Kegg Pathway: Circadian rhythm

Neurosci Lett. 2008 Jul 10;
Merino B, Somoza B, Ruiz-Gayo M, Cano V

Cholecystokinin (CCK) and leptin act coordinately in the brain to regulate food intake and energy balance. Recently we have reported that CCK enhances the permeability of brain barriers to leptin and we have proposed that CCK enhances energy expenditure in rats by activating in the hypothalamus the janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway, which is coupled to leptin receptors. Because plasma leptin concentration follows a Circadian rhythm (plasma leptin concentration rise maximal values during the night, after rats start eating), we have hypothesized that the interaction between leptin and CCK should be more intense in animals receiving CCK during the night, i.e., during periods of positive energy balance. In order to further characterize the physiological relevance of the interplay between leptin and CCK we have compared the effect of diurnal vs. nocturnal administration of the C-terminal octapeptide of CCK (CCK-8) on (i) body weight and food intake, and (ii) STAT3 activation, by analyzing phosphorylated STAT3 (pSTAT3) immunostaining within the arcuate nucleus of the hypothalamus. Our results show that CCK decreases body weight and food intake only after p.m. administration. Accordingly pSTAT3 immunostaining within the hypothalamus was more intense in p.m. than in a.m.-treated animals. These data suggest that the effect of CCK on leptin pathways follows a Circadian rhythm linked to the energy balance status and gives further support to the interaction between leptin and CCK.

World J Gastroenterol. 2008 Jul 14; 14(26): 4190-5
Velissaris D, Karanikolas M, Kalogeropoulos A, Solomou E, Polychronopoulos P, Thomopoulos K, Labropoulou-Karatza C

AIM: To analyze pituitary hormone and melatonin Circadian rhythms, and to correlate hormonal alterations with clinical performance, hepatic disease severity and diagnostic tests used for the detection of hepatic encephalopathy in cirrhosis. METHODS: Twenty-six patients with cirrhosis were enrolled in the study. Thirteen patients hospitalized for systemic diseases not affecting the liver were included as controls. Liver disease severity was assessed by the Child-Pugh score. All patients underwent detailed neurological assessment, electroencephalogram (EEG), brain magnetic resonance imaging (MRI), assays of pituitary hormone, cortisol and melatonin, and complete blood chemistry evaluation. RESULTS: Pituitary hormone and melatonin Circadian patterns were altered in cirrhosis patients without clinical encephalopathy. Circadian hormone alterations were different in cirrhosis patients compared with controls. Although cortisol secretion was not altered in any patient with cirrhosis, the basal cortisol levels were low and correlated with EEG and brain MRI abnormalities. Melatonin was the only hormone associated with the severity of liver insufficiency. CONCLUSION: Abnormal pituitary hormone and melatonin Circadian patterns are present in cirrhosis before the development of hepatic encephalopathy. These abnormalities may be early indicators of impending hepatic encephalopathy. Factors affecting the human biologic clock at the early stages of liver insufficiency require further study.

Int J Mol Med. 2008 Aug; 22(2): 149-53
Zhang X, Zhao F, Xu C, Lu C, Jin H, Chen S, Qian R

Plaque rupture and subsequent embolism as well as thrombosis are major causes of acute myocardial infarction and stroke secondary to atherosclerosis. Pai-1, t-PA, TF and ET-1 are thrombosis- and thrombolysis-related factors which play important roles in thrombosis formation and plaque rupture. Since acute myocardial infarction and stroke are more likely to occur between 6 a.m. and 12 p.m. than at another time of the day, we studied the relationship between Circadian rhythm and Pai-1, t-PA, TF and ET-1 in normal and atherosclerotic mice. Atherosclerosis was developed in apoE-/- mice fed a normal diet or a high cholesterol diet. The expression of Pai-1, t-PA, TF and ET-1 in the hearts of control C57BL/6J mice and atherosclerotic mice was measured by real-time RT-PCR at different Zeitgeber times (ZT) including ZT0, ZT4, ZT8, ZT10, ZT12, ZT14, ZT16 and ZT20. The expression of Pai-1, t-PA, TF and ET-1 peaked between ZT14 and ZT16 and bottomed at ZT10 in C57BL/6J mice. Their expression in apoE-/- mice fed a normal diet lost Circadian rhythm. Their expression in apoE-/- mice fed a high cholesterol diet peaked at ZT4, indicating a reverse Circadian rhythm. Our result indicates that Circadian changes in the expression of Pai-1, t-PA, TF and ET-1 may be involved in the onset of myocardial infarction and stroke.

