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Biomedical subjects

J Arendt

Publications and source records attributed to J Arendt.

At least 145 records · Page 8Linked to original sources
PubMed1986

Persistent 24-h variations of urinary 6-hydroxy melatonin sulphate and cortisol in Antarctica.

Bright light (2000-3000 lux) of sufficient intensity to suppress human melatonin secretion, acts as a strong zeitgeber in the entrainment of circadian rhythms in man. In polar conditions, light of this intensity is not experienced for several weeks during the winter. The entrainment of human circadian rhythms, in particular that of melatonin, is clearly of interest in these circumstances. Urinary 6-hydroxy melatonin sulphate (aMT6s) is a good index of melatonin secretion in man. In a limited study of seven male volunteers living on an Antarctic base the overall 24-h rhythm of aMT6s excretion was maintained at four different times of year (spring, summer, autumn and winter) and no significant seasonal effects were noted. Cortisol excretion, appeared to be markedly affected by the season although other factors such as social and environmental stress cannot be discounted. These observations suggest that in the absence of a strong light-dark cycle melatonin production may be entrained by other factors.

Antarctic Regions↗
PubMed1986

Phototherapy of seasonal affective disorder. Time of day and suppression of melatonin are not critical for antidepressant effects.

Seasonal affective disorder is characterized by recurring cycles of fall-winter depression and spring-summer hypomania (or euthymia). In winter, depressed patients with seasonal affective disorder respond to daily treatments with five to six hours of bright artificial light in two to three days. They relapse two to three days after light is withdrawn. In this study carefully controlled experimental conditions were used to determine whether phototherapy acts via a photoperiodic mechanism in which the timing of light is critical for its therapeutic effect. Photoperiodism is a common regulatory mechanism in animal seasonal rhythms and depends for its effect on light-induced changes in the pattern of nocturnal melatonin secretion. The results reported herein of "skeleton photoperiod" experiments indicate that the efficacy of phototherapy may not depend on its timing or its effect on melatonin secretion.

Circadian Rhythm↗
PubMed1986

Neuroendocrine and other studies of the mechanism of antidepressant action of desipramine.

It is not known whether in depressed patients antidepressant treatment increases or reduces monoaminergic neurotransmission. Clinical studies are therefore reviewed that investigate adaptive changes at adrenoceptors in depressed patients treated with desipramine, and the net effect of these changes upon neurotransmission. Although in animals chronic desipramine treatment enhances the responsiveness of alpha 1-adrenoceptors to phenylephrine, no such effect could be demonstrated in patients upon the responsiveness of pupil diameter to phenylephrine. However, in keeping with animal studies, clinical evidence of altered responsiveness of alpha 2-adrenoceptors could be demonstrated after chronic desipramine treatment. The alpha 2-mediated growth hormone response to clonidine was increased after one week's treatment with desipramine and then reduced during the second and third weeks of treatment. No clinical measure of the responsiveness of central beta-adrenoceptors is available. However, the secretion of melatonin is a measure of neurotransmission at noradrenergic terminals in the pineal with alpha 1-, alpha 2- and beta 1-adrenoceptors. In normal volunteers the secretion of melatonin was increased by the noradrenaline uptake inhibitors desipramine and (+)-oxaprotiline; (-)-oxaprotiline had no effect. In depressed patients melatonin secretion was increased after three weeks' treatment with desipramine. These and other clinical studies suggest that antidepressant treatments increase noradrenergic neurotransmission in depressed patients.

Animals↗
PubMed1986

Acute treatment with desipramine stimulates melatonin and 6-sulphatoxy melatonin production in man.

Acute administration of the antidepressant drug desipramine (DMI) in man, increased evening melatonin secretion, which reached peak plasma levels 2-4 h earlier than after placebo administration. The increase at set time points 21.00 h-22.00 h was directly proportional to an individual's integrated night-time secretion of melatonin. We have shown that this stimulation was not an effect of DMI inhibition on the hepatic metabolism of melatonin to 6-sulphatoxy melatonin (aMT6s), indeed aMT6s is in itself a good index of the evening melatonin rise. The stimulation of early evening melatonin by DMI might be exploited as a simple pineal function test.

Adult↗
PubMed1986

Abnormal circadian rhythm of melatonin in diabetic autonomic neuropathy.

