Chronobiological Studies Research Articles

Diurnality and nocturnality in nonhuman primates: comparative chronobiological studies in laboratory and nature

Looking for differences in circadian clock characteristics of diurnal and nocturnal nonhuman primates, this article summarizes results of chronobiological studies carried out in various nocturnal, diurnal, and cathemeral prosimian and anthropoid primate species under controlled laboratory conditions, under seminatural conditions, and in the wild. In almost all circadian parameters investigated, no differences were discernible between the two main chrono-ecotypes, either in circadian period length and the influence upon it of after-effects, of light intensity, and ambient temperature, or in the PRC, re-entrainment behavior, rhythm splitting, and internal desynchronization. Diurnal and nocturnal or cathemeral species differed only in the phase of artificial or natural LDs to which their circadian activity phase was adjusted as well as in the characteristics of masking activity upon the rhythms produced by the direct inhibiting or enhancing effects of light. Pronounced lunar periodicity—observed in the activity rhythm of nocturnal neotropical owl monkeys, genus Aotus, in seminatural and natural environments as well as in wild cathemeral Malagasy lemurs, genus Eulemur—is shown to result from masking effects of moonlight. In captive Eulemur fulvus albifrons, a change from dark-active over cathemeral to light-active behavior, without concurrently changing the circadian phase-setting of activity to D, was produced by direct masking effects of a stepwise reduction of darktime luminosity on an LD 12:12 cycle. Long-term activity recordings carried out in wild diurnal Malagasy sifakas (Propithecus verreauxi) and cathemeral redfronted lemurs (Eulemur fulvus rufus), as well as in wild nocturnal owl monkeys (Aotus a. azarai) of the North Argentinean Chaco, yielded in all species distinct bimodal long- and short-day activity patterns with pronounced peaks during dusk and dawn. Applying Pittendrigh's two-oscillator concept to these results, it is hypothesized that the differences in chrono-ecotype behavior may result from variations in internal coupling and external phase-setting of morning and evening oscillators (m, e) to dawn and dusk, interacting with direct masking effects of light.

Regularity of Daily Activities in Stroke

Various studies have been performed using the Social Rhythm Metric (SRM), though none has been developed with stroke patients. Stroke is a pathology that provokes a strong physical and social impact caused by an abnormality in cerebral circulation. Consequently, we performed two studies to validate the SRM and translate it into Portuguese, and to evaluate the regularity of the daily activities of stroke patients. Both healthy individuals and patients with unilateral cerebral lesions were evaluated. Subjects were of both sexes and between 45 and 65 yrs of age. Participants underwent clinical evaluation and recorded the time of 17 daily activities on the SRM for two weeks. Data were analyzed by the Pearson correlation and Fisher tests. After conceptual translation into Portuguese, corrections were made to arrive at the final version. Normative SRM scores varied from 3.2 to 7.0, suggesting that the activities presented in SRM adequately represented the daily routines of the patients. A correlation was found in SRM between the weeks (r=0.84; p=0.0001), indicating instrument reliability. The mean (±SD) score of the stoke patients was 4.8 (±1.0), and the correlation between the SRM and level of neurological damage showed that patients with lower SRM values were more physically compromised (r=−0.29; p=0.04), suggesting that SRM may be a clinical predictor. Activities related to eating and the sleep‐wake cycle were rated by most patients. In all, 71% of the patients did not work, while 84% of healthy individuals did (p=0.001). Only 64% of patients left home compared to 90% of the healthy subjects (p=0.001), and 59% of patients recorded the activity of going home compared to 82% of healthy individuals (p=0.001). According to the results, there is evidence of the validity and reliability of the SRM, enabling it to be reliably used in chronobiological studies of stroke patients. Given that a less regular lifestyle may be associated with neurological compromise and a decrease in social activities, we suggest new studies with the repeated application of this instrument over the clinical evolution of the disease to better define improvement or worsening of the patient's condition in terms of their social and health aspects.

