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Biomedical subjects

J Arendt

Publications and source records attributed to J Arendt.

At least 127 records · Page 7Linked to original sources
PubMed1988

Annual changes in 6-sulphatoxymelatonin excretion in man.

A recently developed RIA for 6-sulphatoxymelatonin, the major urinary metabolite of melatonin, has been used to investigate the annual change in melatonin secretion in humans. Twenty plasma samples were taken from 18 volunteers throughout a 24-h period and simultaneous 6-hourly urine samples were also collected. Plasma melatonin and urinary 6-sulphatoxymelatonin were measured by RIA. 6-Sulphatoxymelatonin assayed in the urine samples was shown to be a good index of the rhythmic characteristics of the plasma melatonin secretion. To study annual changes in excretion four sequential 6-hourly urine samples were collected at monthly intervals from 16 normal volunteers for 13 months. Cosinor curves were fitted to the 6-sulphatoxymelatonin excretion data and the 24-h rhythm was described by the cosinor parameters: amplitude, mesor and acrophase. Significant differences in the acrophase were found during the year. The summer acrophase was phase advanced relative to the winter acrophase by about 1.5 h while intermediate phase positions were observed in spring/autumn. The 24-h excretion of urinary 6-sulphatoxymelatonin was remarkably consistent and there was no annual rhythm. In contrast, the daytime 6-sulphatoxymelatonin excretion between 12.00-18.00 h showed a statistically significant seasonal rhythm, with peaks in December/January and in July.

Adult↗
PubMed1988

Sleep and circadian rhythms of temperature and urinary excretion on a 22.8 hr "day".

Two groups of subjects (total N = 6) were studied in an isolation chamber for a period of 3 weeks whilst living on a 22.8 hr "day". Regular samples of urine were taken when the subjects were awake, deep body temperature was recorded continuously and polygraphic EEG recordings were made of alternate sleeps. The excretion in the urine of potassium, sodium, phosphate, calcium and a metabolite of melatonin were estimated. Measurements of the quantity and quality of sleep were made together with assessments of the temperature profiles associated with sleep. In addition, cosinor analysis of circadian rhythmicity in urinary variables and temperature was performed. The 22.8 hr "days" affected variables and subjects differently. These differences were interpreted as indicating that the endogenous component of half the subjects adjusted to the 22.8 hr "days" but that, for the other three, adjustment did not occur. When the behaviour of different variables was considered then some (including urinary potassium and melatonin, sleep length and REM sleep) appeared to possess a larger endogenous component than others (for example, urinary sodium, phosphate and calcium), with rectal temperature behaving in an intermediate manner. In addition, a comparison between different rhythms in any subject enabled inferences to be drawn regarding any links (or lack of them) that might exist between the rhythms. In this respect also, there was a considerable range in the results and no links between any of the rhythms appeared to exist in the group of subjects as a whole. Two further groups (total N = 8) were treated similarly except that the chamber clock ran at the correct rate. In these subjects, circadian rhythms of urinary excretion and deep body temperature (sleep stages and urinary melatonin were not measured) gave no evidence for deterioration. We conclude, therefore, that the results on the 22.8 hr "day" were directly due to the abnormal "day" length rather than to a prolonged stay in the isolation chamber.

Adolescent↗
PubMed1987

Bright light phase shifts the human melatonin rhythm during the Antarctic winter.

In most species daily and seasonal changes in the light-dark cycle are the most important synchronisers (zeitgebers) of daily and seasonal rhythms. In humans only bright light (2500 lux) appears to be an effective circadian zeitgeber. Seasonal effects of light on human physiology have not been investigated. We have exploited the low intensity illumination of the Antarctic winter to investigate the effects of bright- or dim-light treatment for an hour in the morning and in the evening (a 'skeleton' 12.5-h day) for 6 weeks on the plasma melatonin rhythm, together with mood and a number of behavioural variables. In parallel seasonal changes in melatonin were observed. Melatonin is known to convey daylength information in photoperiodic seasonal breeders through characteristics of its night-time secretion profile. Bright-, but not dim-, light treatment in winter induced a marked phase advance of the melatonin rhythm, similar to that found in the summer, without marked effect on the other variables. Thus at least one human seasonal change appears to be light-dependent.