The circadian rhythm of melatonin secretion from the pineal body is entrained to the light-dark cycle and is controlled via sympathetic fibres originating from the superior cervical ganglia. We have therefore examined plasma melatonin profiles in diabetics with and without evidence of autonomic neuropathy and in normal matched controls. The physiological increase in nocturnal plasma melatonin concentration was not observed in diabetics neuropaths. There was no consistent pattern in the diabetics without neuropathy; only three out of the eight subjects in this group had a sustained nocturnal increase in melatonin. Normal diurnal variation of plasma cortisol was present in all groups of subjects. The present study shows that diabetic patients with evidence of autonomic neuropathy lack the normal circadian changes of plasma melatonin concentration. This provides confirmation for the control of pineal function via the sympathetic nervous system in man. The impaired melatonin profiles observed in diabetic patients without apparent autonomic neuropathy suggest that a subclinical state of sympathetic denervation may exist in this group of diabetics.

Aged↗
PubMed1986

The effects of exogenous melatonin on endocrine function in man.

At two different times of year (spring and autumn) an oral preparation of the pineal neurohormone melatonin, or placebo, was administered to 12 healthy volunteers (10 men and two women in spring: the same group minus one man in autumn) daily at 1700 h for 1 month (spring), or 3 weeks (autumn) using a double-blind cross-over protocol. The daily dose was 2 mg melatonin in 5 ml corn-oil, and placebo consisted of the vehicle only. In spring the anterior pituitary hormones LH, PRL, GH together with T4, cortisol, testosterone and melatonin were measured at 1- to 6-h intervals for 24 h in plasma on the day following the last dose. In autumn PRL, cortisol and melatonin levels were measured on the last day of treatment. Subjective fatigue, mood and sleep records were kept throughout the studies. Melatonin increased early evening fatigue and actual sleep, but had no effect on mood: these results are reported in full elsewhere. Melatonin administration had no effect on the levels or 24-h rhythm of LH, GH, T4, testosterone or cortisol. An earlier fall in the nocturnal PRL was observed on both occasions. Overall PRL levels were higher in spring than in autumn. In five of the subjects, the secretion of endogenous melatonin was advanced by 1-3 h in the presence of exogenous melatonin. These observations suggest that the potential therapeutic use of melatonin as a hypnotic or in the treatment of jet lag is unlikely to be complicated by undesirable endocrine effects.

Adult↗
PubMed1986

Does melatonin deficiency cause the enlarged genitalia of the fragile-X syndrome?

Melatonin profiles were studied in five males with cytogenetic and clinical features of the fragile-X syndrome including megalo-orchidia and macrogenitosomia. In comparison with age-matched normal controls, the fragile-X group showed lower melatonin values and a significant impairment of the nocturnal rise in this hormone. Melatonin deficiency may thus be responsible for some of the phenotypic features of this disorder.

Aged↗
PubMed1986

A comparison of the efficiency of melatonin treatments in advancing oestrus in ewes.

Early oestrous cycles were induced in adult, maiden, 18-month-old Suffolk-cross ewes, maintained from birth in natural photoperiod by the following treatments applied from mid-June: subcutaneous implantation of melatonin (1 g) in Silastic packets, daily, oral, melatonin administration (3 mg/ewe) at 15:30 h, an artificial photoperiod of 8L:16D (lights on 07:30 h). Ovarian cycles began 5-10 weeks before those of control ewes maintained in a natural photoperiod. In contrast, the onset of ovarian cycles in ewes given s.c. implants of melatonin (1 g) in April, and a further group in May, was highly variable, and not significantly different from that of the control ewes. Plasma melatonin profiles in sheep with implants showed a night-time rise super-imposed on a constant level, which was itself within the physiological night-time range. Implant-derived melatonin declined with time but remained at or above physiological night-time levels for at least 3 1/2 months. These results indicate that melatonin implants in June, but not in April or May, advance onset of oestrus in the non-lactating, adult ewe. The effects of melatonin implants in June on onset of ovarian cycles were indistinguishable from those of melatonin feeding or artificial short photoperiod initiated at this time of year.

Administration, Oral↗
PubMed1986

Effects of various melatonin treatments on plasma prolactin concentrations in the ewe.

Ewes were treated with s.c. implants of melatonin in mid-April, mid-May and mid-June. From mid-June, other animals were given oral doses of melatonin daily at 16.30 h and another group was maintained under a short (8 h light:16 h darkness) artificial photoperiod (lights out 16.30 h). Serial blood samples were taken from all animals in June and July. Plasma prolactin concentrations were significantly reduced in ewes treated in May and June (implant, oral and photoperiod treatments) but not in those treated in April. After treatment in June, prolactin levels were significantly suppressed after 7 days of oral and implant melatonin therapy, and after 28 days of a short artificial photoperiod. Melatonin treatment appeared more efficient than an artificial photoperiod in reducing plasma prolactin concentrations.

Animals↗
PubMed1986

Radioimmunoassay of pineal 5-methoxytryptophol in different species: comparison with pineal melatonin content.

