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Nocturnal Elevation of Plasma Melatonin and Urinary 5-Hydroxyindoleacetic Acid in Young Men: Attempts at Modification by Brief Changes in Environmental Lighting and Sleep and by Autonomic Drugs.  

Science.gov (United States)

In order to determine if the human pattern of circulating melatonin resembles that described in lower animals, men 19 to 32 years old were exposed to a light-dark cycle with 14 hours of light per day (L:D 14:10). In whites and blacks, nocturnal (dark phas...

G. M. Vaughan R. W. Pelham S. F. Pang K. M. Wilson K. L. Sandock

1976-01-01

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Nocturnal urinary melatonin excretion is associated with non-dipper pattern in elderly hypertensives.  

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Although oral melatonin administration may enhance a nocturnal blood pressure fall, it remains unclear whether endogenous melatonin, which is present at considerably lower levels than pharmacological melatonin, is associated with the non-dipper pattern. The present cross-sectional study aimed to determine the association between urinary melatonin excretion, an index of endogenous melatonin, and the non-dipper pattern. We measured the following variables in 141 elderly hypertensives: overnight urinary melatonin excretion, ambulatory blood pressure and actigraphic physical activity. We defined a non-dipper pattern as a dipper pattern with age, diabetes, higher urinary melatonin excretion (high vs. low) and daytime activity. In a multivariate analysis after adjustment for age, diabetes and daytime activity, the odds ratio for the non-dipper pattern in the high melatonin group was significantly lower than that in the low melatonin group (odds ratio: 0.39, 95% confidence interval (CI): 0.17-0.91, P=0.03). Moreover, the mean percentage systolic blood pressure nocturnal fall, adjusted for the former covariates, was significantly higher in the high melatonin group than the low melatonin group (difference 3.5%, 95% CI: 0.0-7.0%, P=0.048). Among elderly hypertensive individuals, nocturnal urinary melatonin excretion is significantly and inversely associated with the non-dipper pattern. PMID:23575383

Obayashi, Kenji; Saeki, Keigo; Iwamoto, Junko; Okamoto, Nozomi; Tomioka, Kimiko; Nezu, Satoko; Ikada, Yoshito; Kurumatani, Norio

2013-08-01

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The flavonoid myricetin reduces nocturnal melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase.  

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Melatonin is secreted during the hours of darkness and is thought to influence the circadian and seasonal timing of a variety of physiological processes. AANAT, which is expressed in the pineal gland, retina, and various other tissues, catalyzes the conversion of serotonin to N-acetylserotonin and is the rate-limiting enzyme in the biosynthetic pathway of melatonin. The compounds that modulate the activity of AANAT can be used to treat patients with circadian rhythm disorders that are associated with specific circadian rhythm alterations, such as shift work disorder. In the present study, we screened modulators of AANAT activity from the water extracts of medicinal plants. Among the 267 tested medicinal plant extracts, Myricae Cortex (Myrica rubra), Perillae Herba (Perilla sikokiana), and Eriobotryae Folium (Eriobotrya japonica) showed potent inhibition of AANAT activity. Myricetin (5,7,3',4',5'-pentahydroxyflavonol), a main component of the Myricae Cortex, strongly inhibited the activity of AANAT and probably block the access to the substrate by docking to the catalytic residues that are important for AANAT activity. Myricetin significantly decreased the nocturnal serum melatonin levels in rats. In addition, the locomotor activity of rats treated with myricetin decreased during the nighttime and slightly increased throughout the day. These results suggest that myricetin could be used as a therapy to increase nighttime alertness by changing the circadian rhythm of serum melatonin and locomotor activity. PMID:24076393

Shin, Jae-Cheon; Jung, Hoe-Yune; Harikishore, Amaravadhi; Kwon, Oh-Deog; Yoon, Ho Sup; Kim, Kyong-Tai; Choi, Bo-Hwa

2013-10-18

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Identification of highly elevated levels of melatonin in bone marrow: its origin and significance.  

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Bone marrow is an important tissue in generation of immunocompetent and peripheral blood cells. The progenitors of hematopoietic cells in bone marrow exhibit continuous proliferation and differentiation and they are highly vulnerable to acute or chronic oxidative stress. In this investigation, highly elevated levels of the antioxidant melatonin were identified in rat bone marrow using immunocytochemistry, radioimmunoassay, high performance liquid chromatography with electrochemical detection and mass spectrometry. Night-time melatonin concentrations (expressed as pg melatonin/mg protein) in the bone marrow of rats were roughly two orders of magnitude higher than those in peripheral blood. Measurement of the activities of the two enzymes (N-acetyltransferase (NAT) and hydroxyindole-O-methoxyltransferase (HIOMT)) which synthesize melatonin from serotonin showed that bone marrow cells have measurable NAT activity, but they have very low levels of HIOMT activity (at the one time they were measured). From these studies we could not definitively determine whether melatonin was produced in bone marrow cells or elsewhere. To investigate the potential pineal origin of bone marrow melatonin, long-term (8-month) pinealectomized rats were used to ascertain if the pineal gland is the primary source of this antioxidant. The bone marrow of pinealectomized rats, however, still exhibited high levels of melatonin. These results indicate that a major portion of the bone marrow's melatonin is of extrapineal origin. Immunocytochemistry clearly showed a positive melatonin reaction intracellularly in bone marrow cells. A melatonin concentrating mechanism in these cells is suggested by these findings and this may involve a specific melatonin binding protein. Since melatonin is an endogenous free radical scavenger and an immune-enhancing agent, the high levels of melatonin in bone marrow cells may provide on-site protection to reduce oxidative damage to these highly vulnerable hematopoietic cells and may enhance the immune capacity of cells such as lymphocytes. PMID:10572942

Tan, D X; Manchester, L C; Reiter, R J; Qi, W B; Zhang, M; Weintraub, S T; Cabrera, J; Sainz, R M; Mayo, J C

1999-10-18

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Melatonin elevates apoptosis in human platelets via ROS mediated mitochondrial damage.  

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Melatonin is a pineal hormone that regulates circadian and seasonal rhythms. The chronobiotic role of melatonin corresponds with a repertoire of pharmacological properties. Besides, it has a wide range of therapeutic applications. However, recent studies have demonstrated its direct interaction with platelets: at physiological concentration it promotes platelet aggregation; on the other hand, at pharmacological doses it raises intracellular Ca(2+) leading to platelet activation, thrombus formation and cardiovascular disorders. In order to further probe its effects on platelets, the current study targeted platelet apoptosis and melatonin was found to stimulate apoptosis. The mitochondrial pathway of apoptosis was mainly investigated because of its susceptibility to oxidative stress-inducing factors including therapeutic and dietary elements. Melatonin significantly increased the generation of intracellular ROS and Ca(2+), facilitating mitochondrial membrane depolarization, cytochrome c release, caspase activation, protein phosphorylation and phosphatidylserine externalization. Further, the overall toxicity of melatonin on platelets was confirmed by MTT and lactate dehydrogenase assays. The elevated rate of platelet apoptosis has far reaching consequences including thrombocytopenia. Besides, platelets undergoing apoptosis release microparticles, which fuel thrombus formation and play a significant role in the pathophysiology of a number of diseases. In many parts of the world melatonin is an over-the-counter dietary supplement and alternative medicine. Since, melatonin displays platelet proapoptotic effect at a concentration attainable through therapeutic dosage, the present study sends a warning signal to the chronic use of melatonin as a therapeutic drug and questions its availability without a medical prescription. PMID:23880341

Girish, Kesturu Subbaiah; Paul, Manoj; Thushara, Ram Mohan; Hemshekhar, Mahadevappa; Shanmuga Sundaram, Mahalingam; Rangappa, Kanchugarakoppal Subbegowda; Kemparaju, Kempaiah

2013-08-16

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Relationship between nocturnal serotonin surge and melatonin onset in rodent pineal gland  

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Abstract Background We have recently reported dynamic circadian rhythms of serotonin (5-HT, 5-hydroxytryptamine) output in the pineal gland of rat, which precedes the onset of N-acetylserotonin (NAS) and melatonin secretion at night. The present study was aimed at investigating in detail the relationship between 5-HT onset (5HT-on) and melatonin onset (MT-on) in multiple strains of rats and comparing them with those of hamsters. Methods Animals were maintained i...

2006-01-01

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

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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. PMID:22622709

Bravo, R; Matito, S; Cubero, J; Paredes, S D; Franco, L; Rivero, M; Rodríguez, A B; Barriga, C

2013-08-01

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Melatonin.  

Science.gov (United States)

Melatonin, originally discovered as a hormone of the pineal gland, is produced by bacteria, protozoa, plants, fungi, invertebrates, and various extrapineal sites of vertebrates, including gut, skin, Harderian gland, and leukocytes. Biosynthetic pathways seem to be identical. Actions are pleiotropic, mediated by membrane and nuclear receptors, other binding sites or chemical interactions. Melatonin regulates the sleep/wake cycle, other circadian and seasonal rhythms, and acts as an immunostimulator and cytoprotective agent. Circulating melatonin is mostly 6-hydroxylated by hepatic P450 monooxygenases and excreted as 6-sulfatoxymelatonin. Pyrrole-ring cleavage is of higher importance in other tissues, especially the brain. The product, N1-acetyl-N2-formyl-5-methoxykynuramine, is formed by enzymatic, pseudoenzymatic, photocatalytic, and numerous free-radical reactions. Additional metabolites result from hydroxylation and nitrosation. The secondary metabolite, N1-acetyl-5-methoxykynuramine, supports mitochondrial function and downregulates cyclooxygenase 2. Antioxidative protection, safeguarding of mitochondrial electron flux, and in particular, neuroprotection, have been demonstrated in many experimental systems. Findings are encouraging to use melatonin as a sleep promoter and in preventing progression of neurodegenerative diseases. PMID:16219483

Hardeland, Rüdiger; Pandi-Perumal, S R; Cardinali, Daniel P

2006-03-01

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

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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 infarct...

Grossman E; Laudon M; Zisapel N

2011-01-01

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URINARY MELATONIN IN DEPRESSION  

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This report is based on a study of 12 cases of depression (8 endogenous, 4 neurotic) with a view to explore the possible association between urinary melatonin and the illness prior to and following treatment. While cases of endogenous depression had low 24 hour as well as nocturnal urinary melatonin levels, the neurotic depressives showed higher than normal levels. A rise in the 24 hour melatonin levels occurred in all cases of endogenous depression though this did not apply, to the nocturnal...

Rao, A. Venkoba; Devi, S. Parvathi; Srinivasan, V.

1983-01-01

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Variation in nocturnal urinary excretion of melatonin in a group of patients older than 55 years suffering from urogenital tract disorders.  