Antarctic Regions↗
PubMed1987

The effect of abolition of the endogenous corticosteroid rhythm on the circadian variation in methotrexate toxicity in the rat.

Monitoring of indices of haematological, renal and hepatic toxicity in rats after a single i.v. bolus of methotrexate has shown that they vary with the time of day at which the drug is administered. Maximum toxicity occurs after administration at 0600 h. Further experimentation has shown that the amount of corticosteroid present in the blood has a profound effect on the toxicity of methotrexate in the rat. If the endogenous production of corticosterone is suppressed by treatment with dexamethasone the toxicity of methotrexate is markedly increased at whatever clock time it is administered. However, if constantly high plasma levels are achieved by giving supplementary corticosterone methotrexate toxicity is diminished regardless of what time it is given. Since the timing of maximum methotrexate toxicity corresponds to the circadian nadir of endogenous plasma corticosterone concentration in the rat the possibility that it might be related to corticosterone production must be considered. Whether this phenomenon occurs in man and has any clinical relevance has yet to be investigated.

Adrenal Cortex Hormones↗
PubMed1987

Chronic methamphetamine and its withdrawal modify behavioral and neuroendocrine circadian rhythms.

Chronic methamphetamine (MA) administration via the drinking water not only induced hyperactivity, but phase delayed the rat rest-activity cycle under entrained conditions. The minimum and/or maximum of the rhythms in eating, drinking, body weight, core body temperature and plasma/urine corticosterone were delayed. The different phase shifts of peak and trough values can also be a result of modulation in the wave form of the rhythms. The fall, but not the rise, of nocturnal pineal melatonin secretion occurred 4 hours earlier in MA-treated rats than in controls: this pattern was still present 1 week after withdrawal, but no longer after 4 weeks withdrawal. Neither chronic MA nor its withdrawal had any effect on plasma thyrotropin. These patterns after chronic MA intake fall into two groups: those rhythms whose peak and/or trough are delayed and those that are not. We thus interpret chronic MA application as modulating the eating rhythm (though not directly through rhythmic MA levels in the CNS), and that this in turn changes all food-dependent rhythms. In contrast, the circadian rhythms of melatonin and thyrotropin remain independent.

Animals↗
PubMed1987

Suppression of nocturnal plasma melatonin and 6-sulphatoxymelatonin by bright and dim light in man.

Previous studies have shown that bright light (2500 lux) suppresses nocturnal secretion of melatonin, while dim light (500 lux) has little or no effect. We have studied the effect of varying intensities of light on 5 normal male volunteers (age 18-28). The experiment was divided into 3 parts which took place at weekly intervals. Subjects remained under artificial light (fluorescent strip 150-250 lux) between 2000 h-2300 h, they then retired to bed in darkness. On each occasion, between 0030 h and 0100 h, the subjects were required to get up and were treated with light of different intensities; (a) less than 1 lux, (b) 300 lux and (c) 2500 lux respectively. Subjects returned to bed in darkness until 0700 h. Blood was sampled hourly from 2000 h-1000 h with additional samples at 2330 h, 0015 h, 0030 h, 0045 h, 0115 h and 0130 h. Plasma melatonin and 6-sulphatoxymelatonin (aMT6s), the major melatonin metabolite, were measured by radioimmunoassay. Dim (300 lux) and bright (2500 lux) light, both significantly suppressed melatonin levels compared to less than 1 lux (P less than 0.05 and P less than 0.01 respectively) at the following time points 0100 h, 0115 h and 0130 h. One subject did not show suppression with 300 lux. There was also a significant suppression of aMT6s levels, compared to less than 1 lux, after both 300 lux and 2500 lux at 0115 h (P less than 0.05, P less than 0.01), 0130 h (P less than 0.01, P less than 0.01) and 0200 h (P less than 0.01, P less than 0.001) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Metabolism and pharmacokinetics of melatonin in the ewe.