Pol Merkur Lekarski. 2008 May; 24(143): 381-4
Goch A, Ogórek M, Goch JH

Arterial blood pressure is one of the main factors of the development of organ vascular changes. Clinical studies have demonstrated that not only blood pressure absolute values but its 24h profile as well may be of significance for the rate and severity of organ damage. The study analyses the results and observations of the so far carried out investigations concerning the lack of nocturnal fall of blood pressure on the development of vascular changes in brain, carotid artery, myocardial hypertrophy and renal lesions. The results of the study indicate that in subjects with the lack of nocturnal fall of blood pressure the frequency of organ changes is more pronounced. Thus, for normal monitoring of the course and the treatment of arterial hypertension, its 24h monitoring seems to be an indispensable procedure. When evaluating blood pressure 24h profile age, sex, organ changes, physical activity and real sleep-wake period should be taken into account. In hypertensive patients without organ changes with nondippers blood pressure profile, repetition of 24h blood pressure monitoring seems to be an indication.

Georgian Med News. 2008 Jun; 21-6
Rekhviashvili A, Tsinamdzgvrishvili B, Chkhetia M, Labakhua G

The purpose of the study was to investigate relationships between sex, blood pressure level, duration of arterial hypertension (AH), 24-hour blood pressure (BP) rhythm, endothelial function (EF) and blood rheological parameters. 23 (mean age 50+/-8.73) outpatients with AH were included in the study. All subjects underwent off-therapy 24-hour ambulatory BP monitoring, investigation of blood rheological parameters and high resolution vascular dopplerography Dipper patients showed lower rate of platelet aggregation and platelet adhesion, than it was in non-dippers (86.42+/-8.20 vs. 99.36+/-5.93; P=0.0018 and 24.2+/-11.54 vs. 42.16+/-13.71; P=0.01). Viscosity was higher in patients with endothelial dysfunction, than it was in patients without it (0.064+/-0.01 vs. 0.051+/-0.0035; P=0.004). Compared with dippers, non-dippers showed an impaired EF (11.4+/-2% vs. 3.5+/-2.6%; p= 0.0006). The present data suggest the presence of disturbed endothelium-dependent vasodilatation and alterations in rheological indices in AH. According to the results obtained, the main factor, which leads to endothelial dysfunction and increase in platelet aggregative and adhesive activity, is the shortage in the lowering BP during the night. Consequently, hypertensive patients with non-dipper Circadian blood pressure profile have to be assessed as a high risk group for development of future cardiovascular and cerebrovascular complications.

Nat Clin Pract Neurol. 2008 Jul 15;
Pandi-Perumal SR, Trakht I, Spence DW, Srinivasan V, Dagan Y, Cardinali DP

Normal Circadian rhythms are synchronized to a regular 24 h environmental light-dark cycle, and the suprachiasmatic nucleus and the hormone melatonin have important roles in this process. Desynchronization of Circadian rhythms, as occurs in chronobiological disorders, can produce severe disturbances in sleep patterns. According to the International Classification of Sleep Disorders, Circadian rhythm sleep disorders (CRSDs) include delayed sleep phase syndrome, advanced sleep phase syndrome, non-24 h sleep-wake disorder, jet lag and shift-work sleep disorder. Disturbances in the Circadian phase position of plasma melatonin levels have been documented in all of these disorders. There is compelling evidence to implicate endogenous melatonin as an important mediator in CRSD pathophysiology, although further research involving large numbers of patients will be required to clarify whether the disruption of melatonin secretion is a causal factor in CRSDs. In this Review, we focus on the use of exogenous melatonin and light therapy to treat the disturbed sleep-wake rhythms seen in CRSDs.

