Showing papers in "Chronobiology International in 1999"

Bright Light Therapy: Improved Sensitivity to Its Effects on Rest-Activity Rhythms in Alzheimer Patients by Application of Nonparametric Methods

Abstract: Sleep-wake rhythm disturbances in patients with Alzheimer's disease (AD) make a strong demand on caregivers and are among the most important reasons for institutionalization. Several previous studies reported that the disturbances improve with increased environmental light, which, through the retinohypothalamic tract, activates the suprachiasmatic nucleus (SCN), the biological clock of the brain. The data of recently published positive and negative reports on the effect of bright light on actigraphically assessed rest-activity rhythms in demented elderly were reanalyzed using several statistical procedures. It was demonstrated that the light-induced improvement in coupling of the rest-activity rhythm to the environmental zeitgeber of bright light is better detected using nonparametric procedures. Cosinor, complex demodulation, and Lomb-Scargle periodogram-derived variables are much less sensitive to this effect because of the highly nonsinusoidal waveform of the rest-activity rhythm. Guidelines for analyses of actigraphic data are given to improve the sensitivity to treatment effects in future studies.

Masking: History, Definitions, and Measurement

Abstract: Masking and entrainment are two different processes that result in rhythms in physiology and behavior. Considering its functional importance, lamentably little study has been devoted to masking compared to that lavished on entrainment. This paper discusses the origin and definition of terminology (positive and negative masking, paradoxical masking) and methods of quantifying masking. How masking is scored can greatly influence the interpretation of results.

Biologic Rhythms in the Immune System

Abstract: In all of its components, the immune system shows regularly recurring, rhythmic variations in numerous frequencies; the circadian (about 24 h) rhythms are the best explored. The circadian variations in immunocompetent cells circulating in the peripheral blood are of a magnitude to require attention in medical diagnostics. Both the humoral arm and the delayed (cellular) arm of the immune system function in a rhythmic manner. The response of the immune system to introduction of an antigen and to challenge of the sensitized organism varies in extent in the circadian frequency range and also in lower frequencies, for example, of about a week (circaseptan) or seasonally (circannual). The medical application of the biologic rhythms of the immune system extends to diagnostic measures, as well as treatment.

Forty Years of Prcs-What Have We Learned?

Abstract: What are phase-response curves (PRCs)? How can they be measured? How should they be plotted? These questions and many other fascinating facets of PRCs are addressed in this review, including research topics in which phase-resetting data have provided crucial insights: entrainment, phototransduction, pacemaker mechanism, phase markers of the pacemaker, and gauges of oscillator amplitude. PRCs have enlightened us and will continue to be a valuable tool in clock research.

Time perception and temporal processing levels of the brain

Abstract: A classification is presented to structure divergent empirical findings on temporal mechanisms of the brain. Proceeding from our time experiences of simultaneity, nonsimultaneity, temporal order, d...

From a static to a dynamic concept of risk: the circadian epidemiology of cardiovascular events.

Abstract: A growing body of evidence substantiates that the occurrence of cardiovascular events in unevenly distributed in time, especially during the 24 h. These temporal patterns are indicative of temporal variation in the (1) pathophysiological mechanisms that trigger cardiovascular events and (2) physiological status of the cardiovascular system, which combine to give rise to 24 h and other periodicities in the susceptibility to disease. The classic assumption of epidemiologic studies is constancy (or homeostasis) in one's risk to disease during the 24 h, as well as other, time domains. However, we propose a new concept, that of chronorisk since it takes into account the temporal variability in the pathophysiological mechanisms and their reciprocal temporal interactions that lead to day-night and other time-dependent patterns in cardiovascular events. This chronobiological approach, which is expected to contribute new insight into the prognostic and therapeutic assessment of cardiovascular events, is worthy of broader application in cardiovascular and other fields of medicine and warrants further investigation.

Circadian rhythm sleep disorders: toward a more precise definition and diagnosis.

