摘要:

Abstract:In the past several years, interest in the immunophysiological role of the pineal gland and melatonin has grown to the extent that now their immunoregulatory role is widely recognized. Melatonin has immunoenhancing properties and it is able to counteract the immunodepression induced by acute stress, drug treatment (i.e., anticancer drugs), and viral infections. Here we review the therapeutic efficacy of melatonin alone or in combination with interleukin‐2 (IL‐2) in cancer patients who did not respond to standard anticancer chemotherapies and/or refused any aggressive treatment. In this review, we summarize a series of reports from 1986 through 1994 in which patients affected by metastatic solid tumors, metastatic non‐small‐cell lung cancer, advanced solid neoplasms, myelodysplastic syndrome, hepatocellular carcinoma, and advanced endocrine tumors were studied. The conclusion drawn from these studies is that melatonin protects against IL‐2 and synergizes with the IL‐2 anticancer action. This combined strategy represents a well tolerated intervention to control tumor growth. In most cases performance status and quality of life se

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00177.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The pineal hormone melatonin has been shown to directly scavenge free radicals and to stimulate, in the mammalian brain, at least one enzyme, glutathione peroxidase, which reduces free radical generation. In the present studies, we examined the effect of melatonin on glutathione peroxidase activity in several tissues of an avian species. Melatonin (500 μg/kg), when injected into chicks, increased glutathione peroxidase activity within 90 min in every tissue examined. Tissue melatonin levels, measured by radioimmunoassay, also increased following its peripheral administration. Depending on the tissue, the measured increases in melatonin varied from 75% to 1,300% over the control values. The melatonin‐induced increases in glutathione peroxidase activity varied with the tissue and were between 22% and 134%. These percentage increases in glutathione peroxidase activity were directly correlated with tissue melatonin content. These results suggest that melatonin induces the activity of the detoxifying enzyme, glutathione peroxidase, in several tissues in the chick. The findings also suggest that melatonin would reduce the generation of highly toxic hydroxyl radicals by metabolizing its precursor, hydrogen peroxide. Because of this ability to stimulate glutathione peroxidase activity, melatonin should be considered as a component of the antioxidative defense system in this avian speci

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00178.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Polysomnographic sleep patterns and melatonin secretion were investigated in 10 patients (age: 41.3 ± 9.5 years) who suffered from chronic primary insomnia and complained predominantly about difficulties in maintaining sleep and in five healthy controls (age 27.2 ± 0.7 years). Nocturnal plasma melatonin concentrations were obtained hourly, measured by direct radioimmunoassay and statistically compared between insomniacs and controls with age as a covariate. Plasma melatonin levels in the patient group tended to begin increasing earlier in the evening and were significantly (P ± 0.01) lower during the middle of the night (peak value 82.5 ± 26.5 pg/ml) than in the healthy controls (peak value 116.8 ± 13.5 pg/ml). Among the patients, the most severely reduced nocturnal plasma melatonin levels were found in those patients with a history of sleep disturbance lasting for longer than five years (N = 6; age 41.8 ± 11.7 years; duration 15.3 ± 5.9 years; peak value 72.1 ± 25.0 pg/ml); whereas those chronic insomniacs affected for fewer than five years had relatively higher nocturnal levels (N = 4; age 40.6 ± 6.5 years; duration 3.8 ± 1.5 years; peak value 98.2 ± 23.9 pg/ml). These results show that the circadian rhythm of melatonin secretion is disturbed in patients with chronic primary insomnia, and that the nocturnal plasma melatonin secretion is increasingly more affected the longer the patients are unable to maintain a regular sle

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00179.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Melatonin, the chief hormone of the pineal gland, has been reported to interact with a variety of different cells. This ubiquitously acting hormone has been found to interact with protein receptors both at the cell membrane and in the nucleus. Moreover, melatonin was recently shown to be a very potent hydroxyl radical scavenger. The present work focuses on the interaction of melatonin with pure lipid bilayers. It is shown that melatonin can cross multilamellar lipid vesicles, which are used here as model systems for the lipid phase of biological membranes. Thus, the data prove that melatonin can easily pass through the cell membrane and bath every part of the cell, as previously suggested in the literature. Melatonin lipid association constant was calculated based on the change of the hormone fluorescence intensity due to its penetration into the hydrophobic lipid phase. Though melatonin was recently shown to be highly soluble in aqueous media, its lipid association constant is rather high, indicating that the biological action of the hormone is likely to be at the membrane level, either via its interaction with membrane receptors, and/or as a lipoperoxidation radical scavenger.

