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Biomedical subjects

J Arendt

Publications and source records attributed to J Arendt.

At least 37 records · Page 2Linked to original sources

Complex effects of melatonin: evidence for photoperiodic responses in humans?

The primary function of melatonin in mammals is to convey information about the changing length of the night in the course of the year. This information is used by photoperiodic species to ensure the correct timing of seasonally variable functions such as reproduction, coat growth, and probably the duration and organization of sleep. Melatonin appears not to be essential for circadian organization but reinforces functions associated with darkness. In diurnal humans this of course includes sleep and lowered body temperature. It may act as an adjunct to light for the maintenance of synchrony with the solar day. Exogenous melatonin can both advance and delay the timing of sleep and other circadian functions and appears to stabilize sleep to a 24 h period taken daily at an appropriate time in free running conditions. However, there is as yet little evidence that it can consistently synchronize free running strongly endogenous variables such as core temperature. Its effects on sleep in free run are complex, depend on circadian time of administration, and can in part be interpreted on a photoperiodic basis.

Animals↗

Methods for estimating areas under receiver-operating characteristic curves: illustration with somatic-cell scores in subclinical intramammary infections.

The aim of this study was to demonstrate receiver-operating characteristic (ROC) methodology in the context of bovine intramammary infection (IMI). Quarter somatic cell scores (SCS) were available to evaluate quarter IMI, and the final IMI diagnosis was made from milk bacteriologic cultures. Data consisted of 11,453 quarter-milk samples collected on 2084 clinically healthy cows located in 154 Belgian herds. Bacteriological analyses showed 16.2%, 7.2%, and 11.9% of quarters infected with coagulase-positive Staphylococcus spp., Streptococcus agalactiae, and coagulase-negative Staphylococcus spp., respectively. The ROC curve indicated all the combinations of sensitivity and specificity that quarter SCS was able to provide as a test to identify quarter IMI. Among parametric, semi-parametric, and non-parametric methods to estimate area under ROC curves, the parametric method seemed the least appropriate for analyzing SCS in this study. With the non-parametric method, the total area under the ROC curves showed quarter SCS could identify quarter IMI with an overall accuracy of 69%, 76%, and 59% for coagulase-positive Staphylococcus spp., S. agalactiae, and coagulase-negative Staphylococcus spp., respectively. Parametric and non-parametric statistical tests showed that overall SCS diagnostic capability was significantly (p<0.01) different from chance and was different (p<0.01) across the three bacteria. However, the SCS thresholds yielding the highest percentage of quarters correctly classified as infected (for the observed prevalence and for equal costs assigned to false-positive and false-negative results) were so high that they had no practical value. The major advantage of ROC analysis is the comprehensive description of the discrimination capacity of SCS for all possible choices of critical values. The major disadvantage is the dependency upon the gold standard used for the final diagnosis--but recent improvements of the methodology will correct the problem.

Animals↗

Use of melatonin in the treatment of phase shift and sleep disorders.

When administered to humans the pineal hormone melatonin can phase shift a number of circadian rhythms. This property has prompted the investigation of exogenous melatonin in sleep disorders known to have an underlying chronophysiological basis (i.e. circadian rhythm sleep disorders). Both in field and simulated studies of jet lag and shift work suitably timed melatonin improved sleep and, in some cases, hastened readaptation of the circadian rhythms following the phase shift. Melatonin treatment has also been evaluated in the circadian sleep disorders: delayed sleep phase syndrome (DSPS) and non-24-hour sleep wake disorder. Compared with placebo, melatonin advanced the sleep period in subjects with DSPS. Melatonin also improved a number of sleep parameters in blind subjects suffering from non-24-hour sleep wake disorder.

Blindness↗

The prevention and treatment of jet lag.

Travel across multiple time zones is a common feature of modern life. After transmeridian flights, the internal clocks are desynchronized from the external environment and it can take several days to readjust to the new external time cues. The time taken is related to the direction of the flight and to the number of time zones crossed as well as to individual variability. The result of this desynchronization between the human circadian system and the new environmental timing is described as "jet lag". Although the term "jet lag" refers to disturbances in a variety of symptoms, jet-lagged travellers mostly complain of loss of sleep and of its consequences (e.g., diurnal sleepiness, depressed mood, decreased efficiency, premature awakening, etc.). The direct reason for sleep disturbances after a multiple time-zone flight is that sleep is very sensitive to changes in its temporal setting. The present report reviews current data concerning the symptoms of jet lag, the approaches proposed for the alleviation of jet lag and the effectiveness of these strategies.