Abstract: The present article presents a survey of the characteristics of our case series of 322 patients suffering from circadian rhythm sleep disorders (CRSDs), a case-control study comparing a group of 50 CRSD patients and 56 age- and gender-matched normal subjects, and a proposal for new guidelines for improving the diagnosis of CRSD. The major findings were that 83.5% of our CRSD patients who seek medical help are of the delayed sleep phase syndrome (DSPS) type; 89.6% report that the onset of CRSD occurred in early childhood or adolescence; CRSD exhibits no gender differences; a familial trait exists in 44% of patients; and learning disorders (19.3%) and personality disorders (22.4%) in the DSPS-type patients are of high prevalence. The findings of this study point to the importance of clinician awareness of the clinical picture of patients presenting with CRSD so that early diagnosis and effective treatment can be achieved to prevent harmful consequences.

Bright Light Exposure During the Daytime Affects Circadian Rhythms of Urinary Melatonin and Salivary Immunoglobulin A

Abstract: The effects of bright light exposure during the daytime on circadian urinary melatonin and salivary immunoglobulin A (IgA) rhythms were investigated in an environmental chamber controlled at a global temperature of 27 degrees C+/-0.2 degrees C and a relative humidity of 60%+/-5%. Seven diurnally active healthy females were studied twice, in bright and dim light conditions. Bright light of 5000 lux was provided by placing fluorescent lamps about 1 meter in front of the subjects during the daytime exposure (06:30-19:30) from 06:30 on day 1 to 10:30 on day 3. Dim light was controlled at 200 lux, and the subjects were allowed to sleep from 22:30 to 06:30 under both light exposure conditions. Urine and saliva were collected at 4h intervals for assessing melatonin and IgA. Melatonin excretion in the urine was significantly greater during the nighttime (i.e., at 06:30 on day 1 and at 02:30 on day 2) after the bright light condition than during the dim light condition. Furthermore, the concentration and the amount of salivary IgA tended to be higher in the bright light than in the dim light condition, especially during the night-time. Also, salivary IgA concentration and the total amount secreted in the saliva were significantly positively correlated with urinary melatonin. These results are consistent with the hypothesis that bright light exposure during the daytime enhances the nocturnal melatonin increase and activates the mucosal immune response.

Are age differences in sleep due to phase differences in the output of the circadian timing system

Abstract: Our aim was to evaluate whether age-related changes in the phase of the output of the circadian timing system (CTS) can explain age differences in habitual bedtime/wake time and in sleep consolidation parameters. Analyses focused on a group of healthy elderly people (older than 70 years) with no sleep problems and with similar subjective sleep quality as a young control group. The 2-week sleep diary data and 24h laboratory temperature recordings were examined for 70 subjects (22 young men [YM], 19 old men [OM], 29 old women [OW]). Polysomnographic (PSG) sleep data recorded during temperature data acquisition were also available for 62 subjects. These analyses made use of our recently developed technique to demask temperature rhythm data. As expected, compared to the young subjects, older subjects showed earlier habitual bedtime and wake time, more disturbed sleep, and a tendency for an earlier minimum of the circadian temperature rhythm. Despite sleep consolidation differences, the groups showed very simi...

Ultradian and circadian rhythms of sleep-wake and food-intake behavior during early infancy.