Biologische Rhythmen und ihre Bedeutung für das Wohlbefinden des Menschen

Already in the 18 th century C. W. Hufeland published detailed observations on body rhythms and sleep combined with helpful recommendations for a healthy life. Since about 1950 worldwide chronobiological research studies on humans and animals these empirical theses could be based on sound data. Referring to Hufeland's work basic principles of biological rhythms and sleep control are introduced in this paper. They show the possibilities of applied chronobiology and chronomedicine and suggest - like Hufeland - to accept the biological rhythms as given and organise everyday life according to a strict chrono- and sleep hygiene. This will support well being and a more effective prevention and treatment of diseases and sleep problems.

An automated tracking system for Caenorhabditis elegans locomotor behavior and circadian studies application

Automation of simple behavioral patterns, such as locomotor activity, is fundamental for pharmacological and genetic screening studies. Recently, circadian behaviors in locomotor activity and stress responses were reported in the nematode Caenorhabditis elegans, a well-known model in genetics and developmental studies. Here we present a new method for long-term recordings of C. elegans (as well as other similar-sized animals) locomotor activity based on an infrared microbeam scattering. Individual nematodes were cultured in a 96-well microtiter plate; we tested L15, CeMM and E. coli liquid cultures in long-term activity tracking experiments, and found CeMM to be the optimal medium. Treatment with 0.2% azide caused an immediate decrease in locomotor activity as recorded with our system. In addition to the validation of the method (including hardware and software details), we report its application in chronobiological studies. Circadian rhythms in animals entrained to light–dark and constant dark conditions ( n = 48 and 96 worms, respectively) at 16 °C, were analyzed by LS periodograms. We obtained a 24.2 ± 0.44 h period (52% of significantly rhythmic animals) in LD, and a 23.1 ± 0.40 h period (37.5% of significantly rhythmic animals) under DD. The system is automateable using microcontrollers, of low-cost construction and highly reproducible.

Twenty‐Four‐Hour and Annual Variation in Onset of Epistaxis in Osler Disease

Osler disease is an autosomal dominant disorder of the fibrovascular tissue characterized by arteriovenous malformations with multi‐systemic haemorrhages. Recurrent epistaxis is the predominant symptom in more than 90% of patients. Recent studies showed circadian and seasonal patterns in the onset of nosebleeds, similar to acute cardiovascular events, such as myocardial infarction and stroke. The aim of this study was to determine whether such patterns would also apply to the onset of epistaxis in patients with Osler disease. In all, 110 patients with Osler disease who were under treatment for recurrent epistaxis at the University Hospital of Mannheim were requested to complete a questionnaire addressing the intensity and frequency of epistaxis according to the classification of Bergler et al., as well as circadian and circannual rhythmicity in the occurrence of epistaxis according to visual analogue scales (VAS). More than half of the patients claimed to experience daily to weekly episodes of recurrent epistaxis. The occurrence of epistaxis showed a biphasic 24 h pattern, with a primary peak in the morning (05∶00–8∶00 h) and smaller secondary peaks in the evening (17∶00–20∶00 h and 21∶00–00∶00 h). No significant seasonal variation was found in the onset of epistaxis. However, a slight tendency, with a peak in winter months, was observed. Similar to other chronobiological studies on nosebleeds, this study showed that the 24 h pattern and seasonal tendency in the onset of epistaxis even applied to patients with Osler disease. Further investigations are necessary to determine the pathological mechanism underlying this phenomenon.

Malondialdehyde Content and Circadian Variations in Brain, Kidney, Liver, and Plasma of Mice

In aerobic organisms, the use of oxygen (O2) to produce energy is associated with the production of Reactive Oxygen Species (ROS), which reacts with biological molecules to produce oxidized metabolites such as malondialdehyde (MDA). This experiment focused on male Swiss mice 12 weeks of age synchronized for 3 weeks by the 12 h light (rest)/12 h dark (activity) span. Different and comparable groups of animals (n=10) were sacrificed at six different circadian stages: 1, 5, 9, 13, 17, and 21 h after light onset (HALO). The 24 h mean MDA level varied among organs of mice in non‐stress conditions and was comparable in brain and liver but lower than in kidney. As the MDA 24 h status constitutes only a part of ROS damages in sites differing by their oxygen use, lipid composition, and detoxification capacity, the temporal patterns of their MDA content were comparatively studied in relationship to the animal rest‐activity cycle. The results revealed significant circadian rhythms with the peak time located during the rest span (5 HALO) for both brain and liver, but during the activity span for the kidney (21 HALO) and plasma (13 HALO). This chronobiological study showed that under physiological conditions, lipid peroxidation depends on several factors. The MDA peak/trough might be used as a tool to detect moments of high/low sensitivity of tissues to ROS attack in rodents.