Journal Article↗

Correlation between urinary cortisol and 6-sulphatoxymelatonin rhythms in field studies of blind subjects.

OBJECTIVE: Blind individuals have different types of circadian rhythm disorders. In order to study these in the field reliable markers of circadian phase are required. The aim of the present study was to determine the usefulness of urinary cortisol as a marker rhythm in field studies. This was assessed by investigating the relationship between the cortisol rhythms and the previously determined melatonin rhythms from a large sample of blind people with different types of circadian rhythm disorders. DESIGN: Field study SUBJECT: Registered blind subjects (n = 49) classified as having light perception or better (n = 19, 12 men, 7 women, aged 23-61 years) or having no conscious perception of light (n = 30, 24 men, 6 women, aged 19-72 years) were studied in their normal environment. MEASUREMENT: Sequential 4-hourly urine samples (plus an overnight sample) were collected for 48 h each week for 3-5 weeks. Urinary cortisol and 6-sulphatoxymelatonin were measured by radioimmunoassay. RESULT: Irrespective of the type of circadian rhythm (entrained or free-running), there was a significant correlation between the characteristics of the 6-sulphatoxymelatonin and cortisol rhythms in the blind subjects. CONCLUSION: Urinary cortisol is recommended as a useful marker of circadian phase in field studies in addition to urinary 6-sulphatoxymelatonin measurements.

Adult↗

Comparison between subjective and actigraphic measurement of sleep and sleep rhythms.

Sleep is often assessed in circadian rhythm studies and long-term monitoring is required to detect any changes in sleep over time. The present study aims to investigate the ability of the two most commonly employed methods, actigraphy and sleep logs, to identify circadian sleep/wake disorders and measure changes in sleep patterns over time. In addition, the study assesses whether sleep measured by both methods shows the same relationship with an established circadian phase marker, urinary 6-sulphatoxymelatonin. A total of 49 registered blind subjects with different types of circadian rhythms were studied daily for at least four weeks. Grouped analysis of all study days for all subjects was performed for all sleep parameters (1062-1150 days data per sleep parameter). Good correlations were observed when comparing the measurement of sleep timing and duration (sleep onset, sleep offset, night sleep duration, day-time nap duration). However, the methods were poorly correlated in their assessment of transitions between sleep and wake states (sleep latency, number and duration of night awakenings, number of day-time naps). There were also large and inconsistent differences in the measurement of the absolute sleep parameters. Overall, actigraphs recorded a shorter sleep latency, advanced onset time, increased number and duration of night awakenings, delayed offset, increased night sleep duration and increased number and duration of naps compared with the subjective sleep logs. Despite this, there was good agreement between the methods for measuring changes in sleep patterns over time. In particular, the methods agreed when assessing changes in sleep in relation to a circadian phase marker (the 6-sulphatoxymelatonin (aMT6s) rhythm) in both entrained (n = 30) and free-running (n = 4) subjects.

Circadian Rhythm↗

Effects of maintaining solstice light and temperature on reproductive activity, coat growth, plasma prolactin and melatonin in goats.

Interactive effects of light and temperature on aspects of seasonality were studied in female British Saanen dairy goats. Four groups of adult non-pregnant non-lactating goats (n = 5) were housed under the following conditions: controls (July-June): natural photoperiod and temperature; group 1 (July-December): long days (16 h light: 8 h dark) and natural temperature; group 2 (July-December): long days and average summer temperature (17.6 degrees C); group 3 (December-June): short days (8 h light: 16 h dark) and winter temperature (8.4 degrees C). Plasma prolactin and progesterone were measured once a week, circadian changes in prolactin and melatonin were determined in December and May, and coat development was assessed. Seasonal variation in prolactin was influenced by manipulation of both daylength and temperature. In group 1, prolactin concentrations decreased as the environmental temperature decreased, despite maintenance of long days. When light and temperature were maintained under summer (group 2) and winter (group 3) conditions, prolactin remained relatively constant, although at different high and low set points, respectively, but with indications of a seasonal rhythm. An asymptotic relationship between prolactin and temperature was maintained under all daylengths. The circadian pattern of melatonin was related to daylength and was not influenced significantly by temperature. Onset of oestrus was unaltered. In group 3 (maintained winter solstice light and temperature), anoestrus was delayed (P < 0.05) from a median control date of 17 March to a median date of 28 April. Winter coat development was delayed in group 1; group 2 showed premature moulting of the winter coat; and in group 3, development of the summer coat was delayed. The results imply that temperature modifies the influence of daylength on prolactin secretion and hair follicle growth by mechanisms that do not involve melatonin.