Biochem Biophys Res Commun. 2008 Jul 12;
Krishnan N, Davis AJ, Giebultowicz JM

Circadian rhythms are fundamental biological phenomena generated by molecular genetic mechanisms known as Circadian clocks. There is increasing evidence that Circadian synchronization of physiological and cellular processes contribute to the wellness of organisms, curbing pathologies such as cancer and premature aging. Therefore, there is a need to understand how Circadian clocks orchestrate interactions between the organism's internal processes and the environment. Here, we explore the nexus between the clock and oxidative stress susceptibility in Drosophila melanogaster. We exposed flies to acute oxidative stress induced by hydrogen peroxide (H(2)O(2)), and determined that mortality rates were dependent on time at which exposure occurred during the day/night cycle. The daily susceptibility rhythm was abolished in flies with a null mutation in the core clock gene period (per) abrogating clock function. Furthermore, lack of per increased susceptibility to H(2)O(2) compared to wild-type flies, coinciding with enhanced generation of mitochondrial H(2)O(2) and decreased catalase activity due to oxidative damage. Taken together, our data suggest that the Circadian clock gene period is essential for maintaining a robust anti-oxidative defense.

J Physiol Sci. 2008 Jul 17;
Piccione G, Fazio F, Caola G, Refinetti R

Daily rhythmicity of physiological processes has been described for numerous variables in numerous species. A major source of this rhythmicity is a Circadian pacemaker located in the mammalian hypothalamus, but very little is known about how the pacemaker generates the multiplicity of bodily rhythms. Research on rats has shown that the rhythm of blood glucose concentration is not a mere consequence of the rhythm of food ingestion but is rather generated directly by the pacemaker. In this study, we investigated the rhythm of blood glucose concentration in four different species of domestic animals under four different feeding regimes. Our results suggest that, as in rats, the rhythm of blood glucose concentration is not a mere consequence of the rhythm of food ingestion in sheep and cattle. In dogs and horses, however, rhythmicity of blood glucose concentration seems to be contingent on the presence of a feeding regime.

J Neurosci Res. 2008 Jul 14;
Wu T, Jin Y, Kato H, Fu Z

Light and food signals are two dominant Zeitgeber for central and peripheral Circadian clocks, respectively. However, whether and how changes in light and food stimuli affect Circadian rhythms of mammalian pineal clock genes are still largely unknown. For the first time, in the present study, we established a method for analysis of the expression levels of most clock genes (Bmal1, Per1, Per2, Per3, Cry1, Dec1 and Dec2) and AANAT in a single rat pineal gland and used it to investigate individual and cooperative effects of feeding and light cycle reversals on the pineal Circadian system. Feeding reversal (RF) alone for 7 days had only weak effect on the rhythmicity of clock gene expression in the pineal gland, whereas light/dark reversal for the same period without any change in the feeding regime could not absolutely reverse the expression phases of all examined genes either. However, reversal of the LD cycle together with the feeding regime completely resynchronized the Circadian gene expression in the pineal gland within 7 days. These data suggest that photic regulation is the dominant cue that synchronizes the pineal Circadian rhythm more efficiently than the feeding-related cue, but food availability does contribute to reentrainment of the pineal Circadian system. In addition, the inability of RF in the pineal Circadian system suggests that the pineal gland is more strongly coupled to the master clock than other peripheral organs and alternatively distinguishes it from other peripheral organs in the hierarchically organized mammalian Circadian systems. (c) 2008 Wiley-Liss, Inc.

Zoolog Sci. 2008 Jun; 25(6): 561-71
Tatsumori S, Terumi Y, Kunikatsu H, Haruhiko S, Lino S, Norio I, Masami S

Drosophila FMR1 mutants are models of human fragile X syndrome. They show a loss of locomotor activity rhythm and severe degradation of eclosion timing. We analyzed the Circadian behavior of FMR1 mutants (dfmr1(B55)) in two genetic backgrounds, yellow white (yw) and Canton S (CS). The arrhythmic phenotype of Circadian locomotor activity in constant darkness (DD) did not significantly change in either genetic background. Surprisingly, eclosion timing was completely restored by backcrossing dfmr1(B55) with yw or CS flies. Morphological analysis of the small ventrally located lateral neurons of FMR1 mutants revealed that the dorsal-projection area was significantly larger in arrhythmic than rhythmic flies. In addition, dfmr1(B55) mutants in both genetic backgrounds had a significantly lower evening peak in the light-dark (LD) cycle. These results indicate that lack of FMR1 does not affect eclosion timing, but alters locomotor activity patterns in both LD and DD conditions by affecting the arborization of small ventrally located lateral neurons. Thus, the FMR1 gene may regulate the Circadian-related locomotor activity of Drosophila.