Biological Rhythms Workshop IC: Sleep and Rhythms

Rhythms of sleep and wakefulness (typically measured as rest/activity rhythms) are among the most prominent of biological rhythms and therefore were among the first to be recorded in early chronobiological studies. These rhythms can provide useful information about the central biological clock, although an appreciation of the problems associated with using rest/activity to infer central clock function is important in the design and interpretation of chronobiological experiments in both animals and humans. Here, we review the anatomical and neurophysiologic bases of sleep regulation in mammals as well as similarities and differences between the sleep of humans and that of other organisms. We outline how human sleep is measured, the role of the circadian system in models of human sleep regulation, and human circadian rhythm sleep disorders. Although the function of sleep is still not completely understood, sleep has a critical role for human health, and we have attempted to outline the role that the circadian timing system has in regulating human sleep and in contributing to sleep disorders.

Chronopharmacology and Antimicrobial Therapeutics

Chronobiology studies the phenomenon of rhythmicity in living organisms. Circadian rhythms are genetically determined and are regulated by external synchronizers (i.e. light/day cycle). Several biological processes involved in the pharmacokinetics and pharmacodynamics of drugs are subject to circadian variations. Chronopharmacology studies how biological rhythms impact on drug pharmacokinetic (chronokinetics), pharmacodynamics (chronoesthesy) and toxicity and determines whether time of day administration modifies drug's pharmacological characteristics. Chronotherapy applies chronopharmacological studies to clinical treatments, determining the best biological time for its dosing, i.e. when beneficial effects are maximal and incidence and/or intensity of related side-effects and toxicity are minimal. Significant variations in the pharmacokinetics and toxicity of antibiotics (aminoglycosides, beta-lactams and fluoroquinolones) related to administration time are well known. The aims of this review are to discuss, briefly, the currently accepted model of the circadian system that substantiates endogenous rhythmicity and to provide an update on the knowledge of circadian rhythms applied to drugs used as medicines, with a special mention to the possible impact on antimicrobial treatments. It is concluded that the dosing time of an antimicrobial agent might be clinically relevant in some treatments, thus, clinicians should be aware that the dosing time might affect the clinical response of a drug.

Method for studying behavioural activity patterns during long-term recordings using a force-plate actometer

The motor activity (MA) patterns of rodents are commonly detected in the laboratory using infrared photo-beams or running wheels. In chronobiological studies, the MA rhythm is considered as a behavioural output of the circadian pacemaker. This paper describes a method to obtain long-term records of MA in rodents, with a 1 mm spatial resolution and a 1 s temporal resolution. The device comprised a square platform laid on top of three force transducers, allowed the calculation of the coordinates of the centre of force exerted by a freely moving rodent, and continuously monitored its displacements. A specific computer program processed the trajectories, providing an exhaustive analysis of motion. To test this method, motor behavioural activity was studied in rats exposed to conditions that favoured rhythmicity: light–dark cycles of both 24 h (LD) and 22 h (T22), and constant darkness (DD). In addition, arrhythmicity patterns were studied under constant light (LL) conditions, and in animals with permanent lesions of the hypothalamic suprachiasmatic nucleus (SCNx). A single description of the general MA distribution at 24 h was obtained using infrared photo-beams. By contrast, under LD conditions, a 24-h rhythm with ultradian components was seen in the total distance travelled, whereas that detected in the number of slow motions showed less ultradian components. In addition, a regional preference in the nesting place was detected under both LD and DD conditions. In one SCNx animal and another exposed to LL conditions, both showing arrhythmicity in photo-beam-detected MA, a 24 h rhythm was observed in regional preference; other LL animal presented a 24 h rhythm in the number of slow motions. This method has capabilities lacking in commonly used techniques. The potential uses of this approach, principally in cronobiological studies, are discussed.

