short wavelengths (“blue‐blockers”)—while traveling home after the shifts, and sleep in the dark (08:30–15:30 h) after each night shift. Control subjects remain in typical dim room light (<50 lux) throughout the night shift, wear sunglasses that do not attenuate as much light, and sleep whenever they want after the night shifts. Circadian phase is determined from the circadian rhythm of melatonin collected during a dim light phase assessment at the beginning and end of each study. The sleepiest time of day, approximated by the body temperature minimum (T_min), is estimated by adding 7 h to the dim light melatonin onset. In this first study, circadian phase was measured after two night shifts and day sleep periods. The T_min of the experimental subjects (n=11) was 04:24±0.8 h (mean±SD) at baseline and 7:36±1.4 h after the night shifts. Thus, after two night shifts, the T_min had not yet delayed into the daytime sleep period, which began at 08:30 h. The T_min of the control subjects (n=12) was 04:00±1.2 h at baseline and drifted to 4:36±1.4 h after the night shifts. Thus, two night shifts with a practical pattern of intermittent bright light, the wearing of sunglasses on the way home from night shifts, and a regular sleep period early in the daytime, phase delayed the circadian clock toward the desired compromise phase position for permanent night shift workers. Additional night shifts with bright light pulses and daytime sleep in the dark are expected to displace the sleepiest time of day into the daytime sleep period, improving both nighttime alertness and daytime sleep but not precluding adequate sleep on days off.     

Influence of the Amount of Light Received during the Day and Night Times on the Circadian Rhythm of Melatonin Secretion in Women Living Diurnally

The study investigated the relationship between the circadian variation of salivary melatonin and the amount of light received during the day and night. Forty one females served as subjects. An illuminance meter worn on the wrist of the non-dominant arm measured the amount of light which subjects leading a diurnal lifestyle received during two consecutive days. Light received from the time of rising to 18:00h was defined as ‘daytime light’, and that from 18:00h to the time of retiring as ‘nighttime light’. The average amount of light over the two days was 48 × 10 4 lx during the daytime and 11 × 10 4 lx during the nighttime. Saliva was collected every 4h in order to measure melatonin secretion. Peaks of melatonin secretion were observed at 14:00h and 18:00h in the subjects who had received lesser amounts of light during the daytime and nighttime. Melatonin secretion was high around 22:00h and peaked around 02:00h in the subjects who had received greater amounts of light during the daytime and lesser amounts of light during the nighttime. Nocturnal melatonin secretion was suppressed in the subjects who received greater amounts of light during the nighttime. Thus, the amount of light received during the daytime and the nighttime during the course of a diurnal lifestyle could have a profound influence on the circadian pattern of melatonin secretion.     

基于遥测技术对巴马小型猪部分生理指标的观测

目的：应用遥测技术观察巴马小型猪在清醒自由状态下心电、血压、呼吸、活动等指标昼夜波动变化。方法取雄性6月龄巴马小型猪6只,行浅表股动脉VAP血管通路植入手术,恢复7 d后,用EMAK遥测系统进行24 h连续清醒自由状态下心电、血压、呼吸、活动指标监测,并用EMAK分析软件对上述指标进行分析。结果6月龄巴马小型猪心电、血压、呼吸、活动都有昼夜节律变化,白昼心率显著高于黑夜心率（ P ＜0.01）,且白昼PR间期、QRS间期与QT间期均显著低于黑夜（P ＜0.05,P ＜0.01）,白昼平均心率为76.22次/分,黑夜平均心率为67.03次/分,白昼平均PR间期、QRS间期和QT间期分别为109.97 ms、42.72 ms、380.37 ms,黑夜平均PR间期、QRS间期和QT间期为112.32 ms、44.01 ms、389.24 ms。巴马小型猪白昼收缩压、舒张压、平均压都显著高于夜间（ P ＜0.01）,白昼平均收缩压、舒张压、平均压分别为129.57 mmHg、96.75 mmHg、111.73 mmHg,夜间平均收缩压、舒张压、平均压分别为122.81 mmHg、92.65 mmHg、106.19 mmHg,且黑夜收缩压、舒张压、平均压下降率分别为19.89％、19.05％、19.35％。另外,巴马小型猪在白昼的活动情况与呼吸频率都要显著高于夜间（ P ＜0.01）。结论利用遥测技术可以对清醒自由状态下巴马小型猪心电、血压、呼吸、活动等进行连续监测,能真实的反应小型猪在24 h内上述生理指标的变化规律,为巴马小型猪在药理毒理研究中的应用提供参考。     