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00180.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The possible effects of melatonin on testosterone and androstenedione production in vitro by testes of wild‐caught bats,Scotophilus heathi, during different reproductive phases were investigated. Bats were captured during reproductive quiescent (April‐August), recrudescent (September‐October), breeding (November‐February), and winter dormancy (late December‐January) phases. Testes were incubated in media‐199 for 2 h at 37°C with luteinizing hormone (LH) and with or without melatonin. Melatonin had no effect on LH‐induced testosterone (T) or androstenedione (A) production during the quiescent, recrudescent, and breeding phases. However, it significantly (P<0.05) suppressed LH‐induced T production but had no effect on A during winter dormancy. Testicular 17β‐hydroxy steroid dehydrogenase (17β‐HSD) activity was then measured in the testes from bats trapped during quiescence, breeding, and winter dormancy. Interestingly, melatonin along with LH caused suppression of 17β‐HSD activities (3.56 ± 0.03 unit/min/mg protein) when compared with levels of LH treated testes (7.10 ± 1.15 unit/min/mg protein) during winter dormancy, while it had no significant effect on 17β‐HSD activity during quiescence and breeding phases. These results suggest that inS. heathi, melatonin during winter dormancy suppresses LH‐induced T production by the testes via the suppression of 17β‐HSD activity. This may be the reason for the decline in testicu

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00181.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The influence of several classes of drugs on the melatonin‐induced vasorelaxation of isolated rat aorta were examined. Melatonin caused a dose‐dependent relaxation of precontracted (30 mM KC1) aorta. This relaxant response was blocked by preincubating vessels with antagonists of vasoactive intestinal peptide. Substance P antagonists did not alter the response to melatonin. Pretreatment of vessels with 6‐hydroxydopamine, lidocaine, or tetrodotoxin antagonized the relaxant response to melatonin. On the other hand, pretreatment with atropine + propranolol did not alter the response to melatonin. These experiments suggest that melatonin may exert part of its vasoactive actions by an interaction with perivascular nerve term

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00182.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:This study examined the diurnal changes in the content of 5‐hydroxytryptophan (5‐HTP), serotonin (5‐HT), 5‐hydroxyindoleacetic acid (5‐HIAA), N‐acetylserotonin (NAS), melatonin, 5‐methoxytryptophol (5‐ML), noradrenaline (NA), dopamine (DA), and 3,4‐dihydroxyphenylacetic acid (DOPAC) in the pineal gland of Syrian hamsters kept under long (14L: 10D) and short (10L: 14D) photoperiods. The nocturnal increase in NAS and melatonin levels was dependent upon the prevailing photoperiod, with a prolonged duration when the night lengthened. In both photoperiods, NAS and melatonin contents increased several hours after the onset of darkness, and, in animals kept in short photoperiod, the levels of both compounds began to decrease before light onset. On the contrary, decreases were noted in 5‐HT, 5‐HIAA, and 5‐ML contents during the night, which was directly proportional to the dark phase. 5‐HTP levels did not show a rhythmic variation. Correlations between the mean values of 5‐HT‐related compounds showing daily rhythms were very high when group means were compared, but they decreased when values from individual animals were considered. In addition, when correlations were calculated on per‐animal basis during the night phase, a weak negative correlation was found for 5‐HT vs NAS and 5‐HT vs melatonin, although the correlation of 5‐HT with positively 5‐HT‐correlated compounds (5‐HIAA and 5‐ML) continued to be high. These results indicate that the nocturnal increase in the N‐acetyl transferase activity is the major factor generating the rhythm of pineal 5‐HT content, but that other photoperiod‐dependent mechanisms (i.e., 5‐HT synthesis or release) seem to be also implicated. On the other hand, this study shows that NA content in the Syrian hamster pineal gland does not exhibit daily variations, although marked nocturnal increases in the levels of DA and DOPAC were evident. These results suggest the existence of parallel daily alterations in pineal catecholamine synthesis and release, and su

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00183.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY