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Biomedical subjects

J Arendt

Publications and source records attributed to J Arendt.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

Long-term studies on immunoreactive human melatonin.

Immunoreactive melatonin has been studied in normal human volunteers, both men and women, at different times of day and different times of the year. At 2400, but not at 0800 or 1200, there are very large inter-individual variations in mean levels, the maximum difference being fivefold. Intra-individual variations are seen at different times of the year at 2400 and 0800, with low values in spring and autumn and high values in summer and winter.

Acetyltransferases

Effects of oestrogen and progesterone on rat pineal N-acetyl transferase activity and melatonin production.

We have extended previous studies on pineal beta-receptors to include effects of oestradiol or PMSG treatment in the immature female rat. Neither manipulation has any effect on norepinephrine-induced N-acetyl transferase (NAT) activity in vitro. In the adult ovariectomised rat oestrogen/progesterone priming exerts a small sensitising effect to beta-stimulation with isoproterenol. Progesterone alone, in vitro, inhibits the release of melatonin from pineals of adult ovariectomised rats.

Acetyltransferases

Melatonin assays in body fluids.

A variety of methods now exist for the assay of melatonin in body fluids. Their relative merits are compared and the validation of one in particular (RIA) described. Physiological studies of melatonin by RIA have shown probable modulation of its secretion by gonadal steroids. The circadian activity maximum in the dark phase of one of the pineal melatonin synthesizing enzymes, N-acetyltransferase, is reflected in peripheral melatonin levels. Man, like all other species studied so far, has a dark phase rise in circulating melatonin. During the menstrual cycle, melatonin shows a luteal phase rise. Further evidence of pineal rhythmicity is found in seasonal melatonin variations in man. The study of the rhythmic properties of peripheral melatonin in man may provide important information on central nervous function.

Acetyltransferases

Tentative immunohistochemical demonstration of melatonin in the rat pineal gland.

In the present study an attempt was made to demonstrate melatonin in the rat pineal gland by means of immunohistochemistry. The anitbody used was raised against 5-methoxy-N-acetyltryptophan which is chemically similar to melatonin. Specific fluorescence was demonstrable only in pineals from rats killed during the night, when melatonin formation is high. It was restricted to parenchymal cells lying in a marginal zone of the organ. These results are discussed in relation to a subdivision of the pineal parenchyma into cortical and medullary areas.

Animals

Microcephalic dwarfism with associated low amniotic fluid 5-hydroxyindole-3-acetic acid (5HIAA). Report of a case of Cornelia de Lange syndrome.

A very low level of 5HIAA in the amniotic fluid was found in a microcephalic dwarf presenting subsequently with Cornelia de Lange syndrome. Since both the amount of amniotic fluid and the renal function after birth were normal this observation suggests that low amniotic fluid 5HIAA may be secondary to abnormalities in foetal neurological development.

Adult