Light-induced Fos expression in the suprachiasmatic nucleus of the four-striped field mouse, Rhabdomys pumilio: A southern African diurnal rodent

Previous studies have suggested that nocturnal and diurnal species of rodents differ in their circadian responses to light including phase shifts and early gene expression. Rhabdomys pumilio, the four-striped field mouse, is diurnal both in nature and in the laboratory. We studied in this species the response of the suprachiasmatic nucleus (SCN) to light stimuli at different time periods using light-induced expression of Fos as marker of neuronal activity. Fos induction in the SCN was investigated using immunohistochemistry and quantitative image analysis. The animals were exposed to a 15 min light pulse with monochromatic green light at different circadian times throughout a 24-h cycle. Animals maintained in constant darkness served as controls. R. pumilio exhibited an endogenous Fos rhythm in the SCN during constant darkness with highest expression during the subjective day at circadian time (CT) 2 and CT10. Photic stimulation resulted in significant Fos induction in the SCN at CT6, CT14, CT18 and CT22, compared to controls kept in constant darkness, with a peak of expression at CT22, i.e. during late subjective night, mainly due to expression in the ventral SCN. In tract tracing experiments based on the use of cholera toxin subunit B, we found that retinal fibres innervate mainly the contralateral ventral SCN. The intergeniculate leaflet received bilateral retinal innervation with overlap between ipsilateral and contralateral fibres. Altogether the data show that the rodent R. pumilio is a unique diurnal model for chronobiological studies.

Chronobiological Considerations for Exercise and Heart Disease

Although regular physical activity is beneficial for many clinical conditions, an acute bout of exercise might increase the risk of an adverse clinical event, such as sudden cardiac death or myocardial infarction, particularly in vulnerable individuals. Since it is also known that the incidence of these events peaks in the morning and that some cardiac patients prefer to schedule leisure-time physical activity before lunch, the question arises as to whether morning exercise is 'inherently' more risky than physical activity performed at other times of day. We attempt to answer this question by reviewing the relevant epidemiological data as well as the results of chronobiological and exercise-related studies that have concentrated on the pathophysiological mechanisms for sudden cardiac events. We also consider generally how chronobiology might impact on exercise prescription in heart disease. We performed a structured literature search in the PubMed and WEBofSCIENCE databases for relevant studies published between 1981 and 2004. The limited amount of published epidemiological data did not allow us to conclude that a bout of vigorous exercise in the morning increases the relative risk of either primary cardiac events in apparently healthy individuals, or secondary events in cardiac patients enrolled in supervised exercise programmes. Nevertheless, these data are not directly relevant to individuals who have a history of heart disease and perform uncontrolled habitual activities. It appears as though the influence of time of day on the cardiovascular safety of this type of exercise has not been examined in this population. There is evidence that several pathophysiological variables (e.g. blood pressure, endothelial function, fibrinolysis) vary in parallel with typical diurnal changes in freely chosen activity. Nevertheless, few studies have been designed to examine specifically whether such variables respond differently to a 'set' level of exercise in the morning compared with the afternoon or evening. Even fewer researchers have adequately separated the influences of waking from sleep, adopting an upright posture and physical exertion per se on these pathophysiological responses at different times of day. In healthy individuals, exercise is generally perceived as more difficult and functional performance is decreased in the morning hours. These observations have been confirmed for patients with heart disease in only one small study. It has also not been confirmed, using an adequately powered study involving cardiac patients, that the responses of heart rate and oxygen consumption (VO(2)) to a set bout of exercise show the highest reactivity in the afternoon and evening, which is the case with healthy individuals. Confirmation of this circadian variation would be important, since it would mean that exercise might be prescribed at too high an intensity in the morning if heart rate or VO(2) responses are employed as markers of exercise load. We conclude that there is some parallelism between the diurnal changes in physical activity and those in the pathophysiological mechanisms associated with acute cardiac events. Nevertheless, more studies are needed to ascertain whether the responses of endothelial function, fibrinolysis and blood pressure to a set exercise regimen differ according to time of day. The results of epidemiological studies suggest that morning exercise is just as safe as afternoon exercise for cardiac patients enrolled in a supervised rehabilitation programme. Nevertheless, it is unclear whether time of day alters the risk of a cardiac event occurring during spontaneous physical activity performed by individuals with established risk factors for heart disease.