Analysis of Variance↗

Shift type and season affect adaptation of the 6-sulphatoxymelatonin rhythm in offshore oil rig workers.

Previously we have shown that the 6-sulphatoxymelatonin rhythm of oil rig workers on a 2-week night shift (1800-0600 h) adapts to the shift via a phase delay. We now report the findings of a study on two offshore drill crews working a 1 week day (1200-0000 h), 1 week night (0000-1200 h) swing shift. Urine samples were collected every 2-3 h throughout the subjective days, with over-sleep collections, for the measurement of 6-sulphatoxymelatonin by radioimmunoassay. One crew (n = 11), studied in November, showed no change in their 6-sulphatoxymelatonin rhythm during night shift. The other crew (n = 7), studied in March, showed a significant phase advance of the rhythm during night shift. The data indicate that both the type of shift and the season influence the direction and degree of adaptation.

Adult↗

Atenolol facilitates light-induced phase shifts in humans.

During time-zone travel, the endogenous melatonin rhythm is often out of phase with the new local time cues. Since endogenous melatonin could act as an endogenous zeitgeber, when its secretory rhythm is out of phase it may hinder adaptation by natural zeitgebers. It is possible that by temporarily suppressing the production of melatonin, by beta-blockers for example, adaptation may be facilitated. In a double-blind, crossover study eight healthy volunteers (aged 23-30 years) took 100 mg atenolol or placebo at 1900 h on Day (D) 1. Volunteers were then exposed to bright light (approx. 1000 lux) from 0000 to 0400 h during the following night and remained in dim light (<50 lux) or darkness until 1200 h on D3. Salivary melatonin (MT) and urinary 6-sulphatoxymelatonin (aMT6s) were measured every 30-60 min and every 2 h (except when asleep), respectively. Subjective alertness and core body temperature (cBT) were also measured. aMT6s and MT were significantly suppressed under atenolol treatment on the night of D1 only. Atenolol significantly phase delayed the salivary melatonin onset by 1.8+/-0.6 h and 1.28+/-0.35 h compared with the onsets on D1 placebo leg and D2 placebo leg (i.e. onset times before and after light treatment), respectively. There were no detrimental effects on cBT or alertness. Temporary suppression of melatonin by beta-blockers may facilitate adaptation to phase shifts.

Administration, Oral↗

Jet-lag.

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Circadian Rhythm↗

Adaptation of the 6-sulphatoxymelatonin rhythm in shiftworkers on offshore oil installations during a 2-week 12-h night shift.

The circadian rhythms of most shiftworkers do not adapt to night shift. We have studied oil workers on a rotating system involving 2 weeks day shift (0600-1800 h) and 2 weeks night shift (1800-0600 h) throughout a day and night shift sequence. Urine samples were collected 3-hourly whilst awake, with an over-sleep collection, for the measurement of 6-sulphatoxymelatonin by radioimmunoassay. In three separate groups results showed adaptation by delay of the 6-sulphatoxymelatonin rhythm in the first week of night shift. The rates of phase shift (mean +/- SEM) were 1.51 +/- 0.16 h/day (n = 5), 1.32 +/- 0.41 h/day (n = 5) and 1.77 +/- 0.31 h/day (n = 17). Specific environmental and social factors together with the shift schedule on oil rigs may facilitate adaptation to a 12 h night shift within a week.

Adaptation, Physiological↗

Disturbance of sleep in blindness.