Chronobiol Int. 2008 Jul; 25(4): 625-43
Reinberg A, Ashkenazi I

Intolerance to shift work may result from individual susceptibility to an internal desynchronization. Some shift workers (SW) who show desynchronization of their Circadian rhythms (e.g., sleep-wake, body temperature, and grip strength of both hands) exhibit symptoms of SW intolerance, such as sleep alteration, persistent fatigue, sleep medication dependence, and mood disturbances, including depression. Existing time series data previously collected from 48 male Caucasian French SW were reanalyzed specifically to test the hypothesis that internal synchronization of Circadian rhythms is associated with SW intolerance and symptoms. The entry of the subjects into the study was randomized. Three groups were formed thereafter: SW with good tolerance (n=14); SW with poor tolerance, as evident by medical complaints for at least one year (n=19); and former SW (n=15) with very poor tolerance and who had been discharged from night work for at 1.5 yr span but who were symptom-free at the time of the study. Individual and longitudinal time series of selected variables (self-recorded sleep-wake data using a sleep log, self-measured grip strength of both hands using a Colin Gentile dynamometer, and oral temperature using a clinical thermometer) were gathered for at least 15 days, including during one or two night shifts. Measurements were performed 4-5 times/24 h. Power spectra used to quantify the prominent period (tau) and t-test, chi square, and correlation coefficient were used as statistical tools. The mean (+/-SEM) age of SW with good tolerance was greater than that of SW with poor tolerance (44.9+/-2.1 yrs vs. 40.1+/-2.6 yrs, p<.001) and of former SW discharged from night work (very poor tolerance; 33.4+/-1.7, p<.001). The shift-work duration (yrs) was longer in SW with good than poor tolerance (19.9+/-2.2 yrs vs. 15.7+/-2.2; p<0.002) and former SW (10.7+/-1.2; p<.0001). The correlation between subject age and shift-work duration was stronger in tolerant SW (r=0.97, p<.0001) than in non-tolerant SW (r=0.80, p<0.001) and greater than that of former SW (r=0.72, p<.01). The mean sleep-wake rhythm tau was 24 h for all 48 subjects. The number of desynchronized Circadian rhythms (tau differing from 24 h) was greater in non-tolerant than in tolerant SW (chi square=38.9, p<.0001). In Former SW (i.e., 15 individuals assessed in follow-up studies done 1.5 to 20 yrs after return to day work), both symptoms of intolerance and internal desynchronization were reduced or absent. The results suggest that non-tolerant SW are particularly sensitive to the internal desynchronization of their Circadian time organization.

Chronobiol Int. 2008 Jul; 25(4): 511-32
Rossano C, Morgan E, Scapini F

The expression of biological rhythms was investigated in five populations of three different species of talitrid amphipods from various habitats in the Maremma Regional Park, Grosseto, Italy: Talitrus saltator (from a sandy beach and a canal), Orchestia montagui (form a Posidonia banquette), and O. gammarellus (from a cave entrance and a river bank). Locomotor activity rhythms were recorded in individual animals over 21 days in constant dark at a temperature of 18 degrees +/-1 degrees C. A high variability in rhythm expression was evident, not only among species and populations but also within populations and the activity pattern of individuals. Activity rhythms of T. saltator and O. montagui were similar, with a good definition and precise Circadian periodicity, whereas O. gammarellus showed a high variability and low definition of the Circadian rhythm. Significant differences were also observed between two populations of O. gammarellus and T. saltator from different habitats. Within the O. gammarellus species, a significantly higher percentage of active animals (p<0.001) was observed in the cave than the river-bank population; within T. saltator, a significantly lower percentage of active animals (p<0.01) and higher percentage of periodic animals (p<0.05) was found in the canal than the sandy beach population. With reference to environmental stability and variability, the differences observed are explained as a need for plasticity to adapt to environmental changes.