On the use of microwave radar devices in chronobiology studies: An application withPeriplaneta americana

Modified motion detectors can be used to monitor locomotor activity and measure endogenous rhythms. Although these devices can help monitor insects in their home cages, the small size of the animals requires a very short wavelength detector. We modified a commercial microwave-based detection device, connected the detector's output to the digital input of a computer, and validated the device by recording circadian and ultradian rhythms. Periplaneta americana were housed in individual cages, and their activity was monitored at 18 degrees C and subsequently at 28 degrees C in constant darkness. Time series were analyzed by a discrete Fourier transform and a chi-square periodogram. Q10 values and the circadian free-running period confirmed the data reported in the literature, validating the apparatus. Moreover, the spectral analysis and periodogram revealed the presence of ultradian rhythmicity in the range of 1-8 h.

Trauma does not happen at random: Predictable rhythm pattern of injury occurrence in a cohort of 15,110 children

Background Several adult chronobiologic studies have shown that accidents do not occur at random. Comparing a large cohort of injured children with uninjured children living in an urban setting, we evaluated the rhythmicity of pediatric injury occurrence. Methods A data review of a prospective cohort study of child trauma over an 8-year period was recorded in a Swiss urban setting. Chronological and demographic information of preschool as well as school-aged injured children were compared with a similar sample of children assessed in the emergency department for nontraumatic events. Results Statistically significant circadian rhythms of injury occurrence were detected with a peak around 4 pm. No sex- or age-related differences were detected between preschool and school-aged children. Type of activity and place of occurrence revealed statistically significant differences in the circadian rhythm of trauma occurrence. No weekly rhythm was validated. A circannual rhythm was validated with a peak on June 14 (±10 days). Conclusions Pediatric trauma did not occur at random. Circadian rhythms of pediatric trauma were not influenced by age, sex, or motor vehicle traffic load. Specific circadian and circannual pattern of injury occurrence in children could influence safety campaigns and prevention programs, as well as optimize workforce distribution in medical facilities.

