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Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials  

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Full Text Available Ehud Grossman1,4, Moshe Laudon2, Nava Zisapel2,31Department of Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel; 2Neurim Pharmaceuticals Ltd, Tel Aviv, Israel and 3Department of Neurobiology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel; 4Sackler School of Medicine, Tel Aviv University, Tel Aviv, IsraelBackground: Patients with nocturnal hypertension are at higher risk for cardiovascular complications such as myocardial infarction and cerebrovascular insult. Published studies inconsistently reported decreases in nocturnal blood pressure with melatonin.Methods: A meta-analysis of the efficacy and safety of exogenous melatonin in ameliorating nocturnal blood pressure was performed using a random effects model of all studies fitting the inclusion criteria, with subgroup analysis of fast-release versus controlled-release preparations.Results: Seven trials (three of controlled-release and four of fast-release melatonin) with 221 participants were included. Meta-analysis of all seven studies did not reveal significant effects of melatonin versus placebo on nocturnal blood pressure. However, subgroup analysis revealed that controlled-release melatonin significantly reduced nocturnal blood pressure whereas fast-release melatonin had no effect. Systolic blood pressure decreased significantly with controlled-release melatonin (-6.1 mmHg; 95% confidence interval [CI] -10.7 to -1.5; P = 0.009) but not fast-release melatonin (-0.3 mmHg; 95% CI -5.9 to 5.30; P = 0.92). Diastolic blood pressure also decreased significantly with controlled-release melatonin (-3.5 mmHg; 95% CI -6.1 to -0.9; P = 0.009) but not fast-release melatonin (-0.2 mmHg; 95% CI -3.8 to 3.3; P = 0.89). No safety concerns were raised.Conclusion: Add-on controlled-release melatonin to antihypertensive therapy is effective and safe in ameliorating nocturnal hypertension, whereas fast-release melatonin is ineffective. It is necessary that larger trials of longer duration be conducted in order to determine the long-term beneficial effects of controlled-release melatonin in patients with nocturnal hypertension.Keywords: melatonin, nocturnal blood pressure, meta-analysis 

Grossman E; Laudon M; Zisapel N

2011-01-01

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Association of nocturnal melatonin secretion with insulin resistance in nondiabetic young women.  

UK PubMed Central (United Kingdom)

Exogenous melatonin ameliorates insulin resistance in animals, while among humans, polymorphisms in the melatonin receptor gene are associated with insulin resistance. We aimed to investigate the association of endogenous nocturnal melatonin secretion with insulin resistance in humans. We analyzed the association between endogenous nocturnal melatonin secretion, estimated by measuring the main melatonin metabolite, 6-sulfatoxymelatonin, from the first morning urinary void, and the prevalence of insulin resistance based on fasting blood samples collected in a cross-sectional study of 1,075 US women (1997-1999) without diabetes, hypertension, or malignancy. Urinary 6-sulfatoxymelatonin level was standardized to urinary creatinine level; insulin resistance was defined as an insulin sensitivity index value (using the McAuley formula) less than 7.85. Logistic regression models included adjustment for age, body mass index, smoking, physical activity, alcohol intake, dietary glycemic index, family history of diabetes mellitus, blood pressure, plasma total cholesterol, uric acid, and estimated glomerular filtration rate. Higher nocturnal melatonin secretion was inversely associated with insulin levels and insulin resistance. In fully adjusted models, the odds ratio for insulin resistance was 0.45 (95% confidence interval: 0.28, 0.74) among women in the highest quartile of urinary 6-sulfatoxymelatonin:creatinine ratio compared with women in the lowest quartile. Nocturnal melatonin secretion is independently and inversely associated with insulin resistance.

McMullan CJ; Curhan GC; Schernhammer ES; Forman JP

2013-07-01

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Nocturnal activity in the green sea turtle alters daily profiles of melatonin and corticosterone.  

Science.gov (United States)

In nature, green turtles (Chelonia mydas) can exhibit nocturnal activity in addition to their typically diurnal activity cycle. We examined whether nocturnal activity in captive and free-living green turtles altered daily plasma profiles of melatonin (MEL) and corticosterone (CORT). In captivity, diurnally active green turtles expressed distinct diel cycles in MEL and CORT; a nocturnal rise was observed in MEL and a diurnal rise was observed in CORT. However, when induced to perform both low- and high-intensity nocturnal activity, captive green turtles exhibited a significant decrease in MEL, compared to inactive controls. In contrast, plasma CORT increased significantly with nocturnal activity, and further, the relative increase in CORT was correlated with the intensity of the nocturnal behavior. In free-living green turtles that performed nocturnal activity including: nesting, mate searching, and feeding/swimming behaviors, plasma profiles in MEL and CORT exhibited relatively little, or no, daily fluctuation. Our findings demonstrate that nocturnal activity in green turtles is often associated with MEL and CORT profiles that resemble those measured during the day. We speculate that these conspicuous changes in MEL and CORT during nocturnal activity could either support or promote behaviors that enable acquisition of transient resources important to the survival and reproductive success of green turtles. PMID:12018931

Jessop, Tim S; Limpus, Colin J; Whittier, Joan M

2002-06-01

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Nocturnal activity in the green sea turtle alters daily profiles of melatonin and corticosterone.  

UK PubMed Central (United Kingdom)

In nature, green turtles (Chelonia mydas) can exhibit nocturnal activity in addition to their typically diurnal activity cycle. We examined whether nocturnal activity in captive and free-living green turtles altered daily plasma profiles of melatonin (MEL) and corticosterone (CORT). In captivity, diurnally active green turtles expressed distinct diel cycles in MEL and CORT; a nocturnal rise was observed in MEL and a diurnal rise was observed in CORT. However, when induced to perform both low- and high-intensity nocturnal activity, captive green turtles exhibited a significant decrease in MEL, compared to inactive controls. In contrast, plasma CORT increased significantly with nocturnal activity, and further, the relative increase in CORT was correlated with the intensity of the nocturnal behavior. In free-living green turtles that performed nocturnal activity including: nesting, mate searching, and feeding/swimming behaviors, plasma profiles in MEL and CORT exhibited relatively little, or no, daily fluctuation. Our findings demonstrate that nocturnal activity in green turtles is often associated with MEL and CORT profiles that resemble those measured during the day. We speculate that these conspicuous changes in MEL and CORT during nocturnal activity could either support or promote behaviors that enable acquisition of transient resources important to the survival and reproductive success of green turtles.

Jessop TS; Limpus CJ; Whittier JM

2002-06-01

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Early evening melatonin and S-20098 advance circadian phase and nocturnal regulation of core body temperature.  

UK PubMed Central (United Kingdom)

The phase-shifting capacity and thermoregulatory effects of a single oral administration at 18 h of melatonin (5 mg) or S-20098, a melatonin agonist (5 or 100 mg), was investigated in eight healthy young men in a double-blind placebo crossover design. The unmasking conditions of a shortened constant-routine protocol (mini-CR) were used to collect evening phase markers of physiological parameters. In comparison to placebo, all three drug administrations induced an earlier dim-light melatonin onset (DLMO), an earlier increase in distal skin temperature, and an earlier decrease in core body temperature (CBT), heart rate, and proximal skin temperature. This indicates that administration at 18 h of both melatonin and S-20098 (more pronounced with 100 than 5 mg) induced an earlier regulation of the endogenous circadian nocturnal decline in CBT. On the posttreatment day a second mini-CR revealed persistent significantly phase-advanced circadian rhythms as estimated by DLMO, as well as by the midrange crossing time of CBT and heart rate decline. There were no significant differences between the two doses of S-20098. The data suggest that, in addition to immediate thermoregulatory changes, a phase advance of the circadian system had occurred and that the phase advance could still be measured on the posttreatment day.

Kräuchi K; Cajochen C; Möri D; Graw P; Wirz-Justice A

1997-04-01

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Alteraciones de la secreción nocturna de melatonina y neuropatías ópticas/ Alterations in nocturnal melatonin levels in patients with optic neuropathies  

Scientific Electronic Library Online (English)

Full Text Available Abstract in spanish Objetivo: Evaluar la supresión de la secreción nocturna de melatonina inducida por exposición a la luz en pacientes con neuropatías ópticas bilaterales. Métodos: Estudio clínico de casos controles, observacional y prospectivo. Tamaño muestral de 20 pacientes distribuidos en 3 grupos: Grupo A (n=5, Sujetos Sanos Controles), Grupo B (n=10, Pacientes Experimentales) y Grupo C (n=5, Sujetos Controles Ciegos). Se analiza la mejor agudeza visual corregida LogMAR, la des (more) viación media en perimetría estática automatizada, el espesor medio de la capa de fibras nerviosas retinianas mediante Tomografía de Coherencia Óptica y los registros de electrorretinografía multifocal (mfERG). Se realizan determinaciones de melatonina en saliva por radioinmunoensayo tras exposición a una luz de 600 lux durante 1 hora (Test de supresión nocturna de melatonina). Resultados: Se encontraron diferencias estadísticamente significativas entre los grupos. No se observaron cambios en los registros de mf ERG. El test de supresión nocturna de melatonina fue positivo en todos los casos del Grupo A, en el 50% de los casos del Grupo B y en todos los casos del Grupo C fue negativo. Conclusiones: El 50% de los pacientes con neuropatías ópticas y pérdida visual severa exhiben alteraciones significativas en la secreción nocturna de melatonina, probablemente debido a una disfunción de las células ganglionares de la retina intrínsecamente fotosensibles (ipCGR). Abstract in english Objective: To study nocturnal melatonin suppression induced by exposure to light in patients with bilateral optic neuropathies. Methods: Observational, prospective case control study. Twenty patients were included in this study and distributed in 3 groups: Group A (n=5, Healthy Control Subjects), Group B (n=10, Experimental Patients) and Group C (n=5, Blind Control Subjects). LogMAR best-corrected visual acuity, standard automated perimetry mean deviation, retinal nerve f (more) iber layer thickness by Optical Coherence Tomography and multifocal electroretinograpy (mfERG) were used to evaluate the changes. Melatonin was analysed in the saliva by radioimmunoassay after exposure to light (600 lux for 1 hour) (nocturnal melatonin suppression test). Results: Statistically significant differences between the groups were found. No changes in the mfERG results were detected. The nocturnal melatonin suppression test was positive in all cases in Group A, 50 % in Group B and none in Group C. Conclusions: Half of the patients with optic neuropathies and severe visual loss were shown to suffer significant melatonin regulation anomalies, probably due to the dysfunction of the intrinsically photosensitive retinal ganglion cells (ipRGC).

Pérez-Rico, C.; De la Villa, P.; Blanco, R.; Germain, F.; Paz-Moreno, J.; Arribas-Gómez, I.

2009-05-01

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Nocturnal secretion of melatonin in patients with functional dyspepsia --- Nocne wydzielanie melatoniny u osob z dyspepsjs czynnosciows  

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Full Text Available Introduction: It has been suggested that disturbances of circadian and seasonal rhythmicity in the release of melatonin (MLT) may be amongthe causes of recurrence of peptic ulcers. Similar seasonal regularity is observed in clinical pictures of functional dyspepsia (FD). However, there are no reports on possible role of MLT in pathogenesis of dyspepsia. Aim of study: The aim of the study was to investigate nocturnal secretion in subjects in different subgroups of FD. Material and methods: The investigations were carried out in 53 patients, aged 20-54 years. According to the results of clinical and enodoscopic examinations and Rome III Criteria - epigastric pain syndrome (EPS) was diagnosed in 28 patients and postprandial distress syndrome (PDS) in 25 patients. 25 healthy persons, aged 25-45 years, constituted the control group (K). Blood samples were taken from each subject at 10.00 p.m., 2.00 a.m. and 6.00 a.m. Melatonin concentration was measured with EUSA method (enzyme linked immunosorbentassay). Results: The average concentration of MLT in healthy subjects was 34.7s8.1 pg/ml, in patients with EPS - 40.4s9.1 pg/ml (p>0.05) and with PDS - 60.1s10.2 pg/ml (p<0.05). Conclusions: 1. Nocturnal secretion of MLT in patients with different subgroups of FD is varied. 2. Diversity of MLT secretion may be the cause of different dyspeptic symptoms

Grazyna Klupinska; Agnieszka Harasiuk; Tomasz Poplawski; Cezary Chojnacki; Janusz Blasiak; Jan Chojnacki

2007-01-01

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Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth  

Energy Technology Data Exchange (ETDEWEB)

Rats exposed to 60-Hz electric fields of either 10, 65, or 130 kV/m from conception to 23 days of age exhibited reduced peak nighttime pineal melatonin contents compared to unexposed controls. As a group, the exposed rats also exhibited a phase delay, estimated at approximately 1.4 hours, in the occurrence of the nocturnal melatonin peak. No clear dose-response relationship was noticed over the range of electric field strengths used as treatments in these experiments. These are the first studies concerned with the effects of electric field exposure on the pineal melatonin rhythm in immature rats. The findings are generally consistent with those obtained using adult rats, where electric field exposure has been shown to abolish the nighttime rhythm in pineal melatonin concentrations.

Reiter, R.J.; Anderson, L.E.; Buschbom, R.L.; Wilson, B.W.

1988-01-01

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Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth  

Energy Technology Data Exchange (ETDEWEB)

Rats exposed to 60-Hz electric fields of either 10, 65, or 130 kV/m from conception to 23 days of age exhibited reduced peak nighttime pineal melatonin contents compared to unexposed controls. As a group, the exposed rats also exhibited a phase delay, estimated at approximately 1.4 hours, in the occurrence of the nocturnal melatonin peak. No clear dose-response relationship was noticed over the range of electric field strengths used as treatments in these experiments. These are the first studies concerned with the effects of electric field exposure on the pineal melatonin rhythm in immature rats and the findings are generally consistent with those obtained using adult rats, where electric field exposure has been shown to abolish the nighttime rhythm in pineal melatonin concentrations. 15 refs., 1 fig., 1 tab.

Reiter, R.J.; Anderson, L.E.; Buschbom, R.I.; Wilson, B.W.

1988-02-01

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Rapid-onset/offset, variably scheduled 60 Hz electric and magnetic field exposure reduces nocturnal serum melatonin concentration in nonhuman primates  

Energy Technology Data Exchange (ETDEWEB)

Experiments with rodents indicate that power-frequency electric field (EF) or magnetic field (MF) exposure can suppress the normal nocturnal increase in melatonin concentration in pineal gland and blood. In a separate set of three experiments conducted with nonhuman primates, the authors did not observe melatonin suppression as a result of 6 weeks of day-time exposure to combined 60 Hz electric and magnetic fields (E/MF) with regularly schedule ``slow`` E/MF onsets/offsets. The study described here used a different exposure paradigm in which two baboons were exposed to E/MF with ``rapid`` E/MF onsets/offsets accompanied by EF transients not found with slowly ramped E/MF onset/offset; profound reductions in nocturnal serum melatonin concentration were observed in this experiment. If replicated in a more extensive experiment, the observation of melatonin suppression only in the presence of E/MF transients would suggest that very specific exposure parameters determine the effects of 60 Hz E/MF on melatonin.

Rogers, W.R.; Smith, H.D. [Southwest Research Inst., San Antonio, TX (United States). Dept. of Biosciences and Bioengineering; Reiter, R.J.; Barlow-Walden, L. [Univ. of Texas Health Science Center, San Antonio, TX (United States). Dept. of Cellular and Structural Biology

1995-12-31

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Tryptophan-enriched cereal intake improves nocturnal sleep, melatonin, serotonin, and total antioxidant capacity levels and mood in elderly humans.  

UK PubMed Central (United Kingdom)

Melatonin and serotonin rhythms, which exhibit a close association with the endogenous circadian component of sleep, are attenuated with increasing age. This decrease seems to be linked to sleep alterations in the elderly. Chrononutrition is a field of chronobiology that establishes the principle of consuming foodstuffs at times of the day when they are more useful for health, improving, therefore, biorhythms and physical performance. Our aim was to analyze whether the consumption of cereals enriched with tryptophan, the precursor of both serotonin and melatonin, may help in the reconsolidation of the sleep/wake cycle and counteract depression and anxiety in 35 middle-aged/elderly (aged 55-75 year) volunteers in a simple blind assay. Data were collected for 3 weeks according to the following schedule: The control week participants consumed standard cereals (22.5 mg tryptophan in 30 g cereals per dose) at breakfast and dinner; for the treatment week, cereals enriched with a higher dose of tryptophan (60 mg tryptophan in 30 g cereals per dose) were eaten at both breakfast and dinner; the posttreatment week volunteers consumed their usual diet. Each participant wore a wrist actimeter that logged activity during the whole experiment. Urine was collected to analyze melatonin and serotonin urinary metabolites and to measure total antioxidant capacity. The consumption of cereals containing the higher dose in tryptophan increased sleep efficiency, actual sleep time, immobile time, and decreased total nocturnal activity, sleep fragmentation index, and sleep latency. Urinary 6-sulfatoxymelatonin, 5-hydroxyindoleacetic acid levels, and urinary total antioxidant capacity also increased respectively after tryptophan-enriched cereal ingestion as well as improving anxiety and depression symptoms. Cereals enriched with tryptophan may be useful as a chrononutrition tool for alterations in the sleep/wake cycle due to age.

Bravo R; Matito S; Cubero J; Paredes SD; Franco L; Rivero M; Rodríguez AB; Barriga C

2013-08-01

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Exposure to light at night, nocturnal urinary melatonin excretion, and obesity/dyslipidemia in the elderly: a cross-sectional analysis of the HEIJO-KYO study.  

UK PubMed Central (United Kingdom)

CONTEXT: Obesity and exposure to light at night (LAN) have increased globally. Although LAN suppresses melatonin secretion and disturbs body mass regulation in experimental settings, its associations with melatonin secretion, obesity, and other metabolic consequences in uncontrolled home settings remain unclear. OBJECTIVE: The aim of this study was to determine the association of exposure to LAN in an uncontrolled home setting with melatonin secretion, obesity, dyslipidemia, and diabetes. DESIGN AND PARTICIPANTS: A cross-sectional study was performed in 528 elderly individuals (mean age, 72.8 yr). MEASURES: The intensity of LAN in the bedroom was measured at 1-min intervals during two consecutive nights, along with overnight urinary melatonin excretion and metabolic parameters. RESULTS: Compared with the Dim group (average <3 lux; n = 383), the LAN group (average ?3 lux; n = 145) showed significantly higher body weight (adjusted mean, 58.8 vs. 56.6 kg; P = 0.01), body mass index (23.3 vs. 22.7 kg/m(2); P = 0.04), waist circumference (84.9 vs. 82.8 cm; P = 0.01), triglyceride levels (119.7 vs. 99.5 mg/dl; P < 0.01), and low-density lipoprotein cholesterol levels (128.6 vs. 122.2 mg/dl; P = 0.04), and showed significantly lower high-density lipoprotein cholesterol levels (57.4 vs. 61.3 mg/dl; P = 0.02). These associations were independent of numerous potential confounders, including urinary melatonin excretion. Furthermore, LAN exposure is associated with higher odds ratios (ORs) for obesity (body mass index: OR, 1.89; P = 0.02; abdominal: OR, 1.62; P = 0.04) and dyslipidemia (OR, 1.72; P = 0.02) independent of demographic and socioeconomic parameters. In contrast, urinary melatonin excretion and glucose parameters did not show significant differences between the two groups. CONCLUSIONS: Exposure to LAN in an uncontrolled home setting is associated with impaired obese and lipid parameters independent of nocturnal urinary melatonin excretion in elderly individuals. Moreover, LAN exposure is associated with higher ORs for obesity and dyslipidemia independent of demographic and socioeconomic parameters.

Obayashi K; Saeki K; Iwamoto J; Okamoto N; Tomioka K; Nezu S; Ikada Y; Kurumatani N

2013-01-01

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Effect of bed head elevation during sleep in symptomatic patients of nocturnal gastroesophageal reflux.  

UK PubMed Central (United Kingdom)

BACKGROUND AND AIM: Nocturnal gastro-esophageal reflux causes heartburn and sleep disturbances impairing quality of life. Lifestyle modifications, like bed head elevation during sleep, are thought to alleviate the symptoms of gastroesophageal reflux. We tested the hypothesis that bed head elevation might decrease recumbent acid exposure compared to sleeping in a flat bed. METHODS: Patients of symptomatic nocturnal reflux and documented recumbent (supine) reflux verified by esophageal pH test entered the trial. On day 1, baseline pH was measured while the patient slept on a flat bed. Then patients slept on a bed with the head end elevated by a 20-cm block for the next 6 consecutive days from day 2 to day 7. The pH test was repeated on day 2 and day 7. Each patient acted as his own control. RESULTS: Twenty of 24 (83.3%) patients with mean age of 36 ± 5.5 years completed the trial. The mean (± SD) supine reflux time %, acid clearance time, number of refluxes 5 min longer and symptom score on day 1 and day 7 were 15.0 ± 8.4 and 13.7 ± 7.2; P = 0.001, 3.8 ± 2.0 and 3.0 ± 1.6; P = 0.001, 3.3 ± 2.2 and 1.0 ± 1.2; P = 0.001, and 2.3 ± 0.6 and 1.5 ± 0.6; P = 0.04, respectively. The sleep disturbances improved in 13 (65%) patients. CONCLUSIONS: Bed head elevation reduced esophageal acid exposure and acid clearance time in nocturnal (supine) refluxers and led to some relief from heartburn and sleep disturbance.

Khan BA; Sodhi JS; Zargar SA; Javid G; Yattoo GN; Shah A; Gulzar GM; Khan MA

2012-06-01

14

Abnormal melatonin secretion in male patients with hypogonadism.  

UK PubMed Central (United Kingdom)

Recently we have demonstrated that melatonin secretion is increased in untreated male patients with GnRH deficiency. Testosterone administration to these patients decreased melatonin secretion to normal levels. These data, however, did not exclude a gonadotropic effect on melatonin secretion. To further elucidate whether gonadal steroids and/or gonadotropins modulate melatonin secretion in humans we compared untreated young males with hypogonadotropic hypogonadism (IGD, n = 6), and hypergonadotropic hypogonadism caused by KlinEfelter's syndrome (KS, n = 11) to normal pubertal male controls (n = 7). KS patients were subdivided into two groups: KS-1, with low testosterone; and KS-2, with normal testosterone levels. Serum samples for melatonin concentrations were obtained every 15 min from 7 PM to 7 AM in a controlled light-dark environment with simultaneous sleep recordings. All KS patients had elevated gonadotropin levels and decreased melatonin levels. Mean (+/- SD) dark-time nocturnal melatonin levels in KS-1 were 92 +/- 21 pmol/L and were 146 +/- 46 pmol/L in KS-2 compared with 178 +/- 64 pmol/L in controls. Integrated nocturnal melatonin secretion values (AUC) were 64 +/- 14 pmol/min x L x 10(3) in KS-1 and 96 +/- 29 pmol/min x L x 10(3) in KS-2 compared with 116 +/- 42 pmol/min x L x 10(3) in controls. All IGD patients had low gonadotropin and testosterone levels. Their dark-time melatonin levels (286 +/- 26 pmol/L) and the AUC values (184 +/- 15 pmol/min/L x 10(3)) were increased. These data indicate that melatonin secretion is increased in male patients with GnRH deficiency and decreased in low testosterone hypergonadotropic hypogonadal patients. Taken together, our results suggest that both gonadotropins and gonadal steroids modulate melatonin secretion in humans.

Luboshitzky R; Wagner O; Lavi S; Herer P; Lavie P

1996-01-01

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Melatonin effects on luteinizing hormone in postmenopausal women: a pilot clinical trial NCT00288262  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background In many mammals, the duration of the nocturnal melatonin elevation regulates seasonal changes in reproductive hormones such as luteinizing hormone (LH). Melatonin's effects on human reproductive endocrinology are uncertain. It is thought that the same hypothalamic pulse generator may both trigger the pulsatile release of GnRH and LH and also cause hot flashes. Thus, if melatonin suppressed this pulse generator in postmenopausal women, it might moderate hot flashes. This clinical trial tested the hypothesis that melatonin could suppress LH and relieve hot flashes. Methods Twenty postmenopausal women troubled by hot flashes underwent one week of baseline observation followed by 4 weeks of a randomized controlled trial of melatonin or matched placebo. The three randomized treatments were melatonin 0.5 mg 2.5–3 hours before bedtime, melatonin 0.5 mg upon morning awakening, or placebo capsules. Twelve of the women were admitted to the GCRC at baseline and at the end of randomized treatment for 24-hour sampling of blood for LH. Morning urine samples were collected twice weekly to measure LH excretion. Subjective responses measured throughout baseline and treatment included sleep and hot flash logs, the CESD and QIDS depression self-ratings, and the SAFTEE physical symptom inventory. Results Urinary LH tended to increase from baseline to the end of treatment. Contrasts among the 3 randomized groups were statistically marginal, but there was relative suppression combining the groups given melatonin as contrasted to the placebo group (p Conclusion The data are consistent with the hypothesis that melatonin suppresses LH in postmenopausal women. An effect related to the duration of nocturnal melatonin elevation is suggested. Effects of melatonin on reproductive endocrinology should be studied further in younger women and in men. Larger studies of melatonin effects on postmenopausal symptoms would be worthwhile.

Kripke Daniel F; Kline Lawrence E; Shadan Farhad F; Dawson Arthur; Poceta J Steven; Elliott Jeffrey A

2006-01-01

16

Occurrence, diel patterns, and the influence of melatonin on the photosynthetic performance of cultured Symbiodinium.  

UK PubMed Central (United Kingdom)

Dinoflagellata is the earliest phylum in which true circadian regulation of melatonin rhythms has been convincingly demonstrated. Here, diel profiling of melatonin in a cultured member of this phylum belonging to the genus Symbiodinium indicated that melatonin levels oscillate with significant nocturnal peaks. However, unlike in other previously studied dinoflagellate species, the diel rhythmicity of melatonin in Symbiodinium did not persist under constant dark conditions. Thus, the oscillating pattern of melatonin in Symbiodinium is presumed not to be driven by endogenous circadian control of melatonin production, but rather by changes in the daily photocycle, most likely through a mechanism involving the enhanced photo-consumption of melatonin by free radicals. Although direct interactions of melatonin with detrimental radicals have been previously studied in several basal species, including dinoflagellates, none of these investigations addressed the effects that this molecule may have on photosynthesis, a major source of radical species in unicellular algae. In the present work, real-time monitoring of oxygen evolution in Symbiodinium cultures indicated a significant decrease in photosynthesis rates upon treatment with various doses of melatonin. Analyses of chlorophyll a fluorescence and xanthophyll cycle activity confirmed this effect and further revealed that this slowdown may occur through an enhanced engagement of photoprotective mechanisms in melatonin-treated cells. These findings are of great importance as they demonstrate that in certain photoautotroph species, the interactions of elevated melatonin levels with photosynthesis may extend beyond the general purpose of antioxidant protection.

Roopin M; Yacobi YZ; Levy O

2013-01-01

17

Occurrence, diel patterns, and the influence of melatonin on the photosynthetic performance of cultured Symbiodinium.  

Science.gov (United States)

Dinoflagellata is the earliest phylum in which true circadian regulation of melatonin rhythms has been convincingly demonstrated. Here, diel profiling of melatonin in a cultured member of this phylum belonging to the genus Symbiodinium indicated that melatonin levels oscillate with significant nocturnal peaks. However, unlike in other previously studied dinoflagellate species, the diel rhythmicity of melatonin in Symbiodinium did not persist under constant dark conditions. Thus, the oscillating pattern of melatonin in Symbiodinium is presumed not to be driven by endogenous circadian control of melatonin production, but rather by changes in the daily photocycle, most likely through a mechanism involving the enhanced photo-consumption of melatonin by free radicals. Although direct interactions of melatonin with detrimental radicals have been previously studied in several basal species, including dinoflagellates, none of these investigations addressed the effects that this molecule may have on photosynthesis, a major source of radical species in unicellular algae. In the present work, real-time monitoring of oxygen evolution in Symbiodinium cultures indicated a significant decrease in photosynthesis rates upon treatment with various doses of melatonin. Analyses of chlorophyll a fluorescence and xanthophyll cycle activity confirmed this effect and further revealed that this slowdown may occur through an enhanced engagement of photoprotective mechanisms in melatonin-treated cells. These findings are of great importance as they demonstrate that in certain photoautotroph species, the interactions of elevated melatonin levels with photosynthesis may extend beyond the general purpose of antioxidant protection. PMID:23496383

Roopin, Modi; Yacobi, Yosef Z; Levy, Oren

2013-01-30

18

Elevation of plasma basic fibroblast growth factor after nocturnal hypoxic events in patients with obstructive sleep apnea syndrome.  

UK PubMed Central (United Kingdom)

Obstructive sleep apnea syndrome (OSAS) is associated with recurrent nocturnal hypoxia during sleep; this hypoxia has been implicated in the pathogenesis of cardiovascular complication. However, a useful soluble factor that is sensitively correlated with OSAS severity for the diagnosis remains unidentified. We hypothesized that systemic levels of basic fibroblast growth factor (bFGF), a hypoxia-induced cytokine, were affected by nocturnal hypoxemia in OSAS patients, and we assessed whether the degree of change in the plasma bFGF concentrations before and after nocturnal hypoxia is correlated with the severity of OSAS. Thirty subjects who had suspected OSAS and had been investigated by nocturnal polysomnography (PSG) were enrolled. Plasma bFGF and vascular endothelial growth factor (VEGF) concentrations the night before PSG and the next morning were measured by sandwich enzyme-linked immunosorbent assay. Correlations between the changes in these factors and hypoxia-associated parameters for OSAS severity were analyzed. Patients with OSAS had significantly elevated levels of plasma bFGF but not VEGF and hemoglobin after rising. The degree of change in bFGF concentrations after nocturnal apnea episodes was significantly correlated with diagnostic parameters for OSAS severity. The change in plasma bFGF levels is associated with the degree of hypoxic state in OSAS patients, implying that bFGF might be a useful soluble factor for evaluating OSAS severity.

Hirata Y; Nabekura T; Maruyama H; Aonuma K; Satoh M

2013-12-01

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Effects of naphthalene, beta-naphthoflavone and benzo(a)pyrene on the diurnal and nocturnal indoleamine metabolism and melatonin content in the pineal organ of rainbow trout, Oncorhynchus mykiss.  

UK PubMed Central (United Kingdom)

Polycyclic aromatic hydrocarbons (PAHs) have deleterious effects on neuroendocrine systems in teleost fish affecting, among other processes, reproductive function or stress responses. The hormone melatonin, mainly produced in the pineal organ of vertebrates, is involved in the regulation of biological rhythms as well as other important functions, and may also act as an antioxidant molecule. The effects of environmental pollutants on the endocrine and metabolic activity of the pineal organ have been studied only in mammals. We here evaluate the effects of the PAHs naphthalene (NAP) and benzo(a)pyrene (BaP) and the flavonoid beta-naphthoflavone (BNF) on the pineal organ of rainbow trout by quantifying the diurnal and nocturnal pineal content of some indoles and methoxyindoles, including melatonin. NAP mainly induced diurnal increases in the pineal content of melatonin and other methoxyindoles like 5-methoxytryptamine (5-MT), 5-methoxyindole-3-acetic acid (5-MIAA) or 5-methoxytryptophol (5-MTOL). Those increases did not occur at night, when even occasional decreases were observed compared with controls. NAP also induced some diurnal and nocturnal decreases in the levels of indolic compounds like serotonin (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA), while pineal content of 5-hydroxytryptophan (5-HTP) was first decreased (few hours after injection) and then increased (few days after injection) during the day. BaP and BNF induced strong increases in diurnal levels of melatonin, whereas other pineal compounds were unaffected. It seems that an increase of the methylation capacity of the pineal organ takes place during the day, and a decrease occurs at night. Those effects could be mediated by changes in the activity of key enzymes involved in pineal melatonin biosynthesis, maybe as a result of the alteration of the cellular phototransduction mechanisms involved in the light-induced inhibition of melatonin synthesis in the pineal photoreceptor cells. These results demonstrate for the first time that environmental pollutants can disrupt the activity of the pineal organ of teleost fish. This disruption could be a threat for the survival of the animals in their natural environment, although the increases observed in melatonin levels could play a relevant role as a toxicity-protection factor.

Gesto M; Tintos A; Rodríguez-Illamola A; Soengas JL; Míguez JM

2009-04-01

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Daily pattern of melatonin secretion in an antarctic bird, the emperor penguin, Aptenodytes forsteri: seasonal variations, effect of constant illumination and of administration of isoproterenol or propranolol.  

UK PubMed Central (United Kingdom)

Daily variations in circulating melatonin concentrations have been measured at monthly intervals from April to December 1986 in an Antarctic bird, the emperor penguin, Aptenodytes forsteri, maintained under natural conditions. Both duration of the elevated nighttime melatonin levels and amplitude of the day-night rhythm displays an annual variation closely related to variations in the daylength. Duration of the nocturnal peak of melatonin secretion depended upon the duration of the darkness, decreasing with increasing daylength and disappearing completely during the summer solstice. The duration of the nighttime melatonin peak melatonin increased inversely with decreasing daylength. The amplitude of the day-night rhythm decreased in such a way that the nocturnal peak of melatonin completely disappeared during the winter solstice. Three days of constant illumination in September did not suppress the nighttime peak of melatonin secretion. The response of melatonin secretion, decreasing after beta-adrenergic agonist treatment and increasing after antagonist treatment, reinforces the hypothesis that in birds the regulation of melatonin synthesis differs from that of the rat. Receptors other than beta receptors may be involved.

Miché F; Vivien-Roels B; Pévet P; Spehner C; Robin JP; Le Maho Y

1991-11-01

 
 
 
 
21

Melatonin secretion in children with epilepsy.  

Science.gov (United States)

This study examined melatonin (MLT) system in children with epilepsy. Diurnal patterns of salivary MLT, urinary metabolite 6-sulphatoxymelatonin, core body temperature, pulse and blood pressure were measured in 51 children with epilepsy (6.6-17.9 years) and 29 comparison children (5.5-17.3 years). The children with epilepsy preserved MLT and other circadian rhythms. In nine children with epilepsy (17.6%), peak salivary MLT concentrations were very high. There were no associations between MLT secretion/excretion parameters (diurnal profile, peak nocturnal concentrations, area under the time curve, duration of elevated concentrations, acrophase) and seizure characteristics (time, type of seizures, antiepileptic medications). The study observations are important for understanding of the MLT system in epilepsy and for exploring the potential for seizure treatment with melatonin. PMID:23103303

Praninskiene, Ruta; Dumalakiene, Irena; Kemezys, Robertas; Mauricas, Mykolas; Jucaite, Aurelija

2012-10-24

22

Melatonin secretion in children with epilepsy.  

UK PubMed Central (United Kingdom)

This study examined melatonin (MLT) system in children with epilepsy. Diurnal patterns of salivary MLT, urinary metabolite 6-sulphatoxymelatonin, core body temperature, pulse and blood pressure were measured in 51 children with epilepsy (6.6-17.9 years) and 29 comparison children (5.5-17.3 years). The children with epilepsy preserved MLT and other circadian rhythms. In nine children with epilepsy (17.6%), peak salivary MLT concentrations were very high. There were no associations between MLT secretion/excretion parameters (diurnal profile, peak nocturnal concentrations, area under the time curve, duration of elevated concentrations, acrophase) and seizure characteristics (time, type of seizures, antiepileptic medications). The study observations are important for understanding of the MLT system in epilepsy and for exploring the potential for seizure treatment with melatonin.

Praninskiene R; Dumalakiene I; Kemezys R; Mauricas M; Jucaite A

2012-11-01

23

Breast cancer therapy based on melatonin.  

UK PubMed Central (United Kingdom)

The usefulness of melatonin and melatoninergic drugs in breast cancer therapy is based on its Selective Estrogen Receptor Modulator (SERM) and Selective Estrogen Enzyme Modulator (SEEM) properties. Because of the oncostatic properties of melatonin, its nocturnal suppression by light-at-night (LAN) has been considered a risk-factor for breast cancer. Melatonin's SERM actions include modulation of estrogen-regulated cell proliferation, invasiveness and expression of proteins, growth factors and proto-oncogenes (hTERT, p53, p21, TGF?, E-cadherin, etc.). These actions are observable with physiologic doses of melatonin only in cells expressing ER?, and mediated by MT1 melatonin receptors. Melatonin acts like a SEEM, inhibiting expression and activity of P450 aromatase, estrogen sulfatase and type 1, 17?- hydroxysteroid dehydrogenase, but stimulating that of estrogen sulfotransferase. This double action mechanism (SERM and SEEM), and the specificity for ER? bestows melatonin with potential advantages for breast cancer treatments, associated with other antiestrogenic drugs, and idea already patented. LAN enhances the growth of rat mammary tumors by decreasing or suppressing melatonin production. Epidemiologic studies have also described increased breast cancer risk in women exposed to LAN. Since the strongest suppression of nocturnal melatonin occurs with wavelength light of the blue spectral region, optical and lightening devices filtering the blue light spectrum have been proposed to avoid the risks of light-induced suppression of nocturnal melatonin.

Sanchez-Barcelo EJ; Mediavilla MD; Alonso-Gonzalez C; Rueda N

2012-05-01

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Nocturnal plasma levels of melatonin in quails (Coturnix japonica) injected with l-5-hydroxy-tryptophan/ Níveis plasmáticos noturnos de melatonina em codornas (Coturnix japonica) injetadas com l-5-hidroxi-triptofano  

Scientific Electronic Library Online (English)

Full Text Available Abstract in portuguese Este trabalho objetivou demonstrar a influência da administração sistêmica de l-5-hidroxi-triptofano (L-HTP) sobre os níveis plasmáticos de melatonina durante o período noturno em codornas. Ao longo do período claro, os níveis plasmáticos de melatonina não diferiram significativamente, oscilando entre 110,2 ± 15,8 pg.mL-1 e 157,4 ± 34,8 pg.mL-1, de 8 às 16 horas. L-HTP (25 mg.kg-1, via intracelomática), administrado às 18 horas atenuou signific (more) ativamente a elevação noturna dos níveis plasmáticos de melatonina (controles, 327,3 ± 20,1 e 315,8 ± 20,9 pg.mL-1 vs. 242,1 ± 24,8 e 217,5 ± 21 pg.mL-1, respectivamente, às 20 e 24 horas, P Abstract in english This study aimed to demonstrate the influence of the systemic administration of l-5-hydroxy-tryptophan (L-HTP) on the plasma levels of melatonin during the dark period in quails. Throughout daylight, the plasma levels of melatonin did not differ significantly, oscillating between 110.2 ± 15.8 pg.mL-1 and 157.4 ± 34.8 pg.mL-1, from 8 to 16 hours. L-HTP (25 mg.kg-1, through the intracelomic route) administered at 18 hours lessened significantly the nocturnal i (more) ncrease of the plasma levels of melatonin (controls, 327.3 ± 20.1 and 315.8 ± 20.9 pg.mL-1 vs. 242.1 ± 24.8 and 217.5 ± 21 pg.mL-1, respectively, at 20 and 24 hours, P

Reis, LC.; Almeida, AC.; Ribeiro, MC.; Polo, PA.; Olivares, EL.; Medeiros, MA.; Nonaka, KO.; Castilhos, LR.

2007-05-01

25

Melatonin and LH secretion patterns in pubertal boys  

International Nuclear Information System (INIS)

Plasma melatonin and LH were measured at 20 minute intervals for 24 hours in four normal pubertal boys. All four subjects showed a significant augmentation of LH and melatonin during nocturnal sleep. There was also a significant correlation between the LH and melatonin levels (p

1979-01-01

26

Direct effect of elevated CO{sub 2} on nocturnal in situ leaf respiration in nine temperate deciduous tree species is small  

Energy Technology Data Exchange (ETDEWEB)

The short-term effects of elevated carbon dioxide concentration in nocturnal leaf respiration rate were measured in nine deciduous tree species. Measurements included alternating 400 and 800 ppm carbon dioxide over a 3.5 to 4.0 hour period on 20 separate occasions. Results showed a small increase in nocturnal leaf respiration rate (median response to 400 ppm CO{sub 2} showed 1.5 per cent decrease in respiration rate, with responses ranging from 5.6 per cent inhibition to a 0.4 per cent stimulation). Moreover, the direct effects of elevated carbon dioxide concentration were similar among the nine species, which suggests that the small variation in nocturnal respiration rate to short-term increase in carbon dioxide was of no practical significance to the accuracy of measurements of respiration rates. Extrapolating from these results, it was concluded that the respiratory responses of leaves to elevated carbon dioxide concentrations would have little, if any, effect on the carbon balance of temperate deciduous forests. 28 refs., 1 tab., 1 fig.

Amthor, J. S. [Oak Ridge National Laboratory, Environmental Sciences Div., Oak Ridge, TN (United States)

2000-01-01

27

The Achilles Heel in Melatonin: Asthma  

Directory of Open Access Journals (Sweden)

Full Text Available Asthma is a clinical syndrome characterized by chronic airway inflammation, airway responsiveness, and expiratory airflow limitation. Nocturnal symptoms and decreases in lung function are common aspects of the asthma clinical syndrome. Nocturnal symptoms also appear to be associated with asthma-related mortality.In addition to its importance to the regulation of human circadian rhythms, an accumulating body of evidence also suggests that melatonin is also involved in the regulation of smooth muscle tone. For this reason, this study aimed to evaluate contraction and relaxation responses in tracheal smooth muscle rings obtained from rats treated with melatonin.Following administration of melatonin (50mg/kg/day) at the same time every day for 6 weeks, in vitro organ bath experiments were performed with rat tracheal preparations exposed to contractile (acetycholine and serotonin) and relaxant (theophylline and papaverine) agents. Melatonin treatment strengthened contraction responses, but did not affect relaxation responses in rat tracheal preparations. We think that melatonin might play a role in the pathogenesis of nocturnal asthma.Therefore, clinicians should be aware of the importance of melatonin to nocturnal exacerbation of asthma symptoms and alert asthmatic patients that use exogenous melatonin supplementation of its potential negative effects.

Edibe Karasu-Minareci; Yasemin Kaya; Fatos Belgin Yildirim

2012-01-01

28

Experimental models of melatonin-deficient hypertension.  

UK PubMed Central (United Kingdom)

Melatonin secreted by the pineal gland plays an important role in the regulation of blood pressure (BP) and its administration reduces hypertension both in animals and humans. There are two experimental models of melatonin-deficient hypertension: one induced by pinealectomy and another by continuous 24 hour exposure to light. Both models cause melatonin deficiency and prevent darkness-mediated nocturnal melatonin secretion and are associated with increased BP and myocardial, vascular and renal dysfunction. These models also lead to neurohumoral activation of the renin-angiotensin system, sympathetic nervous system, adrenocorticotrophin-glucocorticoid axis and cause insulin resistance. Together, these alterations contribute to rise in blood pressure by vasoconstrictive or circulatory fluid volume overload. The light induced hypertension model mimics the melatonin deficiency in patients with insufficient nocturnal BP decline, in those who have night shift or who are exposed to environmental light pollution. For this reason, this model is useful in development of anti-hypertensive drugs.

Simko F; Reiter RJ; Pechanova O; Paulis L

2013-01-01

29

Human melatonin during continuous magnetic field exposure  

Energy Technology Data Exchange (ETDEWEB)

This report describes the third in a series of double-blind, laboratory-based studies that were aimed at determining the effects of nocturnal exposure to power frequency magnetic fields on blood levels of melatonin in human volunteers. The two earlier studies evaluated effects on melatonin of intermittent exposure to 60 Hz circularly polarized magnetic fields at 10 and 200 mG. No overall effects on melatonin levels were found. In the present study, men were exposed continuously rather than intermittently through the night to the same 200 mG magnetic field condition that was used previously; again, no overall effects on melatonin levels were found. The authors conclude that the intermittent and continuous exposure conditions used in the laboratory to date are not effective in altering nocturnal blood levels of melatonin in human volunteers.

Graham, C.; Cook, M.R.; Riffle, D.W. [Midwest Research Inst., Kansas City, MO (United States)

1997-05-01

30

Nocturnal polysomnographic sleep across the menstrual cycle in premenstrual dysphoric disorder.  

UK PubMed Central (United Kingdom)

OBJECTIVES: Women with premenstrual dysphoric disorder (PMDD) experience disturbed mood, altered melatonin circadian rhythms, and frequent reports of insomnia during the luteal phase (LP) of their menstrual cycle. In this study we aimed to investigate nocturnal polysomnographic (PSG) sleep across the menstrual cycle in PMDD women and controls. METHODS: Seven PMDD women who indicated insomnia during LP, and five controls, spent every third night throughout a complete menstrual cycle sleeping in the laboratory. RESULTS: In PMDD and controls progesterone and core body temperature (BT(core)) were elevated during LP compared to the follicular phase (FP). Stage 2 sleep showed a significant main effect of menstrual phase and was significantly increased during mid-LP compared to early-FP in both groups. Rapid eye movement (REM) sleep for both groups was decreased during early-LP compared to early-FP. Slow wave sleep (SWS) was significantly increased, and melatonin significantly decreased, in PMDD women compared to controls. CONCLUSIONS: PMDD women who experience insomnia during LP had decreased melatonin secretion and increased SWS compared to controls. The sleep and melatonin findings in PMDD women may be functionally linked. Results also suggest an altered homeostatic regulation of the sleep-wake cycle in PMDD, perhaps implicating melatonin in the homeostatic process of sleep-wake regulation.

Shechter A; Lespérance P; Ng Ying Kin NM; Boivin DB

2012-09-01

31

Nocturnal Asthma  

Science.gov (United States)

... Medical Director, Health Initiatives View full profile Nocturnal Asthma Worsening of asthma at night, or nocturnal asthma, ... View Daily Pollen Count Receive Health-e-News Asthma Programs At National Jewish Health, we offer a ...

32

Non-vertebrate melatonin.  

UK PubMed Central (United Kingdom)

Melatonin has been detected in bacteria, eukaryotic unicells, macroalgae, plants, fungi and various taxa of invertebrates. Although precise determinations are missing in many of these organisms and the roles of melatonin are still unknown, investigations in some species allow more detailed conclusions. Non-vertebrate melatonin is not necessarily circadian, and if so, not always peaking at night, although nocturnal maxima are frequently found. In the cases under study, the major biosynthetic pathway is identical with that of vertebrates. Mimicking of photoperiodic responses and concentration changes upon temperature decreases have been studied in more detail only in dinoflagellates. In plants, an involvement in photoperiodism seems conceivable but requires further support. No stimulation of flowering has been demonstrated to date. A participation in antioxidative protection might be possible in many aerobic non-vertebrates, although evidence for a contribution at physiological levels is mostly missing. Protection from stress by oxidotoxins or/and extensions of lifespan have been shown in very different organisms, such as the dinoflagellate Lingulodinium, the ciliate Paramecium, the rotifer Philodina and Drosophila. Melatonin can be taken up from the food, findings with possible implications in ecophysiology as well as for human nutrition and, with regard to high levels in medicinal plants, also in pharmacology.

Hardeland R; Poeggeler B

2003-05-01

33

Non-vertebrate melatonin.  

Science.gov (United States)

Melatonin has been detected in bacteria, eukaryotic unicells, macroalgae, plants, fungi and various taxa of invertebrates. Although precise determinations are missing in many of these organisms and the roles of melatonin are still unknown, investigations in some species allow more detailed conclusions. Non-vertebrate melatonin is not necessarily circadian, and if so, not always peaking at night, although nocturnal maxima are frequently found. In the cases under study, the major biosynthetic pathway is identical with that of vertebrates. Mimicking of photoperiodic responses and concentration changes upon temperature decreases have been studied in more detail only in dinoflagellates. In plants, an involvement in photoperiodism seems conceivable but requires further support. No stimulation of flowering has been demonstrated to date. A participation in antioxidative protection might be possible in many aerobic non-vertebrates, although evidence for a contribution at physiological levels is mostly missing. Protection from stress by oxidotoxins or/and extensions of lifespan have been shown in very different organisms, such as the dinoflagellate Lingulodinium, the ciliate Paramecium, the rotifer Philodina and Drosophila. Melatonin can be taken up from the food, findings with possible implications in ecophysiology as well as for human nutrition and, with regard to high levels in medicinal plants, also in pharmacology. PMID:12662344

Hardeland, Rüdiger; Poeggeler, Burkhard

2003-05-01

34

Dietary factors and fluctuating levels of melatonin  

Directory of Open Access Journals (Sweden)

Full Text Available Melatonin is secreted principally by the pineal gland and mainly at nighttime. The primary physiological function is to convey information of the daily cycle of light and darkness to the body. In addition, it may have other health-related functions. Melatonin is synthesized from tryptophan, an essential dietary amino acid. It has been demonstrated that some nutritional factors, such as intake of vegetables, caffeine, and some vitamins and minerals, could modify melatonin production but with less intensity than light, the most dominant synchronizer of melatonin production. This review will focus on the nutritional factors apart from the intake of tryptophan that affect melatonin levels in humans. Overall, foods containing melatonin or promoting the synthesis of it by impacting the availability of tryptophan, as well those containing vitamins and minerals which are needed as co-factors and activators in the synthesis of melatonin, may modulate the levels of melatonin. Even so, the influence of daytime diet on the synthesis of nocturnal melatonin is limited, however, the influence of the diet seems to be more obvious on the daytime levels.

Katri Peuhkuri; Nora Sihvola; Riitta Korpela

2012-01-01

35

Dietary factors and fluctuating levels of melatonin.  

UK PubMed Central (United Kingdom)

Melatonin is secreted principally by the pineal gland and mainly at nighttime. The primary physiological function is to convey information of the daily cycle of light and darkness to the body. In addition, it may have other health-related functions. Melatonin is synthesized from tryptophan, an essential dietary amino acid. It has been demonstrated that some nutritional factors, such as intake of vegetables, caffeine, and some vitamins and minerals, could modify melatonin production but with less intensity than light, the most dominant synchronizer of melatonin production. This review will focus on the nutritional factors apart from the intake of tryptophan that affect melatonin levels in humans. Overall, foods containing melatonin or promoting the synthesis of it by impacting the availability of tryptophan, as well those containing vitamins and minerals which are needed as co-factors and activators in the synthesis of melatonin, may modulate the levels of melatonin. Even so, the influence of daytime diet on the synthesis of nocturnal melatonin is limited, however, the influence of the diet seems to be more obvious on the daytime levels.

Peuhkuri K; Sihvola N; Korpela R

2012-01-01

36

Seasonal Patterns of Melatonin, Cortisol, and Progesterone Secretion in Female Lambs Raised Beneath a 500-kV Transmission Line.  

Energy Technology Data Exchange (ETDEWEB)

Although several kinds of biological effects of electric and magnetic fields have been reported from laboratory studies, few have been independently replicated. When this study was being planned, the suppression of nighttime melatonin in rodents was thought to represent one of the strongest known effects of these fields. The effect had been replicated by a single laboratory for 60-Hz electric fields, and by multiple laboratories for d-c magnetic fields. The primary objective of this study was to determine whether the effect of electric and magnetic fields on melatonin would also occur in sheep exposed to a high voltage transmission line. The specific hypothesis tested by this experiment was as follows: The electrical environment produced by a 60-Hz, 500-kV transmission line causes a depression in nocturnal melatonin in chronically exposed female lambs. This may mimic effects of pinealectomy or constant long-day photoperiods, thus delaying the onset of reproductive cycles. Results of the study do not provide evidence to support the hypothesis. Melatonin concentrations in the sheep exposed to the transmission line showed the normal pattern of low daytime and high nighttime serum levels. As compared to the control group, there were no statistically significant group differences in the mean amplitude, phase, or duration of the nighttime melatonin elevation.

Lee, Jack M.

1992-06-01

37

Agomelatine, melatonin and depressive disorder.  

Science.gov (United States)

Alteration of nocturnal melatonin production, along with circadian rhythm disturbance, has been demonstrated in several psychiatric disorders. It has been postulated that such disturbances might be causal reflecting a more fundamental abnormality of the function of the suprachiasmatic nucleus (SCN). The SCN contains the body's master 'clock' while the pineal-SCN nexus is intricate to the nighttime production of melatonin. The more compelling case for causality is made for major depressive disorder (MDD). Lending weight to this proposition is the introduction of agomelatine as an antidepressant agent. Through its actions on melatonin receptors agomelatine can resynchronise circadian rhythms. The circadian hypothesis would posit that normalisation of disturbance would be sufficient of itself to alleviate the symptoms of MDD. Thus, strategies designed to bring about resynchronisation of circadian rhythms should be therapeutically effective in depression. Critical examination of the efficacy of such interventions in MDD suggests that the circadian alteration may be necessary but is not sufficient for an antidepressant effect. Exogenous melatonin administration and bright light therapy have mixed results in limited controlled clinical evaluations. Furthermore, agomelatine has other actions which pre-clinical studies suggest are as important to its therapeutic effects as are its actions on melatonin receptors ipso facto its resynchronising properties. Whether circadian effects are antidepressant remains a moot point and awaits the clinical evaluation of highly selective resynchronising agents. PMID:23484857

Norman, Trevor R

2013-04-01

38

Agomelatine, melatonin and depressive disorder.  

UK PubMed Central (United Kingdom)

Alteration of nocturnal melatonin production, along with circadian rhythm disturbance, has been demonstrated in several psychiatric disorders. It has been postulated that such disturbances might be causal reflecting a more fundamental abnormality of the function of the suprachiasmatic nucleus (SCN). The SCN contains the body's master 'clock' while the pineal-SCN nexus is intricate to the nighttime production of melatonin. The more compelling case for causality is made for major depressive disorder (MDD). Lending weight to this proposition is the introduction of agomelatine as an antidepressant agent. Through its actions on melatonin receptors agomelatine can resynchronise circadian rhythms. The circadian hypothesis would posit that normalisation of disturbance would be sufficient of itself to alleviate the symptoms of MDD. Thus, strategies designed to bring about resynchronisation of circadian rhythms should be therapeutically effective in depression. Critical examination of the efficacy of such interventions in MDD suggests that the circadian alteration may be necessary but is not sufficient for an antidepressant effect. Exogenous melatonin administration and bright light therapy have mixed results in limited controlled clinical evaluations. Furthermore, agomelatine has other actions which pre-clinical studies suggest are as important to its therapeutic effects as are its actions on melatonin receptors ipso facto its resynchronising properties. Whether circadian effects are antidepressant remains a moot point and awaits the clinical evaluation of highly selective resynchronising agents.

Norman TR

2013-04-01

39

MELATONIN: POTENTIAL UTILITY FOR IMPROVING PUBLIC HEALTH  

Directory of Open Access Journals (Sweden)

Full Text Available This review summarizes the beneficial actions of melatonin in various experimental conditions/diseases and identifies where the use of melatonin may be helpful in improving public health. The nightly use of melatonin supplements by humans often improves their sleep and helps correct the circadian dyssynchronization associated with “jet lag”. Additionally, melatonin has been found effective in curtailing the growth of a variety of experimental cancers. Mechanistically, this is achieved by melatonin’s ability to limit fatty acid uptake, especially linoleic acid, by tumor cells. Fatty acids are growth factors for many tumors. Additionally, melatonin inhibits the elevated telomerase activity of tumor cells thus making them more fragile and vulnerable to chemotherapies. Melatonin also may inhibit angiogenesis in tumors by suppressing endothelin-1 production and the indole interferes with the stimulatory action of steroids on hormone-responsive tumors. As an ubiquitously-acting antioxidant, melatonin reduces cardiac damage during ischemia/reperfusion (I/R) injury (heart attack) and during I/R to the brain (stroke). Melatonin also limits the toxicity of amyloid ? peptide and of neurofibrillary tangles, two of the cardinal signs of Alzheimer’s disease. Collectively, these data suggest supplementation with melatonin, whose endogenous levels decrease with age, may improve the quality of life in the aged and, as a consequence, be beneficial for public health generally. [TAF Prev Med Bull 2006; 5(2.000): 131-158

Russel J REITER; Fatih GULTEKIN; Luis J FLORES; Ma Pilar TERRON; Dun-Xian TAN

2006-01-01

40

Melatonin as a free radical scavenger in the ovarian follicle.  

UK PubMed Central (United Kingdom)

This review summarizes new findings related to beneficial effects of melatonin (N-acetyl-5-methoxytryptamine) on reproductive physiology. Recently many researchers have begun to study the local role of melatonin as an antioxidant. We focused on intra-follicular role of melatonin in the ovary. Melatonin, secreted by the pineal gland, is taken up into the follicular fluid from the blood. Reactive oxygen species (ROS) are produced within the follicles, during the ovulatory process. Melatonin reduces oxidative stress as an antioxidant, and contribute to oocyte maturation, embryo development and luteinization of granulosa cells. Our clinical study demonstrated that melatonin treatment for infertile women increases intra-follicular melatonin concentrations, reduces intra-follicular oxidative damage, and elevates fertilization and pregnancy rates. Melatonin treatment also improves progesterone production by corpus luteum in infertile women with luteal phase defect. Melatonin treatment could become a new cure for improving oocyte quality and luteal function in infertile women.

Tamura H; Takasaki A; Taketani T; Tanabe M; Kizuka F; Lee L; Tamura I; Maekawa R; Asada H; Yamagata Y; Sugino N

2013-01-01

 
 
 
 
41

Melatonin secretion and metabolism in patients with hepatic encephalopathy.  

