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Biomedical subjects

J Arendt

Publications and source records attributed to J Arendt.

At least 109 records · Page 6Linked to original sources

Effects of light treatment upon mood and melatonin in patients with seasonal affective disorder.

Ten patients with seasonal affective disorder received the following treatments for 5 days each: (a) artificial daylight (2500 lux) from 20.00 to 23.00 and from 07.00 to 10.00 hours; (b) red light (300 lux) from 20.00 to 23.00 and from 07.00 to 10.00 hours; (c) artificial daylight (2500 lux) from 22.00 to 23.00 and from 07.00 to 08.00 hours. The antidepressant effect of treatment (a) was superior to that of treatment (b), suggesting that the effect of light treatment in winter depression is more than that of a placebo. The antidepressant effect of treatment (a) was superior to that of treatment (c), although these two treatments equally suppressed plasma melatonin concentrations. Consequently, in these patients there is a dissociation between the effect of light treatment on melatonin and the reduction of depression ratings.

Adult↗

A study of the mutagenicity of melatonin and 6-hydroxymelatonin.

The mutagenicity of melatonin and its major metabolite 6-hydroxymelatonin were evaluated using the Ames test and three strains of Salmonella typhimurium--TA 97, TA 98, and TA 100. Neither compound exhibited mutagenicity whether in the presence or absence of an activation system derived from rats induced with Aroclor 1254. Positive controls were employed throughout and gave the expected response. We conclude that melatonin, 6-hydroxymelatonin, and their microsomal metabolites are not mutagenic in the Ames test.

Animals↗

Plasma prolactin concentrations in pinealectomized ewes receiving melatonin treatment and in pineal intact ewes maintained under a non-24-hour photoperiod.

We have investigated the profiles of prolactin secretion in relation to onset of breeding activity in Suffolk-Cross ewes with artificially modified melatonin rhythms. With treatments commencing in midsummer, groups of ewes were 1) subjected to a 8L:16D photoperiod, 2) maintained under a "short" (6L:16D) photoperiod repeated over a 22-h cycle that induces an elevation in plasma melatonin that does not endure for the entire dark phase, 3) pinealectomized (pnx) to abolish plasma melatonin levels, and 4) pinealectomized and treated with a melatonin implant (subcutaneous) to provide a constant (no 24-h rhythm) elevation in plasma melatonin. The onset of breeding activity was significantly advanced in both the 8L:16D and pnx/implant groups compared to the 6L:16D and untreated pnx ewes. The two latter groups displayed a normal timing in seasonal breeding activity. Low and high plasma prolactin levels corresponded with short and long photoperiods during both the 24 and 22-h cycles. There was no clearcut "seasonal" rhythm in plasma prolactin in either of the pnx groups. A clear differentiation was seen between reproductive response and prolactin response, particularly in the case of ewes monitored on 22-h cycles of short photoperiod.

Animals↗

A study of the effects of desipramine treatment alone and in combination with L-triiodothyronine on 6-sulphatoxymelatonin excretion in depressed patients.

Urinary 6-sulphatoxymelatonin (alpha MT6s) excretion was measured after one day and one, two and three weeks of desipramine treatment in eight depressed patients. There was significant increase in the urinary excretion of alpha MT6s after one week of treatment, and at no time was there any decrease in alpha MT6s excretion. These findings are opposed to the hypothesis that desipramine reduces noradrenergic neurotransmission in the human pineal. In a further five patients whose depression was resistant to desipramine alone, urinary alpha MT6s excretion was measured during treatment with adjunctive L-triiodothyronine (T3). There was no change in alpha MT6s excretion, and thus the previously reported potentiation of the efficacy of tricyclic antidepressants in combination with T3 does not appear to be mediated through an alteration in noradrenergic neurotransmission.

Adult↗

Entrainment of melatonin rhythms in rams by symmetrical light-dark cycles of different period length.

The objective of this study was to investigate the entrainment of melatonin rhythms in rams using symmetrical light-dark cycles of different period length. Five groups of six Ile de France rams were kept in 12L:12D for 7 weeks and then (i) 12L:12D, (ii) 11L:11D, (iii) 10L:10D, (iv) 13L:13D and (v) 14L:14D for a further 3 weeks. Environmental factors other than the light dark cycle were not controlled. The onset and offset of the plasma melatonin rhythm in DD after 3 weeks of the respective light treatments was assessed for 48 hr, immediately after transferring to DD. The duration of secretion in DD was positively related to the length of the previous dark phase. The phase of the melatonin rhythm with respect to the anticipated dark phase suggested entrainment with no change in phase-relationship to the zeitgeber by 12L:12D and 13L:13D. Entrainment with a phase-delay or a phase-advance was apparent after 11L:11D and 14L:14D, but the individual rhythms were not all synchronized with respect to each other after 10L:10D. Activity recordings for 2-3-week periods during 12L:12D, 10L:10D and 14L:14D all showed a major 24-hr component at all times, with activity during the light phase in 12L:12D. It appears that melatonin may be readily desynchronized from overt activity-rest cycles in sheep. The upper and lower entrainment limits are probably greater than 28 hr and close to 20 hr cycles, respectively.