Sports Med. 2008; 38(8): 671-85
Atkinson G, Fullick S, Grindey C, Maclaren D

Shift work is now common in society and is not restricted to heavy industry or emergency services, but is increasingly found amongst 'white collar' occupations and the growing number of service industries. Participation in shift work is associated with increased body mass index, prevalence of obesity and other health problems. We review the behavioural and biological disturbances that occur during shift work and discuss their impact on leisure-time physical activity and energy balance.Shift work generally decreases opportunities for physical activity and participation in sports. For those shift workers who are able to exercise, subjective and biological responses can be altered if the exercise is taken at unusual times of day and/or if the shift worker is sleep deprived. These altered responses may in turn impact on the longer-term adherence to an exercise programme. The favourable effects of exercise on body mass control and sleep quality in shift workers have not been confirmed. Similarly, recent reports of relationships between sleep duration and obesity have not been examined in a shift work context. There is no evidence that exercise can mediate certain Circadian rhythm characteristics (e.g. amplitude or timing) for improved tolerance to shift work.Total energy intake and meal composition do not seem to be affected by participation in shift work. Meal frequency is generally reduced but snacking is increased on the night shift. Unavailability of preferred foods in the workplace, a lack of time, and a reduced desire to eat at night explain these findings. 'Normal' eating habits with the family are also disrupted. The metabolic responses to food are also altered by shift work-mediated disruptions to sleep and Circadian rhythms. Whether any interactions on human metabolism exist between timing or content of food intake and physical activity during shift work is not known at present.There are very few randomized controlled studies on the efficacy of physical activity or dietary interventions during shift work. Some favourable effects of such interventions on fatigue levels at work have been reported, but biological and behavioural outcomes relevant to long-term health and energy balance have not been studied adequately. In addition, recruitment and retention of research participants for randomized controlled trials of physical activity or dietary interventions have been very difficult. We present a model of the various behavioural and biological factors relevant to exercise and energy balance during shift work as a framework for future research.

Arch Insect Biochem Physiol. 2008 Jul 10; 68(4): 215-231
Wen CJ, Lee HJ

The German cockroach, Blattella germanica, and the double-striped cockroach, B. bisignata, are sibling species with a similar period sequence but a distinctive Circadian rhythm in locomotion. The cell distribution of immunoreactivity (ir) against three clock-related proteins, Period (PER), Pigment Dispersing Factor (PDF), and Corazonin (CRZ), was compared between the species. The PER-ir cells tend to form clusters and are sprayed out in the central nervous system. Three major PER-ir cells are located in the optic lobes, which are the sites of the major Circadian clock. They are interconnected with PER-ir axon bundles. Interestingly, the potential output signal of the Circadian clock, PDF, is co-localized with PER in all three groups of cells. However, only two CRZ-ir cells and their axons are found in the optic lobes and they are not co-localized with PER-ir or PDF-ir cells and axons. Since only one Circadian rhythm is expressed in locomotion, the time signals from both major clocks in optic lobes are coupled by connection with PDF-ir axons. A group of 3-4 PER-ir cells in the protocerebrum display typical characteristics of neurosecretary cells. In addition, there are numerous, small PER-ir and PDF-ir co-localized cells in the pars intercerebralis (PI), which have direct connections with the neurohemoorgan, corpora cardiaca, through PER-ir and PDF-ir axons. Based on these findings, the cellular connection shows a Circadian control through the endocrine route. For the rest of central nervous system, only a few PER-ir and PDF-ir cells or axons are detected. This finding implies the Circadian clock for locomotion is not located in subesophageal ganglion, thoracic or abdominal ganglia, but may use other neural messengers to pass on Circadian signals. Since the overall distribution pattern of the clock cells are the same for B. germanica and B. bisignata, the possible explanation for the different expressions of locomotion between the species depends on genes downstream of per, pdf, and crz. Arch. Insect Biochem. Physiol. 68:215-231, 2008. (c) 2008 Wiley-Liss, Inc.