Abstract: The early development of sleep-wake and food-intake rhythms in human infants is reviewed. The development of a 24 h day-night rhythm contains two observable developmental processes: the alterations in the periodic structure of behavior (decreased ultradian, increased circadian components) and the process of synchronization to external time (entrainment). The authors present the results of their studies involving 26 German children and compare them with previous investigations. In their research, it became evident that, during the first weeks of life, the time pattern of sleep-wake and food-intake behavior is characterized by different ultradian periodicities, ranging from 2 h to 8 h. In the course of further ontogenesis, the share of ultradian rhythms in the sleep-wake behavior decreases, while it remains dominant for food-intake behavior. The circadian component is established as early as the first weeks of life and increases in the months that follow. Besides, the authors' study supports the notion of broad interindividual variation in ultradian rhythms and in the development of a day-night rhythm. Examples of free-running rhythms of sleep-wake and food-intake behavior by various authors are strong indicators of the endogenous nature of the circadian rhythms in infants and show that the internal clock is already functioning at birth. It is still uncertain when the process of synchronization to external and social time cues begins and how differences in the maturation of perceptive organs affect the importance of time cues for the entrainment. Prepartally, the physiological maternal entrainment factors and mother-fetus interactions may be most important; during the first weeks of life, the social time cues gain importance, while light acts as a dominant "zeitgeber" at a later time only.

Role of posttranscriptional regulation in circadian clocks: lessons from Drosophila.

Abstract: Incredible progress has been made in the last few years in our understanding of the molecular mechanisms underlying circadian clocks. Many of the recent insights have been gained by the isolation and characterization of novel clock mutants and their associated gene products. As might be expected based on theoretical considerations and earlier studies that indicated the importance of temporally regulated macromolecular synthesis for the manifestation of overt rhythms, daily oscillations in the levels of “clock” RNAs and proteins are a pervasive feature of these timekeeping devices. How are these molecular rhythms generated and synchronized? Recent evidence accumulated from a wide variety of model organisms, ranging from bacteria to mammals, points toward an emerging trend; at the “heart” of circadian oscillators lies a cell autonomous transcriptional feedback loop that is composed of alternatively functioning positive and negative elements. Nonetheless, it is also clear that to bring this transcriptional f...

The circadian system of Arabidopsis thaliana: forward and reverse genetic approaches.

Abstract: It is now widely accepted that autoregulatory circuits involving transcription/translation of clock genes form the molecular basis of the endogenous circadian clock in different organisms. In Arabidopsis thaliana, the RNA-binding protein AtGRP7 (Arabidopsis thaliana glycine-rich protein) has been identified as part of a negative-feedback loop through which AtGRP7 regulates the circadian oscillations of its own transcript. Experimental evidence indicates that this feedback loop also is influenced by another oscillator. Support for this hypothesis comes from the characterization of the clock mutant toc1 (timing of cab expression) and the recent isolation of two candidate clock molecules, LHY (late elongated hypocotyl) and CCA1 (circadian clock associated). TOC1, as well as the LHY and CCA1 oscillatory feedback loops, influence several rhythmic physiological and molecular processes in Arabidopsis, including cyclic Atgrp7 gene expression. We discuss the features of these feedback loops with relation to the organization of the circadian system in Arabidopsis.

Clinical Chronobiology and Chronotherapeutics with Applications to Asthma

Abstract: The concept of homeostasis (i.e., constancy of the milieu interne) has long dominated the teaching and practice of medicine. Concepts and findings from chronobiology, the scientific study of biological rhythms, challenge this construct. Biological processes and functions are not at all constant; rather, they are organized in time as rhythms with period lengths that range in duration from as short as a second or less to as long as a year. It is the body's circadian (24 h) rhythms that have been researched most intensely. The peak and trough of these rhythms are ordered rather precisely in time to support the biological requirements of activity during the day and sleep at night. The timing of the peak and trough plus the magnitude of variation (amplitude) of physiological and biochemical functions during the 24 h give rise to predictable-in-time, day-night patterns in the manifestation and exacerbation of many common medical conditions. Circadian rhythms also can influence the response of patients to diagnostic tests and therapeutic interventions according to their timing with reference to body rhythms. Rhythms in the pathophysiology of medical conditions and patient tolerance to medications constitute the basis for chronotherapeutics, the timing of treatment in relation to biological rhythm determinants as a means of optimizing beneficial effects and safety. The article discusses recent advances in medical chronobiology and chronotherapeutics and their relevance to clinical medicine in general and the management of asthma in particular. Indeed, since asthma is a disease that exhibits rather profound circadian rhythmicity, investigation of its pathophysiology and therapy necessitates a chronobiologic approach.

