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Biomedical subjects

J Arendt

Publications and source records attributed to J Arendt.

At least 19 recordsLinked to original sources
PubMed1992

Melatonin suppression in human subjects by bright and dim light in antarctica: time and season-dependent effects.

Full-spectrum light, of sufficiently high intensity, will suppress the secretion of melatonin at night in humans. Individual sensitivity to such suppression is variable, and the factors determining such sensitivity are largely unknown. By analogy with animal work previous short or long-term exposure to different light intensities may be an important determinant. We exploited the Antarctic environment to investigate these possibilities. Groups of healthy men, living on the British Antarctic Survey Base at Halley (75 degrees South) were exposed to dim (range 290-310 lux) and bright (range 2100-2300 lux) light either from 01.00-02.00 h or 05.00-0.600 h, both in winter and in summer. Plasma melatonin concentrations were determined by radioimmunoassay in serial blood samples taken before, during and after light treatment, and in control (darkness) conditions. Light suppression of melatonin was more effective in the latter part of the night in winter and this was particularly well-differentiated for dim light.

Adult↗
PubMed1992

The acute and chronic effects of (+) and (-) oxaprotiline upon melatonin secretion in normal subjects.

Ten healthy male subjects were treated for three weeks with (+)oxaprotiline, a selective inhibitor of noradrenaline (NA) uptake and with (-)oxaprotiline which does not inhibit NA uptake. Plasma melatonin concentrations were measured throughout the night at 0, 1, 7 and 21 days and were higher during treatment with (+)oxaprotiline than with (-)oxaprotiline for the entire three weeks of treatment. Since NA stimulates the production and secretion of melatonin, these results are consistent with a sustained increase in noradrenergic activity within the pineal, during 21 days of treatment with an effective NA uptake inhibitor.

Administration, Oral↗
PubMed1992

In vitro autoradiographical localization of melatonin binding sites in the caprine brain.

The recent development of a specific 2-[125I]-iodo-melatonin ligand has led to the identification of 125I-melatonin binding sites in the brains of numerous mammalian species. The present study reports the localization of 125I-melatonin binding sites in the brain of the dairy goat. Six previously untreated female goats, aged 5-7 years, were culled under natural light between 0900 and 1100. Brains and pituitaries were immediately dissected out and frozen on dry ice. Both transverse and sagittal sections of frozen brain were cut 20 microns thick and thaw-mounted onto gelatin-coated slides. Three consecutive sections were cut at intervals throughout the brain, mounted onto three slides, labeled A, B, and C, and thusly treated: (A) incubated for 2 hr at room temperature in a 50 pM solution of 125I-melatonin; (B) incubated for 2 hr at room temperature in a 50 pM solution of 125I-melatonin plus 1 microM cold melatonin; (C) fixed in Clarke's fluid and stained with toluidine blue. After incubation, A (specific) and B (nonspecific) slides were washed three times in ice-cold Tris-HCl buffer (pH 7.7), air-dried, exposed to an X-ray film for 2 weeks at -20 degrees C, and then fixed and stained. Specific 125I-melatonin binding sites were found in the pars tuberalis (PT), the area of the suprachiasmatic nucleus (SCN), preoptic area (POA), fornix/mediolateral septal areas, hippocampus, and the cerebral cortex. 125I-melatonin did not bind in the hindbrain, midbrain, neurohypophysis, pars intermedia or pars distalis of the adenohypophysis, or the pineal.

Animals↗
PubMed1992

Diurnal variations of urinary 6-sulphatoxymelatonin in male intact or ganglionectomized mink.

The existence of the major urinary metabolite of melatonin, 6-sulphatoxymelatonin (aMT6s), was validated for mink and the 24 hr urinary excretion pattern was determined in intact and superior cervical ganglionectomized animals under different photoperiodic conditions. Within- and between-assay variations, parallelism between serially mid-night pooled urine dilutions and standard curves in aMT6s free urine of mink at 1:125 dilution and recovery of aMT6s in mid-day pooled urine at 1:125 dilution provided a good validation for the mink urinary a MT6s assay. In natural photoperiods (January, LD 9:15; April, LD 13:11) the diurnal rhythm was characterized by low aMT6s values during the day and high values at night. There were no differences in the nocturnal values measured under long- (April, 4.11 +/- 0.40 ng/hr) or short-day (January, 4.74 +/- 0.36 ng/hr) conditions. In an experimental long photoperiod (LD 15:9), the same result was obtained on the 24 hr rhythm in intact animals, but in ganglionectomized mink the nocturnal rise in aMT6s was abolished and the nocturnal values were always low (0.88 +/- 0.09 ng/hr). Our results agree with those obtained in other species concerning plasma melatonin rhythm and urinary aMT6s excretion; we thus conclude that this is an effective assay for measuring pineal activity in mink.