A sensitive, specific, reproducible and practical radioimmunoassay for the determination of 5-methoxytryptophol (ML) in pineal glands of different species has been developed. High-affinity specific antisera were produced by immunization of sheep with ML-bovine serum albumin. Iodinated ML, used as the radiolabel, was synthesized by direct iodination of ML using 1, 3, 4, 6, -tetrachloro-3, 6-diphenylglycouril as the oxidant. Sensitivity of the assay was 0.005 pmol/tube. The validity of the assay was checked using classical techniques. Cross-reactivity with other indoles was negligible. Parallel inhibition curves were obtained for rat, hamster, sheep and tortoise pineal homogenates. Using thin-layer chromatography, tortoise pineal immunoreactivity also co-chromatographed with standard ML. Samples (n = 5) with ML concentrations of 0.013, 0.052 and 0.209 pmol/tube had intra-assay coefficients of variation of 9.8, 5.7 and 7.6% respectively. Their respective interassay coefficients of variation were 17.7, 16.5 and 11.4% (n = 8). The pineal concentration of ML was found to be species dependent. Afternoon ML levels were 0.052 +/- 0.002 (S.E.M.) pmol/gland in the rat (n = 16), 0.539 +/- 0.089 pmol/gland in the hamster (n = 16), 1.73 +/- 0.225 nmol/g in the sheep (n = 10) and 7.15 +/- 0.465 pmol/gland in the tortoise (n = 4). The ratio of ML:melatonin content in the pineal gland also showed a large interspecies variation with values of 0.02 in the rat, 0.22 in the sheep, 2.7 in the hamster and 17 in the tortoise.

Animals↗
PubMed1986

Assay of melatonin and its metabolites: results in normal and unusual environments.

The pineal gland, via its hormone melatonin, is of major importance in the transduction of photoperiodic information in animals. It is concerned both with the synchronisation of annual cycles in photoperiodic mammals and with regulation of circadian rhythmicity in lower vertebrates. Its role, if any, in mammalian circadian systems is still speculative. By analogy with animal work the function of the human pineal is most likely to be concerned with seasonal and circadian rhythms. The study of human pineal function depends heavily on the measurement of melatonin in plasma or urine. Radioimmunoassay (RIA) and gaschromatography-mass-spectrometry (GCMS) have been successfully employed to establish the basic 24-hour rhythm. GCMS has also served to validate RIA. Following early work the reported human plasma levels of melatonin have stabilized approximately at less than 20 pg/ml in daytime with mean night time levels around 40-80 pg/ml. The high sensitivity of GCMS measures daytime levels of 2-5 pg/ml. With confidence established in melatonin assays, its physiological and pathological variations can be investigated in full. Development of assays for urinary melatonin metabolites has made possible the longterm study of circadian variations in different environments. The rhythm of melatonin production can be dissociated from the sleep wake cycle in environmental isolation and behaves like a "strong" oscillator variable. In the unusual social and photoperiodic conditions of Antarctica it remains strongly entrained to the 24 hour day. Whilst measurement of melatonin can provide circumstantial evidence of its function, abolition of its production and its administration in humans can uncover causal relationships. The effects of abolition of the melatonin rhythm by beta-adrenergic antagonists or pinealectomy has not yet been extensively studied in man. Melatonin administration, always (to date), in pharmacological amounts has hypnotic effects in man and may, in some individuals modify the rhythmic characteristics of its own secretion. It remains to be seen whether, in physiological amounts, it is causally related to aspects of human sleep and other circadian or seasonal rhythms.

Animals↗
PubMed1986

Melatonin in seasonal affective disorder and phototherapy.

In several studies we have found that treatment with bright environmental light, capable of suppressing human melatonin, reverses the winter depressive symptoms of patients with seasonal affective disorder (SAD), whereas light too dim to suppress human melatonin is therapeutically ineffective. This finding, as well as the central importance of melatonin as a hormonal mediator of photoperiodic changes on seasonal rhythms in animals, led us to test the hypothesis that melatonin mediates the effects of shortening days on the winter symptoms of SAD and that the modification of melatonin secretion by bright light mediates its antidepressant effects. We partially reversed the antidepressant effects of phototherapy in 8 SAD patients by oral melatonin administration, but in another study of 19 SAD patients we failed to find any therapeutic difference between the beta-adrenergic blocker, atenolol, which inhibits melatonin secretion, and placebo. In a third study of 7 SAD patients we showed that the anti-depressant effects of phototherapy were not photoperiodic and appeared to be independent of melatonin suppression. There is some preliminary evidence that melatonin secretion may be abnormal in SAD. We conclude that while melatonin may play some role in the symptoms of SAD and the effects of phototherapy, it cannot by itself account for these phenomena.