A Time to Reap

oets and sages throughout the centuries havebeen moved to speak about the mystery oftime and thepoignancy ofits passage,yet until recently,books about bio-logical time and the biological clocks that record it have beenscarce.Over the past half-century,however,the entire scien-tific field of chronobiology,the study of biological time,hasbeen growing in both size and reputation.Its modern inception could be traced to a pivotal meetingin 1960 on biological clocks,held at Cold Spring Harbor,NewYork.Many ofthe central questions about biological clock be-havior, experimental design, and nomenclature were firstenunciated at that meeting.Some termsNfor example, chrono-biology (the study of biological time) and circadian rhythm(from circa, Oapproximately,Oand diem, OdayO;Aschoff1960)Nentered common scientific parlance as a result.Chronobiol-ogists have since progressed from describing biologicaltimekeeping in nearly all types ofliving things to identifyingthe structures and processes associated with it,including thebiochemical and molecular genetic mechanisms responsiblefor it.Even more astounding,several researchers have iden-tified mutations in human clock-related genes that result inabnormal sleepÐwake cycles;some have identified disordersin clock mechanisms that predispose us to cancers and car-diovascular disease,and others are trying to determine whenin the circadian cycle treatments for cancer and other diseasesare most efficacious.Thus chronobiology has matured to astate that beckons the interest of the general public,calls forcollege courses to be taught,and attracts researchers from re-lated disciplines. It is therefore heartening to see the fieldexplained at different levels of sophistication in several newbooks.John D. PalmerOs The Living Clock (2002) provides anamusing and enjoyable personal journey through the studyof chronobiology. Palmer, a professor at the University ofMassachusetts,has over the years documented a wide arrayofrhythmic behaviors,primarily in marine microorganismsand invertebrates. He has shown, for example, that crabsdwelling in the intertidal zone synchronize their behavior bothto the time ofday and to the tide.In The Living Clock, his fifthbook on chronobiology,Palmer introduces the subject witha discussion ofwhat he clearly knows best,the phenomenallydiverse chronobiological adaptations found among micro-organisms.He follows this with three chapters devoted to bio-logical timekeeping in humans,including an account of theformal properties ofcircadian rhythms,drawn from clinicalstudies. He describes the effects of biological clocksNandhence time of dayNon patientsOresponses to drugs and onour attempts to adapt to unnatural shift-work schedules,toartificial lighting,and to the more modern problem ofjet lag.Surprisingly (to me,at least),Palmer concludes this sectionwith a rather uncritical endorsement ofthe use ofthe pinealhormone melatonin for amelioration ofthe symptoms causedby these hazards of modern life.This is my own area of re-search and interest, and I was disappointed to find thatPalmerOs discussion included several minor inaccuracies.These seem to derive mainly from an incautious enthusiasm,but they gave me cause to wonder about the accuracy ofother sections.Subsequent chapters return to more familiar chronobi-ological territory:rhythmic processes in microorganisms,in-tertidal invertebrates, higher animals, and plants. Palmersaves the most recent advances in the field for the last,cu-riously short chapter,prematurely entitled ODenouement.OHere,Palmer gives lamentably short shrift to studies iden-tifying and demonstrating the activity ofspecialized clock-related structures in higher animals, such as the pinealorgan and the suprachiasmatic nucleus in vertebrates.He alsoglosses over the tremendous advances made over the past 25years as a result of developments in molecular genetics andgenomics.After explaining the phenomenon of biologicaltime with great enthusiasm,Palmer seems to relegate to anafterthought the news that science can now tell a good storyabout the intricate interplay of genes and accumulatingproteins that drives many biological clocks.His failure to ad-equately explain these pathbreaking discoveries robs thedenouement of much of its force.Yet despite this unsatis-factory closing and some overstatement, I could recom-mend PalmerOs book to an intelligent lay reader looking foran introduction to the topic.In the same vein but deeper into the lode, Rhythms ofLife,by Russell G.Foster and Leon Kreitzman (2004),will appealto a more technically sophisticated audience.Foster is a pro-fessor ofmolecular neuroscience at Imperial College,London,and a highly regarded chronobiology researcher who has

Melatonin, refractory hypertension, myocardial ischemia and other challenges in nightly blood pressure lowering

A test of the relative merits of timed melatonin for the treatment of cardiac ischemia as well as hypertension refractory to other drugs is documented against the background of earlier chronobiological studies on blood pressure (BP), disease risks, circadian hyper-amplitude-tension and melatonin effects broadly.

Chronobiological features of dream production.

A review of the scientific literature clarifies several chronobiological features of dreaming. The literature supports the conclusions that dreaming 'intensity' and, to a lesser extent dream-like quality, is modulated by (1) a sinusoidal, 90-min ultradian oscillation, (2) a 'switch-like' circadian oscillation, (3) a 12-h circasemidian rhythm, and (4) a 28-day circatrigintan rhythm (for women). Further, access to dream memory sources appears to be modulated by (5) a 7-day circaseptan rhythm. Further study of these rhythmic influences on dreaming may help to explain diverse and often contradictory findings in the dream research literature, to clarify relationships between dreaming and waking cognitive processes, to explain relationships between disturbed phase relationships and dream disturbances and to shed new light on the problems of dreaming's functions and biological markers. Further chronobiological studies of dreaming will likely enable the development of theoretical models that explain how interactions between and within major levels of oscillation determine the variable characteristics of dreaming.