Activity Cycles↗

Radioimmunoassay of 5-methoxytryptophol in plasma.

5-Methoxytryptophol (ML) is synthesized by the pineal gland, but no radioimmunoassay has been described for its routine measurement in human plasma. We have developed and validated such an RIA. The assay is sensitive (detecting as little as 8 ng/L) and specific, and requires no extraction stage. A preliminary study of healthy volunteers showed an intra-individual variation in plasma ML that was independent of the sex of the subject and the time of daytime collection. Investigation of the 24-h pattern of ML in seven men revealed a low-amplitude daily rhythm (P less than 0.03). Mean concentrations of ML between noon and midnight significantly exceeded those between 0030 and 1130 hours in each individual (P less than 0.05). This assay is practical and convenient, and it should greatly assist in investigation of factors affecting concentrations of ML in human plasma.

Adult↗

Use of an intraruminal soluble glass bolus containing melatonin for early lamb production.

The use of melatonin to advance the onset of seasonal oestrus is potentially useful for early lamb production. A number of delivery systems for melatonin have been developed and this study evaluates an intraruminal soluble glass bolus under field conditions. Anoestrous, non-lactating mule and Dorset cross mule ewes were treated in late June with two types of bolus of different solubilities (melatonin 1, 'slow release' and melatonin 2, 'extra slow release'). Rams were introduced in mid-August for a target lambing pattern in mid-January. The percentage pregnancy/lambing rates were 80/78, 97/92 and 100/100 in the control, melatonin 1 and melatonin 2 groups, respectively. The number of lambs born per ewe put to the ram was significantly increased by treatment with melatonin 2 (P less than 0.05) from 1.17 to 1.64 in the mule ewes and 1.64 to 1.72 in the Dorset cross mule ewes. The melatonin containing soluble glass bolus is a novel and convenient method of reducing the number of barren ewes in an early lambing flock.

Animals↗

How does melatonin control seasonal reproductive cycles?

The pineal gland is essential for the perception of photoperiod change in many species. Information about photoperiod length is conveyed through pineal secretion of the methoxyindole melatonin. Melatonin, suitably administered in physiological quantities is equipotent with artificial photoperiod in the induction of photoperiodic responses. Most experimental work suggests that it is the duration of high night time melatonin secretion (positively correlated with the length of the natural or artificial dark phase) which conveys the photoperiodic signal. Continuous release implants induce short day effects in ewes, entirely comparable to daily feeding of melatonin or short photoperiod. A minimum duration of secretion rather than a specific duration is therefore probably critical to short day effects. There appears to be a seasonal variation in sensitivity to short day melatonin effects (induction of early oestrus) which can be shifted to an earlier time of year following one oestrus advance the previous year. Short duration melatonin is read as a long day even secreted with 22 hour periodicity, suggesting a lack of circadian variation in sensitivity to melatonin.

Animals↗

Pineal and ovarian response to 22- and 24-h days in the ewe.

Melatonin secretion in ewes was entrained by 22-h light-dark cycles whether of long (16L:6D) or short (6L:16D) photoperiod. In photoperiods of 6L:16D, a phase-delay of melatonin secretion was evident, leading to a dark-phase duration shorter than that found in 8L:16D. Early onset of estrus was induced in anestrous ewes kept in 8L:16D, but not 6L:16D, from 22 July compared to controls in natural light. In photoperiods of 16L:6D, the melatonin profile corresponded precisely to the dark phase. Early offset of estrus was induced in estrous ewes kept in both 18L:6D and 16L:6D from 18 December compared to controls in natural light. Thus, when the duration of melatonin secretion was appropriate to the long photoperiod (16L:6D), but with a constantly changing phase position, a long-day reproductive response was found. Activity-rest cycles were not entrained by 16L:6D; thus the synchronization of melatonin and activity-rest cycles does not appear to be essential for the induction of a long-day reproductive response. These results support the hypothesis that the duration, not the circadian-phase position, of melatonin is critical to the induction of photoperiodic effects.