UK PubMed Central (United Kingdom)

BACKGROUND AND AIM: The rhythm of melatonin secretion and its blood level changes in cirrhotic patients, but the causes of these alterations have not been sufficiently appreciated. The aim of study was to estimate the dependence between melatonin secretion and metabolism and the severity of hepatic encephalopathy. METHODS: The study included 75 alcoholic cirrhotic patients (A, B, C) with hepatic insufficiency and 25 healthy subjects (group K). Three groups of patients were identified, 25 patients each, with grade 1, 2, and 3 hepatic encephalopathy according to West-Haven Scale. Immunoenzymatic method was used to measure serum melatonin (at 02:00?h and 09:00?h) level and 6-sulfatoxymelatonin (6-HMS) excretion in the urine (during night and day). RESULTS: Nocturnal serum melatonin levels (pg/mL) in groups were: K-57.1?±?11.4, A-38.5?±?11.2, B-53.4?±?17.9, C-79.5?±?27.9 (P?melatonin and ammonia levels in all groups was found. CONCLUSIONS: The elevated melatonin blood levels both at night and day may account for some of the clinical manifestations of hepatic encephalopathy (daytime sleepiness, fatigue).

Chojnacki C; Wachowska-Kelly P; B?asiak J; Reiter RJ; Chojnacki J

2013-02-01

42

Nocturnal Animals  

Science.gov (United States)

Over time, human beings have blazed their way into the night with fire and artificial light, but we are not true creatures of the night. This Topic in Depth explores the world of nocturnal animals. From Island Discovery & Training, the first site allows visitors to listen to the sounds of several nocturnal animals. After guessing who made the sound, visitors can link to information pages for all but one of the mystery animals (1). Next is an information sheet (2) from BioMedia that answers the question: How Do Animals See In the Dark? The third site, from Enchanted Learning, provides coloring sheets and brief profiles for many nocturnal animals including the Amur Tiger, Badger, Crocodile, and Kinkajou-just to name a few (3). From the Fairbanks Museum & Planetarium in Vermont, the fourth website contains a six-page lesson plan (for students in grades one to eight) emphasizing different senses; and the roles and adaptations of nocturnal species (4). The fifth site, from Science News Online, contains an article addressing research on the ecological impact of artificial nighttime light on nocturnal animals (5). From Wild Asia, the next site contains an article by travel writer and environmental educator David Bowden, that describes his experience watching a marine turtle lay her eggs on Malaysia's Turtle Island (6). The seventh site, from PBS-Nova Online, briefly describes the work of zoologists who study nocturnal and burrowing animals of the Kalahari (7). From this site visitors can also link to a section that discusses how several different animals see at night. The final site, from the University of Utah-John Moran Eye Center, contains information about the role of photoreceptors in vision (8). This Photoreceptors section is part of a comprehensive electronic tutorial regarding neural organization of the mammalian retina.

43

Thermoregulatory effects of melatonin in relation to sleepiness.  

UK PubMed Central (United Kingdom)

Thermoregulatory processes have long been implicated in the initiation of human sleep. In this paper, we review our own studies conducted over the last decade showing a crucial role for melatonin as a mediator between the thermoregulatory and arousal system in humans. Distal heat loss, via increased skin temperature, seems to be intimately coupled with increased sleepiness and sleep induction. Exogenous melatonin administration during the day when melatonin is essentially absent mimics the endogenous thermophysiological processes occurring in the evening and induces sleepiness. Using a cold thermic challenge test, it was shown that melatonin-induced sleepiness occurs in parallel with reduction in the thermoregulatory set-point (threshold); thus, melatonin may act as a circadian modulator of the thermoregulatory set-point. In addition, an orthostatic challenge can partially block the melatonin-induced effects, suggesting an important role of the sympathetic nervous system as a link between the thermoregulatory and arousal systems. A topographical analysis of finger skin temperature with infrared thermometry revealed that the most distal parts of the fingers, i.e., fingertips, represent the important skin regions for heat loss regulation, most probably via opening the arteriovenous anastomoses, and this is clearly potentiated by melatonin. Taken together, melatonin is involved in the fine-tuning of vascular tone in selective vascular beds, as circulating melatonin levels rise and fall throughout the night. Besides the role of melatonin as "nature's soporific", it can also serve as nature's nocturnal vascular modulator.

Kräuchi K; Cajochen C; Pache M; Flammer J; Wirz-Justice A

2006-01-01

44

Thermoregulatory effects of melatonin in relation to sleepiness.  

Science.gov (United States)

Thermoregulatory processes have long been implicated in the initiation of human sleep. In this paper, we review our own studies conducted over the last decade showing a crucial role for melatonin as a mediator between the thermoregulatory and arousal system in humans. Distal heat loss, via increased skin temperature, seems to be intimately coupled with increased sleepiness and sleep induction. Exogenous melatonin administration during the day when melatonin is essentially absent mimics the endogenous thermophysiological processes occurring in the evening and induces sleepiness. Using a cold thermic challenge test, it was shown that melatonin-induced sleepiness occurs in parallel with reduction in the thermoregulatory set-point (threshold); thus, melatonin may act as a circadian modulator of the thermoregulatory set-point. In addition, an orthostatic challenge can partially block the melatonin-induced effects, suggesting an important role of the sympathetic nervous system as a link between the thermoregulatory and arousal systems. A topographical analysis of finger skin temperature with infrared thermometry revealed that the most distal parts of the fingers, i.e., fingertips, represent the important skin regions for heat loss regulation, most probably via opening the arteriovenous anastomoses, and this is clearly potentiated by melatonin. Taken together, melatonin is involved in the fine-tuning of vascular tone in selective vascular beds, as circulating melatonin levels rise and fall throughout the night. Besides the role of melatonin as "nature's soporific", it can also serve as nature's nocturnal vascular modulator. PMID:16687320

Kräuchi, Kurt; Cajochen, Christian; Pache, Mona; Flammer, Josef; Wirz-Justice, Anna

2006-01-01

45

Nocturnal enuresis.  

UK PubMed Central (United Kingdom)

Nocturnal enuresis (NE) is increasingly seen as part of a heterogeneous phenomenon that at times will include daytime lower urinary tract symptoms such as urgency, frequency and wetting - with reduced bladder storage, usually due to an overactive bladder. In turn, these may be associated with constipation and/or faecal soiling. This paper discusses these considerations in the management of NE.

Harari MD

2013-04-01

46

Homeostatic versus circadian effects of melatonin on core body temperature in humans.  

UK PubMed Central (United Kingdom)

Evidence obtained in animals has suggested a link of the pineal gland and its hormone melatonin with the regulation of core body temperature (CBT). Depending on the species considered, melatonin intervenes in generating seasonal rhythms of daily torpor and hibernation, in heat stress tolerance, and in setting the CBT set point. In humans, the circadian rhythms of melatonin is strictly associated with that of CBT, the nocturnal decline of CBT being inversely related to the rise of melatonin. Whereas there is inconsistent evidence for the suggestion that the decline of CBT may prompt the release of melatonin, conversely, stringent data indicate that melatonin decreases CBT. Administration of melatonin during the day, when it is not normally secreted, decreases CBT by about 0.3 to 0.4 degree C, and suppression of melatonin at night enhances CBT by about the same magnitude. Accordingly, the nocturnal rise of melatonin contributes to the circadian amplitude of CBT. The mechanisms through which melatonin decreases CBT are unclear. It is known that melatonin enhances heat loss, but a reduction of heat production cannot be excluded. Besides actions on peripheral vessels aimed to favor heat loss, it is likely that the effect of melatonin to reduce CBT is exerted mainly in the hypothalamus, where thermoregulatory centers are located. Recent observations have shown that the acute thermoregulatory effects induced by melatonin and bright light are independent of their circadian phase-shifting effects. The effect of melatonin ultimately brings a saving of energy and is reduced in at least two physiological situations: aging and the luteal menstrual phase. In both conditions, melatonin does not exert its CBT-lowering effects. Whereas in older women this effect may represent an age-related alteration, in the luteal phase this modification may represent a mechanism of keeping CBT higher at night to promote a better embryo implantation and survival.

Cagnacci A; Kräuchi K; Wirz-Justice A; Volpe A

1997-12-01

47

Melatonin levels in premenopausal women with fibromyalgia syndrome.  

UK PubMed Central (United Kingdom)

The fibromyalgia syndrome (FMS) is a chronic, widespread pain disorder of unknown etiology. It has been suggest that familial component, environmental factors, endocrine and neurotransmitter alterations, and psychological factors may contribute to the development of FMS. The role of melatonin in FMS is unclear. Some studies describe a lower nocturnal peak and a decreased secretion of melatonin in women with FMS when compared with healthy matched controls. The aim of the present study was to determine the possible role of melatonin in FMS patients. We examined the characteristics and levels of melatonin in 25 consecutive premenopausal women with FMS. Serum blood samples were collected from 25 patients and 20 the age and gender matched healthy controls. Melatonin levels were measured by enzyme-linked immunosorbent assay. Then, the results were compared with those from healthy subjects. Serum melatonin levels of FMS patients were not statistically different from those of controls (P > 0.05). No association was observed between melatonin levels of patients with FMS and disease duration, sleep disturbances, fatigue, and pain scores. Our results demonstrate that melatonin levels were similar in patients with FMS and healthy controls. Further studies are needed to determine the possible role of melatonin.

Senel K; Baygutalp F; Baykal T; Erdal A; Ugur M

2013-06-01

48

Advances in the research of melatonin in autism spectrum disorders: literature review and new perspectives.  

UK PubMed Central (United Kingdom)

Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests.

Tordjman S; Najjar I; Bellissant E; Anderson GM; Barburoth M; Cohen D; Jaafari N; Schischmanoff O; Fagard R; Lagdas E; Kermarrec S; Ribardiere S; Botbol M; Fougerou C; Bronsard G; Vernay-Leconte J

2013-01-01

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Advances in the Research of Melatonin in Autism Spectrum Disorders: Literature Review and New Perspectives  

Directory of Open Access Journals (Sweden)

Full Text Available Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests.

Sylvie Tordjman; Imen Najjar; Eric Bellissant; George M. Anderson; Marianne Barburoth; David Cohen; Nemat Jaafari; Olivier Schischmanoff; Rémi Fagard; Enas Lagdas; Solenn Kermarrec; Sophie Ribardiere; Michel Botbol; Claire Fougerou; Guillaume Bronsard; Julie Vernay-Leconte

2013-01-01

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Agomelatine in the tree shrew model of depression: Effects on stress-induced nocturnal hyperthermia and hormonal status.  

UK PubMed Central (United Kingdom)

The antidepressive drug agomelatine combines the properties of an agonist of melatonergic receptors 1 and 2 with an antagonist of the 5-HT2C receptor. We analyzed the effects of agomelatine in psychosocially stressed male tree shrews, an established preclinical model of depression. Tree shrews experienced daily social stress for a period of 5 weeks and were concomitantly treated with different drugs daily for 4 weeks. The effects of agomelatine (40mg/kg/day) were compared with those of the agonist melatonin (40mg/kg/day), the inverse 5-HT2C antagonist S32006 (10mg/kg/day), and the SSRI fluoxetine (15mg/kg/day). Nocturnal core body temperature (CBT) was recorded by telemetry, and urinary norepinephrine and cortisol concentrations were measured. Chronic social stress induced nocturnal hyperthermia. Agomelatine normalized the CBT in the fourth week of the treatment (T4), whereas the other drugs did not significantly counteract the stress-induced hyperthermia. Agomelatine also reversed the stress-induced reduction in locomotor activity. Norepinephrine concentration was elevated by the stress indicating sympathetic hyperactivity, and was normalized in the stressed animals treated with agomelatine or fluoxetine but not in those treated with melatonin or S32006. Cortisol concentration was elevated by stress but returned to basal levels by T4 in all animals, irrespective of the treatment. These observations show that agomelatine has positive effects to counteract stress-induced physiological processes and to restore the normal rhythm of nocturnal CBT. The data underpin the antidepressant properties of agomelatine and are consistent with a distinctive profile compared to its constituent pharmacological components and other conventional agents.

Schmelting B; Corbach-Söhle S; Kohlhause S; Schlumbohm C; Flügge G; Fuchs E

2013-08-01

51

Seasonal Patterns of Melatonin, Cortisol, and Progesterone Secretion in Female Lambs Raised Beneath a 500-KV Transmission Line  

Science.gov (United States)

There is ongoing controversy about the possibility of adverse biological effects from environmental exposures to electric and magnetic fields. These fields are produced by all electrical equipment and appliances including electrical transmission lines. The objective of this environmental science study was to investigate the possible effects of a high voltage transmission line on domestic sheep (Ovis aries L.), a species that can often be found near such lines. The study was primarily designed to determine whether a specific effect of electric and magnetic fields found in laboratory animals also occurs in livestock under natural environmental conditions. The effect is the ability of fields, at levels found in the environment, to significantly depress the normally high nocturnal concentrations of the pineal hormone-melatonin. Ten female Suffolk lambs were penned for 10 months directly beneath a 500-kV transmission line near Estacada, Oregon. Ten other lambs of the same type were penned in a control area away from the transmission line where electric and magnetic fields were at ambient levels. Serum melatonin was analyzed by radioimmunoassay (RIA) from 6618 blood samples collected at 0.5 to 3-hour intervals over eight 48-hour periods. Serum progesterone was analyzed by RIA from blood samples collected twice weekly. Serum cortisol was also assayed by RIA from the blood samples collected during the 48-hour samples. Results showed that lambs in both the control and line groups had the typical pattern of melatonin secretion consisting of low daytime and high nighttime serum concentrations. There were no statistically significant differences between groups in melatonin levels, or in the phase or duration of the nighttime melatonin elevation. Age at puberty and number of reproductive cycles also did not differ between groups. Serum cortisol showed a circadian rhythm with highest concentrations during the day. There were, however, no differences in cortisol concentrations between groups. Statistical analyses on other biological parameters revealed no differences between groups for body weight gain, wool growth, or behavior.

Lee, Jack Monroe, Jr.

52

Diets enriched with a Jerte Valley cherry-based nutraceutical product reinforce nocturnal behaviour in young and old animals of nocturnal (Rattus norvegicus) and diurnal (Streptopelia risoria) chronotypes.  

UK PubMed Central (United Kingdom)

The decline in melatonin secretion with age seems to be one of the major reasons for increased sleep disruption in older animals. Previously, we showed that the administration with melatonin or its precursor, tryptophan, improved activity/rest rhythms in aged individuals. Here, it was evaluated the effect of a 10-day consumption of a Jerte Valley cherry-based nutraceutical product (patent no. ES2342141B1), which contains high levels of tryptophan, serotonin and melatonin, on the activity/rest rhythms of young and old rats (Rattus norvegicus) and ringdoves (Streptopelia risoria) as representatives of animals with nocturnal and diurnal habits, respectively, and its possible relationship with the serum levels of melatonin and glucose. Total diurnal and nocturnal activity pulses were logged at control, during, and up to 3?days after the treatment. Melatonin and glucose were measured with ELISA and testing kits respectively. In both young and old rats, the intake of the cherry nutraceutical decreased diurnal activity, whereas nocturnal activity increased. The opposite effect was observed for ringdoves. The treatment increased the circulating levels of melatonin in both species and restored the amplitude of the activity rhythm in the old animals to that of the non-treated young groups. The consumption of a Jerte Valley cherry-based nutraceutical product may help to counteract the impaired activity/rest rhythm found in aged animals.

Delgado J; Terrón MP; Garrido M; Pariente JA; Barriga C; Rodríguez AB; Paredes SD

2013-02-01

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Molecular changes underlying reduced pineal melatonin levels in Alzheimer disease: alterations in preclinical and clinical stages.  

UK PubMed Central (United Kingdom)

A disturbed sleep-wake rhythm is common in Alzheimer disease (AD) patients and correlated with decreased melatonin levels and a disrupted circadian melatonin rhythm. Melatonin levels in the cerebrospinal fluid are decreased during the progression of AD neuropathology (as determined by the Braak stages), already in cognitively intact subjects with the earliest AD neuropathology (Braak stages I-II) (preclinical AD). To investigate the molecular mechanisms behind the decreased melatonin levels, we measured monoamines and mRNA levels of enzymes of the melatonin synthesis and its noradrenergic regulation in pineal glands from 18 controls, 33 preclinical AD subjects, and 25 definite AD patients. Pineal melatonin levels were highly correlated with cerebrospinal fluid melatonin levels. The circadian melatonin rhythm disappeared because of decreased nocturnal melatonin levels in both the preclinical AD and AD patients. Also the circadian rhythm of beta(1)-adrenergic receptor mRNA disappeared in both patient groups. The precursor of melatonin, serotonin was stepwise depleted during the course of AD, as indicated by the up-regulated monoamine oxidase A mRNA and activity (5-hydroxyindoleacetic acid:serotonin ratio). We conclude that a dysfunction of noradrenergic regulation and the depletion of serotonin by increased monoamine oxidase A result in the loss of melatonin rhythm already in preclinical AD.

Wu YH; Feenstra MG; Zhou JN; Liu RY; Toranõ JS; Van Kan HJ; Fischer DF; Ravid R; Swaab DF

2003-12-01

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[Nocturnal choking sensation].  

UK PubMed Central (United Kingdom)

There are many different types of sleep disorders. The majority of sleep-related breathing disorders can be attributed to sleep apnoea syndrome. Nocturnal choking sensation is a different symptom, for which we present two cases. Nocturnal choking sensation is a terrifying symptom for the patient and the diagnostic approach can be challenging. Aside from sleep choking syndrome, this symptom may appear with nocturnal laryngospasm, insular epilepsy and nocturnal gastro-oesophageal reflux. A thorough patient history and observation of the nocturnal event, sometimes supported by EEG findings, may provide the clue to the diagnosis. These kinds of nocturnal symptoms are best analyzed in a clinic specialized in both epilepsy and sleep disorders.

Busger Op Vollenbroek RJ; de Weerd AW

2013-01-01

55

Complex nocturnal behaviors: nocturnal seizures and parasomnias.  

UK PubMed Central (United Kingdom)

PURPOSE OF REVIEW: This article summarizes the clinical and electrophysiologic manifestations of nocturnal seizures, particularly nocturnal frontal lobe epilepsy (NFLE), parasomnias, and other disorders presenting with complex behaviors in sleep. The evaluation and treatment of patients with complex nocturnal behaviors can be challenging. While the differential diagnosis of sleep-related movements, including physiologic and pathologic phenomena, is extensive, the focus of evaluation in patients with complex nocturnal behaviors distinguishes between nocturnal seizures and parasomnias. RECENT FINDINGS: Seizures in NFLE have a wide range of complexity and severity, overlapping considerably with the disorders of arousal from non-REM (NREM) sleep. Video polysomnography with EEG (VPSG-EEG) has identified key clinical features useful in differentiating these disorders. A dysfunctional arousal mechanism involving the cholinergic system is involved in the pathophysiology of the autosomal dominant form of NFLE and NREM parasomnias. The high prevalence of parasomnias in NFLE families further confounds their distinction. VPSG-EEG combines PSG with comprehensive EEG to evaluate unexplained nocturnal behaviors when epileptic seizures are suspected. This procedure provides improved detection of interictal and ictal EEG abnormalities and time-synchronized correlation of clinical and neurophysiologic phenomena. SUMMARY: The diagnosis of complex nocturnal behaviors is among the most difficult to establish in sleep medicine clinics and laboratories. VPSG-EEG is indicated in the evaluation of patients with complex nocturnal behaviors when routine EEG is nondiagnostic. Ongoing research is necessary to fully elucidate the pathophysiology of these disorders, which share a host of clinical manifestations.

Foldvary-Schaefer N; Alsheikhtaha Z

2013-02-01

56

Outpatient safety assessment of an in-home predictive low-glucose suspend system with type 1 diabetes subjects at elevated risk of nocturnal hypoglycemia.  

Science.gov (United States)

Abstract Objective: Nocturnal hypoglycemia is a common problem with type 1 diabetes. In the home setting, we conducted a pilot study to evaluate the safety of a system consisting of an insulin pump and continuous glucose monitor communicating wirelessly with a bedside computer running an algorithm that temporarily suspends insulin delivery when hypoglycemia is predicted. Research Design and Methods: After the run-in phase, a 21-night randomized trial was conducted in which each night was randomly assigned 2:1 to have either the predictive low-glucose suspend (PLGS) system active (intervention night) or inactive (control night). Three predictive algorithm versions were studied sequentially during the study for a total of 252 intervention and 123 control nights. The trial included 19 participants 18-56 years old with type 1 diabetes (hemoglobin A1c level of 6.0-7.7%) who were current users of the MiniMed Paradigm(®) REAL-Time Revel™ System and Sof-sensor(®) glucose sensor (Medtronic Diabetes, Northridge, CA). Results: With the final algorithm, pump suspension occurred on 53% of 77 intervention nights. Mean morning glucose level was 144±48?mg/dL on the 77 intervention nights versus 133±57?mg/dL on the 37 control nights, with morning blood ketones >0.6 mmol/L following one intervention night. Overnight hypoglycemia was lower on intervention than control nights, with at least one value ?70?mg/dL occurring on 16% versus 30% of nights, respectively, with the final algorithm. Conclusions: This study demonstrated that the PLGS system in the home setting is safe and feasible. The preliminary efficacy data appear promising with the final algorithm reducing nocturnal hypoglycemia by almost 50%. PMID:23883408

Buckingham, Bruce A; Cameron, Fraser; Calhoun, Peter; Maahs, David M; Wilson, Darrell M; Chase, H Peter; Bequette, B Wayne; Lum, John; Sibayan, Judy; Beck, Roy W; Kollman, Craig

2013-07-24

57

Outpatient safety assessment of an in-home predictive low-glucose suspend system with type 1 diabetes subjects at elevated risk of nocturnal hypoglycemia.  

UK PubMed Central (United Kingdom)

Abstract Objective: Nocturnal hypoglycemia is a common problem with type 1 diabetes. In the home setting, we conducted a pilot study to evaluate the safety of a system consisting of an insulin pump and continuous glucose monitor communicating wirelessly with a bedside computer running an algorithm that temporarily suspends insulin delivery when hypoglycemia is predicted. Research Design and Methods: After the run-in phase, a 21-night randomized trial was conducted in which each night was randomly assigned 2:1 to have either the predictive low-glucose suspend (PLGS) system active (intervention night) or inactive (control night). Three predictive algorithm versions were studied sequentially during the study for a total of 252 intervention and 123 control nights. The trial included 19 participants 18-56 years old with type 1 diabetes (hemoglobin A1c level of 6.0-7.7%) who were current users of the MiniMed Paradigm(®) REAL-Time Revel™ System and Sof-sensor(®) glucose sensor (Medtronic Diabetes, Northridge, CA). Results: With the final algorithm, pump suspension occurred on 53% of 77 intervention nights. Mean morning glucose level was 144±48?mg/dL on the 77 intervention nights versus 133±57?mg/dL on the 37 control nights, with morning blood ketones >0.6 mmol/L following one intervention night. Overnight hypoglycemia was lower on intervention than control nights, with at least one value ?70?mg/dL occurring on 16% versus 30% of nights, respectively, with the final algorithm. Conclusions: This study demonstrated that the PLGS system in the home setting is safe and feasible. The preliminary efficacy data appear promising with the final algorithm reducing nocturnal hypoglycemia by almost 50%.

Buckingham BA; Cameron F; Calhoun P; Maahs DM; Wilson DM; Chase HP; Bequette BW; Lum J; Sibayan J; Beck RW; Kollman C

2013-08-01

58

Melatonin and sleep-related problems in children with intractable epilepsy.  

UK PubMed Central (United Kingdom)

Children with epilepsy have high rates of sleep problems. Melatonin has been advocated in treatment of sleep disorders, and its beneficial effect has been confirmed in insomnia. The aim of this study was to assess melatonin levels in children with intractable epilepsy and its relation to pattern of sleep and characteristics of seizure disorder, as well as the effect of melatonin therapy on those parameters. The study was conducted on 23 children with intractable epilepsy and 14 children with controlled seizures. Patients were evaluated by psychometric sleep assessment and assay of diurnal and nocturnal melatonin levels. Children with intractable epilepsy received oral melatonin before bedtime. They were reassessed after 3 months. Children with intractable epilepsy had higher scores for each category of sleep walking, forcible teeth grinding, and sleep apnea. At the end of therapeutic trial, patients with intractable epilepsy exhibited significant improvement in bedtime resistance, sleep duration, sleep latency, frequent nocturnal arousals, sleep walking, excessive daytime sleepiness, nocturnal enuresis, forcible teeth grinding, sleep apnea, and Epworth sleepiness scores. There was also significant reduction in seizure severity. Thus, use of melatonin in patients with intractable seizures was associated with improvement of both many sleep-related phenomena and the severity of seizures.

Elkhayat HA; Hassanein SM; Tomoum HY; Abd-Elhamid IA; Asaad T; Elwakkad AS

2010-04-01

59

Melatonin and the skeleton.  

UK PubMed Central (United Kingdom)

Melatonin may affect bone metabolism through bone anabolic as well as antiresorptive effects. An age-related decrease in peak melatonin levels at nighttime is well documented, which may increase bone resorption and bone loss in the elderly. In vitro, melatonin reduces oxidative stress on bone cells by acting as an antioxidant. Furthermore, melatonin improves bone formation by promoting differentiation of human mesenchymal stem cell (hMSC) into the osteoblastic cell linage. Bone resorption is reduced by increased synthesis of osteoprogeterin (OPG), a decoy receptor that prevents receptor activator of NK-?B ligand (RANKL) in binding to its receptor. Moreover, melatonin is believed to reduce the synthesis of RANKL preventing further bone resorption. In ovariectomized as well as nonovariectomized rodents, melatonin has shown beneficial effects on bone as assessed by biochemical bone turnover markers, DXA, and ?CT scans. Furthermore, in pinealectomized animals, bone mineral density (BMD) is significantly decreased compared to controls, supporting the importance of sufficient melatonin levels. In humans, dysfunction of the melatonin signaling pathway may be involved in idiopathic scoliosis, and the increased fracture risk in nighttime workers may be related to changes in the circadian rhythm of melatonin. In the so-far only randomized study on melatonin treatment, no effects were, however, found on bone turnover markers. In conclusion, melatonin may have beneficial effects on the skeleton, but more studies on humans are warranted in order to find out whether supplementation with melatonin at bedtime may preserve bone mass and improve bone biomechanical competence.

Amstrup AK; Sikjaer T; Mosekilde L; Rejnmark L

2013-05-01

60

[Melatonin for diagnosis of cancer and assessment of prognosis in elderly patients].  

Science.gov (United States)

A review is given on the analysis of melatonin (MT) and of its main peripheral metabolite 6-sulfatoxymelatonin (aMT6s) in old patients with different types of primary unoperated carcinomas. A very low production of melatonin (as estimated by the nocturnal urinary excretion of aMT6s) was found in male patients with lung or stomach cancer compared to aged-matched controls as well as in female patients with thyroid cancer. The levels of these women, however, did not differ from female patients with benign thyroid diseases indicating a general suppressive effect of thyroid diseases on the pineal gland. A similar but opposite phenomenon was observed in male patients with primary unoperatide colorectal cancer which showed an elevated production of mellatonin when compared to healthy men but not when compared to patients with colitis ulcerosa. The mechanisms involved in these phenomena are poorly understood and seem to include central as well as peripheral components. This view is supported by the finding that in spite of varying urinary aMT6s excretion measured in patients with different types of tumor, aMT6s shows comparable positive correlations with the degree of tumor cell proliferation (as estimated by the number of PCNA-immunopositive cells). Therefore the amount of aMT6s excreted (as well as the corresponding concentration of circulating MT) has to be understood as the net result of a number of different effects by the tumor on organism. PMID:14743611

Kvetnaia, T V

2003-01-01

 
 
 
 
61

Metabolic syndrome, its pathophysiology and the role of melatonin.  

UK PubMed Central (United Kingdom)

Metabolic syndrome (MetS) is characterised by symptoms of obesity, insulin resistance, hypertension, dyslipidemia and diabetes mellitus. The pathophysiological mechanisms involved in MetS are complex and involved dysregulation of many biochemical and physiological regulatory mechanisms of the body. Elevated levels of low density lipoproteins like VLDL, and LDL with reduction of HDL seen in patients with MetS contribute to atherogenic dyslipedemia. Melatonin has been suggested to be effective in improving MetS through its anti-hyperlipidemic action. Melatonin reduced both adiposity, and body weight in experimental animal studies and also attenuated weight gain and obesityinduced metabolic alterations and this effect of melatonin is attributed to its anti-oxidative effects. Melatonin administration has been shown to inhibit insulin release by acting through both MT1 and MT2 melatonin receptors present in pancreatic ?-cells. Melatonin also increased insulin sensitivity and glucose tolerance in animals fed with either high fat or high sucrose diet. Melatonin exerts most of its beneficial actions by acting through MT1 and MT2 melatonin receptors present in various tissues of the body and some of the metabolic actions of melatonin have been blocked by melatonin antagonist like luzindole. Ramelteon, the newly available melatonin agonist will also have more promising role in the control of MetS. The numbers of patents are available with regard to treatment of MetS. Drug related to antidepressant fluoxetine is used for treatment of MetS (US Patent No. 2008001400450). Anti-oxidants like S-adenosyl-methionine, Vitamin E, and Vitamin C have been found beneficial in treating MetS (US Patent No. 8063024). Melatonin being a powerful Antioxidant will have a promising role in treating patients with metabolic syndrome.

Srinivasan V; Ohta Y; Espino J; Pariente JA; Rodriguez AB; Mohamed M; Zakaria R

2013-01-01

62

Melatonin in treatment of chronic sleep disorders in adults with autism: a retrospective study.  

UK PubMed Central (United Kingdom)

BACKGROUND: Melatonin may be used to treat sleep disorders in both children and adults with intellectual disability. The evidence for its efficacy, potential adverse effects and drug interactions are reviewed in the context of prescription of melatonin to patients with autism. METHODS: This study presents the use of melatonin to treat severe circadian sleep-wake disturbances in 6 adults with autism. Melatonin was initiated at a daily dose of 3 mg at nocturnal bedtime. If this proved ineffective, the melatonin dose was titrated over the following 4 weeks at increments of 3 mg/2 weeks up to a maximum of 9 mg, unless it was tolerated. Assessments included Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I). RESULTS: Melatonin administered in the evening dramatically improved the sleep-wake pattern in all patients. Melatonin appears to be effective in reducing sleep onset latency and is probably effective in improving nocturnal awakenings and total sleep time in adults with autism. Its effectiveness remained stable for the 6-month period of administration. Melatonin was well tolerated in all patients and no side effects were noted during the therapy. CONCLUSIONS: Melatonin appears to be promising as an efficient and seemingly safe alternative for treatment of severe circadian sleep disturbances in adults with autism. There may be heterogeneity of response depending on the nature of the sleep problem and cause of the intellectual disability or associated disabilities. Further studies are necessary before firm conclusions can be drawn and guidelines for the use of melatonin in people with autism formulated.

Galli-Carminati G; Deriaz N; Bertschy G

2009-05-01

63

New developments in the treatment of primary insomnia in elderly patients: focus on prolonged-release melatonin  

Directory of Open Access Journals (Sweden)

Full Text Available Daniel P Cardinali, María F Vidal, Daniel E VigoDepartment of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Buenos Aires, ArgentinaAbstract: A temporal relationship between the nocturnal rise in melatonin secretion and the increase in sleep propensity at the beginning of the night, coupled with the sleep-promoting effects of exogenous melatonin, indicate that melatonin is involved in the regulation of sleep. This action is attributed to the MT1 and MT2 melatonin receptors present in the hypothalamic suprachiasmatic nucleus and other brain areas. The sleep-promoting actions of melatonin, which are demonstrable in healthy humans, have been found to be useful in subjects suffering from circadian rhythm sleep disorders and in elderly patients, who had low nocturnal melatonin production and secretion. The effectiveness of melatonin in treating sleep disturbances in these patients is relevant because the sleep-promoting compounds that are usually prescribed, such as benzodiazepines and related drugs, have many adverse effects, such as next-day hangover, dependence, and impairment of memory. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause any hangover or show any addictive potential. However, there is a lack of consistency concerning its therapeutic value (partly because of its short half-life and the small quantities of melatonin used). Thus, attention has been focused either on the development of more potent melatonin analogs with prolonged effects or on the design of slow-release melatonin preparations. A prolonged-release preparation of melatonin 2 mg (Circadin®) has been approved for the treatment of primary insomnia in patients aged ?55 years in the European Union. This prolonged-release preparation of melatonin had no effect on psychomotor functions, memory recall, or driving skills during the night or the next morning relative to placebo, and was associated with significantly less impairment on many of these tasks relative to zolpidem alone or in combination with prolonged-release melatonin. In 3-week and 6-month randomized, double-blind, clinical trials in patients with primary insomnia aged ?55 years, prolonged-release melatonin was associated with improvements relative to placebo in many sleep and daytime parameters, including sleep quality and latency, morning alertness, and quality of life. Prolonged-release melatonin was very well tolerated in clinical trials in older patients, with a tolerability profile similar to that of placebo. Short-term or longer-term treatment with prolonged-release melatonin was not associated with dependence, tolerance, rebound insomnia, or withdrawal symptoms.Keywords: insomnia, melatonin, Circadin®, clinical trials

Cardinali DP; Vidal MF; Vigo DE

2012-01-01

64

High endogenous melatonin levels in critically ill children: a pilot study.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To evaluate the serum melatonin levels in critically ill pediatric patients and to test the effect of light on the melatonin's circadian rhythm. Data on melatonin secretion in critically ill pediatric subjects are lacking. STUDY DESIGN: We investigated the serum melatonin levels of 16 sedated and mechanically ventilated patients in a pediatric intensive care unit. Children (mean age, 5.1 ± 3.1 years) were randomly assigned to a dark-exposed or to a light-exposed group to evaluate the effects of light on serum melatonin concentrations. Blood samples for serum melatonin analysis were collected at 10 p.m., 1 a.m., 3 a.m., 5 a.m., 8 a.m., and 12 p.m. RESULTS: The melatonin circadian rhythm was severely disrupted in critically ill children; light exposure lowered serum melatonin even in a context of highly altered circadian cycle; melatonin peaks were greater for healthy age-matched children. CONCLUSION: The high melatonin levels in the critically ill children may be a response to counteract the elevated oxidative stress associated with serious diseases. Whether these elevated melatonin levels confer any beneficial effects in pediatric critically ill patients remains unknown.

Marseglia L; Aversa S; Barberi I; Salpietro CD; Cusumano E; Speciale A; Saija A; Romeo C; Trimarchi G; Reiter RJ; Gitto E

2013-02-01

65

Independence of circadian entrainment state and responses to melatonin in male Siberian hamsters  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Seasonal fluctuations in physiology and behavior depend on the duration of nocturnal melatonin secretion programmed by the circadian system. A melatonin signal of a given duration, however, can elicit different responses depending on whether an animal was previously exposed to longer or shorter photoperiod signals (i.e., its photoperiodic history). This report examined in male Siberian hamsters which of two aspects of photoperiod history – prior melatonin exposure or entrainment state of the circadian system – is critical for generating contingent responses to a common photoperiodic signal. Results In Experiment #1, daily melatonin infusions of 5 or 10 h duration stimulated or inhibited gonadal growth, respectively, but had no effect on entrainment of the locomotor activity rhythm to long or short daylengths, thereby demonstrating that melatonin history and entrainment status could be experimentally dissociated. These manipulations were repeated in Experiment #2, and animals were subsequently exposed to a 12 week regimen of naturalistic melatonin signals shown in previous experiments to reveal photoperiodic history effects. Gonadal responses differed as a function of prior melatonin exposure but were unaffected by the circadian entrainment state. Experiment #3 demonstrated that a new photoperiodic history could be imparted during four weeks of exposure to long photoperiods. This effect, moreover, was blocked in animals treated concurrently with constant release melatonin capsules that obscured the endogenous melatonin signal: Following removal of the implants, the gonadal response depended not on the immediately antecedent circadian entrainment state, but on the more remote photoperiodic conditions prior to the melatonin implant. Conclusions The interpretation of photoperiodic signals as a function of prior conditions depends specifically on the history of melatonin exposure. The photoperiodic regulation of circadian entrainment state contributes minimally to the interpretation of melatonin signals.

Gorman Michael R

2003-01-01

66

Behavior, sleep and melatonin.  

UK PubMed Central (United Kingdom)

The focus of most behavioral studies on melatonin relate to sleep, arousal levels and circadian rhythms of alertness. It has also been suggested that melatonin administration can reduce anxiety (Golus and King, 1981), affect learning (Datta and King, 1980), and exacerbate symptoms in patients suffering from severe depression (Carman et al., 1976). For a variety of reasons the effects of exogenous melatonin on sleep and circadian rhythms seem most likely to reflect the actual physiological functions of the endogenous hormone; however, definitive relationships between melatonin secretion and these effects have not yet been established. Administration of melatonin to humans in pharmacologic doses produces acute hypnotic-like effects (Vollrath et al., 1981; Lieberman et al., 1984). Available evidence suggests that melatonin may participate in the physiological regulation of sleep, particularly in determining the phase of circadian rhythms of sleep and sleepiness (Redman et al., 1983; Wurtman and Lieberman, 1985).

Lieberman HR

1986-01-01

67

Aging and vascular dysfunction: beneficial melatonin effects.  

UK PubMed Central (United Kingdom)

Aging is characterized by a progressive deterioration of physiological functions and metabolic processes. In aging and in diseases associated with the elderly, the loss of cells in vital structures or organs may be related to several factors. Sirtuin1 (SIRT1) is a member of the sirtuin family of protein deacetylases involved in life span extension; however, its involvement in the aging is not yet completely defined. Recently, melatonin, a pleiotropic molecule, shown to activate SIRT1 in primary neurons of young animals, as well as in aged neurons of a murine model of senescence. Melatonin is known to modulate oxidative stress-induced senescence and pro-survival pathways. We treated 6- and 15-week-old apolipoprotein E (APOE)-deficient mice (APOE 6w and 15w) with two melatonin formulations (FAST and RETARD) to evaluate their anti-aging effect. Morphological changes in vessels (aortic arch) of APOE mice were evaluated SIRT1, p53, endothelial nitric oxide synthase (eNOS), and endothelin-1 (ET-1) markers. We demonstrate that SIRT1 and eNOS decresed in APOE mice between 6 and 15 weeks and that aging induced an elevated expression of p53 and ET-1 in APOE animals. Melatonin improved the impairment of endothelial damage and reduced loss of SIRT1 and eNOS decreasing p53 and ET-1 expression. The RETARD melatonin preparation caused a greater improvement of vessel cytoarchitecture. In summary, we indicate that SIRT1-p53-eNOS axis as one of the important marker of advanced vascular dysfunctions linked to aging. Finally, we suggest that extended-release melatonin (RETARD) provides a more appropriate option for contrasting these dysfunctions compared with rapid release melatonin (FAST) administration.

Rodella LF; Favero G; Rossini C; Foglio E; Bonomini F; Reiter RJ; Rezzani R

2013-02-01

68

Melatonin deficiencies in women.  

Science.gov (United States)

The pineal hormone melatonin is the mediator of external light to physiologic adaptation to day and night rhythms, it regulates reproduction in animals but attempts to utilize melatonin in women for contraception have failed. Melatonin seems to be the natural hormone to facilitate sleep in insomniac patients and causes no hang over. When applied together with benzodiazepine it allows reduction of benzodiazepine without withdrawal effects. It should be applied 2 h before sleeping time in doses between 3 and 5 mg. Melatonin acts via the gamma-aminobutyric acid- and benzodiazepine receptor explaining its success in treatment of seizures in children and in adults. Constant application of benzodiazepine reduced the production of natural melatonin in rats, supporting the evidence that long-term application of benzodiazepine in humans does not restore sleeping habits but reduces natural sleeping habits even more. Low melatonin levels were seen in bulimia or neuralgia and in women with fibromyalgia; replacement reduced pain, sleeping disorders, and depression in fibromyalgia and bulimia. Melatonin profiles are a diagnostic tool to distinguish between several forms of depression, like major depression, winter depression (SAD), unipolar depression, delayed sleep phase syndrome (DSPS). In patients with a major depression success with antidepressants correlated with an increase in their melatonin profiles but only patients suffering from DSPS can be successfully treated with melatonin. In perimenopausal women melatonin administration did produce a change in LH, FSH and thyroid hormones. Some oncostatic properties are supported by cell culture work and studies in animals. In Nordic countries indigenous people suffer less from breast and prostate cancer, winter darkness seems to protect. The supposedly increased melatonin levels created the 'melatonin hypothesis'. Epidemiological studies did show that blind people indeed have half the rate of breast cancers, supporting the hypothesis. Controversial results concerning melatonin and insulin resistance and glucose tolerance have been published. In postmenopausal women application of melatonin reduced glucose tolerance and insulin sensitivity. Pregnant women should avoid melatonin, since its teratogenic effect is not known. Patients suffering from non-hormone dependent tumors, like leukemia, should avoid melanin, since tumor growth was promoted in animal experiments. It can be expected that melatonin will receive wide consideration for treatment of sleeping disturbances, jet lag, and fibromyalgia once an oral formulation becomes available in Europe. PMID:11955797

Rohr, Uwe D; Herold, Jens

2002-04-15

69

Melatonin-induced changes in the expression of thyroid hormone-converting enzymes in hypothalamus depend on the timing of melatonin injections and genetic background in mice.  

UK PubMed Central (United Kingdom)

Recent studies have identified TSHB, Dio2, and Dio3 as key genes for the photoperiodic regulation of gonads. In mammals, the expression of these genes is controlled by melatonin. Surprisingly, this effect of melatonin was shown to be conserved in several reproductively non-photoperiodic laboratory mouse strains that have thus become a valuable model to decipher the mechanisms through which melatonin controls the expression of TSHB, Dio2, and Dio3. In this study, we assessed the effects of intraperitoneal melatonin injections and of their timing on the expression of TSHB, TSHR, Dio2, and Dio3 in the hypothalamo-hypophysial systems of melatonin-proficient CBA/N and melatonin-deficient C57BL/6J mice kept under long-day conditions. In CBA/N mice, Dio3 expression was induced by a daily melatonin injection at ZT14 only, whereas in C57BL/6J mice, a daily melatonin injection induced Dio3 expression at all time points investigated (ZT8, 14, and 20) without changes in TSHB expression in both strains. Dio2 expression was suppressed by a daily melatonin injection only in C57BL/6J mice and only at ZT8. Effect of a daily melatonin injection on TSHR expression was strain- and region- specific. Melatonin levels elevated in plasma and hypothalamus after intraperitoneal injections of melatonin at ZT8 for 7days in C57BL/6J returned to basal levels within 1h after the final injection, while in CBA/N mice melatonin levels in hypothalamus remained high for at least 1h. These data suggest that Dio2 and Dio3 expression in the hypothalamus is differentially regulated by the timing of melatonin injections through strain-specific mechanisms.

Goto M; Matsuo H; Iigo M; Furuse M; Korf HW; Yasuo S

2013-06-01

70

Serum Melatonin in Juvenile Rheumatoid Arthritis: Correlation with Disease Activity  

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Full Text Available The study was conducted to investigate the abnormalities in early morning serum melatonin among patients with Juvenile Rheumatoid Arthritis (JRA) and to outline its relation to disease activity and severity. Twenty one patients with JRA and twenty healthy age and sex matched controls were enrolled in the study. Fifteen patients had polyarticular JRA, 3 had oligoarticular and 3 had systemic onset JRA. Evaluation was carried out clinically, functionally and radiologically by using disease activity score, Juvenile Arthritis Functional Assessment Report for Children (JAFAR-C score) and modified Larsen score, respectively. Laboratory investigations included Complete Blood Picture (CBC), The Erythrocyte Sedimentation Rate ( ESR), C-Reactive Protein (CRP), classic IgM Rheumatoid Factor (RF), Anti-nuclear Antibodies (ANA) and melatonin estimation in serum. The serum levels of melatonin were significantly increased in JRA patients (mean±SD = 13.9±8 pg mL-1) as compared to healthy controls (mean±SD = 8.1±2.7 pg mL-1, p-1) (n = 15) and group II with normal melatonin level (less than 11 pg mL-1) (n = 6). Patients with elevated melatonin levels had higher ESR (p0.05). Hence the study conclude that the elevated melatonin levels among JRA patients with active synovitis and its close relation to disease activity rather than disease severity suggests that melatonin might play a promoting role in rheumatoid arthritis. Hence, inhibition of its synthesis and/or action by specific antagonists may be of therapeutic value.

Hanaa Mahmoud El-Awady; Amany Salah El-Dien El-Wakkad; Maysa Tawheed Saleh; Saadia Ibraheem Muhammad; Eiman Mahmoud Ghaniema

2007-01-01

71

Melatonin: Buffering the Immune System  

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Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is ...

Antonio Carrillo-Vico; Patricia J. Lardone; Nuria Álvarez-Sánchez; Ana Rodríguez-Rodríguez; Juan M. Guerrero

72

Melatonin accelerates the process of wound repair in full-thickness incisional wounds.  

UK PubMed Central (United Kingdom)

The pineal gland hormone melatonin is known to have both anti-inflammatory and immunomodulatory effects. Given this, we propose that melatonin is an ideal candidate to enhance the process of wound healing. The present study assessed the effects of exogenously administered melatonin (1.2 mg/kg intra-dermal), on scar formation using a full-thickness incisional rat model of dermal wound healing. Melatonin treatment significantly improved the quality of scarring, both in terms of maturity and orientation of collagen fibres. An increase in nitric oxide synthase (NOS) activity and therefore nitric oxide production is detrimental during inflammation but is favourable during granulation tissue formation. Melatonin treatment significantly decreased inducible NOS (iNOS) activity during the acute inflammatory phase but significantly increased iNOS activity during the resolving phase. Cyclooxygenase-2, which has been shown to have anti-inflammatory effects, was elevated in the melatonin-treated rats following wounding. In addition, melatonin treatment also accelerated the angiogenic process, increasing the formation of new blood vessels and elevating the level of vascular endothelial growth factor protein expression during granulation tissue formation. Melatonin treatment increased arginase activity (which generates proline, a building block for collagen synthesis) from earlier time points. The protein profiles of hemoxygenase-1 (HO-1) and HO-2 isoforms, vital participants in the repair process, were also up-regulated upon melatonin treatment. This study has therefore demonstrated, for the first time, that melatonin can significantly improve the quality of wound healing and scar formation.

Pugazhenthi K; Kapoor M; Clarkson AN; Hall I; Appleton I

2008-05-01

73

Melatonin and Diabetes  

Medline Plus

Full Text Available ... HealthDay April 3, 2013 Related MedlinePlus Pages Diabetes Type 2 Sleep Disorders Transcript Melatonin is a hormone secreted ... in melatonin levels may increase your risk of Type 2 diabetes. Boston-based researchers used urine and blood ...

74

Thermal sensitivity of reptilian melatonin rhythms: "cold" tuatara vs. "warm" skink.  

UK PubMed Central (United Kingdom)

Daily rhythms in plasma melatonin levels were compared in two ecologically diverse reptilian species under natural environmental conditions in autumn. The nocturnal, cold temperature-adapted tuatara (Sphenodon punctatus) had a melatonin rhythm of much lower amplitude than did the diurnal desert-adapted sleepy lizard (Tiliqua rugosa). Experiments in controlled laboratory environments showed that, although both species are capable of attaining a comparable melatonin peak (approximately 750 pmol/l), the threshold temperature at which a significant daily rhythm occurs is approximately 15 degrees C in S. punctatus compared with approximately 25 degrees C in T. rugosa. This difference probably reflects the disparate thermoregulatory adaptations of the two species, S. punctatus favoring mean activity temperatures of 11.5 degrees C and T. rugosa, 32.5 degrees C. In ectotherms such as reptiles, therefore, species-typical thermoregulatory behavior may provide thermal cues that interact with photoperiod to provide the appropriate melatonin signal for the regulation of annual physiological cycles.

Firth BT; Thompson MB; Kennaway DJ; Belan I

1989-05-01

75

Melatonin supplementation in rat ameliorates ovariectomy-induced oxidative stress.  

UK PubMed Central (United Kingdom)

OBJECTIVE: The present study aims to determine the potential of melatonin supplementation in ameliorating tissue oxidative stress, elevated serum corticosterone and hepatic and renal dysfunction. MATERIALS AND METHODS: Adult Wistar rats, either ovariectomized or sham-operated, served as experimental or control groups, respectively. Rats received either melatonin, estrogen, progesterone or a combination of melatonin and estrogen for a period of 15 days. Tissue oxidative stress, serum markers of hepatic and renal dysfunction and serum corticosterone level formed the parameters of assay in all groups at the end of the treatment schedule. RESULTS: Ovariectomized rats showed significant increases in levels of tissue lipid peroxidation, serum levels of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase, acid phosphatase and corticosterone and significant decrement in enzymatic and non-enzymatic antioxidant status. All parameters showed maximal reversal to control levels on supplementation with high-dose melatonin or estrogen + melatonin treatment. CONCLUSION: Melatonin supplementation proved better than estrogen replacement therapy, with the higher dose being more effective in preventing ovariectomy-induced increases in oxidative stress and serum levels of marker parameters of hepatic and renal dysfunction and corticosterone titer. Overall, melatonin supplementation therapy qualifies as a more potent and safe alternative to estrogen replacement therapy in alleviating postmenopausal increases in oxidative stress and hepatic and renal dysfunction.

Baxi DB; Singh PK; Vachhrajani KD; Ramachandran AV

2013-04-01

76

Melatonin pretreatment attenuates diazinon-induced testicular damage in mice  

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Full Text Available Background: Diazinon is one of widely used organophosphrous pesticides, can affect both animals and man even after a single exposure. It has a dual toxicity due to acetylcholinestrase inhibition and formation of free oxygen radicals .So, the current work aimed to evaluate the effects of diazinon on the mice testes and the possible protective effect of melatonin. Material and Methods: Male CD-1 adult mice were divided into 6 groups, (1) control group,(2) melatonin group 10mg/kg,(3) diazinon group (30mg/kg), (4) diazinon group (60mg/kg),(5) diazinon 30mg + melatonin and (6) diazinon 60mg/kg + melatonin. Diazinon was orally administrated 1 and 28 days of treatment, whereas, melatonin was administrated intraperitoneally at a single dose. Testicular damage was examined by using hematoxyline and eosin staining. Results: Diazinon treated groups diminished the plasma acetylcholinestrase activity on day 1 of treatment. Morphometrical analysis showed a decrease in seminiferous thickness (day 1 and 28), with increased testicular superoxide dismutase (SOD) activity (day28). Melatonin pre-treatment prevented alterations induced by diazinon, except diminution of acetylcholinestrase activity. Conclusion: These results suggest that testicular damage observed post-treatment might be due to elevated concentration of free oxygen radicals (ROS) with diazinon while, pretreatment with a single dose of melatonin is a potentially beneficial agent to reduce testicular damage in adult mice probably by decreasing oxidative stress.

El-Mazoudy R. H*. and Abdou H. M

2009-01-01

77

Melatonin binding sites  

Energy Technology Data Exchange (ETDEWEB)

The distribution and characterization of specific melatonin binding sites were studied using /sup 125/I-melatonin. Autoradiography revealed only three sites of specific melatonin binding in brain: the suprachiasmatic nuclei, the median eminence, and the small part of choroid plexus at the caudal end of the fourth ventricle. Two other sites were detected outside the CNS: the anterior pituitary and the retina. The specific binding of /sup 125/I-melatonin was saturable and reversible. The dissociation constant (KD) of the binding sites was 60 pM. The concentration of the binding sites (Bmax) in the median eminence was 26 fmol/mg protein, and in the pituitary 3 fmol/mg protein. Specificity of the binding sites was tested by displacement of /sup 125/I-melatonin. The order of potency--melatonin much less than N-acetyl-5-hydroxytryptamine less than 5-methoxytryptamine much less than 5-hydroxytryptamine = 3,4-dihydroxyphenylethylamine = noradrenaline--shows high specificity of the binding sites for melatonin.

Vanecek, J.

1988-11-01

78

Melatonin and female reproduction.  

UK PubMed Central (United Kingdom)

Melatonin (N-acetyl-5-methoxytryptamine) is secreted during the dark hours at night by the pineal gland. After entering the circulation, melatonin acts as an endocrine factor and a chemical messenger of light and darkness. It regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. It also affects the brain, immune, gastrointestinal, cardiovascular, renal, bone and endocrine functions and acts as an oncostatic and anti-aging molecule. Many of melatonin's actions are mediated through interactions with specific membrane-bound receptors expressed not only in the central nervous system, but also in peripheral tissues. Melatonin also acts through non-receptor-mediated mechanisms, for example serving as a scavenger for reactive oxygen species and reactive nitrogen species. At both physiological and pharmacological concentrations, melatonin attenuates and counteracts oxidative stress and regulates cellular metabolism. Growing scientific evidence of reproductive physiology supports the role of melatonin in human reproduction. This review was conducted to investigate the effects of melatonin on female reproduction and to summarize our findings in this field.

Tamura H; Takasaki A; Taketani T; Tanabe M; Lee L; Tamura I; Maekawa R; Aasada H; Yamagata Y; Sugino N

2013-10-01

79

Sleep and melatonin in infants: a preliminary study.  

UK PubMed Central (United Kingdom)

Sleep-wake patterns of 20 normal, healthy infants (16 girls and four boys; age range: 26-37 weeks) were recorded for a period of 1 week with a miniature activity monitor. Urine samples were extracted from the infants' disposable diapers that were collected during a 60-hour period to determine the levels of 6-sulphatoxymelatonin (aMT6s, a melatonin metabolite) using a radioimmunoassay test. Infants with "mature" secretion patterns (i.e. with an adult-like circadian rhythm) had a significantly delayed sleep-wake cycle in comparison to those with "immature" patterns. The onset of their nocturnal-sleep episode was delayed by almost 1 hour (22.1 vs. 21.2 hours; p < 0.05). Higher secretion rates of aMT6s during the evening hours (6:00-10:00 p.m.) were associated with earlier onset of nocturnal sleep (r = 0.51; p < 0.05). A delayed peak of melatonin was associated with more fragmented sleep during the night (e.g. r = 0.49; p < 0.05; for lower sleep percent). These findings suggest that melatonin plays an important role in the evolution of the sleep-wake system.

Sadeh A

1997-03-01

80

Effects of electromagnetic fields on photophasic circulating melatonin levels in American kestrels.  

UK PubMed Central (United Kingdom)

Birds reproduce within electromagnetic fields (EMFs) from transmission lines. Melatonin influences physiologic and behavioral processes that are critical to survival, and melatonin has been equivocally suppressed by EMFs in mammalian species. We examined whether EMFs affect photophasic plasma melatonin in reproducing adult and fledgling American kestrels (Falco sparverius), and whether melatonin was correlated with body mass to explain previously reported results. Captive kestrel pairs were bred under control or EMF conditions for one (short-term) or two (long-term) breeding seasons. EMF exposure had an overall effect on plasma melatonin in male kestrels, with plasma levels suppressed at 42 days and elevated at 70 days of EMF exposure. The similarity in melatonin levels between EMF males at 42 days and controls at 70 days suggests a seasonal phase-shift of the melatonin profile caused by EMF exposure. Melatonin was also suppressed in long-term fledglings, but not in short-term fledglings or adult females. Melatonin levels in adult males were higher than in adult females, possibly explaining the sexually dimorphic response to EMFs. Melatonin and body mass were not associated in American kestrels. It is likely that the results are relevant to wild raptors nesting within EMFs.

Fernie KJ; Bird DM; Petitclerc D

1999-11-01

 
 
 
 
81

Identification of genes for melatonin synthetic enzymes in 'Red Fuji' apple (Malus domestica Borkh.cv.Red) and their expression and melatonin production during fruit development.  

UK PubMed Central (United Kingdom)

Melatonin is present in many edible fruits; however, the presence of melatonin in apple has not previously been reported. In this study, the genes for melatonin synthetic enzymes including tryptophan decarboxylase, tryptamine 5-hydroxylase (T5H), arylalkylamine N-acetyltransferase, and N-acetylserotonin methyltransferase were identified in 'Red Fuji' apple. Each gene has several homologous genes. Sequence analysis shows that these genes have little homology with those of animals and they only have limited homology with known genes of rice melatonin synthetic enzymes. Multiple origins of melatonin synthetic genes during the evolution are expected. The expression of these genes is fully coordinated with melatonin production in apple development. Melatonin levels in apple exhibit an inverse relationship with the content of malondialdehyde, a product of lipid peroxidation. Two major melatonin synthetic peaks appeared on July 17 and on October 8 in both unbagged and bagged apple samples. At the periods mentioned above, apples experienced rapid expansion and increased respiration. These episodes significantly elevate reactive oxygen species production in the apple. Current data further confirmed that melatonin produced in apple was used to neutralize the toxic oxidants and protect the developing apple against oxidative stress.