Chronobiological Study of the Pharmacological Response of Rats to Combination Ketamine–Midazolam

Ketamine is commonly administered in combination with benzodiazepines to achieve surgical anaesthesia in rats. The aim of the present study was to analyze the pharmacological response of the combination ketamine–midazolam injected intraperitoneally at different times of day to rats. The study was conducted in July 2003, during the winter in the Southern hemisphere. Female prepuberal Sprague-Dawley rats synchronized to a 12 h light:12 h dark cycle (light, 07:00–19:00 h) were used as experimental animals. A combination treatment of ketamine (40 mg/kg) and midazolam (2 mg/kg) was administered to five different clock-time groups of rats (n = 7/group). Duration of the latency period, ataxia, loss-of-righting reflex (LRR), post-LRR ataxia, and total pharmacological response were assessed by visual assessment. Significant treatment-time differences were detected in the duration of LRR, post-LRR ataxia, and total pharmacological response duration. The longest pharmacological response occurred in rats injected during the light (rest) phase, and the shortest pharmacological response occurred in rats injected during the dark (activity) phase. Cosinor analysis documented circadian rhythmicity in the duration of post-LRR ataxia. The findings of the study indicate the duration of CNS-depression of the ketamine–midazolam combination exhibits treatment-time-dependent variation in the rat.

Seasonal variations in the larval burden distribution of Oestrus ovis in sheep in the southwest of Spain

A chronobiological study of oestrosis was conducted for larval instars of Oestrus ovis from November 2000 to September 2002 with the examination of 477 adult sheep of the southwest region of Spain. Skulls from slaughtered sheep were examined and the different O. ovis larval stages (L1, L2, L3) were recovered from the nasal-sinus cavities. O. ovis larvae were detected in 339 sheep, reaching a prevalence of 71.1%. Only one farm was free of infested sheep indicating a prevalence of the 97.91% among studied flocks. The mean larval burden was 18.54 larvae per infested head during the coldest months in the southwest of Spain when the larval burden reached its highest levels, especially of the first larval stage (L1). However, the maximum percentage of L1 coincided with the minimum percentage of the second larval stage (L2). The third larval stage (L3) was observed in relatively low levels during the entered study period, but two peaks occurred in April–May and in September–October. During the 2 years of sampling, all the different larval stages were simultaneously recovered throughout the year, indicating the existence of a long favourable period for the evolution and development of the larval instars, which would start between February and March and finishing in November.

Neuroendocrine profiles in mood disorders.

The study of neuroendocrine abnormalities in major mental illness, such as the unipolar and bipolar affective syndromes, has been the focus of interest in the past few years. The neuroendocrine window into the brain has been considered as a fruitful and promising approach to the study of mental disorders, as suggested by studies of some neuroendocrine challenge tests in depression that demonstrated their potential use as biological markers. The modern approach to hormonal dynamics focuses on the circadian and pulsatile profiles that truly represent physiological modulation and tests the hypothesis that an abnormality in circadian rhythms is present in affective illness. From the fundamental point of view, such studies performed using a frequent sampling interval over the 24-h cycle aim to clarify the control and significance of the temporal sleep and wake fluctuations of neuroendocrine system activities. Twenty-four-hour hypersecretion of cortisol, diurnal hypersecretion of growth hormone, and normal 24-h levels of prolactin have been reported in careful chronobiological studies of depressed patients, along with sleep recordings. In addition, a nocturnal quiescent period, and a subsequent increase towards the morning maximum, have been consistently found in a subset of depressed patients suffering from endogenous depression. After successful treatment with antidepressants, most of these abnormalities (with the exception of those found in the prolactin study) tend to correct. The normalization of the timing of hormonal secretion was accompanied by a correction of sleep abnormalities and in particular, a lengthening of the REM latencies. Normalization of cortisol secretion was associated with a decrease in the magnitude of episodic cortisol pulses whereas normalization of growth hormone secretion was due to a diminished number of secretory pulses. In conclusion, a disorder of circadian time-keeping seems to characterize acute episodes of major endogenous depression in some patients. This abnormality as well as the associated increases in adrenocorticotropic and somatotropic activities seem to be a state-, rather than trait-dependent phenomenon.

In this Issue

In this Issue