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Melatonin (MLT) is directly or indirectly related to cell growth (both of normal and neoplastic cells), to the immune system stimulation and to the endocrine system modulation. This controlled study was carried out to evaluate urinary excretion of MLT in patients suffering from urogenital tract disorders. Eighty-one patients affected by urogenital disorders were divided in two groups (neoplastic and non-neoplastic) and urinary excretion of MLT was evaluated. Mean diurnal (from 8 a.m. to p.m.) urinary excretion of MLT was 4.97 + 6.08 pg/12 h in non-oncologic patients and 4.82 + 6.21 pg/12 h in oncologic patients (p = 0.50). Mean nocturnal (from 8 p.m. at 8 a.m.) urinary excretion of MLT was 11.97 + 9.34 pg/12 h in non-oncologic patients while in oncologic patients it was 7.86 + 8.95 pg/12 h. Statistically significant variation in nocturnal urinary excretion of melatonin was observed in oncologic patients (p = 0.022) versus non oncologic patients. PMID:9477613

Taverna, G; Trinchieri, A; Mandressi, A; Del Nero, A; Mangiarotti, B; Antonelli, D; Chisena, S; Pisani, E

1997-12-01

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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  

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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 increase of the plasma...

Lc, Reis; Ac, Almeida; Mc, Ribeiro; Pa, Polo; El, Olivares; Ma, Medeiros; Ko, Nonaka; Lr, Castilhos

2007-01-01

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

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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.

Kline Lawrence E

2006-05-01

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Elevated production of melatonin in transgenic rice seeds expressing rice tryptophan decarboxylase.  

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A major goal of plant biotechnology is to improve the nutritional qualities of crop plants through metabolic engineering. Melatonin is a well-known bioactive molecule with an array of health-promoting properties, including potent antioxidant capability. To generate melatonin-rich rice plants, we first independently overexpressed three tryptophan decarboxylase isogenes in the rice genome. Melatonin levels were altered in the transgenic lines through overexpression of TDC1, TDC2, and TDC3; TDC3 transgenic seed (TDC3-1) had melatonin concentrations 31-fold higher than those of wild-type seeds. In TDC3 transgenic seedlings, however, only a doubling of melatonin content occurred over wild-type levels. Thus, a seed-specific accumulation of melatonin appears to occur in TDC3 transgenic lines. In addition to increased melatonin content, TDC3 transgenic lines also had enhanced levels of melatonin intermediates including 5-hydroxytryptophan, tryptamine, serotonin, and N-acetylserotonin. In contrast, expression levels of melatonin biosynthetic mRNA did not increase in TDC3 transgenic lines, indicating that increases in melatonin and its intermediates in these lines are attributable exclusively to overexpression of the TDC3 gene. PMID:24433490

Byeon, Yeong; Park, Sangkyu; Lee, Hyoung Yool; Kim, Young-Soon; Back, Kyoungwhan

2014-04-01

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Nocturnal but not short hours quotidian hemodialysis requires an elevated dialysate calcium concentration.  

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Interest in quotidian (daily) hemodialysis (HD) is growing. Some advocate short-hours high-efficiency daily HD (SDH) and others long-hours slow-flow nocturnal HD (NH) while the patient is asleep, both being used 5 to 7 d/week. The London Daily/Nocturnal Hemodialysis Study was the first attempt to obtain data of SDH and NH that may be compared with conventional thrice weekly HD (CH). This was a 4-yr observational study designed to enter and follow 40 patients: 10 receiving SDH, 10 receiving NH, and 20 receiving CH. The CH patients were cohort control subjects matched for each SDH and NH patient by age, gender, comorbidity, and original dialysis modality (in-center, home, self-care, or satellite HD). All SDH and NH treatments were at home. Data collection to December 2001 was analyzed. Then enrollment had been completed and all patients had been followed for 15 mo, eight SDH plus six NH for 18 mo, seven SDH plus six NH for 21 mo, and seven SDH and five NH for 24 mo. This report gives data on calcium and phosphorus metabolism in these patients. All patients were initially dialyzed against a 1.25-mmol/L calcium bath. Predialysis serum calcium levels became lower in NH versus SDH patients by the first month and at 9 mo were 2.67 +/- 0.25 mmol/L (M +/- SD) in SDH, 2.40 +/- 0.16 mmol/L in NH, and 2.52 +/- 0.21 mmol/L in CH (SDH versus NH, P = 0.038; SDH versus CH versus NH, NS). Predialysis phosphorus levels were better controlled by NH than by SDH or CH, and with NH, all phosphate binders were discontinued. By 12 mo, a rise in bone alkaline phosphatase was seen in NH patients (but not in SDH or CH patients), which peaked at 15 to 18 mo (NH 191 IU/L +/- 70; SDH 82 +/- 34; CH 80 +/- 36; P < 0.002) and similarly with intact parathyroid hormone (iPTH) levels (NH 159 pmol/L +/- 75; SDH 13.1 +/- 10; CH 18 +/- 18; P < 0.00001). Because of these changes, the dialysate calcium concentration was increased to 1.75 mmol/L for the NH patients. Postdialysis calcium then rose to 2.57 +/- 0.21, and alkaline phosphatase and iPTH normalized completely by 21 mo. These observations prompted mass balance studies that showed that a 1.25-mmol/L calcium dialysate was associated with a mean net calcium loss of 2.1 mmol/h of dialysis time, whereas 1.75-mmol/L calcium dialysate provides a net gain of 3.7 mmol/h. In addition, the mass balance studies showed that phosphate removal by NH (43.5 +/- 20.7 mmol) was significantly (P < 0.05) higher than by SHD (24.2 +/- 13.9 mmol) but not by CH (34.0 +/- 8.7 mmol) on a per-treatment basis. With the increased frequency of treatments provided by quotidian dialysis, the weekly phosphorus removal (261.2 +/- 124.2 mmol) by NH was significantly higher than by SDH (P = 0.014) and CH (P = 0.03). This allowed the discontinuation of P binders in the NH group, which in turn eliminated approximately 8 g elemental Ca/wk oral intake. This, together with a 4 g elemental Ca/wk dialysate loss induced by a 1.25-mmol/L Ca bath, explains the changes in Ca, alkaline phosphatase, and iPTH seen in the NH patients. The SDH patients have weekly dialysis times similar to CH and still require P binders and do not become Ca deficient using 1.25-mmol/L Ca dialysate. With NH but not SDH, an elevated dialysate Ca concentration is required. PMID:12937309

Al-Hejaili, Fayez; Kortas, Claude; Leitch, Rosemary; Heidenheim, A Paul; Clement, Laurie; Nesrallah, Gihad; Lindsay, Robert M

2003-09-01

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Melatonin Induces Follicle Maturation in Danio rerio  

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Most organisms modulate their reproductive activity responding to day length by the nocturnal release of melatonin by the pineal gland. This hormone is also responsible for synchronizing reproduction with specific external environment stimuli in order to optimize reproductive success.

Carnevali, Oliana; Gioacchini, Giorgia; Maradonna, Francesca; Olivotto, Ike; Migliarini, Beatrice

2011-01-01

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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  

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Full Text Available SciELO Brazil | Language: English 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 ent [...] re 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 significativamente 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 increase 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

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

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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  

Directory of Open Access Journals (Sweden)

Full Text Available 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 increase 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 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 significativamente 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 < 0,05. Os resultados obtidos mostraram que a administração de L-HTP reduziu a liberação noturna de melatonina, possivelmente por suscitar um aumento da síntese e liberação sináptica de serotonina na pineal. Portanto, a transmissão serotoninérgica da rafe para a pineal constituiria um mecanismo de modulação da síntese e/ou liberação de melatonina em codornas.

LC. Reis

2007-05-01

19

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

20

Nocturnal Asthma  

Science.gov (United States)

... Medical Director, Health Initiatives View full profile Nocturnal Asthma Worsening of asthma at night, or nocturnal asthma, ... Calendar Read the News View Daily Pollen Count Asthma Treatment Program At National Jewish Health, we offer ...

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

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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 centr...

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

2013-01-01

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Dietary factors and fluctuating levels of melatonin  

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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

2012-07-01

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Variability of plasma melatonin level in pony mares (Equus caballus), comparison with the hybrid : mules and with jennies (Equus asinus)  

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In long-day breeders like horses, the length of nocturnal melatonin secretion is the main messenger of photoperiod. Previous studies have shown that the nocturnal jugular melatonin concentration is lower in horses, than in mules but is unknown in donkeys. The aim of this study was to estimate the inter-animal variability of plasma melatonin concentration in domestic mares and to compare this concentration with those observed in domestic jennies and in their hybrid mules. In the...

Guillaume, Daniel; Zarazaga Garce?s, Luis A?ngel; Malpaux, Benoi?t; Chemineau, Phileppe

2006-01-01

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Melatonin Production in the Sea Star Echinaster brasiliensis (Echinodermata).  

Science.gov (United States)

The primary hormone of the vertebrate pineal gland, melatonin, has been identified broadly throughout the tree of life, in animals, plants, and fungi, supporting a deep evolutionary origin for this signaling molecule. However, some key groups have not been studied. Echinoderms, deuterostome animals, are one of these groups. Herein we study the presence of melatonin and enzymes of its pathway in the sea star Echinaster brasiliensis. We demonstrate that E. brasiliensis produces endogenous melatonin, in the gonads, under a circadian pattern with a nocturnal peak of production. We also show that the enzymes arylalkylamine N-acetyltransferase (AANAT) and tryptophan hydroxylase (TPH) are present and are probably regulating the melatonin production. PMID:24797096

Peres, Rafael; Amaral, Fernanda Gaspardo; Marques, Antonio Carlos; Neto, José Cipolla

2014-04-01

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<0.001). There were periods of episodic secretion of melanin during the diurnal waking period which seemed related to 'stress'. These data indicate that the peripheral concentrations of melatonin which occur during sleep are insufficient to prevent spontaneous LH secretion during puberty

1979-01-01

26

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

27

Npas4 Is Activated by Melatonin, and Drives the Clock Gene Cry1 in the Ovine Pars Tuberalis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Seasonal mammals integrate changes in the duration of nocturnal melatonin secretion to drive annual physiologic cycles. Melatonin receptors within the proximal pituitary region, the pars tuberalis (PT), are essential in regulating seasonal neuroendocrine responses. In the ovine PT, melatonin is known to influence acute changes in transcriptional dynamics coupled to the onset (dusk) and offset (dawn) of melatonin secretion, leading to a potential interval-timing mechanism capable of decoding c...

West, A.; Dupre?, S. M.; Yu, L.; Paton, I. R.; Miedzinska, K.; Mcneilly, A. S.; Davis, J. R. E.; Burt, D. W.; Loudon, A. S. I.