Circadian expression of the light-harvesting complex protein genes in plants.

Abstract: Photosynthesis is one of the important processes that enable life on earth. To optimize photosynthesis reactions during a solar day, most of them are timed to be active during the light phase. This includes the components of the thylakoid membranes in chloroplasts. Prominent representatives are the proteins of the light-harvesting complex (LHC). The synthesis of both the Lhc mRNA and the LHC protein occurs during the day and is regulated by the circadian clock, exhibiting the following pattern: increasing levels after sunrise, reaching a maximum around noon, and decreasing levels in the afternoon. To elucidate the involved control elements and regulatory circuits, the following strategies were applied:(1) analysis of promoters of Lhc genes, (2) analysis of DNA binding proteins, and (3) screening and investigation of mutants. The most promising elements found so far that may be involved in mediating the circadian rhythmicity of Lhc mRNA oscillations are a myb-like transcription factor CCA1 (Wang et al. 199...

Sleep, respiratory physiology, and nocturnal asthma.

Abstract: The nocturnal worsening of asthma is a common feature of this disease that recently has received extensive investigation. Most recent efforts have focused on the role of circadian biorhythms that could promote a nocturnal increase in airway inflammation, leading to a subsequent increase in airflow obstruction and asthma symptoms. However, definitive studies remain lacking. As discussed in this review, there is also substantial evidence that sleep itself may play a direct role in the nocturnal worsening of asthma. Potential mechanisms for such a sleep-related effect could include the supine posture, alterations in sympathetic and parasympathetic "balance," sleep-associated reductions in lung volume, intrapulmonary pooling of blood, and sleep-associated upper airway narrowing, both with and without snoring and obstructive sleep apnea (OSA). These potential contributors to this troublesome phenomenon deserve further consideration when investigating mechanisms of nocturnal asthma.

Nocturnal asthma: role of nocturnal gastroesophageal reflux.

Abstract: Gastroesophageal reflux (GER) is common in those with asthma, with 77% of asthmatics complaining of heartburn, with 41% experiencing reflux-associated respiratory symptoms. Likewise, 24% of those with asthma that is difficult to control have "clinically silent" GER. There are no studies examining nocturnal reflux symptoms in asthmatics. Esophageal dysmotility is also common, and abnormal esophageal acid contact times on 24h esophageal pH tests were found in 82% of asthmatics examined consecutively. Most asthmatics with GER also have abnormal esophageal acid contact times while in the supine position, reflecting sleep time. Endoscopic evidence of esophagitis was found in 43% of asthmatics. Two mechanisms of bronchoconstriction induced by esophageal acid have been proposed: a vagally mediated reflex, by which esophageal acid in the distal esophagus causes reflex bronchoconstriction, and microaspiration. Although there is conflicting evidence, distal esophageal acid causes a decrease in peak expiratory flow rates, an increase in respiratory resistance, and an increase in minute ventilation. If microaspiration is present, there is further augmentation of this airway response. Although only a few studies have been performed in those with nocturnal asthma with GER, one study in a pediatric population showed that esophageal acid infusions caused more airway responses at 04:00 than at 24:00. Also, asthmatic children with nocturnal asthma symptoms have a higher reflux score, with a positive correlation between reflux score and nighttime-associated wheezing. Despite these findings in children, a study performed in sleeping adults with nocturnal asthma noted no alterations in airflow resistance with esophageal acid, concluding that GER contributed little to the nocturnal worsening of asthma. There are also gastroesophageal circadian issues that may influence GER in asthmatics. Gastric acid secretion peaks at approximately 21:00, and gastric emptying is delayed when a meal is given at 20:00 versus 08:00. Esophageal acid clearance is delayed significantly during sleep, and acid clearance occurs during arousals. Upper esophageal sphincter (UES) pressure also decreases with sleep onset, which may predispose to microaspiration. Further research is needed to clarify what role nocturnal reflux has on nocturnal asthma and airway inflammation and whether circadian rhythm factors alter airway responses to esophageal acid.