Plant Physiol. 2008 Jul 9;
Knight H, Thomson AJ, McWatters HG

The sensitive to freezing 6 (sfr6) mutant of Arabidopsis thaliana is late flowering in long days due to reduced expression of components in the photoperiodic flowering pathway in long day photoperiods. Microarray analysis of gene expression showed that a Circadian clock-associated motif, the evening element, was over-represented in promoters of genes down-regulated in sfr6 plants. Analysis of leaf movement rhythms found sfr6 plants showed a sucrose-dependent long period phenotype; unlike wild type Arabidopsis, the clock in sfr6 plants did not have a shorter rhythm in the presence of sucrose. Other developmental responses to sucrose were unaltered in sfr6 plants, suggesting insensitivity to sucrose is restricted to the clock. We investigated the effect of sfr6 and sucrose upon clock gene expression over twenty-four hours. The sfr6 mutation resulted in reduced expression of the clock components Circadian CLOCK ASSOCIATED 1, GIGANTEA and TIMING OF CAB1. These changes occurred independently of sucrose-supplementation. Wild type plants showed small increases clock gene expression in the presence of sucrose; this response to sucrose was reduced in sfr6 plants. This study shows that large changes in level and timing of clock gene expression may have little effect upon clock outputs. Moreover, although sucrose influences the period and accuracy of the Arabidopsis clock it results in relatively minor changes in clock gene expression.

Brain Res. 2008 Jun 3;
Gompf HS, Aston-Jones G

Activation of noradrenergic locus coeruleus (LC) neurons promotes wakefulness and behavioral arousal. In rats, LC neurons receive Circadian inputs via a circuit that originates in the suprachiasmatic nucleus (SCN) and relays through the dorsomedial hypothalamus (DMH) to LC; this circuit input increases LC activity during the active period. DMH neurons expressing the peptide neurotransmitter orexin/hypocretin are ideally situated to act as a relay between SCN and LC due to their synaptic inputs from SCN and innervation of LC. Here, we examined the hypothesis that orexin is involved in transmitting Circadian signals to LC using single-unit recordings of LC neurons in anesthetized rats maintained in 12:12 light-dark housing. We replicated earlier findings from this lab that LC neurons fire significantly faster on average during the active compared to rest periods. Local microinjection of an orexin antagonist, SB-334867-A attenuated the impulse activities of the fastest firing population of LC neurons during the active period. We also found that DMH orexin neurons project preferentially to LC and express a diurnal rhythm of activation that correlates with LC neuronal firing frequency. Therefore, we propose that DMH orexin neurons play a role in modulating the day-night differences of LC impulse activity.

Indian J Chest Dis Allied Sci. 2008 Jan-Mar; 50(1): 129-35
Kumar VM

Sleep is a complex neurological state, with its primary function of providing rest and restoring the body's energy levels. The importance of sleep could be seen from the fact that people spend about one-third of their lifespan in sleep. Normal human sleep is divided into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, and the alteration between NREM and REM occurs about 4-5 times during a night of normal sleep. Human NREM sleep could be classified into four stages, namely, stage I, II, III and IV, representing successively deeper stages of sleep. Sleep is an active rhythmic neural process produced by several brain areas, of which the preoptic and other basal forebrain areas play a major role in the generation of NREM sleep. Interaction of the pedenculo-pontine and lateral dorsal tegmental areas with the dorsal raphae nucleus and locus coeruleus, is important for REM sleep generation. Suprachiasmatic nucleus of the hypothalamus and the pineal gland ensure that sleep and wakefulness follow a Circadian periodicity of nearly 24 hours. Alterations in the quality, quantity and pattern of sleep result in sleep disorders. Persistent and repeated interruption of sleep affects the health of an individual. Undiagnosed and untreated wake/sleep complaints cause not only misery to the sufferer, but it also has socio-economic consequences. Sleep disorders cover a wide spectrum of diseases. Though there are more than 100 identified sleep/wake disorders, most sleep complaints can be categorised into five, namely, hypersomnia, insomnia, Circadian rhythm disorders, parasomnias, and sleep disorders associated with mental, neurological, and other medical disorders. Researches during the last 50 years, and the advances made in clinical sleep medicine, have lead to more effective treatments for the myriad human sleep disorders. It is not possible to assign a specific reason for many of the sleep disorders, but some aspects of sleep and wakefulness are genetically influenced. But, most commonly, sleepiness during waking hours, results from volitional or forced sleep deprivation during previous nights, due to social, economic and environmental reasons. So, public awareness about sleep disorders should be an essential part of any programme aimed at global management of sleep disorders.