Animals↗
PubMed1992

Plasma melatonin levels in anorexia nervosa.

Plasma melatonin levels were measured at three-hourly intervals over 24 hours in 11 women with untreated anorexia nervosa, and in nine healthy women of normal weight. The circadian rhythm was unaltered but the nocturnal secretion of melatonin was significantly greater in anorectics. It is possible that this was related to nocturnal hypoglycaemia.

Adolescent↗
PubMed1992

Retardation of pubertal development by prenatal long days in goat kids born in autumn.

Goat kids born in spring attain sexual maturity during the first autumn after birth in temperate regions, at about 30 weeks of age. This study observed sexual development in autumn-born kids and the influence of late-summer, prenatal light treatment on onset of puberty. The breeding season of 14 female British Saanen dairy goats was artificially advanced by 4 months, using a treatment of long days during the winter followed by melatonin treatment in spring. Five goats were treated with a photoperiod of 20 h light:4 h dark (lights on 04.00 h) for 62.1 +/- 1.4 days (mean +/- SEM, n = 5) prepartum (14 August to 15 October). The remaining nine goats were kept under a natural photoperiod: 20 kids from these mothers were followed, five males and five females from each group. Testicular development was assessed by means of weekly measurement of scrotal circumference. Blood samples were taken once a week from all kids from 4 weeks of age for 5 months. Plasma was assayed for progesterone in females and testosterone in males. Autumn-born female kids initiated oestrous cyclicity in January, at a mean age of 12.8 +/- 0.8 weeks. Puberty onset was significantly delayed (P less than 0.03, unpaired Student's t test) in females exposed to 20 h light:4 h dark in utero and occurred at a mean age of 16.5 +/- 1.4 weeks. Testicular development was significantly delayed and plasma testosterone concentrations were lower in autumn-born male kids that experienced 20 h light:4 h dark in utero than in kids from mothers in a natural photoperiod.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Long-term 24-hour rest-activity pattern of sheep in stalls and in the field.

Motor activity of sheep was continuously recorded for 2-3 weeks with an ambulatory monitoring device. Recordings were obtained from free-ranging animals in the field and from animals maintained under various controlled conditions in stalls. The sheep were diurnal under all conditions. While the daily amount of activity and the frequency of rest episodes showed only small differences between the conditions, the rest-activity pattern showed prominent differences. The pattern differed particularly between the field and the stalls. In the field, activity started to increase one hour after dawn, reaching a first maximum towards noon; a second, higher peak in the evening was followed by a rapid decline after dusk. In the stalls the onset and offset of activity was more abrupt; activity peaks coincided with feeding and human activity; the onset of rest with lights off. Activity was lowest and rest most prominent in those stalls where the animals were most isolated from human influence.

Animals↗
PubMed1991

Delayed sleep phase syndrome response to melatonin.

The actions of melatonin on the sleep-wake cycle were investigated by means of a randomised, double-blind, placebo-controlled trial in 8 subjects with a delayed sleep phase syndrome attending a sleep disorders clinic. In randomised order the subjects received placebo or melatonin 5 mg daily for 4 weeks with a 1 week washout period between the treatments. Drug or placebo was given at 2200 h, 5 h before the mean time of sleep onset determined by pretrial sleep logs. In all 8 subjects sleep onset time (mean advance 82 [range 19-124] min; p less than 0.01) and wake time (117 [10-187] min; p less than 0.01) were significantly earlier during melatonin treatment than during placebo. Mean total sleep time was slightly less on melatonin (8 h 12 min) than on placebo (8 h 46 min). Alertness acrophase calculated from the subjects' ratings of alertness made every 2 h while awake was unaltered. Melatonin may act as a phase-setter for sleep-wake cycles in subjects with a delayed sleep phase syndrome.

Administration, Oral↗
PubMed1991

Adaptation of the melatonin rhythm in human subjects following night-shift work in Antarctica.