Lei Q; Wang L; Tan DX; Zhao Y; Zheng XD; Chen H; Li QT; Zuo BX; Kong J

2013-09-01

82

Genetic variability of the pattern of night melatonin blood levels in relation to coat changes development in rabbits  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract To assess the genetic variability in both the nocturnal increase pattern of melatonin concentration and photoresponsiveness in coat changes, an experiment on 422 Rex rabbits (from 23 males) raised under a constant light programme from birth was performed. The animals were sampled at 12 weeks of age, according to 4 periods over a year. Blood samples were taken 7 times during the dark phase and up to 1 h after the lighting began. Maturity of the fur was assessed at pelting. Heritability estimates of blood melatonin concentration (0.42, 0.17 and 0.11 at mid-night, 13 and 15 h after lights-out respectively) and strong genetic correlations between fur maturity and melatonin levels at the end of the dark phase (-0.64) indicates that (i) the variability of the nocturnal pattern of melatonin levels is under genetic control and (ii) the duration of the nocturnal melatonin increase is a genetic component of photoresponsiveness in coat changes.

Allain Daniel; Malpaux Benoit; Puechal François; Thébault René; de Rochambeau Hubert; Chemineau Philippe

2004-01-01

83

New developments in the treatment of primary insomnia in elderly patients: focus on prolonged-release melatonin  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Daniel P Cardinali, María F Vidal, Daniel E VigoDepartment of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Buenos Aires, ArgentinaAbstract: A temporal relationship between the nocturnal rise in melatonin secretion and the increase in s...

Cardinali DP; Vidal MF; Vigo DE

84

Melatonin and Diabetes  

Medline Plus

Full Text Available ... FAQs Contact Us Search MedlinePlus Health Topics Drugs & Supplements Videos & Cool Tools To use the sharing features ... if prolonged exposure to the dark or melatonin supplements can increase insulin sensitivity and decrease Type 2 ...

85

Melatonin in Autism Spectrum Disorders.  

UK PubMed Central (United Kingdom)

Melatonin is an endogenous neurohormone produced predominantly in the pineal gland. Recent studies have implicated abnormalities in melatonin physiology and the circadian rhythm in individuals with autism spectrum disorders (ASD). These physiological abnormalities include lower nighttime melatonin or melatonin metabolite concentrations in ASD compared to controls. These abnormalities in melatonin concentrations may be directly attributed to variations in melatonin pathway physiology as both functional and genetic variations in this pathway have been reported in children with ASD. Four studies have observed a correlation between abnormal melatonin concentrations and the severity of autistic behaviors. Twenty clinical studies have reported improvements in sleep parameters with exogenous melatonin supplementation in ASD, including longer sleep duration, less nighttime awakenings and quicker sleep onset. A recent meta-analysis of five randomized, double-blind, placebo-controlled crossover trials examining exogenous melatonin supplementation in ASD reported significant improvements with large effect sizes in total sleep duration and sleep onset latency compared to both baseline and placebo. Six studies reported that the nighttime administration of exogenous melatonin was associated with better daytime behaviors. Four studies reported improvements with exogenous melatonin supplementation when other sleep medications had previously failed. Adverse effects of melatonin were minimal to none in the twenty treatment studies. These studies indicate that the administration of exogenous melatonin for abnormal sleep parameters in ASD is evidence-based. Further studies examining optimal effective dosing and timing of dosing are warranted.

Rossignol DA; Frye RE

2013-09-01

86

Nocturnal panic attacks  

Directory of Open Access Journals (Sweden)

Full Text Available The panic-respiration connection has been presented with increasing evidences in the literature. We report three panic disorder patients with nocturnal panic attacks with prominent respiratory symptoms, the overlapping of the symptoms with the sleep apnea syndrome and a change of the diurnal panic attacks, from spontaneous to situational pattern. The implication of these findings and awareness to the distinct core of the nocturnal panic attacks symptoms may help to differentiate them from sleep disorders and the search for specific treatment.

Lopes Fabiana L.; Nardi Antonio E.; Nascimento Isabella; Valença Alexandre M.; Zin Walter A

2002-01-01

87

New perspectives in melatonin uses.  

Science.gov (United States)

This review summarizes the metabolism, secretion, regulation and sites of action of melatonin. An updated description of the melatonin receptors, including their signal transduction mechanisms, distribution and characterization of receptor genes, is given. Special emphasis is focused on the clinical aspects and potential uses of melatonin in the sleep-wake rhythms, in the immune function, in cancer therapy, in neuroprotection against oxidative damage and antioxidant activities in different tissues. Finally, combined effects of melatonin with other drugs are discussed. PMID:22311380

Carpentieri, A; Díaz de Barboza, G; Areco, V; Peralta López, M; Tolosa de Talamoni, N

2012-01-30

88

Failure to respond to endogenous or exogenous melatonin may cause nonphotoresponsiveness in Harlan Sprague Dawley rats  

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Full Text Available Abstract Background Responsiveness to changing photoperiods from summer to winter seasons is an important but variable physiological trait in most temperate-zone mammals. Variation may be due to disorders of melatonin secretion or excretion, or to differences in physiological responses to similar patterns of melatonin secretion and excretion. One potential cause of nonphotoresponsiveness is a failure to secrete or metabolize melatonin in a pattern that reflects photoperiod length. Methods This study was performed to test whether a strongly photoresponsive rat strain (F344) and strongly nonphotoresponsive rat strain (HSD) have similar circadian urinary excretion profiles of the major metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s), in long-day (L:D 16:8) and short-day (L:D 8:16) photoperiods. The question of whether young male HSD rats would have reproductive responses to constant dark or to supplemental melatonin injections was also tested. Urinary 24-hour aMT6s profiles were measured under L:D 8:16 and L:D 16:8 in young male laboratory rats of a strain known to be reproductively responsive to the short-day photoperiod (F344) and another known to be nonresponsive (HSD). Results Both strains exhibited nocturnal rises and diurnal falls in aMT6s excretion during both photoperiods, and the duration of the both strains' nocturnal rise was longer in short photoperiod treatments. In other experiments, young HSD rats failed to suppress reproduction or reduce body weight in response to either constant dark or twice-daily supplemental melatonin injections. Conclusion The results suggest that HSD rats may be nonphotoresponsive because their reproductive system and regulatory system for body mass are unresponsive to melatonin.

Price Matthew; Kruse Julie; Galvez M Eric; Lorincz Annaka M; Avigdor Mauricio; Heideman Paul D

2005-01-01

89

Clinical Aspects of Melatonin Hormone  

Directory of Open Access Journals (Sweden)

Full Text Available Melatonin is a hormone secreted by the pineal gland in the brain. It helps regulate other hormones andmaintains the body's circadian rhythm. In animals circulating levels of the hormone melatonin vary in adaily cycle, thereby allowing the entrainment of the circadian rhythm of several biological function.Chemically melatonin and its metabolites can function as endogenous free-radical scavengers andbroad-spectrum antioxidants. Jet lag, shift work, and poor vision can disrupt melatonin cycles.Melatonin also helps control the timing and release of female reproductive hormones. It helpsdetermine when a woman starts to menstruate the frequency and duration of menstrual cycles and whena woman stops menstruating (menopause). Some researchers also believe that melatonin levels may berelated to aging for example, young children have the highest levels of night time melatonin.Researchers believe these levels drop as we age. Some people think lower levels of melatonin mayexplain why some older adults have sleep problems and tend to go to bed and wake up earlier thanwhen they were younger. However, newer research calls this theory into question. Melatonin has strongantioxidant effects. The immunomodulatory properties of melatonin are well known and it acts on theimmune system by regulating cytokine production of immunocompetent cells. Experimental andclinical data showing that melatonin reduces adhesion molecules and pro-inflammatory cytokines andmodifies serum inflammatory parameters. As a consequence melatonin improves the clinical course ofillnesses which have anti-inflammatory etiology.

Faisal Mohd; Singh M K; Singh Savita1; D. Gyaneshwari; Tabish Mohd

2011-01-01

90

Role of melatonin on diabetes-related metabolic disorders  

Directory of Open Access Journals (Sweden)

Full Text Available Melatonin is a circulating hormone that is mainly released from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Interestingly, insulin levels are also adapted to day/night changes through melatonin-dependent synchronization. This regulation may be explained by the inhibiting action of melatonin on insulin release, which is transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 and MT2 and the second messengers 3’,5’-cyclic adenosine monophosphate, 3’,5’-cyclic guanosine monophosphate and inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion, but also by providing protection against reactive oxygen species, since pancreatic ?-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. On the other hand, in several genetic association studies, single nucleotide polymorphysms of the human MT2 receptor have been described as being causally linked to an elevated risk of developing type 2 diabetes. This suggests that these individuals may be more sensitive to the actions of melatonin, thereby leading to impaired insulin secretion. Therefore, blocking the melatonin-induced inhibition of insulin secretion may be a novel therapeutic avenue for type 2 diabetes.

Javier Espino; José A Pariente; Ana B Rodríguez

2011-01-01

91

Melatonin und das kardiovaskuläre System  

Directory of Open Access Journals (Sweden)

Full Text Available Melatonin, das physiologisch bedeutendste Hormon der Epiphyse, zog nicht zuletzt aufgrund zahlreicher populärer Bücher über seine "wundersamen Effekte" die Aufmerksamkeit auf sich. Synthese und Sekretion von Melatonin werden wesentlich durch den Hell/Dunkel-Zyklus beeinflußt: Trifft Licht auf die Retina, so wird die Melatoninsekretion supprimiert. Melatonin beeinflußt endogene zirkadiane Rhythmen sowie Köpertemperatur und Stimmungslage. In der vorliegenden Arbeit wird das derzeitige Wissen um Interaktionen von Melatonin und dem kardiovaskulären System kritisch beleuchtet. Zusammenfassend muß die Rolle von Melatonin im menschlichen Organismus äußerst kontroversiell betrachtet werden.

Sakotnik A; Eber B; Liebmann PM; Stoschitzky K; Zweiker R

1999-01-01

92

Role of Melatonin in Schizophrenia  

Directory of Open Access Journals (Sweden)

Full Text Available Schizophrenia is a chronic mental disease that disturbs several cognitive functions, such as memory, thought, perception and volition. Schizophrenia’s biological etiology is multifactorial and is still under investigation. Melatonin has been involved in schizophrenia since the first decades of the twentieth century. Research into melatonin regarding schizophrenia has followed two different approaches. The first approach is related to the use of melatonin as a biological marker. The second approach deals with the clinical applications of melatonin as a drug treatment. In this paper, both aspects of melatonin application are reviewed. Its clinical use in schizophrenia is emphasized.

Armando L. Morera-Fumero; Pedro Abreu-Gonzalez

2013-01-01

93

Melatonin labeled with hydrogen isotopes  

International Nuclear Information System (INIS)

[en] A study has been made of isotope exchange between melatonin and deuterium (D2O) or tritium (HTO) oxide under different conditions. The ease of isotope exchange for the indole ring hydrogens of melatonin in an acidic medium decreases over the series H4 > H2 H6 >> H7, enabling the authors to process a route for production of melatonin labeled with hydrogen isotopes at positions 4,6, and 2 of the indole ring. A method has been suggested for producing melatonin labeled with hydrogen isotopes at position 2 by desulfurization of 2-(2,4-dinitro-phenylsulfenyl)melatonin at Ni(Re) (D)

1989-01-10

94

Evaluation And Comparison Of Serum Melatonin Determination In Normal Individuals And Migraine Patients  

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Full Text Available Background: Migraine is a chronic hereditary and relapsing headache. With regard to the prevalence of this ancient disease and its economic complications in country, in this study , nocturnal serum melatonin of migraine patients and control subjects have been evaluated and compared by ELISA kit. Materials and Methods: Fifty migraine patients (mostly women) were compared to a control group (mostly men) matched according to age. Results: Statistical analysis revealed a decrease in nocturnal serum melatonin levels for migraine patients (32.9 28.4) compared to the control one (75.6 56.8). With using of t-test by ELISA kit showed significant difference (p=0.0064). Conclusion: With regard to this, the pineal gland has the main role in the synchronization of the organism with the environmental conditions and migrainous headaches.

Fooladsaz K; Ansari M; Javad Rassaie M

2004-01-01

95

Paroxysmal nocturnal hemoglobinuria.  

UK PubMed Central (United Kingdom)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hemolytic disorder of acquired origin and is clinically manifested by chronic hemolysis, thromboses in various sites, and bone marrow failure. The disease is so rare that the delay in the diagnosis is not uncommon and this bears a tremendous impact on patient management. We present this case to draw attention to this uncommon cause of hemolytic anemia, which should be considered in any patient, of any age, who has signs of chronic hemolysis.

Paudyal BP; Zimmerman M; Karki A; Neupane H; Kayastha G

2005-01-01

96

Paroxysmal nocturnal hemoglobinuria.  

Science.gov (United States)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hemolytic disorder of acquired origin and is clinically manifested by chronic hemolysis, thromboses in various sites, and bone marrow failure. The disease is so rare that the delay in the diagnosis is not uncommon and this bears a tremendous impact on patient management. We present this case to draw attention to this uncommon cause of hemolytic anemia, which should be considered in any patient, of any age, who has signs of chronic hemolysis. PMID:16082407

Paudyal, B P; Zimmerman, M; Karki, A; Neupane, H; Kayastha, G

97

Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease  

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Full Text Available Disturbed sleep is common in chronic obstructive pulmonary disease (COPD). Conventional hypnotics worsen nocturnal hypoxemia and, in severe cases, can lead to respiratory failure. Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions. This randomized, double-blind, placebo-controlled study was carried out to determine the effects of melatonin on sleep in COPD. Thirty consecutive patients with moderate to very severe COPD were initially recruited for the study. None of the participants had a history of disease exacerbation 4 weeks prior to the study, obstructive sleep apnea, mental disorders, current use of oral steroids, methylxanthines or hypnotic-sedative medication, nocturnal oxygen therapy, and shift work. Patients received 3 mg melatonin (N = 12) or placebo (N = 13), orally in a single dose, 1 h before bedtime for 21 consecutive days. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness was measured by the Epworth Sleepiness Scale. Pulmonary function and functional exercise level were assessed by spirometry and the 6-min walk test, respectively. Twenty-five patients completed the study protocol and were included in the final analysis. Melatonin treatment significantly improved global PSQI scores (P = 0.012), particularly sleep latency (P = 0.008) and sleep duration (P = 0.046). No differences in daytime sleepiness, lung function and functional exercise level were observed. We conclude that melatonin can improve sleep in COPD. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.

D.M. Nunes; R.M.S. Mota; M.O. Machado; E.D.B. Pereira; V.M.S. de Bruin; P.F.C. de Bruin

2008-01-01

98

Melatonin and the wintering strategy of the tundra vole, Microtus oeconomus.  

UK PubMed Central (United Kingdom)

Short photoperiod induces physiological changes connected to the wintering of the tundra vole, Microtus oeconomus. The aim of the present study was to investigate the effects of continuous melatonin treatment on selected hormones and enzyme activities associated with energy metabolism in the species. Liver, kidney, and muscle glycogen concentrations and glycogen phosphorylase activities, as well as liver and kidney glucose-6-phosphatase and lipase esterase activities were determined. Plasma leptin, ghrelin, thyroxine, testosterone, cortisol, and melatonin concentrations were also measured. Exogenous melatonin stimulated gluconeogenesis, increased glycogen stores, and reduced fat mobilization in kidneys. Melatonin treatment also increased the food intake of the voles. This may have been mediated via elevated ghrelin levels of the melatonin-treated animals, as ghrelin is known to increase appetite of rodents. Winter metabolism of the species does not seem to require accumulation of fat or extra stores of liver or muscle glycogen. On the contrary, successful wintering of the tundra vole presumably depends on continuous food availability.

Mustonen AM; Nieminen P; Hyvärinen H

2002-06-01

99

Melatonin and Diabetes  

Medline Plus

Full Text Available ... in melatonin levels may increase your risk of Type 2 diabetes. Boston-based researchers used urine and blood sample ... They identified 370 women who did not have Type 2 diabetes at the start, but later developed the disease ...

100

Melatonin Anticancer Effects: Review  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Melatonin (N-acetyl-5-methoxytryptamine, MLT), the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel end...

Di Bella, Giuseppe; Mascia, Fabrizio; Gualano, Luciano; Di Bella, Luigi

 
 
 
 
101

Endogenous melatonin and oxidatively damaged guanine in DNA  

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Full Text Available Abstract Background A significant body of literature indicates that melatonin, a hormone primarily produced nocturnally by the pineal gland, is an important scavenger of hydroxyl radicals and other reactive oxygen species. Melatonin may also lower the rate of DNA base damage resulting from hydroxyl radical attack and increase the rate of repair of that damage. This paper reports the results of a study relating the level of overnight melatonin production to the overnight excretion of the two primary urinary metabolites of the repair of oxidatively damaged guanine in DNA. Methods Mother-father-daughter(s) families (n = 55) were recruited and provided complete overnight urine samples. Total overnight creatinine-adjusted 6-sulphatoxymelatonin (aMT6s/Cr) has been shown to be highly correlated with total overnight melatonin production. Urinary 8-oxo-7,8-dihydro-guanine (8-oxoGua) results from the repair of DNA or RNA guanine via the nucleobase excision repair pathway, while urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) may possibly result from the repair of DNA guanine via the nucleotide excision repair pathway. Total overnight urinary levels of 8-oxodG and 8-oxoGua are therefore a measure of total overnight guanine DNA damage. 8-oxodG and 8-oxoGua were measured using a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry assay. The mother, father, and oldest sampled daughter were used for these analyses. Comparisons between the mothers, fathers, and daughters were calculated for aMT6s/Cr, 8-oxodG, and 8-oxoGua. Regression analyses of 8-oxodG and 8-oxoGua on aMT6s/Cr were conducted for mothers, fathers, and daughters separately, adjusting for age and BMI (or weight). Results Among the mothers, age range 42-80, lower melatonin production (as measured by aMT6s/CR) was associated with significantly higher levels of 8-oxodG (p Conclusion Low levels of endogenous melatonin production among older individuals may lead to higher levels of oxidatively damaged guanine in DNA, thereby possibly increasing the risk of developing cancer. The possible different effects of melatonin in the rates of utilization of pathways for repair of oxidatively damaged guanine in DNA identified between older women and older men are intriguing.

Davanipour Zoreh; Poulsen Henrik E; Weimann Allan; Sobel Eugene

2009-01-01

102

Melatonin: Buffering the Immune System  

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Full Text Available Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed.

Antonio Carrillo-Vico; Patricia J. Lardone; Nuria Álvarez-Sánchez; Ana Rodríguez-Rodríguez; Juan M. Guerrero

2013-01-01

103

Melatonin: buffering the immune system.  

Science.gov (United States)

Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed. PMID:23609496

Carrillo-Vico, Antonio; Lardone, Patricia J; Alvarez-Sánchez, Nuria; Rodríguez-Rodríguez, Ana; Guerrero, Juan M

2013-04-22

104

Melatonin Poisoning: A Case Report  

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Full Text Available Melatonin, also known chemically as N-acetyl-5-methoxytryptamine, is produced in the pineal gland from the precursor tryptophan and secreted into the blood. Its exogenous forms are used for the treatment of sleep disorders and jet lag. Melatonin is sold as a sleep drug at pharmacies in Turkey and throughout the world. In this study, we present a case of attempted suicide by the ingestion of melatonin.

Mehmet Gül; Cesareddin Dikmeta?; Ba?ar Cander; M. Akif Önal; Z. Defne Dündar; At?f Harmankaya

2012-01-01

105

Chronic fluoxetine treatment increases daytime melatonin synthesis in the rodent  

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Full Text Available Gillian W Reierson, Claudio A Mastronardi, Julio Licinio, Ma-Li WongCenter on Pharmacogenomics, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USAAbstract: Circadian rhythm disturbances can occur as part of the clinical symptoms of major depressive disorder and have been found to resolve with antidepressant therapy. The pineal gland is relevant to circadian rhythms as it secretes the hormone melatonin following activation of the cyclic adenosine monophosphate (cAMP) signaling cascade and of arylalkylamine N-acetyltransferase (AA-NAT), the rate-limiting enzyme for its synthesis. Cyclic AMP is synthesized by adenylate cyclases (AC) and degraded by phosphodiesterases (PDEs). Little is known about the contribution of the PDE system to antidepressant-induced alterations in pineal cAMP signaling and melatonin synthesis. In the present study we used enzyme immunoassay to measure plasma melatonin levels and pineal cAMP levels and as well as quantitative real-time polymerase chain reaction to measure pineal expression of PDE, AC, and AA-NAT genes in rats chronically treated with the prototypic antidepressant fluoxetine. We found elevated melatonin synthesis with increased pineal AA-NAT gene expression and daytime plasma melatonin levels and downregulated cAMP signaling with increased PDE and unchanged AC pineal gene expression, and decreased content of pineal cAMP. We conclude that chronic fluoxetine treatment increases daytime plasma melatonin and pineal AA-NAT gene expression despite downregulated pineal cAMP signaling in the rodent.Keywords: antidepressant, melatonin, pineal, nucleotides, cyclic, phosphodiesterase, rat

Gillian W Reierson; Claudio A Mastronardi; Julio Licinio; et al

2009-01-01

106

Melatonin Receptor Genes in Vertebrates  

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Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

Di Yan Li; David Glenn Smith; Rüdiger Hardeland; Ming Yao Yang; Huai Liang Xu; Long Zhang; Hua Dong Yin; Qing Zhu

2013-01-01

107

Melatonin receptor genes in vertebrates.  

UK PubMed Central (United Kingdom)

Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

Li DY; Smith DG; Hardeland R; Yang MY; Xu HL; Zhang L; Yin HD; Zhu Q

2013-01-01

108

Melatonin receptor genes in vertebrates.  

Science.gov (United States)

Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor. PMID:23712359

Li, Di Yan; Smith, David Glenn; Hardeland, Rüdiger; Yang, Ming Yao; Xu, Huai Liang; Zhang, Long; Yin, Hua Dong; Zhu, Qing

2013-05-27

109

A pilot study of the phase angle between cortisol and melatonin in major depression - a potential biomarker?  

UK PubMed Central (United Kingdom)

INTRODUCTION: Hypothalamic-pituitary-adrenal (HPA) axis and melatonin rhythm alterations have been independently reported in major depression (MDD) as well as in insomnia. In this pilot study, we link cortisol and melatonin rhythms and propose that the phase angle between cortisol acrophase (CA) and dim-light melatonin onset (20 pg/ml) (DLMO-20) may yield a useful state specific biomarker for MDD. METHODS: Six healthy (HC) and six depressed (MDD) psychotropic free subjects were admitted to the General Clinical Research Center. Blood was sampled for cortisol and melatonin from 1600h to 1000h, under dim lights (<20lux) and constant routine. Time for DLMO-20 and peak cortisol concentration was determined for each subject. Phase angle was computed as the difference in time between CA and DLMO-20. RESULTS: Phase angle was significantly increased in MDD's versus HC's (13.40+/-1.61h. versus 11.61+/-1.66h, p=0.026). Using ROC analysis, a phase angle greater than 13.57h distinguished MDD's from HC's (sensitivity=0.83, specificity=1.0). Mean nocturnal melatonin (1600-1000h) was significantly decreased in MDD's versus HC's (22.67+/-9.08 pg/ml versus 47.82+/-14.76 pg/ml, p=0.015). CONCLUSIONS: The phase angle between CA and DLMO-20 appears to distinguish HC's from MDD's and may be a useful biomarker to aid biologic assessment as well as treatment. Lower nocturnal melatonin in MDD's highlights its importance in MDD's pathophysiology. Additional study with larger sample size is needed to confirm the results of this pilot study. The mechanism for this phase angle difference and decreased melatonin, itself, requires further study.

Buckley TM; Schatzberg AF

2010-01-01

110

Hepatoprotective actions of melatonin: Possible mediation by melatonin receptors  

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Full Text Available Melatonin, the hormone of darkness and messenger of the photoperiod, is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone’s intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo, and summarizes the extensive literature showing that melatonin may be a suitable experimental substance to reduce liver damage after sepsis, hemorrhagic shock, ischemia/reperfusion, and in numerous models of toxic liver injury. Melatonin’s influence on hepatic antioxidant enzymes and other potentially relevant pathways, such as nitric oxide signaling, hepatic cytokine and heat shock protein expression, are evaluated. Based on recent literature demonstrating the functional relevance of melatonin receptor activation for hepatic organ protection, this article finally suggests that melatonin receptors could mediate the hepatoprotective actions of melatonin therapy.

Alexander M Mathes

2010-01-01

111

Manipulating melatonin in managing mood.  

UK PubMed Central (United Kingdom)

OBJECTIVE: Disturbances in circadian rhythms have been associated with major depression and may be an underlying mechanism for the disorder. Resynchronisation of circadian rhythms may provide a new approach to treatment, especially by manipulating melatonin secretion. Melatonin is secreted at night and is a stable marker of circadian rhythms. The timing of its secretion can be changed by exogenous melatonin, agonism of specific melatonin receptors in the suprachiasmatic nucleus, its suppression by light and by sleep deprivation. METHOD: As part of a series of papers ['Chronobiology of mood disorders' Malhi & Kuiper. Acta Psychiatr Scand 2013;128 (Suppl. 444): 2-15; and 'Getting depression clinical practice guidelines right: time for change?' Kuiper et al. Acta Psychiatr Scand 2013;128 (Suppl. 444): 24-30.] addressing chronobiology, in this article, we conducted a selective review of studies that have examined the antidepressant effects of exogenous melatonin, light therapy, sleep deprivation and melatonin receptor agonists. RESULTS: Antidepressant effects were identified for bright light therapy, especially for seasonal affective disorder; sleep deprivation, although its antidepressant effect is time limited; and for the novel antidepressant agomelatine with agonistic properties for the MT1 and MT2 receptors and antagonism of 5HT2c receptor. The role of melatonin as an antidepressant has yet to be demonstrated. CONCLUSION: Shifting the circadian secretion of melatonin using the strategies reviewed offers a new approach to treating depression.

Boyce P; Hopwood M

2013-01-01

112

Melatonin and human skin aging.  

UK PubMed Central (United Kingdom)

Like the whole organism, skin follows the process of aging during life-time. Additional to internal factors, several environmental factors, such as solar radiation, considerably contribute to this process. While fundamental mechanisms regarding skin aging are known, new aspects of anti-aging agents such as melatonin are introduced. Melatonin is a hormone produced in the glandula pinealis that follows a circadian light-dependent rhythm of secretion. It has been experimentally implicated in skin functions such as hair cycling and fur pigmentation, and melatonin receptors are expressed in many skin cell types including normal and malignant keratinocytes, melanocytes and fibroblasts. It possesses a wide range of endocrine properties as well as strong antioxidative activity. Regarding UV-induced solar damage, melatonin distinctly counteracts massive generation of reactive oxygen species, mitochondrial and DNA damage. Thus, there is considerable evidence for melatonin to be an effective anti-skin aging compound, and its various properties in this context are described in this review.

Kleszczynski K; Fischer TW

2012-07-01

113

A cherry nutraceutical modulates melatonin, serotonin, corticosterone, and total antioxidant capacity levels: effect on ageing and chronotype  

Directory of Open Access Journals (Sweden)

Full Text Available Impaired daily rhythms in vertebrate physiology occur with age. Particularly, age-related changes in melatonin and serotonin rhythms and hypercortisolemia have been reported to be linked to age-related disorders. This study was aimed at assessing the effect of a Jerte Valley cherry-based nutraceutical product (patent no ES 2342141 B1), which contains high levels of tryptophan, serotonin, and melatonin, on the serum melatonin, serotonin, corticosterone, and total antioxidant capacity (TAC) levels in young and old ring doves (Streptopelia risoria) and rats (Rattus norvegicus) as representatives of animals with diurnal and nocturnal habits, respectively. The animals consumed the cherry product for 10 days. Serum melatonin, serotonin, corticosterone, and TAC were measured with commercial ELISA kits. The consumption of the cherry product induced a significant increase in the circulating levels of melatonin and serotonin, as well as in the serum TAC and a significant decrease in the circulating levels of corticosterone in both species and groups of age as compared to their respective values in the control groups. The consumption of a Jerte Valley cherry-based nutraceutical product may help to counteract the decrease in melatonin and serotonin and the increase in oxidative stress, suggesting a potential health benefit especially in aged populations where these parameters have been found to be altered.

Jonathan Delgado; Maria Pilar Terron; Jose Antonio Pariente; Carmen Barriga; Ana Beatriz Rodriguez; Sergio Damian Pared

2012-01-01

114

Effects of melatonin on behavioral changes of neonatal rats in a model of cortical dysplasia.  

UK PubMed Central (United Kingdom)

BACKGROUND: Cortical dysplasia (CD) is associated with several behavioral disorders in both the pediatric and the adult population. The effect of melatonin on behavioral disorders in rats generated CD has not been investigated so far. AIM: To investigate the effects of melatonin administration on activity and anxietic behavior of neonatal rats in a model of CD. MATERIALS AND METHODS: Newborn Sprague-Dawley rats (n=21) were randomized into three groups. On postnatal day 1, one freeze lesion was carried out in 14 rats between bregma and lambda to create a CD model. Another group of neonatal rats served as control group (n=7). Those 14 rats were either administered melatonin (n=7) or vehicle solution (n=7). Melatonin treatment (4 mg/kg/day, i.p.) was initiated ten days after induction of cold injury and continued for three weeks. Animal activity and anxiety were analyzed by using open field and elevated plus maze tests 24h after the last melatonin administration (day 32) in a blind manner. RESULTS: It was observed that CD induced animals spent significantly less time in the open field area when compared to the other groups (p < 0.01). Additionally, the time spent in the open field area was significantly elevated in the melatonin-treated animals compared to both the control and the CD groups (p < 0.01). Accordingly, anxiety scores in the CD group was significantly increased (p < 0.01), and this effect could be reversed by administration of melatonin. CONCLUSIONS: Melatonin exerts protective behavioral effects against cortical dysplasia in newborn rats. Further clinical investigations may prove melatonin as a useful therapeutic adjunct to prevent from possible behavioural damages of cortical dysplasia.

Karadeli HH; Aktekin B; Yilmaz B; Kilic E; Uzar E; Aci A; Bingol CA

2013-08-01

115

Circadian oscillation of melatonin, gonadotropins, sex hormones and SHBG in post-menopausal women showing android and gynoid type obesity.  

Science.gov (United States)

Many clinical manifestations shown by obese women point to the disturbances of secretory activity of hypothalamus-pituitary-ovary axis (h-p-o). Because of antigonadotropic activity of melatonin (MEL) it is essential to define this hormone participation in inducing the disturbances of the h-p-o axis. We evaluated the relationship between MEL secretion and circadian concentrations of LH, FSH, E[_2], P, TT, FT, SHBG as measured at 3 h intervals, in 9 obese women showing android type of adipose tissue distribution (BMI > 30 kg/m[^2]; WHR > 0.8) and in 6 women showing gynoid type of adipose tissue distribution (BMI > 30 kg/m[^2]; WHR < 0.8). All patients were between 55 and 62 years of age. A considerable increase of circadian MEL secretion was observed in all obese patients. Suppression of MEL rhythmicity was observed in all patients, while nocturnal phase shift of MEL occurred only in women showing android type of adipose tissue distribution. Significant decrease of circadian LH, P and SHBG values which was accompanied by the elevation of E[_2], TT and FT levels was observed in women with a disturbed rhythmicity of MEL secretion (particularly in case of androidal-type obesity). Based on these results it is suggested that MEL participates in inducing h-p-o axis disturbances in obese women of post-menopausal age. PMID:10979044

Ostrowska; Buntner; Zwirska-Korczala; Marek; Nowak

1996-09-01

116

Circadian oscillation of melatonin, gonadotropins, sex hormones and SHBG in post-menopausal women showing android and gynoid type obesity.  

UK PubMed Central (United Kingdom)

Many clinical manifestations shown by obese women point to the disturbances of secretory activity of hypothalamus-pituitary-ovary axis (h-p-o). Because of antigonadotropic activity of melatonin (MEL) it is essential to define this hormone participation in inducing the disturbances of the h-p-o axis. We evaluated the relationship between MEL secretion and circadian concentrations of LH, FSH, E[_2], P, TT, FT, SHBG as measured at 3 h intervals, in 9 obese women showing android type of adipose tissue distribution (BMI > 30 kg/m[^2]; WHR > 0.8) and in 6 women showing gynoid type of adipose tissue distribution (BMI > 30 kg/m[^2]; WHR < 0.8). All patients were between 55 and 62 years of age. A considerable increase of circadian MEL secretion was observed in all obese patients. Suppression of MEL rhythmicity was observed in all patients, while nocturnal phase shift of MEL occurred only in women showing android type of adipose tissue distribution. Significant decrease of circadian LH, P and SHBG values which was accompanied by the elevation of E[_2], TT and FT levels was observed in women with a disturbed rhythmicity of MEL secretion (particularly in case of androidal-type obesity). Based on these results it is suggested that MEL participates in inducing h-p-o axis disturbances in obese women of post-menopausal age.

Ostrowska Z; Buntner B; Zwirska-Korczala K; Marek B; Nowak M

1996-09-01

117

Nocturnal catecholamines and immune function in insomniacs, depressed patients, and control subjects.  

UK PubMed Central (United Kingdom)

Insomnia predicts cardiovascular and non-cardiovascular disease mortality. This study evaluated EEG sleep, nocturnal sympathetic activity, and daytime measures of immune function in subjects with primary insomnia (n = 17) and patients with current major depression (n = 14) as compared to controls (n = 31). Insomniacs showed disordered sleep continuity along with nocturnal increases of average levels of circulating norepinephrine and decreases of natural killer cell responses, whereas depressed patients showed declines of natural killer cell activity, but no differences of EEG sleep or nocturnal catecholamines as compared to controls. Impairments of sleep efficiency correlated with nocturnal elevations of norepinephrine in the insomniacs but not in the depressives or controls. These data indicate that insomnia is associated with nocturnal sympathetic arousal and declines of natural immunity, and further support the role of sleep in the regulation of sympathetic nervous and immune system functioning.

Irwin M; Clark C; Kennedy B; Christian Gillin J; Ziegler M

2003-10-01

118

Beneficial effects of melatonin on reperfusion injury in rat sciatic nerve.  

Science.gov (United States)

Studies have shown that ischemia-reperfusion (I/R) produces free radicals leading to lipid peroxidation and to damage of the nervous tissue. Melatonin, a main secretory product of the pineal gland, has free radical scavenging and antioxidant properties and has been shown to diminish I/R injury in many tissues. There are a limited number of studies related to the effects of melatonin on I/R injury in the peripheral nervous system. Therefore, in the present study, the protective effect of melatonin was investigated in rats subjected to 2 hr of sciatic nerve ischemia followed by 3 hr of reperfusion. Following reperfusion, nerve tissue samples were collected for quantitative assessment of malondialdehyde (MDA), an oxidative stress marker, and superoxide dismutase (SOD), a principal antioxidant enzyme. Samples were further evaluated at electron microscopic level to examine the neuropathological changes. I/R elevated the concentration of MDA significantly while there was a reduction at SOD levels. Melatonin treatment reversed the I/R-induced increase and decrease in MDA and SOD levels, respectively. Furthermore, melatonin salvaged the nerve fibers from ischemic degeneration. Histopathologic findings in the samples of melatonin-treated animals indicated less edema and less damage to the myelin sheaths and axons than those observed in the control samples. Our results suggest that administration of melatonin protects the sciatic nerve from I/R injury, which may be attributed to its antioxidant property. PMID:15357657

Sayan, Hale; Ozacmak, V Haktan; Ozen, Oguz Aslan; Coskun, Omer; Arslan, S Oktay; Sezen, S Cem; Aktas, R Gulhan

2004-10-01

119

Beneficial effects of melatonin on reperfusion injury in rat sciatic nerve.  

UK PubMed Central (United Kingdom)

Studies have shown that ischemia-reperfusion (I/R) produces free radicals leading to lipid peroxidation and to damage of the nervous tissue. Melatonin, a main secretory product of the pineal gland, has free radical scavenging and antioxidant properties and has been shown to diminish I/R injury in many tissues. There are a limited number of studies related to the effects of melatonin on I/R injury in the peripheral nervous system. Therefore, in the present study, the protective effect of melatonin was investigated in rats subjected to 2 hr of sciatic nerve ischemia followed by 3 hr of reperfusion. Following reperfusion, nerve tissue samples were collected for quantitative assessment of malondialdehyde (MDA), an oxidative stress marker, and superoxide dismutase (SOD), a principal antioxidant enzyme. Samples were further evaluated at electron microscopic level to examine the neuropathological changes. I/R elevated the concentration of MDA significantly while there was a reduction at SOD levels. Melatonin treatment reversed the I/R-induced increase and decrease in MDA and SOD levels, respectively. Furthermore, melatonin salvaged the nerve fibers from ischemic degeneration. Histopathologic findings in the samples of melatonin-treated animals indicated less edema and less damage to the myelin sheaths and axons than those observed in the control samples. Our results suggest that administration of melatonin protects the sciatic nerve from I/R injury, which may be attributed to its antioxidant property.

Sayan H; Ozacmak VH; Ozen OA; Coskun O; Arslan SO; Sezen SC; Aktas RG

2004-10-01

120

Variation in nocturnality and circadian activity rhythms between photoresponsive F344 and nonphotoresponsive Sprague Dawley rats  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Variation in circadian rhythms and nocturnality may, hypothetically, be related to or independent of genetic variation in photoperiodic mediation of seasonal changes in physiology and behavior. We hypothesized that strain variation in photoperiodism between photoperiodic F344 rats and nonphotoperiodic Harlan Sprague Dawley (HSD) rats might be caused by underlying variation in clock function. We predicted that HSD rats would have more activity during the day or subjective day, longer free-running rhythms, poor entrainment to short day length, and shorter duration of activity, traits that have been associated with nonphotoperiodism in other laboratory rodent species, relative to F344 rats. An alternative hypothesis, that differences are due to variation in melatonin secretion or responses to melatonin, predicts either no such differences or inconsistent combinations of differences. Methods We tested these predictions by examining activity rhythms of young male F344 and HSD rats given access to running wheels in constant dark (DD), short day length (L8:D16; SD), and long day length (L16:D8; LD). We compared nocturnality (the proportion of activity during night or subjective night), duration of activity (alpha), activity onset and offset, phase angle of entrainment, and free running rhythms (tau) of F344 and HSD rats. Results HSD rats had significantly greater activity during the day, were sometimes arrhythmic in DD, and had significantly longer tau than F344 rats, consistent with predictions. However, HSD rats had significantly longer alpha than F344 rats and both strains entrained to SD, inconsistent with predictions. Conclusion The ability of HSD rats to entrain to SD, combined with longer alpha than F344 rats, suggests that the circadian system of HSD rats responds correctly to SD. These data offer best support for the alternative hypothesis, that differences in photoresponsiveness between F344 and HSD rats are caused by non-circadian differences in melatonin secretion or the response to melatonin.

Seroka Cheryl D; Johnson Cynthia E; Heideman Paul D

2008-01-01

 
 
 
 
121

The Effects of Red and Blue Lights on Circadian Variations in Cortisol, Alpha Amylase, and Melatonin  

Directory of Open Access Journals (Sweden)

Full Text Available The primary purpose of the present study was to expand our understanding of the impact of light exposures on the endocrine and autonomic systems as measured by acute cortisol, alpha amylase, and melatonin responses. We utilized exposures from narrowband long-wavelength (red) and from narrow-band short-wavelength (blue) lights to more precisely understand the role of the suprachiasmatic nuclei (SCN) in these responses. In a within-subjects experimental design, twelve subjects periodically received one-hour corneal exposures of 40 lux from the blue or from the red lights while continuously awake for 27 hours. Results showed-that, as expected, only the blue light reduced nocturnal melatonin. In contrast, both blue and red lights affected cortisol levels and, although less clear, alpha amylase levels as well. The present data bring into question whether the nonvisual pathway mediating nocturnal melatonin suppression is the same as that mediating other responses to light exhibited by the endocrine and the autonomic nervous systems.

Mariana G. Figueiro; Mark S. Rea

2010-01-01

122

Poor sleep in PCOS; is melatonin the culprit?  

UK PubMed Central (United Kingdom)

STUDY QUESTION: Are daily cycles in urinary melatonin and oxidative stress marker levels (8-hydroxydeoxyguanosine) altered in PCOS, and is this associated with changes in sleep quality? SUMMARY ANSWER: There is an association between elevated nighttime melatonin and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, and poor sleep quality in our PCOS study group. WHAT IS KNOWN ALREADY: Women with PCOS are known to have poorer sleep. However, there have been few studies examining the possible association between melatonin levels and sleep quality in women with polycystic ovarian syndrome (PCOS). STUDY DESIGN, SIZE, DURATION: This is a case-control study of PCOS (n = 26) and non-PCOS control (n = 26) subjects recruited from a tertiary gynaecological centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: The participants were requested to complete sleep questionnaires for a month. In a subgroup from these cohorts (PCOS, n = 15; controls, n = 18), urine samples were also collected at various time points over a 24-h period. In addition, their sleep patterns and lighting environment were monitored for 3 consecutive days and nights using a wrist-mounted Actiwatch device. MAIN RESULTS AND THE ROLE OF CHANCE: PCOS women had significantly elevated night-time urinary levels of the melatonin metabolite 6-sulfatoxymelatonin (aMT6s) and of 8-OHdG (both at P < 0.05), as well as significantly reduced sleep quality (P < 0.05), compared with the controls. LIMITATIONS, REASONS FOR CAUTION: Due to the small sample size of the study, further studies will be required to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: Our preliminary work provides a possible new insight into the interactions between melatonin, increased oxidative stress and sleep in women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Faculty of Medicine, University of Southampton.

Shreeve N; Cagampang F; Sadek K; Tolhurst M; Houldey A; Hill CM; Brook N; Macklon N; Cheong Y

2013-05-01

123

Thermoperiodic influences on plasma melatonin rhythms in the lizard Tiliqua rugosa: effect of thermophase duration.  

Science.gov (United States)

Rhythms of plasma melatonin levels were determined in lizards (Tiliqua rugosa) subjected to a 12 h photocycle (12 h light: 12 h dark) at constant 33 degrees C, and at 7 different thermoperiods (33 degrees C thermophase and 15 degrees C cryophase) whose thermophase duration ranged from 1.5 to 21 h. The melatonin secretion rate, as measured by the amplitude and duration of elevated melatonin levels and the area under the curve, was maximal at thermoperiods whose thermophase was between 9 and 18 h in duration. The results indicate that in ectothermic vertebrates the prevailing thermoperiod as well as the photoperiod may influence melatonin rhythms and hence the timing of annual physiological cycles. PMID:2020370

Firth, B T; Kennaway, D J; Belan, I

1991-01-01

124

Thermoperiodic influences on plasma melatonin rhythms in the lizard Tiliqua rugosa: effect of thermophase duration.  

UK PubMed Central (United Kingdom)

Rhythms of plasma melatonin levels were determined in lizards (Tiliqua rugosa) subjected to a 12 h photocycle (12 h light: 12 h dark) at constant 33 degrees C, and at 7 different thermoperiods (33 degrees C thermophase and 15 degrees C cryophase) whose thermophase duration ranged from 1.5 to 21 h. The melatonin secretion rate, as measured by the amplitude and duration of elevated melatonin levels and the area under the curve, was maximal at thermoperiods whose thermophase was between 9 and 18 h in duration. The results indicate that in ectothermic vertebrates the prevailing thermoperiod as well as the photoperiod may influence melatonin rhythms and hence the timing of annual physiological cycles.

Firth BT; Kennaway DJ; Belan I

1991-01-01

125

Regularly scheduled, day-time, slow-onset 60 Hz electric and magnetic field exposure does not depress serum melatonin concentration in nonhuman primates  

Energy Technology Data Exchange (ETDEWEB)

Experiments conducted with laboratory rodents indicate that exposure to 60 Hz electric fields or magnetic fields can suppress nocturnal melatonin concentrations in pineal gland and blood. In three experiments employing three field-exposed and three sham-exposed nonhuman primates, each implanted with an indwelling venous cannula to allow repeated blood sampling, the authors studied the effects of either 6 kV/m and 50 {micro}T (0.5 G) or 30 kV/m and 100 {micro}T (1.0 G) on serum melatonin patterns. The fields were ramped on and off slowly, so that no transients occurred. Extensive quality control for the melatonin assay, computerized control and monitoring of field intensities, and consistent exposure protocols were used. No changes in nocturnal serum melatonin concentration resulted from 6 weeks of day-time exposure with slow field onset/offset and a highly regular exposure protocol. These results indicate that, under the conditions tested, day-time exposure to 60 Hz electric and magnetic fields in combination does not result in melatonin suppression in primates.

Rogers, W.R.; Smith, H.D.; Orr, J.L. [Southwest Research Inst., San Antonio, TX (United States); Reiter, R.J.; Barlow-Walden, L. [Univ. of Texas Health Science Center, San Antonio, TX (United States)

1995-12-31

126

Evidence for a seasonal variation in the ability of exogenous melatonin to suppress prolactin secretion in the mare.  

UK PubMed Central (United Kingdom)

In seasonally breeding species photoperiodic information is thought to be conveyed to the reproductive and prolactin axis via changes in circulating concentrations of melatonin. For some species, a constant melatonin stimulus is perceived as a short day, whereas in others no photoperiodic information is provided. In the mare, a preliminary study demonstrated that constant administration of melatonin did not modify prolactin secretion, suggesting that this treatment regimen failed to provide photoperiodic information. To further investigate this proposal and to investigate an alternative explanation, namely a seasonal variation in response to melatonin, 4 experiments were performed. In experiments 1-3, the effects of constant administration of melatonin on prolactin secretion were investigated. In each study the time of treatment initiation varied beginning before the summer solstice, (May 9; Exp. 1), at the autumnal equinox (Sept. 21; Exp. 2) or the winter solstice (Dec. 21; Exp. 3). In Experiment 4, melatonin was administered as a timed daily injection (5 PM) for 6 months, beginning at the summer solstice (June 21). Constantly elevated physiological concentrations of melatonin (expts. 1-3) and an extended nighttime elevation of melatonin (exp. 4) suppressed prolactin concentrations only during the spring and early summer months (April-August). At other times during the year prolactin concentrations were similar to untreated mares. In the presence of a continuous melatonin implant the circannual rhythm of prolactin secretion was not disturbed. The results suggest that the prolactin axis of the mare is sensitive to an inhibitory melatonin signal during a restricted period of time and that at other times is refractory to this signal.

Fitzgerald BP; Davison LA; McManus CJ

2000-05-01

127

Melatonin in pathogenesis and therapy of cancer  

Directory of Open Access Journals (Sweden)

Full Text Available Melatonin is a neuroendocrine hormone secreted by the pineal gland to transduce the body?s circadian rhythms. An internal 24 hour time keeping system (biological clock) regulated by melatonin, controls the sleep-wake cycle. Melatonin production is a highly conserved evolutionary phenomenon. The indole hormone is synthesized in the pinealocytes derived from photoreceptors. Altered patterns and/or levels of melatonin secretion have been reported to coincide with sleep disorders, jetlag, depression, stress, reproductive activities, some forms of cancer and immunological disorders. Lately, the physiological and pathological role of melatonin has become a priority area of investigation, particularly in breast cancer, melanoma, colon cancer, lung cancer and leukemia. According to the ?melatonin hypothesis? of cancer, the exposure to light at night (LAN) and anthropogenic electric and magnetic fields (EMFs) is related to the increased incidence of breast cancer and childhood leukaemia via melatonin disruption. Melatonin?s hypothermic, antioxidant and free radical scavenging properties, attribute it to an immunomodulator and an oncostatic agent as well. Many clinical studies have envisaged the potential therapeutic role of melatonin in various pathophysiological disorders, particularly cancer. A substantial reduction in risk of death and low adverse effects were reported from various randomized controlled trials of melatonin treatment in cancer patients. This review summarizes the physiological significance of melatonin and its potential role in cancer therapy. Furthermore, the article focuses on melatonin hypothesis to represent the cause-effect relationship of the three aspects: EMF, LAN and cancer.

Ravindra T; Lakshmi N; Ahuja Y

2006-01-01

128

Altered metabolism in the melatonin-related receptor (GPR50) knockout mouse.  

UK PubMed Central (United Kingdom)

The X-linked orphan receptor GPR50 shares 45% homology with the melatonin receptors, yet its ligand and physiological function remain unknown. Here we report that mice lacking functional GPR50 through insertion of a lacZ gene into the coding sequence of GPR50 exhibit an altered metabolic phenotype. GPR50 knockout mice maintained on normal chow exhibit lower body weight than age-matched wild-type littermates by 10 wk of age. Furthermore, knockout mice were partially resistant to diet-induced obesity. When placed on a high-energy diet (HED) for 5 wk, knockout mice consumed significantly more food per unit body weight yet exhibited an attenuated weight gain and reduced body fat content compared with wild-type mice. Wheel-running activity records revealed that, although GPR50 knockout mice showed no alteration of circadian period, the overall levels of activity were significantly increased over wild types in both nocturnal and diurnal phases. In line with this, basal metabolic rate (O2 consumption, CO2 production, and respiratory quotient) was found to be elevated in knockout mice. Using in situ hybridization (wild-type mice) and beta-galactosidase activity (from LacZ insertion element in knockout mice), brain expression of GPR50 was found to be restricted to the ependymal layer of the third ventricle and dorsomedial nucleus of the hypothalamus. GPR50 expression was highly responsive to energy status, showing a significantly reduced expression following both fasting and 5 wk of HED. These data implicate GPR50 as an important regulator of energy metabolism.

Ivanova EA; Bechtold DA; Dupré SM; Brennand J; Barrett P; Luckman SM; Loudon AS

2008-01-01

129

Altered metabolism in the melatonin-related receptor (GPR50) knockout mouse.  

Science.gov (United States)

The X-linked orphan receptor GPR50 shares 45% homology with the melatonin receptors, yet its ligand and physiological function remain unknown. Here we report that mice lacking functional GPR50 through insertion of a lacZ gene into the coding sequence of GPR50 exhibit an altered metabolic phenotype. GPR50 knockout mice maintained on normal chow exhibit lower body weight than age-matched wild-type littermates by 10 wk of age. Furthermore, knockout mice were partially resistant to diet-induced obesity. When placed on a high-energy diet (HED) for 5 wk, knockout mice consumed significantly more food per unit body weight yet exhibited an attenuated weight gain and reduced body fat content compared with wild-type mice. Wheel-running activity records revealed that, although GPR50 knockout mice showed no alteration of circadian period, the overall levels of activity were significantly increased over wild types in both nocturnal and diurnal phases. In line with this, basal metabolic rate (O2 consumption, CO2 production, and respiratory quotient) was found to be elevated in knockout mice. Using in situ hybridization (wild-type mice) and beta-galactosidase activity (from LacZ insertion element in knockout mice), brain expression of GPR50 was found to be restricted to the ependymal layer of the third ventricle and dorsomedial nucleus of the hypothalamus. GPR50 expression was highly responsive to energy status, showing a significantly reduced expression following both fasting and 5 wk of HED. These data implicate GPR50 as an important regulator of energy metabolism. PMID:17957037

Ivanova, Elena A; Bechtold, David A; Dupré, Sandrine M; Brennand, John; Barrett, Perry; Luckman, Simon M; Loudon, Andrew S I

2007-10-23

130

Nocturnal polyuria in monosymptomatic nocturnal enuresis refractory to desmopressin treatment  

DEFF Research Database (Denmark)

The transition from day to night is associated with a pronounced decline in diuresis with reductions in the amount of excreted water, electrolytes, and other end products of our metabolism. Failure to do so leads to a large urine output at night, a condition known as nocturnal polyuria, encountered in a large proportion of children with nocturnal enuresis. The aim of this study was to clarify the mechanisms responsible for the nocturnal polyuria seen in enuretics with inadequate response to desmopressin (dDAVP). Forty-six enuretics (7-14 yr of age) and fifteen age-matched controls were admitted for a 24-h protocol with standardized fluid and sodium intake, comprising urine collections, blood sampling, and blood pressure monitoring. We included patients with severe enuresis (5 +/- 1 wet nights/wk) showing

Kamperis, K; Rittig, S

2006-01-01

131

The rat oocyte synthesises melatonin.  

UK PubMed Central (United Kingdom)

Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine originally identified in the pineal gland, where it is synthesised enzymatically from serotonin (5-hydroxytryptamine) by the sequential action of arylalkylamine N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT; also known as hydroxyindole O-methyltransferase). Melatonin directly affects ovarian functions and previous studies have suggested that melatonin is synthesised in the ovary. In the present study, we examined whether AANAT and ASMT are expressed in the adult rat ovary. Reverse transcription-polymerase chain reaction analyses demonstrated that both AANAT and ASMT mRNAs are expressed in the ovary. Western blotting for AANAT protein showed that the ovary, like the pineal gland, contains this enzymatic protein with a molecular mass of 24kDa. Immunohistochemistry revealed that the AANAT protein is localised to the oocyte, corpus luteum and medulla, including mast cells. AANAT protein was found in oocytes at all stages of follicular development, and its levels in oocytes increased progressively throughout follicular development. Furthermore, isolated oocytes metabolised exogenous serotonin to melatonin. These findings demonstrate that melatonin is synthesised from serotonin in oocytes. Melatonin synthesised in the oocyte may be implicated in its own growth or maturation, for example, by acting as a calmodulin antagonist or an antioxidant.

Sakaguchi K; Itoh MT; Takahashi N; Tarumi W; Ishizuka B

2013-01-01

132

Nocturnal aircraft noise effects.  

UK PubMed Central (United Kingdom)

Noise protection associated with the construction and extension of airports in the Federal Republic of Germany has been regulated by the law for protection against aircraft noise since 1971. This legislation is due for revision because of different aspects. One aspect is the growth of air traffic which has led many airports to the limits of their capacity and in search of new ways of adaptation to the increasing demand for flight services. Another aspect is the increasing concern of the population about noise effects which has to be addressed by better protection against the effects of aircraft noise. The framework conditions of policy in terms of society as a whole, its health and economic environment need to be put into effect by political action. Science can contribute to this goal by performing noise effects research and by providing recommendations to the political body. However, it remains controversial, what measures are necessary or adequate to assure effective protection of the population against aircraft noise. This is particularly true for the protection of rest and sleep at night. The problem of finding a common basis for adequate recommendations is associated with (1) the low number of primary studies, which also exhibited highly variable results and assessments, (2) the handling of acoustic or psycho-acoustic dimensions for quantifying psychological or physiological reactions, and (3) the conception of how far preventive measures have to go to prove effective. With this in mind, the DLR Institute for Aerospace Medicine is conducting a large-scale, multi-stage study for investigating the acute effects of nocturnal aircraft noise on human sleep. This enterprise is implemented in the framework of the HGF/DLR project "Quiet Air Traffic" for developing sustainable assessment criteria for human-specific effects of aircraft noise at night.

Basner M; Samel A

2004-01-01

133

21 CFR 522.1350 - Melatonin implant.  

Science.gov (United States)

... 2010-04-01 false Melatonin implant. 522.1350 Section 522.1350...ANIMAL DRUGS § 522.1350 Melatonin implant. (a) Specifications . The drug is a silicone rubber elastomer implant containing 2.7 milligrams of...

2010-04-01

134

Thermal sensitivity of reptilian melatonin rhythms: "cold" tuatara vs. "warm" skink.  

Science.gov (United States)

Daily rhythms in plasma melatonin levels were compared in two ecologically diverse reptilian species under natural environmental conditions in autumn. The nocturnal, cold temperature-adapted tuatara (Sphenodon punctatus) had a melatonin rhythm of much lower amplitude than did the diurnal desert-adapted sleepy lizard (Tiliqua rugosa). Experiments in controlled laboratory environments showed that, although both species are capable of attaining a comparable melatonin peak (approximately 750 pmol/l), the threshold temperature at which a significant daily rhythm occurs is approximately 15 degrees C in S. punctatus compared with approximately 25 degrees C in T. rugosa. This difference probably reflects the disparate thermoregulatory adaptations of the two species, S. punctatus favoring mean activity temperatures of 11.5 degrees C and T. rugosa, 32.5 degrees C. In ectotherms such as reptiles, therefore, species-typical thermoregulatory behavior may provide thermal cues that interact with photoperiod to provide the appropriate melatonin signal for the regulation of annual physiological cycles. PMID:2719158

Firth, B T; Thompson, M B; Kennaway, D J; Belan, I

1989-05-01

135

Nocturnal 6-hydroxymelatonin sulfate excretion in female workers exposed to magnetic fields  

Energy Technology Data Exchange (ETDEWEB)

The objective of this study was to determine whether daytime occupational exposure to extremely low frequency magnetic fields (MFs) suppresses nocturnal melatonin production. Sixty female volunteers were recruited. Thirty-nine worked in a garment factory, and 21 office workers served as a reference group. Exposure assessment was based on the type of sewing machine used and MF measurements around each type of machine. Eye-level MF flux density was used to classify the operators to higher (> 1 microT) and lower (0.3-1 microT) exposure categories. A third group of factory workers had diverse MF exposures from other sources. The reference group had average exposure of about 0.15 microT. Urine samples were collected on Friday and Monday for three consecutive weeks. Melatonin production was assessed as urinary 6-hydroxymelatonin sulfate (6-OHMS) excretion. The ratio of Friday morning/Monday morning 6-OHMS was used to test the hypothesis that melatonin production is suppressed after 4 days of occupational MF exposure with significant recovery during the weekend. Possible chronic suppression of melatonin production was evaluated by studying exposure-related differences in the Friday values by multivariate regression analysis. The Monday/Friday ratios were close to 1.0, suggesting that there is no increase in melatonin production over the weekend. The average 6-OHMS excretion on Friday was lower among the factory workers than in the reference group, but no monotonous dose-response was observed. Multivariate regression analysis identified MF exposure, smoking, and age as significant explanatory variables associated with decreased 6-OHMS excretion.