2013-01-01

28

Modeling and measuring the nocturnal drainage flow in a high-elevation, subalpine forest with complex terrain  

Science.gov (United States)

The nocturnal drainage flow of air causes significant uncertainty in ecosystem CO2, H2O, and energy budgets determined with the eddy covariance measurement approach. In this study, we examined the magnitude, nature, and dynamics of the nocturnal drainage flow in a subalpine forest ecosystem with complex terrain. We used an experimental approach involving four towers, each with vertical profiling of wind speed to measure the magnitude of drainage flows and dynamics in their occurrence. We developed an analytical drainage flow model, constrained with measurements of canopy structure and SF6 diffusion, to help us interpret the tower profile results. Model predictions were in good agreement with observed profiles of wind speed, leaf area density, and wind drag coefficient. Using theory, we showed that this one-dimensional model is reduced to the widely used exponential wind profile model under conditions where vertical leaf area density and drag coefficient are uniformly distributed. We used the model for stability analysis, which predicted the presence of a very stable layer near the height of maximum leaf area density. This stable layer acts as a flow impediment, minimizing vertical dispersion between the subcanopy air space and the atmosphere above the canopy. The prediction is consistent with the results of SF6 diffusion observations that showed minimal vertical dispersion of nighttime, subcanopy drainage flows. The stable within-canopy air layer coincided with the height of maximum wake-to-shear production ratio. We concluded that nighttime drainage flows are restricted to a relatively shallow layer of air beneath the canopy, with little vertical mixing across a relatively long horizontal fetch. Insight into the horizontal and vertical structure of the drainage flow is crucial for understanding the magnitude and dynamics of the mean advective CO2 flux that becomes significant during stable nighttime conditions and are typically missed during measurement of the turbulent CO2 flux. The model and interpretation provided in this study should lead to research strategies for the measurement of these advective fluxes and their inclusion in the overall mass balance for CO2 at this site with complex terrain. Copyright 2005 by the American Geophysical Union.

Yi, C.; Monson, R. K.; Zhai, Z.; Anderson, D. E.; Lamb, B.; Allwine, G.; Turnipseed, A. A.; Burns, S. P.

2005-01-01

29

Melatonin, hormone of darkness and more – occurrence, control mechanisms, actions and bioactive metabolites  

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In its role as a pineal hormone, melatonin is a pleiotropic, nocturnally peaking and systemically acting chronobiotic. These effects are largely explained by actions via G protein-coupled membrane receptors found in the suprachiasmatic nucleus, but also in numerous other sites. Nuclear (ROR/RZR), cytoplasmic (quinone reductase-2, calmodulin, calreticulin) and mitochondrial binding sites and radical-scavenging properties contribute to the actions of melatonin. Regulation of pineal melatonin bi...

Hardeland, R.

2008-01-01

30

Gonadotrophin-releasing hormone drives melatonin receptor down-regulation in the developing pituitary gland  

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Melatonin is produced nocturnally by the pineal gland and is a neurochemical representation of time. It regulates neuroendocrine target tissues through G-protein-coupled receptors, of which MT1 is the predominant subtype. These receptors are transiently expressed in several fetal and neonatal tissues, suggesting distinct roles for melatonin in development and that specific developmental cues define time windows for melatonin sensitivity. We have investigated MT1 gene expression in the rat pit...

Johnston, Jonathan D.; Messager, Sophie; Ebling, Francis J. P.; Williams, Lynda M.; Barrett, Perry; Hazlerigg, David G.

2003-01-01

31

Dissociation of circadian and light inhibition of melatonin release through forced desynchronization in the rat  

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Pineal melatonin release exhibits a circadian rhythm with a tight nocturnal pattern. Melatonin synthesis is regulated by the master circadian clock within the hypothalamic suprachiasmatic nucleus (SCN) and is also directly inhibited by light. The SCN is necessary for both circadian regulation and light inhibition of melatonin synthesis and thus it has been difficult to isolate these two regulatory limbs to define the output pathways by which the SCN conveys circadian and light phase informati...

Schwartz, Michael D.; Wotus, Cheryl; Liu, Tiecheng; Friesen, W. Otto; Borjigin, Jimo; Oda, Gisele A.; La Iglesia, Horacio O.

2009-01-01

32

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

Science.gov (United States)

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. PMID:9406024

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

1997-12-01

33

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

Science.gov (United States)

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. PMID:24129182

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

2013-01-01

34

Melatonin responses to clonidine and yohimbine challenges.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Melatonin (MT) release from the pineal gland has been used as a marker for central noradrenergic function in major depression. Norepinephrine acts at both alpha and beta adrenergic receptors on the pinealocyte membrane to mediate nocturnal MT release, but in humans the contribution of each receptor class is unclear. In order to explore the effect of alpha 2 receptors on MT release, 10 female subjects were given oral challenges, in separate placebo-controlled trials, of either 10.8 mg of yohim...

Kennedy, S. H.; Gnam, W.; Ralevski, E.; Brown, G. M.

1995-01-01

35

Nocturnal enuresis  

Directory of Open Access Journals (Sweden)

Full Text Available Nocturnal enuresis is one of the most common urinary problems in children and is observed in about 15-20 percent of children 5 years of age. Nocturnal enuresis resolves at a rate of 15% per year, so 99% of children are dry by the age of fifteen years. Enuresis can be defined as repetative bed wetting while sleeping. Enuresis in children without any other lower urinary tract (LUT symptoms -excluding nocturia- and without a history of bladder dysfunction is defined as monosymptomatic enuresis. Most of the enuretic children belong to this group. A bladder dysfunction must be kept in mind in an enuretic child having day time symptoms. Behavioral treatment approaches, alarm treatment and pharmacological treatment are the most frequently used approaches for treatment. In all treatment modalities and especially in alarm treatment, the motivation and active involvement of the family and the child are very important. (Turk Arch Ped 2012; 47: 78-83

R. Yavuz Akman

2012-06-01

36

Melatonin Metabolism in the Central Nervous System  

Science.gov (United States)

The metabolism of melatonin in the central nervous system is of interest for several reasons. Melatonin enters the brain either via the pineal recess or by uptake from the blood. It has been assumed to be also formed in some brain areas. Neuroprotection by melatonin has been demonstrated in numerous model systems, and various attempts have been undertaken to counteract neurodegeneration by melatonin treatment. Several concurrent pathways lead to different products. Cytochrome P450 subforms have been demonstrated in the brain. They either demethylate melatonin to N-acetylserotonin, or produce 6-hydroxymelatonin, which is mostly sulfated already in the CNS. Melatonin is deacetylated, at least in pineal gland and retina, to 5-methoxytryptamine. N1-acetyl-N2-formyl-5-methoxykynuramine is formed by pyrrole-ring cleavage, by myeloperoxidase, indoleamine 2,3-dioxygenase and various non-enzymatic oxidants. Its product, N1-acetyl-5-methoxykynuramine, is of interest as a scavenger of reactive oxygen and nitrogen species, mitochondrial modulator, downregulator of cyclooxygenase-2, inhibitor of cyclooxygenase, neuronal and inducible NO synthases. Contrary to other nitrosated aromates, the nitrosated kynuramine metabolite, 3-acetamidomethyl-6-methoxycinnolinone, does not re-donate NO. Various other products are formed from melatonin and its metabolites by interaction with reactive oxygen and nitrogen species. The relative contribution of the various pathways to melatonin catabolism seems to be influenced by microglia activation, oxidative stress and brain levels of melatonin, which may be strongly changed in experiments on neuroprotection. Many of the melatonin metabolites, which may appear in elevated concentrations after melatonin administration, possess biological or pharmacological properties, including N-acetylserotonin, 5-methoxytryptamine and some of its derivatives, and especially the 5-methoxylated kynuramines.

Hardeland, Rudiger

2010-01-01

37

Melatonin metabolism in the central nervous system.  

Science.gov (United States)

The metabolism of melatonin in the central nervous system is of interest for several reasons. Melatonin enters the brain either via the pineal recess or by uptake from the blood. It has been assumed to be also formed in some brain areas. Neuroprotection by melatonin has been demonstrated in numerous model systems, and various attempts have been undertaken to counteract neurodegeneration by melatonin treatment. Several concurrent pathways lead to different products. Cytochrome P(450) subforms have been demonstrated in the brain. They either demethylate melatonin to N-acetylserotonin, or produce 6-hydroxymelatonin, which is mostly sulfated already in the CNS. Melatonin is deacetylated, at least in pineal gland and retina, to 5-methoxytryptamine. N(1)-acetyl-N(2)-formyl-5-methoxykynuramine is formed by pyrrole-ring cleavage, by myeloperoxidase, indoleamine 2,3-dioxygenase and various non-enzymatic oxidants. Its product, N(1)-acetyl-5-methoxykynuramine, is of interest as a scavenger of reactive oxygen and nitrogen species, mitochondrial modulator, downregulator of cyclooxygenase-2, inhibitor of cyclooxygenase, neuronal and inducible NO synthases. Contrary to other nitrosated aromates, the nitrosated kynuramine metabolite, 3-acetamidomethyl-6-methoxycinnolinone, does not re-donate NO. Various other products are formed from melatonin and its metabolites by interaction with reactive oxygen and nitrogen species. The relative contribution of the various pathways to melatonin catabolism seems to be influenced by microglia activation, oxidative stress and brain levels of melatonin, which may be strongly changed in experiments on neuroprotection. Many of the melatonin metabolites, which may appear in elevated concentrations after melatonin administration, possess biological or pharmacological properties, including N-acetylserotonin, 5-methoxytryptamine and some of its derivatives, and especially the 5-methoxylated kynuramines. PMID:21358968

Hardeland, Rüdiger

2010-09-01

38

Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

1. Acute administration of the specific serotonin uptake inhibitor, fluvoxamine (100 mg at 16.00 h), markedly increased nocturnal plasma melatonin concentrations, with high levels extending into the morning hours. 2. Acute administration of the noradrenaline uptake inhibitor, desipramine (DMI) (100 mg at 16.00 h), increased evening plasma melatonin concentrations. 3. Both drug treatments increased the duration of melatonin secretion, fluvoxamine significantly delaying the offset time and DMI ...

Skene, D. J.; Bojkowski, C. J.; Arendt, J.

1994-01-01

39

Increased delta aminolevulinic acid and decreased pineal melatonin production. A common event in acute porphyria studies in the rat.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Tryptophan (TRP) is the precursor of melatonin, the primary secretory product of the pineal gland. Hepatic heme deficiency decreases the activity of liver tryptophan pyrrolase, leading to increased plasma TRP and serotonin. As a paradox, patients with attacks of acute intermittent porphyria (AIP), exhibit low nocturnal plasma melatonin levels. This study using a rat experimental model was designed to produce a pattern of TRP and melatonin production similar to that in AIP patients. Pineal mel...

Puy, H.; Deybach, J. C.; Bogdan, A.; Callebert, J.; Baumgartner, M.; Voisin, P.; Nordmann, Y.; Touitou, Y.

1996-01-01

40

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

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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 attribu...

Dp, Cardinali; Mf, Vidal; Vigo DE

2012-01-01

 
 
 
 
41

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

Science.gov (United States)

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 (40 mg/kg/day) were compared with those of the agonist melatonin (40 mg/kg/day), the inverse 5-HT2C antagonist S32006 (10mg/kg/day), and the SSRI fluoxetine (15 mg/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. PMID:23978391

Schmelting, Barthel; Corbach-Söhle, Silke; Kohlhause, Susan; Schlumbohm, Christina; Flügge, Gabriele; Fuchs, Eberhard

2014-03-01

42

The effects of nocturnal life on endocrine circadian patterns in healthy adults.  