The effect of activity on the waking temperature rhythm in humans

Abstract: 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 degrees C (0.12 degrees C, 0.32 degrees 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.

Development of inverse circadian blood pressure pattern in transgenic hypertensive TGR(mREN2)27 rats.

Abstract: TGR(mREN2)27 (TGR) rats are transgenic animals with an additional mouse renin gene, which leads to overactivity of the renin-angiotensin system. Adult TGR rats are characterized by fulminant hypertension, hypertensive end-organ damage, and an inverse circadian blood pressure pattern. To study the ontogenetic development of cardiovascular circadian rhythms, telemetric blood pressure transmitters were implanted in male Sprague-Dawley (SPRD, n = 5) and heterozygous, transgenic TGR rats before 5 weeks of age. The TGR received either drinking water or enalapril 10 mg/L in drinking water (n = 5 per group). Drug intake was measured throughout the study by computerized monitoring of drinking volume. Circadian patterns in blood pressure and heart rate were analyzed from 5 to 11 weeks of age. In the first week after transmitter implantation, blood pressure did not differ among SPRD, untreated, and enalapril-treated TGR rats. In parallel with the rise in blood pressure of untreated TGR rats, a continuous delay of th...

Circadian phase-dependent antinociceptive reaction in mice determined by the hot-plate test and the tail-flick test after intravenous injection of dalargin-loaded nanoparticles.

Abstract: Peptides normally do not cross the blood-brain barrier (BBB). Previously, it has been shown that the hexapeptide enkephalin analogue dalargin with polysorbate-80-coated nanoparticles (DAL/NP) can be transported across the BBB and is able to exhibit an antinociceptive effect in mice. In the present study, the circadian time and dose dependencies of the antinociceptive effect of different dalargin preparations were investigated. The active preparation (DAL/NP, 5 mg/kg, 10 mg/kg), as well as a dalargin solution in phosphate buffered saline (DAL/SOL, 10 mg/kg) were injected intravenously to groups of 10-12 inbred DBA/2 mice at 12 different circadian times; mice were synchronized to a light-dark (LD) 12:12 regimen. The antinociceptive effect was determined 15 minutes postinjection by the hot-plate test. Experiments with DAL/NP were repeated using the tail-flick test system at two selected times (08:00 and 20:00) to test for dose dependency (2.5, 5, 7.5, 10 mg/kg). Hot-plate latencies were rhythmic under baseline and after DAL/SOL, with acrophases in the dark phase; DAL/SOL did not influence latency time. In contrast, DAL/NP significantly increased reaction time dose dependently; the maximal possible effect was rhythmic with the 10 mg/kg preparation, with a peak effect in the early light phase. Results were confirmed by the tail-flick test. The experiments demonstrate that an enkephalin analogue coated with nanoparticles can easily cross the BBB and is able to display a dose- and time-dependent antinociceptive effect.

Circadian variation in allergen and nonspecific bronchial responsiveness in asthma.

Abstract: In a majority of patients, exacerbations of asthma occur more frequently during the night than day. Many hypotheses have been proposed to explain such variation in asthma. The airways of asthmatic persons are characterized by an abnormal degree of inflammation and bronchial hyperresponsiveness to both nonspecific and specific challenges. Studies of both children and adults with asthma document marked circadian rhythmicity in the response of airways to bronchial challenges with histamine, methacholine, acetylcholine, saline, and house dust mite. Taken together, the findings of these investigations indicate that the hyperreactivity of airways to these agents is more profound and prolonged following evening and overnight tests compared to tests conducted in the midday and afternoon. The temporal pattern in bronchial response to the hyperventilation of cold dry air is different. The hyperresponsiveness of airways to this challenge is greatest in the afternoon. The amplitude of the circadian rhythm in airway hyperreactivity seems to be correlated to the amplitude of the circadian rhythm of pulmonary function; the greater the day-night difference in bronchial reactivity is, the greater is the day-night difference in flow rates.