Juutilainen, J (Kuopio, University of); Stevens, Richard G.(BATTELLE (PACIFIC NW LAB)); Anderson, Larry E.(BATTELLE (PACIFIC NW LAB)); Hansen, Norman H.(WAVEID); Kilpelainen, M (Kuopio, University of); Kumlin, T (Kuopio, University of); Laitinen, J T.(Kuopio, University of); Sobell, Eugene (Southern California, Univ Of); Wilson, Bary W.(BATTELLE (PACIFIC NW LAB))

2000-03-15

136

Sleepless in America: Compounding with Melatonin.  

UK PubMed Central (United Kingdom)

Studies of Melatonin in the 1970s and 1980s revealed sedative and hypnotic properties of the compound, which have led to its use in treating sleep disorders. Commonly used for jet lag, melatonin is relatively inexpensive and associated with minimal side effects. Regulation of melatonin secretion appears to be abnormal in children and adults in which pervasive development disorders have been observed. Alteration in melatonin rhythm may be responsible for sleep-onset and maintenance difficulties in autism. A recent review concluded that melatonin primarily acts on the total length of time needed to fall asleep and on the total length of sleep. In addition, melatonin, which does not induce dependence or withdrawal syndromes, may have advantages compared to commonly prescribed benzodiazepines. While there is an enormous amount of anecdotal information available, additional studies are necessary involving melatonin for the treatment of sleep disorders. The condition of these well-controlled studies must be clearly defined, especially in regards to the melatonin formulation and pharmacology of the products used. Various areas remain unclear, such as how the effects of melatonin vary by age, gender, ethnicity, and comorbid conditions of the population, as well as formulation, timing, and duration of melatonin administration. While the U.S. Food and Drug Administration does not strictly regulate herbs and supplements, based on available studies and clinical use, melatonin is generally regarded as safe in recommended doses when used in the short term. The safety of melatonin when used in the long term remains unclear.

Wynn T Rph; Rawlings K

2010-01-01

137

Electric power, melatonin, and breast cancer  

Energy Technology Data Exchange (ETDEWEB)

In this paper, the epidemiology of breast cancer will be discussed, followed by a brief description of the effect of electric fields on melatonin and the relation of melatonin to mammary cancer in rats. Finally, there will be a consideration of factors such as alcohol that affect melatonin and their relation to breast cancer risk. 55 refs.

Stevens, R.G.

1987-08-01

138

The effect of night illumination, red and infrared light, on locomotor activity, behaviour and melatonin of Senegalese sole (Solea senegalensis) broodstock.  

UK PubMed Central (United Kingdom)

The present study aimed to determine a non-invasive nocturnal lighting system for the behavioural observation of a highly light sensitive species, Senegalese sole (Solea senegalensis). Locomotor activity, four types of behaviour and plasma melatonin were analysed in groups of 12 adult Senegalese sole (Solea senegalensis) reared in captivity and held under four night illumination treatments: total darkness (control), high 50lux intensity red light (group RH), low 5lux intensity red light (group RL) and infrared light (group IR). All groups experienced the same conditions during the day (lights on from 07:00 to 19:00) with white lighting of 125lux. Clarity of video images taken at night for the observation of fish behaviour were ranked as follows: group RH>RL>IR>control. All treatments presented a daily rhythm in locomotor activity with high activity from 14:00 to 18:00 and low activity from 21:00 to 12:00. The sole exposed to the high intensity red light at night appeared to be disturbed as during the low nocturnal locomotor activity period group RH presented higher activity and significantly higher nocturnal behaviour related to escape or fear than was observed in the other groups. The groups control, RL and IR exhibited similar levels of nocturnal locomotor activity and nocturnal behaviour related to escape or fear. Plasma melatonin, at mid-dark was not significantly different between the control and groups RL and IR, while melatonin was significantly lower in group RH compared to the control. The authors recommended low intensity red night illumination for the non-invasive study of nocturnal behaviour of Senegalese sole adults.

Carazo I; Norambuena F; Oliveira C; Sánchez-Vázquez FJ; Duncan NJ

2013-06-01

139

Ketotifen-induced nocturnal bruxism.  

UK PubMed Central (United Kingdom)

Nocturnal bruxism is a common oromandibular movement disorder highly prevalent in children, but its pathophysiological mechanism has not been fully explained. Iatrogenic sleep bruxism has been described following treatment with several psychotropic medications. However, no case of antihistamine-induced bruxism has been reported to date. Herein, we describe a 4-year-old child who experienced nocturnal bruxism during treatment for bronchospasm and rhinitis with the antihistamine ketotifen. Drug rechallenge was also performed. Conclusion: The present case adds useful information to our knowledge of bruxism. Complex and poorly understood interactions between multiple central nervous system neurotransmitters, such as histamine, serotonin, and dopamine, are involved.

Italiano D; Bramanti P; Militi D; Mondello S; Calabro RS

2013-08-01

140

Mood disorders, circadian rhythms, melatonin and melatonin agonists.  

UK PubMed Central (United Kingdom)

Recent advances in the understanding of circadian rhythms have led to an interest in the treatment of major depressive disorder with chronobiotic agents. Many tissues have autonomous circadian rhythms, which are orchestrated by the master clock, situated in the suprachiasmatic nucleus (SNC). Melatonin (N-acetyl-5-hydroxytryptamine) is secreted from the pineal gland during darkness. Melatonin acts mainly on MT1 and MT2 receptors, which are present in the SNC, regulating physiological and neuroendocrine functions, including circadian entrainment, referred to as the chronobiotic effet. Circadian rhythms has been shown to be either misaligned or phase shifted or decreased in amplitude in both acute episodes and relapse of major depressive disorder (MDD) and bipolar disorder. Manipulation of circadian rhythms either using physical treatments (such as high intensity light) or behavioral therapy has shown promise in improving symptoms. Pharmacotherapy using melatonin and pure melatonin receptor agonists, while improving sleep, has not been shown to improve symptoms of depression. A novel antidepressant, agomelatine, combines 5HT2c antagonist and melatonin agonist action, and has shown promise in both acute treatment of MDD and in preventing relapse.

Quera Salva MA; Hartley S

2012-01-01

 
 
 
 
141

Methylphenidate effects on blood serotonin and melatonin levels may help to synchronise biological rhythms in children with ADHD.  

UK PubMed Central (United Kingdom)

UNLABELLED: The neuroendocrine mediators that may contribute to ADHD (Attention deficit and hyperactivity disorder), serotonin and melatonin, are both thought to regulate circadian rhythms, neurological function and stress response. The objective of this study was to determine the effect of the chronic administration of prolonged release methylphenidate (PRMPH) on daily variations in blood serotonin and melatonin and on the excretion of 6-sulphatoxy-melatonin. A total of 179 children (136 males, 42 females) between the ages of 5 and 14 (9.70 ± 2.55) years were enrolled in a controlled quasi-experimental open clinical study. Of the sample, there were 136 Children with ADHD (based on DSM-IV-TR criteria), who were further grouped into subtypes, and the 42 siblings of the participants who did not ADHD patients. Blood samples were taken at 20:00 and 09:00; urine was collected between 21:00 and 09:00. In the ADHD group, the study protocol was repeated after 4.61 ± 2.3 months of treatment. Measurements included melatonin and serotonin by RIA and urine 6-S-aMT by ELISA. Factorial analyses were conducted by STATA 12.0. RESULTS: ADHD patients showed reduced morning serotonin with a daily profile that was different than the control group due to the predominance of nocturnal concentrations. PRMPH did not result in any significant changes. Melatonin and its daily profile did not differ between controls and the ADHD group with a diurnal rhythm showing higher morning levels that disappear after PRMPH administration. Melatonin was higher in children with predominantly hyperactive-impulsive/conduct disorder subtype. PRMPH resulted in a decrease in 6-S-aMT excretion for both ADHD subtypes. CONCLUSION: Chronic treatment with prolonged release methylphenidate induces subtle changes in the daily fluctuations and concentrations of both serotonin and melatonin. Improvement in Children's Depression Inventory (CDI) scores was not related to a morning increase in serotonin.

Molina-Carballo A; Naranjo-Gómez A; Uberos J; Justicia-Martínez F; Ruiz-Ramos MJ; Cubero-Millán I; Contreras-Chova F; Augustin-Morales MD; Khaldy-Belkadi H; Muñoz-Hoyos A

2013-03-01

142

Is the melatonin receptor type 1 involved in the pathogenesis of glaucoma?  

Science.gov (United States)

Melatonin in the mammalian eye is synthesized by the photoreceptors and its levels show a clear daily pattern with high levels at night and lower levels during the day. It is synthesized in the ciliary body and secreted into the aqueous humor with a pattern similar to what has been reported for the retina. It acts by interacting with a family of G-protein coupled receptors that are negatively coupled with adenylate cyclase. Melatonin receptor subtypes MT1 and MT2 have been identified in the retina. Both are found in the inner nuclear layer (horizontal and amacrine cells), in the inner plexiform layer, ganglion cells (RGC) and retinal pigmented epithelium. They are also present in the ciliary body. Several studies implicate melatonin in the rhythmic regulation of intraocular pressure. MT1 and MT2 melatonin receptors are expressed in many parts of the eye. Melatonin receptors are expressed in the iris and ciliary body. Recent studies showed that mice lacking MT1 receptors have elevated intraocular pressure during the night and show a significantly reduced number of RGCs. These new studies suggest that dysfunctional melatonin signaling may be considered a possible risk factor in the pathogenesis of glaucoma and that mice deficient in MT1 receptors may be an animal model of glaucoma. PMID:23733129

Tosini, Gianluca; Boatright, Jeffrey H

143

Is the melatonin receptor type 1 involved in the pathogenesis of glaucoma?  

UK PubMed Central (United Kingdom)

Melatonin in the mammalian eye is synthesized by the photoreceptors and its levels show a clear daily pattern with high levels at night and lower levels during the day. It is synthesized in the ciliary body and secreted into the aqueous humor with a pattern similar to what has been reported for the retina. It acts by interacting with a family of G-protein coupled receptors that are negatively coupled with adenylate cyclase. Melatonin receptor subtypes MT1 and MT2 have been identified in the retina. Both are found in the inner nuclear layer (horizontal and amacrine cells), in the inner plexiform layer, ganglion cells (RGC) and retinal pigmented epithelium. They are also present in the ciliary body. Several studies implicate melatonin in the rhythmic regulation of intraocular pressure. MT1 and MT2 melatonin receptors are expressed in many parts of the eye. Melatonin receptors are expressed in the iris and ciliary body. Recent studies showed that mice lacking MT1 receptors have elevated intraocular pressure during the night and show a significantly reduced number of RGCs. These new studies suggest that dysfunctional melatonin signaling may be considered a possible risk factor in the pathogenesis of glaucoma and that mice deficient in MT1 receptors may be an animal model of glaucoma.

Tosini G; Boatright JH

2013-06-01

144

Correlations between behavioural and oxidative parameters in a rat quinolinic acid model of Huntington's disease: protective effect of melatonin.  

UK PubMed Central (United Kingdom)

The present study was designed to examine the correlations between behavioural and oxidative parameters in a quinolinic acid model of Huntington's disease in rats. The protective effect of melatonin against the excitotoxicity induced by quinolinic acid was investigated. Rats were pre-treated with melatonin (5 or 20mg/kg) before injection of quinolinic acid (240nmol/site; 1?l) into their right corpora striata. The locomotor and exploratory activities as well as the circling behaviour were recorded. The elevated body swing test was also performed. After behavioural experiments, biochemical determinations were carried out. Melatonin partially protected against the increase of circling behaviour caused by quinolinic acid injection. No alteration was found in the number of crossings and rearings of animals treated with melatonin and/or quinolinic acid. Melatonin decreased the percentage of contralateral biased swings induced by quinolinic acid. Melatonin protected against the increase in reactive species and protein carbonyl levels as well as the inhibition of superoxide dismutase activity resulting from quinolinic acid injection. Melatonin was partially effective against the inhibition of striatal catalase activity and a decrease of non-protein thiol levels induced by quinolinic acid. Melatonin was not effective against the inhibition of Na(+), K(+) ATPase activity caused by quinolinic acid injection. There were significant correlations between circling behaviour and oxidative parameters. The antioxidant property of melatonin is involved, at least in part, in its neuroprotective effect. The results reinforce the idea that melatonin could be useful in overwhelming neurotoxicity caused by quinolinic acid, a rat model of Huntington's disease.

Antunes Wilhelm E; Ricardo Jesse C; Folharini Bortolatto C; Wayne Nogueira C

2013-02-01

145

Dopamine D2 receptor as a cellular component controlling nocturnal hyperactivities in Drosophila melanogaster.  

UK PubMed Central (United Kingdom)

Dysfunctional regulation of brain dopamine (DA) functions has been found in patients with drug addiction and various neurological disorders that frequently accompany disturbance in sleep behavior. In this study, the roles of the dopaminergic nervous system on the regulation of daily locomotor activity rhythm were investigated in Drosophila melanogaster. Reduced synaptic DA release by expressing tetanus toxin gradually attenuated peak activity levels by altering activity patterns, particularly under constant darkness. Besides, flies with a mutant dopamine transporter fumin (fmn), in which the synaptic DA levels were elevated, displayed increased activities in both daytime and nighttime, but did more so at nighttime, suggesting that DA function is involved in regulation of fruit fly's nocturnal locomotor activities. Furthermore, flies treated with bromocriptine, an agonist of Drosophila dopamine D2 receptor (dD2R), exhibited nocturnal locomotor hyperactivity in a dose-dependent manner and this effect was inhibited in dD2R knockdown flies. When mutant flies null for period (per), timeless (tim), dClock (dClk), or cycle (cyc) were treated with bromocriptine, only cycle-null flies (cyc(01)) did not show induced nocturnal hyperactivities, suggesting that cyc might play a role in bromocriptine-induced nocturnal hyperactivities. Elevation of experimental temperature also increased nocturnal activities at the expense of daytime activities. The heat-induced increase in nocturnal activities gradually returned to basal levels at continuously elevated temperature. Inhibition of DA synthesis did not suppress heat-induced early development of nocturnal hyperactivity but prevented gradual decrement of initially elevated nocturnal activities, suggesting that DA impinges on certain adaptive roles in response to changes in environmental temperature. These results overall suggest that controlling dopaminergic transmission is important for daily locomotor behavior and bromocriptine-induced nocturnal hyperactivity which is mediated through dD2R receptor and CYC functions. In parallel to these results, excessive activation of dopaminergic neurotransmission, the primary cause of schizophrenia, is associated with abnormally elevated nocturnal locomotor activities through D2-type receptor in Drosophila. The results suggest that fruit flies are an excellent model system to provide some answers to previously unexplainable observations regarding the compromised dopaminergic nervous system and the related therapeutic agents.

Lee G; Kikuno K; Bahn JH; Kim KM; Park JH

2013-05-01

146

Melatonin, immune function and aging  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence of cancer, infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. A decrease in functional competence of individual natural killer (NK) cells is found with advancing age. Macrophages and granulocytes show functional decline in aging as evidenced by their diminished phagocytic activity and impairment of superoxide generation. There is also marked shift in cytokine profile as age advances, e.g., CD3+ and CD4+ cells decline in number whereas CD8+ cells increase in elderly individuals. A decline in organ specific antibodies occurs causing reduced humoral responsiveness. Circulating melatonin decreases with age and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes-macrophages. It also stimulates the production of NK cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from NK cells and T-helper lymphocytes also are enhanced by melatonin. Melatonin presumably regulates immune function by acting on the immune-opioid network, by affecting G protein-cAMP signal pathway and by regulating intracellular glutathione levels. Melatonin has the potential therapeutic value to enhance immune function in aged individuals and in patients in an immunocompromised state.

Srinivasan V; Maestroni GJM; Cardinali DP; Esquifino AI; Perumal SR Pandi; Miller SC

2005-01-01

147

The effects of melatonin on the antioxidant systems in experimental spinal injury.  

UK PubMed Central (United Kingdom)

Melatonin has been recently shown by various in-vivo and in-vitro studies to exert potent neutralising effects on hydroxyl radicals, stimulate glutathione peroxidase (GSH-Px) activity, and protect catalase (CAT) from the destructive activity of hydroxyl radicals in neural tissue. We aimed to investigate the possible effects of pharmacological dose of melatonin on some of the antioxidant defence systems in an in-vivo study of experimental spinal injury. Seven groups of adult male Sprague Dawley rats were used in the following scheme: Group I: Naive (n = 6), Group II: Lesion (n = 8), Group III: Melatonin (n = 5), Group IV: Melatonin + Lesion (n = 8), Group V: Placebo + Lesion (n = 5), Group VI: Sham operation (n = 5), and Group VII: Placebo (n = 5). Experimental spinal injury was induced at level T7-T8 by 5 sec compression of the total cord with an aneurysm clip on anaesthetised and laminectomized animals. The total 10 mg/kg dose of melatonin (Sigma) dissolved in alcohol-water was administered i.p. four times in 2.5 mg/kg doses, at 20 min pre-, at the time of and at 1 h and 2h post-compression. At 24 +/- 2h post-injury, the rats were euthanized and the lesioned segments of cord were dissected and homogenised with special care taken to distribute equal amount of injured tissue in each sample for analysis of reduced glutathione (GSH), oxidised glutathione (GSSG), superoxide dismutase (SOD), and CAT activity. Compression injury decreased GSH/GSSG ratio significantly (p < .0001). Melatonin, by itself, significantly decreased GSSG content (p < .05) and increased CAT activity (p < .05) in the naïve rats. Melatonin treatment decreased GSSG activity, thus elevating GSH/GSSG ratio, and also increased SOD and CAT activity without reaching statistical significance in the lesioned animals. In conclusion, pharmacological dose of systemically applied melatonin seemed to support some features of the antioxidant defence systems in our hands.

Taskiran D; Tanyalcin T; Sozmen EY; Peker GO; Gulmen V; Cagli S; Kanit L; Tekeli G; Barcin E; Zileli M; Kutay FZ

2000-09-01

148

The effects of melatonin on the antioxidant systems in experimental spinal injury.  

Science.gov (United States)

Melatonin has been recently shown by various in-vivo and in-vitro studies to exert potent neutralising effects on hydroxyl radicals, stimulate glutathione peroxidase (GSH-Px) activity, and protect catalase (CAT) from the destructive activity of hydroxyl radicals in neural tissue. We aimed to investigate the possible effects of pharmacological dose of melatonin on some of the antioxidant defence systems in an in-vivo study of experimental spinal injury. Seven groups of adult male Sprague Dawley rats were used in the following scheme: Group I: Naive (n = 6), Group II: Lesion (n = 8), Group III: Melatonin (n = 5), Group IV: Melatonin + Lesion (n = 8), Group V: Placebo + Lesion (n = 5), Group VI: Sham operation (n = 5), and Group VII: Placebo (n = 5). Experimental spinal injury was induced at level T7-T8 by 5 sec compression of the total cord with an aneurysm clip on anaesthetised and laminectomized animals. The total 10 mg/kg dose of melatonin (Sigma) dissolved in alcohol-water was administered i.p. four times in 2.5 mg/kg doses, at 20 min pre-, at the time of and at 1 h and 2h post-compression. At 24 +/- 2h post-injury, the rats were euthanized and the lesioned segments of cord were dissected and homogenised with special care taken to distribute equal amount of injured tissue in each sample for analysis of reduced glutathione (GSH), oxidised glutathione (GSSG), superoxide dismutase (SOD), and CAT activity. Compression injury decreased GSH/GSSG ratio significantly (p < .0001). Melatonin, by itself, significantly decreased GSSG content (p < .05) and increased CAT activity (p < .05) in the naïve rats. Melatonin treatment decreased GSSG activity, thus elevating GSH/GSSG ratio, and also increased SOD and CAT activity without reaching statistical significance in the lesioned animals. In conclusion, pharmacological dose of systemically applied melatonin seemed to support some features of the antioxidant defence systems in our hands. PMID:11011974

Taskiran, D; Tanyalcin, T; Sozmen, E Y; Peker, G O; Gulmen, V; Cagli, S; Kanit, L; Tekeli, G; Barcin, E; Zileli, M; Kutay, F Z

149

Melatonin Reduces Ulcerative Colitis-Associated Local and Systemic Damage in Mice: Investigation on Possible Mechanisms.  

UK PubMed Central (United Kingdom)

BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic gastrointestinal disorder. Substantial research reveals that melatonin has beneficial effects in ulcerative colitis both experimentally and clinically. We have previously reported that ulcerative colitis was associated with local and systemic damage in mice. The purpose of this study was to reveal the novel targets of melatonin in its protective mechanism against ulcerative colitis in mice. We also wished to determine whether or not melatonin protected against ulcerative colitis-induced systemic damage in mice. METHODS: Ulcerative colitis was induced in mice by use of 3 % (w/v) dextran sulfate sodium for two cycles. One cycle comprised 7 days of DSS-treated water followed by 14 days of normal drinking water. Melatonin was administered at doses of 2, 4, or 8 mg/kg bw/day, po throughout. The effect of melatonin in mice with UC was evaluated by use of biochemical data, histological evaluation, comet and micronucleus assays, immunohistochemistry, and western blot analysis. RESULTS: The results indicated that melatonin treatment ameliorated the severity of ulcerative colitis by modulating a variety of molecular targets, for example nuclear factor kappa B, cyclooxygenase-2, interleukin 17, signal transducer and activator of transcription 3, nuclear erythroid 2-related factor 2, matrix metalloproteinase-9, and connective tissue growth factor. Further, ulcerative colitis increased gut permeability, plasma lipopolysaccharide level, systemic inflammation, and genotoxicity. Melatonin treatment led to mucosal healing and reduced ulcerative colitis-induced elevated gut permeability and reduced the plasma LPS level, systemic inflammation, and genotoxicity. CONCLUSION: Melatonin ameliorated ulcerative colitis-associated local and systemic damage in mice.

Trivedi PP; Jena GB

2013-08-01

150

Microdialysis of melatonin in the confluens sinuum of the rat following quantification by gas chromatography-mass spectrometry in the negative chemical ion mode.  

UK PubMed Central (United Kingdom)

In this study, an original surgical implantation technique in the confluens sinuum via the superior sagittal vein was developed to quantify melatonin secretion by the pineal gland. Melatonin (CAS 73-31-4) was determined using gas chromatography couples to negative ion chemical ionisation mass spectrometry following liquid extraction and derivatisation by penta-fluoropropionic acid anhydride (PFPA). The minimum detectable amount was 40 fg per injection, corresponding to 1 pg.ml-1 in dialysate. The assay was linear in the range 20-1000 pg.ml-1. This method was suitable for routine melatonin determination in dialysats of peripheral and central circulation with coefficients of variation of 11.2 and 24.6%, respectively for within and between analyses. Profiles of melatonin concentration were obtained (n = 3 rats) over a 2-day experimentation with a slowly diminution of the filtration capacity of the probe during the second day. The nocturnal concentrations of melatonin in the confluens sinuum dialysat ranged from 1003.9 to 2345 pg.ml-1 in the dialysat, indicating wide interindividual variations in the melatonin levels.

Boudra H; Saivin S; Delagrange P; Malmary MF; Genissel P; Houin G

1999-10-01

151

Microdialysis of melatonin in the confluens sinuum of the rat following quantification by gas chromatography-mass spectrometry in the negative chemical ion mode.  

Science.gov (United States)

In this study, an original surgical implantation technique in the confluens sinuum via the superior sagittal vein was developed to quantify melatonin secretion by the pineal gland. Melatonin (CAS 73-31-4) was determined using gas chromatography couples to negative ion chemical ionisation mass spectrometry following liquid extraction and derivatisation by penta-fluoropropionic acid anhydride (PFPA). The minimum detectable amount was 40 fg per injection, corresponding to 1 pg.ml-1 in dialysate. The assay was linear in the range 20-1000 pg.ml-1. This method was suitable for routine melatonin determination in dialysats of peripheral and central circulation with coefficients of variation of 11.2 and 24.6%, respectively for within and between analyses. Profiles of melatonin concentration were obtained (n = 3 rats) over a 2-day experimentation with a slowly diminution of the filtration capacity of the probe during the second day. The nocturnal concentrations of melatonin in the confluens sinuum dialysat ranged from 1003.9 to 2345 pg.ml-1 in the dialysat, indicating wide interindividual variations in the melatonin levels. PMID:10554663

Boudra, H; Saivin, S; Delagrange, P; Malmary, M F; Genissel, P; Houin, G

1999-10-01

152

Karanl???n hormonu: Melatonin  

Directory of Open Access Journals (Sweden)

Full Text Available Melatonin (5-methoxy-N-acetyltryptamine) hormonu pineal bez ve retina ba?ta olmak üzere çe?itli periferik organ ve dokularda sentezlenir. Melatonin sekresyonunun endojen ritmi suprakiazmatik nukleus taraf?ndan düzenlenir ve karanl?k ayd?nl?k siklüsü ile sürdürülür. Melatonin di?er hormonlar?n regülasyonunu ve organizman?n sirkadyen ritmini düzenler. Amfofilik yap?s? ve küçük moleküllü olmas? nedeniyle organizmada yayg?n da??l?m gösterir, hücresel kompartmanlara kolayca girer. Güçlü antioksidan özelli?i olan bu do?al bile?ik in vitro ve in vivo güçlü bir sitostatik ajand?r. Melatoninin etkinli?i oküler hastal?klarda, diyabette, romatoid artritte, fibromyaljide, kronik yogrunluk sendromunda, enfeksiyon hastal?klar?nda, nörolojik hastal?klarda, uyku bozukluklar?nda, ya?lanmada ve depresyonda gösterilmi?tir. Bu derlemede melatoninin farmakokinetik özellikleri, fizyolojik ve farmakolojik etkileri özetlenmi?tir.

Göksel ?ener

2010-01-01

153

Polysomnographic determinants of nocturnal hypercapnia in patients with sleep apnea.  

UK PubMed Central (United Kingdom)

STUDY OBJECTIVES: Identify polysomnographic and demographic factors associated with elevation of nocturnal end-tidal CO2 in patients with obstructive sleep apnea. METHODS: Forty-four adult patients with obstructive sleep apnea were selected such that the maximal nocturnal end-tidal CO2 was below 45 mm Hg in 15 studies, between 45 and 50 mm Hg in 14, and above 50 mm Hg in 15. Measurements included mean event (i.e., apneas or hypopneas) and mean inter-event duration, ratio of mean post- to mean pre-event amplitude, and percentage of total sleep time spent at an end-tidal CO2 < 45, 45-50, and > 50 mm Hg. An integrated nocturnal CO2 was calculated as the sum of the products of average end-tidal CO2 at each time interval by percent of total sleep time spent at the corresponding time interval. RESULTS: The integrated nocturnal CO2 was inversely correlated with mean post-apnea duration, with lesser contributions from mean apnea duration and age (R (2) = 0.56), but did not correlate with the apnea-hypopnea index, or the body mass index. Mean post-event to mean pre-event amplitude correlated with mean post-apnea duration (r = 0.88, p < 0.001). Mean apnea duration did not correlate with mean post-apnea duration. CONCLUSIONS: Nocturnal capnometry reflects pathophysiologic features of sleep apnea, such as the balance of apnea and post-apnea duration, which are not captured by the apnea-hypopnea index. This study expands the indications of capnometry beyond apnea detection and quantification of hypoventilation syndromes.

Jaimchariyatam N; Dweik RA; Kaw R; Aboussouan LS

2013-03-01

154

Simulation of peak pineal melatonin release restores sensitivity to evening melatonin injections in pinealectomized hamsters.  

UK PubMed Central (United Kingdom)

In intact hamsters held on LD 14:10, pineal melatonin production and release peaks late in the evening. If these animals receive a daily injection of melatonin approximately 8 h before the endogenous peak (at the time of lights out), they respond with testicular regression. Pinealectomized hamsters receiving only this evening injection do not respond. The hypothesis tested here is very simple: replacement of the pineal melatonin rhythm in pinealectomized hamsters with a daily melatonin injection at the time of peak melatonin release in intact hamsters should reestablish sensitivity to evening (lights out) injections of melatonin. Conversely, melatonin replacement at times other than this should be ineffective. Pinealectomized hamsters maintained on LD 14:10 (lights 0600 - 2000 h) were injected with melatonin (15 microgram) at the time of the endogenous melatonin peak (2 h prior to lights on) and in the evening (0.5 h prior to lights out). This injection paradigm produced a rapid testicular regression that appears to be dependent on the timing of melatonin injections with respect to the animal's circadian system. Two daily injections given with the same frequency (8.5 h apart) but during a different time of the day were not effective. The results suggest that rhythmic sensitivity to melatonin is not affected by removal of the pineal, and that this gland serves as the source of endogenous melatonin, which must be present at the proper time for exogenous injections of melatonin to produce testicular regression.

Watson-Whitmyre M; Stetson MH

1983-02-01

155

Melatonin anticancer effects: review.  

Science.gov (United States)

Melatonin (N-acetyl-5-methoxytryptamine, MLT), the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate). The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation). All these particular characteristics suggest the use of MLT in oncological diseases. PMID:23348932

Di Bella, Giuseppe; Mascia, Fabrizio; Gualano, Luciano; Di Bella, Luigi

2013-01-24

156

Melatonin anticancer effects: review.  

UK PubMed Central (United Kingdom)

Melatonin (N-acetyl-5-methoxytryptamine, MLT), the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate). The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation). All these particular characteristics suggest the use of MLT in oncological diseases.

Di Bella G; Mascia F; Gualano L; Di Bella L

2013-01-01

157

Melatonin reduces X-ray radiation-induced lung injury in mice by modulating oxidative stress and cytokine expression.  

UK PubMed Central (United Kingdom)

PURPOSE: The modification of radiation-induced lung injuries by melatonin was studied by measuring changes in oxidative stress, cytokine expression and histopathology in the lung tissue of mice following irradiation. MATERIALS AND METHODS: The thoraces of C57BL/6 mice were exposed to a single X-ray radiation dose of 12 Gy with or without 200 mg/kg of melatonin pretreatment. The level and localization of transforming growth factor (TGF)-?1 protein were measured using an enzyme-linked immunosorbent assay (ELISA) method and immunohistochemical staining, respectively. Real-time quantitative polymerase chain reaction (PCR) was established to evaluate the relative mRNA expression levels of TGF-?1, tumor necrosis factor (TNF)-?, interleukin (IL)-1? and IL-6. RESULTS: Malondialdehyde (MDA) levels increased after irradiation and then significantly reduced (1.9-fold) under melatonin treatment. Changes in superoxide dismutase (SOD) and catalase activities, as well as glutathione (GSH) levels, after irradiation were significantly reduced by melatonin, including a notable 5.4-fold difference in catalase activity. We observed increased expression of TGF-?1 and TNF-? after irradiation and a significant reduction in the elevation of their expression by melatonin treatment. Furthermore, irradiation-induced histopathologic alterations were obviously abated in the melatonin-pretreated mice. CONCLUSIONS: The present results suggest that melatonin reduces radiation-induced lung injury via a significant reduction of oxidative stress and of the production of cytokines, such as TGF-?1 and TNF-?, the production of which increased following lung irradiation.

Jang SS; Kim HG; Lee JS; Han JM; Park HJ; Huh GJ; Son CG

2013-02-01

158

Transcriptional suppression of tryptamine 5-hydroxylase, a terminal serotonin biosynthetic gene, induces melatonin biosynthesis in rice (Oryza sativa L.).  

Science.gov (United States)

Rice tryptamine 5-hydroxylase (T5H) is the second enzyme in melatonin biosynthesis, catalyzing tryptamine into serotonin. Transgenic rice plants, in which the expression of endogenous T5H was either overexpressed or repressed, were examined for alteration in melatonin biosynthesis. Unexpectedly, the overexpression genotypes showed reduced levels of melatonin, while the repression genotypes had elevated levels with an average increase of fourfold. With regard to melatonin intermediates, tryptamine and serotonin levels decreased, but tryptophan and N-acetylserotonin were unaltered in the overexpression genotypes compared with the wild type. In contrast, the repression genotypes had sevenfold higher tryptamine levels than the wild type. In addition, tryptophan and 5-hydroxytryptophan were present at higher levels in the repression genotypes than in both the wild-type and the overexpression genotypes. The enhanced melatonin synthesis in the repression genotypes was closely associated with a transcriptional increase in TDC1. When these rice plants were challenged by oxidative stressors such as herbicides, much higher melatonin synthesis was also observed in the repression genotypes than in either the wild-type or overexpression genotypes. These results suggest that the tryptamine increase through the suppression of T5H plays an important signaling role in triggering melatonin biosynthesis in rice, although the exact role of tryptamine remains to be uncovered. PMID:23521226

Park, Sangkyu; Byeon, Yeong; Back, Kyoungwhan

2013-03-22

159

From nocturnal paroxysmal dystonia to nocturnal frontal lobe epilepsy.  

UK PubMed Central (United Kingdom)

Nocturnal paroxysmal dystonia (NPD) is the term used to describe motor attacks characterized by complex behavior, with dystonic-dyskinetic or ballic movements arising from NREM sleep. NPD together with paroxysmal arousals (PA), the briefest attacks, and episodic nocturnal wanderings (ENW), the most prolonged ones, constitute nocturnal frontal lobe epilepsy (NFLE). PA are sudden awakenings associated with stereotyped dystonic-dyskinetic movements, sometimes accompanied by screaming and a frightened expression. ENW are episodes of agitated ambulation, with complex, sometimes violent, motor behavior and dystonic postures involving head, trunk and limbs. NPD, PA and ENW coexist in most patients. NFLE is predominant in males and usually begins during adolescence. A familial recurrence of parasomnias in NFLE patients is much more common than in the general population. Autosomal dominant inheritance has been documented in 6% of our cases. Few patients present personal antecedents or positive neuroradiological findings. Seizures are frequent, occurring every or almost every night, many times per night. Interictal wake and sleep EEG tracings are often normal and ictal epileptic activity is recorded in a relatively small number of cases. Carbamazepine controls or significantly reduces seizures in about 70% of cases; the remainder are drug-resistant. Videopolysomnographic recordings, showing stereotyped abnormal movements during attacks, are mandatory to confirm the diagnosis of NFLE.

Provini F; Plazzi G; Lugaresi E

2000-09-01

160

Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon  

Directory of Open Access Journals (Sweden)

Full Text Available The pineal hormone melatonin exerts its influence in the periphery through activation of two specific trans-membrane receptors: MT1 and MT2. Both isoforms are expressed in the islet of Langerhans and are involved in the modulation of insulin secretion from ?-cells and in glucagon secretion from ?-cells. De-synchrony of receptor signaling may lead to the development of type 2 diabetes. This notion has recently been supported by genome-wide association studies identifying particularly the MT2 as a risk factor for this rapidly spreading metabolic disturbance. Since melatonin is secreted in a clearly diurnal fashion, it is safe to assume that it also has a diurnal impact on the blood-glucose-regulating function of the islet. This factor has hitherto been underestimated; the disruption of diurnal signaling within the islet may be one of the most important mechanisms leading to metabolic disturbances. The study of melatonin–insulin interactions in diabetic rat models has revealed an inverse relationship: an increase in melatonin levels leads to a down-regulation of insulin secretion and vice versa. Elucidation of the possible inverse interrelationship in man may open new avenues in the therapy of diabetes.

Elmar Peschke; Ina Bähr; Eckhard Mühlbauer

2013-01-01

 
 
 
 
161

Pharmacology and function of melatonin receptors  

Energy Technology Data Exchange (ETDEWEB)

The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the pharmacological characteristics and function of melatonin receptors in the central nervous system, and the role of melatonin in mediating physiological functions in mammals. Melatonin and melatonin agonists, at picomolar concentrations, inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the novel melatonin receptor antagonist luzindole (N-0774), which suggests that melatonin activates a presynaptic melatonin receptor. In chicken and rabbit retina, the pharmacological characteristics of the presynaptic melatonin receptor and the site labeled by 2-(125I)iodomelatonin are identical. It is proposed that 2-(125I)iodomelatonin binding sites (e.g., chicken brain) that possess the pharmacological characteristics of the retinal melatonin receptor site (order of affinities: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-di-chloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin greater than N-acetyltryptamine greater than or equal to luzindole greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine much greater than 5-hydroxytryptamine) be classified as ML-1 (melatonin 1). The 2-(125I)iodomelatonin binding site of hamster brain membranes possesses different binding and pharmacological characteristics from the retinal melatonin receptor site and should be classified as ML-2. 64 references.

Dubocovich, M.L.

1988-09-01

162

Pharmacology and function of melatonin receptors  

International Nuclear Information System (INIS)

The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the pharmacological characteristics and function of melatonin receptors in the central nervous system, and the role of melatonin in mediating physiological functions in mammals. Melatonin and melatonin agonists, at picomolar concentrations, inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the novel melatonin receptor antagonist luzindole (N-0774), which suggests that melatonin activates a presynaptic melatonin receptor. In chicken and rabbit retina, the pharmacological characteristics of the presynaptic melatonin receptor and the site labeled by 2-[125I]iodomelatonin are identical. It is proposed that 2-[125I]iodomelatonin binding sites (e.g., chicken brain) that possess the pharmacological characteristics of the retinal melatonin receptor site (order of affinities: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-di-chloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin greater than N-acetyltryptamine greater than or equal to luzindole greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine much greater than 5-hydroxytryptamine) be classified as ML-1 (melatonin 1). The 2-[125I]iodomelatonin binding site of hamster brain membranes possesses different binding and pharmacological characteristics from the retinal melatonin receptor site and should be classified as ML-2. 64 references

1988-01-01

163

Neuromodulatory role of melatonin in retinal information processing.  

UK PubMed Central (United Kingdom)

The neurohormone melatonin is implicated in a variety of physiological processes. In the retina, a major source for melatonin production, melatonin is involved in modulation of neuronal activities. In this article we review recent advances in this research field, which is preceded by a concise account of general information about melatonin, melatonin receptors and intracellular signaling pathways for melatonin actions. Melatonin is mainly synthesized in and released from photoreceptors in the retina. Different subtypes of melatonin receptors are present on major types of retinal neurons, and the expression of these receptors is highly species- and neuron subtype-dependent. By activating different melatonin receptor subtypes, melatonin modulates activities of retinal neurons. In the outer retina, melatonin regulates the activity of photoreceptors. In addition, melatonin reduces the light responsiveness of cone-driven horizontal cells, but potentiates rod signal to rod-dominant ON type bipolar cells in teleost fish or inhibits the TEA-sensitive potassium channel of rod-driven ON type bipolar cells in rats. In the inner retina, melatonin potentiates inputs from glycinergic amacrine cells to ganglion cells in rats. These actions of melatonin on retinal neurons are mediated by distinct intracellular signaling pathways via different subtypes of melatonin receptors and all serve to improve visual performance in a world of changing ambient illumination. The topics, concerning allosteric action of melatonin, interplay between melatonin and dopamine systems, and potential interaction between melatonin and melanopsin systems, are also discussed. An in-depth discussion of future directions in this research field is presented.

Huang H; Wang Z; Weng SJ; Sun XH; Yang XL

2013-01-01

164

[Nocturnal polyuria, treatment with desmopressin].  

Science.gov (United States)

Nonpharmacologic and especially pharmacologic treatment options are available for nocturnal polyuria. Desmopressin represents the basis of pharmacologic treatment. Desmopressin acetate is a synthetic analogue of arginine vasopressin with high affinity to V2 receptors with antidiuretic effect. It is the only medicament currently registered for antidiuretic treatment. Desmopressin has not any relevant affinity to V1 receptors, and therefore there is no hypertensive effect in contrary to natural vasopressin. Desmopressin use before a bedtime leads to reduced production of urine during a sleep, therefore time between desires to void is prolonged and number of nocturia is reduced. Clinical effect, in a meaning of reduced urine production and increased osmolality of urine, lasts approximately 8-12 hours. In the treatment of nocturnal polyuria desmopressin is used orally one hour before a bedtime. It is essential to titrate an ideal dose, the initial dose is 60 µg of MELT formula (fast melting oral formulation) and it can be increased according to the clinical effect up to the maximal recommended daily dose 240 µg. Patients treated with desmopressin should cut down a fluid intake 1 hour before and 8 hours after the use of desmopressin. Total number of adverse events connected withdesmopressin treatment in clinical studies was higher compared to placebo but the side effects were mostly mild. The most common adverse events were headaches, nausea, diarrhoea, abdominal pain, dry mouth and hyponatremia both in the short-term and long-term clinical trials. Hyponatremia was observed mainly in patients over 65 year of age. Therefore treatment with desmopressin should not be commended in patients over 65 year of age without close monitoring of the natrium level in serum and all patients should be informed about the first symptoms of hyponatremia - headache, nausea and insomnia. According to Evidence Based Medicine, the level of evidence for treatment of nocturnal polyuria with desmopressin is 1b and the grade of recommendation for treatment is A. Keywords: nocturnal polyuria - treatment - desmopressin. PMID:24040989

Zachoval, R; Krhut, J; Sottner, O; Hanuš, T; Martan, A; Hor?i?ka, L; Feyereisl, J; Halaška, M; Svabík, K; Krofta, L

2013-08-01

165

[Nocturnal polyuria, treatment with desmopressin].  

UK PubMed Central (United Kingdom)

Nonpharmacologic and especially pharmacologic treatment options are available for nocturnal polyuria. Desmopressin represents the basis of pharmacologic treatment. Desmopressin acetate is a synthetic analogue of arginine vasopressin with high affinity to V2 receptors with antidiuretic effect. It is the only medicament currently registered for antidiuretic treatment. Desmopressin has not any relevant affinity to V1 receptors, and therefore there is no hypertensive effect in contrary to natural vasopressin. Desmopressin use before a bedtime leads to reduced production of urine during a sleep, therefore time between desires to void is prolonged and number of nocturia is reduced. Clinical effect, in a meaning of reduced urine production and increased osmolality of urine, lasts approximately 8-12 hours. In the treatment of nocturnal polyuria desmopressin is used orally one hour before a bedtime. It is essential to titrate an ideal dose, the initial dose is 60 µg of MELT formula (fast melting oral formulation) and it can be increased according to the clinical effect up to the maximal recommended daily dose 240 µg. Patients treated with desmopressin should cut down a fluid intake 1 hour before and 8 hours after the use of desmopressin. Total number of adverse events connected withdesmopressin treatment in clinical studies was higher compared to placebo but the side effects were mostly mild. The most common adverse events were headaches, nausea, diarrhoea, abdominal pain, dry mouth and hyponatremia both in the short-term and long-term clinical trials. Hyponatremia was observed mainly in patients over 65 year of age. Therefore treatment with desmopressin should not be commended in patients over 65 year of age without close monitoring of the natrium level in serum and all patients should be informed about the first symptoms of hyponatremia - headache, nausea and insomnia. According to Evidence Based Medicine, the level of evidence for treatment of nocturnal polyuria with desmopressin is 1b and the grade of recommendation for treatment is A. Keywords: nocturnal polyuria - treatment - desmopressin.

Zachoval R; Krhut J; Sottner O; Hanuš T; Martan A; Hor?i?ka L; Feyereisl J; Halaška M; Svabík K; Krofta L

2013-08-01

166

Effect of indomethacin on desmopressin resistant nocturnal polyuria and nocturnal enuresis  

DEFF Research Database (Denmark)

We evaluated the acute effect of indomethacin on renal water and solute handling in children with coexisting monosymptomatic nocturnal enuresis and desmopressin resistant nocturnal polyuria, and in healthy controls.

Kamperis, Konstantinos; Rittig, SØren

2012-01-01

167

The Angiotensin-melatonin axis.  

UK PubMed Central (United Kingdom)

Accumulating evidence indicates that various biological and neuroendocrine circadian rhythms may be disrupted in cardiovascular and metabolic disorders. These circadian alterations may contribute to the progression of disease. Our studies direct to an important role of angiotensin II and melatonin in the modulation of circadian rhythms. The brain renin-angiotensin system (RAS) may modulate melatonin synthesis, a hormone with well-established roles in regulating circadian rhythms. Angiotensin production in the central nervous system may not only influence hypertension but also appears to affect the circadian rhythm of blood pressure. Drugs acting on RAS have been proven effective in the treatment of cardiovascular and metabolic disorders including hypertension and diabetes mellitus (DM). On the other hand, since melatonin is capable of ameliorating metabolic abnormalities in DM and insulin resistance, the beneficial effects of RAS blockade could be improved through combined RAS blocker and melatonin therapy. Contemporary research is evidencing the existence of specific clock genes forming central and peripheral clocks governing circadian rhythms. Further research on the interaction between these two neurohormones and the clock genes governing circadian clocks may progress our understanding on the pathophysiology of disease with possible impact on chronotherapeutic strategies.

Campos LA; Cipolla-Neto J; Amaral FG; Michelini LC; Bader M; Baltatu OC

2013-01-01

168

Circadian rhythms, melatonin and depression.  

UK PubMed Central (United Kingdom)

The master biological clock situated in the suprachiasmatic nuclei of the anterior hypothalamus plays a vital role in orchestrating the circadian rhythms of multiple biological processes. Increasing evidence points to a role of the biological clock in the development of depression. In seasonal depression and in bipolar disorders it seems likely that the circadian system plays a vital role in the genesis of the disorder. For major unipolar depressive disorder (MDD) available data suggest a primary involvement of the circadian system but further and larger studies are necessary to conclude. Melatonin and melatonin agonists have chronobiotic effects, which mean that they can readjust the circadian system. Seasonal affective disorders and mood disturbances caused by circadian malfunction are theoretically treatable by manipulating the circadian system using chronobiotic drugs, chronotherapy or bright light therapy. In MDD, melatonin alone has no antidepressant action but novel melatoninergic compounds demonstrate antidepressant properties. Of these, the most advanced is the novel melatonin agonist agomelatine, which combines joint MT1 and MT2 agonism with 5-HT(2C) receptor antagonism. Adding a chronobiotic effect to the inhibition of 5-HT(2C) receptors may explain the rapid impact of agomelatine on depression, since studies showed that agomelatine had an early impact on sleep quality and alertness at awakening. Further studies are necessary in order to better characterize the effect of agomelatine and other novel melatoninergic drugs on the circadian system of MDD patients. In summary, antidepressants with intrinsic chronobiotic properties offer a novel approach to treatment of depression.

Quera Salva MA; Hartley S; Barbot F; Alvarez JC; Lofaso F; Guilleminault C

2011-01-01

169

Chronobiology of Melatonin beyond the Feedback to the Suprachiasmatic Nucleus-Consequences to Melatonin Dysfunction.  

UK PubMed Central (United Kingdom)

The mammalian circadian system is composed of numerous oscillators, which gradually differ with regard to their dependence on the pacemaker, the suprachiasmatic nucleus (SCN). Actions of melatonin on extra-SCN oscillators represent an emerging field. Melatonin receptors are widely expressed in numerous peripheral and central nervous tissues. Therefore, the circadian rhythm of circulating, pineal-derived melatonin can have profound consequences for the temporal organization of almost all organs, without necessarily involving the melatonin feedback to the suprachiasmatic nucleus. Experiments with melatonin-deficient mouse strains, pinealectomized animals and melatonin receptor knockouts, as well as phase-shifting experiments with explants, reveal a chronobiological role of melatonin in various tissues. In addition to directly steering melatonin-regulated gene expression, the pineal hormone is required for the rhythmic expression of circadian oscillator genes in peripheral organs and to enhance the coupling of parallel oscillators within the same tissue. It exerts additional effects by modulating the secretion of other hormones. The importance of melatonin for numerous organs is underlined by the association of various diseases with gene polymorphisms concerning melatonin receptors and the melatonin biosynthetic pathway. The possibilities and limits of melatonergic treatment are discussed with regard to reductions of melatonin during aging and in various diseases.

Hardeland R

2013-01-01

170

Chronobiology of Melatonin beyond the Feedback to the Suprachiasmatic Nucleus—Consequences to Melatonin Dysfunction  

Directory of Open Access Journals (Sweden)

Full Text Available The mammalian circadian system is composed of numerous oscillators, which gradually differ with regard to their dependence on the pacemaker, the suprachiasmatic nucleus (SCN). Actions of melatonin on extra-SCN oscillators represent an emerging field. Melatonin receptors are widely expressed in numerous peripheral and central nervous tissues. Therefore, the circadian rhythm of circulating, pineal-derived melatonin can have profound consequences for the temporal organization of almost all organs, without necessarily involving the melatonin feedback to the suprachiasmatic nucleus. Experiments with melatonin-deficient mouse strains, pinealectomized animals and melatonin receptor knockouts, as well as phase-shifting experiments with explants, reveal a chronobiological role of melatonin in various tissues. In addition to directly steering melatonin-regulated gene expression, the pineal hormone is required for the rhythmic expression of circadian oscillator genes in peripheral organs and to enhance the coupling of parallel oscillators within the same tissue. It exerts additional effects by modulating the secretion of other hormones. The importance of melatonin for numerous organs is underlined by the association of various diseases with gene polymorphisms concerning melatonin receptors and the melatonin biosynthetic pathway. The possibilities and limits of melatonergic treatment are discussed with regard to reductions of melatonin during aging and in various diseases.

Rüdiger Hardeland

2013-01-01

171

Effects of evening light conditions on salivary melatonin of Japanese junior high school students  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background In a previous study, when adult subjects were exposed to a level of 400 lux light for more than 30 min or a level of 300 lux light for more than 2 hours, salivary melatonin concentration during the night dropped lower than when the subjects were exposed to dim illumination. It was suggested that such light exposure in adolescents or children during the first half of subjective night in normal life might decrease the melatonin level and prevent the falling into sleep. However, there has been no actual study on the effects of light exposure in adolescents. Methods Effects of exposure to the bright light (2000 lux) from fluorescent light bulbs during a period of three hours from 19:30 to 22:30 in one evening were examined on evening salivary melatonin concentrations from 19:45 to 23:40. The control group was exposed to dim light (60 lux) during these three hours. Both the dim light control group [DLCG] and the bright light experimental group [BLEG] consisted of two female and three male adolescent participants aged 14–15 y. Results The salivary melatonin level increased rapidly from 3.00 pg/ml at 21:45 to 9.18 pg/ml at 23:40 in DLCG, whereas it remained at less than 1.3 pg/ml for the three hours in BLEG. Melatonin concentration by BLEG at 22:30 of the experimental day was lower than that at the same time on the day before the experimental day, whereas it was significantly higher in the experimental day than on the day before the experimental day in DLCG. Conclusions Bright lights of 2000 lux and even moderate lights of 200–300 lux from fluorescent light bulbs can inhibit nocturnal melatonin concentration in adolescents. Ancient Japanese lighting from a traditional Japanese hearth, oil lamp or candle (20–30 lux) could be healthier for children and adolescents because rapid and clear increase in melatonin concentration in blood seems to occur at night under such dim light, thus facilitating a smooth falling into night sleep.

Harada Tetsuo

2004-01-01

172

The Impact of Melatonin on Glucose Homeostasis  

Directory of Open Access Journals (Sweden)

Full Text Available Objective: Melatonin is a pineal product mainly charged with the maintenance of antioxidant conditions in human. This study is performed to identify the short-term effect of melatonin on glucose homeostasis in diabetic patients. Materials and Methods: Melatonin and placebo were given perorally to sixty patients. Blood glucose and insulin levels were measured with constant intervals. Results: No significant correlation was found among the levels of glucose, insulin and HOMA-IR index at any time after melatonin/placebo administration.Conclusions: Prospective studies with long-term use of melatonin are needed to define the exact role of melatonin in glucose homeostasis. Turk Jem 2009; 13: 52-5

Zeynep Arzu Ye?in; Rüya Mutluay; ?ehri Elbeg; Resul Karaku?; Nuri Çak?r

2009-01-01

173

Melatonin modulation of presynaptic nicotinic acetylcholine receptors located on short noradrenergic neurons of the rat vas deferens: a pharmacological characterization  

Scientific Electronic Library Online (English)

Full Text Available Abstract in english Melatonin, the pineal hormone produced during the dark phase of the light-dark cycle, modulates neuronal acetylcholine receptors located presynaptically on nerve terminals of the rat vas deferens. Recently we showed the presence of high affinity nicotine-binding sites during the light phase, and low and high affinity binding sites during the dark phase. The appearance of the low affinity binding sites was due to the nocturnal melatonin surge and could be mimicked by expos (more) ure to melatonin in vitro. The aim of the present research was to identify the receptor subtypes responsible for the functional response during the light and the dark phase. The rank order of potency of agonists was dimethylphenylpiperazinium (DMPP) = cytisine > nicotine > carbachol and DMPP = nicotine = cytisine > carbachol, during the light and dark phase, respectively, due to an increase in apparent affinity for nicotine. Mecamylamine similarly blocked the DMPP response during the light and the dark phase, while the response to nicotine was more efficiently blocked during the light phase. In contrast, methyllycaconitine inhibited the nicotine-induced response only at 21:00 h. Since a7 nicotinic acetylcholine receptors (nAChRs) have low affinity for nicotine in binding assays, we suggest that a mixed population composed of a3ß4 - plus a7-bearing nAChR subtypes is present at night. This plasticity in receptor subtypes is probably driven by melatonin since nicotine-induced contraction in organs from animals sacrificed at 15:00 h and incubated with melatonin (100 pg/ml, 4 h) is not totally blocked by mecamylamine. Thus melatonin, by acting directly on the short adrenergic neurons that innervate the rat vas deferens, induces the appearance of the low affinity binding site, probably an a7 nAChR subtype.

Zago, W.M.; Markus, R.P.

1999-08-01

174

Melatonin modulation of presynaptic nicotinic acetylcholine receptors located on short noradrenergic neurons of the rat vas deferens: a pharmacological characterization  

Directory of Open Access Journals (Sweden)

Full Text Available Melatonin, the pineal hormone produced during the dark phase of the light-dark cycle, modulates neuronal acetylcholine receptors located presynaptically on nerve terminals of the rat vas deferens. Recently we showed the presence of high affinity nicotine-binding sites during the light phase, and low and high affinity binding sites during the dark phase. The appearance of the low affinity binding sites was due to the nocturnal melatonin surge and could be mimicked by exposure to melatonin in vitro. The aim of the present research was to identify the receptor subtypes responsible for the functional response during the light and the dark phase. The rank order of potency of agonists was dimethylphenylpiperazinium (DMPP) = cytisine > nicotine > carbachol and DMPP = nicotine = cytisine > carbachol, during the light and dark phase, respectively, due to an increase in apparent affinity for nicotine. Mecamylamine similarly blocked the DMPP response during the light and the dark phase, while the response to nicotine was more efficiently blocked during the light phase. In contrast, methyllycaconitine inhibited the nicotine-induced response only at 21:00 h. Since a7 nicotinic acetylcholine receptors (nAChRs) have low affinity for nicotine in binding assays, we suggest that a mixed population composed of a3ß4 - plus a7-bearing nAChR subtypes is present at night. This plasticity in receptor subtypes is probably driven by melatonin since nicotine-induced contraction in organs from animals sacrificed at 15:00 h and incubated with melatonin (100 pg/ml, 4 h) is not totally blocked by mecamylamine. Thus melatonin, by acting directly on the short adrenergic neurons that innervate the rat vas deferens, induces the appearance of the low affinity binding site, probably an a7 nAChR subtype.

W.M. Zago; R.P. Markus

1999-01-01

175

Melatonin improves sleep quality in hemodialysis patients.  

UK PubMed Central (United Kingdom)

Disturbed sleep is common in end-stage renal disease (ESRD). Exogenous melatonin has somniferous properties in normal subjects and can improve sleep quality (SQ) in several clinical conditions. Recent studies have shown that melatonin may play a role in improving sleep in patients undergoing dialysis. The goal of the present study was to assess the effect of exogenous melatonin administration on SQ improvement in daytime hemodialysis patients. Lipid profile and the required dose of erythropoietin (EPO) are also reported as secondary outcomes. In a 6-week randomized, double-blind cross-over clinical trial, 3 mg melatonin or placebo was administered to 68 patients at bedtime. A 72-h washout preceded the switch from melatonin to placebo, or vice versa. SQ was assessed by the Pittsburgh sleep quality index (PSQI). Sixty-eight patients completed the study protocol and were included in the final analysis. Melatonin treatment significantly improved the global PSQI scores (P < 0.001), particularly subjective SQ (P < 0.001), sleep efficiency (P = 0.005) and sleep duration (P < 0.001). No differences in sleep latency and daytime sleepiness were observed. Melatonin also increased the high-density lipoprotein (HDL) cholesterol (P = 0.003). The need for EPO prescription decreased after melatonin treatment (P < 0.001). We conclude that melatonin can improve sleep in ESRD. The modest increase in HDL cholesterol and decrease in the EPO requirement are other benefits associated with this treatment.

Edalat-Nejad M; Haqhverdi F; Hossein-Tabar T; Ahmadian M

2013-07-01

176

Melatonin and the wintering strategy of the tundra vole, Microtus oeconomus.  