Science.gov (United States)

We observed the 24-hour patterns of endocrine in medical students who lived either a diurnal life or nocturnal life. Nocturnal life was designed by skipping their breakfast but consuming much (>50% of their daily food intake) in the evening and at night with the sleep from 0130 h to 0830 h the next morning. After 3 weeks in the experimental life, the 24-hour plasma concentrations of melatonin, leptin, glucose and insulin were measured every three hours. Both plasma melatonin and leptin showed peaks at 0300 h in the diurnal lifestyle group, and the night peaks decreased in the nocturnal lifestyle group. The changes in the patterns of melatonin and leptin were highly consistent with that of night-eating syndrome (NES). Plasma glucose increased after all meals in both groups. Its concentration maintained a high level in the nocturnal lifestyle group between midnight and early morning while insulin secretion decreased markedly during this period. Furthermore, the strong association between glucose and insulin in the diurnal lifestyle group after meals was damaged in the nocturnal lifestyle group. It was suggested that nocturnal life leads to the impairment of insulin response to glucose. Taking these results together, nocturnal life is likely to be one of the risk factors to health of modern people, including NES, obesity and diabetes. PMID:12954455

Qin, Li-Qiang; Li, Jue; Wang, Yuan; Wang, Jing; Xu, Jia-Ying; Kaneko, Takashi

2003-09-26

43

Melatonin in cardiovascular disease.  

Science.gov (United States)

This editorial refers to "Cardiovascular effects of melatonin receptor agonists". The hormone melatonin is synthesized primarily in the pineal gland, retina, several peripheral tissues and organs. In the circulation, the concentration of melatonin follows a circadian rhythm, with high levels at night providing timing cues to target tissues endowed with melatonin receptors. Based on the data available, the last 18 years indicate that melatonin influences multiple factors of the cardiovascular function. Multiple evidences reveal that the rhythmicity of melatonin has a crucial role in a variety of cardiovascular pathophysiological processes including anti-inflammatory, antioxidant, anti-hypertensive and possibly as an antilipidemic function. Melatonin receptors receive and transduce melatonin's message to influence daily and seasonal rhythms of physiology. The melatonin message is translated through the interaction between the melatonin receptors (MT1 and MT2) and its coupling to G proteins, which are potential therapeutic targets in disorders ranging from insomnia, circadian sleep disorders, depression and cardiovascular diseases. Based on the data available, melatonin seems to have cardioprotective properties via its direct free radical scavenger activity. Melatonin efficiently interacts with several reactive oxygen species (receptor-independent actions). Collectively, these protective actions of melatonin may have potential clinical applicability for individuals with cardiovascular disease. PMID:22916801

Dominguez-Rodriguez, Alberto

2012-11-01

44

Melatonin and melatonergic drugs on sleep: possible mechanisms of action.  

Science.gov (United States)

Pineal melatonin is synthesized and secreted in close association with the light/dark cycle. The temporal relationship between the nocturnal rise in melatonin secretion and the "opening of the sleep gate" (i.e., the increase in sleep propensity at the beginning of the night), coupled with the sleep-promoting effects of exogenous melatonin, suggest that melatonin is involved in the regulation of sleep. The sleep-promoting and sleep/wake rhythm regulating effects of melatonin are attributed to its action on MT(1) and MT(2) melatonin receptors present in the suprachiasmatic nucleus (SCN) of the hypothalamus. Animal experiments carried out in rats, cats, and monkeys have revealed that melatonin has the ability to reduce sleep onset time and increase sleep duration. However, clinical studies reveal inconsistent findings, with some of them reporting beneficial effects of melatonin on sleep, whereas in others only marginal effects are documented. Recently a prolonged-release 2-mg melatonin preparation (Circadin(TM)) was approved by the European Medicines Agency as a monotherapy for the short-term treatment of primary insomnia in patients who are aged 55 or above. Several melatonin derivatives have been shown to increase nonrapid eye movement (NREM) in rats and are of potential pharmacological importance. So far only one of these melatonin derivatives, ramelteon, has received approval from the U.S. Food and Drug Administration to be used as a sleep promoter. Ramelteon is a novel MT(1) and MT(2) melatonergic agonist that has specific effects on melatonin receptors in the SCN and is effective in promoting sleep in experimental animals such as cats and monkeys. In clinical trials, ramelteon reduced sleep onset latency and promoted sleep in patients with chronic insomnia, including an older adult population. Both melatonin and ramelteon promote sleep by regulating the sleep/wake rhythm through their actions on melatonin receptors in the SCN, a unique mechanism of action not shared by any other hypnotics. Moreover, unlike benzodiazepines, ramelteon causes neither withdrawal effects nor dependence. Agomelatine, another novel melatonergic antidepressant in its final phase of approval for clinical use, has been shown to improve sleep in depressed patients and to have an antidepressant efficacy that is partially attributed to its effects on sleep-regulating mechanisms. PMID:19326288

Srinivasan, Venkataramanujan; Pandi-Perumal, Seithikurippu R; Trahkt, Ilya; Spence, D Warren; Poeggeler, Burkhard; Hardeland, Ruediger; Cardinali, Daniel P

2009-01-01

45

The effects of skin pressure by clothing on circadian rhythms of core temperature and salivary melatonin.  

Science.gov (United States)

The present experiment investigated the effects of skin pressure by foundation garments (girdle and brassiere) on the circadian rhythms of core temperature and salivary melatonin. Ten healthy females (18-23 years) maintained regular sleep-wake cycles for a week prior to participation in the experiment. The experiments were performed from June to August 1999 using a bioclimatic chamber controlled at 26.5 degrees C +/- 0.2 degrees C and 62% +/- 3% RH. Ambient light intensity was controlled at 500 lux from 07:30 to 17:30, 100 lux from 17:30 to 19:30, 20 lux from 19:30 to 23:30; there was total darkness from 23:30 to 07:30. The experiment lasted for 58h over three nights. The participants arose at 07:30 on the first full day and retired at 23:30, adhering to a set schedule for 24h, but without wearing foundation garments. For the final 24h of the second full day, the subjects wore foundation garments. Rectal and leg skin temperatures were measured continuously throughout the experiment. Saliva and urine were collected every 4h for the analysis of melatonin and catecholamines, respectively. Skin pressure applied by the foundation garments was in the range 11-17 gf/cm2 at the regions of the abdomen, hip, chest, and back. The main results were as follows: (1) Rectal temperatures were significantly higher throughout the day and night when wearing foundation garments. (2) The nocturnal level of salivary melatonin measured at 03:30 was 115.2 +/- 40.4 pg/mL (mean +/- SEM, N = 10) without and 51.3 +/- 18.4 pg/mL (mean +/- SEM, N = 10) with foundation garments. (3) Mean urinary noradrenaline excretion was significantly lower throughout the day and night when wearing foundation garments (p < .05), but mean urinary adrenaline excretion was not different. The results suggest that skin pressure by clothing could markedly suppress the nocturnal elevation of salivary melatonin, resulting in an increase of rectal temperature. PMID:11128295

Lee, Y A; Hyun, K J; Tokura, H

2000-11-01

46

A Melatonin-Independent Seasonal Timer Induces Neuroendocrine Refractoriness to Short Day Lengths  

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The duration of nocturnal pineal melatonin secretion transduces effects of day length (DL) on the neuroendocrine axis of photoperiodic rodents. Long DLs support reproduction, and short DLs induce testicular regression, followed several months later by spontaneous recrudescence; gonadal regrowth is thought to reflect development of tissue refractoriness to melatonin. In most photoperiodic species, pinealectomy does not diminish reproductive competence in long DLs. Turkish hamsters (Mesocricetu...

Butler, Matthew P.; Turner, Kevin W.; Zucker, Irving

2008-01-01

47

Melatonin and the skeleton  

DEFF Research Database (Denmark)

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-κB 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 μCT scans. Furthermore, in pinealectomized animals, bone mineral density (BMD) is significantly decreasedcompared 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, A K; Sikjaer, T

2013-01-01

48

Adrenaline and nocturnal asthma.  

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OBJECTIVE--To determine whether the nocturnal fall in plasma adrenaline is a cause of nocturnal asthma. DESIGN--Double blind placebo controlled cross-over study. In the first experiment the nocturnal fall in plasma adrenaline at 4 am was corrected in 10 asthmatic subjects with an infusion of adrenaline after parasympathetic blockade with 30 micrograms/kg intravenous atropine. In the second experiment 11 asthmatic subjects showing similar variations in peak expiratory flow rate had the nocturn...

Morrison, J. F.; Teale, C.; Pearson, S. B.; Marshall, P.; Dwyer, N. M.; Jones, S.; Dean, H. G.

1990-01-01

49

Circadian profile of serum melatonin in Cushing's disease and acromegaly.  

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We evaluated the circadian profiles of serum melatonin (MT) and cortisol in 6 patients with Cushing's disease while those of serum MT and GH were evaluated in 8 patients with acromegaly. The control group consisted of 15 healthy subjects in whom MT, cortisol and GH were determined. The presence of a circadian rhythmicity was validated by the cosinor method, while the diurnal and nocturnal amount of MT secretion were expressed in terms of area under the curve. Gross alterations of MT rhythm we...

Paccotti, Piero; Angeli, Alberto; Terzolo, Massimo

1990-01-01

50

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

Vigo DE

2012-10-01

51

Season-dependent postembryonic maturation of the diurnal rhythm of melatonin biosynthesis in the chicken pineal gland.  

Science.gov (United States)

Previously, we have demonstrated that the timing of the nocturnal peak of activity of the pineal arylalkylamine-N-acetyltransferase - a key enzyme in the melatonin biosynthesis pathway - in 3-wk-old chickens kept from the day of hatch under controlled laboratory conditions (L:D 12:12) varies depending on the season of hatch (summer vs. winter). The present study was undertaken to answer the following questions: (1) are season-related differences seen in the level of transcription of genes encoding enzymes of the melatonin biosynthesis pathway? (2) Does the pineal content of the main precursor (serotonin) and the final product (melatonin) exhibit age- and season-related changes? (3) At which step in postembryonic development are these season-related variations in pineal gland function most pronounced? Male Hy-line chickens hatched in the summer or winter, from eggs laid by hens held on L:D 16:8, were kept from the day of hatch under L:D 12:12 conditions. At the age of 2, 9, or 16 d, chickens were sacrificed every 2 h over a 24-h period and their pineal glands, isolated under dim red light, were processed for the measurement of (i) the level of Aanat and Asmt (acetylserotonin O-methyltransferase) mRNAs encoding the two last enzymes involved in melatonin biosynthesis, (ii) the activity of these enzymes, and (iii) the pineal content of serotonin and melatonin. Circadian rhythmicity of all the measured parameters was evaluated by the cosinor method. The levels of Aanat mRNA, AANAT enzymatic activity, and the pineal melatonin content changed during postembryonic development in a manner that was dependent on the season of hatch. Furthermore, the diurnal profile of Asmt mRNA was elevated during the light phase. In "winter" birds, the pattern and amplitude of the diurnal rhythm of accumulation of this transcript did not change with age, while in "summer" birds it increased in an age-related way. In contrast, the enzymatic activity of hydroxyindole-O-methyltransferase (HIOMT; encoded by the Asmt gene) did not change rhythmically, although it increased with age in a season-related way. In "winter" chickens, the pineal serotonin content was low, regardless of age, and did not change rhythmically, whereas in "summer" individuals the serotonin rhythm was already well established by day 2, with the amplitude increasing with age. These results confirm the existence of a "seasonal memory" operating within the chicken pineal gland, although the mechanism(s) underlying this phenomenon have yet to be characterized. PMID:23003334

Piesiewicz, A; Kedzierska, U; Podobas, E; Adamska, I; Zuzewicz, K; Majewski, P M

2012-11-01

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Interactions of the pineal hormone melatonin with oxygen-centered free radicals: a brief review.  