Effect of ambient temperature on the circadian activity rhythm in common marmosets, Callithrix j. jacchus (primates).

Abstract: Whereas the (zeitgeber) effect of ambient temperature Ta and temperature cycles TaC's on circadian rhythmicity has been well documented for heterothermic mammals, inconsistent results have been obtained for strictly homeothermic species. Hence, it might be inferred that the susceptibility of the mammalian circadian timing system (CTS) to Ta and TaC's depends on the range of the animals' core and/or brain temperature rhythm. This hypothesis was tested in the common marmoset (Callithrix j. jacchus, n = 12), a small diurnal primate with an amplitude in body temperature rhythm that is larger than for other homeothermic primates studied so far. Within the range 20-30 degrees C, no systematic effects of constant Ta on most parameters of the marmosets' light-dark (LD)-entrained and free-running circadian activity rhythm (CAR) were found. Significant differences could be established in the average amount of activity per circadian cycle. It was highest at Ta 25 degrees C (LD) and 20 degrees C (light-light, LL) and most probably reflected a temperature-induced masking effect. A 24 h trapezoidal TaC of 20:30 degrees C entrained the free-running CAR in two of six marmosets and produced relative coordination in all others. Accordingly, in all animals tested, it had an effect on the CTS. In marmosets free running in LL at a Ta of 20 degrees C or 30 degrees C, 3 h warm and cold pulses of 30 degrees C and 20 degrees C, respectively, produced neither systematic phase responses nor period responses of the CAR. So, there is no evidence of a phase-response mechanism underlying circadian entrainment. The results show that large-amplitude TaC's function as a weak zeitgeber for the marmosets' CTS. Since this zeitgeber effect is significantly larger than that found in owl monkeys, the results are consistent with the starting hypothesis that the zeitgeber effect of a given TaC on the mammalian CTS may be related to the amplitude of the species' core and/or brain temperature cycle.

Location of airway inflammation in asthma and the relationship to circadian change in lung function.

Abstract: Nocturnal asthma is an important part of asthma as the majority of patients with asthma have nocturnal worsening in lung function. The etiology of this process is multifactorial and interactive. There are many naturally occurring circadian rhythms, which for the normal individual have only a minor effect on lung function. However, in the asthmatic patient, these day-to-night alterations produce increased airway inflammation and worsening of asthma. Although asthma is considered an airway disease, the location of the inflammatory response may be greater in the alveolar tissue area. If correct, this could alter the therapeutic approach to this disease.

Keeping an eye on retinal clocks

Abstract: Circadian pacemakers that drive rhythmicity in retinal function are found in both invertebrates and vertebrates. They have been localized to photoreceptors in molluscs, amphibians, and mammals. Like other circadian pacemakers, they entrain to light, oscillate based on a negative feedback between transcription and translation of clock genes, and control a variety of physiological and behavioral rhythms that often includes rhythmic melatonin production. As a highly organized and accessible tissue, the retina is particularly well suited for the study of the input-output pathways and the mechanism for rhythm generation. Impressive advances can now be expected as researchers apply new molecular techniques toward looking into the eye's clock.

Is sleeping sickness a circadian disorder? The serotonergic hypothesis.