The pineal hormone melatonin has been used to advance the onset of the breeding season in sheep and thus produce lambs earlier in the year. If this reproductive manipulation is to be used commercially, some knowledge of the route of metabolism and identity of possible metabolites is necessary. A major metabolite of melatonin in rodents and man is 6-hydroxymelatonin sulphate (acetyl-methoxytryptamine-6-sulphate [aMT6S]). No significant amounts of this metabolite could be found in the plasma of untreated ewes. After subcutaneous implantation of melatonin for 5 months, plasma levels of aMT6S were also insignificant. On the other hand, both a single oral dose of melatonin (3 mg) and daily oral dosing gave rise to circulating levels of aMT6S in the range of 150 to 1,500 pg/ml for at least 18 h. The profiles seen after 180 days treatment were similar to those seen after a single dose, indicating that this route of melatonin metabolism is not induced by chronic administration. Intravenous injection of melatonin (200 or 20 micrograms) gave rise to detectable levels of aMT6S in the plasma. These results indicate that the quantitative aspects of melatonin metabolism differ according to the route of administration.

Administration, Oral↗
PubMed1987

Short-term variations of circulating melatonin in the ewe.

Melatonin levels have been studied in venous blood sampled at different frequencies (0.5-, 2-, and 60-min intervals) form intact ewes. All samples were taken during the dark phase of either natural or artificial photoperiods. In one experiment samples were taken simultaneously from both jugular veins to investigate the possible effects of "streaming" on the levels measured. Plasma cortisol was measured to ascertain whether or not the frequent removal of blood activated the ACTH stress axis. Plasma melatonin levels showed considerable variation with peaks of up to 365 pg/ml on a baseline of between 30 and 60 pg/ml. There was consistent evidence of intermittent peaks, the frequency of which increased with an increase in sampling frequency. Plasma cortisol showed no correlation with either the frequency or the amplitude of the melatonin peaks. When plasma samples were taken from both jugular veins a similar melatonin pattern was seen in the samples from both sides, but samples taken from the left jugular vein invariably showed higher levels than those taken from the right vein. This may be due to differential vascular drainage of the pineal to the two sides.

Animals↗
PubMed1987

Intraruminal soluble glass boluses containing melatonin can induce early onset of ovarian activity in ewes.

Soluble phosphate glass boluses (preparations A, B, and C) have been developed to release melatonin into the reticulo-rumen of ewes at relatively different (fast, medium or slow) rates. A fourth type (preparation D) containing no melatonin was used as a sham control. Four groups of seasonally anoestrous Suffolk-cross ewes were respectively dosed with preparations A, B, C or D on 4 July. Plasma samples were collected twice weekly for melatonin and progesterone assay. In Groups A, B and C, elevated daytime plasma concentrations of melatonin could be detected for about 5 weeks after bolus administration. However, the pattern of hormone release was variable between groups, with Group C animals maintaining higher plasma melatonin concentrations for a longer period. The control animals had undetectable daytime melatonin levels. The onset of cyclic ovarian activity in the animals treated with the 'slow' release bolus (Group C) was significantly (P less than 0.05) advanced compared to the control group. The 'fast' and 'medium' release treatments (Groups A and B) did not significantly alter the onset of ovarian activity. The results indicate the potential of a novel and convenient method of melatonin delivery for induction of early breeding activity in ewes.

Animals↗
PubMed1987

Changes in plasma concentrations of LH, FSH and prolactin in ewes receiving melatonin and short-photoperiod treatments to induce early onset of breeding activity.

Breeding activity was similarly advanced in ewes given continuous (s.c. implant) or timed (oral dose at 15.30 h) melatonin treatments or subjected to a short (8 h light: 16 h darkness) artificial photoperiod. Treatments commenced in mid-June and were terminated in mid-November. Weekly and serial blood samples were collected before and after treatments commenced, to ascertain the effects on plasma prolactin, LH and FSH concentrations. In addition, serial blood samples were collected for 24 h plasma prolactin and melatonin estimations before and after cessation of the treatments. Plasma prolactin levels were significantly reduced immediately following the start of the melatonin (implant and oral) and short-photoperiod treatments but 'rebounded' to levels greater than control values. The normal seasonal (spring) rise in plasma prolactin was noted in the following year. Before the onset of breeding activity, mean plasma LH and FSH concentrations and LH pulse frequency did not change following any of the treatments. The 24-h plasma melatonin profile accurately reflected the various applied treatments but had re-entrained to the prevailing (natural) photoperiod 1 week after termination of the treatments. There were no significant group differences in 24-h plasma prolactin levels 1 week before or 1 and 11 weeks after the treatments had ceased. Such treatments, although successfully advancing the onset of breeding activity and modifying the seasonal plasma prolactin rhythm, were not manifested through any apparent change in peripheral LH or FSH.