Circadian Aspects of Postprandial Metabolism

Time‐dependent variations in the hormonal and metabolic responses to food are of importance to human health, as postprandial metabolic responses have been implicated as risk factors in a number of major diseases, including cardiovascular disease. Early work reported decreasing glucose tolerance in the evening and at night with evidence for insulin resistance at night. Subsequently an endogenous circadian component, assessed in constant routine (CR), as well as an influence of sleep time, was described for glucose and insulin. Plasma triacylglycerol (TAG), the major lipid component of dietary fat circulating after a meal, also appears to be influenced by both the circadian clock and sleep time with higher levels during biological night (defined as the time between the onset and offset of melatonin secretion) despite identical hourly nutrient intake. These time‐dependent differences in postprandial responses have implications for shiftworkers. In the case of an unadapted night shift worker, meals during work time will be taken during biological night. In simulated night shift conditions the TAG response to a standard meal, preceded by either a low‐fat or a high‐fat premeal, was higher after a nighttime meal than during a daytime meal, and the day/night difference was larger in men than in women. In real night shift workers in Antarctica, insulin, glucose, and TAG all showed an increased response after a nighttime meal (second day of night shift) compared to a daytime meal. Night shift workers are reported to have an approximately 1.5 times higher incidence of heart disease risk and also demonstrate higher TAG levels compared with matched dayworkers. As both insulin resistance and elevated circulating TAG are independent risk factors for heart disease, it is possible that meals at night may contribute to this risk.     

Circadian aspects of postprandial metabolism

Time-dependent variations in the hormonal and metabolic responses to food are of importance to human health, as postprandial metabolic responses have been implicated as risk factors in a number of major diseases, including cardiovascular disease. Early work reported decreasing glucose tolerance in the evening and at night with evidence for insulin resistance at night. Subsequently an endogenous circadian component, assessed in constant routine (CR), as well as an influence of sleep time, was described for glucose and insulin. Plasma triacylglycerol (TAG), the major lipid component of dietary fat circulating after a meal, also appears to be influenced by both the circadian clock and sleep time with higher levels during biological night (defined as the time between the onset and offset of melatonin secretion) despite identical hourly nutrient intake. These time-dependent differences in postprandial responses have implications for shiftworkers. In the case of an unadapted night shift worker, meals during work time will be taken during biological night. In simulated night shift conditions the TAG response to a standard meal, preceded by either a low-fat or a high-fat premeal, was higher after a nighttime meal than during a daytime meal, and the day/night difference was larger in men than in women. In real night shift workers in Antarctica, insulin, glucose, and TAG all showed an increased response after a nighttime meal (second day of night shift) compared to a daytime meal. Night shift workers are reported to have an approximately 1.5 times higher incidence of heart disease risk and also demonstrate higher TAG levels compared with matched dayworkers. As both insulin resistance and elevated circulating TAG are independent risk factors for heart disease, it is possible that meals at night may contribute to this risk.     

Circadian Adaptation to Night Shift Work Influences Sleep,Performance, Mood and the Autonomic Modulation of the Heart

Our aim was to investigate how circadian adaptation to night shift work affects psychomotor performance, sleep, subjective alertness and mood, melatonin levels, and heart rate variability (HRV). Fifteen healthy police officers on patrol working rotating shifts participated to a bright light intervention study with 2 participants studied under two conditions. The participants entered the laboratory for 48 h before and after a series of 7 consecutive night shifts in the field. The nighttime and daytime sleep periods were scheduled during the first and second laboratory visit, respectively. The subjects were considered “adapted” to night shifts if their peak salivary melatonin occurred during their daytime sleep period during the second visit. The sleep duration and quality were comparable between laboratory visits in the adapted group, whereas they were reduced during visit 2 in the non-adapted group. Reaction speed was higher at the end of the waking period during the second laboratory visit in the adapted compared to the non-adapted group. Sleep onset latency (SOL) and subjective mood levels were significantly reduced and the LF∶HF ratio during daytime sleep was significantly increased in the non-adapted group compared to the adapted group. Circadian adaptation to night shift work led to better performance, alertness and mood levels, longer daytime sleep, and lower sympathetic dominance during daytime sleep. These results suggest that the degree of circadian adaptation to night shift work is associated to different health indices. Longitudinal studies are required to investigate long-term clinical implications of circadian misalignment to atypical work schedules.     