Different environmental conditions, particularly daylength and intensity of natural light, may influence the ability of shiftworkers to adapt to the abrupt phase-shifts of 24 h time cues imposed by the nature of their work. We have investigated this problem in terms of the circadian rhythm of the pineal hormone melatonin in nightshift workers on the British Antarctic Survey Base at Halley (75 degrees South). Melatonin production was assessed by measurement of its major urinary metabolite 6-sulphatoxymelatonin (aMT6s) by radio-immunoassay in sequential urine samples collected for 48 h at weekly intervals. The acrophase of the melatonin rhythm was significantly delayed from 5.22 h. min to 14.54 h. min (summer) and 8.73 h.min to 13.23 h.min (winter) during a week of night-shift work. Readaptation of the rhythm following night-shift work was markedly slower during the Antarctic winter taking 3 weeks compared to summer where the baseline phase position was re-established after 1 week. Morning and evening treatment (08.00-09.00 h, 16.00-17.00 h) with bright (greater than 2500 lux) full spectrum white light did not significantly modify this phenomenon in summer, but a trend to faster adaptation with light treatment was seen in winter. These observations are likely to be of importance to shift-workers in temperate zones. Further investigations of phase-shifting techniques, such as appropriately timed bright light and administration of melatonin itself, are indicated, particularly in relation to performance at work.

Adult↗
PubMed1991

PET and plasma pharmacokinetic studies after bolus intravenous administration of [11C]melatonin in humans.

A human PET study was performed with carbon-11 labelled melatonin in a healthy volunteer. Plasma pharmacokinetics of melatonin and 6-sulfatoxymelatonin were simultaneously determined using radioimmunoassay. Analysis of tracer kinetics showed maximum activity in the brain 8.5 min following injection, which was different from the curve observed for the plasma radioactivity (maximum at 3.5 min). The results confirmed that melatonin readily crosses the blood-brain barrier and that 6-sulfatoxymelatonin is the main plasma metabolite. The distribution of tracer as a function of time in this study failed to reveal any specific binding.

Adult↗
PubMed1991

Green light attenuates melatonin output and sleepiness during sleep deprivation.

Melatonin output covaries with sleepiness, with both peaking early morning. Bright white light suppresses this output, but it is not known if such treatment ameliorates nighttime sleepiness during sleep deprivation. However, sleep-deprived subjects find such light irritating. Humans are particularly sensitive to green light, and melatonin output is more readily suppressed by this hue. A pilot study using different green light regimens showed that sleep-deprived subjects well tolerated 2,000 lux green light given 10 min hourly, and that this dose reduced nighttime melatonin output. The main study gave this light treatment vs. a low intensity red/green light control, from 1900 hr for 11 hr, to two groups of subjects (n = 6 each) sleep deprived for 36 hr. Urine was collected at 6-hr intervals during sleep loss and on a baseline day. Vigilance performance, subjective sleepiness, and oral temperature were monitored during sleep loss. The experimental condition suppressed urine 6-hydroxymelatonin sulfate (aMT6s) output between 0000 hr and 0600 hr, and increased it 0600-1200 hr; but there was no change in total 24-hr values. The control condition had no such effects. The oral temperature rhythm remained unchanged. Vigilance and subjective sleepiness were improved significantly relative to control values during 0000-0600 hr; these improvements were maintained somewhat over the 0600-1200-hr period, contrary to what one might expect if the delayed melatonin surge at this time was increasing sleepiness. Although the bright green light helped counteract sleepiness, any causal link with changes in melatonin output seem tenuous.

Adult↗
PubMed1990

Melatonin stabilises sleep onset time in a blind man without entrainment of cortisol or temperature rhythms.

The pineal hormone melatonin (N-acetyl-5-methoxytryptamine) is normally secreted at night: in animals it serves to transmit information about light-dark cycles to body physiology Suitable timed administration will alleviate 'jet-lag' severity ratings in humans, the major effect being to improve sleep. It has been suggested that this may be mediated by melatonin re-entraining the endogenous circadian oscillator. We have examined this possibility by feeding melatonin to a blind individual (HK) with a free-running temperature rhythm and a pronounced 35-day cycle in his ability to fall asleep at 'normal' times. Our results show a clear stabilizing effect of melatonin on sleep onset time with elimination of day time sleep, but no entrainment of rectal temperature or urinary cortisol rhythms. Thus melatonin may act on the timing mechanism of sleep onset, rather than as a entrainer of all circadian rhythms. It may well help shiftworkers to sleep at inappropriate phases of their circadian oscillators.

Blindness↗
PubMed1990

Morning or night-time melatonin is ineffective in seasonal affective disorder.

Melatonin, at the same doses used to treat circadian-rhythm related sleep disturbances, had no effect on the depressive symptoms in seasonal affective disorder (SAD) patients, whether given early (7 a.m.) or late (11 p.m.) for a week. Slight improvements in sleep were seen with nighttime administration. The circadian rhythmicity of urinary 6-sulphatoxymelatonin was not modified in any way. Melatonin at this dosage (5 mg/day) or at these two times is therefore not a potential alternative treatment for SAD; light remains the therapy of choice.