Abstract: Patients with human African trypanosomiasis (HAT, sleeping sickness), due to the inoculation of Trypanosoma brucei gambiense or rhodesiense by the tsetse fly, are “sleepy by day and restless by night.” The first 24h poly-somnographic recording (electroencephalogram [EEG], electromyogram [EMG], electrooculogram [EOG]), showing a disappearance of the 24h rhyth-micity of sleep and wakefulness, was performed in 1988. Thereafter, our team recorded 18 patients and 6 control volunteers at bed rest during 24h sessions. Blood samples were taken hourly from 8 of the patients through a venous catheter and every 10 minutes from the remaining 10 patients. Plasma Cortisol, prolactin, growth hormone (GH), melatonin, and plasma renin activity were analyzed. No disruptions of the circadian rhythms of sleep and wakefulness were described in the 6 healthy African subjects, and there also were no disturbances of 24h hormone profiles. The patients experienced a dysregulation of the circadian rhythmicity of sleep and wakefulne...

Latitude-related changes in the amplitude of annual mortality rhythm. The biological equator in man.

Abstract: There is extensive literature describing the effect of season on mortality rates, especially in cardiovascular and respiratory disease. This study compares latitude with the extent of seasonal variation of monthly deaths from all causes. In developed countries, there is a peak of deaths in winter and a trough in summer. Monthly numbers of deaths were established in 89 countries in the Northern and Southern Hemisphere. Using cosinor analysis, the extent of seasonal variation (amplitude) was established and correlated with latitude. The amplitude of seasonality was greatest in mid-latitude around 35 degrees, but low or absent near the equator and subpolar regions. The amplitude can differ at the same latitude. The weather in equatorial regions and in habitations near the Arctic Circle is very different, but death has a similar seasonal rhythm. The purpose is to record this epidemiological finding even though no simple explanation is provided. Weather alone cannot explain it, and it is possible that day length (photoperiod) has an important, but complex, underlying role.

Purification of masked temperature data from humans: some preliminary observations on a comparison of the use of an activity diary, wrist actimetry, and heart rate monitoring.

Abstract: Fourteen ambulatory subjects, varying in their amount of habitual physical activity, were studied for 24 h during a total of 25 "typical" days. Rectal temperature was recorded every 6 minutes, an activity diary was filled in every half hour, and wrist activity and heart rate were monitored every minute. Actimetry and heart rate data generally showed close parallelism with each other and with the masking effects on body temperature. Psychological stressors such as public speaking produced a greater effect on heart rate and body temperature than on wrist movement, while typing produced high values for wrist movement, but affected heart rate and temperature much less. When data for the circadian rhythm of body temperature were purified, the diary, actimetry, and measurement of heart rate were all useful in reducing masking effects, but the present evidence indicates that heart rate can be more successful than actimetry--as judged by the closeness of the purified data to a sinusoid. This superiority of heart rate monitoring over wrist activity as a method of purification might be because core temperature can be increased by stressor-induced thermogenesis, as well as by physical activity, and because wrist movement can, with some activities, give an inaccurate estimate of the factors that contribute to whole-body thermogenesis.

Assessment of the effects of nocturnal exposure to 50-Hz magnetic fields on the human circadian system. A comprehensive study of biochemical variables.

Abstract: The proposed laboratory investigation was designed to evaluate the effects of acute exposure to both continuous and intermittent magnetic fields (MFs) (50 Hz-10 microT) on the circadian rhythm of clinical chemistry variables in humans: electrolytes (magnesium, calcium, phosphorus, sodium, potassium, and chloride), enzymes (amylase, lipase, aldolase, gamma glutamyl-transferase [GGT], lactate dehydrogenase [LDH], aspartate aminotransferase [ASAT], and alkaline phosphatase [ALP]), lipids (cholesterol, high-density lipoprotein [HDL], apolipoprotein A1 [ApoA1], and ApoB), proteins (total proteins and albumin), nitrogen substances (uric acid, urea, and creatinine), iron, glycemia, and transferrin. Young volunteers (32 subjects; 16 exposed and 16 sham exposed) were selected according to the screening criteria. Each subject participated in two sessions held within a 4-week period. In the first session, one group of volunteers (16 subjects) was exposed to a continuous MF and then, in the second session, to an intermittent MF. The second group (16 subjects) served as a control for both sessions. At each session, blood samples were collected at 3 h intervals from 11:00 to 20:00 and hourly from 22:00 to 08:00. The results indicate that both continuous and intermittent 50-Hz linearly polarized MFs of 10 microT intensity have no effects on the circadian rhythms or on the levels of the variables studied here.