Influence of the Amount of Light Received during the Day and Night Times on the Circadian Rhythm of Melatonin Secretion in Women Living Diurnally

The study investigated the relationship between the circadian variation of salivary melatonin and the amount of light received during the day and night. Forty one females served as subjects. An illuminance meter worn on the wrist of the non-dominant arm measured the amount of light which subjects leading a diurnal lifestyle received during two consecutive days. Light received from the time of rising to 18:00h was defined as 'daytime light', and that from 18:00h to the time of retiring as 'nighttime light'. The average amount of light over the two days was 48 × 10 4 lx during the daytime and 11 × 10 4 lx during the nighttime. Saliva was collected every 4h in order to measure melatonin secretion. Peaks of melatonin secretion were observed at 14:00h and 18:00h in the subjects who had received lesser amounts of light during the daytime and nighttime. Melatonin secretion was high around 22:00h and peaked around 02:00h in the subjects who had received greater amounts of light during the daytime and lesser amounts of light during the nighttime. Nocturnal melatonin secretion was suppressed in the subjects who received greater amounts of light during the nighttime. Thus, the amount of light received during the daytime and the nighttime during the course of a diurnal lifestyle could have a profound influence on the circadian pattern of melatonin secretion.     

Fluid conservation in athletes: responses to water intake, supine posture, and immersion

The roles of antidiuretic hormone (ADH) and aldosterone in the elicited diuretic responses of trained and untrained men to seated, supine, and head-out water immersed conditions were studied. Volunteers were comprised of groups of six untrained individuals, six trained swimmers, and six trained runners. Each subject underwent three protocols, six hours in a seated position, supine position, or immersion (35 degrees C water). The last two protocols were preceded and followed by 1 h of seated position. After 10 h of fasting, 0.5% body wt of water was drunk. One hour later the trained groups had higher urine osmolalities (P less than 0.05) and urinary excretion rates of ADH (P less than 0.05) and lower urine flow rates (P less than 0.05) than untrained subjects. Throughout the sitting protocol, urinary ADH was also higher in both trained groups (P less than 0.05). Both supine posture and immersion resulted in significant decreases in urinary ADH in the untrained subjects (P less than 0.05) but no changes wer noted in swimmers and only during the second hour of immersion in the runners (P less than 0.05). The natriuresis and kaliuresis were greater during immersion than in the supine position but plasma renin activity, measured only in trained groups, and plasma aldosterone, measured in the untrained group, were decreased similarly with both protocols. The increases in urinary sodium excretion and urine flow rate were lower in trained than untrained subjects during the supine and immersion protocols (P less than 0.05). The data are compatible with an increased osmotic but decreased volume sensitivity of ADH control in trained men.     

Sleep and sleepiness among Brazilian shift-working bus drivers

The aim of this study was to evaluate daytime and nighttime sleep, as well as daytime and nighttime sleepiness of professional shift-working bus drivers. Thirty-two licensed bus drivers were assessed by nocturnal and diurnal polysomnography (PSG) recording and multiple sleep latency testing (MSLT) sessions. Sleep length was shorter and sleep efficiency reduced during daytime sleep compared with nighttime sleep. Thirty-eight percent of the drivers had indices of obstructive apnea and hypopnea syndrome (>5/h sleep) during nighttime and daytime sleep; more drivers snored during daytime than nighttime sleep (50% vs. 35%, p < 0.05), and 38% of the drivers evidenced periodic leg movements. The MSLT revealed that 42 and 38% of the bus drivers met the criteria for sleepiness when the test was conducted during the day and night, respectively. The daytime as compared to nighttime sleep of shift-working bus drivers was shorter and more fragmented and was associated in many with evidence of excessive sleepiness. Respiratory disorder was a common finding among the professional shift-working bus drivers. All these sleep deficiencies may adversely affect on the job driving performance.     