PURPOSE: To determine the prevalence and severity of sleep disturbance in blind subjects and its relation to the form and duration of visual loss. METHODS: Of 403 blind subjects (visual acuity of less than 20/200 or a visual field of less than 5 degrees) recruited for the study, 15 were excluded because of affective disorder as identified by Montgomery Asberg Depression Scale. The remaining 388 subjects and a comparison group of 44 normally sighted individuals underwent an interview, and the Pittsburgh Sleep Quality Index questionnaire was administered. Sleep disturbance was classified as mild, moderate, or severe. RESULTS: Disturbance of sleep was recorded in 189 (48.7%) of the blind subjects. The prevalence was higher and the sleep disturbance was more severe in those with no perception of light than in those with light perception or better visual acuity. In the comparison group, four (9.1%) had mild sleep disturbance only. The differences between blind subjects and normally sighted individuals were highly significant (P < .001). The most common sleep-related problem among the blind subjects was interrupted sleep, followed by increased sleep latency, short sleep duration, and daytime naps. Among the blind subjects, no correlation was found between the extent of sleep disturbance and the duration and pattern of visual loss. CONCLUSIONS: Blind subjects who retain light perception, as well as those with total loss of vision, have a high frequency of sleep disturbance, although disorder is more common and more severe in subjects with no light perception. Management of the sleep disturbance may improve the quality of life in the visually handicapped.

Adult↗

Extraocular light exposure does not suppress plasma melatonin in humans.

Light affects the circadian axis in at least two ways. It can cause the acute suppression of pineal melatonin synthesis, and/or a phase-shift of the circadian oscillator. As recent evidence has suggested that extraocular light exposure may cause phase-shifts of the circadian clock, we have investigated whether suppression of melatonin can be induced by the same type of light exposure. In the first study subjects' eyes were exposed to white light (2250 lux for 30 mins) via a fibre optic cable. As expected, suppression of nighttime plasma melatonin levels (61 +/- 6%) was observed. In the second study, light of the same quality but higher intensity (14,000 or 67,500 lux for 180 mins) was delivered in the same manner to the popliteal region behind the subjects' knees, whilst shielding their eyes. No suppression of plasma melatonin levels (4 +/- 7%) was detected in any of the subjects. Thus, extraocular photoreception, if it exists in mammals, does not affect the suprachiasmatic nucleipineal pathway.

Adolescent↗

Melatonin and the pineal gland: influence on mammalian seasonal and circadian physiology.

The pineal hormone melatonin is secreted with a marked circadian rhythm. Normally, maximum production occurs during the dark phase of the day and the duration of secretion reflects the duration of the night. The changing profile of secretion as a function of daylength conveys photoperiodic information for the organization of seasonal rhythms in mammals. The role of melatonin in mammalian circadian physiology is less clear. However, exogenous melatonin can phase shift, and in some cases entrain, circadian rhythms in rodents and humans. It can also lower body temperature and induce transient sleepiness. These properties indicate that melatonin can be used therapeutically in circadian rhythm disorder. Successful outcomes have been reported, for example in jet lag and shift work, and with cyclic sleep disorder of some blind subjects. Melatonin receptors of several subtypes are found in the brain, the retina, the pituitary and elsewhere. They are currently under intense investigation. Melatonin agonists and antagonists are under development.

Animals↗

Effects of the endogenous clock and sleep time on melatonin, insulin, glucose and lipid metabolism.

This study was undertaken to determine whether the internal clock contributes to the hormone and metabolic responses following food, in an experiment designed to dissociate internal clock effects from other factors. Nine female subjects participated. They lived indoors for 31 days with normal time cues, including the natural light: darkness cycle. For 7 days they retired to bed from 0000 h to 0800 h. They then underwent a 26-h 'constant routine' (CR) starting at 0800 h, being seated awake in dim light with hourly 88 Kcal drinks. They then lived on an imposed 27-h day (18 h of wakefulness, 9 h allowed for sleep), for a total of 27 days. A second 26-h CR, starting at 2200 h, was completed. During each CR salivary melatonin and plasma glucose, triacylglycerol (TAG), non-essential fatty acids (NEFA), insulin, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured hourly. Melatonin and body temperature data indicated no shift in the endogenous clock during the 27-h imposed schedule. Postprandial NEFA, GIP and GLP-1 showed no consistent effects. Glucose, TAG and insulin increased during the night in the first CR. There was a significant effect of both the endogenous clock and sleep for glucose and TAG, but not for insulin. These findings may be relevant to the known increased risk of cardiovascular disease amongst shift workers.

Adult↗