Food-entrained feeding and locomotor circadian rhythms in rats under different lighting conditions

Abstract: It has been suggested that two endogenous timekeeping systems, a light-entrainable pacemaker (LEP) and a food-entrainable pacemaker (FEP), control circadian rhythms. To understand the function and interaction between these two mechanisms better, we studied two behavioral circadian rhythmicities, feeding and locomotor activity, in rats exposed to two conflicting zeitgebers, food restriction and light-dark cycles. For this, the food approaches and wheel-running activity of rats kept under light-dark (LD) 12:12, constant darkness (DD), or constant light (LL) conditions and subjected to different scheduled feeding patterns were continuously recorded. To facilitate comparison of the results obtained under the different lighting conditions, the period of the feeding cycles was set in all three cases about 1h less than the light-entrained or free-running circadian rhythms. The results showed that, depending on the lighting conditions, some components of the feeding and wheel-running circadian rhythms could be entrained by food pulses, while others retained their free-running or light-entrained state. Under LD, food pulses had little influence on the light-entrained feeding and locomotor rhythms. Under DD, relative coordination between free-running and food-associated rhythms may appear. In both cases, the feeding activity associated with the food pulses could be divided into a prominent phase-dependent peak of activity within the period of food availability and another afterward. Wheel-running activity mainly followed the food pulses. Under LL conditions, the food-entrained activity consisted mainly of feeding and wheel-running anticipatory activity. The results provide new evidence that lighting conditions influence the establishment and persistence of food-entrained circadian rhythms in rats. The existence of two coupled pacemakers, LEP and FEP, or a multioscillatory LEP may both explain our experimental results.

Forced desynchrony of circadian rhythms of body temperature and activity in rats.

Abstract: The daily rhythm in body temperature is thought to be the result of the direct effects of activity and the effects of an endogenous circadian clock. Forced desynchrony (FD) is a tool used in human circadian rhythm research to disentangle endogenous and activity-related effects on daily rhythms. In the present study, we applied an FD protocol to rats. We subjected 8 rats for 5 days to a 20 h forced activity cycle consisting of 10 h of forced wakefulness and 10 h for rest and sleep. The procedure aimed to introduce a 10 h sleep/10 h wake cycle, which period was different from the endogenous circadian (about 24 h) rhythm. Of the variation in the raw body temperature data, 68-77% could be explained by a summation of estimated endogenous circadian cycle and forced activity cycle components of body temperature. Free-running circadian periods of body temperature during FD were similar to free-running periods measured in constant conditions. The applied forced activity cycle reduced clock-related circadian modulation of activity. This reduction of circadian modulation of activity did not affect body temperature. Also, the effects of the forced activity on body temperature were remarkably small.

From Ultradian to Infradian Rhythms: LH Releases Patterns In Vitro

Abstract: In the present study, we examined in vitro luteinizing hormone (LH) release patterns from pituitaries and from pituitary cell cultures (3 and 7 days in culture) to elucidate the endogenous period generated by the gonadotroph cell population and to evaluate the relationship between the basic period generated at the cellular level and the output pattern observed at the organ level. In addition, we examined the effect of photic environmental signals perceived by the animals on LH release patterns from pituitaries in vitro. When the animals were exposed to circadian photoperiodic signals, the in vitro LH release pattern from the pituitaries exhibited ultradian, circadian, and infra-dian frequencies. When the animals were exposed to continuous illumination, the in vitro patterns exhibited only ultradian and infradian frequencies. Furthermore, free running is a process, not a state. This process is driven by a change in the relative dominance of different frequencies that construct the pattern without changing ...