Animals↗
PubMed1985

Some effects of melatonin and the control of its secretion in humans.

Whether or not the pineal gland has a significant physiological role in humans is not known. There has nevertheless been speculation about the potential therapeutic use of melatonin (in view of its hypnotic and possible zeitgeber properties) in conditions such as insomnia and jet lag, and in shift-workers. Our work concerns the effects of melatonin administration in humans and the interactions between melatonin and other circadian variables. Chronic (one month), timed (1700 h), low-dose (2 mg daily) melatonin administration to normal subjects without environmental control consistently increased evening fatigue and slightly modified the 24 h prolactin rhythm without effect on cortisol, growth hormone, luteinizing hormone, thyroxine, testosterone or self-rated mood. In five out of 11 subjects the endogenous melatonin rhythm was advanced by one to three hours. During fractional desynchronization of circadian rhythms by increasing imposed 'day' length (26-29 h, 24 days, 500 lux), 5 mg melatonin per os at lights-out in two subjects resulted in better entrainment of the fatigue rhythm to the zeitgeber than in five out of six control subjects, without major consistent effects on other measured circadian variables. Using a new radioimmunoassay for 6-hydroxymelatonin sulphate (aMT6s), the major melatonin metabolite, we have shown that the urinary aMT6s rhythm is closely correlated to that of melatonin in plasma and is completely suppressed by an acute dose of atenolol (100 mg per os), a peripheral beta-adrenergic antagonist. During fractional desynchronization by increasing imposed 'day' length in one subject and decreasing imposed 'day' length in two subjects, the urinary aMT6s rhythm behaved similarly to that of core temperature. The results suggest that fatigue (or alertness) may be entrained by melatonin, but whether critical performance rhythms can be suitably manipulated remains to be clarified. It is likely that melatonin production is linked to the so-called 'strong' circadian oscillator.

Circadian Rhythm↗
PubMed1985

Clinical studies of the effect of (+) and (-)-oxaprotiline upon noradrenaline uptake.

In six normal male subjects the mydriatic effect of tyramine eye drops was inhibited by 1 day's treatment with desipramine and the (+)- but not the (-)-enantiomer of oxaprotiline. In the same experiment, the secretion of melatonin was increased after treatment with (+)- but not with (-)-oxaprotiline. The effects of (+)-oxaprotiline and of desipramine treatment were similar, as were those of (-)-oxaprotiline and placebo. These findings extend to clinical studies the demonstration in animal experiments of stereo-specificity for the effects of (+)- and (-)-oxaprotiline upon noradrenaline uptake. A comparison of the effects of the two enantiomers should provide an ideal strategy for studying effects of noradrenaline uptake blockade in clinical studies.

Anthracenes↗
PubMed1985

Chronopharmacology.

The time of day that drugs are given can have a profound effect upon both their pharmacodynamics, i.e. their effectiveness and toxicity, and their pharmacokinetics, i.e. the way they themselves behave in the body. The chronopharmacokinetics of relatively few drugs have been investigated and are mostly those used for the treatment of cancer. We have shown that the toxicity and chronopharmacokinetics of drugs can be altered by pretreatment with steroids or melatonin.

Adrenal Cortex Hormones↗
PubMed1985

Plasma concentrations of melatonin in man following oral absorption of different preparations.

The plasma concentrations of melatonin in man, fasting and fed, were determined after ingestion of three different oral preparations. A dose of 2 mg was given as either a gelatine capsule, a solution in corn oil or as a slow-release pill. Gelatine capsules and the corn oil preparation gave reproducibly timed peak plasma concentrations, 30 to 60 min after ingestion regardless of nutritional status, and plasma melatonin remained at or above endogenous night-time levels for 3-4 h with mean elimination half-lives of 0.54 to 0.67 h. The slow-release preparation usefully extended high plasma melatonin concentrations for 5-7 h after ingestion but the timing of peak concentrations was very dependent on nutritional status. These preparations should be of use in the study of timed melatonin administration in man.

Adult↗
PubMed1985

The effect of desipramine upon melatonin and cortisol secretion in depressed and normal subjects.

Melatonin and cortisol values in plasma were measured hourly over 24 hours in six depressed patients and six normal volunteers before treatment and after one and three weeks of treatment with desipramine. The normal volunteers were further tested one week after withdrawal of desipramine. The mydriatic effects of tyramine and phenylephrine eye drops were also recorded in the normal volunteers. In neither group of subjects did desipramine treatment reduce melatonin secretion, suggesting that functionally significant down-regulation of beta andrenoceptors was not caused by this treatment. Melatonin secretion was significantly increased after three weeks of treatment in depressed patients. This increase was not found in normal subjects.

Adolescent↗