ScientificWorldJournal. 2008; 8: 598-603
Mitrovic P, Stefanovic B, Vasiljevic Z, Radovanovic M, Radovanovic N, Krljanac G, Rajic D, Erceg P, Vukcevic V, Nedeljkovic I, Ostojic M

Circadian variation of onset of acute myocardial infarction (AMI) has been noted in many studies, but there are no data about subgroups of patients with previous coronary artery bypass grafting (CABG). Because of abnormalities in the Circadian rhythm of autonomic tone after surgery, it was very interesting to analyze the Circadian patterns in the onset of symptoms of AMI in various subgroups of 1784 patients with previous CABG. As in the other studies, a peak occurred in the morning hours with 26.3% of the patients, but there was a second nearly equal, but higher, peak (26.4%) in the evening hours. The subgroups with specific clinical characteristics exhibited different patterns that determined these peaks in all populations. In patients older than 70 years of age, in both sexes, in smokers, diabetics, in patients with hypertension, in those undergoing beta-blocker therapy, and in patients without previous angina, two nearly equal peaks were observed, with higher evening peaks, except in those patients with hypertension and without angina. Only one peak in the evening hours was observed in a subgroup of patients with previous congestive heart failure (CHF) and non-STEMI. The subgroup of patients with previous angina and previous AMI exhibited no discernible peaks. The distribution of time of onset within the four intervals was not uniform, and the difference was statistically significant only for patients undergoing beta-blocker therapy at time of onset (p = 0.0013), nonsmokers (p = 0.0283), and patients with non-STEMI (p = 0.0412). It is well known that patients with AMI have a dominant morning peak of Circadian variation of onset. However, analyzing a different subgroup of patients with AMI after previous CABG, it was found that some subgroups had two peaks of onset, but a higher evening peak (patients older than 70 years of age, smokers, diabetics, and a group of patients who were taking beta-blocker therapy). This subgroup of patients, together with the subgroups of patients with a dominant evening peak (patients with CHF and those with non-STEMI) and with patients with no peak (patients with previous angina and previous AMI), probably appear to modify characteristic Circadian variation of infarction onset, expressing a higher evening peak, respectively to the previous CABG, with adverse consequences for central nervous system functioning.

Sleep Med Rev. 2008 Aug; 12(4): 307-17
Lack LC, Gradisar M, Van Someren EJ, Wright HR, Lushington K

Sleepiness and sleep propensity are strongly influenced by our Circadian clock as indicated by many Circadian rhythms, most commonly by that of core body temperature. Sleep is most conducive in the temperature minimum phase, but is inhibited in a "wake maintenance zone" before the minimum phase, and is disrupted in a zone following that phase. Different types of insomnia symptoms have been associated with abnormalities of the body temperature rhythm. Sleep onset insomnia is associated with a delayed temperature rhythm presumably, at least partly, because sleep is attempted during a delayed evening wake maintenance zone. Morning bright light has been used to phase advance Circadian rhythms and successfully treat sleep onset insomnia. Conversely, early morning awakening insomnia has been associated with a phase advanced temperature rhythm and has been successfully treated with the phase delaying effects of evening bright light. Sleep maintenance insomnia has been associated not with a Circadian rhythm timing abnormality, but with nocturnally elevated core body temperature. Combination of sleep onset and maintenance insomnia has been associated with a 24-h elevation of core body temperature supporting the chronic hyper-arousal model of insomnia. The possibility that these last two types of insomnia may be related to impaired thermoregulation, particularly a reduced ability to dissipate body heat from distal skin areas, has not been consistently supported in laboratory studies. Further studies of thermoregulation are needed in the typical home environment in which the insomnia is most evident.

AORN J. 2008 Jul; 88(1): 79-87
Johnson J

ANESTHETIC ADVERSE EVENTS have been found to occur more frequently in surgical procedures performed after 4 PM. THE MAJOR FACTORS that contribute to increased anesthetic adverse events include fatigue, Circadian rhythm lows or dips, and administrative delays. AN INCREASED SHORTAGE of anesthesia care providers is likely to create longer work hours, thus increasing fatigue, which can lead to more anesthetic adverse events. Awareness of and education about adverse events and solutions are imperative. AORN J 88 (July 2008) 79-87. (c) AORN, Inc, 2008.