Animals↗
PubMed1987

Effect of different photoperiods on concentrations of 5-methoxytryptophol and melatonin in the pineal gland of the Syrian hamster.

Specific, sensitive and direct radioimmunoassays have been used to determine the daily patterns of 5-methoxytryptophol (ML) and melatonin in the pineal glands of Syrian hamsters kept in different photoperiods: 8 h light: 16 h darkness (8L:16D), 14L:10D and 16L:8D. A rhythm in pineal ML was evident in animals in all the photoperiods, with high daytime levels (641 +/- 35 (S.E.M.) fmol/gland; n = 162) which dropped to 119 +/- 16 fmol/gland (n = 44) 7.1-7.5 h after lights out. The duration of low night-time ML levels was proportional to the length of the dark phase (1.2 h in 16L:8D, 5.4 h in 14L:10D and 8.4 h in 8L:16D). A marked daily rhythm in melatonin was also present in hamsters in the different photoperiods, with daytime levels of 323 +/- 34 fmol/gland (n = 129) and night-time peak concentrations of 3676 +/- 336 fmol/gland (n = 22). The duration of high nocturnal melatonin levels was dependent upon the length of the dark phase (4.1 h in 16L:8D, 4.5 h in 14L:10D and 12.5 h in 8L:16D). Linear regression analysis revealed a statistically significant inverse relationship between pineal ML and melatonin levels in 8L:16D (P less than 0.001), 14L:10D normal (P less than 0.05) and 14L:10D shifted (P less than 0.001) photoperiods. After advancing the lighting schedule by 10 h (14L:10D, lights off at 04.00 h), pineal ML and melatonin rhythms became entrained to the new lighting regimen. The daily rhythms in pineal ML and melatonin in the Syrian hamster thus depend on the prevailing photoperiod, a reciprocal relationship existing between pineal ML and melatonin concentrations.

Animals↗
PubMed1987

Induction of early seasonal sensitivity to melatonin in Suffolk-Cross ewes.

Anoestrous Suffolk-Cross ewes can be induced into early seasonal ovarian activity by administration of melatonin at the appropriate time of day or by melatonin implants. This treatment is successful if commenced in June, but not earlier in April or May and suggests that a critical period of long days may be necessary before artificial short-day melatonin profiles act as winter time-cues. We have investigated whether the lack of sensitivity to melatonin in April could be overcome in ewes in which breeding activity had been artificially moved forward the previous season. The results indicate that this was indeed the case and that the breeding season in untreated ewes which also previously experienced an early induced breeding season reverted to the normal timing for the Suffolk-Cross breed.

Animals↗
PubMed1987

Melatonin secretion in humans assessed by measuring its metabolite, 6-sulfatoxymelatonin.

Comparing a direct radioimmunoassay for 6-sulfatoxymelatonin (aMT6s) with an established gas chromatographic/mass spectrometric method for 6-hydroxymelatonin, we found a good correlation r = 0.94 (P less than 0.001, n = 100). aMT6s was stable, both in urine and plasma samples, without preservative, for at least two years at -20 degrees C and for five days at room temperature. Urinary excretion of aMT6s showed considerable inter-individual differences; however, the aMT6s excretion of any one individual was consistent over a four-day period, as assessed by continuous collection from 18 normal volunteers. Total 24-h urinary excretion of aMT6s was significantly correlated with the area under the curve of the respective profiles for plasma melatonin (r = 0.75, P = 0.0002) and plasma aMT6s (r = 0.70, P = 0.0005) for 22 healthy volunteers. At 24:00 h and 03:00 h, sampling plasma at 30-s intervals provided no evidence for episodic secretion (in short pulses) of either melatonin or aMT6s.

Adolescent↗