Science.gov (United States)

Short photoperiod induces physiological changes connected to the wintering of the tundra vole, Microtus oeconomus. The aim of the present study was to investigate the effects of continuous melatonin treatment on selected hormones and enzyme activities associated with energy metabolism in the species. Liver, kidney, and muscle glycogen concentrations and glycogen phosphorylase activities, as well as liver and kidney glucose-6-phosphatase and lipase esterase activities were determined. Plasma leptin, ghrelin, thyroxine, testosterone, cortisol, and melatonin concentrations were also measured. Exogenous melatonin stimulated gluconeogenesis, increased glycogen stores, and reduced fat mobilization in kidneys. Melatonin treatment also increased the food intake of the voles. This may have been mediated via elevated ghrelin levels of the melatonin-treated animals, as ghrelin is known to increase appetite of rodents. Winter metabolism of the species does not seem to require accumulation of fat or extra stores of liver or muscle glycogen. On the contrary, successful wintering of the tundra vole presumably depends on continuous food availability. PMID:12130797

Mustonen, Anne-Mari; Nieminen, Petteri; Hyvärinen, Heikki

2002-06-01

177

Nonstationary nocturnal drainage flow model  

Energy Technology Data Exchange (ETDEWEB)

The evolution and structure of the steady state of an idealized nocturnal drainage flow over a large uniformly-sloping surface are studied usig a nonstationary model with a height-dependent eddy diffusivity profile and a specified surface cooling rate. The predicted mean velocity and temperature profiles are compared with Prandtl's stationary analytical solutions based on the assumption of a constant eddy diffusivity in the drainage layer. The effects of important physical parameters, such as the slope angle, surface cooling, atmospheric stability, and surface roughness, on the steady drainage flow are investigated.

Rao, K.S.; Snodgrass, H.F.

1981-01-01

178

Nocturnal drainage wind characteristics in two converging air sheds  

Energy Technology Data Exchange (ETDEWEB)

During the short experimental period in the Grants Basin of Northeastern New Mexico a survey was conducted on the complex meteorology of this area. Emphasis was placed on the nocturnal drainage flow because of the potential hazards to the populated areas of Milan and Grants from the effluents of the uranium mining and milling operation in this area. This investigation has shown that the nocturnal drainage flow patterns agree with the winds predicted on the basis of the complex terrain of the area. Because of the surface cooling at night (over 25/sup 0/C during summer and about 20/sup 0/C during winter), air from elevated surrounding areas flows to the low lying regions consequently setting up a nocturnal drainage flow. This regime exists over 60% of the time during summer months and over 65% of the time during winter months with a depth generally less than 200 m. In the San Mateo air shed the drainage flow is east northeast, and in the Ambrosia Lake air shed it is from northwest. The confluence of these two air flows contributes mainly to the drainage flow through the channel formed by La Ja Mesa and Mesa Montanosa. The analysis of data collected by the recording Flats Station confirms the prediction that although the area south of the channel region broadens considerably causing a reduction in flow speed, contributions from the southside of La Jara Mesa and Mesa Montanosa partly compensate for this reduction. The position of this recording station is 15 to 20 km from the populated towns of Milan and Grants. A drainage flow speed of approximately 2.2 m s/sup -1/ and the duration of over 11 hours as recorded by this station indicates that air from the San Mateo and Ambrosia Lake regions may be transported southwards to these population centers during a nocturnal period. In order to test this prediction, a series of multi-atmospheric tracer experiments were conducted in the Grants Basin.

Gedayloo, T.; Clements, W.E.; Barr, S.; Archuleta, J.A.

1980-01-01

179

Nocturnal drainage wind characteristics in two converging air sheds  

International Nuclear Information System (INIS)

During the short experimental period in the Grants Basin of Northeastern New Mexico a survey was conducted on the complex meteorology of this area. Emphasis was placed on the nocturnal drainage flow because of the potential hazards to the populated areas of Milan and Grants from the effluents of the uranium mining and milling operation in this area. This investigation has shown that the nocturnal drainage flow patterns agree with the winds predicted on the basis of the complex terrain of the area. Because of the surface cooling at night (over 250C during summer and about 200C during winter), air from elevated surrounding areas flows to the low lying regions consequently setting up a nocturnal drainage flow. This regime exists over 60% of the time during summer months and over 65% of the time during winter months with a depth generally less than 200 m. In the San Mateo air shed the drainage flow is east northeast, and in the Ambrosia Lake air shed it is from northwest. The confluence of these two air flows contributes mainly to the drainage flow through the channel formed by La Ja Mesa and Mesa Montanosa. The analysis of data collected by the recording Flats Station confirms the prediction that although the area south of the channel region broadens considerably causing a reduction in flow speed, contributions from the southside of La Jara Mesa and Mesa Montanosa partly compensate for this reduction. The position of this recording station is 15 to 20 km from the populated towns of Milan and Grants. A drainage flow speed of approximately 2.2 m s-1 and the duration of over 11 hours as recorded by this station indicates that air from the San Mateo and Ambrosia Lake regions may be transported southwards to these population centers during a nocturnal period. In order to test this prediction, a series of multi-atmospheric tracer experiments were conducted in the Grants Basin

1980-03-27

180

Concentração plasmática de melatonina em novilhas bubalinas (Bubalus bubalis) ao longo do ano/ Plasma melatonin in bufallo heifers (Bubalus bubalis) during a year  

Scientific Electronic Library Online (English)

Full Text Available Abstract in portuguese Coletaram-se nove amostras de sangue ao longo do dia, mês-a-mês durante um ano, de seis novilhas bubalinas da raça Mediterrâneo, para determinação da melatonina plasmática dos animais mantidos na latitude 22° Sul. A concentração plasmática de melatonina se elevou lentamente até atingir o pico entre 21 e 23 horas, permanecendo elevada até as 3-5 horas. A seguir, a concentração diminuiu para valores baixos antes do nascer do sol. A duração da elevação not (more) urna de melatonina plasmática não acompanhou a duração do período noturno ao longo do ano e a diminuição da concentração diurna de melatonina plasmática ocorreu na época de maior atividade reprodutiva estimada do rebanho. Abstract in english Nine blood samples were taken to determine plasma melatonin in a 24h-period/month for a year. The six buffalo heifers used were kept at latitude 22° South. Plasma melatonin rose slowly, peaking at night (between 9 and 11pm) and maintained until 3 to 5am. Melatonin concentration decreased day-time to lower levels until sunrise. Nocturnal higher plasmatic melatonin did not vary with night length over the year. Diurnal melatonin concentrations were lower when estimated reproductive rate was the highest for the herd.

Mattos, P.S.R.; Franzolin, R.; Nonaka, K.O.

2000-10-01

 
 
 
 
181

Melatonin-Based Therapeutics for Neuroprotection in Stroke  

Directory of Open Access Journals (Sweden)

Full Text Available The present review paper supports the approach to deliver melatonin and to target melatonin receptors for neuroprotection in stroke. We discuss laboratory evidence demonstrating neuroprotective effects of exogenous melatonin treatment and transplantation of melatonin-secreting cells in stroke. In addition, we describe a novel mechanism of action underlying the therapeutic benefits of stem cell therapy in stroke, implicating the role of melatonin receptors. As we envision the clinical entry of melatonin-based therapeutics, we discuss translational experiments that warrant consideration to reveal an optimal melatonin treatment strategy that is safe and effective for human application.

Kazutaka Shinozuka; Meaghan Staples; Cesar V. Borlongan

2013-01-01

182

Melatonin-based therapeutics for neuroprotection in stroke.  

UK PubMed Central (United Kingdom)

The present review paper supports the approach to deliver melatonin and to target melatonin receptors for neuroprotection in stroke. We discuss laboratory evidence demonstrating neuroprotective effects of exogenous melatonin treatment and transplantation of melatonin-secreting cells in stroke. In addition, we describe a novel mechanism of action underlying the therapeutic benefits of stem cell therapy in stroke, implicating the role of melatonin receptors. As we envision the clinical entry of melatonin-based therapeutics, we discuss translational experiments that warrant consideration to reveal an optimal melatonin treatment strategy that is safe and effective for human application.

Shinozuka K; Staples M; Borlongan CV

2013-01-01

183

Gastrointestinal tract and melatonin: reducing pathophysiology  

Directory of Open Access Journals (Sweden)

Full Text Available Due to its receptor-independent actions as a free radical scavenger and its receptor-mediated functions, melatonin has the capability of reducing a number of pathophysiologies that are common throughout the alimentary canal. The large quantities of melatonin in gut tissues from the stomach to the colon, as well as the exceptionally high levels in bile, support the notion that melatonin is functionally relevant in the gastrointestinal tract. The area of greatest research endeavor to date has related to the ability of melatonin to reduce oxidative damage to the lower esophagus during gastroesophageal reflux and its marked action in reducing gastric ulcers due to a variety of processes, e.g., water immersion and restraint stress, aspirin toxicity, prescription drug toxicity (especially those used to treat osteoporosis) and ethanol. In each of these cases, the concurrent administration of melatonin either partially or totally, prevented the damage resulting from these treatments in experimental animals. A recent study has also revealed that melatonin prevents aspirin toxicity in the stomach of humans. Besides preventing ulcer formation, melatonin has also been found to hasten healing of pre-existing lesions. Finally, melatonin has been shown to reduce gallstone formation; the means by which it does so are multiple. It is the hope of the authors that the data summarized herein will serve as a stimulus for clinical studies of a similar nature.

Russel J. Reiter; Dun-Xian Tan; Lucien C. Manchester; Eloisa Gitto; Lorena Fuentes-Broto

2010-01-01

184

Nocturnal light and nocturnal rodents: similar regulation of disparate functions?  

UK PubMed Central (United Kingdom)

Investigators typically study one function of the circadian visual system at a time, be it photoreception, transmission of photic information to the suprachiasmatic nucleus (SCN), light control of rhythm phase, locomotor activity, or gene expression. There are good reasons for such a focused approach, but sometimes it is advantageous to look at the broader picture, asking how all the parts and functions complete the whole. Here, several seemingly disparate functions of the circadian visual system are examined. They share common characteristics with respect to regulation by light and, to the extent known, share a common input neuroanatomy. The argument presented is that the 3 hypothalamically mediated effects of light for which there are the most data, circadian clock phase shifts, suppression of nocturnal locomotion ("negative masking"), and suppression of nocturnal pineal function, are regulated by a common photic input pathway terminating in the SCN. For each, light triggers a relatively fixed interval response that is irradiance-dependent, the effective stimulus can be very brief light exposure, and the response continues to completion in the absence of additional light. The presence of a triggered, fixed-length response interval is of particular importance to the understanding of the circuitry and mechanisms regulating circadian rhythm phase shifts because it implies that the SCN clock response to light is not instantaneous. It also may explain why certain stimuli (neuropeptide Y or novel wheel running) administered many minutes after light exposure are able to block light-induced phase shifts. The understanding of negative masking is complicated by the fact that it can be represented as a positive change, that is, light-induced sleep, not just as a reduction in locomotion. Acute nocturnal light exposure also induces adrenal hormone secretion and a rapid drop in body temperature, physiological responses that appear to be regulated similarly to the other light effects. The likelihood of a common regulatory basis for the several responses suggests that additional light-induced responses will be forthcoming and raises questions about the relationships between light, SCN cellular anatomy, the molecular clockworks of SCN neurons, and SCN throughput mechanisms for regulating disparate downstream activities.

Morin LP

2013-04-01

185

Seasonal differences in melatonin concentrations and heart rates during sleep in obese subjects in Japan.  

UK PubMed Central (United Kingdom)

During the past several decades, obesity has been increasing globally. In Japan, obesity is defined by a BMI of 25 kg/m(2) or over; 28.6 % of men and 20.6 % of women are obese. Obese people have an increased incidence of developing cardiovascular, renal, and hormonal diseases and sleep disorders. Obese people also have shortened sleep durations. We investigated seasonal differences in melatonin concentrations, heart rates, and heart rate variability during sleep in obese subjects in Japan. Five obese (BMI, 32.0?±?4.9 kg/m(2)) and five non-obese (BMI, 23.2?±?2.9 kg/m(2)) men participated in this study in the summer and winter. Electrocardiograms were measured continuously overnight in a climatic chamber at 26 °C with a relative humidity of 50 %. Saliva samples for melatonin were collected at 2300 hours, 0200 hours, and 0600 hours. We found that melatonin concentrations during sleep in obese subjects were significantly lower than those in non-obese subjects in the winter. Heart rate during sleep in winter was significantly higher than that in summer in both obese and non-obese subjects. Heart rate variability was not significantly different in the summer and winter in both obese and non-obese subjects. Our results show that decreased nocturnal melatonin concentrations during winter in obese men may be related to higher heart rates, and this may suggest that obese men are at an increased risk of a cardiovascular incident during sleep, especially in the winter.

Sato M; Kanikowska D; Iwase S; Shimizu Y; Nishimura N; Inukai Y; Sato M; Sugenoya J

2013-09-01

186

Seasonal differences in melatonin concentrations and heart rates during sleep in obese subjects in Japan  

Science.gov (United States)

During the past several decades, obesity has been increasing globally. In Japan, obesity is defined by a BMI of 25 kg/m2 or over; 28.6 % of men and 20.6 % of women are obese. Obese people have an increased incidence of developing cardiovascular, renal, and hormonal diseases and sleep disorders. Obese people also have shortened sleep durations. We investigated seasonal differences in melatonin concentrations, heart rates, and heart rate variability during sleep in obese subjects in Japan. Five obese (BMI, 32.0 ± 4.9 kg/m2) and five non-obese (BMI, 23.2 ± 2.9 kg/m2) men participated in this study in the summer and winter. Electrocardiograms were measured continuously overnight in a climatic chamber at 26 °C with a relative humidity of 50 %. Saliva samples for melatonin were collected at 2300 hours, 0200 hours, and 0600 hours. We found that melatonin concentrations during sleep in obese subjects were significantly lower than those in non-obese subjects in the winter. Heart rate during sleep in winter was significantly higher than that in summer in both obese and non-obese subjects. Heart rate variability was not significantly different in the summer and winter in both obese and non-obese subjects. Our results show that decreased nocturnal melatonin concentrations during winter in obese men may be related to higher heart rates, and this may suggest that obese men are at an increased risk of a cardiovascular incident during sleep, especially in the winter.

Sato, Maki; Kanikowska, Dominika; Iwase, Satoshi; Shimizu, Yuuki; Nishimura, Naoki; Inukai, Yoko; Sato, Motohiko; Sugenoya, Junichi

2013-09-01

187

Early morning melatonin administration impairs psychomotor vigilance.  

UK PubMed Central (United Kingdom)

The acute soporific effect of melatonin in humans has been demonstrated in a range of studies. How alertness and performance are changed after melatonin given in the morning is not yet known. In a double-blind, placebo-controlled study of nine healthy young men, melatonin was given at 0700 h under controlled conditions of a modified constant routine protocol lasting 56 h (2 days, 3 nights with sleep). A clear decrement in neurobehavioral functions as measured by the Psychomotor Vigilance Test lasted for 6 h after melatonin administration (particularly in the lapse domain and median of the reaction time) without any effect on a letter cancellation task. A subjective soporific effect was present but less pronounced. Thus, melatonin taken in the morning requires caution in situations where high attention is needed.

Graw P; Werth E; Kräuchi K; Gutzwiller F; Cajochen C; Wirz-Justice A

2001-06-01

188

Melatonin and hypothalamic-pituitary-gonadal axis.  

UK PubMed Central (United Kingdom)

Melatonin (N-acetyl-5-methoxy-tryptamine), a principal product of the pineal gland, is produced mainly during the dark phase of the circadian cycle. This hormone plays a crucial role in the regulation of circadian and seasonal changes in various aspects of physiology and neuroendocrine functions. In mammals, melatonin can influence sexual maturation and reproductive functions via activation of its receptors and binding sites in the hypothalamic-pituitary-gonadal (HPG) axis. This review summarizes current knowledge of melatonin on the hypothalamus, pituitary gland, and gonads. We also review recent progress in clinical applications of melatonin or potentials of using melatonin, as a reducer of oxidative stress, to improve reproductive functions for the diseases such as women infertility.

Shi L; Li N; Bo L; Xu Z

2013-01-01

189

Melatonin and hypothalamic-pituitary-gonadal axis.  

Science.gov (United States)

Melatonin (N-acetyl-5-methoxy-tryptamine), a principal product of the pineal gland, is produced mainly during the dark phase of the circadian cycle. This hormone plays a crucial role in the regulation of circadian and seasonal changes in various aspects of physiology and neuroendocrine functions. In mammals, melatonin can influence sexual maturation and reproductive functions via activation of its receptors and binding sites in the hypothalamic-pituitary-gonadal (HPG) axis. This review summarizes current knowledge of melatonin on the hypothalamus, pituitary gland, and gonads. We also review recent progress in clinical applications of melatonin or potentials of using melatonin, as a reducer of oxidative stress, to improve reproductive functions for the diseases such as women infertility. PMID:23410151

Shi, L; Li, N; Bo, L; Xu, Z

2013-01-01

190

Differential regulation of kiss1 expression by melatonin and gonadal hormones in male and female Syrian hamsters  

DEFF Research Database (Denmark)

In seasonal breeders, reproduction is synchronized to seasons by day length via the pineal hormone melatonin. Recently, we have demonstrated that Kiss1, a key activator of the reproductive function, is down-regulated in sexually inactive hamsters maintained in inhibitory short days (SDs). In rodents, Kiss1 is expressed in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus (ARC). Because both the duration of the nocturnal peak of melatonin and circulating sex steroid levels vary with photoperiod, the aim of this study was to determine whether melatonin and sex steroids differentially regulate Kiss1 expression in the ARC and the AVPV. Kiss1 expression was examined by in situ hybridization in both male and female hamsters kept in various experimental conditions, and we observed that 1) SD exposure markedly reduced Kiss1 expression in the ARC and AVPV of male and female hamsters as compared to LD animals, 2) sex steroid treatment in SD-adapted male and female hamsters increased the numberof Kiss1 neurons in the AVPV but decreased it in the ARC, 3) melatonin administration to LD-adapted hamsters decreased Kiss1 mRNA level in both the AVPV and the ARC in intact animals, whereas in castrated hamsters, melatonin rapidly inhibited Kiss1 expression in the ARC but not in the AVPV, and 4) pinealectomy of male or female SD-adapted hamsters increased the number of Kiss1 neurons in the ARC but not in the AVPV. In conclusion, our data demonstrate that Kiss1 expression in the Syrian hamster hypothalamus is down-regulated in SD via different mechanisms. In the ARC, melatonin inhibits Kiss1 via a direct effect on the hypothalamus, and this effect is probably sex steroid dependent, whereas in the AVPV, the decrease in Kiss1 expression appears to be secondary to the melatonin-driven reduction of sex steroid levels. Taken together, our data support the hypothesis that ARC Kiss1 neurons mediate melatonin effects on the gonadotropic axis of the Syrian hamster.

Ansel, L; Bolborea, M

2010-01-01

191

ADDITIVE FOR ENRICHED MELATONIN, THE PRODUCTION METHOD OF MILK ENRICHED MELATONIN AND THEREOF THE MILK  

UK PubMed Central (United Kingdom)

A melatonin-enriched additive and a method for producing melatonin-enriched milk are provided to increase the content of melatonin included in milk using functional feed. A melatonin-enriched additive is composed of 5-18wt% of sweet flag, 5-18wt% of Zizyphs jujube miller, 2-10wt% of Polygala tenuifolia L., 5-18wt% of Cyperus rotundus L., 12-28wt% of Glycyrrhizae radix and an excipient. A method for producing melatonin-enriched milk comprises the following steps of: preparing functional feed containing melatonin-enriched additive(S110) breeding milk cows with the functional feed(S120) and milking the milk cows(S130). The functional feed consists of cow feed and melatonin-enriched additive. The content of the melatonin-enriched additive is 0.2-1.0wt% on a gross weight basis of the functional feed. The milking step is performed at 2-4 am. The melatonin-enriched milk contains 35-85pg/ml of melatonin.

KIM KEE IL; PARK JUNG GIL

192

Reversal of the inhibitory effect of light and high temperature on germination of Phacelia tanacetifolia seeds by melatonin.  

UK PubMed Central (United Kingdom)

Possible role of melatonin in the germination of negatively photoblastic and thermosensitive seeds of Phacelia tanacetifolia Benth was studied. Final germination percentage (FGP) was determined in the presence or absence of light at various temperatures, ranging from 0 to 40°C. The highest FGP was determined as 48.7% and 92% at temperature of 15°C in the presence and absence of light, respectively. Seeds were primed with 1% KNO(3) containing various concentrations (0.3, 1, 6, 12, 30, 60, or 90 ?M) of melatonin for 2 days at 15°C in darkness. Primed seeds were germinated at an inhibitory temperature of 30°C, and results were compared to those occurring at the optimum temperature of 15°C under both light and no light conditions. Melatonin incorporated into priming medium significantly reversed the inhibitory effects of light and high temperature. Germination was elevated from 2.5% to 52% of FGP for seeds primed in the presence of 6 ?M melatonin in darkness at 30°C, while 1 ?M melatonin had the highest FGP (21.0%) in the presence of light at 30°C. The highest FGP (47.5%) was obtained from seeds primed in the presence of 0.3 ?M melatonin under the light condition at 15°C, while untreated seeds had 1.5% of FGP. The fastest seed germination was determined from seeds primed in the presence of 0.3 ?M melatonin (G(50) = 0.56 days) at 15°C in darkness. The possible roles of melatonin in promoting germination parameters of photo- and thermosensitive seed germination are discussed.

Tiryaki I; Keles H

2012-04-01

193

Effects of memantine and melatonin on signal transduction pathways vascular leakage and brain injury after focal cerebral ischemia in mice.  

UK PubMed Central (United Kingdom)

Because of their favorable action profiles in humans, both memantine and melatonin are particularly interesting candidates as neuroprotectants in acute ischemic stroke. Until now, the signaling mechanisms mediating memantine's neuroprotective actions remained essentially uninvestigated. In addition, we have combined memantine with melatonin, which is a well-known neuroprotective molecule. Herein, we examined the effects of memantine (20mg/kg, i.p.) administered alone or in combination with melatonin (4 mg/kg, i.p.) on the activation of signaling transduction pathways, IgG extravasation and ischemic injury in mice submitted to 90 min of intraluminal middle cerebral artery occlusion, followed by 24h of reperfusion. In these studies, both agents reduced ischemic injury and the density of DNA-fragmentation. Notably, melatonin/memantine combination reduced ischemic injury further as compared with memantine treatment, which was associated with reduced IgG extravasation, indicating vascular leakage in the brain. Animals receiving memantine exhibited elevated ERK-1/2 and decreased p21 and p38/MAPK activations, while it had no significant effect on phosphorylated Akt and SAPK/JNK1/2 in the ischemic brain. However, melatonin increased the activation of Akt and reduced the activations of ERK-1/2, p21, p38/MAPK and SAPK/JNK1/2 significantly. Synergistic effects of memantine and melatonin were observed in the inactivation of p21, p38/MAPK and SAPK/JNK1/2 pathways. Moreover, memantine reversed the effects of melatonin on the activation of ERK-1/2 pathway. Here, we provide evidence that free radical scavenger melatonin potentiates the effects of memantine on ischemic brain injury via inactivations of p21 and stress kinases p38/MAPK and SAPK/JNK1/2 pathways.

Kilic U; Yilmaz B; Reiter RJ; Yüksel A; Kilic E

2013-05-01

194

Effects of memantine and melatonin on signal transduction pathways vascular leakage and brain injury after focal cerebral ischemia in mice.  

Science.gov (United States)

Because of their favorable action profiles in humans, both memantine and melatonin are particularly interesting candidates as neuroprotectants in acute ischemic stroke. Until now, the signaling mechanisms mediating memantine's neuroprotective actions remained essentially uninvestigated. In addition, we have combined memantine with melatonin, which is a well-known neuroprotective molecule. Herein, we examined the effects of memantine (20mg/kg, i.p.) administered alone or in combination with melatonin (4 mg/kg, i.p.) on the activation of signaling transduction pathways, IgG extravasation and ischemic injury in mice submitted to 90 min of intraluminal middle cerebral artery occlusion, followed by 24h of reperfusion. In these studies, both agents reduced ischemic injury and the density of DNA-fragmentation. Notably, melatonin/memantine combination reduced ischemic injury further as compared with memantine treatment, which was associated with reduced IgG extravasation, indicating vascular leakage in the brain. Animals receiving memantine exhibited elevated ERK-1/2 and decreased p21 and p38/MAPK activations, while it had no significant effect on phosphorylated Akt and SAPK/JNK1/2 in the ischemic brain. However, melatonin increased the activation of Akt and reduced the activations of ERK-1/2, p21, p38/MAPK and SAPK/JNK1/2 significantly. Synergistic effects of memantine and melatonin were observed in the inactivation of p21, p38/MAPK and SAPK/JNK1/2 pathways. Moreover, memantine reversed the effects of melatonin on the activation of ERK-1/2 pathway. Here, we provide evidence that free radical scavenger melatonin potentiates the effects of memantine on ischemic brain injury via inactivations of p21 and stress kinases p38/MAPK and SAPK/JNK1/2 pathways. PMID:23396088

Kilic, U; Yilmaz, B; Reiter, R J; Yüksel, A; Kilic, E

2013-02-08

195

JAK2/STAT3 activation by melatonin attenuates the mitochondrial oxidative damage induced by myocardial ischemia/reperfusion injury.  

Science.gov (United States)

Ischemia/reperfusion injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Numerous data indicate that the JAK2/STAT3 signaling pathway is specifically involved in preventing myocardial IRI. Melatonin has potent activity against IRI and may regulate JAK2/STAT3 signaling. This study investigated the protective effect of melatonin pretreatment on myocardial IRI and elucidated its potential mechanism. Perfused isolated rat hearts and cultured neonatal rat cardiomyocytes were exposed to melatonin in the absence or presence of the JAK2/STAT3 inhibitor AG490 or JAK2 siRNA and then subjected to IR. Melatonin conferred a cardio-protective effect, as shown by improved postischemic cardiac function, decreased infarct size, reduced apoptotic index, diminished lactate dehydrogenase release, up-regulation of the anti-apoptotic protein Bcl2, and down-regulation of the pro-apoptotic protein Bax. AG490 or JAK2 siRNA blocked melatonin-mediated cardio-protection by inhibiting JAK2/STAT3 signaling. Melatonin exposure also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase (SOD) activity, and decreased formation of mitochondrial hydrogen peroxide (H2 O2 ) and malondialdehyde (MDA), which indicates that the IR-induced mitochondrial oxidative damage was significantly attenuated. However, this melatonin-induced effect on mitochondrial function was reversed by AG490 or JAK2 siRNA treatment. In summary, our results demonstrate that melatonin pretreatment can attenuate IRI by reducing IR-induced mitochondrial oxidative damage via the activation of the JAK2/STAT3 signaling pathway. PMID:23796350

Yang, Yang; Duan, Weixun; Jin, Zhenxiao; Yi, Wei; Yan, Juanjuan; Zhang, Song; Wang, Ning; Liang, Zhenxing; Li, Yue; Chen, Wensheng; Yi, Dinghua; Yu, Shiqiang

2013-06-25

196

Nocturnal light environments and species ecology: implications for nocturnal color vision in forests.  

UK PubMed Central (United Kingdom)

Although variation in the color of light in terrestrial diurnal and twilight environments has been well documented, relatively little work has examined the color of light in nocturnal habitats. Understanding the range and sources of variation in nocturnal light environments has important implications for nocturnal vision, particularly following recent discoveries of nocturnal color vision. In this study, we measured nocturnal irradiance in a dry forest/woodland and a rainforest in Madagascar over 34 nights. We found that a simple linear model including the additive effects of lunar altitude, lunar phase and canopy openness successfully predicted total irradiance flux measurements across 242 clear sky measurements (r=0.85, P<0.0001). However, the relationship between these variables and spectral irradiance was more complex, as interactions between lunar altitude, lunar phase and canopy openness were also important predictors of spectral variation. Further, in contrast to diurnal conditions, nocturnal forests and woodlands share a yellow-green-dominant light environment with peak flux at 560 nm. To explore how nocturnal light environments influence nocturnal vision, we compared photoreceptor spectral tuning, habitat preference and diet in 32 nocturnal mammals. In many species, long-wavelength-sensitive cone spectral sensitivity matched the peak flux present in nocturnal forests and woodlands, suggesting a possible adaptation to maximize photon absorption at night. Further, controlling for phylogeny, we found that fruit/flower consumption significantly predicted short-wavelength-sensitive cone spectral tuning in nocturnal mammals (P=0.002). These results suggest that variation in nocturnal light environments and species ecology together influence cone spectral tuning and color vision in nocturnal mammals.

Veilleux CC; Cummings ME

2012-12-01

197

Antepartum Depression Severity is Increased During Seasonally Longer Nights: Relationship to Melatonin and Cortisol Timing and Quantity.  

Science.gov (United States)

Current research suggests that mood varies from season to season in some individuals, in conjunction with light-modulated alterations in chronobiologic indices such as melatonin and cortisol. The primary aim of this study was to evaluate the effects of seasonal variations in darkness on mood in depressed antepartum women, and to determine the relationship of seasonal mood variations to contemporaneous blood melatonin and cortisol measures; a secondary aim was to evaluate the influence of seasonal factors on measures of melancholic versus atypical depressive symptoms. We obtained measures of mood and overnight concentrations of plasma melatonin and serum cortisol in 19 depressed patients (DP) and 12 healthy control (HC) antepartum women, during on-going seasonal variations in daylight/darkness, in a cross-sectional design. Analyses of variance showed that in DP, but not HC, Hamilton Depression Rating Scale (HRSD) scores were significantly higher in women tested during seasonally longer versus shorter nights. This exacerbation of depressive symptoms occurred when the dim light melatonin onset, the melatonin synthesis offset, and the time of maximum cortisol secretion (acrophase) were phase-advanced (temporally shifted earlier), and melatonin quantity was reduced, in DP but not HC. Serum cortisol increased across gestational weeks in both the HC and DP groups, which did not differ significantly in cortisol concentration. Nevertheless, serum cortisol concentration correlated positively with HRSD score in DP but not HC; notably, HC showed neither significant mood changes nor altered melatonin and cortisol timing or quantity in association with seasonal variations. These findings suggest that depression severity during pregnancy may become elevated in association with seasonally related phase advances in melatonin and cortisol timing and reduced melatonin quantity that occur in DP, but not HC. Thus, women who experience antepartum depression may be more susceptible than their nondepressed counterparts to phase alterations in melatonin and cortisol timing during seasonally longer nights. Interventions that phase delay melatonin and/or cortisol timing-for example, increased exposure to bright evening light-might serve as an effective intervention for antepartum depressions whose severity is increased during seasonally longer nights. PMID:23998286

Meliska, Charles J; Martínez, Luis F; López, Ana M; Sorenson, Diane L; Nowakowski, Sara; Kripke, Daniel F; Elliott, Jeffrey; Parry, Barbara L

2013-09-03

198

Nocturnal blood pressure fall as predictor of diabetic nephropathy in hypertensive patients with type 2 diabetes  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Hypertensive patients with reduced blood pressure fall (BPF) at night are at higher risk of cardiovascular events (CVE). Methods We evaluated in hypertensive diabetic patients, if a reduced nocturnal BPF can precedes the development of diabetic nephropathy (DN). We followed 70 patients with normal urinary albumin excretion (UAE) for two years. We performed 24-hours ambulatory BP monitoring in baseline and at the end of the study. Results Fourteen (20%) patients (GI) developed DN (N = 11) and/or CVE (n = 4). Compared to the remaining 56 patients (GII) in baseline, GI had similar diurnal systolic (SBP) and diastolic BP (DBP), but higher nocturnal SBP (138 ± 15 vs 129 ± 16 mmHg; p Conclusions Our results suggests that elevations in nocturnal BP precedes DN and increases the risk to develop CVE in hypertensive patients with T2DM.

Felício João S; de Souza Ana Carolina CB; Kohlmann Nárcia; Kohlmann Oswaldo; Ribeiro Arthur B; Zanella Maria T

2010-01-01

199

Design and rationale of a randomized controlled trial of melatonin supplementation in men and women with the metabolic syndrome  

Directory of Open Access Journals (Sweden)

Full Text Available Paul D Terry,1 Abhinav Goyal,2,3 Lawrence S Phillips,3 Hillary M Superak,4 Michael H Kutner4 1Departments of Public Health and Surgery, University of Tennessee, Knoxville, TN, 2Department of Epidemiology, Emory Rollins School of Public Health, 3Department of Medicine, Emory School of Medicine, 4Department of Biostatistics and Bioinformatics, Emory Rollins School of Public Health, Atlanta, GA, USA Background: The metabolic syndrome is a constellation of interrelated metabolic risk factors that appear to increase the risk of atherosclerotic cardiovascular disease, type 2 diabetes mellitus, and possibly some cancers. Animal studies and observational clinical data in humans suggest that supplemental melatonin may ameliorate a number of components of the metabolic syndrome, including elevated glucose, elevated blood pressure, dyslipidemia, and obesity. The primary objective of this clinical trial was to determine the feasibility, efficacy, and safety of melatonin supplementation in men and women with the metabolic syndrome. Methods: Thirty-nine men and women of mixed race/ethnicity were enrolled into a randomized, double-blind, placebo-controlled clinical trial with two arms: placebo for 10 weeks followed by melatonin for 10 weeks, or vice versa, with an interval 6-week washout period, in a crossover trial design. Outcome measures include metabolic syndrome components (blood pressure, glucose, triglycerides, high-density lipoprotein cholesterol, waist circumference), oxidative stress, and inflammation biomarkers. These biomarkers, along with sleep duration and quality and pretreatment endogenous melatonin levels, were measured to explore possible underlying biologic mechanisms. Discussion: This trial will provide knowledge of the effects of melatonin in metabolic syndrome subjects, and lay the groundwork for future clinical trials of melatonin in metabolic syndrome subjects. Keywords: melatonin, metabolic syndrome, diabetes, blood pressure, sleep

Terry PD; Goyal A; Phillips LS; Superak HM; Kutner MH

2013-01-01

200

[Desmopressin: the treatment of primary nocturnal enuresis  

UK PubMed Central (United Kingdom)

OBJECTIVES: The efficacy of desmopressin, a drug that reduces nocturnal urine volume with no side effects, was evaluated in a group of 21 patients. METHODS: 20 boys and 1 girl with primary nocturnal enuresis were treated with intranasal desmopressin (DDAVP) for a period of 12 weeks. RESULTS: An improvement in 80.95% was achieved. Following treatment enuresis recurred, but to a lesser degree than before therapy. CONCLUSIONS: DDAVP is useful in the treatment of primary nocturnal enuresis whose etiology is not organic or functional.

Granados EA; Garat JM

1995-04-01

 
 
 
 
201

Melatonin Protects Against Diazinon-Induced Neurobehavioral Changes in Rats.  

UK PubMed Central (United Kingdom)

Diazinon is an organophosphorous pesticide with a prominent toxicity on many body organs. Multiple mechanisms contribute to diazinon-induced deleterious effects. Inhibition of acetyl-cholinesterase, cholinergic hyperstimulation, and formation of reactive oxygen species may play a role. On the other hand, melatonin is a pineal hormone with a well-known potent antioxidant activity and a remarkable modulatory effect on many behavioral processes. The present study revealed that oral diazinon administration (25 mg/kg) increased anxiety behavior in rats subjected to elevated plus maze and open-field tests possibly via the induction of changes in brain monoamines levels (dopamine, norepinephrine, and serotonin). Additionally, brain lipid peroxides measured as malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-?) levels were elevated, while the activity of brain glutathione peroxidase enzyme was reduced by diazinon. Co-administration of oral melatonin (10 mg/kg) significantly attenuated the anxiogenic activity of diazinon, rebalanced brain monoamines levels, decreased brain MDA and TNF-? levels, and increased the activity of brain glutathione peroxidase enzyme.

Ahmed MA; Ahmed HI; El-Morsy EM

2013-08-01

202

Daily illumination exposure and melatonin: influence of ophthalmic dysfunction and sleep duration  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Ocular pathology lessens light's efficacy to maintain optimal circadian entrainment. We examined whether ophthalmic dysfunction explains unique variance in melatonin excretion of older adults over and above the variance explained by daily illumination, medical, and sociodemographic factors. We also examined whether ophthalmic dysfunction influences relationships between ambient illumination and melatonin. Methods Thirty older adults (mean age = 69 years; Blacks = 42% and Whites = 58%) of both genders participated in the study. Demographic and health data were collected at baseline. Participants underwent eye exams at SUNY Downstate Medical Center, wore an actigraph to monitor illumination and sleep, and collected urine specimens to estimate aMT6s concentrations. Results Hierarchical regression analysis showed that illumination factors explained 29% of the variance in aMT6s mesor. The proportion of variance explained by ophthalmic factors, sleep duration, and race was 10%, 2%, and 2%, respectively. Illumination factors explained 19% of the variance in aMT6s acrophase. The proportion of variance explained by ophthalmic factors, sleep duration, and race was 11%; 17%; and 2%, respectively. Controlling for sleep duration and race reduced the correlations between illumination and melatonin, whereas controlling for ophthalmic factors did not. Conclusion Ophthalmic exams showed that elevated intraocular pressure and large cup-to-disk ratios were independently associated with earlier melatonin timing. Lower illumination exposure also had independent associations with earlier melatonin timing. Conceivably, ophthalmic and illumination factors might have an additive effect on the timing of melatonin excretion, which in turn might predispose individuals to experience early morning awakenings.

Jean-Louis Girardin; Kripke Daniel F; Elliott Jeffrey A; Zizi Ferdinand; Wolintz Arthur H; Lazzaro Douglas R

2005-01-01

203

Melatonin reduces the severity of experimental amoebiasis.  

UK PubMed Central (United Kingdom)

BACKGROUND: Melatonin has immunomodulatory effects but very little is known about its influence in protozoan infections, such as Entamoeba histolytica, which causes amoebiasis, a disease with significant morbidity and mortality. In this study, we evaluated the effects of exogenous melatonin interference in experimental amoebiasis and on interactions between human blood cells and E. histolytica trophozoites. METHODS: The effect of melatonin was investigated in models of experimental amoebiasis in hamsters and rats by evaluating the area of necrosis induced by E. histolytica. The activity of melatonin on the interactions between leukocytes and amoebae was determined by examining leukophagocytosis. For in vitro tests, polymorphonuclear and mononuclear human blood leucocytes were incubated with E. histolytica trophozoites. RESULTS: The areas of amoebic necrosis were significantly reduced in animals treated with melatonin. Melatonin treatment increased leukophagocytosis but was associated with a greater number of dead amoebae. CONCLUSIONS: These results suggest that melatonin may play a beneficial role in the control of amoebic lesions, raising the possibility that this drug may be used as an adjuvant in anti-amoebic therapy.

França-Botelho AC; França JL; Oliveira FM; Franca EL; Honório-França AC; Caliari MV; Gomes MA

2011-01-01

204

Melatonin reduces the severity of experimental amoebiasis  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Melatonin has immunomodulatory effects but very little is known about its influence in protozoan infections, such as Entamoeba histolytica, which causes amoebiasis, a disease with significant morbidity and mortality. In this study, we evaluated the effects of exogenous melatonin interference in experimental amoebiasis and on interactions between human blood cells and E. histolytica trophozoites. Methods The effect of melatonin was investigated in models of experimental amoebiasis in hamsters and rats by evaluating the area of necrosis induced by E. histolytica. The activity of melatonin on the interactions between leukocytes and amoebae was determined by examining leukophagocytosis. For in vitro tests, polymorphonuclear and mononuclear human blood leucocytes were incubated with E. histolytica trophozoites. Results The areas of amoebic necrosis were significantly reduced in animals treated with melatonin. Melatonin treatment increased leukophagocytosis but was associated with a greater number of dead amoebae. Conclusions These results suggest that melatonin may play a beneficial role in the control of amoebic lesions, raising the possibility that this drug may be used as an adjuvant in anti-amoebic therapy.

França-Botelho Aline C; França Juliana L; Oliveira Fabrício MS; Franca Eduardo L; Honório-França Adenilda C; Caliari Marcelo V; Gomes Maria A

2011-01-01

205

Neuroprotection by melatonin on astrocytoma cell death.  

Science.gov (United States)

Glial cells play an active role in the homeostatic regulation of the central nervous system (CNS). Astrocytes, the most abundant glial cell types in the brain, provide mechanical and metabolic support for neurons. The regulation of astrocyte apoptosis, therefore, is important for physiological and pathological processes in the CNS. Melatonin is a neurohormone that regulates target cells via binding to specific high-affinity plasma membrane receptors, MT1/MT2. In addition to regulating circadian rhythms, melatonin has recently attracted much interest for its potential regulation of cell apoptosis. We recently showed that melatonin antagonizes apoptosis on U937 cells via intersecting signal transduction events involving binding to MT1/MT2 and activation of lipoxygenase. Here we describe the neuroprotective potential of melatonin, showing that melatonin significantly reduces damage-induced apoptosis in astrocytoma cells. The mechanism of protection is different from that shown in U937 cells, because it does not involve MT1/MT2 or lipoxygenase; likewise, Ca(2+) influx is not involved. Intriguingly, inhibition of phospholipase C (PLC) with neomycin reverses melatonin protection, suggesting that a PLC-dependent signal transduction, different from that triggered by MT1/MT2, is involved in the antiapoptotic pathway of melatonin. PMID:19723097

Radogna, Flavia; Nuccitelli, Silvia; Mengoni, Fabio; Ghibelli, Lina

2009-08-01

206

Melatonin modulates baroreflex control via area postrema.  

UK PubMed Central (United Kingdom)

Pineal gland and its hormone melatonin have been implicated in modulation of cardiovascular system. We aimed at studying the effects of melatonin on baroreflex sensitivity and the role of area postrema, as a component modulator of baroreflex arch. Mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious freely moving rats. Baroreceptor reflex sensitivity was assessed by determining the HR responses to ramped infusions of phenylephrine (PE) and sodium nitroprusside (SNP)-induced MAP changes. Melatonin bolus (0.11 mg/kg) immediately followed by its continuous infusion (0.43 × 10(-9) mol/L at a rate of 0.65 mL/h for 30 min) in healthy normotensive rats produced a downward shift of baroreceptor reflex control with a substantial inhibition of reflex tachycardia (-32%) and potentiation of reflex bradycardia (+20%). Ablation of area postrema (APX group) induced a sustained decrease of MAP (101 ± 3 vs. 116 ± 3 mmHg, P < 0.05 in comparison with sham rats, respectively). The melatonin-induced alterations of baroreflex function observed in the sham group were abolished in the APX group. We conclude that circulating melatonin can modulate baroreceptor reflex control of HR, thus resetting it toward lower HR values. The modulatory effects of melatonin may be mediated via melatonin receptors in the area postrema, located outside the blood-brain barrier.

Campos LA; Cipolla-Neto J; Michelini LC

2013-03-01

207

Melatonin in Alzheimer’s Disease  

Directory of Open Access Journals (Sweden)

Full Text Available Alzheimer’s disease (AD), an age-related neurodegenerative disorder with progressive cognition deficit, is characterized by extracellular senile plaques (SP) of aggregated ?-amyloid (A?) and intracellular neurofibrillary tangles, mainly containing the hyperphosphorylated microtubule-associated protein tau. Multiple factors contribute to the etiology of AD in terms of initiation and progression. Melatonin is an endogenously produced hormone in the brain and decreases during aging and in patients with AD. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning and slows down the progression of cognitive impairment in AD patients. Melatonin efficiently protects neuronal cells from A?-mediated toxicity via antioxidant and anti-amyloid properties. It not only inhibits A? generation, but also arrests the formation of amyloid fibrils by a structure-dependent interaction with A?. Our studies have demonstrated that melatonin efficiently attenuates Alzheimer-like tau hyperphosphorylation. Although the exact mechanism is still not fully understood, a direct regulatory influence of melatonin on the activities of protein kinases and protein phosphatases is proposed. Additionally, melatonin also plays a role in protecting the cholinergic system and in anti-inflammation. The aim of this review is to stimulate interest in melatonin as a potentially useful agent in the prevention and treatment of AD.

Li Lin; Qiong-Xia Huang; Shu-Sheng Yang; Jiang Chu; Jian-Zhi Wang; Qing Tian

2013-01-01

208

Melatonin: General Features and its Role in Psychiatric Disorders  

Directory of Open Access Journals (Sweden)

Full Text Available In recent years, there is a growing interest in melatonin all over the world. The main task of protecting the body's biological clock, which set the rhythm of melatonin, involves many biological and physiological processes of the body. Cell renewal, strengthening of the immune system and body temperature regulation are other tasks of melatonin. Melatonin, with its lipophilic property, is the most powerful antioxidant as it can reach all body areas and can easily pass the blood-brain barrier. The fact that individuals with low levels of melatonin have sleep problems lead to the consideration of melatonin as a therapeutic medicine in this field. The detailed researches have shown that melatonin can improve sleep quality without changing the total duration of sleep. Nevertheless, despite high number of researches done, the functions of melatonin have not yet fully understood. Therefore, review of the available information related to melatonin will be guide for researchers in the field.

Fatih Ozcelik; Murat Erdem; Abdullah Bolu; Murat Gulsun

2013-01-01

209

Evening melatonin and bright light administration induce additive phase shifts in dim light melatonin onset.  

UK PubMed Central (United Kingdom)

In healthy young men, administration of a single light pulse (5000 lux for 3 hr) or a single melatonin pill (5 mg) at 20:40 hr under controlled constant routine conditions of <10 lux, yielded a phase delay and a phase advance, respectively, in the circadian marker of dim light melatonin onset 24 hr later. Phase shifts after combining the two interventions were additive. Melatonin suppression is not necessary for a phase shift by light, and melatonin is not a 'weak' Zeitgeber relative to bright light when ambient lighting is strictly controlled.

Wirz-Justice A; Kräuchi K; Cajochen C; Danilenko KV; Renz C; Weber JM

2004-04-01

210

Uterine infusion of melatonin or melatonin receptor antagonist alters ovine feto-placental hemodynamics during midgestation.  

UK PubMed Central (United Kingdom)

Dietary melatonin supplementation from mid- to late gestation increases umbilical artery blood flow and causes disproportionate fetal growth. Melatonin receptors have been described throughout the cardiovascular system; however, there is a paucity of data on the function of placental melatonin receptors. The objectives of the current experiment were to determine fetal descending aorta blood flow, umbilical artery blood flow, and placental and fetal development following a 4-wk uterine infusion of melatonin (MEL), melatonin receptor 1 and 2 antagonist (luzindole; LUZ), or vehicle (CON) from Day 62 to Day 90 of gestation. After 4 wk of infusion, umbilical artery blood flow and umbilical artery blood flow relative to placentome weight were increased (P < 0.05) in MEL- versus CON- and LUZ-infused dams. Fetal descending aorta blood flow was increased (P < 0.05) in MEL- versus CON- and LUZ-infused dams, while fetal descending aorta blood flow relative to fetal weight was increased in MEL- versus CON-infused dams and decreased in LUZ- versus CON-infused dams. Following the 4-wk infusion, we observed an increase in placental efficiency (fetal-placentome weight ratio) in MEL- versus LUZ-infused dams. The increase in umbilical artery blood flow due to chronic uterine melatonin infusion is potentiated by an increased fetal cardiac output through the descending aorta. Moreover, melatonin receptor antagonism decreased fetal descending aorta blood flow relative to fetal weight. Therefore, melatonin receptor activation may partially mediate the observed increase in fetal blood flow following dietary melatonin supplementation.

Lemley CO; Camacho LE; Vonnahme KA

2013-08-01

211

Alpha-2 adrenergic activity of bromocriptine and quinpirole in chicken pineal gland. Effects on melatonin synthesis and ( sup 3 H)rauwolscine binding  

Energy Technology Data Exchange (ETDEWEB)

In the pineal gland and retina of chickens, serotonin N-acetyl-transferase (NAT) activity and melatonin content are modulated by different receptors, alpha-2 adrenergic receptors in pineal gland and D2-dopamine receptors in retina. The effect of two D2-dopamine receptor agonists, bromocriptine and quinpirole (LY 171555), on melatonin synthesis in these tissues was investigated. Systemic administrations of bromocriptine and quinpirole decreased nocturnal NAT activity and melatonin content of both pineal gland and retina. Bromocriptine was equipotent in the two tissues, whereas quinpirole was approximately 100-fold more potent in retina than in pineal gland. In pineal gland, the suppressive effects of bromocriptine and quinpirole on NAT activity were blocked by yohimbine, a selective alpha-2 adrenergic receptor antagonist, but not by spiperone, a D2-dopamine receptor antagonist. In contrast, bromocriptine- and quinpirole-induced decreases of the enzyme activity in retina were antagonized by spiperone, and not affected by yohimbine. The nocturnal increase of NAT activity of pineal glands in vitro was inhibited with an order of potency clonidine greater than bromocriptine greater than quinpirole. Additionally, bromocriptine and quinpirole displaced the specific binding of (3H)rauwolscine, an alpha-2 adrenergic receptor antagonist, to membranes from chicken pineal gland, with potencies comparable to those observed for inhibition of NAT activity in vitro. It is suggested that bromocriptine and quinpirole, in addition to their D2-dopaminergic activity, can stimulate alpha-2 adrenergic receptors in pineal gland of chicken.

Zawilska, J.; Iuvone, P.M. (Emory Univ. School of Medicine, Atlanta, GA (USA))

1990-12-01

212

Melatonin in perioperative medicine: Current perspective.  

UK PubMed Central (United Kingdom)

Melatonin, a new addition to the armamentarium of anesthesiologist, has some unique properties that are highly desirable in routine peri-operative care. Available clinical data show that preoperative melatonin is as effective as benzodiazepines in reducing preoperative anxiety with minimal action on psychomotor performance and sleep wake cycle. It may be considered as a safe and effective alternative of benzodiazepines as preoperative anxiolytic. It may have opioid sparing effect, may reduce intraocular pressure, and have role in prevention of postoperative delirium. The short-term administration of melatonin is free from significant adverse effects also.

Maitra S; Baidya DK; Khanna P

2013-07-01

213

Improving the treatment of nocturnal asthma: use of an office questionnaire to identify nocturnal asthma symptoms.  

UK PubMed Central (United Kingdom)

Nocturnal asthma is a major problem in many asthma patients and it is important to recognize and treat it. We previously reported the incidence of nocturnal asthma in our practice (1); the current study was done to try to improve upon the incidence of nocturnal asthma in our patients. After our previous survey, which indicated a 67% incidence of nocturnal asthma in our practice, we instituted a previsit questionnaire regarding nocturnal asthma to be filled out by all follow-up asthma patients in our office. After a period of time, we mailed a nocturnal asthma questionnaire to all asthma patients to see if the intervention had improved our incidence of nocturnal asthma. This questionnaire was identical to the one used in our prior study and was mailed to 2019 patients. We had 602 responders, 560 of whom had asthma. A total of 328 of these patients (59%) had nocturnal asthma. This was similar to the results of our previous survey, and our initial conclusion was that the new in-office questionnaire that we instituted had not improved the situation. Then we discovered that the in-office questionnaire had inadvertently been distributed only to the patients of one or our physicians (Dr. A). His patients were then compared with those of the other two doctors (Drs. B and C), and it was found that Dr. A's patients had fewer nocturnal symptoms than did the patients of the other doctors. The percent of asthmatics with nocturnal asthma 4-7 nights per week (more than half the nights in a week) for Dr. A was 16%, for Dr. B 47%, and for Dr. C 39%. The use of a short office questinnaire for asthma patients before they see the doctor for follow-up visits leads to greater recognition and better treatment of nocturnal asthma.

Storms WW; Nathan RA; Bodman SF; Byer P

1996-01-01

214

Improving the treatment of nocturnal asthma: use of an office questionnaire to identify nocturnal asthma symptoms.  

Science.gov (United States)

Nocturnal asthma is a major problem in many asthma patients and it is important to recognize and treat it. We previously reported the incidence of nocturnal asthma in our practice (1); the current study was done to try to improve upon the incidence of nocturnal asthma in our patients. After our previous survey, which indicated a 67% incidence of nocturnal asthma in our practice, we instituted a previsit questionnaire regarding nocturnal asthma to be filled out by all follow-up asthma patients in our office. After a period of time, we mailed a nocturnal asthma questionnaire to all asthma patients to see if the intervention had improved our incidence of nocturnal asthma. This questionnaire was identical to the one used in our prior study and was mailed to 2019 patients. We had 602 responders, 560 of whom had asthma. A total of 328 of these patients (59%) had nocturnal asthma. This was similar to the results of our previous survey, and our initial conclusion was that the new in-office questionnaire that we instituted had not improved the situation. Then we discovered that the in-office questionnaire had inadvertently been distributed only to the patients of one or our physicians (Dr. A). His patients were then compared with those of the other two doctors (Drs. B and C), and it was found that Dr. A's patients had fewer nocturnal symptoms than did the patients of the other doctors. The percent of asthmatics with nocturnal asthma 4-7 nights per week (more than half the nights in a week) for Dr. A was 16%, for Dr. B 47%, and for Dr. C 39%. The use of a short office questinnaire for asthma patients before they see the doctor for follow-up visits leads to greater recognition and better treatment of nocturnal asthma. PMID:8675495

Storms, W W; Nathan, R A; Bodman, S F; Byer, P

1996-01-01

215

Melatonin reduces the expression of chemokines in rat with trinitrobenzene sulfonic acid-induced colitis  

International Nuclear Information System (INIS)

[en] Objective was to investigate the effect of melatonin on the colon inflammatory injury of rats with colitis and determine whether this effect is associated with inhibition of chemoattractant molecules interleukins (IL-8) and monocyte chemoattractant protein (MCP)-1.The study was designed and implemented in JingMen No.1 People's Hospital, HuBei Province, from May 2006 to April 2007. It involved 72 animals divided into 6 groups of 12 each: normal group, model group, 5-aminosalisalicylic acid group, and melatonin group (dose of 2.5, 5.0 and 10.0mg/kg). Rat colitis model was established by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) enema. Interleukin-8 and MCP-1 proteins in colon tissue were examined by immunohistochemistry and western blot. The messenger-RNA expressions of chemokines were determined by reverse transcription polymerase chain reaction analysis. Trinitrobenzene sulfonic acid enema resulted in pronounced pathological changes of colonic mucosa in model rats, which were in accordance with the significantly elevated Myeloperoxidase activity. Expressions of chemokines were up-regulated in colitis. Melatonin treatment reduced colonic lesions and improved colitis symptom, and decreased the protein and mRNA expressions of IL-8 and MCP-1 significantly in colon tissues of rats with colitis. Chemokines IL-8 and MCP-1 are elevated in mucosal tissues in colitis and play an important role in the perpetuation of tissue destructive inflammatory process; melatonin reduces colonic inflammatory injury of rats colitis through down-regulating the expressions of chemokines. Melatonin can be considered as a novel therapeutic alternative for the treatment of inflammatory bowel disease. (author)

2008-01-01

216

The use of melatonin to combat mustard toxicity. REVIEW.  

Science.gov (United States)

Among the most readily available chemical warfare agents, sulfur mustard (SM) has been the most widely used chemical weapon. The toxicity of SM as an incapacitating agent is of much greater importance than its ability to cause lethality. Oxidative stress is the first and key event in the pathogenesis of SM toxicity. The involvement of inducible nitric oxide (iNOS) in SM toxicity, however, also leads to elevated nitrosative stress; thus, the damage caused by SM is nitro-oxidative stress because of peroxynitrite (ONOO-) production. Once ONOO- is formed, it activates nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) leading to pro-inflammatory gene expression thereby promoting inflammation; additionally, ONOO- directly exerts harmful effects by damaging all biomolecules including lipids, proteins and DNA within cells. DNA damage is sensed by an important DNA repair enzyme, poly (ADP-ribose) polymerase (PARP); this enzyme repairs molecular damage by using nicotinamide adenine dinucleotide (NAD+) as a substrate. Over-activation of PARP, due to severe DNA damage, consumes vast amounts of the respiratory coenzyme NAD+ leading to a cellular energy crisis. This pathophysiologic mechanism eventually results in cellular dysfunction, apoptosis or necrosis. Therefore, classic antioxidants may have limited beneficial effects on SM toxicity. Melatonin is a multifunctional indolamine which counteracts virtually all pathophysiologic steps and displays significant beneficial effects against ONOO--induced cellular toxicity. Melatonin has the capability of scavenging both oxygen and nitrogen-based reactants including ONOO- and blocking transcriptional factors which induce pro-inflammatory cytokines. The delayed toxicity of SM, however, currently has no mechanistic explanation. We propose that epigenetic aberrations may be responsible for delayed detrimental effects of mustard poisoning. Therefore, as a putative epigenetic modulator, melatonin may also be beneficial to subjects with delayed toxicity of SM. PMID:18987575

Korkmaz, Ahmet; Kunak, Zeki I; Paredes, Sergio D; Yaren, Hakan; Tan, Duan-Xian; Reiter, Russel J

2008-10-01

217

The use of melatonin to combat mustard toxicity. REVIEW.  