Adult↗
PubMed1990

Factors influencing urinary 6-sulphatoxymelatonin, a major melatonin metabolite, in normal human subjects.

6-Sulphatoxymelatonin (aMT6s) has been measured, by a direct radioimmunoassay, in urine from 130 normal volunteers aged 2-80 years. Its relationship to a number of physiological parameters has been assessed. Total urinary excretion of aMT6s did not vary in a group of 40 children aged 2-20 years (24 boys and 16 girls) except when expressed as a function of body weight. In this case, total aMT6s excretion over 24 h decreased as a function of age. In 90 adult volunteers (44 men and 46 women) aged 20-80 years, there was an age-related decline in total 24 h aMT6s excretion with significantly lower values in elderly subjects. In this same adult group no relationships were found between total aMT6s excretion and body weight or height. No sex differences were found either in the 2-20 years or the 20-80 years groups. Pineal calcification was assessed by lateral skull X-ray in 26 adult volunteers (17 men and 9 women) aged 20-50 years. No significant differences in aMT6s excretion were found as a function of pineal calcification. In 16 of these subjects plasma melatonin and aMT6s also showed no relationship to pineal calcification. These studies confirm the usefulness of aMT6s as an index of melatonin secretion in normal volunteers.

Adolescent↗
PubMed1990

Sensitivity of goats to a light pulse during the night as assessed by suppression of melatonin concentrations in the plasma.

This study investigates the ability of a 1 h light pulse of different intensities at night to suppress plasma melatonin in goats. Six female Saanen dairy goats, about 2 yr old, were housed in a light-tight shed. The goats were habituated for 1 wk to an 8L:16D photoperiod (40.70 +/- 4.16 microW/cm2; 137 +/- 14 lux), lights on 0800 h. A 1 h light pulse, of different intensity on each occasion, was given from 1900 to 2000 h. Light intensity was measured by using a lux meter (mean of 36 measurements at goat's eye level). Five different light intensities were given during December in the order 4.22 +/- 0.62 microW/cm2 (14.2 +/- 2.1 lux), 0.68 +/- 0.09 microW/cm2 (2.3 +/- 0.3 lux), 0.26 +/- 0.004 microW/cm2 (0.87 +/- 0.14 lux), darkness, 40.70 +/- 4.16 microW/cm2 (137 +/- 14 lux), with 1-3 d between treatments. The goats were bled hourly from 1500 to 1900 h and every 15 min from 1900 to 2100 h, and a last bleed occurred at 2200 h. Dark-phase samples were taken in dim red light (less than 0.03 microW/cm2; 0.1 lux). Plasma was assayed for melatonin by radioimmunoassay. Suppression of melatonin concentrations increased as light intensity increased as follows: Darkness, 0%; 0.26 +/- 0.004 microW/cm2; 0%; 0.68 +/- 0.09 microW/cm2; 43.1%; 4.22 +/- 0.62 microW/cm2, 71.1%; 40.70 +/- 4.16 microW/cm2, 81.2%. Suppression was significant (P less than 0.05) at light intensities greater than 0.68 microW/cm2, 2.3 lux. A hyperbolic relationship existed between percent suppression and light intensities.

Analysis of Variance↗
PubMed1990

6-sulphatoxymelatonin production in breast cancer patients.

The daily pattern of the major urinary metabolite of melatonin, 6-sulphatoxymelatonin (aMT6s), was determined in women prior to having a breast biopsy. Women with malignant tumors appeared to have significantly lower 24 h concentrations of aMT6s with a decrease in the amplitude of the rhythm compared to women with benign tumors. The amount of urinary aMT6s was dependent upon the age of the subject but was not affected by either menopausal status or body mass index. However, when the women with malignant tumors were compared with a large group of normal women of the same age their aMT6s levels were not outside the normal range. The results show that a large control group and very accurate age matching are essential when investigating melatonin production in different groups of subjects.

Adult↗
PubMed1990

Quantitative structure-activity relationships within a series of melatonin analogs and related indolealkylamines.

The results of molecular orbital calculations by the complete neglect of differential overlap, 2nd version on 10 indolealkylamines and amides related to melatonin are reported. Quantitative structure-activity relationships have been derived by regression analysis of electronic structural parameters and biological data in the form of melatonin receptor affinities. On the basis of these results, together with electrostatic potential energy calculations, a possible receptor binding site model is proposed.

Binding Sites↗