Science.gov (United States)

Melatonin,N-acetyl-5-methoxytryptamine, is a hormonal product of the pineal gland. Its synthesis is higher at night than during the day in all vertebrates including man. Once melatonin is produced in the pineal gland it is quickly released into the vascular system. The rapid release of melatonin is generally believed to relate to its high lipophilicity which allows it to readily pass through the membrane of the pinealocytes and the endothelial cells which line the capillaries. The result of the nocturnal synthesis and secretion of melatonin is high blood levels at night. Also because of its highly lipophilic nature, melatonin from the blood readily escapes into every other bodily fluid and all cells in the body. Until recently it was generally thought that melatonin's action in the organism depended on its exclusive interaction with specific receptors on cells located in discrete locations. Certainly, the interactions of melatonin with these membrane-bound receptors are believed to mediate the endocrine and circadian rhythm effects of melatonin. It was recently discovered, however, that melatonin's primary action may not depend on the previously described membrane receptors. We have found that melatonin is a very potent hydroxyl radical scavenger; free radicals and the hydroxyl radical in particular, because of its very high reactivity, can be extremely damaging to macromolecules in cells. Compared to glutathione and mannitol, two well known free radical scavengers, melatonin is a more powerful scavenger and affords protection of molecules, especially DNA, from oxidative damage. Melatonin's extremely high diffusibility is important for its scavenging action because this feature allows it to enter all cells and every subcellular compartment. Whereas the free radical quenching activity of melatonin does not require a receptor, we also have evidence that it may be bound in the nucleus thereby providing on-site protection to DNA. Besides scavenging the highly toxic hydroxyl radical, melatonin also stimulates glutathione peroxidase activity which metabolizes the precursor of the hydroxyl radical, hydrogen peroxide, to water. Thus, melatonin has at least two means to protect the cell from oxidative damage, i.e., it breaks down hydrogen peroxide to harmless water and, in the event any hydroxyl radicals are formed, melatonin scavenges them. Melatonin may be the premier molecule to protect the organism from oxidative damage. PMID:8136717

Reiter, R J

1993-11-01

53

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<0.01. A significant positive correlation could link serum melatonin levels to disease activity scores and ESR (r = 0.91, p<0.001 and r = 0.55, p<0.01, respectively. No significant correlation was found between melatonin and either Larsen or JAFAR scores (r = 0.19, r = 0.15, respectively. According to melatonin levels, there were 2 groups of patients: Group I with elevated melatonin level (more than 11 pg mL-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 (p<0.05, higher disease activity scores (p<0.01 and Larsen scores (p<0.05, than the group of patients with normal serum melatonin. The results of GAFAR scores were comparable between the two groups (p>0.05. 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

2007-01-01

54

Melatonin in Alzheimer's disease.  

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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. PMID:23857055

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

2013-01-01

55

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.  

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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. PMID:24102635

Lei, Qiong; Wang, Lin; Tan, Dun-Xian; Zhao, Yu; Zheng, Xiao-Dong; Chen, Hao; Li, Qing-Tian; Zuo, Bi-Xiao; Kong, Jin

2013-11-01

56

Blood glucose and nocturnal blood pressure in African and caucasian men: the SABPA study  

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To investigate the relationship between nocturnal blood pressure and chronically elevated blood glucose to determine if these elevated blood glucose concentrations contribute to a non-dipping blood pressure, especially in high-risk groups such as Africans.

Lammertyn, Leandi; Schutte, Aletta Elisabeth; Schutte, Rudolph

2011-01-01

57

Isolation of Cryptococcus neoformans in Antwerp Zoo's nocturnal house  

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Cryptococcosis was diagnosed postmortem in a striped grass mouse (Lemniscomys barbarus) housed in the nocturnal department of Antwerp Zoo. Eight of the remaining mice in the cage were captured. Cryptococcus neoformans was isolated from the lung of one animal. Two mice had an elevated serum cryptococcal antigen titre. On examination of the pooled faecal samples collected from 17 animal species housed in 23 cages of the nocturnal department, the pathogenic yeast was isolated from the faeces of ...

Bauwens, L.; Vercammen, F.; Wuytack, C.; Looveren, K.; Swinne, D.

2004-01-01

58

Role of Melatonin in Schizophrenia  

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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

2013-04-01

59

Melatonin Receptor Genes in Vertebrates  

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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 m...

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

2013-01-01

60

Melatonin Therapy Prevents Programmed Hypertension and Nitric Oxide Deficiency in Offspring Exposed to Maternal Caloric Restriction  

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Nitric oxide (NO) deficiency is involved in the development of hypertension, a condition that can originate early in life. We examined whether NO deficiency contributed to programmed hypertension in offspring from mothers with calorie-restricted diets and whether melatonin therapy prevented this process. We examined 3-month-old male rat offspring from four maternal groups: untreated controls, 50% calorie-restricted (CR) rats, controls treated with melatonin (0.01% in drinking water), and CR rats treated with melatonin (CR + M). The effect of melatonin on nephrogenesis was analyzed using next-generation sequencing. The CR group developed hypertension associated with elevated plasma asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor), decreased L-arginine, decreased L-arginine-to-ADMA ratio (AAR), and decreased renal NO production. Maternal melatonin treatment prevented these effects. Melatonin prevented CR-induced renin and prorenin receptor expression. Renal angiotensin-converting enzyme 2 protein levels in the M and CR + M groups were also significantly increased by melatonin therapy. Maternal melatonin therapy had long-term epigenetic effects on global gene expression in the kidneys of offspring. Conclusively, we attributed these protective effects of melatonin on CR-induced programmed hypertension to the reduction of plasma ADMA, restoration of plasma AAR, increase of renal NO level, alteration of renin-angiotensin system, and epigenetic changes in numerous genes.

Huang, Li-Tung; Hsu, Chien-Ning; Lee, Chien-Te

2014-01-01

 
 
 
 
61

Nocturnal panic attacks  

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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.

2002-01-01

62

The effect of acute exogenous melatonin on P50 suppression in healthy male volunteers stratified for low and high gating levels  

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Sensory gating is frequently found to be disturbed in patients with schizophrenia. In addition, a disruption of the circadian rhythm together with a low nocturnal melatonin output is regularly found in these patients. Since there is some evidence that a brief period of sleep normalizes sensory gating in schizophrenia patients, it is conceivable that their disrupted melatonin level may contribute to the deficits in P50 suppression. In this initial study, the effects of acutely administered melatonin on sensory gating in healthy subjects were investigated. In a double-blind placebo-controlled crossover design, 21 healthy male volunteers were administered melatonin (4 mg) or placebo, after which they were tested in a P50 suppression paradigm. In the group as a whole, melatonin did not affect P50 suppression. However, melatonin increased the P50 ratio in the individuals with high baseline suppression. In contrast to what was expected, melatonin reduced P50 suppression, albeit only in those individuals with high baseline suppression. The current study does not support a beneficial effect of acute exposure to exogenous melatonin on sensory gating. Future research should focus on melatonin's ability to restore basic sleep rhythms and its subsequent effects on sensory gating, in both healthy volunteers and patients with schizophrenia.

Ucar, Ebru; Lehtinen, Emilia K

2012-01-01

63

The effect of acute exogenous melatonin on P50 suppression in healthy male volunteers stratified for low and high gating levels.  

Science.gov (United States)

Sensory gating is frequently found to be disturbed in patients with schizophrenia. In addition, a disruption of the circadian rhythm together with a low nocturnal melatonin output is regularly found in these patients. Since there is some evidence that a brief period of sleep normalizes sensory gating in schizophrenia patients, it is conceivable that their disrupted melatonin level may contribute to the deficits in P50 suppression. In this initial study, the effects of acutely administered melatonin on sensory gating in healthy subjects were investigated. In a double-blind placebo-controlled crossover design, 21 healthy male volunteers were administered melatonin (4 mg) or placebo, after which they were tested in a P50 suppression paradigm. In the group as a whole, melatonin did not affect P50 suppression. However, melatonin increased the P50 ratio in the individuals with high baseline suppression. In contrast to what was expected, melatonin reduced P50 suppression, albeit only in those individuals with high baseline suppression. The current study does not support a beneficial effect of acute exposure to exogenous melatonin on sensory gating. Future research should focus on melatonin's ability to restore basic sleep rhythms and its subsequent effects on sensory gating, in both healthy volunteers and patients with schizophrenia. PMID:22331175

Ucar, Ebru; Lehtinen, Emilia K; Glenthøj, Birte Y; Oranje, Bob

2012-08-01

64

Stress inhibition of melatonin synthesis in the pineal organ of rainbow trout (Oncorhynchus mykiss) is mediated by cortisol.  

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Cortisol has been suggested to mediate the effect of stress on pineal melatonin synthesis in fish. Therefore, we aimed to determine how pineal melatonin synthesis is affected by exposing rainbow trout to different stressors, such as hypoxia, chasing and high stocking density. In addition, to test the hypothesis that cortisol is a mediator of such stress-induced effects, a set of animals were intraperitoneally implanted with coconut oil alone or containing cortisol (50 mg kg(-1) body mass) and sampled 5 or 48 h post-injection at midday and midnight. The specificity of such effect was also assessed in cultured pineal organs exposed to cortisol alone or with the general glucocorticoid receptor antagonist, mifepristone (RU486). Stress (in particular chasing and high stocking density) affected the patterns of plasma and pineal organ melatonin content during both day and night, with the greatest reduction occurring at night. The decrease in nocturnal melatonin levels in the pineal organ of stressed fish was accompanied by increased serotonin content and decreased AANAT2 enzymatic activity and mRNA abundance. Similar effects on pineal melatonin synthesis to those elicited by stress were observed in trout implanted with cortisol for either 5 or 48 h. These data indicate that stress negatively influences the synthesis of melatonin in the pineal organ, thus attenuating the day-night variations of circulating melatonin. The effect might be mediated by increased cortisol, which binds to trout pineal organ-specific glucocorticoid receptors to modulate melatonin rhythms. Our results in cultured pineal organs support this. Considering the role of melatonin in the synchronization of daily and annual rhythms, the results suggest that stress-induced alterations in melatonin synthesis could affect the availability of fish to integrate rhythmic environmental information. PMID:24436377

López-Patiño, Marcos A; Gesto, Manuel; Conde-Sieira, Marta; Soengas, José L; Míguez, Jesús M

2014-04-15

65

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english 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. T [...] his 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.

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

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Melatonin Inhibits Endoplasmic Reticulum Stress and Epithelial-Mesenchymal Transition during Bleomycin-Induced Pulmonary Fibrosis in Mice.  