Animals↗

Melatonin.

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Animals↗

Suppression of melatonin secretion in Ile-de-France rams by different light intensities.

The intensity of cool, white, fluorescent light required to suppress melatonin secretion in Ile-de-France rams was investigated. Animals were conditioned to 12L:12D, lights on 0600 hours, 104 microW/cm2 (350 lux) at eye level and subjected to a 1-hour light pulse beginning 3 hours after lights off. Plasma melatonin measurements indicated that secretion was significantly suppressed by 0.30, 7.46, and 26.32 microW/cm2 (1.02, 25.10, and 88.60 lux, respectively) but not by 0.043 microW/cm2 (0.15 lux). A clear dose-response relationship was apparent between light intensity and degree of melatonin suppression.

Animals↗

Effect of melatonin on the human electrocardiogram and simple reaction time responses.

It has been suggested that melatonin may have therapeutic potential for alleviating jet lag. In an attempt to define further the effects of low pharmacological doses of melatonin on the human body, 5 mg of melatonin was given orally to one subject in a blind experiment. The electrocardiogram (ECG) was recorded together with simple reaction time (SRT) responses over a 5-h period after taking melatonin. The main part of the project was carried out under artificial domestic lighting conditions and involved ten evening sessions. Microprocessor analysis of the ECG of one subject clearly showed that melatonin had the effect of lengthening the RR interval, that between the peak of the P wave and the onset of the R wave, and the interval between the onset of the R wave and the peak of the T wave. A model to explain the cubic curve, which was fitted by regression analysis to the data, implies that the natural evening increase in melatonin may also increase these intervals. The results suggest that melatonin may affect both the phase and the amplitude of the observed ECG phenomenon. Analysis of more than 40,000 SRT responses to both visual and auditory stimuli implied that these responses might also be lengthened by melatonin. Frequency histograms of the responses and observations on premature and missed responses were not able to reproduce the results of other workers who found that higher doses (240 mg) of melatonin decreased the number of incorrect responses to simple reaction time tasks.

Acoustic Stimulation↗

Atenolol in seasonal affective disorder: a test of the melatonin hypothesis.

To test the hypothesis that the antidepressant effects of bright light in seasonal affective disorder are mediated by the suppression of melatonin, 19 patients with this disorder were given atenolol, which suppresses melatonin secretion, and placebo in a double-blind crossover study. No difference in antidepressant efficacy was found between drug and placebo in the sample as a whole, which argues against the melatonin hypothesis of phototherapy. However, in three of the patients atenolol provided repeated, marked, and sustained relief of symptoms, suggesting that it may be useful in treating the winter depressive symptoms of some patients with seasonal affective disorder.

Adult↗

Radioimmunoassay for 6-sulphatoxymelatonin in urine using an iodinated tracer.

A radioimmunoassay (RIA) for urinary 6-sulphatoxymelatonin (aMT6s) using an 125I-aMT6s tracer is described. Iodinated aMT6s used as the label was synthesised by direct iodination of aMT6s using 1,3,4,6 tetrachloro 3,6 diphenylglycouril as the oxidant. The assay shows low cross reactivity with related compounds. Serial dilutions of 1:250 and 1:125 diluted urine gave parallel displacement curves. Comparison of the new RIA using 125I-aMT6s with the RIA using 3H-aMT6s label gave good correlation, as did comparison with a gas chromatography mass spectroscopy (GCMS) for total free and conjugated 6-hydroxymelatonin.

Cross Reactions↗

A comparison of melatonin secretion in depressed patients and normal subjects.

Depressed patients were carefully matched in pairs with normal subjects for the variables which are known to influence the secretion of melatonin in humans. In contrast to the previous literature, nocturnal melatonin secretion was not lower in the depressed group than in the normal group, and there was no difference in the timing of secretion; indeed, the trend was for greater melatonin secretion in the depressed group. The results are discussed in relation to previous studies, none of which has been so carefully controlled for the relevant variables.

Adult↗

A study of sulphatoxymelatonin excretion and gonadotrophin status during weight gain in anorexia nervosa.

To clarify a controversy as to whether melatonin secretion is related to body weight, urinary sulphatoxymelatonin (aMT6s) excretion was estimated in 10 patients with anorexia nervosa before and after weight gain, and compared with 10 age-matched controls. There was no change in aMT6s excretion after weight gain, and no significant difference between the patients and control groups at either point. Significant increases in plasma LH, FSH, and estradiol were detected after weight gain in anorexic patients, independent of aMT6s excretion.

Adult↗