Circadian Variation in the Response to Experimental Endotoxemia and Modulatory Effects of Exogenous Melatonin

Disturbances in circadian rhythms are commonly observed in the development of several medical conditions and may also be involved in the pathophysiology of sepsis. Melatonin, with its antioxidative and anti-inflammatory effects, is known to modulate the response to endotoxemia. In this paper, we investigated the circadian variation with or without melatonin administration in an experimental endotoxemia model based on lipopolysaccharide (LPS). Sixty male Sprague-Dawley rats were assigned to six groups receiving an intraperitoneal injection of either LPS (5?mg/kg), LPS?+?melatonin (1?mg/kg), or LPS?+?melatonin (10?mg/kg) at either daytime or nighttime. Superoxide dismutase (SOD) was analyzed in liver samples collected after decapitation. Furthermore, inflammatory plasma markers (cytokines interleukin [IL]-6, IL-10) and oxidative plasma markers (ascorbic acid [AA], dehydroascorbic acid [DHA], and malondialdehyde [MDA]) were analyzed before and 5?h after the onset of endotoxemia. There were significant higher levels of SOD (p?<?0.05), IL-6 (p?<?0.01), and IL-10 (p?<?0.05) during nighttime endotoxemia compared with daytime. At daytime, melatonin 1 and 10?mg reduced the levels of MDA and increased SOD, IL-6, IL-10, and DHA (p?<?0.05). At nighttime, melatonin reduced the levels of MDA and increased DHA (p?<?0.05). Additionally, 10?mg melatonin resulted in lower levels of AA during daytime (p?<?0.05). No dose relationship of melatonin was observed. The results showed that the response induced by experimental endotoxemia was dependent on time of day. Melatonin administration modulated the inflammatory and oxidative stress responses induced by endotoxemia and also resulted in higher levels of antioxidants during daytime. The effect of circadian time on the endotoxemia response and possible modulatory effects of melatonin need further investigations in a human endotoxemia model.     

Sleep and Sleepiness among Brazilian Shift-Working Bus Drivers

The aim of this study was to evaluate daytime and nighttime sleep, as well as daytime and nighttime sleepiness of professional shift-working bus drivers. Thirty-two licensed bus drivers were assessed by nocturnal and diurnal polysomnography (PSG) recording and multiple sleep latency testing (MSLT) sessions. Sleep length was shorter and sleep efficiency reduced during daytime sleep compared with nighttime sleep. Thirty-eight percent of the drivers had indices of obstructive apnea and hypopnea syndrome (>5/h sleep) during nighttime and daytime sleep; more drivers snored during daytime than nighttime sleep (50% vs. 35%, p < 0.05), and 38% of the drivers evidenced periodic leg movements. The MSLT revealed that 42 and 38% of the bus drivers met the criteria for sleepiness when the test was conducted during the day and night, respectively. The daytime as compared to nighttime sleep of shift-working bus drivers was shorter and more fragmented and was associated in many with evidence of excessive sleepiness. Respiratory disorder was a common finding among the professional shift-working bus drivers. All these sleep deficiencies may adversely affect on the job driving performance.     

The impact of sleep timing and bright light exposure on attentional impairment during night work

The prevalence of hazardous incidents induced by attentional impairment during night work and ensuing commute times is attributable to circadian misalignment and increased sleep pressure. In a 10-day shift work simulation protocol (4 day shifts and 3 night shifts), the efficacies of 2 countermeasures against nighttime (2300 to 0700 h) attentional impairment were compared: (1) Morning Sleep (0800 to 1600 h; n = 18) in conjunction with a phase-delaying light exposure (2300 to 0300 h), and (2) Evening Sleep (1400 to 2200 h; n = 17) in conjunction with a phase-advancing light exposure (0300 to 0700 h). Analysis of the dim light salivary melatonin onset indicated a modest but significant circadian realignment in both sleep groups (evening sleep: 2.27 +/- 0.6 h phase advance, p < 0.01; morning sleep: 4.98 +/- 0.43 h phase delay, p < 0.01). Daytime sleep efficiency and total sleep time did not differ between them or from their respective baseline sleep (2200 to 0600 h; p > 0.05). However, on the final night shift, the evening sleep subjects had 37% fewer episodes of attentional impairment (long response times: 22 +/- 4 vs. 35 +/- 4; p = 0.02) and quicker responses (p < 0.01) on the Psychomotor Vigilance Task than their morning sleep counterparts. Their response speed recovered to near daytime levels (p = 0.47), whereas those of the morning sleep subjects continued to be slower than their daytime levels (p = 0.008). It is concluded that partial circadian realignment to night work in combination with reduced homeostatic pressure contributed to the greater efficacy of a schedule of Evening Sleep with a phase-advancing light exposure as a countermeasure against attentional impairment, over a schedule of Morning Sleep with a phase-delaying light exposure. These results have important implications for managing patients with shift work disorder.