UK PubMed Central (United Kingdom)

Among the most readily available chemical warfare agents, sulfur mustard (SM) has been the most widely used chemical weapon. The toxicity of SM as an incapacitating agent is of much greater importance than its ability to cause lethality. Oxidative stress is the first and key event in the pathogenesis of SM toxicity. The involvement of inducible nitric oxide (iNOS) in SM toxicity, however, also leads to elevated nitrosative stress; thus, the damage caused by SM is nitro-oxidative stress because of peroxynitrite (ONOO-) production. Once ONOO- is formed, it activates nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) leading to pro-inflammatory gene expression thereby promoting inflammation; additionally, ONOO- directly exerts harmful effects by damaging all biomolecules including lipids, proteins and DNA within cells. DNA damage is sensed by an important DNA repair enzyme, poly (ADP-ribose) polymerase (PARP); this enzyme repairs molecular damage by using nicotinamide adenine dinucleotide (NAD+) as a substrate. Over-activation of PARP, due to severe DNA damage, consumes vast amounts of the respiratory coenzyme NAD+ leading to a cellular energy crisis. This pathophysiologic mechanism eventually results in cellular dysfunction, apoptosis or necrosis. Therefore, classic antioxidants may have limited beneficial effects on SM toxicity. Melatonin is a multifunctional indolamine which counteracts virtually all pathophysiologic steps and displays significant beneficial effects against ONOO--induced cellular toxicity. Melatonin has the capability of scavenging both oxygen and nitrogen-based reactants including ONOO- and blocking transcriptional factors which induce pro-inflammatory cytokines. The delayed toxicity of SM, however, currently has no mechanistic explanation. We propose that epigenetic aberrations may be responsible for delayed detrimental effects of mustard poisoning. Therefore, as a putative epigenetic modulator, melatonin may also be beneficial to subjects with delayed toxicity of SM.

Korkmaz A; Kunak ZI; Paredes SD; Yaren H; Tan DX; Reiter RJ

2008-10-01

218

Non-surgical periodontal therapy influences salivary melatonin levels.  

UK PubMed Central (United Kingdom)

OBJECTIVES: Melatonin is a hormone, which is involved in the control of the circadian rhythm, but also acts as an antioxidant and immune modulator. Previous studies reported decreased salivary and serum melatonin levels in periodontitis. This prospective cohort trial assessed the effect of non-surgical periodontal therapy on melatonin levels. METHODS: Salivary and serum samples of 60 participants (30 patients suffering from a severe generalized form of periodontitis, 30 healthy controls) were collected at baseline and 19 samples of periodontitis patients after treatment. Salivary and serum melatonin levels were determined by a commercially available ELISA kit and serum C-reactive protein (CRP) by a routine laboratory test. RESULTS: At baseline, periodontitis patients showed significantly increased serum CRP values and significantly decreased salivary melatonin levels compared to the control group. Clinical periodontal parameters significantly correlated with salivary melatonin levels and serum CRP. Periodontal therapy resulted in a recovery of the decreased salivary melatonin levels and a negative correlation was detected for the changes of salivary melatonin and the inflammatory parameter bleeding on probing. Serum melatonin levels showed no significant differences. CONCLUSIONS: Salivary melatonin levels recovered after periodontal therapy and correlated with a decrease of local periodontal inflammation. This may imply the local involvement of melatonin in the pathogenesis of periodontitis due to its antioxidant abilities. However, the exact role of melatonin in periodontal disease remains to be investigated in future trials. CLINICAL RELEVANCE: The present results suggest salivary melatonin as a risk indicator for the severity of periodontal disease.

Bertl K; Schoiber A; Haririan H; Laky M; Steiner I; Rausch WD; Andrukhov O; Rausch-Fan X

2013-05-01

219

Desmopressin is an Effective Treatment for Mixed Nocturia with Nocturnal Polyuria and Decreased Nocturnal Bladder Capacity  

Digital Repository Infrastructure Vision for European Research (DRIVER)

To investigate the efficacy and safety of desmopressin in patients with mixed nocturia, Patients aged ?18 yr with mixed nocturia (?2 voids/night and a nocturnal polyuria index [NPi] >33% and a nocturnal bladder capacity index [NBCi] >1) were recruited. The optimum dose of oral desmopressin was deter...

Lee, Hye Won; Choo, Myung-Soo; Lee, Jeong Gu; Park, Choal Hee; Paick, Jae-Seung; Lee, Jeong Zoo; Han, Deok Hyun; Park, Won Hee

220

[Disruptive nocturnal behavior in elderly subjects: could it be a parasomnia?].  

Science.gov (United States)

Parasomnias are sleep-related abnormal behaviors. They are frequent and overlooked causes of nocturnal disruptive behavior in the elderly, especially when patients are cognitively impaired. Confusion and violence can result in sleep disruption, injuries for the patients or their bed partners, caregivers distress, and they can be a motive for institutionalization. Parasomnias include the NonREM sleep disorders of arousal (sleepwalking, sleep terrors, confusional arousals and sleep-related eating disorder), the REM sleep behavior disorder (RBD) and more rarely the parasomnia overlap syndrome, which associates both NREM and REM parasomnias. Patients with NREM sleep parasomnias are confused, eyes open, with a glazed look during their nocturnal behaviors, and they have a post-episode amnesia. They shout and bolt from the bed (night terrors), look about in a confused manner, walk and speak (sleepwalking), and eat peculiar or inedible food (sleep-related eating disorders). These behaviors, which are frequent in young adults, may be triggered by short-half live hypnotics in elderly. During the parasomnia, the brain is partially awake (enough to perform complex motor and verbal action), and partially asleep (without conscious awareness or responsibility). RBD is characterized by a loss of the normal muscle atonia that accompanies REM sleep. Patients have excessive motor activity such as punching, kicking, or crying out in association with dream content. RBD are frequent in Parkinson's disease and dementia with Lewy bodies and may precede the cognitive or motor symptoms of these diseases by 5 to 10 years. RBD can also be promoted by antidepressants. When combined with thorough clinical interviews, the video-polysomnography is a powerful tool, especially for discriminating the parasomnia from nocturnal frontal lobe epilepsy, sleep apneas and periodic leg movements. Ensuring safety and withdrawing deleterious treatments are useful in patients with violent activities, potential injurious or bothersome to other household members. Clonazepam and melatonin (3-12 mg) are highly effective for treating RBD. PMID:20525541

Leu-Semenescu, Smaranda; Arnulf, Isabelle

2010-06-01

 
 
 
 
221

Diurnal and seasonal variations of melatonin and serotonin in women with seasonal affective disorder.  

Science.gov (United States)

In winters 1990-1991 and 1991-1992 women with and without seasonal affective disorder, winter type, were treated by light at 2500 lux either in the morning (0800h-1000h) or afternoon (1600h-1800h). In winter before light treatment, melatonin levels in serum in daytime (1200h and 1600h) were higher in patients compared to controls (p < 0.05). This difference disappeared in the summer or after light treatment in the winter. Also, light treatment and change in season resulted in a phase advance shift of melatonin rhythm in patients. The decline in melatonin levels correlated with the decline in specific SAD symptoms of hyperphagia and carbohydrate craving. In winter, neither patients nor controls showed significant diurnal variations in levels of whole blood serotonin. In both patients and controls, levels of serotonin were higher in summer as compared with winter, especially at 2000h. Our data suggest that elevated daytime melatonin can be a state marker of winter depression, and that seasonal change of photoperiod may also affect the circadian amplitude and daytime levels of blood serotonin. PMID:7986318

Danilenko, K V; Putilov, A A; Russkikh, G S; Duffy, L K; Ebbesson, S O

1994-07-01

222

Diurnal and seasonal variations of melatonin and serotonin in women with seasonal affective disorder.  

UK PubMed Central (United Kingdom)

In winters 1990-1991 and 1991-1992 women with and without seasonal affective disorder, winter type, were treated by light at 2500 lux either in the morning (0800h-1000h) or afternoon (1600h-1800h). In winter before light treatment, melatonin levels in serum in daytime (1200h and 1600h) were higher in patients compared to controls (p < 0.05). This difference disappeared in the summer or after light treatment in the winter. Also, light treatment and change in season resulted in a phase advance shift of melatonin rhythm in patients. The decline in melatonin levels correlated with the decline in specific SAD symptoms of hyperphagia and carbohydrate craving. In winter, neither patients nor controls showed significant diurnal variations in levels of whole blood serotonin. In both patients and controls, levels of serotonin were higher in summer as compared with winter, especially at 2000h. Our data suggest that elevated daytime melatonin can be a state marker of winter depression, and that seasonal change of photoperiod may also affect the circadian amplitude and daytime levels of blood serotonin.

Danilenko KV; Putilov AA; Russkikh GS; Duffy LK; Ebbesson SO

1994-07-01

223

Abnormal melatonin synthesis in autism spectrum disorders.  

UK PubMed Central (United Kingdom)

Melatonin is produced in the dark by the pineal gland and is a key regulator of circadian and seasonal rhythms. A low melatonin level has been reported in individuals with autism spectrum disorders (ASD), but the underlying cause of this deficit was unknown. The ASMT gene, encoding the last enzyme of melatonin synthesis, is located on the pseudo-autosomal region 1 of the sex chromosomes, deleted in several individuals with ASD. In this study, we sequenced all ASMT exons and promoters in individuals with ASD (n=250) and compared the allelic frequencies with controls (n=255). Non-conservative variations of ASMT were identified, including a splicing mutation present in two families with ASD, but not in controls. Two polymorphisms located in the promoter (rs4446909 and rs5989681) were more frequent in ASD compared to controls (P=0.0006) and were associated with a dramatic decrease in ASMT transcripts in blood cell lines (P=2 x 10(-10)). Biochemical analyses performed on blood platelets and/or cultured cells revealed a highly significant decrease in ASMT activity (P=2 x 10(-12)) and melatonin level (P=3 x 10(-11)) in individuals with ASD. These results indicate that a low melatonin level, caused by a primary deficit in ASMT activity, is a risk factor for ASD. They also support ASMT as a susceptibility gene for ASD and highlight the crucial role of melatonin in human cognition and behavior.

Melke J; Goubran Botros H; Chaste P; Betancur C; Nygren G; Anckarsäter H; Rastam M; Ståhlberg O; Gillberg IC; Delorme R; Chabane N; Mouren-Simeoni MC; Fauchereau F; Durand CM; Chevalier F; Drouot X; Collet C; Launay JM; Leboyer M; Gillberg C; Bourgeron T

2008-01-01

224

Abnormal melatonin synthesis in autism spectrum disorders.  

Science.gov (United States)

Melatonin is produced in the dark by the pineal gland and is a key regulator of circadian and seasonal rhythms. A low melatonin level has been reported in individuals with autism spectrum disorders (ASD), but the underlying cause of this deficit was unknown. The ASMT gene, encoding the last enzyme of melatonin synthesis, is located on the pseudo-autosomal region 1 of the sex chromosomes, deleted in several individuals with ASD. In this study, we sequenced all ASMT exons and promoters in individuals with ASD (n=250) and compared the allelic frequencies with controls (n=255). Non-conservative variations of ASMT were identified, including a splicing mutation present in two families with ASD, but not in controls. Two polymorphisms located in the promoter (rs4446909 and rs5989681) were more frequent in ASD compared to controls (P=0.0006) and were associated with a dramatic decrease in ASMT transcripts in blood cell lines (P=2 x 10(-10)). Biochemical analyses performed on blood platelets and/or cultured cells revealed a highly significant decrease in ASMT activity (P=2 x 10(-12)) and melatonin level (P=3 x 10(-11)) in individuals with ASD. These results indicate that a low melatonin level, caused by a primary deficit in ASMT activity, is a risk factor for ASD. They also support ASMT as a susceptibility gene for ASD and highlight the crucial role of melatonin in human cognition and behavior. PMID:17505466

Melke, J; Goubran Botros, H; Chaste, P; Betancur, C; Nygren, G; Anckarsäter, H; Rastam, M; Ståhlberg, O; Gillberg, I C; Delorme, R; Chabane, N; Mouren-Simeoni, M-C; Fauchereau, F; Durand, C M; Chevalier, F; Drouot, X; Collet, C; Launay, J-M; Leboyer, M; Gillberg, C; Bourgeron, T

2007-05-15

225

Melatonin modulates baroreflex control via area postrema.  

Science.gov (United States)

Pineal gland and its hormone melatonin have been implicated in modulation of cardiovascular system. We aimed at studying the effects of melatonin on baroreflex sensitivity and the role of area postrema, as a component modulator of baroreflex arch. Mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious freely moving rats. Baroreceptor reflex sensitivity was assessed by determining the HR responses to ramped infusions of phenylephrine (PE) and sodium nitroprusside (SNP)-induced MAP changes. Melatonin bolus (0.11 mg/kg) immediately followed by its continuous infusion (0.43 × 10(-9) mol/L at a rate of 0.65 mL/h for 30 min) in healthy normotensive rats produced a downward shift of baroreceptor reflex control with a substantial inhibition of reflex tachycardia (-32%) and potentiation of reflex bradycardia (+20%). Ablation of area postrema (APX group) induced a sustained decrease of MAP (101 ± 3 vs. 116 ± 3 mmHg, P APX group. We conclude that circulating melatonin can modulate baroreceptor reflex control of HR, thus resetting it toward lower HR values. The modulatory effects of melatonin may be mediated via melatonin receptors in the area postrema, located outside the blood-brain barrier. PMID:23531786

Campos, Luciana A; Cipolla-Neto, Jose; Michelini, Lisete C

2013-02-17

226

Putative melatonin receptors in a human biological clock  

Energy Technology Data Exchange (ETDEWEB)

In vitro autoradiography with /sup 125/I-labeled melatonin was used to examine melatonin binding sites in human hypothalamus. Specific /sup 125/I-labeled melatonin binding was localized to the suprachiasmatic nuclei, the site of a putative biological clock, and was not apparent in other hypothalamic regions. Specific /sup 125/I-labeled melatonin binding was consistently found in the suprachiasmatic nuclei of hypothalami from adults and fetuses. Densitometric analysis of competition experiments with varying concentrations of melatonin showed monophasic competition curves, with comparable half-maximal inhibition values for the suprachiasmatic nuclei of adults (150 picomolar) and fetuses (110 picomolar). Micromolar concentrations of the melatonin agonist 6-chloromelatonin completely inhibited specific /sup 125/I-labeled melatonin binding, whereas the same concentrations of serotonin and norepinephrine caused only a partial reduction in specific binding. The results suggest that putative melatonin receptors are located in a human biological clock.

Reppert, S.M.; Weaver, D.R.; Rivkees, S.A.; Stopa, E.G.

1988-10-07

227

Melatonin for preventing and treating jet lag.  

UK PubMed Central (United Kingdom)

BACKGROUND: Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. OBJECTIVES: To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. SELECTION CRITERIA: Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. DATA COLLECTION AND ANALYSIS: : Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. MAIN RESULTS: : Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. Based on the review, the number needed to treat (NNT) is 2. The benefit is likely to be greater the more time zones are crossed, and less for westward flights. The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low. Case reports suggest that people with epilepsy, and patients taking warfarin may come to harm from melatonin. REVIEWER'S CONCLUSIONS: Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It should be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.

Herxheimer A; Petrie KJ

2001-01-01

228

The effect of sleep on nocturnal urine output  

DEFF Research Database (Denmark)

  Hypothesis / aims of studyAim of this study was to elucidate the impact of sleep on the quantity and quality of the nocturnal urine production in healthy individuals.Our hypothesis was that sleep deprivation is related to excess nocturnal urine production.Study design, materials and methodsThe study protocol was approved by the local Ethics Committee.Twenty healthy volunteers with no history of enuresis, incontinence or nocturia were investigated in the present study. The participants were admitted in the hospital for two 24-hour periods under standardized conditions regarding sodium (2 mmol/kg) and water (25 ml/kg). Normal activities were allowed during the day. Blood samples were drawn every 3 hours and urine was fractionally collected with 3-hour intervals during daytime and following spontaneous voidings at night. During one of the two experimental 24-hour periods subjects were deprived from sleep and the sequence was randomized. During these nights with sleep deprivation, participants were in lying position in a dimly lit room and physical activities, food and fluid intake were not allowed. Smoking was not allowed throughout the entire experimental protocol. Determinations of electrolytes (Na+, K+, Ca2+) creatinine, urea and osmolality were made in plasma and urine. Blood pressure and heart rate were monitored every hour, using an ambulatory device. Arginine vasopressin (AVP) was measured in plasma by means of radioimmunoassay. Prostaglandin E2 (PGE2) was directly measured in urine using an enzyme immunoassay. 6-sulfatoxy-melatonin (MEL) was measured in urine using and ELISA assay. Clearances, excretions and fractional excretions were calculated for electrolytes, creatinine, urea, osmoles and solute free water. Comparisons were made between the nights with and without sleep deprivation. The circadian rhythm of AVP, PGE2 and MEL was evaluated at baseline and during sleep deprivation.ResultsNo significant differences were found in the urinary production at daytime between the two experimental 24-h periods. Males excreted significantly higher amounts of urine on a 24-h basis. During nighttime and on the nights of sleep deprivation, both males and females produced markedly larger amounts of urine even though the effect was more pronounced for males (males from 1.05 ± 0.10 ml/h/kg to 1.82 ± 0.22 ml/h/kg, p<0.001, females from 0.98 ± 0.09 ml/h/kg to 1.41 ± 0.11 ml/h/kg). A similar effect was found for the urinary excretion of sodium (baseline: 0.06 ± 0.01 mmol/kg/h, sleep deprivation: 0.12 ± 0.01 mmol/kg/h), potassium and urine osmolality (baseline: 416 ± 142 mosm/kg, sleep deprivation: 366 ± 66 mosm/kg). No differences were seen in urinary calcium excretion between baseline night and the night with sleep deprivation. The circadian rhythm in plasma AVP was not influenced by sleep deprivation. In accordance with this, solute free water reabsorption was not significantly different between baseline and during sleep deprivation (baseline 0.45 ± 0.08, sleep deprivation 0.47 ± 0.07 ml/min).We found a significant correlation between hemodynamics as these were assessed by blood pressure and heart rate and the degree of nocturnal polyuria following sleep deprivation.Interpretation of resultsResearch into the field of incontinence has therefore during the past years taken sleep related physiological mechanisms into consideration. In the present study we report that acute sleep deprivation has a dramatic effect on the volume of nocturnal urine production in both genders although the effect is more pronounced in males. Natriuresis and kaliuresis were observed on nights with sleep deprivation and were related to differences in hemodynamics between nights with and without sleep deprivation. The circadian rhythms in AVP, PGE2 and melatonin all seem unaffected by sleep deprivation. Furthermore renal water handling was not influenced by sleep deprivation. Concluding messageSleep seems to be a major regulator of urine production at night and its deprivation leads to natriuresis, kaliuresis and the production of excess amounts

Kamperis, Konstantinos; HagstrØm, SØren

2005-01-01

229

Modulation of Pineal Melatonin Synthesis by Glutamate Involves Paracrine Interactions between Pinealocytes and Astrocytes through NF-?B Activation  

Science.gov (United States)

The glutamatergic modulation of melatonin synthesis is well known, along with the importance of astrocytes in mediating glutamatergic signaling in the central nervous system. Pinealocytes and astrocytes are the main cell types in the pineal gland. The objective of this work was to investigate the interactions between astrocytes and pinealocytes as a part of the glutamate inhibitory effect on melatonin synthesis. Rat pinealocytes isolated or in coculture with astrocytes were incubated with glutamate in the presence of norepinephrine, and the melatonin content, was quantified. The expression of glutamate receptors, the intracellular calcium content and the NF-?B activation were analyzed in astrocytes and pinealocytes. TNF-?'s possible mediation of the effect of glutamate was also investigated. The results showed that glutamate's inhibitory effect on melatonin synthesis involves interactions between astrocytes and pinealocytes, possibly through the release of TNF-?. Moreover, the activation of the astrocytic NF-?B seems to be a necessary step. In astrocytes and pinealocytes, AMPA, NMDA, and group I metabotropic glutamate receptors were observed, as well as the intracellular calcium elevation. In conclusion, there is evidence that the modulation of melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through the activation of the astrocytic NF-?B transcription factor and possibly by subsequent TNF-? release.

Atherino, Victoria Fairbanks; Lima, Larissa de Sa; Moutinho, Anderson Augusto; do Amaral, Fernanda Gaspar; Peres, Rafael; Martins de Lima, Thais; Torrao, Andrea da Silva; Cipolla-Neto, Jose; Scavone, Cristoforo; Afeche, Solange Castro

2013-01-01

230

Folic acid and melatonin ameliorate carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats.  

UK PubMed Central (United Kingdom)

This study investigated the protective effects of melatonin and folic acid against carbon tetrachloride (CCl4)-induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. The levels of protein kinase B (Akt1), interferon gamma (IFN-?), programmed cell death-receptor (Fas) and Tumor necrosis factor-alpha (TNF-?) mRNA expression were analyzed. CCl4 significantly elevated the levels of lipid peroxidation (MDA), cholesterol, LDL, triglycerides, bilirubin and urea. In addition, CCl4 was found to significantly suppress the activity of both catalase and glutathione (GSH) and decrease the levels of serum total protein and HDL-cholesterol. All of these parameters were restored to their normal levels by treatment with melatonin, folic acid or their combination. An improvement of the general hepatic architecture was observed in rats that were treated with the combination of melatonin and folic acid along with CCl4. Furthermore, the CCl4-induced upregulation of TNF-? and Fas mRNA expression was significantly restored by the three treatments. Melatonin, folic acid or their combination also restored the baseline levels of IFN-? and Akt1 mRNA expression. The combination of melatonin and folic acid exhibited ability to reduce the markers of liver injury induced by CCl4 and restore the oxidative stability, the level of inflammatory cytokines, the lipid profile and the cell survival Akt1 signals.

Ebaid H; Bashandy SA; Alhazza IM; Rady A; El-Shehry S

2013-01-01

231

Modulation of Pineal Melatonin Synthesis by Glutamate Involves Paracrine Interactions between Pinealocytes and Astrocytes through NF-?B Activation.  

UK PubMed Central (United Kingdom)

The glutamatergic modulation of melatonin synthesis is well known, along with the importance of astrocytes in mediating glutamatergic signaling in the central nervous system. Pinealocytes and astrocytes are the main cell types in the pineal gland. The objective of this work was to investigate the interactions between astrocytes and pinealocytes as a part of the glutamate inhibitory effect on melatonin synthesis. Rat pinealocytes isolated or in coculture with astrocytes were incubated with glutamate in the presence of norepinephrine, and the melatonin content, was quantified. The expression of glutamate receptors, the intracellular calcium content and the NF- ? B activation were analyzed in astrocytes and pinealocytes. TNF- ? 's possible mediation of the effect of glutamate was also investigated. The results showed that glutamate's inhibitory effect on melatonin synthesis involves interactions between astrocytes and pinealocytes, possibly through the release of TNF- ? . Moreover, the activation of the astrocytic NF- ? B seems to be a necessary step. In astrocytes and pinealocytes, AMPA, NMDA, and group I metabotropic glutamate receptors were observed, as well as the intracellular calcium elevation. In conclusion, there is evidence that the modulation of melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through the activation of the astrocytic NF- ? B transcription factor and possibly by subsequent TNF- ? release.

Villela D; Atherino VF; Lima Lde S; Moutinho AA; do Amaral FG; Peres R; Martins de Lima T; Torrão Ada S; Cipolla-Neto J; Scavone C; Afeche SC

2013-01-01

232

Folic acid and melatonin ameliorate carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract This study investigated the protective effects of melatonin and folic acid against carbon tetrachloride (CCl4)-induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. The levels of protein kinase B (Akt1), interferon gamma (IFN-?), programmed cell death-receptor (Fas) and Tumor necrosis factor-alpha (TNF-?) mRNA expression were analyzed. CCl4 significantly elevated the levels of lipid peroxidation (MDA), cholesterol, LDL, triglycerides, bilirubin and urea. In addition, CCl4 was found to significantly suppress the activity of both catalase and glutathione (GSH) and decrease the levels of serum total protein and HDL-cholesterol. All of these parameters were restored to their normal levels by treatment with melatonin, folic acid or their combination. An improvement of the general hepatic architecture was observed in rats that were treated with the combination of melatonin and folic acid along with CCl4. Furthermore, the CCl4-induced upregulation of TNF-? and Fas mRNA expression was significantly restored by the three treatments. Melatonin, folic acid or their combination also restored the baseline levels of IFN-? and Akt1 mRNA expression. The combination of melatonin and folic acid exhibited ability to reduce the markers of liver injury induced by CCl4 and restore the oxidative stability, the level of inflammatory cytokines, the lipid profile and the cell survival Akt1 signals.

Ebaid Hossam; Bashandy Samir AE; Alhazza Ibrahim M; Rady Ahmed; El-Shehry Sultan

2013-01-01

233

Evidence for feedback control of pineal melatonin secretion.  

UK PubMed Central (United Kingdom)

Melatonin is the principle hormonal product of the pineal gland. It is secreted with a robust daily rhythm, peaking near the middle of the night. During the daytime, concentrations remain very low, as exposure to light robustly suppresses its secretion. The regulation of melatonin by light is well-characterized, but an interesting feature of the daily melatonin rhythm is that its peak occurs near the middle of the night and then levels begin to drop hours before morning light exposure. The mechanism underlying the light-independent drop in melatonin during late night remains unspecified. Feedback control is one mechanism of hormone regulation, but no studies thus far have explored the possibility of such regulation in the pineal of white-footed mice (Peromyscus leucopus). The pineal gland and SCN express melatonin receptors, and melatonin regulates its own receptor density in the brain. We investigated the possibility of feedback control of melatonin by administering melatonin receptor antagonists to female white-footed mice and then measuring plasma melatonin concentrations. In the first experiment, we observed that luzindole, a dual MT1/MT2 receptor antagonist administered 1h after lights off, caused an increase in plasma melatonin both 1 and 2h later. In a second experiment, we did not observe a change in melatonin concentrations following injection of an antagonist specific for the MT2 subtype. These results suggest the possibility of feedback control of melatonin release, occurring preferentially through the MT1 receptor subtype.

Bedrosian TA; Herring KL; Walton JC; Fonken LK; Weil ZM; Nelson RJ

2013-05-01

234

Genetics Home Reference: Autosomal dominant nocturnal frontal lobe epilepsy  

Science.gov (United States)

... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Autosomal dominant nocturnal frontal lobe epilepsy (often shortened to ADNFLE ) On ... Glossary definitions Reviewed April 2009 What is ADNFLE? Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon form ...

235

Protective effect of melatonin on acute pancreatitis.  

UK PubMed Central (United Kingdom)

Melatonin, a product of the pineal gland, is released from the gut mucosa in response to food ingestion. Specific receptors for melatonin have been detected in many gastrointestinal tissues including the pancreas. Melatonin as well as its precursor, L-tryptophan, attenuates the severity of acute pancreatitis and protects the pancreatic tissue from the damage caused by acute inflammation. The beneficial effect of melatonin on acute pancreatitis, which has been reported in many experimental studies and supported by clinical observations, is related to: (1) enhancement of antioxidant defense of the pancreatic tissue, through direct scavenging of toxic radical oxygen (ROS) and nitrogen (RNS) species, (2) preservation of the activity of antioxidant enzymes; such as superoxide dismutase (SOD), catalase (CAT), or glutathione peroxidase (GPx), (3) the decline of pro-inflammatory cytokine tumor necrosis ? (TNF?) production, accompanied by stimulation of an anti-inflammatory IL-10, (4) improvement of pancreatic blood flow and decrease of neutrophil infiltration, (5) reduction of apoptosis and necrosis in the inflamed pancreatic tissue, (6) increased production of chaperon protein (HSP60), and (7) promotion of regenerative process in the pancreas. Conclusion. Endogenous melatonin produced from L-tryptophan could be one of the native mechanisms protecting the pancreas from acute damage and accelerating regeneration of this gland. The beneficial effects of melatonin shown in experimental studies suggest that melatonin ought to be employed in the clinical trials as a supportive therapy in acute pancreatitis and could be used in people at high risk for acute pancreatitis to prevent the development of pancreatic inflammation.

Jaworek J; Szklarczyk J; Jaworek AK; Nawrot-Por?bka K; Leja-Szpak A; Bonior J; Kot M

2012-01-01

236

Nocturnal acid breakthrough: consequences and confronting  

Directory of Open Access Journals (Sweden)

Full Text Available SUMMARY Nocturnal Acid Breakthrough is defined as the appearance of gastric acid in the antrum of pH<4 overnight for a period longer than one hour during the administration of proton pump inhibitors. The prevalence of this phenomenon ranges between 69-79% in normal volunteers and patients with gastroesophageal reflux disease respectively. It typically appears in the second 6-hour period after the evening dose of a PPI when patients are sleeping. The significance of nocturnal acid breakthrough is uncertain despite intense clinical and laboratory investigation. The available data do not lead to firm conclusions, so this interesting matter requires more research in different parts of the world. The relationship between Helicobacter pylori infection and nocturnal acid breakthrough both in health and upper GI disorders disease has not been fully investigated. However, it seems that the Helicobacter pylori status must be taken into account when dealing with nocturnal acid breakthrough, both in patients and normal controls. Despite the fact that data concerning the exact significance of nocturnal acid breakthrough are not conclusive it must be stressed that it is a common phenomenon in proton pump inhibitor therapy. Although esophageal reflux in not a frequent event, it is more likely to occur in patients with poor motility, severe gastroesophageal reflux disease, Barrett?s esophagus and scleroderma. It seems that in every day clinical practice, the administration of a proton pump inhibitor before meals and ranitidine at bedtime may well be the most cost-effective method available to control gastroesophageal reflux disease.Key Words: Nocturnal acid breakthrough, Reflux, Gastroesophageal reflux disease, Helicobacter pylori, Extraesophageal manifestations of GERD, H2 receptor antagonists, Proton pump inhibitors

K. Triantafillidis, Maria Mylonaki, F. Georgopoulos

2007-01-01

237

Nocturnal acid breakthrough: consequences and confronting  

Directory of Open Access Journals (Sweden)

Full Text Available SUMMARY Nocturnal Acid Breakthrough is defined as the appearance of gastric acid in the antrum of pH<4 overnight for a period longer than one hour during the administration of proton pump inhibitors. The prevalence of this phenomenon ranges between 69-79% in normal volunteers and patients with gastroesophageal reflux disease respectively. It typically appears in the second 6-hour period after the evening dose of a PPI when patients are sleeping. The significance of nocturnal acid breakthrough is uncertain despite intense clinical and laboratory investigation. The available data do not lead to firm conclusions, so this interesting matter requires more research in different parts of the world. The relationship between Helicobacter pylori infection and nocturnal acid breakthrough both in health and upper GI disorders disease has not been fully investigated. However, it seems that the Helicobacter pylori status must be taken into account when dealing with nocturnal acid breakthrough, both in patients and normal controls. Despite the fact that data concerning the exact significance of nocturnal acid breakthrough are not conclusive it must be stressed that it is a common phenomenon in proton pump inhibitor therapy. Although esophageal reflux in not a frequent event, it is more likely to occur in patients with poor motility, severe gastroesophageal reflux disease, Barrett?s esophagus and scleroderma. It seems that in every day clinical practice, the administration of a proton pump inhibitor before meals and ranitidine at bedtime may well be the most cost-effective method available to control gastroesophageal reflux disease. Key Words: Nocturnal acid breakthrough, Reflux, Gastroesophageal reflux disease, Helicobacter pylori, Extraesophageal manifestations of GERD, H2 receptor antagonists, Proton pump inhibitors

J.K. Triantafillidis, Maria Mylonaki, F. Georgopoulos

2007-01-01

238

Nocturnal frontal lobe epilepsy: new pathophysiological interpretations.  

Science.gov (United States)

Since the first descriptions of Nocturnal Frontal Lobe Epilepsy (NFLE) many theories have been proposed to explain its pathophysiological mechanisms. The aim of this paper is to formulate a tentative hypothesis designed to unify the clinical, anatomo-physiological, and genetic aspects underlying this condition. According to this hypothesis, NFLE is due to a disorder in the thalamocortical circuit involved in the arousal mechanism. Other cortical-networks involving the limbic system may explain, for instance, primitive behaviors. The role of the cholinergic system and related pathways in the pathogenesis of nocturnal seizures and parasomnias is also discussed. PMID:22136898

Tinuper, Paolo; Bisulli, Francesca; Provini, Federica; Montagna, Pasquale; Lugaresi, Elio

2011-12-01

239

Nocturnal frontal lobe epilepsy: new pathophysiological interpretations.  

UK PubMed Central (United Kingdom)

Since the first descriptions of Nocturnal Frontal Lobe Epilepsy (NFLE) many theories have been proposed to explain its pathophysiological mechanisms. The aim of this paper is to formulate a tentative hypothesis designed to unify the clinical, anatomo-physiological, and genetic aspects underlying this condition. According to this hypothesis, NFLE is due to a disorder in the thalamocortical circuit involved in the arousal mechanism. Other cortical-networks involving the limbic system may explain, for instance, primitive behaviors. The role of the cholinergic system and related pathways in the pathogenesis of nocturnal seizures and parasomnias is also discussed.

Tinuper P; Bisulli F; Provini F; Montagna P; Lugaresi E

2011-12-01

240

Circulating immune complexes in paroxysmal nocturnal hemoglobinuria.  

UK PubMed Central (United Kingdom)

Circulating immune complexes were investigated in sera of 13 patients with paroxysmal nocturnal hemoglobinuria. A significant inhibition was observed in the complement-dependent rosette formation (EAC) in 6 cases; 2 patients presented an increased anticomplementary activity; antilymphocyte antibodies were demonstrated in 2 patients. The levels of C3d and immunoconglutinins were also increased; there were no differences in the total hemolytic complement between patients and normal controls. There was a significant correlation between C3d and immunoconglutinins with the inhibition of the EAC rosette formation test. These results provide evidence for the presence of circulating immune complexes in paroxysmal nocturnal hemoglobinuria.

Villaescusa R; Santos MN; García Y; Trujillo Y; Bernal B; Ballester JM; Hernández P

1982-01-01

 
 
 
 
241

Melatonin levels in periodontal health and disease.  

UK PubMed Central (United Kingdom)

BACKGROUND AND OBJECTIVE: The aim of this study was to measure melatonin levels in the gingival crevicular fluid and saliva of subjects with healthy periodontal tissues, plaque-induced gingival inflammation, chronic periodontitis and aggressive periodontitis. MATERIAL AND METHODS: A total of 70 subjects were examined and assigned to four groups: healthy periodontium (10 subjects); plaque-induced gingival inflammation (20 subjects); chronic periodontitis (20 subjects); and aggressive periodontitis (20 subjects). Gingival crevicular fluid and saliva samples were collected from each subject and analyzed using ELISAs. RESULTS: The melatonin levels in both gingival crevicular fluid and saliva were lower in patients with chronic periodontitis (10.4 and 12.8 pg/mL, respectively) and aggressive periodontitis (8.4 and 8.8 pg/mL, respectively) than in patients with gingivitis (13.9 and 17.6 pg/mL, respectively) and in healthy subjects (16.6 and 22.9 pg/mL, respectively). The mean melatonin levels in both gingival crevicular fluid and saliva were statistically significantly higher in healthy patients compared with patients with chronic periodontitis and aggressive periodontitis; however, there was no significant difference in the plaque-induced gingival inflammation between the study groups. CONCLUSIONS: The melatonin levels in gingival crevicular fluid and saliva are decreased in diseased periodontal tissues, especially periodontitis. The melatonin level was lowest in the aggressive periodontitis group.

Almughrabi OM; Marzouk KM; Hasanato RM; Shafik SS

2013-06-01

242

Melatonin and the pathophysiology of cellular membranes  

Directory of Open Access Journals (Sweden)

Full Text Available The ability of melatonin to influence the physiology of cell membranes is reviewed in this report. Publications related to this field from 1993 – present. Melatonin is a ubiquitously acting indoleamine which is associated with a variety of important functions within both unicellular and multicellular organisms. By virtue of its ability to protect lipids from free radical damage, melatonin is remarkably beneficial in preserving the morphological and functional integrity of cell membranes. In doing so, it reduces the quantity of oxidized lipids in membranes and maintains them at optimal fluidity, i.e., prevents them from becoming rigid. This contributes significantly to the function of proteins (receptors, channels, pores, etc.) in the cell membranes and helps in preserving the normal physiology of the cells. In addition to these indirect effects of melatonin on membrane function, there is evidence that this indoleamine also may act directly on channels assisting membranes in maintaining proper ion gradients and current. The role of melatonin in the functioning of membrane channels and pores is an area of research that should be experimentally exploited.

Russel J. Reiter; Lorena Fuentes-Broto; Sergio D. Paredes; Dun-Xian Tan; Joaquin J. Garcia

2010-01-01

243

The role of melatonin as an antioxidant in the follicle  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Melatonin (N-acetyl-5-methoxytryptamine) is secreted during the dark hours at night by pineal gland, and it regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. It has been believed that melatonin regulates ovarian function by the regulation of gonadotropin release in the hypothalamus-pituitary gland axis via its specific receptors. In addition to the receptor mediated action, the discovery of melatonin as a direct free radical scavenger has greatly broadened the understanding of melatonin's mechanisms which benefit reproductive physiology. Higher concentrations of melatonin have been found in human preovulatory follicular fluid compared to serum, and there is growing evidence of the direct effects of melatonin on ovarian function especially oocyte maturation and embryo development. Many scientists have focused on the direct role of melatonin on oocyte maturation and embryo development as an anti-oxidant to reduce oxidative stress induced by reactive oxygen species, which are produced during ovulation process. The beneficial effects of melatonin administration on oocyte maturation and embryo development have been confirmed by in vitro and in vivo experiments in animals. This review also discusses the first application of melatonin to the clinical treatment of infertile women and confirms that melatonin administration reduces intrafollicular oxidative damage and increase fertilization rates. This review summarizes our recent works and new findings related to the reported beneficial effects of melatonin on reproductive physiology in its role as a reducer of oxidative stress, especially on oocyte maturation and embryo development.

Tamura Hiroshi; Takasaki Akihisa; Taketani Toshiaki; Tanabe Manabu; Kizuka Fumie; Lee Lifa; Tamura Isao; Maekawa Ryo; Aasada Hiromi; Yamagata Yoshiaki; Sugino Norihiro

2012-01-01

244

Melatonin: An Underappreciated Player in Retinal Physiology and Pathophysiology  

Science.gov (United States)

In the vertebrate retina, melatonin is synthesized by the photoreceptors with high levels of melatonin at night and lower levels during the day. Melatonin exerts its influence by interacting with a family of G-protein-coupled receptors that are negatively coupled with adenylyl cyclase. Melatonin receptors belonging to the subtypes MT1 and MT2 have been identified in the mammalian retina. MT1 and MT2 receptors are found in all layers of the neural retina and in the retinal pigmented epithelium. Melatonin in the eye is believed to be involved in the modulation of many important retinal functions; it can modulate the electroretinogram (ERG), and administration of exogenous melatonin increases light-induced photoreceptor degeneration. Melatonin may also have protective effects on retinal pigment epithelial cells, photoreceptors and ganglion cells. A series of studies have implicated melatonin in the pathogenesis of age-related macular degeneration, and melatonin administration may represent a useful approach to prevent and treat glaucoma. Melatonin is used by millions of people around the world to retard aging, improve sleep performance, mitigate jet lag symptoms, and treat depression. Administration of exogenous melatonin at night may also be beneficial for ocular health, but additional investigation is needed to establish its potential.

Tosini, Gianluca; Baba, Kenkichi; Hwang, Christopher K.; Iuvone, P. Michael

2012-01-01

245

Expression of melatonin receptors in arteries involved in thermoregulation  

Energy Technology Data Exchange (ETDEWEB)

Melatonin binding sites were localized and characterized in the vasculature of the rat by using the melatonin analogue 2-(125I)iodomelatonin (125I-melatonin) and quantitative in vitro autoradiography. The expression of these sites was restricted to the caudal artery and to the arteries that form the circle of Willis at the base of the brain. The arterial 125I-melatonin binding was stable, saturable, and reversible. Saturation studies revealed that the binding represented a single class of high-affinity binding sites with a dissociation constant (Kd) of 3.4 x 10(-11) M in the anterior cerebral artery and 1.05 x 10(-10) M in the caudal artery. The binding capacities (Bmax) in these arteries were 19 and 15 fmol/mg of protein, respectively. The relative order of potency of indoles for inhibition of 125I-melatonin binding at these sites was typical of a melatonin receptor: 2-iodomelatonin greater than melatonin greater than N-acetylserotonin much much greater than 5-hydroxytryptamine. Norepinephrine-induced contraction of the caudal artery in vitro was significantly prolonged and potentiated by melatonin in a concentration-dependent manner, suggesting that these arterial binding sites are functional melatonin receptors. Neither primary steps in smooth muscle contraction (inositol phospholipid hydrolysis) nor relaxation (adenylate cyclase activation) were affected by melatonin. Melatonin, through its action on the tone of these arteries, may cause circulatory adjustments in these arteries, which are believed to be involved in thermoregulation.

Viswanathan, M.; Laitinen, J.T.; Saavedra, J.M. (National Institute of Mental Health, Bethesda, MD (USA))

1990-08-01

246

Enhancement of melatonin photostability by encapsulation in lipospheres.  

UK PubMed Central (United Kingdom)

The effect of lipid microparticle carrier systems on the light-induced degradation of melatonin was investigated. Microspheres loaded with melatonin were prepared using tristearin or tripalmitin as the lipid material and hydrogenated phosphatidylcholine or polysorbate 60 as the emulsifier. The obtained lipid microspheres were characterized by scanning-electron microscopy and differential scanning calorimetry. Free or microencapsulated melatonin was incorporated in a model cream formulation (oil-in-water emulsion) and irradiated with a solar simulator. The extent of photodegradation was measured by high-performance liquid chromatography. The photolysis experiments demonstrated that the light-induced decomposition of melatonin was markedly decreased by encapsulation into lipid microspheres based on tristearin and phosphatidylcholine (the extent of degradation was 19.6% for unencapsulated melatonin compared to 5.6% for the melatonin-loaded microparticles). Therefore, incorporation in lipid microparticles can be considered an effective system to enhance the photostability of melatonin.

Tursilli R; Casolari A; Iannuccelli V; Scalia S

2006-03-01

247

A de novo mutation in sporadic nocturnal frontal lobe epilepsy.  

Science.gov (United States)

Autosomal dominant nocturnal frontal lobe epilepsy is sometimes due to mutations in CHRNA4. The commoner presentation of sporadic nocturnal frontal lobe epilepsy has not been associated with genetic defects. A 30-year-old woman diagnosed as having sporadic nocturnal frontal lobe epilepsy was found to have a de novo Ser252Leu CHRNA4 mutation. A pattern is emerging of site-specific mutation within the second transmembrane domain of CHRNA4 in association with autosomal dominant nocturnal frontal lobe epilepsy and sporadic nocturnal frontal lobe epilepsy in families with different ethnic backgrounds. PMID:10939581

Phillips, H A; Marini, C; Scheffer, I E; Sutherland, G R; Mulley, J C; Berkovic, S F

2000-08-01

248

A de novo mutation in sporadic nocturnal frontal lobe epilepsy.  

UK PubMed Central (United Kingdom)

Autosomal dominant nocturnal frontal lobe epilepsy is sometimes due to mutations in CHRNA4. The commoner presentation of sporadic nocturnal frontal lobe epilepsy has not been associated with genetic defects. A 30-year-old woman diagnosed as having sporadic nocturnal frontal lobe epilepsy was found to have a de novo Ser252Leu CHRNA4 mutation. A pattern is emerging of site-specific mutation within the second transmembrane domain of CHRNA4 in association with autosomal dominant nocturnal frontal lobe epilepsy and sporadic nocturnal frontal lobe epilepsy in families with different ethnic backgrounds.

Phillips HA; Marini C; Scheffer IE; Sutherland GR; Mulley JC; Berkovic SF

2000-08-01

249

Green Light for Nocturnally Migrating Birds  

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The nighttime sky is increasingly illuminated by artificial light sources. Although this ecological light pollution is damaging ecosystems throughout the world, the topic has received relatively little attention. Many nocturnally migrating birds die or lose a large amount of their energy reserves du...

Hanneke Poot; Bruno J. Ens; Han de Vries; Maurice A. H. Donners; Marcel R. Wernand; Joop M. Marquenie

250

Melatonin and its precursors scavenge nitric oxide  

Energy Technology Data Exchange (ETDEWEB)

Nitric oxide (NO) scavenging activity of melatonin, N-acetyl-5-hydroxytryptamine, serotonin, 5-hydroxytryptophan and L-tryptophan was examined by the Griess reaction using flow injection analysis. 1-Hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene(NOC-7) was used as NO generator. The Griess reagent stoichiometrically reacts with NO2-, which was converted by a cadmium-copper reduction column from the stable end products of NO oxidation. Except for tryptophan, all the compounds examined scavenged NO in a dose-dependent manner. Melatonin, which has a methoxy group in the 5-position and an acetyl side chain, exhibited the most potent scavenging activity among the compounds tested. Serotonin, N-acetyl-5-hydroxytryptamine, and 5-hydroxytryptophan, respectively, showed moderate scavenging activity compared to melatonin. Tryptophan, which has neither a methoxy nor a hydroxyl group in the 5-position, exhibited the least NO scavenging activity.

Noda, Y.; Mori, A.; Liburdy, R.; Packer, L.

1998-12-01

251

Nocturnal position in the Panamanian Golden Frog, Atelopus zeteki (Anura, Bufonidae), with notes on fluorescent pigment tracking  

Directory of Open Access Journals (Sweden)

Full Text Available The endangered Panamanian golden frog, Atelopus zeteki, is a stream dweller of middle elevation rain forests of the Panamanian isthmus. In order to better understand this species for conservation, we set out to determine the nocturnal whereabouts of this diurnally activeanimal. It was expected that adult males and juveniles might occupy different nocturnal microhabitats based on differences in size, coloration and patterning. Findings presented here demonstrate that adult males climb significantly higher than juveniles at night and that movement distances to final resting positions also significantlydiffered. This change in diurnal and nocturnal position in adult males may be related to predator vigilance and avoidance. Lastly, this study demonstrated that individual rain forest amphibians can be successfully tracked over short to moderate distances in humid to wet environments using fluorescent pigments.

Erik D. Lindquist; Scott A. Sapoznick; Edgardo J. Griffith Rodriguez; Peter B. Johantgen; Joni M. Criswell

2007-01-01

252

Effect of melatonin supplementation and cross-fostering on renal glutathione system and development of hypertension in spontaneously hypertensive rats.  

UK PubMed Central (United Kingdom)

Antenatal and postnatal environments are hypothesised to influence the development of hypertension. This study investigates the synergistic effect of cross-fostering and melatonin supplementation on the development of hypertension and renal glutathione system in spontaneously hypertensive rats (SHR). In one experiment, 1-day-old male SHR pups were fostered to either SHR (shr-SHR) or Wistar-Kyoto rats, (shr-WKY). In a concurrent experiment, SHR dams were given melatonin in drinking water (10 mg/kg body weight) from day 1 of pregnancy. Immediately following delivery, 1-day-old male pups were fostered either to SHR (Mel-shr-SHR) or WKY (Mel-shr-WKY) dams receiving melatonin supplementation until weaning on day 21. Upon weaning, melatonin supplementation was continued to these pups until the age of 16 weeks. Systolic blood pressures (SBP) were recorded at the age of 4, 6, 8, 12 and 16 weeks. Renal antioxidant activities were measured. Mean SBP of shr-WKY, Mel-shr-SHR and Mel-shr-WKY was significantly lower than that in shr-SHR until the age of 8 weeks. At 12 and 16 weeks of age, mean SBP of Mel-shr-WKY was lower than those in non-treated shr-SHR and shr-WKY pups but was not significantly different from that in Mel-shr-SHR. Renal glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were significantly higher in Mel-shr-SHR and Mel-shr-WKY at 16 weeks of age. It appears that combination of cross-fostering and melatonin supplementation exerts no synergistic effect on delaying the rise in blood pressure in SHR. The elevated GPx and GST activities are likely to be due to the effect of melatonin supplementation.

Siew-Keah L; Sundaram A; Sirajudeen KN; Zakaria R; Singh HJ

2013-08-01

253

The effect of the lunar cycle on fecal cortisol metabolite levels and foraging ecology of nocturnally and diurnally active spiny mice.  

Science.gov (United States)

We studied stress hormones and foraging of nocturnal Acomys cahirinus and diurnal A. russatus in field populations as well as in two field enclosures populated by both species and two field enclosures with individuals of A. russatus alone. When alone, A. russatus individuals become also nocturnally active. We asked whether nocturnally active A. russatus will respond to moon phase and whether this response will be obtained also in diurnally active individuals. We studied giving-up densities (GUDs) in artificial foraging patches and fecal cortisol metabolite levels. Both species exhibited elevated fecal cortisol metabolite levels and foraged to higher GUDs in full moon nights; thus A. russatus retains physiological response and behavioral patterns that correlate with full moon conditions, as can be expected in nocturnal rodents, in spite of its diurnal activity. The endocrinological and behavioral response of this diurnal species to moon phase reflects its evolutionary heritage. PMID:21829733

Gutman, Roee; Dayan, Tamar; Levy, Ofir; Schubert, Iris; Kronfeld-Schor, Noga

2011-08-04

254

The effect of the lunar cycle on fecal cortisol metabolite levels and foraging ecology of nocturnally and diurnally active spiny mice.  

UK PubMed Central (United Kingdom)

We studied stress hormones and foraging of nocturnal Acomys cahirinus and diurnal A. russatus in field populations as well as in two field enclosures populated by both species and two field enclosures with individuals of A. russatus alone. When alone, A. russatus individuals become also nocturnally active. We asked whether nocturnally active A. russatus will respond to moon phase and whether this response will be obtained also in diurnally active individuals. We studied giving-up densities (GUDs) in artificial foraging patches and fecal cortisol metabolite levels. Both species exhibited elevated fecal cortisol metabolite levels and foraged to higher GUDs in full moon nights; thus A. russatus retains physiological response and behavioral patterns that correlate with full moon conditions, as can be expected in nocturnal rodents, in spite of its diurnal activity. The endocrinological and behavioral response of this diurnal species to moon phase reflects its evolutionary heritage.

Gutman R; Dayan T; Levy O; Schubert I; Kronfeld-Schor N

2011-01-01

255

Melatonin Attenuates the Skin Sympathetic Nerve Response to Mental Stress.  

UK PubMed Central (United Kingdom)

Melatonin attenuates muscle sympathetic nerve responses to sympathoexcitatory stimuli but it is unknown if melatonin similarly attenuates reflex changes in skin sympathetic nerve activity (SSNA). In this double-blind, placebo- controlled crossover study, we tested the hypothesis that melatonin (3 mg) would attenuate the SSNA response to mental stress (mental arithmetic). Twelve healthy subjects underwent experimental testing on two separate days. Three minutes of mental stress occurred before and 45 min after ingestion of melatonin (3 mg) or placebo. Skin temperature was maintained at 34°C. Reflex increases in SSNA (peroneal nerve), mean arterial pressure (MAP), and heart rate (HR) to mental stress before and after melatonin were determined. Melatonin lowered HR (pre: 66 ± 3 bpm; post: 62 ± 3 bpm, P = 0.046) and SSNA (pre: 14282 ± 3706 au; post: 9571 ± 2609 au, P = 0.034) at rest. In response to mental stress, SSNA increases were significantly attenuated following melatonin ingestion (second minute: 114 ± 30 vs 74 ± 14%; third minute: 111 ± 29 vs 54 ± 12%, both P < 0.05). The MAP increase to mental stress was blunted in the third minute (20 ± 2 vs 17 ± 2 mmHg, P = 0.032) and the HR increase was blunted in the first minute (33 ± 3 vs 29 ± 3 beats/min, P = 0.034) after melatonin. In summary, exogenous melatonin attenuates the SSNA response to mental stress. These data support the concept that melatonin elicits a generalized reduction in reflex increases in sympathetic nerve activity.

Muller MD; Sauder CL; Ray CA

2013-08-01

256

Role of melatonin and its receptors in the vertebrate retina.  

UK PubMed Central (United Kingdom)

Melatonin is a chemical signal of darkness that is produced by retinal photoreceptors and pinealocytes. In the retina, melatonin diffuses from the photoreceptors to bind to specific receptors on a variety of inner retinal neurons to modify their activity. Potential target cells for melatonin in the inner retina are amacrine cells, bipolar cells, horizontal cells, and ganglion cells. Melatonin inhibits the release of dopamine from amacrine cells and increases the light sensitivity of horizontal cells. Melatonin receptor subtypes show differential, cell-specific patterns of expression that are likely to underlie differential functional modulation of specific retinal pathways. Melatonin potentiates rod signals to ON-type bipolar cells, via activation of the melatonin MT2 (Mel1b) receptor, suggesting that melatonin modulates the function of specific retinal circuits based on the differential distribution of its receptors. The selective and differential expression of melatonin receptor subtypes in cone circuits suggest a conserved function for melatonin in enhancing transmission from rods to second-order neurons and thus promote dark adaptation.

Wiechmann AF; Sherry DM

2013-01-01

257

The research of melatonin in hypoxic-ischemic encephalopathy  

International Nuclear Information System (INIS)

Objective: To elucidate the function of melatonin in the pathogenesis and the prognosis of hypoxic-ischemic encephalopathy (HIE) and provide the pathophysiology basis for therapying HIE with melatonin. Methods: The level of plasma melatonin of twenty normal term infants and twenty modest HIE and twenty middle-severity HIE in their acute phase and recovery phase were assayed respectively with radioimmunoassay (RIA). Then compare the difference of the melatonin level among these neonates. Results: (1) For modest HIE, the melatonin level was higher than that in the normal in the acute phase and there was no difference to the normal in the recovery phase. (2) There was no difference between the melatonin level in middle-severity HIE in the acute phase and that in the normal, but in the recovery phase it was higher than that in the normal. (3) For modest HIE, the melatonin level in acute phase was higher than that in the recovery phase, but for middle-severity HIE, it was adverse. (4) In the acute phase, the level in modest HIE was higher than that in the middle-severity HIE, but on the contrary in the recovery phase. Conclusion: Melatonin have protection action on HIE. The prognosis of modest HIE neonates with rising melatonin level in the acute phase is better than that with lower melatonin level of middle-severity HIE. (authors)

2006-01-01

258

Alcoholic fermentation induces melatonin synthesis in orange juice.  

UK PubMed Central (United Kingdom)

Melatonin (N-acetyl-5-methoxytryptamine) is a molecule implicated in multiple biological functions. Its level decreases with age, and the intake of foods rich in melatonin has been considered an exogenous source of this important agent. Orange is a natural source of melatonin. Melatonin synthesis occurs during alcoholic fermentation of grapes, malt and pomegranate. The amino acid tryptophan is the precursor of all 5-methoxytryptamines. Indeed, melatonin appears in a shorter time in wines when tryptophan is added before fermentation. The aim of the study was to measure melatonin content during alcoholic fermentation of orange juice and to evaluate the role of the precursor tryptophan. Identification and quantification of melatonin during the alcoholic fermentation of orange juice was carried out by UHPLC-QqQ-MS/MS. Melatonin significantly increased throughout fermentation from day 0 (3.15 ng/mL) until day 15 (21.80 ng/mL) reaching larger amounts with respect to other foods. Melatonin isomer was also analysed, but its content remained stable ranging from 11.59 to 14.18 ng/mL. The enhancement of melatonin occurred mainly in the soluble fraction. Tryptophan levels significantly dropped from 13.80 mg/L (day 0) up to 3.19 mg/L (day 15) during fermentation. Melatonin was inversely and significantly correlated with tryptophan (r = 0.907). Therefore, the enhancement in melatonin could be due to both the occurrence of tryptophan and the new synthesis by yeast. In summary, the enhancement of melatonin in novel fermented orange beverage would improve the health benefits of orange juice by increasing this bioactive compound.

Fernández-Pachón MS; Medina S; Herrero-Martín G; Cerrillo I; Berná G; Escudero-López B; Ferreres F; Martín F; García-Parrilla MC; Gil-Izquierdo A

2013-09-01

259

Melatonin and gonadotropin hormones in pubertal sportsgirls.  

Science.gov (United States)

In order to determine the influence of physical training on menstrual disturbances in sportsgirls, the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and melatonin have been studied in young athletes of track and field speciality using the Cooper test. Basal hormone levels and anthropometric data were also studied in age matched control girls. No significant differences in LH, FSH and melatonin hormone concentrations were observed between the PRE and POST Cooper test. However, significantly lower basal levels of LH were found in the early follicular phase or luteal phase of sportsgirls when contrasted with the control girls. No differences in FSH levels were observed in the early follicular phase of sportsgirls but higher FSH levels were found in the luteal phase. Daytime melatonin levels of sportsgirls were significantly higher than those in control girls. Age and anthropometric parameters studied showed no differences in height, weight, tricipital skinfold and percentage of body fat, but abdominal and subescapular skinfold measures were greater in control girls than in sportsgirls. It appears that continuous physical training can produce alterations in antireproductive hormone secretion such as melatonin, which can play an inhibitory role on the menstrual cycle hormone patterns in sportsgirls. PMID:8378573

Díaz, B; García, R; Colmenero, M D; Terrados, N; Fernández, B; Marín, B

1993-03-01

260

Melatonin and gonadotropin hormones in pubertal sportsgirls.  