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Several reports indicate that melatonin alleviates bleomycin (BLM)-induced pulmonary fibrosis in rodent animals. Nevertheless, the exact mechanism remains obscure. The present study investigated the effects of melatonin on endoplasmic reticulum (ER) stress and epithelial-mesenchymal transition (EMT) during BLM-induced lung fibrosis. For the induction of pulmonary fibrosis, mice were intratracheally injected with a single dose of BLM (5.0 mg/kg). Some mice were intraperitoneally injected with melatonin (5 mg/kg) daily for a period of 3 wk. Twenty-one days after BLM injection, lung fibrosis was evaluated. As expected, melatonin significantly alleviated BLM-induced pulmonary fibrosis, as evidenced by Sirius red staining. Moreover, melatonin significantly attenuated BLM-induced EMT to myofibroblasts, as determined by its repression of ?-SMA expression. Further analysis showed that melatonin markedly attenuated BLM-induced GRP78 up-regulation and elevation of the cleaved ATF6 in the lungs. Moreover, melatonin obviously attenuated BLM-induced activation of pulmonary eIF2?, a downstream target of the PERK pathway. Finally, melatonin repressed BLM-induced pulmonary IRE1? phosphorylation. Correspondingly, melatonin inhibited BLM-induced activation of XBP-1 and JNK, two downstream targets of the IRE1 pathway. Taken together, these results suggest that melatonin alleviates ER stress and ER stress-mediated EMT in the process of BLM-induced pulmonary fibrosis. PMID:24818755

Zhao, Hui; Wu, Qing-Qing; Cao, Lin-Feng; Qing, Hou-Ying; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Liu, Rong-Ru; Xu, De-Xiang

2014-01-01

67

Role of Melatonin in Schizophrenia  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 a...

Morera-fumero, Armando L.; Pedro Abreu-Gonzalez

2013-01-01

68

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

2013-01-01

69

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.

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

2013-01-01

70

Nocturnal cough in asthma.  

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The timing of nocturnal cough and its association with change in ambient temperature was documented in 11 asthmatic children, median age 5.1 years, while they were receiving continuous prophylaxis. Studies were performed in their homes on three nights. A voice activated system with electronic time signal recorded coughing. Ambient temperature was recorded every five minutes throughout the night on a Grant Squirrel data logger. Ten children coughed on 27 nights with a median of six bouts of co...

Thomson, A. H.; Pratt, C.; Simpson, H.

1987-01-01

71

Chronic fluoxetine treatment increases daytime melatonin synthesis in the rodent  

Directory of Open Access Journals (Sweden)

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

2009-09-01

72

Effects of photoperiod on pineal melatonin in the marsh rice rat (Oryzomys palustris).  

Science.gov (United States)

Pineal melatonin content was examined under four different photoperiods (10L:14D, 12L:12D, 14L:10D, and 16L:8D) in adult female rice rats (Experiment 1). Pineal melatonin was basal during the light and increased beginning 1 hr after lights off. Within 2 hr after lights off, melatonin increased to levels that were maintained throughout the dark period. In all but one photoperiod (10L:14D), melatonin remained elevated prior to light onset and decreased markedly within one hour after lights on. In addition, the duration of pineal melatonin was inversely related to the length of the photoperiod. In Experiment 2, the time course of pineal melatonin content on 16L:8D was examined every 20 min during the first hour after lights off and the first hour after lights on. Melatonin content increased gradually during the first hour and decreased markedly within 20 min after lights on. These data show that pineal melatonin in female rice rats is regulated by photoperiod. PMID:7562372

Edmonds, K E; Rollag, M D; Stetson, M H

1995-04-01

73

Genetics Home Reference: Paroxysmal nocturnal hemoglobinuria  

Science.gov (United States)

... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Paroxysmal nocturnal hemoglobinuria On this page: Description Genetic changes ... names Glossary definitions Reviewed May 2007 What is paroxysmal nocturnal hemoglobinuria? Paroxysmal nocturnal hemoglobinuria is an acquired ...

74

Emergence of naturally occurring melatonin isomers and their proposed nomenclature.  

Science.gov (United States)

Melatonin was considered to be the sole member of this natural family. The emergence of naturally occurring melatonin isomers (MIs) has opened an exciting new research area. Currently, several MIs have been identified in wine, and these molecules are believed to be synthesized by either yeasts or bacteria. A tentative nomenclature for the MIs is proposed in this article. It will be important to explore whether all organisms have the capacity to synthesize MIs, especially under the conditions of environmental stress. These isomers probably share many of the biological functions of melatonin, but their activities seem to exceed those of melatonin. On basis of the limited available information, it seems that MIs differ in their biosynthetic pathways from melatonin. Especially in those compounds in which the aliphatic side chain is not attached to ring atom 3, the starting material may not be tryptophan. Also, the metabolic pathways of MIs remain unknown. This, therefore, is another promising area of research to explore. It is our hypothesis that MIs would increase the performance of yeasts and probiotic bacteria during the processes of fermentation. Therefore, yeasts producing elevated levels of these isomers might have a superior alcohol tolerance and be able to produce higher levels of alcohol. This can be tested by comparing existing yeast strains differing in alcohol tolerance. Selection for MIs may become a strategy for isolating more resistant yeast and Lactobacillus strains, which can be of interest for industrial alcohol production and quality improvements in bacterially fermented foods such as kimchi. PMID:22332602

Tan, Dun-Xian; Hardeland, Ruediger; Manchester, Lucien C; Rosales-Corral, Sergio; Coto-Montes, Ana; Boga, Jose A; Reiter, Russel J

2012-09-01

75

Melatonin, hormone of darkness and more: occurrence, control mechanisms, actions and bioactive metabolites.  

Science.gov (United States)

In its role as a pineal hormone, melatonin is a pleiotropic, nocturnally peaking and systemically acting chronobiotic. These effects are largely explained by actions via G protein-coupled membrane receptors found in the suprachiasmatic nucleus, but also in numerous other sites. Nuclear (ROR/RZR), cytoplasmic (quinone reductase-2, calmodulin, calreticulin) and mitochondrial binding sites and radical-scavenging properties contribute to the actions of melatonin. Regulation of pineal melatonin biosynthesis is largely explained by control mechanisms acting on arylalkylamine N-acetyltransferase, at the levels of gene expression and/or enzyme stability influenced by phosphorylation and interaction with 14-3-3 proteins. Melatonin is not only a hormone but is also synthesized in numerous extrapineal sites, in which it sometimes attains much higher quantities than in the pineal and the circulation. It is also present in many taxonomically distant groups of organisms, including bacteria, fungi, and plants. Moreover, melatonin is a source of bioactive metabolites, such as 5-methoxytryptamine, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine and N(1)-acetyl-5-methoxykynuramine. PMID:18344019

Hardeland, R

2008-07-01

76

Potential drug interactions with melatonin.  

Science.gov (United States)

Possible interactions of melatonin with concurrently administered drugs were investigated in in vitro studies utilising human hepatic post-mitochondrial preparations; similar studies were conducted with rat preparations to ascertain whether rat is a suitable surrogate for human. Drugs were selected based not only on the knowledge that the 6-hydroxylation of exogenous melatonin, its principal pathway of metabolism, is mainly mediated by hepatic CYP1A2, but also on the likelihood of the drug being concurrently administered with melatonin. Hepatic preparations were incubated with either melatonin or 6-hydroxymelatonin in the presence and absence of a range of concentrations of interacting drug, and the production of 6-sulphatoxymelatonin monitored using a radioimmunoassay procedure. Of the drugs screened, only the potent CYP1A2 inhibitor 5-methoxypsoralen impaired the 6-melatonin hydroxylation at pharmacologically relevant concentrations, and is likely to lead to clinical interactions; diazepam, tamoxifen and acetaminophen (paracetamol) did not impair the metabolic conversion of melatonin to 6-sulphatoxymelatonin at concentrations attained following therapeutic administration. 17-Ethinhyloestradiol appeared not to suppress the 6-hydroxylation of melatonin but inhibited the sulphation of 6-hydroxymelatonin, but this is unlikely to result in an interaction following therapeutic intake of the steroid. Species differences in the inhibition of melatonin metabolism in human and rat hepatic post-mitochondrial preparations were evident implying that the rat may not be an appropriate surrogate of human in such studies. PMID:24732412

Papagiannidou, Eleni; Skene, Debra J; Ioannides, Costas

2014-05-28

77

Sleep-wake Cycle Assessment in Type 2 Diabetes and Salivary Melatonin Correlates  

Science.gov (United States)

The aim of this study was to analyze the sleep-wake cycle of T2DM subjects and compare it to healthy controls using the nonparametric approach and to assess the changes in the circadian and homeostatic control of the sleep-wake cycle in type 2 diabetic (T2DM) and correlate it with melatonin concentration. The sample consisted of 21 subjects with diagnosis of T2DM for more than a year and 21 healthy controls matched for gender and age. Subjects were assessed using the Beck's Depression Inventory (BDI), the Apnea Risk Evaluation System (ARES), hemoglobin A1c (HbA1c), actigraphy and melatonin levels. The findings revealed that T2DM subjects demonstrate lower IS (p=.03), higher IV (p=.046) and lower rhythm amplitude (p=.02) when compared to healthy controls. Mean melatonin concentrations collected at bed time were significantly lower in the diabetic subjects than that of controls (11.7+/-7.27 pg/ml vs. 24.13+/-10.80pg/ml; psleep duration (p=.03), efficiency (p=.02); and higher activity counts during the sleep phase (p=.02) in the diabetic group. Sleep efficiency was significantly correlated with melatonin collected two hours before bed time (rho=.61; p=.047). Additionally, there were significant inverse relationships between melatonin collected at two hours before bed time and latency (rho=-.87; p=.001), wake after sleep onset (rho=-.69; p=.02) and nocturnal activity (rho=-.67; p=.03). Latency was inversely correlated with melatonin collected at bed time (rho=-.69; p=.02). These findings suggest that T2DM presents disturbances in the homeostatic and circadian drives, mainly characterized by less consistency across days of the daily circadian signal, higher rhythm fragmentation and lower rhythm amplitude. In addition to the lower melatonin levels, the decrease in the amplitude of the activity rhythm may also be involved in circadian alterations of the sleep-wake cycle.

Cavalcanti, Paula Regina Aguiar

78

Paroxysmal nocturnal hemoglobinuria  

International Nuclear Information System (INIS)

A case of paroxysmal nocturnal hemoglobinuria (PNH) is presented in which MR imaging and CT findings were characteristic. The signal intensity of renal cortex was lower than that of medulla on both T1- and T2-weighted imaging. On CT without contrast enhancement the attenuation of renal cortex was higher than that of renal medulla. These findings at MR imaging and CT were the results of a deposition of hemosiderin in the cells of proximal convoluted tubules, and were helpful for diagnosis of PNH. (orig.)

1991-01-01

79

The effects of pulsing magnetic fields on pineal melatonin synthesis in a teleost fish (brook trout, Salvelinus fontinalis).  

Science.gov (United States)

Based on findings in various mammalian species, where exposure to electromagnetic fields decreased the nocturnal synthesis of the pineal secretory product melatonin, we investigated the effects of magnetic field (MF) exposure in a teleost fish, the brook trout (Salvelinus fontinalis). Fields were generated by Helmholtz coils (maximum flux density 40 microT, frequency 1 Hz, 200 ms on, 800 ms off). Melatonin concentrations were estimated by a specific radioimmunoassay. MF exposure significantly increased night-time pineal (P < 0.001) and serum (P < 0.01) melatonin levels, as compared with the controls. It is suggested that either the pineal glands are directly affected, i.e. by an increased Ca2+-influx into pineal photoreceptors, or that the responses are indirect since induced currents, caused by the rapid rise and decay of the generated MF, may have disturbed the sensory system for electric fields. PMID:9855367

Lerchl, A; Zachmann, A; Ali, M A; Reiter, R J

1998-11-13

80

Reduced oxidative damage in ALS by high-dose enteral melatonin treatment.  

Science.gov (United States)

Amyotrophic lateral sclerosis (ALS) is the collective term for a fatal motoneuron disease of different etiologies, with oxidative stress as a common molecular denominator of disease progression. Melatonin is an amphiphilic molecule with a unique spectrum of antioxidative effects not conveyed by classical antioxidants. In preparation of a possible future clinical trial, we explored the potential of melatonin as neuroprotective compound and antioxidant in: (1) cultured motoneuronal cells (NSC-34), (2) a genetic mouse model of ALS (SOD1(G93A)-transgenic mice), and (3) a group of 31 patients with sporadic ALS. We found that melatonin attenuates glutamate-induced cell death of cultured motoneurons. In SOD1(G93A)-transgenic mice, high-dose oral melatonin delayed disease progression and extended survival. In a clinical safety study, chronic high-dose (300 mg/day) rectal melatonin was well tolerated during an observation period of up to 2 yr. Importantly, circulating serum protein carbonyls, which provide a surrogate marker for oxidative stress, were elevated in ALS patients, but were normalized to control values by melatonin treatment. This combination of preclinical effectiveness and proven safety in humans suggests that high-dose melatonin is suitable for clinical trials aimed at neuroprotection through antioxidation in ALS. PMID:17014688

Weishaupt, Jochen H; Bartels, Claudia; Pölking, Esther; Dietrich, Jeannine; Rohde, Gundula; Poeggeler, Burkhard; Mertens, Nina; Sperling, Swetlana; Bohn, Matthias; Hüther, Gerald; Schneider, Armin; Bach, Alfred; Sirén, Anna-Leena; Hardeland, Rüdiger; Bähr, Mathias; Nave, Klaus-Armin; Ehrenreich, Hannelore

2006-11-01

 
 
 
 
81

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

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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.

Mark S. Rea

2010-01-01

82

Mood Disorders, Circadian Rhythms, Melatonin and Melatonin Agonists  

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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 neuro...

2012-01-01

83

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

2006-12-01

84

Myocardial infarction and nocturnal hypoxaemia  

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Introduction: There is an increased risk of cardiovascular morbidity and mortality in patients with nocturnal intermittent hypoxaemia. Objecive. The aim of this study was to evalute the influence of nocturnal hypoxaemia on ventricular arrhythmias and myocardial ischaemia in patients with myocardial infarction (MI). Method. We studied 77 patients (55.8±7.9 years) with MI free of complications, chronic pulmonary diseases, abnormal awake blood gases tension. All patients underwent overnight pul...

2007-01-01

85

Melatonin: new places in therapy.  

Science.gov (United States)

The fact that the full extent of the function of the pineal gland has not yet been elucidated, has stimulated melatonin research worldwide. This review introduces melatonin's mechanism of action, direct and indirect antioxidant actions as well as the antioxidant properties of its metabolites, 6-hydroxymelatonin (6-OHM) and N-acetyl-N-formyl-5-methoxykynurenamine (AFMK). At present the mechanism of action is proposed to be receptor-, protein- and nonprotein-mediated. From its popular role in the treatment of jetlag, melatonin is now implicated in the reduction of oxidative stess, both as a free radical scavenger and antioxidant. Melatonin's direct scavenging action in respect of the following will be discussed: superoxide anions, hydrogen peroxide, hydroxyl radicals, singlet oxygen, peroxy radicals and nitric oxide/peroxy nitrite anions. In addition melatonin also possesses indirect antioxidant activity and the role of its metabolites, AFMK and 6-OHM will be presented. It is these free radical scavenging and antioxidant properties of melatonin that has shifted the focus from that of merely strengthening circadian rhythms to that of neuroprotectant: a new place in therapy. PMID:17828452

Maharaj, Deepa S; Glass, Beverley D; Daya, Santy

2007-12-01

86

Melatonin and aging. A brief survey.  

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The relationship between the pineal gland and aging has been assumed already nearly a century ago. Recently, melatonin was considered by some authors as a "wonder drug." The present paper tries to summarize the relationship between melatonin and aging in three points. 1. Decline of melatonin production during aging. 2. The role of the pineal gland in the regulation of the ovarian cycle in aged females. 3. The antioxydant effect of melatonin and aging. The age-related decline of pineal melatonin production is due to the degenerative changes of the neural structures (serotonergic and noradrenergic neuron systems) innervating the pineal gland and the suprachiasmatic nuclei rather than to the degeneration of the pineal tissue itself. The decreased melatonin production of the pineal gland preceds the destruction of ovarian cyclicity which can be partly counteracted by melatonin or by 5-hydroxytryptophane administration. The antioxydant effect of melatonin might explain its lifespan-prolonging effect, at least to a certain degree. PMID:11455324

Rúzsás, Csilla; Mess, Béla

2000-01-01

87

Protective effect of melatonin on adriamycin-induced cardiotoxicity in rats.  

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Objectives: Adriamycin is one of the most widely used anticancer drugs. The major limiting factor of using this drug is the development of cardiotoxicity. However, melatonin (N-acetyl-5-methoxytryptamine) is a ubiquitous molecule as a good antioxidant that may protect the heart. We investigated whether or not pretreatment with melatonin can attenuate adriamycin-induced cardiotoxicity. Study design: All procedures and experiments were approved by the Animal Ethics Committee of Gazi Osman Pa?a University (2012-HADYEK-022). Adult male Wistar-Albino rats were randomly divided into four groups, namely control (CON, n=7), melatonin (MEL, n=7), adriamycin (ADR, n=7), and adriamycin+melatonin (ADR+MEL, n=7) groups. Cardiotoxicity in rats was induced by adriamycin injection (cumulative dose: 18 mg/kg, intraperitoneal [i.p.]) at an interval of 24 hours (h) on the 5th, 6th and 7th days. Rats receiving melatonin treatment in the adriamycin group received melatonin (10 mg/kg/day, i.p.) for 7 days and were injected with adriamycin (18 mg/kg, i.p.) on 5th, 6th and 7th days. On the 8th day, gravimetric, electrocardiography (ECG) and biochemical parameters were assessed. Results: Adriamycin induction caused changes in the ECG pattern, including ST-segment elevation and decreased R-amplitude, increase in the serum levels of cardiac injury markers (creatine kinase [CK], CK-MB, aspartate transaminase, and lactate dehydrogenase), decrease in the antioxidant enzymes activity (superoxide dismutase, glutathione peroxidase), elevated lipid peroxidation (malondialdehyde), and altered lipid profile in the serum. Melatonin treatment prevented all the parameters of adriamycin-induced cardiotoxicity in rats. Conclusion: Melatonin has a protective effect on the heart against adriamycin-induced cardiotoxicity in rats. PMID:24769819

Bilgino?lu, Ayça; Ayd?n, Duygu; Ozsoy, Seyma; Aygün, Hatice

2014-04-01

88

Melatonin Inhibits the Migration of Human Lung Adenocarcinoma A549 Cell Lines Involving JNK/MAPK Pathway  

Science.gov (United States)

Objective Melatonin, an indolamine produced and secreted predominately by the pineal gland, exhibits a variety of physiological functions, possesses antioxidant and antitumor properties. But, the mechanisms for the anti-cancer effects are unknown. The present study explored the effects of melatonin on the migration of human lung adenocarcinoma A549 cells and its mechanism. Methods MTT assay was employed to measure the viability of A549 cells treated with different concentrations of melatonin. The effect of melatonin on the migration of A549 cells was analyzed by wound healing assay. Occludin location was observed by immunofluorescence. The expression of occludin, osteopontin (OPN), myosin light chain kinase (MLCK) and phosphorylation of myosin light chain (MLC), JNK were detected by western blots. Results After A549 cells were treated with melatonin, the viability and migration of the cells were inhibited significantly. The relative migration rate of A549 cells treated with melatonin was only about 20% at 24 h. The expression level of OPN, MLCK and phosphorylation of MLC of A549 cells were reduced, while the expression of occludin was conversely elevated, and occludin located on the cell surface was obviously increased. The phosphorylation status of JNK in A549 cells was also reduced when cells were treated by melatonin. Conclusions Melatonin significantly inhibits the migration of A549 cells, and this may be associated with the down-regulation of the expression of OPN, MLCK, phosphorylation of MLC, and up-regulation of the expression of occludin involving JNK/MAPK pathway.

Zhou, Qiaoyun; Gui, Shuyu; Zhou, Qing; Wang, Yuan

2014-01-01

89

Modulation of pineal activity during the 23rd sunspot cycle: melatonin rise during the ascending phase of the cycle is accompanied by an increase of the sympathetic tone.  

Science.gov (United States)

In two groups of female CD-rats nocturnal urine (19-23 h, 23-3 h, 3-7 h) was collected at monthly intervals over 658 days (I: 1997-1999) and 494 days (II: 1999-2000) coinciding with the ascending limb (1996-2000) of the 23rd sunspot cycle (1996-2008). The excretion of 6-sulfatoxymelatonin (aMT6s: I, II) was determined as well as the ratio of noradrenaline/adrenaline (NA/A: I) reflecting the activity of the sympathetic nervous system. AMT6s was higher in II than I (19-7 h: +24%; P < 0.001; 23-3 h: +30% and 3-7 h: +17%, P < 0.001), and progressively increased (19-23 h) showing linear regressions (1: R = +0.737, P = 0.003; II: R = +0.633, 0.008) which correlated (I) with the Planetary Index (Ap: R = +0.598, P = 0.020), an established estimate of geomagnetic disturbances due to solar activity. NA/A rose at all intervals (I: 46-143%) correlating with Ap (R = +0.554-0.768; P = 0.0399-0.0013). These results indicate that melatonin secretion rises as solar activity increases during the ascending limb of a sunspot cycle accompanied by growing geomagnetic disturbances (Ap) which elevate the sympathetic tone and thus affect the pineal gland, initially stimulating the activity of arylalkylamine N-acetyltransferase and subsequently fostering the expression of N-acetylserotonin O-methyltransferase (rate-limiting enzyme for melatonin biosynthesis) if Ap increases further. The potential (patho) physiological significance of these findings is discussed and the need for a systematic continuation of such studies is emphasized. PMID:24851406

Bartsch, Christian; Bartsch, Hella; Seebald, Eckhard; Küpper, Heinz; Mecke, Dieter

2014-05-01

90

Melatonin Metabolism in the Central Nervous System  

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The metabolism of melatonin in the central nervous system is of interest for several reasons. Melatonin enters the brain either via the pineal recess or by uptake from the blood. It has been assumed to be also formed in some brain areas. Neuroprotection by melatonin has been demonstrated in numerous model systems, and various attempts have been undertaken to counteract neurodegeneration by melatonin treatment. Several concurrent pathways lead to different products. Cytochrome P450 subforms ha...