UK PubMed Central (United Kingdom)

In order to determine the influence of physical training on menstrual disturbances in sportsgirls, the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and melatonin have been studied in young athletes of track and field speciality using the Cooper test. Basal hormone levels and anthropometric data were also studied in age matched control girls. No significant differences in LH, FSH and melatonin hormone concentrations were observed between the PRE and POST Cooper test. However, significantly lower basal levels of LH were found in the early follicular phase or luteal phase of sportsgirls when contrasted with the control girls. No differences in FSH levels were observed in the early follicular phase of sportsgirls but higher FSH levels were found in the luteal phase. Daytime melatonin levels of sportsgirls were significantly higher than those in control girls. Age and anthropometric parameters studied showed no differences in height, weight, tricipital skinfold and percentage of body fat, but abdominal and subescapular skinfold measures were greater in control girls than in sportsgirls. It appears that continuous physical training can produce alterations in antireproductive hormone secretion such as melatonin, which can play an inhibitory role on the menstrual cycle hormone patterns in sportsgirls.

Díaz B; García R; Colmenero MD; Terrados N; Fernández B; Marín B

1993-03-01

 
 
 
 
261

Shedding light on light: benefits of anthropogenic illumination to a nocturnally foraging shorebird.  

UK PubMed Central (United Kingdom)

Intertidal habitats provide important feeding areas for migratory shorebirds. Anthropogenic developments along coasts can increase ambient light levels at night across adjacent inter-tidal zones. Here, we report the effects of elevated nocturnal light levels upon the foraging strategy of a migratory shorebird (common redshank Tringa totanus) overwintering on an industrialised estuary in Northern Europe. To monitor behaviour across the full intertidal area, individuals were located by day and night using VHF transmitters, and foraging behaviour was inferred from inbuilt posture sensors. Natural light was scored using moon-phase and cloud cover information and nocturnal artificial light levels were obtained using geo-referenced DMSP/OLS night-time satellite imagery at a 1-km resolution. Under high illumination levels, the commonest and apparently preferred foraging behaviour was sight-based. Conversely, birds feeding in areas with low levels of artificial light had an elevated foraging time and fed by touch, but switched to visual rather than tactile foraging behaviour on bright moonlit nights in the absence of cloud cover. Individuals occupying areas which were illuminated continuously by lighting from a large petrochemical complex invariably exhibited a visually based foraging behaviour independently of lunar phase and cloud cover. We show that ambient light levels affect the timing and distribution of foraging opportunities for redshank. We argue that light emitted from an industrial complex improved nocturnal visibility. This allowed sight-based foraging in place of tactile foraging, implying both a preference for sight-feeding and enhanced night-time foraging opportunities under these conditions. The study highlights the value of integrating remotely sensed data and telemetry techniques to assess the effect of anthropogenic change upon nocturnal behaviour and habitat use.

Dwyer RG; Bearhop S; Campbell HA; Bryant DM

2012-11-01

262

Melatonin: signaling mechanisms of a pleiotropic agent.  

Science.gov (United States)

Melatonin acts both as a hormone of the pineal gland and as a local regulator molecule in various tissues. Quantities of total tissue melatonin exceed those released from the pineal. With regard to this dual role, to the orchestrating, systemic action on various target tissues, melatonin is highly pleiotropic. Numerous secondary effects result from the control of the circadian pacemaker and, in seasonal breeders, of the hypothalamic/pituitary hormonal axes. In mammals, various binding sites for melatonin have been identified, the membrane receptors MT(1) and MT(2), which are of utmost chronobiological importance, ROR and RZR isoforms as nuclear receptors from the retinoic acid receptor superfamily, quinone reductase 2, calmodulin, calreticulin, and mitochondrial binding sites. The G protein-coupled receptors (GPCRs) MT(1) and MT(2) are capable of parallel or alternate signaling via different Galpha subforms, in particular, Galpha(i) (2/) (3) and Galpha(q), and via Gbetagamma, as well. Multiple signaling can lead to the activation of different cascades and/or ion channels. Melatonin frequently decreases cAMP, but also activates phospholipase C and protein kinase C, acts via the MAP kinase and PI3 kinase/Akt pathways, modulates large conductance Ca(2+)-activated K(+) and voltage-gated Ca(2+) channels. MT(1) and MT(2) can form homo and heterodimers, and MT(1) interacts with other proteins in the plasma membrane, such as an orphan GPCR, GPR50, and the PDZ domain scaffolding protein MUPP1, effects which negatively or positively influence signaling capacity. Cross-talks between different signaling pathways, including influences of the membrane receptors on nuclear binding sites, are discussed. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc. PMID:19449447

Hardeland, Rüdiger

263

Melatonin: signaling mechanisms of a pleiotropic agent.  

UK PubMed Central (United Kingdom)

Melatonin acts both as a hormone of the pineal gland and as a local regulator molecule in various tissues. Quantities of total tissue melatonin exceed those released from the pineal. With regard to this dual role, to the orchestrating, systemic action on various target tissues, melatonin is highly pleiotropic. Numerous secondary effects result from the control of the circadian pacemaker and, in seasonal breeders, of the hypothalamic/pituitary hormonal axes. In mammals, various binding sites for melatonin have been identified, the membrane receptors MT(1) and MT(2), which are of utmost chronobiological importance, ROR and RZR isoforms as nuclear receptors from the retinoic acid receptor superfamily, quinone reductase 2, calmodulin, calreticulin, and mitochondrial binding sites. The G protein-coupled receptors (GPCRs) MT(1) and MT(2) are capable of parallel or alternate signaling via different Galpha subforms, in particular, Galpha(i) (2/) (3) and Galpha(q), and via Gbetagamma, as well. Multiple signaling can lead to the activation of different cascades and/or ion channels. Melatonin frequently decreases cAMP, but also activates phospholipase C and protein kinase C, acts via the MAP kinase and PI3 kinase/Akt pathways, modulates large conductance Ca(2+)-activated K(+) and voltage-gated Ca(2+) channels. MT(1) and MT(2) can form homo and heterodimers, and MT(1) interacts with other proteins in the plasma membrane, such as an orphan GPCR, GPR50, and the PDZ domain scaffolding protein MUPP1, effects which negatively or positively influence signaling capacity. Cross-talks between different signaling pathways, including influences of the membrane receptors on nuclear binding sites, are discussed. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.

Hardeland R

2009-03-01

264

Growth conditions influence the melatonin content of tomato plants.  

UK PubMed Central (United Kingdom)

Melatonin (N-acetyl-5-methoxytryptamine) is an interesting molecule with well-known functions in vertebrates. Since its discovery in plants in 1995, many data indicate that its role as a cellular antioxidant is very relevant. Agents that induce stress cause increased melatonin levels in plant organs and melatonin levels fluctuate over the light:dark cycle; there are also conflicting data on the influence of environmental conditions on the melatonin content of plants. In this contribution we describe how cultivation conditions decisively influence melatonin levels in roots, stems and leaves of tomato plants, and we establish some guidelines for interpreting data with the intention of opening up new discussion options, given the lack of data on the place/s of melatonin biosynthesis and its mode of action in plant cells as an antioxidant.

Arnao MB; Hernández-Ruiz J

2013-06-01

265

Nocturnal bruxism and its clinical management.  

UK PubMed Central (United Kingdom)

Most individuals, both adults and children, engage in nocturnal bruxist activity at some point in their lives and to varying degrees. The tissues of the masticatory system will generally adapt to this behavior; however, in some individuals the capacity for adaption will be exceeded by the cumulative forces of this mandibular parafunctional behavior, resulting in pain and dysfunction of the masticatory system. This article discusses the history, nature, causes, and effects of bruxism as well as the diagnosis and therapy.

Attanasio R

1991-01-01

266

Slow eye movements distribution during nocturnal sleep.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To assess the distribution across nocturnal sleep of slow eye movements (SEMs). METHODS: We evaluated SEMs distribution in the different sleep stages, and across sleep cycles in nocturnal recordings of 10 healthy women. Sleep was scored according to standard criteria, and the percentage of time occupied by the SEMs was automatically detected. RESULTS: SEMs were differently represented during sleep stages with the following order: wakefulness after sleep onset (WASO): 61%, NREM sleep stage 1: 54%, REM sleep: 43%, NREM sleep stage 2: 21%, NREM sleep stage 3: 7%, and NREM sleep stage 4: 3% (p<0.0001). There was no difference between phasic and tonic REM sleep. SEMs progressively decreased across the NREM sleep cycles (38%, 15%, 13% during NREM sleep stage 2 in the first three sleep cycles, p=0.006), whereas no significant difference was found for REM, NREM sleep stage 1, slow-wave sleep and WASO. CONCLUSIONS: Our findings confirm that SEMs are a phenomenon typical of the sleep onset period, but are also found in REM sleep. The nocturnal evolution of SEMs during NREM sleep stage 2 parallels the homeostatic process underlying slow-wave sleep. SIGNIFICANCE: SEMs are a marker of sleepiness and, potentially, of sleep homeostasis.

Pizza F; Fabbri M; Magosso E; Ursino M; Provini F; Ferri R; Montagna P

2011-08-01

267

[Nocturnal polysomnogram in childhood autism without epilepsy  

UK PubMed Central (United Kingdom)

AIMS: To evaluate the presence of epileptiform discharges and the organisation of nocturnal sleep of autistic children without nocturnal polysomnographic epileptic seizures. SUBJECTS AND METHODS: Cross section analysis. Subjects: 21 boys and girls with autistic spectrum using DSM IV criteria between the ages of 4 and 12, compared with a control group made up of normal children of the same ages. METHODS: nocturnal polysomnogram with a minimum efficiency of 75%. ANALYSIS: t test to compare the cycles and phases of sleep with significance p< 0.05. RESULTS: Subjects presented a maximum of four sleep cycles compared with five or six in the control subjects. From the first third of the night onwards there was an increase in the slowest phases. 66% presented epileptiform paroxysmal discharges, all of which originated in the anterior half of the brain. CONCLUSION: Sleep is not destructured, but it is reduced in length, with epileptiform paroxysms of predominantly frontal origin. This could indicate that these two parameters are intrinsic to the autistic spectrum, as well as indicating a more focused origin of the generalised picture which is possibly closely related with the qualitative alteration of the social experiences of these children.

Valdizán-Usón JR; Abril-Villalba B; Méndez-García M; Sans-Capdevila O

2002-06-01

268

Melatonin prevents damage elicited by the organophosphorous pesticide diazinon on the mouse testis.  

Science.gov (United States)

Organophosphates like O,O-diethyl O-2-isopropyl-6-methyl pyrimidinyl-4-g-1-phosphorothioate (diazinon) are pesticides used worldwide, which can affect both animals and man even after a single exposure. Whereas their toxicity is due to acetylcholinesterase inhibition, their secondary toxic effects have been related to free oxygen radicals. This study evaluates the effects of a single dose of diazinon and melatonin-a powerful antioxidant-on plasmatic acetylcholinesterase activity and testis histopathology in adult mice 1 and 32 days post-treatment. Diazinon diminished the plasma acetylcholinesterase activity on day 1 post-treatment, although testosterone levels remained unaffected. Morphometrical analysis showed a decrease in seminiferous epithelium height (days 1 and 32), whereas an increase in testicular superoxide dismutase (SOD) activity was detected (day 32). Melatonin pretreatment prevented every alteration induced by diazinon, except the diminution of acetylcholinesterase plasmatic activity. Testicular damage might be due to elevated concentrations of free oxygen radicals released upon diazinon exposure, inducing alterations in the DNA and promoting local apoptosis; however, antioxidant pretreatment with melatonin prevents or diminishes this damage. PMID:18565581

Sarabia, L; Maurer, I; Bustos-Obregón, E

2008-06-18

269

Oxytocin and prolactin release after hypertonic saline administration in melatonin-treated male Syrian hamsters  

Energy Technology Data Exchange (ETDEWEB)

The aim of the present investigations was to examine the effects of melatonin (Mel) on oxytocin (OT) release under conditions of osmotic stimulation, brought about by hypertonic saline administration, as well as to determine whether osmotically stimulated OT release in Mel-treated Syrian hamster is associated with alterations in the release of prolactin (PRL) and in norepinephrine (NE) and dopamine (DA) content in the hypothalamus. In both Mel- and vehicle-treated hamsters, injection of hypertonic saline was followed by a significant decrease in OT content in the pituitary neurointermediate lobe (NIL) and elevation of plasma OT and PRL levels. Melatonin injections had no significant affect on NIL OT content in either isotonic- or hypertonic-saline treated animals. Pretreatment with Mel did not alter plasma OT or PRL levels in isotonic saline-injected animals. However, Mel facilitated the release of OT, but prevented the release of PRL after hypertonic saline administration. Melatonin treatment reduced hypothalamic NE content (but not that of DA) in isotonic-saline treated animals. After osmotic stimulation, hypothalamic content of NE and DA was significantly lower in Mel-treated than in vehicle-treated animals. Data from the present study suggest that the osmotically-stimulated release of OT and PRL seems to be related to the activation of noradrenergic rather than dopaminergic transmission. Both dopaminergic and noradrenergic transmission may be, however, involved in mediating the effects of Mel on the osmotically-activated OT and PRL release. (author). 48 refs, 3 figs.

Juszczak, M.; Steger, R.W.; Fadden, C.; Bartke, A. [Southern Illinois Univ., Carbondale, IL (United States)

1996-12-31

270

Oxytocin and prolactin release after hypertonic saline administration in melatonin-treated male Syrian hamsters  

International Nuclear Information System (INIS)

The aim of the present investigations was to examine the effects of melatonin (Mel) on oxytocin (OT) release under conditions of osmotic stimulation, brought about by hypertonic saline administration, as well as to determine whether osmotically stimulated OT release in Mel-treated Syrian hamster is associated with alterations in the release of prolactin (PRL) and in norepinephrine (NE) and dopamine (DA) content in the hypothalamus. In both Mel- and vehicle-treated hamsters, injection of hypertonic saline was followed by a significant decrease in OT content in the pituitary neurointermediate lobe (NIL) and elevation of plasma OT and PRL levels. Melatonin injections had no significant affect on NIL OT content in either isotonic- or hypertonic-saline treated animals. Pretreatment with Mel did not alter plasma OT or PRL levels in isotonic saline-injected animals. However, Mel facilitated the release of OT, but prevented the release of PRL after hypertonic saline administration. Melatonin treatment reduced hypothalamic NE content (but not that of DA) in isotonic-saline treated animals. After osmotic stimulation, hypothalamic content of NE and DA was significantly lower in Mel-treated than in vehicle-treated animals. Data from the present study suggest that the osmotically-stimulated release of OT and PRL seems to be related to the activation of noradrenergic rather than dopaminergic transmission. Both dopaminergic and noradrenergic transmission may be, however, involved in mediating the effects of Mel on the osmotically-activated OT and PRL release. (author). 48 refs, 3 figs.

1996-01-01

271

Melatonin enhances chondrogenic differentiation of human mesenchymal stem cells.  

UK PubMed Central (United Kingdom)

Intramembranous ossification and endochondral ossification are two ways through which bone formation and fracture healing occur. Accumulating amounts of evidence suggests that melatonin affects osteoblast differentiation, but little is known about the effects of melatonin on the process of chondrogenic differentiation. In this study, the effects of melatonin on human mesenchymal stem cells (MSCs) undergoing chondrogenic differentiation were investigated. Cells were induced along chondrogenic differentiation via high-density micromass culture in chondrogenic medium containing vehicle or 50 nm melatonin. Histological study and quantitative analysis of glycosaminoglycan (GAG) showed induced cartilage tissues to be larger and richer in GAG, collagen type II and collagen type X in the melatonin group than in the untreated controls. Real-time RT-PCR analysis demonstrated that melatonin treatment significantly up-regulated the expression of the genes involved in chondrogenic differentiation, including aggrecan (ACAN), collagen type II (COL2A1), collagen type X (COL10A1), SRY (sex-determining region Y)-box 9 (SOX9), runt-related transcription factor 2 (RUNX2) and the potent inducer of chondrogenic differentiation, bone morphogenetic protein 2 (BMP2). And the expression of melatonin membrane receptors (MT) MT1 and MT2 were detected in the chondrogenic-induced-MSCs by immunofluorescence staining. Luzindole, a melatonin receptor antagonist, was found to partially block the ability of melatonin to increase the size and GAG synthesis of the induced cartilage tissues, as well as to completely reverse the effect of melatonin on the gene expression of ACAN, COL2A1, COL10A1, SOX9 and BMP2 after 7 days of differentiation. These findings demonstrate that melatonin enhances chondrogenic differentiation of human MSCs at least partially through melatonin receptors.

Gao W; Lin M; Liang A; Zhang L; Chen C; Liang G; Xu C; Peng Y; Chen C; Huang D; Su P

2013-09-01

272

Melatonin improves liver function in benzene-treated rats.  

UK PubMed Central (United Kingdom)

In this study, we investigated the beneficial effects of melatonin against benzene-induced liver function impairments in Wistar rats. After 30 days of treatment, it significantly lowered hepatosomatic indices, bilirubin, and hydroxyproline in male and female benzene-treated rats. Even though it did not influence aspartate aminotransferase, melatonin had beneficial effects on alanine aminotransferase and alkaline phosphatase. Our results suggest that melatonin is an effective modulator of liver function in benzene-treated rats thanks to its antioxidative properties.

Sharma S; Rana SV

2013-06-01

273

Melatonin and its use in atherosclerosis and dyslipidemia  

Directory of Open Access Journals (Sweden)

Full Text Available Konstantin V Danilenko, Yulia I Ragino Institute of Internal Medicine, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Russia Abstract: A review of pineal melatonin synthesis, regulation, and physiological effects indicates that not only does melatonin act as a hormonal signal of darkness, but also that it possesses antioxidant and anti-inflammatory properties. Although oxidation and inflammation play a pivotal role in atherogenesis, no studies have investigated administration of melatonin for human arterial atherosclerosis. However, 13 clinical trials have investigated use of melatonin in dyslipidemia, which is a close correlate of atherosclerosis. The results of these clinical trials, particularly the five that are placebo-controlled, are inconclusive as to whether melatonin can normalize the blood lipid profile. Significant confounders in these studies might be a phase shift of the cholesterol rhythm by melatonin, a posture effect at venipuncture, uncontrolled diet during the course of melatonin intake, and the phenomenon of regression to the mean. Thus, future studies are required, which should also consider use of higher doses of melatonin and/or measurement of oxidized forms of cholesterol-containing particles (which are the most aggressive in relation to atherogenesis) in addition to lipidic fractions. Keywords: melatonin, serum lipids, atherosclerosis, clinical trials

Danilenko KV; Ragino YI.

2013-01-01

274

Melatonin Effects on Hard Tissues: Bone and Tooth  

Directory of Open Access Journals (Sweden)

Full Text Available Melatonin is an endogenous hormone rhythmically produced in the pineal gland under the control of the suprachiasmatic nucleus (SCN) and the light/dark cycle. This indole plays an important role in many physiological processes including circadian entrainment, blood pressure regulation, seasonal reproduction, ovarian physiology, immune function, etc. Recently, the investigation and applications of melatonin in the hard tissues bone and tooth have received great attention. Melatonin has been investigated relative to bone remolding, osteoporosis, osseointegration of dental implants and dentine formation. In the present review, we discuss the large body of published evidence and review data of melatonin effects on hard tissues, specifically, bone and tooth.

Jie Liu; Fang Huang; Hong-Wen He

2013-01-01

275

Melatonin modulates aromatase activity and expression in endothelial cells.  

UK PubMed Central (United Kingdom)

Melatonin is known to suppress the development of endocrine-responsive breast cancers by interacting with the estrogen signaling pathways. Paracrine interactions between malignant epithelial cells and proximal stromal cells are responsible for local estrogen biosynthesis. In human breast cancer cells and peritumoral adipose tissue, melatonin downregulates aromatase, which transforms androgens into estrogens. The presence of aromatase on endothelial cells indicates that endothelial cells may contribute to tumor growth by producing estrogens. Since human umbilical vein endothelial cells (HUVECs) express both aromatase and melatonin receptors, the aim of the present study was to evaluate the ability of melatonin to regulate the activity and expression of aromatase on endothelial cells, thus, modulating local estrogen biosynthesis. In the present study, we demonstrated that melatonin inhibits the growth of HUVECs and reduces the local biosynthesis of estrogens through the downregulation of aromatase. These results are supported by three lines of evidence. Firstly, 1 mM of melatonin counteracted the testosterone-induced cell proliferation of HUVECs, which is dependent on the local biosynthesis of estrogens from testosterone by the aromatase activity of the cells. Secondly, we found that 1 mM of melatonin reduced the aromatase activity of HUVECs. Finally, by real?time RT-PCR, we demonstrated that melatonin significantly downregulated the expression of aromatase as well as its endothelial-specific aromatase promoter region I.7. We conclude that melatonin inhibits aromatase activity and expression in HUVECs by regulating gene expression of specific aromatase promoter regions, thereby reducing the local production of estrogens.

Alvarez-García V; González A; Martínez-Campa C; Alonso-González C; Cos S

2013-05-01

276

Melatonin Effects on Hard Tissues: Bone and Tooth  

Science.gov (United States)

Melatonin is an endogenous hormone rhythmically produced in the pineal gland under the control of the suprachiasmatic nucleus (SCN) and the light/dark cycle. This indole plays an important role in many physiological processes including circadian entrainment, blood pressure regulation, seasonal reproduction, ovarian physiology, immune function, etc. Recently, the investigation and applications of melatonin in the hard tissues bone and tooth have received great attention. Melatonin has been investigated relative to bone remolding, osteoporosis, osseointegration of dental implants and dentine formation. In the present review, we discuss the large body of published evidence and review data of melatonin effects on hard tissues, specifically, bone and tooth.

Liu, Jie; Huang, Fang; He, Hong-Wen

2013-01-01

277

The protective role of melatonin in experimental hypoxic brain damage.  

UK PubMed Central (United Kingdom)

BACKGROUND: It is known that oxygen-derived free radicals play an important role in the pathogenesis of brain injury. Melatonin is a powerful scavenger of the oxygen free radicals. In this study, the protective effect of melatonin against the damage inflicted by reactive oxygen species during brain hypoxia was investigated in newborn rats using biochemical parameters. METHODS: For biochemical analyses, the levels of lipid peroxidation product (malondialdehyde ([MDA]), levels of reduced glutathione (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT) were estimated. RESULTS: After the third day of brain hypoxia, the brain levels of MDA increased. Pretreatment of animals with melatonin abolished the rise in MDA induced by hypoxia. GSH concentration did not increase by pretreatment with melatonin. Additionally, the activities of two antioxidative enzymes (SOD and CAT) decreased after the experimental period with melatonin only preventing the change of CAT. The activity of SOD was not influenced by melatonin administration as expected. CONCLUSION: In this experimental study, exogenously administered melatonin effectively protected against brain injury by oxidative stress. This protective effect of melatonin may be due to its direct scavenger activity and activation of CAT. Thus, melatonin may potentially be useful in the treatment of neurodegenerative conditions that may involve free radical production, such as perinatal hypoxia.

Tütüncüler F; Eskiocak S; Ba?aran UN; Ekuklu G; Ayvaz S; Vatansever U

2005-08-01

278

Physiology during smoltification in Atlantic salmon: effect of melatonin implants.  

Science.gov (United States)

Melatonin implants were used to override natural melatonin rhythm in groups of juvenile Atlantic salmon, Salmo salar, raised at simulated natural photoperiod (SNP) and constant light (LL) from mid-March until end of August. The experiment contained also both sham control (with non-melatonin implants) and control (no implants). No differences were found in the experimental variables between these two control groups. Growth and food intake were negatively affected by melatonin implantation. Overall, higher GH levels were observed in the SNP melatonin-implanted group, whereas no differences in GH levels were seen between the SNP control, LL control, or the LL melatonin-implanted groups. Highest food intake was seen in the LL control group. No differences in food intake were recorded between the LL melatonin-implanted and SNP control groups. Gill Na(+), K(+), ATPase (NKA) activity was influenced by time as well as the interaction between photoperiod and time. No differences in gill NKA activity or plasma chloride levels following transfer to seawater were seen between the groups with melatonin implants and their controls. Based on the present results, it seems apparent that melatonin does play a role in regulating food intake and growth in Atlantic salmon smolts. PMID:23277099

Handeland, S O; Imsland, A K; Björnsson, B Th; Stefansson, S O; Porter, M

2013-01-01

279

Development of a melatonin RIA and observation on the plasma melatonin contents in rat models of chronic hyperirritable-depression  

International Nuclear Information System (INIS)

[en] Objective: To establish a new melatonin assay and to investigate the changes of plasma melatonin content in rat models of chronic hyperirritable-depression. Methods: Quality melatonin antiserum was obtained from immunization of Newzealand white rabbit with melatonin immunogen derived from conjugation of melatonin to bovine thyroglobulin using formaldehyde. Radioiodinated melatonin was used as tracer and a melatonin assay was developed through non-equilibrium competition. Twenty rat models of chronic hyperirritable-depression were prepared with multiple randomly-combined stimuli as previously reported. Plasma and pineal body tissue contents of melatonin in the models were examined in midsummer (n=10) and mid-winter (n=10) with the newly developed melatonin RIA. Contents of melatonin were also determined in 20 control rats. Results: The antiserum possessed very low cross-reaction rate with several melatonin analogous tested (0.09%-2.3%). At the titer of 1:1800, the maximal combination rate was 41%. The affinity constant was 1.7 x 109 L/M. The specific radioactivity of the tracer 125I-melatonin was 55 ?Ci/?g, with radio-chemical purity of 93% and the tracer was stable at 4 degree C for 65 days. The assay was of high sensitivity (lower detection limit 5pg/ml), intra-CV, 6.5 %; inter-CV, 11%. The plasma and pineal body tissue contents of melatonin in the rat models were consistently significantly lower than those in control rats both during summer and winter, while the contents of melatonin during winter were always significantly higher than those during summer in both groups of animals. Conclusion: The newly developed assay was of good specificity and sensitivity with stable agents (65 days). The experimental results demonstrated definite correlationship between the depression disorder and melatonin contents in the rat models, however, the disorder was not seasonally affective. The seasonal variation of the melatonin contents in the animals was due to different duration and intensity of light exposure. (authors)

2005-01-01

280

Protective effects of melatonin against oxidative stress in Fmr1 knockout mice: a therapeutic research model for the fragile X syndrome.  

UK PubMed Central (United Kingdom)

Fragile X syndrome is the most common form of inherited mental retardation. It is typically caused by a mutation of the Fragile X mental-retardation 1 (Fmr1) gene. To better understand the role of the Fmr1 gene and its gene product, the fragile X mental-retardation protein in central nervous system functions, an fmr1 knockout mouse that is deficient in the fragile X mental-retardation protein was bred. In the present study, fragile X mental retardation 1-knockout and wild-type mice are used to determine behaviour and oxidative stress alterations, including reduced glutathione, oxidized glutathione and thiobarbituric acid-reactive substances, before and after chronic treatment with melatonin or tianeptine. Reduced glutathione levels were reduced in the brain of fmr1-knockout mice and chronic melatonin treatment normalized the glutathione levels compared with the control group. Lipid peroxidation was elevated in brain and testes of fmr1-knockout mice and chronic melatonin treatment prevents lipid peroxidation in both tissues. Interestingly, chronic treatment with melatonin alleviated the altered parameters in the fmr1-knockout mice, including abnormal context-dependent exploratory and anxiety behaviours and learning abnormalities. Chronic treatment with tianeptine (a serotonin reuptake enhancer) did not normalize the behaviour in fmr1-knockout mice. The prevention of oxidative stress in the fragile X mouse model, by an antioxidant compound such as melatonin, emerges as a new and promising approach for further investigation on treatment trials for the disease.

Romero-Zerbo Y; Decara J; el Bekay R; Sanchez-Salido L; Del Arco-Herrera I; de Fonseca FR; de Diego-Otero Y

2009-03-01

 
 
 
 
281

Protective effects of melatonin against oxidative stress in Fmr1 knockout mice: a therapeutic research model for the fragile X syndrome.  

Science.gov (United States)

Fragile X syndrome is the most common form of inherited mental retardation. It is typically caused by a mutation of the Fragile X mental-retardation 1 (Fmr1) gene. To better understand the role of the Fmr1 gene and its gene product, the fragile X mental-retardation protein in central nervous system functions, an fmr1 knockout mouse that is deficient in the fragile X mental-retardation protein was bred. In the present study, fragile X mental retardation 1-knockout and wild-type mice are used to determine behaviour and oxidative stress alterations, including reduced glutathione, oxidized glutathione and thiobarbituric acid-reactive substances, before and after chronic treatment with melatonin or tianeptine. Reduced glutathione levels were reduced in the brain of fmr1-knockout mice and chronic melatonin treatment normalized the glutathione levels compared with the control group. Lipid peroxidation was elevated in brain and testes of fmr1-knockout mice and chronic melatonin treatment prevents lipid peroxidation in both tissues. Interestingly, chronic treatment with melatonin alleviated the altered parameters in the fmr1-knockout mice, including abnormal context-dependent exploratory and anxiety behaviours and learning abnormalities. Chronic treatment with tianeptine (a serotonin reuptake enhancer) did not normalize the behaviour in fmr1-knockout mice. The prevention of oxidative stress in the fragile X mouse model, by an antioxidant compound such as melatonin, emerges as a new and promising approach for further investigation on treatment trials for the disease. PMID:19141086

Romero-Zerbo, Yanina; Decara, Juan; el Bekay, Rajaa; Sanchez-Salido, Lourdes; Del Arco-Herrera, Ignacio; de Fonseca, Fernando Rodríguez; de Diego-Otero, Yolanda

2008-12-23

282

Melatonin in Alzheimer's disease and other neurodegenerative disorders  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Increased oxidative stress and mitochondrial dysfunction have been identified as common pathophysiological phenomena associated with neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). As the age-related decline in the production of melatonin may contribute to increased levels of oxidative stress in the elderly, the role of this neuroprotective agent is attracting increasing attention. Melatonin has multiple actions as a regulator of antioxidant and prooxidant enzymes, radical scavenger and antagonist of mitochondrial radical formation. The ability of melatonin and its kynuramine metabolites to interact directly with the electron transport chain by increasing the electron flow and reducing electron leakage are unique features by which melatonin is able to increase the survival of neurons under enhanced oxidative stress. Moreover, antifibrillogenic actions have been demonstrated in vitro, also in the presence of profibrillogenic apoE4 or apoE3, and in vivo, in a transgenic mouse model. Amyloid-? toxicity is antagonized by melatonin and one of its kynuramine metabolites. Cytoskeletal disorganization and protein hyperphosphorylation, as induced in several cell-line models, have been attenuated by melatonin, effects comprising stress kinase downregulation and extending to neurotrophin expression. Various experimental models of AD, PD and HD indicate the usefulness of melatonin in antagonizing disease progression and/or mitigating some of the symptoms. Melatonin secretion has been found to be altered in AD and PD. Attempts to compensate for age- and disease-dependent melatonin deficiency have shown that administration of this compound can improve sleep efficiency in AD and PD and, to some extent, cognitive function in AD patients. Exogenous melatonin has also been reported to alleviate behavioral symptoms such as sundowning. Taken together, these findings suggest that melatonin, its analogues and kynuric metabolites may have potential value in prevention and treatment of AD and other neurodegenerative disorders.

Srinivasan V; Pandi-Perumal SR; Cardinali DP; Poeggeler B; Hardeland R

2006-01-01

283

Short-wavelength attenuated polychromatic white light during work at night: limited melatonin suppression without substantial decline of alertness.  

Science.gov (United States)

Exposure to light at night increases alertness, but light at night (especially short-wavelength light) also disrupts nocturnal physiology. Such disruption is thought to underlie medical problems for which shiftworkers have increased risk. In 33 male subjects we investigated whether short-wavelength attenuated polychromatic white light (full-spectrum light. All 33 subjects participated in random order during three nights (at least 1 wk apart) either under dim light (3 lux), short-wavelength attenuated polychromatic white light (193 lux), or full-spectrum light (256 lux). Hourly saliva samples for melatonin analysis were collected along with continuous measurements of skin temperature. Subjective sleepiness and activation were assessed via repeated questionnaires and performance was assessed by the accuracy and speed of an addition task. Our results show that short-wavelength attenuated polychromatic white light only marginally (6%) suppressed salivary melatonin. Average distal-to-proximal skin temperature gradient (DPG) and its pattern over time remained similar under short-wavelength attenuated polychromatic white light compared with dim light. Subjects performed equally well on an addition task under short-wavelength attenuated polychromatic white light compared with full-spectrum light. Although subjective ratings of activation were lower under short-wavelength attenuated polychromatic white light compared with full-spectrum light, subjective sleepiness was not increased. Short-wavelength attenuated polychromatic white light at night has some advantages over bright light. It hardly suppresses melatonin concentrations, whereas performance is similar to the bright light condition. Yet, alertness is slightly reduced as compared with bright light, and DPG shows similarity to the dim light condition, which is a physiological sign of reduced alertness. Short-wavelength attenuated polychromatic white light might therefore not be advisable in work settings that require high levels of alertness. PMID:23705821

van de Werken, Maan; Giménez, Marina C; de Vries, Bonnie; Beersma, Domien G M; Gordijn, Marijke C M

2013-05-24

284

Effect of laser acupuncture for monosymptomatic nocturnal enuresis on bladder reservoir function and nocturnal urine output  

DEFF Research Database (Denmark)

The alternative treatments for enuresis have been reported with high efficacy but in noncontrolled studies. Therefore, using a prospective, single-blind, randomized, placebo controlled design we evaluated the effect of laser acupuncture on bladder reservoir function and enuresis frequency in cases of monosymptomatic nocturnal enuresis with reduced maximal voided volume.

Radvanska, E; Kamperis, Konstantinos

2011-01-01

285

Microorganisms for the production of melatonin  

DEFF Research Database (Denmark)

Recombinant microbial cells and methods for producing melatonin and related compounds using such cells are described. More specifically, the recombinant microbial cell may comprise exogenous genes encoding one or more of an L-tryptophan hydroxylase, a 5-hydroxy-L- tryptophan decarboxylyase, a serotonin acetyltransferase, an acetylserotonin O- methyltransferase; an L-tryptophan decarboxy-lyase, and a tryptamine-5-hydroxylase, and means for providing tetrahydrobiopterin (THB). Related sequences and vectors for use in preparing such recombinant microbial cells are also described.

Knight, Eric Michael Technical University of Denmark,

286

Nocturnal Frontal Lobe Epilepsy vs Parasomnias.  

UK PubMed Central (United Kingdom)

OPINION STATEMENT: The diagnosis and treatment of nocturnal events can present significant challenges to the clinician. Correct diagnosis is the first step towards appropriate treatment, but may not be straightforward. In particular, non-rapid eye movement (NREM) arousal parasomnias, such as sleepwalking, sleep terrors, and confusional arousal can present in a similar fashion to nocturnal frontal lobe epilepsy (NFLE); dramatic and often bizarre behaviors from sleep are features of both conditions, and may result in diagnostic confusion. A careful clinical history, however, often enables accurate diagnosis, and the frontal lobe epilepsy and parasomnia (FLEP) scale, a validated questionnaire for the diagnosis of nocturnal events, can add diagnostic confidence. Recording of events on video-EEG-polysomnography is required if diagnostic doubt remains although is not always achievable, particularly if events are occurring infrequently. Treatments for NFLE and parasomnias are different, but lifestyle modification and treatment of coexisting sleep disorders (such as obstructive sleep apnoea) may have a role in both. In NFLE, medical treatment with antiepileptic drugs, particularly carbamazepine and topiramate, forms the mainstay of treatment; a small proportion of individuals with treatment-resistant seizures may benefit from epilepsy surgery. For parasomnias, reassurance and the removal of priming and precipitating factors is often sufficient. A minority of individuals will, however, need medical treatment, usually with benzodiazepines or tricyclic antidepressants. Unfortunately, there are few data on which to base treatment decisions in this area, with the evidence comprising predominantly case reports and case series. Well-designed studies, including randomised control trials, are needed and may require a multicentre approach.

Derry C

2012-10-01

287

Nocturnal temazepam in the treatment of narcolepsy.  

UK PubMed Central (United Kingdom)

Narcolepsy is characterized by fragmented nighttime sleep and frequent arousals. One treatment approach to improve daytime symptoms is to consolidate nighttime sleep through decreasing arousals. Sodium oxybate is the first FDA-approved medication that follows this approach. Benzodiazepines are known to also decrease arousals at night and have been proposed to help with sleep fragmentation. In one report, clonazepam was shown to improve cataplexy in 10 of 14 patients with narcolepsy although no improvement in daytime sleepiness was reported. The purpose of this case review was to share our experience of nocturnal temazepam on daytime sleepiness in patients with narcolepsy as measured by the Epworth Sleepiness Scale (ESS).

Kansagra S; Walter R; Vaughn B

2013-05-01

288

Nocturnal temazepam in the treatment of narcolepsy.  

Science.gov (United States)

Narcolepsy is characterized by fragmented nighttime sleep and frequent arousals. One treatment approach to improve daytime symptoms is to consolidate nighttime sleep through decreasing arousals. Sodium oxybate is the first FDA-approved medication that follows this approach. Benzodiazepines are known to also decrease arousals at night and have been proposed to help with sleep fragmentation. In one report, clonazepam was shown to improve cataplexy in 10 of 14 patients with narcolepsy although no improvement in daytime sleepiness was reported. The purpose of this case review was to share our experience of nocturnal temazepam on daytime sleepiness in patients with narcolepsy as measured by the Epworth Sleepiness Scale (ESS). PMID:23674942

Kansagra, Sujay; Walter, Robert; Vaughn, Bradley

2013-05-15

289

Melatonin improves spatial navigation memory in male diabetic rats  

Directory of Open Access Journals (Sweden)

Full Text Available The aim of the present study was to evaluate the effect of melatonin as an antioxidant on spatial navigation memory in male diabetic rats. Thirty-two male white Wistar rats weighing 200 ± 20 g were divided into four groups, randomly: control, melatonin, diabetic and melatonin-treated diabetic. Experimental diabetes was induced by intraperitoneal injection of 50 mg kg-1 streptozotocin. Melatonin was injected (10 mg kg-1 day-1, ip) for 2 weeks after 21 days of diabetes induction. At the end of administration period, the spatial navigation memory of rats was evaluated by cross-arm maze. In this study lipid peroxidation levels, glutathione-peroxidase and catalase activities were measured in hippocampus. Diabetes caused to significant decrease in alternation percent in the cross-arm maze, as a spatial memory index, compared to the control group (p < 0.05), whereas administration of melatonin prevented the spatial memory deficit in diabetic rats. Also melatonin injection significantly increased the spatial memory in intact animals compared to the control group (p < 0.05). Assessment of hippocampus homogenates indicated an increase in lipid peroxidation levels and a decrease in GSH-Px and CAT activities in the diabetic group compared to the control animals, while melatonin administration ameliorated these indices in diabetic rats. In conclusion, diabetes induction leads to debilitation of spatial navigation memory in rats, and the melatonin treatment improves the memory presumably through the reduction of oxidative stress in hippocampus of diabetic rats.

Farrin Babaei-Balderlou; Samad Zare

2012-01-01

290

Effect of melatonin on vascular responses of porcine ciliary arteries.  

UK PubMed Central (United Kingdom)

PURPOSE: To investigate the effect of melatonin on isolated porcine ciliary arteries. METHODS: Isolated porcine ciliary arteries were suspended in myograph chambers filled with modified Krebs-Ringer solution (37 degrees C; 95% O2/5% CO2) for isometric tension recording. RESULTS: In quiescent porcine ciliary arteries with endothelium, melatonin (10(-11)--10(-5) M) evoked no change in vascular tone. The highest concentration of melatonin (10(-4 ) M) evoked a small but significant contraction. In vessels precontracted with U-46619 (10(-7) M), increasing concentrations of melatonin (10(-11)--10(-5) M) did not evoke a response. In precontracted arteries with endothelium, contractile response of vascular smooth muscle to increasing concentrations of serotonin (10(-10)--10(-5) M) and noradrenaline (10(-10)--10(-5) M) was reduced after preincubation with melatonin (10(-4) M). Melatonin (10(-4) M) did not alter the response to endothelin-1 (10(-10)--10( -7) M) and U-46619 (10(-10)--10(-6 ) M) in precontracted arteries with endothelium. CONCLUSION: These findings demonstrate that melatonin attenuates the effect of serotonin and noradrenaline and is itself a mild vasoconstrictor in porcine ciliary arteries. The role of melatonin in human ocular circulation remains to be established.

Pache M; Kräuchi K; Haefliger IO; Wirz-Justice A; Flammer J; Meyer P

2002-04-01

291

Use of Melatonin in Young Children for Sleep Disorders.  

Science.gov (United States)

|Sleep problems may occur in up to 88% of children with visual impairments who have developmental disabilities. The use of oral melatonin has recently been used for the management of sleep difficulties in children with and without disabilities. Sustained-release melatonin may reduce nighttime awakenings and increase total sleep time. (Contains…

Lin-Dyken, Deborah C.; Dyken, Mark Eric

2002-01-01

292

[Effects of melatonin on oxygen-dependent processes].  

UK PubMed Central (United Kingdom)

Original and literature data on melatonin effects on various oxygen-dependent processes, in particular, blood oxygen transport and the free-radical reactions, are analyzed. Melatonin influences the oxygen binding properties of hemoglobin by changing hemoglobin oxygen affinity and optimizes the process of tissue oxygenation and prooxidant--antioxidant balance by reducing oxygen participation in free-radical processes.

Zinchuk VV; Glutkin SV; Shul'ga EV; Gulia? IÉ

2013-01-01

293

Melatonin Plays a Protective Role in Postburn Rodent Gut Pathophysiology  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Melatonin is a possible protective agent in postburn gut pathophysiological dynamics. We investigated the role of endogenously-produced versus exogenously-administered melatonin in a major thermal injury rat model with well-characterized gut inflammatory complications. Our rationale is that understa...

Al-Ghoul, Walid M.; Abu-Shaqra, Steven; Park, Byeong Gyu; Fazal, Nadeem

294

Decreased Vitamin B12 Levels in Children with Nocturnal Enuresis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Objectives. Nocturnal enuresis is a common pediatric problem, the etiology of which is unclear. In the present study, vitamin B12 and folate levels were measured in children with nocturnal enuresis and compared with those in healthy control group children to investigate whether there was any relati...

Altunoluk, Bülent; Davutoglu, Mehmet; Garipardic, Mesut; Bakan, Vedat

295

Circadian variations of salivary melatonin levels in women of reproductive and postmenopausal age with gynoid and android obesity.  

UK PubMed Central (United Kingdom)

Circadian variations of salivary melatonin (MEL) were examined in 81 women (48 of reproductive and 33 of postmenopausal age), 16 of them with moderate overweight, 32 showing gynoid obesity (BMI>30 kg/m[^2]; WHR<0.8) and 33 showing android obesity (BMI>30 kg/m[^2]; WHR>0.8). The circadian profiles of salivary MEL in women with moderate overweight were parallel to those of controls. However, mean 24-h salivary MEL levels tended to be higher in all obese patients as compared with controls (mainly due to increase of its daytime levels). In addition, the suppression of MEL rhythmicity was observed in all subjects studied irrespectively of gynoid or android obesity, while nocturnal MEL peak shift was observed predominantly in the case of extreme obesity with android distribution of adipose tissue. Despite of increasing tendencies mean 24 h MEL concentrations and stronger suppression of circadian variations and/or nocturnal MEL peak shift in extremely obese women with android distribution of adipose tissue, no significant correlation was found between the values of BMI index, WHR ratio and circadian MEL concentrations.

Ostrowska Z; Buntner B; Banas I I; Kos-Kudla B; Marek B; Zwirska-Korczala K

1996-09-01

296

Circadian variations of salivary melatonin levels in women of reproductive and postmenopausal age with gynoid and android obesity.  

Science.gov (United States)

Circadian variations of salivary melatonin (MEL) were examined in 81 women (48 of reproductive and 33 of postmenopausal age), 16 of them with moderate overweight, 32 showing gynoid obesity (BMI>30 kg/m[^2]; WHR30 kg/m[^2]; WHR>0.8). The circadian profiles of salivary MEL in women with moderate overweight were parallel to those of controls. However, mean 24-h salivary MEL levels tended to be higher in all obese patients as compared with controls (mainly due to increase of its daytime levels). In addition, the suppression of MEL rhythmicity was observed in all subjects studied irrespectively of gynoid or android obesity, while nocturnal MEL peak shift was observed predominantly in the case of extreme obesity with android distribution of adipose tissue. Despite of increasing tendencies mean 24 h MEL concentrations and stronger suppression of circadian variations and/or nocturnal MEL peak shift in extremely obese women with android distribution of adipose tissue, no significant correlation was found between the values of BMI index, WHR ratio and circadian MEL concentrations. PMID:10979045

Ostrowska; Buntner; Banas; Kos-Kudla; Marek; Zwirska-Korczala

1996-09-01

297

Sleep apnea and nocturnal myoclonus in a senior population.  

UK PubMed Central (United Kingdom)

Studies have suggested that sleep apnea is especially prevalent among seniors. We recruited and recorded senior volunteers who reported symptoms raising suspicion of sleep apnea or nocturnal myoclonus. Of 24 subjects, 62.5% had one of these disorders-six had sleep apnea alone, three had sleep apnea and nocturnal myoclonus, ans six had nocturnal myoclonus alone. Sleep stages were also analyzed. Subjects with sleep apnea and/or nocturnal myoclonus had significantly less rapid eye movement sleep, significantly more stage 1 sleep, and significantly more awakenings than other subjects. This sample suggests that the prevalence of sleep apnea and nocturnal myoclonus may be very substantial among seniors. Because of this high prevalence, extreme caution is needed in prescribing hypnotics for older patients with sleep complaints, since most hypnotics are respiratory depressants. We must rethink our approach to treating sleep disorders in the older population.

Ancoli-Israel S; Kripke DF; Mason W; Messin S

1981-01-01

298

[Melatonin treatment of a blind child with serious sleep disorders].  

UK PubMed Central (United Kingdom)

BACKGROUND: Children with developmental and neurological disabilities are prone to develop serious sleep-wake cycle disorders that may be difficult to treat. MATERIAL AND METHODS: Case history. RESULTS: A 5-year old blind boy with multiple disabilities developed a chronic sleep-wake cycle disorder as his main clinical problem. Treatment included introduction of strict sleep habits and strengthening of environmental "zeitgebers". After five months melatonin 3 mg was administered at night for 4 weeks. The observation period also included 3 weeks without melatonin. Sleep was registered prospectively by a sleep diary. Strict sleep habits combined with strengthening of "zeitgebers" partially improved the sleep problems, but did not establish a normal sleep pattern. When melatonin was added, he normalized his sleep pattern in a few days. His sleep problems returned during the weeks in which he did not receive melatonin. No side effects were observed. INTERPRETATION: Melatonin is a promising treatment alternative for serious sleep problems in blind children.

Ramstad K; Loge JH

2002-04-01

299

High levels of melatonin generated during the brewing process.  

UK PubMed Central (United Kingdom)

Beer is a beverage consumed worldwide. It is produced from cereals (barley or wheat) and contains a wide array of bioactive phytochemicals and nutraceutical compounds. Specifically, high melatonin concentrations have been found in beer. Beers with high alcohol content are those that present the greatest concentrations of melatonin and vice versa. In this study, gel filtration chromatography and ELISA were combined for melatonin determination. We brewed beer to determine, for the first time, the beer production steps in which melatonin appears. We conclude that the barley, which is malted and ground in the early process, and the yeast, during the second fermentation, are the largest contributors to the enrichment of the beer with melatonin.

Garcia-Moreno H; Calvo JR; Maldonado MD

2013-08-01

300

Melatonin reduces mortality from Aleutian disease in mink (Mustela vison).  

UK PubMed Central (United Kingdom)

Aleutian disease (AD) results from a persistent parvoviral infection that results in marked hypergammaglobulinemia and immune complex mediated lesions of the kidney, liver, lungs and, arteries. Melatonin protected both a wild type or demi strain and a demi/dark crossed strain of mink from AD. The biogenic amine also afforded protection against other non-diagnosed diseases naturally found on mink farms when it was available from a subcutaneously-placed reservoir. Some genetic strains of mink apparently differed in the resistance of mink to the virus and in the protective ability of melatonin. The demi strain was the most resistant followed by pastels, mahogany, darks, and those strains with the double recessive Aleutian gene. The protective action of melatonin appeared to result from melatonin's ability to scavenge free radicals, but it could also be due to the induction of antioxidant enzymes or to the modulation of immunity. Melatonin also protected mink against distemper.

Ellis LC

1996-11-01

 
 
 
 
301

Subcellular distribution of melatonin receptors in human parotid glands.  

UK PubMed Central (United Kingdom)

The hormone melatonin influences oral health through a variety of actions, such as anti-inflammatory, anti-oxidant, immunomodulatory and antitumour. Many of these melatonin functions are mediated by a family of membrane receptors expressed in the oral epithelium and salivary glands. Using immunoblotting and immunohistochemistry, recent studies have shown that the melatonin membrane receptors, MT1 and MT2, are present in rat and human salivary glands. To date, no investigation has dealt with the ultrastructural distribution of the melatonin receptors. This was the aim of the present study, using the immunogold method applied to the human parotid gland. Reactivity to MT1 and, with less intensity, to MT2 appeared in the secretory granules of acinar cells and in the cytoplasmic vesicles of both acinar and ductal cells. Plasma membranes were also stained, albeit slightly. The peculiar intracytoplasmic distribution of these receptors may indicate that there is an uptake/transport system for melatonin from the circulation into the saliva.

Isola M; Ekström J; Diana M; Solinas P; Cossu M; Lilliu MA; Loy F; Isola R

2013-09-01

302

Topical melatonin for treatment of androgenetic alopecia.  

UK PubMed Central (United Kingdom)

BACKGROUND: In the search for alternative agents to oral finasteride and topical minoxidil for the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth modulator, was identified as a promising candidate based on in vitro and in vivo studies. MATERIALS AND METHODS: One pharmacodynamic study on topical application of melatonin and four clinical pre-post studies were performed in patients with androgenetic alopecia or general hair loss and evaluated by standardised questionnaires, TrichoScan, 60-second hair count test and hair pull test. RESULTS: FIVE CLINICAL STUDIES SHOWED POSITIVE EFFECTS OF A TOPICAL MELATONIN SOLUTION IN THE TREATMENT OF AGA IN MEN AND WOMEN WHILE SHOWING GOOD TOLERABILITY: (1) Pharmacodynamics under once-daily topical application in the evening showed no significant influence on endogenous serum melatonin levels. (2) An observational study involving 30 men and women showed a significant reduction in the degree of severity of alopecia after 30 and 90 days (P < 0.001) based on questionnaires completed by investigators and patients. (3) Using a digital software-supported epiluminescence technique (TrichoScan) in 35 men with AGA, after 3 and 6 months in 54.8% to 58.1% of the patients a significant increase of hair density of 29% and 41%, respectively was measured (M0: 123/cm(2); M3: 159/cm(2); M6: 173/cm(2);) (P < 0,001). (4) In 60 men and women with hair loss, a significant reduction in hair loss was observed in women, while hair loss in men remained constant (P < 0.001). (5) In a large, 3-month, multi-center study with more than 1800 volunteers at 200 centers, the percentage of patients with a 2- to 3-fold positive hair-pull test decreased from 61.6% to 7.8%, while the percentage of patients with a negative hair-pull test increased from 12.2.% to 61.5% (P < 0.001). In addition, a decrease in seborrhea and seborrheic dermatitis of the scalp was observed. CONCLUSIONS: Since safety and tolerability in all of the studies was good, the topical application of a cosmetic melatonin solution can be considered as a treatment option in androgenetic alopecia.

Fischer TW; Trüeb RM; Hänggi G; Innocenti M; Elsner P

2012-10-01

303

Structure of the nocturnal boundary layer over a complex terrain  

Energy Technology Data Exchange (ETDEWEB)

The complex nature of the nocturnal boundary layer (NBL) has been shown extensively in the literature Project STABLE was conducted in 1988 to study NBL turbulence and diffusion over the complex terrain of the Savannah River Site (SRS) near Augusta, Georgia. The third night of the study was particularly interesting because of the unusual phenomena observed in the structure of the NBL. Further analyses of microscale and mesoscale data from this night are presented using data from SRS network of eight 61 m towers over 900 km{sup 2}, from six launches of an instrumented tethersonde, from permanent SRL meteorological instrumentation at seven levels of the 304 m (1,000 ft) WJBF-TV tower near SRS, and additional data collected at 36 m (CC) by North Carolina State University (NCSU) including a one dimensional sonic anemometer, fine wire thermocouple, and a three dimensional propeller anemometer. Also, data from the nearby Plant Vogtle nuclear power plant observation tower and the National Weather Service at Augusta`s Bush Field (AGS) are presented. The passage of a mesoscale phenomenon, defined as a microfront (with an explanation of the nomenclature used), and a vertical composite schematic of the NBL which shows dual low level wind maxima, dual inversions, and a persistent, elevated turbulent layer over a complex terrain are described.

Parker, M.J. [Westinghouse Savannah River Co., Aiken, SC (United States); Raman, S. [North Carolina State Univ., Raleigh, NC (United States). Dept. of Marine, Earth and Atmospheric Sciences

1992-08-01

304

Structure of the nocturnal boundary layer over a complex terrain  

Energy Technology Data Exchange (ETDEWEB)

The complex nature of the nocturnal boundary layer (NBL) has been shown extensively in the literature Project STABLE was conducted in 1988 to study NBL turbulence and diffusion over the complex terrain of the Savannah River Site (SRS) near Augusta, Georgia. The third night of the study was particularly interesting because of the unusual phenomena observed in the structure of the NBL. Further analyses of microscale and mesoscale data from this night are presented using data from SRS network of eight 61 m towers over 900 km{sup 2}, from six launches of an instrumented tethersonde, from permanent SRL meteorological instrumentation at seven levels of the 304 m (1,000 ft) WJBF-TV tower near SRS, and additional data collected at 36 m (CC) by North Carolina State University (NCSU) including a one dimensional sonic anemometer, fine wire thermocouple, and a three dimensional propeller anemometer. Also, data from the nearby Plant Vogtle nuclear power plant observation tower and the National Weather Service at Augusta's Bush Field (AGS) are presented. The passage of a mesoscale phenomenon, defined as a microfront (with an explanation of the nomenclature used), and a vertical composite schematic of the NBL which shows dual low level wind maxima, dual inversions, and a persistent, elevated turbulent layer over a complex terrain are described.

Parker, M.J. (Westinghouse Savannah River Co., Aiken, SC (United States)); Raman, S. (North Carolina State Univ., Raleigh, NC (United States). Dept. of Marine, Earth and Atmospheric Sciences)

1992-01-01

305

Expression of melatonin (MT1, MT2) and melatonin-related receptors in the adult rat testes and during development.  

UK PubMed Central (United Kingdom)

It is well known that melatonin provokes reproductive alterations in response to changes in hours of daylight in seasonally breeding mammals, exerting a regulatory role at different levels of the hypothalamic-pituitary-gonadal axis. Although it has also been demonstrated that melatonin may affect testicular activity in vertebrates, until now, very few data support the hypothesis of a local action of melatonin in the male gonads. The aim of this study was to investigate whether MT1, MT2 melatonin receptors and the H9 melatonin-related receptor, are expressed in the adult rat testes and during development. A semi-quantitative RT-PCR method was used to analyse the expression of MT1, MT2 and H9 receptors mRNAs in several rat tissues, mainly focusing on testes during development and adult life. Our results provide molecular evidences of the presence of both MT1 and, for the first time, MT2 melatonin receptors as well as of the H9 melatonin-related receptor in the examined tissues, including adult testes. During development MT1 and MT2 transcripts are expressed at lower levels in testes of rats from 1 day to 1 week of age, lightly increased at 2 weeks of age and remained permanently expressed throughout development until 6 months. These data strongly support the hypothesis that melatonin acts directly in male vertebrate gonads suggesting that rat testes may be a suitable model to verify the role of indolamine in vertebrate testicular activity.

Izzo G; Francesco A; Ferrara D; Campitiello MR; Serino I; Minucci S; d'Istria M

2010-08-01

306

[The expression of melatonin receptor in human hypertrophic scar].  

UK PubMed Central (United Kingdom)

OBJECTIVE: To investigate the expression and its significance of melatonin receptor in human hypertrophic scarring. METHODS: The expression of melatonin receptor GPR50 was detected with immunohistochemistry and the melatonin receptors (MT1, MT2) mRNA were assessed with RT-PCR method in 10 cases of human hypertrophic scar and normal skin. The positive production was sequenced with auto sequencing instrument. RESULTS: Positive signals of melatonin receptor could be found in the cell membrane and cytoplasm. The melatonin receptor GPR50 was located in the epithelial basal cells,sweat gland cells and hair follicle in both hypertrophic scar and normal skin. The melatonin receptor GPR50 was extensively expressed in fibroblasts of hypertrophic scar, but not in fibroblasts in normal skin. RT-PCR showed that the expression of melatonin receptor (MT1, MT2) mRNA in hypertrophic scar was significantly higher than that in normal skin (P < 0.05). In normal skin and hypertrophic scar group, the expression of MT1 mRNA was higher than MT2 mRNA (P < 0.05). In normal skin and hypertrophic scar group, the expression of MT1 mRNA was 0.99081 +/- 0.26485 and 1.16584 +/- 0.21829 copy number/microl cDNA, respectively; the expression of MT2 mRNA was 0.77083 +/- 0.15927 and 0.99550 +/- 0.14624 copy number/ microl cDNA, respectively. Sequencing results indicated that the positive product coincided with cDNA of human melatonin receptor in GeneBank. CONCLUSIONS: Positive expression of melatonin receptor can be found in human hypertrophic scar and normal skin, but it is higher in scar. The over expression of melatonin receptor in hypertrophic scar may be related to the development of hypertrophic scar.

Zhang JC; Xie YF; Liu SJ; Dai LB; Li JP

2010-05-01

307

Circadian mechanisms in the regulation of melatonin synthesis: disruption with light at night and the pathophysiological consequences  

Directory of Open Access Journals (Sweden)

Full Text Available In the past two decades, the results of a number of epidemiological studies have uncovered an association between excessive light exposure at night and the prevalence of cancer. Whereas the evidence supporting this link is strongest between nighttime light and female breast and male prostate cancer, the frequency of other tumor types may also be elevated. Individuals who have the highest reported increase in cancer are chronic night shift workers and flight attendants who routinely fly across numerous time zones. There are at least two obvious physiological consequences of nighttime light exposure, i.e., a reduction in circulating melatonin levels and disruption of the circadian system (chronodisruption). Both these perturbations in experimental animals aggravate tumor growth. Melatonin has a long investigative history in terms of its ability to stymie the growth of many tumor types. Likewise, in the last decade chronodisruption has been unequivocally linked to a variety of abnormal metabolic conditions including excessive tumor growth. This brief review summarizes the processes by which light after darkness onset impedes melatonin production and disturbs circadian rhythms. The survey also reviews the evidence associating the ostensible danger of excessive nighttime light pollution to cancer risk. If an elevated tumor frequency is definitively proven to be a consequence of light at night and/or chronodisruption, it seems likely that cancer will not be the exclusive pathophysiological change associated with the rampant light pollution characteristic of modern societies. [J Exp Integr Med 2011; 1(1): 13-22

Russel J. Reiter; Dun Xian Tan; Emilio Sanchez-Barcelo; Maria D. Mediavilla; Eloisa Gitto; Ahmet Korkmaz

2011-01-01

308

Visual orientation and navigation in nocturnal arthropods.  

UK PubMed Central (United Kingdom)

With their highly sensitive visual systems, the arthropods have evolved a remarkable capacity to orient and navigate at night. Whereas some navigate under the open sky, and take full advantage of the celestial cues available there, others navigate in more difficult conditions, such as through the dense understory of a tropical rainforest. Four major classes of orientation are performed by arthropods at night, some of which involve true navigation (i.e. travel to a distant goal that lies beyond the range of direct sensory contact): (1) simple straight-line orientation, typically for escape purposes; (2) nightly short-distance movements relative to a shoreline, typically in the context of feeding; (3) long-distance nocturnal migration at high altitude in the quest to locate favorable feeding or breeding sites, and (4) nocturnal excursions to and from a fixed nest or food site (i.e. homing), a task that in most species involves path integration and/or the learning and recollection of visual landmarks. These four classes of orientation--and their visual basis--are reviewed here, with special emphasis given to the best-understood animal systems that are representative of each.

Warrant E; Dacke M

2010-01-01

309

Nocturnal panic attacks Ataques de pânico noturno  

Directory of Open Access Journals (Sweden)

Full Text Available The panic-respiration connection has been presented with increasing evidences in the literature. We report three panic disorder patients with nocturnal panic attacks with prominent respiratory symptoms, the overlapping of the symptoms with the sleep apnea syndrome and a change of the diurnal panic attacks, from spontaneous to situational pattern. The implication of these findings and awareness to the distinct core of the nocturnal panic attacks symptoms may help to differentiate them from sleep disorders and the search for specific treatment.A conexão pânico-respiração vem apresentando evidências crescentes na literatura. Nós relatamos três pacientes com transtorno de pânico com ataques de pânico no sono com sintomas respiratórios proeminentes, a sobreposição de sintomas com a síndrome de apnéia do sono e a mudança dos ataques de pânico em vigília, de um padrão espontâneo a situacional. A implicação destes achados e a necessidade de maior atenção para o conjunto distinto de sintomas dos ataques de pânico no sono poderá ser útil para o diagnóstico diferencial e na busca por tratamento específico.

Fabiana L. Lopes; Antonio E. Nardi; Isabella Nascimento; Alexandre M. Valença; Walter A Zin

2002-01-01

310

Nocturnal flow on a western Colorado slope  

Energy Technology Data Exchange (ETDEWEB)

The Department of Energy sponsored Atmospheric Studies in Complex Terrain (ASCOT) program has conducted a research program designed to increase our knowledge and understanding of terrain-dominated flows with specific emphasis on nocturnal flows within mountain valleys. ASCOT has sponsored both field studies and numerical modeling efforts to improve our understanding of the wind, temperature and turbulence structure of nocturnal drainage flows. One of the most recent ASCOT sponsored field studies involves a study within the Mesa Creek Basin in western Colorado to investigate the seasonal frequency of occurrence of drainage flows along the sloped surfaces and within the basin, and to evaluate the effect of the ambient meteorology on their development. The modeling portion of the study is being undertaken by Lawrence Livermore Laboratory using a three-dimensional prognostic boundary layer model to gain further insight into the dynamics of the seasonal variations and the effect of cloud cover on the development of the drainage flows. It is the purpose of this paper to present preliminary results from a numerical simulation done as part of this study. 4 refs., 7 figs.

Leone, J.M. Jr.; Gudiksen, P.H.

1990-06-01

311

Melatonin, melatonin isomers and stilbenes in Italian traditional grape products and their antiradical capacity.  

UK PubMed Central (United Kingdom)

Although polyphenols represent the paradigm of the health-promoting effects ascribed to grape products, recently, attention has been paid to dietary melatonin, significantly present in Mediterranean foods. In this work, we measured melatonin, its isomers, stilbenes (trans- and cis-resveratrol and their glucosides, piceids) and total polyphenols in some different grape products (red, white and dessert wines, grape juices and Modena balsamic vinegars) of distinct Italian areas. We also evaluated their antiradical activity by DPPH(·) and ABTS(·+) assays. For indoleamine analysis, the separation was carried out on a 1.7-?m C18 BEH column and the detection performed by means of mass spectrometry with electrospray ionization in positive ion mode with multiple reaction monitoring. The confirmation of the peak identity was accomplished by injection into the high-resolution system (Orbitrap) using accurate mass measurements (error below 1.0 ppm). Mass spectrometry analyses revealed, for the first time, the presence of melatonin in dessert wines and balsamic vinegars, as well as the occurrence of three different melatonin isomers in grape products.

Vitalini S; Gardana C; Simonetti P; Fico G; Iriti M

2013-04-01

312

Nocturnal panic attack: is it an another subtype?  

Directory of Open Access Journals (Sweden)

Full Text Available Objective: The aim of this study is to investigate if the nocturnal panic attack has different features and might be considered as a subtype or not. Methods: Sociodemographic data form, SCID-I, SCID-II, Panic and Agoraphobia Scale (PAS), Hamilton Depression Scale (HAM-D), Beck Anxiety Scale, and Bak?rköy Panic Disorder Behavioral Changes Form are applied to the participants. 51 of the 98 patients were suffering from Nocturnal Panic Attacks according to the inclusion/exclusion criteria. Results: It was revealed that 47.9% of the panic disorder patients were suffering from nocturnal panic attacks. The most frequent symptoms in nocturnal panic disorder cases were experiences of feelings like drowning, lethargy, palpitation, vertigo, fear of death, and anxiety. The existence of nocturnal panic attacks is found to be related with severity of the disorder and comorbid depression. Moreover, comorbid sleep disturbances characterized with troubles in falling asleep, difficulty in sustaining sleep, feeling tired in the morning, were observed. There were sleep related avoidances and behavioral changes. Panic disorder patients with nocturnal panic attacks were found to avoid sleeping, or going to bed alone. Conclusions: Panic disorder cases with nocturnal panic attacks had more severe symptoms. From here, it can be concluded that it might be a subtype of panic disorder.

Özlem Girit Çetinkaya; Kür?at Alt?nba?; Derya ?pekçio?lu; Sezgin Erdiman; ?eref Özer

2011-01-01

313

Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal  

Directory of Open Access Journals (Sweden)

Full Text Available Patrick Lemoine1, Doron Garfinkel2, Moshe Laudon3, Tali Nir3, Nava Zisapel3,41The Clinique Lyon-Lumière, Meyzieu, France; 2Geriatric-Palliative Department, Shoham Geriatric Medical Center, Pardes Hanna, Israel; 3Neurim Pharmaceuticals Ltd, Tel-Aviv, Israel; 4Department of Neurobiology Faculty of Life Sciences, Tel Aviv University, Tel Aviv, IsraelBackground: Prolonged-release melatonin (PRM) 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18–80 and lack of withdrawal and rebound symptoms upon discontinuation.Objective: To investigate the efficacy, safety, and withdrawal phenomena associated with 6–12 months PRM treatment.Methods: Data from a prospective 6–12-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary), adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]). Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM.Results: Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as "good" or "very good" was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production.Conclusion: Results support the efficacy and safety of PRM in primary insomnia patients aged 20–80 throughout 6–12 months of continuous therapy. PRM discontinuation even after 12 months was not associated with adverse events, withdrawal symptoms, or suppression of endogenous melatonin production.Keywords: PRM, adverse events, sleep, insomnia, patients

Lemoine P; Garfinkel D; Laudon M; Nir T; Zisapel N

2011-01-01

314

Risk factors for nocturnal enuresis in school-age children.  

UK PubMed Central (United Kingdom)

PURPOSE: Although nocturnal enuresis is common in children, its etiology is multifactorial and not fully understood. We evaluated potential risk factors for presence and severity of nocturnal enuresis. MATERIALS AND METHODS: A validated, reproducible questionnaire was distributed to 8,230 school children in Sydney, Australia. Nocturnal enuresis was defined as any wetting in the previous month and categorized as mild (1 to 6 nights), moderate (7 or more nights but less than nightly) or severe (nightly). RESULTS: Parents of 2,856 children (mean +/- SD age 7.3 +/- 1.3 years) completed the questionnaire (response rate 35%). Overall prevalence of nocturnal enuresis was 18.2%, with 12.3% of patients having mild, 2.5% moderate and 3.6% severe enuresis. Multivariate analysis showed that daytime incontinence (OR 4.8, 95% CI 2.9 to 7.9), encopresis (OR 2.7, 95% CI 1.6 to 4.4), bladder dysfunction (OR 3.6, 95% CI 2.4 to 5.3) and male gender (OR 2.0, 95% CI 1.3 to 3.1) were associated with severe nocturnal enuresis after adjustment for age. Emotional stressors (OR 2.3, 95% CI 1.2 to 4.2) and social concerns (OR 2.4, 95% CI 1.2 to 4.5) were associated with moderate nocturnal enuresis only. CONCLUSIONS: Encopresis and daytime incontinence are significant modifiable risk factors for nocturnal enuresis. Expressed as population attributable risk, 23% of nocturnal enuresis is associated with encopresis and daytime incontinence. Psychosocial factors appear to contribute to moderate but not severe nocturnal enuresis.

Sureshkumar P; Jones M; Caldwell PH; Craig JC

2009-12-01

315

Transdermal delivery of a pineal hormone: melatonin via elastic liposomes.  

UK PubMed Central (United Kingdom)

Melatonin (MT) is a good candidate for transdermal delivery considering its short biological half-life, low molecular weight and a variable oral absorption. The objective of this work was to develop a novel formulation of melatonin for its efficient transdermal delivery. Melatonin loaded elastic liposomal formulation was prepared, characterized and the effect of this developed formulation on the in vitro permeation of melatonin across human cadaver skin was investigated, using a locally fabricated Franz diffusion cell. Skin permeation potential of the developed formulation was assessed using confocal laser scanning microscopy (CLSM), which revealed an enhanced permeation of the formulation to the deeper layers of the skin (up to 180 microm) following channel like pathways. Skin permeation profile of melatonin through elastic liposomal formulations was observed and the investigations revealed an enhanced transdermal flux (51.2+/-2.21 microg/cm(2)/h), decreased lag time (1.1h) and an optimum permeability coefficient (15.06+/-0.52 cm/h) for melatonin. The obtained flux was nearly 5 and 12.3 times higher than conventional liposomal and plain drug solution, respectively (P<0.005). Our result suggests the feasibility of elastic liposomal system for transdermal delivery of melatonin thereby eliminating the limitations of long lag time and poor skin permeation associated with the drug.

Dubey V; Mishra D; Asthana A; Jain NK

2006-06-01

316

Transdermal delivery of a pineal hormone: melatonin via elastic liposomes.  

Science.gov (United States)

Melatonin (MT) is a good candidate for transdermal delivery considering its short biological half-life, low molecular weight and a variable oral absorption. The objective of this work was to develop a novel formulation of melatonin for its efficient transdermal delivery. Melatonin loaded elastic liposomal formulation was prepared, characterized and the effect of this developed formulation on the in vitro permeation of melatonin across human cadaver skin was investigated, using a locally fabricated Franz diffusion cell. Skin permeation potential of the developed formulation was assessed using confocal laser scanning microscopy (CLSM), which revealed an enhanced permeation of the formulation to the deeper layers of the skin (up to 180 microm) following channel like pathways. Skin permeation profile of melatonin through elastic liposomal formulations was observed and the investigations revealed an enhanced transdermal flux (51.2+/-2.21 microg/cm(2)/h), decreased lag time (1.1h) and an optimum permeability coefficient (15.06+/-0.52 cm/h) for melatonin. The obtained flux was nearly 5 and 12.3 times higher than conventional liposomal and plain drug solution, respectively (P<0.005). Our result suggests the feasibility of elastic liposomal system for transdermal delivery of melatonin thereby eliminating the limitations of long lag time and poor skin permeation associated with the drug. PMID:16513163

Dubey, Vaibhav; Mishra, Dinesh; Asthana, Abhay; Jain, Narendra Kumar

2006-03-02

317

Solubilization and purification of melatonin receptors from lizard brain  

International Nuclear Information System (INIS)

Melatonin receptors in lizard brain were identified and characterized using 125I-labeled melatonin ([125I]MEL) after solubilization with the detergent digitonin. Saturation studies of solubilized material revealed a high affinity binding site, with an apparent equilibrium dissociation constant of 181 +/- 45 pM. Binding was reversible and inhibited by melatonin and closely related analogs, but not by serotonin or norepinephrine. Treatment of solubilized material with the non-hydrolyzable GTP analog, guanosine 5'-(3-O-thiotriphosphate) (GTP-gamma-S), significantly reduced receptor affinity. Gel filtration chromatography of solubilized melatonin receptors revealed a high affinity, large (Mr 400,000) peak of specific binding. Pretreatment with GTP-gamma-S before solubilization resulted in elution of a lower affinity, smaller (Mr 150,000) peak of specific binding. To purify solubilized receptors, a novel affinity chromatography resin was developed by coupling 6-hydroxymelatonin with Epoxy-activated Sepharose 6B. Using this resin, melatonin receptors were purified approximately 10,000-fold. Purified material retained the pharmacologic specificity of melatonin receptors. These results show that melatonin receptors that bind ligand after detergent treatment can be solubilized and substantially purified by affinity chromatography.

1990-01-01

318

Solubilization and purification of melatonin receptors from lizard brain  

Energy Technology Data Exchange (ETDEWEB)

Melatonin receptors in lizard brain were identified and characterized using {sup 125}I-labeled melatonin (({sup 125}I)MEL) after solubilization with the detergent digitonin. Saturation studies of solubilized material revealed a high affinity binding site, with an apparent equilibrium dissociation constant of 181 +/- 45 pM. Binding was reversible and inhibited by melatonin and closely related analogs, but not by serotonin or norepinephrine. Treatment of solubilized material with the non-hydrolyzable GTP analog, guanosine 5'-(3-O-thiotriphosphate) (GTP-gamma-S), significantly reduced receptor affinity. Gel filtration chromatography of solubilized melatonin receptors revealed a high affinity, large (Mr 400,000) peak of specific binding. Pretreatment with GTP-gamma-S before solubilization resulted in elution of a lower affinity, smaller (Mr 150,000) peak of specific binding. To purify solubilized receptors, a novel affinity chromatography resin was developed by coupling 6-hydroxymelatonin with Epoxy-activated Sepharose 6B. Using this resin, melatonin receptors were purified approximately 10,000-fold. Purified material retained the pharmacologic specificity of melatonin receptors. These results show that melatonin receptors that bind ligand after detergent treatment can be solubilized and substantially purified by affinity chromatography.

Rivkees, S.A.; Conron, R.W. Jr.; Reppert, S.M. (Massachusetts General Hospital, Boston (USA))

1990-09-01

319

Melatonin and cortisol rhythm in patients with extensive nasal polyposis.  

UK PubMed Central (United Kingdom)

PURPOSE: Extensive nasal polyposis is an inflammatory disease which effects 1%-4% of normal population. The mechanism of its formation and the circadian rhythm of cortisol and melatonin in ENP have not investigated. MATERIALS AND METHODS: Salivary levels of melatonin and cortisol were measured by radioimmunoassay in 31 patients with extensive nasal polyposis and in 27 control subjects matched for age and gender. In both groups none of the subjects did not have obstructive sleep apnea. RESULTS: The baseline and the peak levels of salivary melatonin in the extensive nasal polyposis group were significantly lower than in the control group (p<0.001). However, no differences were found in the acrophase and the peak duration of salivary melatonin between the study and control groups (p>0.05). The highest values of melatonin were recorded at 04:00 h in both the study and control groups. The amplitude and the 24 h mean levels of salivary cortisol in the extensive nasal polyposis group were significantly lower than in the control group (p<0.001). The acrophase was delayed by about 8 h in extensive nasal polyposis patients (p<0.001). CONCLUSION: The circadian rhythms of salivary melatonin and cortisol were found to be disrupted in patients with extensive nasal polyposis. These results may be applicable as therapeutic tools in the future and melatonin drugs might be useful in the therapy of nasal polyposis like cortisol drugs.

Fidan V; Alp HH; Kalkandelen S; Cingi C

2013-01-01

320

Melatonin does not influence sleep deprivation electroencephalogram recordings in children.  

UK PubMed Central (United Kingdom)

UNLABELLED: The electroencephalogram (EEG) is an essential diagnostic tool in children with epilepsy. The recording of a sleep EEG can increase the yield of EEG recordings in certain epileptic syndromes. The primary aim of this study was to assess the influence of melatonin on EEG recording (quality, EEG characteristics) and to assess its efficacy to induce sleep. Children with epilepsy or non-epileptic neurological patients requiring sleep deprivation EEG studies were enrolled into this prospective study at a tertiary University Hospital study. Sequential recording of sleep deprivation EEGs both with and without prior administration of melatonin was performed. A total of 50 patients (27 with epilepsy, 23 non-epileptic neurological patients) were included in this study (median age 9.5 years; range 1-18 years; male 28). The quality and EEG characteristics (abnormal findings, depth of sleep) were not affected by the use of melatonin. In total, 92 of 100 EEGs were successfully performed without significant differences between the two groups (six failures with melatonin, two failures without melatonin; p = 0.289). CONCLUSIONS: We conclude that melatonin does not alter the quality of sleep EEG studies in children with epilepsy or suspected epilepsy. Melatonin does not increase the rate of successfully performed EEG studies in sleep-deprived children.

Sander J; Shamdeen MG; Gottschling S; Gortner L; Gräber S; Meyer S

2012-04-01

 
 
 
 
321

Melatonin receptors, heterodimerization, signal transduction and binding sites: what's new?  

UK PubMed Central (United Kingdom)

Melatonin is a neurohormone that has been claimed to be involved in a wide range of physiological functions. Nevertheless, for most of its effects, the mechanism of action is not really known. In mammals, two melatonin receptors, MT1 and MT2, have been cloned. They belong to the G-protein-coupled receptor (GPCR) superfamily. They share some specific short amino-acid sequences, which suggest that they represent a specific subfamily. Another receptor from the same subfamily, the melatonin-related receptor has been cloned in different species including humans. This orphan receptor also named GPR50 does not bind melatonin and its endogenous ligand is still unknown. Nevertheless, this receptor has been shown to behave as an antagonist of the MT1 receptor, which opens new pharmacological perspectives for GPR50 despite the lack of endogenous or synthetic ligands. Moreover, MT1 and MT2 interact together through the formation of heterodimers at least in cells transfected with the cDNA of these two receptors. Lastly, signalling complexes associated with MT1 and MT2 receptors are starting to be deciphered. A third melatonin-binding site has been purified and characterized as the enzyme quinone reductase 2 (QR2). Inhibition of QR2 by melatonin may explain melatonin's protective effect that has been reported in different animal models and that is generally associated with its well-documented antioxidant properties.

Jockers R; Maurice P; Boutin JA; Delagrange P

2008-07-01

322

Melatonin receptors, heterodimerization, signal transduction and binding sites: what's new?  

Science.gov (United States)

Melatonin is a neurohormone that has been claimed to be involved in a wide range of physiological functions. Nevertheless, for most of its effects, the mechanism of action is not really known. In mammals, two melatonin receptors, MT1 and MT2, have been cloned. They belong to the G-protein-coupled receptor (GPCR) superfamily. They share some specific short amino-acid sequences, which suggest that they represent a specific subfamily. Another receptor from the same subfamily, the melatonin-related receptor has been cloned in different species including humans. This orphan receptor also named GPR50 does not bind melatonin and its endogenous ligand is still unknown. Nevertheless, this receptor has been shown to behave as an antagonist of the MT1 receptor, which opens new pharmacological perspectives for GPR50 despite the lack of endogenous or synthetic ligands. Moreover, MT1 and MT2 interact together through the formation of heterodimers at least in cells transfected with the cDNA of these two receptors. Lastly, signalling complexes associated with MT1 and MT2 receptors are starting to be deciphered. A third melatonin-binding site has been purified and characterized as the enzyme quinone reductase 2 (QR2). Inhibition of QR2 by melatonin may explain melatonin's protective effect that has been reported in different animal models and that is generally associated with its well-documented antioxidant properties. PMID:18493248

Jockers, R; Maurice, P; Boutin, J A; Delagrange, P

2008-05-19

323

Growth conditions determine different melatonin levels in Lupinus albus L.  

Science.gov (United States)

Melatonin, an indoleamine, which has recently been assigned several roles in plant physiology as a growth promoter, as rooting agent, and as antioxidant in senescence delay and cytoprotection, seems to have a relevant function in plant stress situations. The presence of melatonin increases the resistance of lupin plant tissues (Lupinus albus L.) against natural or artificially induced adverse situations. In this work, we studied the response of lupin plants in controlled stress situations (drought-, anaerobic-, pH-, and cold stress and using ZnSO4 , NaCl, and H2 O2 as chemical stressors) and measured the changes in endogenous melatonin levels in lupin plants. Also, the effect of abscisic acid, ethylene, and natural environmental conditions were evaluated. In general, nearly all stressful factors caused an increase in melatonin in the investigated organs. The chemical stress provoked by ZnSO4 or NaCl caused the most pronounced changes in the endogenous level of melatonin, followed by cold and drought stressors. In some cases, the level of melatonin increased 12-fold with respect to the levels in control plants, indicating that melatonin biosynthesis is upregulated in common stress situations, in which it may serve as a signal molecule and/or as a direct antistress agent due to its well-known antioxidative properties. PMID:23600673

Arnao, Marino B; Hernández-Ruiz, Josefa

2013-04-18

324

Melatonin affects the temporal pattern of vocal signatures in birds.  

UK PubMed Central (United Kingdom)

In humans and other animals, melatonin is involved in the control of circadian biological rhythms. Here, we show that melatonin affects the temporal pattern of behavioral sequences in a noncircadian manner. The zebra finch (Taeniopygia guttata) song and the crow of the Japanese quail (Coturnix japonica) are courtship vocalizations composed of a stereotyped sequence of syllables. The zebra finch song is learned from conspecifics during infancy, whereas the Japanese quail crow develops normally without auditory input. We recorded and analyzed the complete vocal activity of adult birds of both species kept in social isolation for several weeks. In both species, we observed a shortening of signal duration following the transfer from a light-dark (LD) cycle to constant light (LL), a condition known to abolish melatonin production and to disrupt circadian rhythmicity. This effect was reversible because signal duration increased when the photoperiod was returned to the previous LD schedule. We then tested whether this effect was directly related to melatonin by removal of the pineal gland, which is the main production site of circulating melatonin. A shortening of the song duration was observed following pinealectomy in LD. Likewise, melatonin treatment induced changes in the temporal structure of the song. In a song learning experiment, young pinealectomized finches and young finches raised in LL failed to copy the temporal pattern of their tutor's song. Taken together, these results suggest that melatonin is involved in the control of motor timing of noncircadian behavioral sequences through an evolutionary conserved neuroendocrine pathway.

Derégnaucourt S; Saar S; Gahr M

2012-10-01

325

Melatonin antioxidative defense: therapeutical implications for aging and neurodegenerative processes.  

UK PubMed Central (United Kingdom)

The pineal product melatonin has remarkable antioxidant properties. It is secreted during darkness and plays a key role in various physiological responses including regulation of circadian rhythms, sleep homeostasis, retinal neuromodulation, and vasomotor responses. It scavenges hydroxyl, carbonate, and various organic radicals as well as a number of reactive nitrogen species. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, and glutathione reductase, and by augmenting glutathione levels. Melatonin preserves mitochondrial homeostasis, reduces free radical generation and protects mitochondrial ATP synthesis by stimulating Complexes I and IV activities. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases. The efficacy of melatonin in preventing oxidative damage in either cultured neuronal cells or in the brains of animals treated with various neurotoxic agents, suggests that melatonin has a potential therapeutic value as a neuroprotective drug in treatment of Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and brain trauma. Therapeutic trials with melatonin indicate that it has a potential therapeutic value as a neuroprotective drug in treatment of AD, ALS, and HD. In the case of other neurological conditions, like PD, the evidence is less compelling. Melatonin's efficacy in combating free radical damage in the brain suggests that it can be a valuable therapeutic agent in the treatment of cerebral edema following traumatic brain injury or stroke. Clinical trials employing melatonin doses in the range of 50-100 mg/day are warranted before its relative merits as a neuroprotective agent is definitively established.

Pandi-Perumal SR; BaHammam AS; Brown GM; Spence DW; Bharti VK; Kaur C; Hardeland R; Cardinali DP

2013-04-01

326

Therapeutic application of melatonin in mild cognitive impairment.  

UK PubMed Central (United Kingdom)

Mild cognitive impairment (MCI) is an etiologically heterogeneous syndrome defined by cognitive impairment in advance of dementia. We previously reported in a retrospective analysis that daily 3 - 9 mg of a fast-release melatonin preparation given p. o. at bedtime for up to 3 years significantly improved cognitive and emotional performance and daily sleep/wake cycle in MCI patients. In a follow up of that study we now report data from another series of 96 MCI outpatients, 61 of who had received daily 3 - 24 mg of a fast-release melatonin preparation p. o. at bedtime for 15 to 60 months. Melatonin was given in addition to the standard medication prescribed by the attending psychiatrist. Patients treated with melatonin exhibited significantly better performance in Mini-Mental State Examination and the cognitive subscale of the Alzheimer's disease Assessment Scale. After application of a neuropsychological battery comprising a Mattis´ test, Digit-symbol test, Trail A and B tasks and the Rey´s verbal test, better performance was found in melatonin-treated patients for every parameter tested. Abnormally high Beck Depression Inventory scores decreased in melatonin-treated patients, concomitantly with the improvement in the quality of sleep and wakefulness. The comparison of the medication profile in both groups of MCI patients indicated that 9.8% in the melatonin group received benzodiazepines vs. 62.8% in the non-melatonin group. The results further support that melatonin can be a useful add-on drug for treating MCI in a clinic environment.

Cardinali DP; Vigo DE; Olivar N; Vidal MF; Furio AM; Brusco LI

2012-01-01

327

Nocturnal choking episodes: under-recognized and misdiagnosed.  

Science.gov (United States)

Causes of nocturnal paroxysmal events include a variety of disorders such as epileptic seizures, parasomnias, sleep-related movement disorders, and psychiatric disturbances. Timing and semiology of the events, simultaneous video-electroencephalographic observation, presence of any daytime events, and relevant psychiatric and medical history may help in sorting out various possibilities considered in the differential diagnosis of such events. Timely diagnosis of these events is crucial for appropriate management; under-recognition and misdiagnosis of nonepileptic events is not uncommon. Described here are two cases within the spectrum of nocturnal paroxysmal events, one with nocturnal panic attacks and the other with frontal lobe epilepsy, each presenting with choking episodes. PMID:20933181

Elkay, Muruvet; Poduri, Annapurna; Prabhu, Sanjay P; Bergin, Ann M; Kothare, Sanjeev V

2010-11-01

328

Nocturnal choking episodes: under-recognized and misdiagnosed.  

UK PubMed Central (United Kingdom)

Causes of nocturnal paroxysmal events include a variety of disorders such as epileptic seizures, parasomnias, sleep-related movement disorders, and psychiatric disturbances. Timing and semiology of the events, simultaneous video-electroencephalographic observation, presence of any daytime events, and relevant psychiatric and medical history may help in sorting out various possibilities considered in the differential diagnosis of such events. Timely diagnosis of these events is crucial for appropriate management; under-recognition and misdiagnosis of nonepileptic events is not uncommon. Described here are two cases within the spectrum of nocturnal paroxysmal events, one with nocturnal panic attacks and the other with frontal lobe epilepsy, each presenting with choking episodes.

Elkay M; Poduri A; Prabhu SP; Bergin AM; Kothare SV

2010-11-01

329

Nocturnal bruxism and hypnotherapy: a case study.  

UK PubMed Central (United Kingdom)

This article describes a case study of a hypnotherapeutic treatment of nocturnal bruxism. The author saw the client for a total of 7 sessions. Hypnotherapy was interspersed with an exploration of tacit and initially denied hostility in the client's life as well as aspects of a somewhat difficult childhood. At the end, the bruxism had disappeared. Follow-up 1 year later indicated that the bruxism had not returned, and the client had become more assertive in her relations with others and had more exploratory activities in her life directions. The latter had not been dealt with in therapy. Thus, there appeared to be a "ripple effect" of successful therapy from one part of her life into its other aspects.

Dowd ET

2013-04-01

330

Tobacco habits in nocturnal frontal lobe epilepsy.  

UK PubMed Central (United Kingdom)

The beneficial effect of nicotine has been reported in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) patients, but not tested in sporadic cases. Recently, a nicotine defect in the arousal pathway has been hypothesized even in sporadic NFLE patients and their relatives. This case-control family study was designed to test whether NFLE subjects were more likely to use tobacco than controls, as an indirect marker of cholinergic arousal system dysregulation. At least four relatives were included for each NFLE proband and control. Each subject was questioned about tobacco habits; 434 individuals were recruited. Moreover, we compared NFLE patients with age- and sex-matched controls to determine whether they are more likely to use tobacco. We found a slightly higher trend of tobacco use in NFLE probands compared to that in control subjects; we did not find any significant difference in the distribution of tobacco use among NFLE group compared to that in the control group.

Naldi I; Bisulli F; Vignatelli L; Licchetta L; Pittau F; Di Vito L; Mostacci B; Menghi V; Provini F; Montagna P; Tinuper P

2013-01-01

331

Tobacco habits in nocturnal frontal lobe epilepsy.  

Science.gov (United States)

The beneficial effect of nicotine has been reported in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) patients, but not tested in sporadic cases. Recently, a nicotine defect in the arousal pathway has been hypothesized even in sporadic NFLE patients and their relatives. This case-control family study was designed to test whether NFLE subjects were more likely to use tobacco than controls, as an indirect marker of cholinergic arousal system dysregulation. At least four relatives were included for each NFLE proband and control. Each subject was questioned about tobacco habits; 434 individuals were recruited. Moreover, we compared NFLE patients with age- and sex-matched controls to determine whether they are more likely to use tobacco. We found a slightly higher trend of tobacco use in NFLE probands compared to that in control subjects; we did not find any significant difference in the distribution of tobacco use among NFLE group compared to that in the control group. PMID:23246147

Naldi, Ilaria; Bisulli, Francesca; Vignatelli, Luca; Licchetta, Laura; Pittau, Francesca; Di Vito, Lidia; Mostacci, Barbara; Menghi, Veronica; Provini, Federica; Montagna, Pasquale; Tinuper, Paolo

2012-12-12

332

Nocturnal flow on a western Colorado slope  

International Nuclear Information System (INIS)

The Department of Energy sponsored Atomspheric Studies in Complex Terrain (ASCOT) program has conducted a research program designed to increase our knowledge and understanding of terrain-dominated flows with specific emphasis on nocturnal flows within mountain valleys. ASCOT has sponsored both field studies and numerical modeling efforts to improve our understanding of the wind, temperature and turbulence structure of nocturnal drainage flows. One of the most recent ASCOT sponsored field studies involves a study within the Mesa Creek Basin in western Colorado to investigate the seasonal frequency of occurrence of drainage flows along the sloped surfaces and within the basin, and to evaluate the effect of the ambient meteorology on their development. The Mesa Creek Basin, situated on the north slope of the Grand Mesa, encompasses a roughly 10 x 20 km area that is approximately 30 km east of Grand Junction. The observational segment of the study was undertaken jointly by the Lawrence Livermore National Laboratory and the NOAA Wave Propagation Laboratory, and involved the operation of network of eight meteorological towers and a monostatic sodar within the Mesa Creek study area over a period of one year that extended from December 1988 through November 1989. These measurements were augmented by tethersonde observations to define the vertical wind and temperature structure during a few nights. The modeling portion of the study is being undertaken by Lawrence Livermore Laboratory using a three-dimensional prognostic boundary layer model to gain further insight into the dynamics of the seasonal variations and the effect of cloud cover on the development of the drainage flows. It is the purpose of this paper to present preliminary results form a numerical simulation done as part of this study. 4 refs., 7 figs.

1990-01-01

333

Nocturnal flow on a western Colorado slope  

Energy Technology Data Exchange (ETDEWEB)

The Department of Energy sponsored Atomspheric Studies in Complex Terrain (ASCOT) program has conducted a research program designed to increase our knowledge and understanding of terrain-dominated flows with specific emphasis on nocturnal flows within mountain valleys. ASCOT has sponsored both field studies and numerical modeling efforts to improve our understanding of the wind, temperature and turbulence structure of nocturnal drainage flows. One of the most recent ASCOT sponsored field studies involves a study within the Mesa Creek Basin in western Colorado to investigate the seasonal frequency of occurrence of drainage flows along the sloped surfaces and within the basin, and to evaluate the effect of the ambient meteorology on their development. The Mesa Creek Basin, situated on the north slope of the Grand Mesa, encompasses a roughly 10 {times} 20 km area that is approximately 30 km east of Grand Junction. The observational segment of the study was undertaken jointly by the Lawrence Livermore National Laboratory and the NOAA Wave Propagation Laboratory, and involved the operation of network of eight meteorological towers and a monostatic sodar within the Mesa Creek study area over a period of one year that extended from December 1988 through November 1989. These measurements were augmented by tethersonde observations to define the vertical wind and temperature structure during a few nights. The modeling portion of the study is being undertaken by Lawrence Livermore Laboratory using a three-dimensional prognostic boundary layer model to gain further insight into the dynamics of the seasonal variations and the effect of cloud cover on the development of the drainage flows. It is the purpose of this paper to present preliminary results form a numerical simulation done as part of this study. 4 refs., 7 figs.

Leone, J.M. Jr.; Gudiksen, P.H.

1990-04-01

334

Use of melatonin in preventing postoperative complications  

UK PubMed Central (United Kingdom)

The invention relates to pharmaceutical composition and the use of melatonin, either alone or in combination with at least one compound selected from the group consisting of L-arginine, a physiologically acceptable salt thereof, one or more other physiologically acceptable compounds associated with the synthesis of nitric oxide and mixtures thereof, for the manufacture of a medicament for the therapeutic treatment, prophylactic treatment and/or prevention of postoperative infectious and/or non-infections complications may be pneumonia, wound infection (wound dehiscence), intra-abdominal abscess, and urinary tract infections (UTI) or wherein the non-infectious complication may be anastomotic leak, or ischemia/reperfusion.

SCHNEIDER HEINZ

335

Diurnal rhythm of melatonin binding in the rat suprachiasmatic nucleus  

Energy Technology Data Exchange (ETDEWEB)

We used quantitative in vitro autoradiography to localize and characterize 2-/sup 125/I-melatonin binding sites in the rat suprachiasmatic nuclei in relation to pineal melatonin production. In a light:dark cycle of 12:12 h, binding density exhibited significant diurnal variation with a peak at the dark-light transition and a trough 12 hours later. Saturation studies suggested that the decreased binding at light-dark transition might be due to a shift of the putative melatonin receptor to a low affinity state.

Laitinen, J.T.; Castren, E.; Vakkuri, O.; Saavedra, J.M.

1989-03-01

336

Protective effect of melatonin on thrombocytopoiesis in irratiated mice  

International Nuclear Information System (INIS)

Objective: To study the protective effect of melatonin on thrombocytopoiesis (T) and its mechanism in total-bodily irradiated mice. Methods: Altogether 18 female BALB/c mice were randomly divided into three experimental groups (6 each): Group 1(normal control, N) received neither irradiation nor melatonin; Group 2 (model control, C); received total body-irradiation for 4 Gy gamma-rays and Group 3 (melatonin, M), received melatonin after irradiation at the dosage of 10 mg?kg-1?d-1 via i. p. injection in consecutive 21 days. In Group C normal saline instead of melatonin was administered in the same way as above. Peripheral blood platelets and white blood cells (WBC) were analyzed for the three groups on day 0, day 7, day 14, and day 21. All the mice were sacrificed to collect bone marrow cells for the assays of colony-forming unit-megakaryocyte (CFU-MK) and of colony-forming unit-fibroblast (CFU-F). The effects of melatonin of different concentrations (0-500 nmol/L) on CFU-MK formation were observed in vitro. Results: The results showed that melatonin enhanced the recovery of T. Moreover, melatonin also promoted the increase of CFU-F (28 ± 10.4 vs 14.6 ± 2.8) and CFU-MK (19.63 ± 3.28 vs 11 ± 2.24) in vivo. The amount of CFU-MK in vitro was dependent on the concentration of melatonin. Compared with the control group, the size of CFU-MK in Group M was much larger and MK cells were more mature, especially when the melatonin concentration was 200 nmol/L. Conclusion: Melatonin provides protective effect on T in irradiated mice. It enhances T in vivo and promotes the growth of bone marrow stromal cells as well as megakaryocytes in vitro. Therefore, we speculate that the T-protective activity of melatonin may be mediated via promoting growth of the progenitors of platelet, megakaryocytes, and bone marrow stromal cells. (authors)

2005-01-01

337

A review of the role of melatonin levels in neoplastic development  

Energy Technology Data Exchange (ETDEWEB)

A brief literature review of the relevant literature was carried out to determine the validity of the hypothesis that melatonin suppression could influence the cancer incidences reported in electromagnetic field (EMF) studies. Evidence was found of melatonin suppression by electric fields, and sensitivity of rodents to magnetic fields. Removal of the melatonin producing organ (pinealectomy) in most animal studies resulted in tumor stimulation, while administration of melatonin to functionally pinealectomized rodents usually resulted in tumor inhibition. Suggestions were found that melatonin impacts the effectiveness of the immune system. It was concluded that melatonin likely plays a role in neoplastic development although the complete mechanism is unknown. 82 refs., 3 figs., 4 tabs.

Arndt, T.

1990-01-05

338

[Melatonin in palate tonsils with recurrent acute tonsillitis and tonsillar hypertrophy  

UK PubMed Central (United Kingdom)

Tonsils are a point of contact between the environment and the immune system. The pineal hormone melatonin is influenced by environmental dark-light variations and modulates the immune system. We measured the amount of melatonin present in pediatric tonsillar infectious and obstructive processes. The highest levels of tonsillar melatonin were found in tonsillar hypertrophy and the lowest levels in recurrent acute tonsillitis, with or without hypertrophy. Melatonin has an immunostimulative function and an antiapoptotic effect. The relationship between low tonsillar melatonin concentrations and infection, as well as high melatonin levels and increased tonsillar size is discussed.

López González MA; Guerrero JM; Ceballo Pedraja JM; Delgado Moreno F

1998-11-01

339

The impact of nocturnal hemodialysis on sexual function  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background Sexual dysfunction is common in patients with end stage renal disease (ESRD) and treatment options are limited. Observational studies suggest that nocturnal hemodialysis may improve sexual function. We compared sexual activity and responses to sexual related ques...

Bass Adam; Ahmed Sofia B; Klarenbach Scott; Culleton Bruce; Hemmelgarn Brenda R; Manns Braden

340

Nocturnal colonization behavior of blowflies (Diptera: Calliphoridae) in southeastern Australia.  

UK PubMed Central (United Kingdom)

Worldwide research into nocturnal colonization by blowflies has produced many contradictory findings, prompting investigation specific to southeastern Australia. Initial experiments showed that blowfly colonization begins shortly after sunrise and continues until sunset; nocturnal colonization never occurred. Colonization peaks occurred at mid-morning, midday, and in the hours preceding sunset. In an additional experiment, wild blowflies were captured and placed in cages with colonization medium supplied nocturnally. Colonization occurred on four of five nights, and Calliphora augur (Fabricius) (Diptera: Calliphoridae) was the main species colonizing baits nocturnally. Results suggest that colonization is most likely to occur during warm weather and when flies are able to walk or crawl to bait. In particular, blowflies trapped within a confined space (such as a room or car) with warmer-than-ambient temperature may be stimulated to colonize nearby remains. Entomologists should consider these findings when estimating minimum postmortem interval under these environmental conditions.

George KA; Archer MS; Toop T

2013-01-01

 
 
 
 
341

[Renal vein infarction, a complication of paroxysmal nocturnal hemoglobinuria].  

UK PubMed Central (United Kingdom)

Paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli disease) is a rare acquired clonal disorder of the hematopoietic cell, to a somatic mutation in the phosphatidylinositol glycan (PIG-A). The most frequent clinical manifestations are hemolytic crisis and venous thrombosis of the mesenteric, hepatic, portal or cerebral territories. We report a case of paroxysmal nocturnal hemoglobinuria with renal vein thrombosis, a rare complication of this disease.

de Charry C; de Charry F; Lemoigne F; Lamboley JL; Pasquet F; Pavic M

2012-12-01

342

Roles of Melatonin in Fetal Programming in Compromised Pregnancies  

Directory of Open Access Journals (Sweden)

Full Text Available Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may affect development at a later stage. Melatonin is an oxidant scavenger that reverses oxidative stress during the prenatal period. Moreover, the role of melatonin in epigenetic modifications in the field of developmental programming has been studied extensively. Here, we describe the physiological function of melatonin in pregnancy and discuss the roles of melatonin in fetal programming in compromised pregnancies, focusing on its involvement in redox and epigenetic mechanisms.

Yu-Chieh Chen; Jiunn-Ming Sheen; Miao-Meng Tiao; You-Lin Tain; Li-Tung Huang

2013-01-01

343

Possible effects of melatonin on the kidney of hyperthyrold rats  

Directory of Open Access Journals (Sweden)

Full Text Available The aim of this study was to investigate structural changes that occur in the kidney of rats with hyperthyroidism and the effect of melatonin on these changes. The rats were divided into 3 groups; group I was designated as the control, group II was injected daily with 3,3,5-triiodo-L-thyronine (Tg) and group III was injected daily with T3+melatonin. After 40 days, tissue specimens of kidney were removed and examined by light and electron microscopy. In the proximal tubule of the Ta injected group, basement membrane thickening, microvillus irregularity and evidence of basal folding were observed. In the glomerule, basal lamina thickening, irregularity of pedicels and somewhere an increase of mesangium were recorded. Moreover, in the melatonin injected group, the findings were similar to the Ts injected group. In conclusion, it was observed that hyperthyroidism caused structural changes in the kidney and melatonin had no important effects on these changes.

Oner J.; Ozan E.; Kukner A.; Oner H.

2002-01-01

344

The effect of melatonin on bovine in vitro embryo development  

Directory of Open Access Journals (Sweden)

Full Text Available The aim of the present study was to evaluate the effect of melatonin supplementation during in vitro maturation on fertilization and embryo development in cattle. Bovine cumulus-oocyte-complexes (COC), recovered from abattoir ovaries, were matured in vitro in the absence (control) and in the presence of 10 ?M, 100 ?M and 1 mM of melatonin. Matured oocytes were fertilized in vitro with frozen-thawed sperm and cultured up to the blastocyst stage. The results of this work demonstrated that melatonin enrichment of the in vitro maturation (IVM) medium does not affect both cleavage (71.0, 72.8, 72.5 and 72.7 % in the control group and in the groups supplemented with 10 ?M, 100 ?M and 1 mM of melatonin respectively) and blastocyst rates (41.3, 33.8, 39.4 and 38.3 % respectively) in cattle.

M. P. Tsantarliotou; L. Attanasio; A. De Rosa; L. Boccia; G. Pellerano; B. Gasparrini

2010-01-01

345

Melatonin and clock genes expression in the cardiovascular system.  

UK PubMed Central (United Kingdom)

Generation of circadian oscillations is based on rhythmic expression of clock genes and subsequent post-transcriptional and post-translational modifications. In addition to the central circadian oscillator - the suprachiasmatic nucleus (SCN), peripheral oscillators have been demonstrated in many tissues, including the heart and blood vessels. Melatonin mediates cyclic lighting conditions to rhythmic endocrine signal and is able to synchronize neuronal firing in the SCN via membrane receptors. Clock gene expression is melatonin sensitive in the pars tuberalis, genes cry1 and tim1 respond to single injection while neurod1 and npas4 are influenced via long lasting mechanisms. In the rat heart, melatonin phase advanced expression of per2 and bmal1 independently from its effects on the SCN. Melatonin is an important endogenous signal able to synchronize circadian oscillations in the cardiovascular system. It may be effective especially in situations when the circadian control is weakened or organism must adapt to rapid changes in rhythmic environmental conditions.

Zeman M; Herichova I

2013-01-01

346

Melatonin and clock genes expression in the cardiovascular system.  

Science.gov (United States)

Generation of circadian oscillations is based on rhythmic expression of clock genes and subsequent post-transcriptional and post-translational modifications. In addition to the central circadian oscillator - the suprachiasmatic nucleus (SCN), peripheral oscillators have been demonstrated in many tissues, including the heart and blood vessels. Melatonin mediates cyclic lighting conditions to rhythmic endocrine signal and is able to synchronize neuronal firing in the SCN via membrane receptors. Clock gene expression is melatonin sensitive in the pars tuberalis, genes cry1 and tim1 respond to single injection while neurod1 and npas4 are influenced via long lasting mechanisms. In the rat heart, melatonin phase advanced expression of per2 and bmal1 independently from its effects on the SCN. Melatonin is an important endogenous signal able to synchronize circadian oscillations in the cardiovascular system. It may be effective especially in situations when the circadian control is weakened or organism must adapt to rapid changes in rhythmic environmental conditions. PMID:23277083

Zeman, Michal; Herichova, Iveta

2013-01-01

347

Autosomal dominant nocturnal frontal lobe epilepsy: electroclinical picture.  

UK PubMed Central (United Kingdom)

PURPOSE: Nocturnal frontal lobe epilepsy is a disorder that is difficult to diagnose because its clinical presentation is often limited to motor behavior during sleep. For this reason, a misleading diagnosis of benign nocturnal parasomnias might be possible. Recently, an inherited form of nocturnal frontal lobe epilepsy was described in some families. The aim of our work was to describe the electroclinical pattern of a sample of familial cases with this syndrome. METHODS: We observed 33 patients, all complaining of frequent nocturnal motor attacks, from eight Italian families. The family trees were strongly supportive of autosomal dominant inheritance. We performed a full-night video-polysomnographic monitoring in 12 patients. RESULTS: The recordings showed attacks in all patients, there being a widespread pattern of motor activity. Ictal and interictal EEG abnormalities were often hidden and, unless associated with a video recording, were of no use for the final diagnosis. Intraindividual stereotypy, abrupt onset, and semiology of attacks allowed differentiation from healthy subjects' nocturnal motor behavior. CONCLUSIONS: Autosomal dominant nocturnal frontal lobe epilepsy is probably not uncommon. Full-night video-polysomnographic monitoring is fundamental for the differential diagnosis of benign parasomnias and, consequently, for appropriate therapy.

Oldani A; Zucconi M; Ferini-Strambi L; Bizzozero D; Smirne S

1996-10-01

348

Oxcarbazepine in children with nocturnal frontal-lobe epilepsy.  

Science.gov (United States)

Nocturnal frontal-lobe epilepsy is characterized by paroxysmal arousals, motor seizures with dystonic or hyperkinetic features, and episodic nocturnal wanderings. Carbamazepine is effective for seizure control in some of these patients, but seizures may be refractory to multiple antiepileptic drugs. We report on eight children between ages 4-16 years with nocturnal frontal-lobe epilepsy who had a dramatic response to oxcarbazepine at standard recommended doses, some of whom were refractory to previous antiepileptic medications. Brain magnetic resonance imaging, routine electroencephalogram, and prolonged, continuous video-electroencephalogram telemetry were performed in all children. Nocturnal frontal-lobe epilepsy was diagnosed by demonstrating ictal electroencephalogram changes originating from the frontal lobes. The children were followed for response of seizures to oxcarbazepine, side effects, and routine blood tests, including serum 10-monohydroxide derivative levels. The mean oxcarbazepine dose was 30.4 mg/kg/day +/- 11.7 (mean +/- SD); the mean 10-monohydroxide level was 23.1 microg/mL +/- 8.6 (mean +/- SD). Seizures improved within 4 days of oxcarbazepine initiation in six children, whereas two children required higher doses. Their follow-up has ranged from 12 to 24 months, without seizure recurrence or serious side effects. Our patients demonstrate the efficacy of oxcarbazepine for nocturnal hyperkinetic seizures in children with nocturnal frontal-lobe epilepsy. PMID:17950420

Raju, G Praveen; Sarco, Dean P; Poduri, Annapurna; Riviello, James J; Bergin, Ann Marie R; Takeoka, Masanori

2007-11-01

349

Melatonin and mitochondrial dysfunction in the central nervous system.  

UK PubMed Central (United Kingdom)

Cell death and survival are critical events for neurodegeneration, mitochondria being increasingly seen as important determinants of both. Mitochondrial dysfunction is considered a major causative factor in Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Increased free radical generation, enhanced mitochondrial inducible nitric oxide (NO) synthase activity and NO production, and disrupted electron transport system and mitochondrial permeability transition, have all been involved in impaired mitochondrial function. Melatonin, the major secretory product of the pineal gland, is an antioxidant and an effective protector of mitochondrial bioenergetic function. Both in vitro and in vivo, melatonin was effective to prevent oxidative stress/nitrosative stress-induced mitochondrial dysfunction seen in experimental models of AD, PD and HD. These effects are seen at doses 2-3 orders of magnitude higher than those required to affect sleep and circadian rhythms, both conspicuous targets of melatonin action. Melatonin is selectively taken up by mitochondria, a function not shared by other antioxidants. A limited number of clinical studies indicate that melatonin can improve sleep and circadian rhythm disruption in PD and AD patients. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects which were employed in clinical trials in sleep-disturbed or depressed patients in doses considerably higher than those employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin in the range of 50-100mg/day are needed to assess its therapeutic validity in neurodegenerative disorders.

Cardinali DP; Pagano ES; Scacchi Bernasconi PA; Reynoso R; Scacchi P

2013-02-01

350

Differential effect of melatonin on ?-irradiated ovarian follicles in mice  

International Nuclear Information System (INIS)

The present study was performed to obtain evidence of the radioprotective function of melatonin on the ovarian follicles in ?-irradiated immature mice. Three weeks old immature mice were i.p. injected with 10 ?g and 100 ?g of melatonin dissolved in 100 ?l of alcoholic saline. Two hours after the treatments, they were whole-body irradiated with a dose of LD80(30) (8.3 Gy). The ovaries were dissected out of the animals at -2, 2, 8, and 14 h after the onset of irradiation and prepared for the histological observation using glutaraldehyde fixation. In terms of morphometry, it was observed that the number of primordial follicles of the irradiation group or the melatonin-treated group was less than that of the control. However, the number of primary, preantral, and early antral follicles was not different from that of the control group. In the group pretreated with 100 ?g of melatonin before irradiation, the percentage of normal primordial follicles was significantly higher than that of the irradiation group at any time after irradiation. The high concentration of melatonin also reduced radiation-induced degeneration of the primary follicles at 14 h after irradiation. The pretreatment of 10 ?g of melatonin had little of no effect on radiation-induced degeneration of the primordial follicles and of the primary follicles. However it gave a protective effect on the radiation-induced degeneration in the preantral and early antral follicles. From the above results, it is concluded that the exogenous melatonin has different functions depending on the follicular stages, and that the radioprotective effect of exogenous melatonin on follicular degeneration is related to its concentration. (author)

2000-01-01

351

Impact of oral melatonin on the electroretinogram cone response  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background In the eye, melatonin plays a role in promoting light sensitivity at night and modulating many aspects of circadian retinal physiology. It is also an inhibitor of retinal dopamine, which is a promoter of day vision through the cone system. Consequently, it is possible that oral melatonin (an inhibitor of retinal dopamine) taken to alleviate circadian disorders may affect cone functioning. Our aim was to assess the impact of melatonin on the cone response of the human retina using electroretinography (ERG). Methods Twelve healthy participants aged between 18 to 52 years old were submitted to a placebo-controlled, double-blind, crossover, and counterbalanced-order design. The subjects were tested on 2 sessions beginning first with a baseline ERG, followed by the administration of the placebo or melatonin condition and then, 30 min later, a second ERG to test the effect. Results Following oral melatonin administration, a significant decrease of about 8% of the cone maximal response was observed (mean 6.9 ?V ± SEM 2.0; P = 0.0065) along with a prolonged b-wave implicit time of 0.4 ms ± 0.1, 50 minutes after ingestion. Conclusion Oral melatonin appears to reach the eye through the circulation. When it is administered at a time of day when it is not usually present, melatonin appears to reduce input to retinal cones. We believe that the impact of melatonin on retinal function should be taken into consideration when used without supervision in chronic self-medication for sleep or circadian disorder treatment.

Gagné Anne-Marie; Danilenko Konstantin V; Rosolen Serge G; Hébert Marc

2009-01-01

352

Wound healing and the effect of pineal gland and melatonin  

Directory of Open Access Journals (Sweden)

Full Text Available Wound healing is a complex phenomenon that is controlled by local and general regulatory mechanisms. The aim of the paper is to analyze recently-published data devoted to the regulation of wound repair by melatonin. The effect of melatonin has been reported in different wound types healed with various mechanisms. The action of the pineal indoleamine is dependent on the used dose, time of application and target organ. Moreover, melatonin influences different phases of wound repair such as inflammation, by regulating the release of inflammatory mediators, cell proliferation and migration, by influencing angiogenesis, and the proliferation of fibroblasts, as well as the synthesis phase, by regulating collagen and glycosaminoglycan accumulation in the wounded milieu. Thus, healing of the skin wound, myocardial infarction, bone fractures and gastric ulcer is influenced by melatonin. In patients with low levels of melatonin (elderly or ?-blocker treated patients), its regulatory effects are expected to be impaired. Thus, the need for melatonin supplementation in those patients is postulated in the study. [J Exp Integr Med 2012; 2(1.000): 3-14

Jacek Drobnik

2012-01-01

353

Cardioprotective effect of melatonin against ischaemia/reperfusion damage.  

UK PubMed Central (United Kingdom)

Melatonin (N-acetyl-5-methoxytryptamine) has been shown by several workers to protect the heart against ischaemia/reperfusion damage. Melatonin, both in the picomolar and micromolar range, significantly reduces infarct size and improves functional recovery during reperfusion. This may be due to its free radical scavenging and anti-oxidant effects, while the melatonin receptor and its marked anti-adrenergic actions may also be involved. The latter is mediated by nitric oxide (NO), guanylyl cyclase and protein kinase C (PKC). Melatonin-induced cardioprotection is associated with activation of protein kinase B (PKB), extracellular signal-regulated kinase (ERK1/2) (the Reperfusion Injury Salvage Kinase (RISK) pathway) and signal activator and transducer 3 (STAT-3) (the Survivor Activating Factor Enhancement (SAFE) pathway) during reperfusion and inhibition of the mitochondrial permeability transition pore (MPTP). Very little is known about the effect of melatonin on myocardial substrate metabolism. Melatonin was demonstrated to be involved in the regulation of whole body glucose homeostasis via its effects on pancreatic insulin secretion and may thus indirectly affect myocardial substrate metabolism in a circadian manner.

Lochner A; Huisamen B; Nduhirabandi F

2013-01-01

354

Melatonin induces histone hyperacetylation in the rat brain.  

UK PubMed Central (United Kingdom)

We have reported that melatonin induces histone hyperacetylation in mouse neural stem cells, suggesting an epigenetic role for this pleiotropic hormone. To support such a role, it is necessary to demonstrate that melatonin produces similar effects in vivo. Histone acetylation, following chronic treatment with melatonin (4?g/ml in drinking water for 17 days), was examined by western blotting in selected rat brain regions. Melatonin induced significant in