Hardeland, Ru?diger

2010-01-01

91

Melatonin in pathogenesis and therapy of cancer  

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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, ...

2006-01-01

92

Gastrointestinal melatonin: localization, function, and clinical relevance.  

Science.gov (United States)

The gastrointestinal tract of vertebrate species is a rich source of extrapineal melatonin. The concentration of melatonin in the gastrointestinal tissues surpasses blood levels by 10-100 times and there is at least 400x more melatonin in the gastrointestinal tract than in the pineal gland. The gastrointestinal tract contributes significantly to circulating concentrations of melatonin, especially during the daytime and melatonin may serve as an endocrine, paracrine, or autocrine hormone influencing the regeneration and function of epithelium, enhancing the immune system of the gut, and reducing the tone of gastrointestinal muscles. As binding sites for melatonin exhibit circadian variation in various species, it has been hypothesized that some melatonin found in the gastrointestinal tract might be of pineal origin. Unlike the photoperiodically regulated production of melatonin in the pineal, the release of gastrointestinal melatonin seems to be related to the periodicity of food intake. Phylogenetically, melatonin and its binding sites were detected in the gastrointestinal tract of lower vertebrates, birds, and mammals. Melatonin was found also in large quantities in the embryonic tissue of the mammalian and avian gastrointestinal tract. Food intake and, paradoxically, also longterm food deprivation resulted in an increase of tissue and plasma concentrations of melatonin. Melatonin release may have a direct effect on many gastrointestinal tissues but may also well influence the digestive tract indirectly, via the central nervous system and the sympathetic and parasympathetic nerves. Melatonin prevents ulcerations of gastrointestinal mucosa by an antioxidant action, reduction of secretion of hydrochloric acid, stimulation of the immune system, fostering epithelial regeneration, and increasing microcirculation. Because of its unique properties, melatonin could be considered for prevention or treatment of colorectal cancer, ulcerative colitis, gastric ulcers, irritable bowel syndrome, and childhood colic. PMID:12395907

Bubenik, George A

2002-10-01

93

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

94

Neuromotor development in nocturnal enuresis.  

Science.gov (United States)

In children with nocturnal enuresis, a higher rate of minor neurological dysfunction has been found. The aim of this study was to assess timed performance (a measure of motor performance speed) and associated movements using a standardized and reliable instrument. The motor function of 37 children with nocturnal enuresis (27 males, 10 females; mean age 10y 7mo [SD 1y 10mo]; age range 8y-14y 8mo) and 40 comparison children without enuresis (17 males, 23 females; mean age 10y 7mo [SD 1y 6mo]; age range 8y-14y 8mo) was assessed using the Zurich Neuromotor Assessment. Children with nocturnal enuresis showed a slower motor performance than comparison children, particularly for repetitive hand and finger movements. This study provides evidence for a maturational deficit in motor performance in children with nocturnal enuresis. In addition to a maturational deficit of the brainstem, it is proposed that there is a possible maturational deficit of the motor cortex circuitry and related cortical areas in children with nocturnal enuresis. PMID:16904021

von Gontard, Alexander; Freitag, Christine M; Seifen, Stephanie; Pukrop, Ralf; Röhling, Dagmar

2006-09-01

95

Duration of Nocturnal Hypoglycemia Before Seizures  

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OBJECTIVE—Despite a high incidence of nocturnal hypoglycemia documented by the use of continuous glucose monitoring (CGM), there are no reports in the literature of nocturnal hypoglycemic seizures while a patient is wearing a CGM device.

Buckingham, Bruce; Wilson, Darrell M.; Lecher, Todd; Hanas, Ragnar; Kaiserman, Kevin; Cameron, Fergus

2008-01-01

96

Intracoronary and systemic melatonin to patients with acute myocardial infarction : protocol for the IMPACT trial  

DEFF Research Database (Denmark)

INTRODUCTION: Ischaemia-reperfusion injury following acute myocardial infarctions (AMI) is an unavoidable consequence of the primary percutaneous coronary intervention (pPCI) procedure. A pivotal mechanism in ischaemia-reperfusion injury is the production of reactive oxygen species following reperfusion. The endogenous hormone, melatonin, works as an antioxidant and could potentially minimise the ischaemia-reperfusion injury. Given intracoronarily, it enables melatonin to work directly at the site of reperfusion. We wish to test if melatonin, as an antioxidant, can minimise the reperfusion injury following pPCI in patients with AMI. MATERIAL AND METHODS: The IMPACT trial is a multicentre, randomised, double-blinded, placebo-controlled study. We wish to include 2 � 20 patients with ST-elevation myocardial infarctions undergoing pPCI within six hours from symptom onset. The primary end-point is the Myocardial Salvage Index assessed by cardiovascular magnetic resonance imaging on day 4 (± 1) after pPCI. The secondary end-points are high-sensitivity troponin, creatinekinase myocardial band and clinical events. CONCLUSION: The aim of the IMPACT trial is to evaluate the effect of melatonin on reperfusion injuries following pPCI. Owing to its relatively non-toxic profile, melatonin is an easily implementable drug in the clinical setting, and melatonin has the potential to reduce morbidity in patients with AMI. FUNDING: This study received no financial support from the industry. TRIAL REGISTRATION: www.clinicaltrials.gov, clinical trials identifier: NCT01172171.

Halladin, Natalie L; Busch, Sarah Ekeløf

2014-01-01

97

Melatonin Inhibits GnRH-1, GnRH-3 and GnRH Receptor Expression in the Brain of the European Sea Bass, Dicentrarchus labrax  

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Full Text Available Several evidences supported the existence of melatonin effects on reproductive system in fish. In order to investigate whether melatonin is involved in the modulation of GnRH systems in the European sea bass, we have injected melatonin (0.5 µg/g body mass in male specimens. The brain mRNA transcript levels of the three GnRH forms and the five GnRH receptors present in this species were determined by real time quantitative PCR. Our findings revealed day–night variations in the brain expression of GnRH-1, GnRH-3 and several GnRH receptors (dlGnRHR-II-1c, -2a, which exhibited higher transcript levels at mid-light compared to mid-dark phase of the photocycle. Moreover, an inhibitory effect of melatonin on the nocturnal expression of GnRH-1, GnRH-3, and GnRH receptors subtypes 1c, 2a and 2b was also demonstrated. Interestingly, the inhibitory effect of melatonin affected the expression of hypophysiotrophic GnRH forms and GnRH receptors that exhibit day–night fluctuations, suggesting that exogenous melatonin reinforce physiological mechanisms already established. These interactions between melatoninergic and GnRH systems could be mediating photoperiod effects on reproductive and other rhythmic physiological events in the European sea bass.

José Antonio Muñoz-Cueto

2013-04-01

98

Melatonin Anticancer Effects: Review  

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Full Text Available 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.

Luigi Di Bella

2013-01-01

99

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

2013-01-01

100

Seasonal and daily variations in plasma melatonin in the high-arctic Svalbard ptarmigan (Lagopus mutus hyperboreus).  

Science.gov (United States)

This study presents the daily rhythm of melatonin secretion throughout one year in a bird from the northern hemisphere, the Svalbard ptarmigan (Lagopus mutus hyperboreus), which lives naturally at 76-80 degrees N. Eight Svalbard ptarmigan were caged outdoors at 70 degrees N and blood sampled throughout one day each month for 13 months. At this latitude, daylight is continuous between May and August, but there is a short period of civil twilight around noon from late November to mid January. There was no daily rhythm in plasma melatonin in May-July. Plasma melatonin levels varied significantly throughout the day in all other months of the year, with the nighttime increase reflecting the duration of darkness. The highest mean plasma concentration occurred at midnight in March (110.1 +/- 16.5 pg/ml) and represented the annual peak in estimated daily production. Around the winter solstice, melatonin levels were significantly reduced at noon and elevated during the nearly 18 h of consecutive darkness, and the estimated mean daily production of melatonin was significantly reduced. Thus, at the times of the year characterized by light-dark cycles, melatonin may convey information concerning the length of the day and, therefore, progression of season. The nearly undetectable low melatonin secretion in summer and the reduced amplitude and production in midwinter indicate a flexible circadian system that may reflect an important adaptation to life in the Arctic. PMID:10447312

Reierth, E; Van't Hof, T J; Stokkan, K A

1999-08-01

 
 
 
 
101

The Angiotensin-melatonin axis.  

Science.gov (United States)

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. PMID:23365722

Campos, Luciana A; Cipolla-Neto, Jose; Amaral, Fernanda G; Michelini, Lisete C; Bader, Michael; Baltatu, Ovidiu C

2013-01-01

102

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

Science.gov (United States)

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, Rudiger

2013-01-01

103

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

Science.gov (United States)

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. PMID:23481642

Hardeland, Rüdiger

2013-01-01

104

Melatonin in human preovulatory follicular fluid  

Science.gov (United States)

Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 rain or less after follicular aspiration. All of the follicular fluids contained melatonim, in concentrations substantially higher than those in the corresponding serum. A positive correlation was found between follicular fluid and serum melatonin levels in each woman; these observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

Brzezinski, Amnon; Seibel, Machelle M.; Lynch, Harry J.; Deng, Mei-Hua; Wurtman, Richard J.

1987-01-01

105

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

2009-12-01

106

Effectiveness of Melatonin, as a Radiation Damage-Mitigating Drug in Modulating Liver Biochemical disorders in ?-Irradiated Rats  

International Nuclear Information System (INIS)

Melatonin has an anti per oxidative effect on several tissues as well as a scavenger effect on reactive oxygen species (ROS). Whilst radiation-hazards due to free radical generation, present enormous challenges for biological and medical safety. Therefore, rats were classified into four groups; control (n= 8), (received 0.5 ml of alcoholic saline as a vehicle for 5 days). Melatonin-treated rats received 10 mg/ kg body wt, for 5 days (given to the animals in the morning via stomach tube). gamma-irradiated rats received 0.5 ml of the melatonin vehicle followed by one shot dose of 3 Gy gamma-rays. Each of these groups was compared with a further group, which-received melatonin for 5 days after 3 Gy gamma-irradiation exposure. The results revealed that all considered biochemical parameters were not changed significantly in melatonin-treated group as compared with control one. In the liver tissue of the gamma-irradiated animals (3 Gy), the oxidative stress markers malondialdehyde (MDA) and protein carbonyl (PC) were significantly increased, while a marked decrease occurred in the contents of deoxy- and ribo-nucleic acids (DNA and RNA) and glutathione (GSH) as well as activity of glutathione-S-transferase (GST). In addition, catalase (CAT) and myeloperoxidase (MPO) activities were increased. Activities of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) were significantly increased in sera of the irradiated rats. Treatment with melatonin for 5 days after gamma-rays exposure significantly modulated the radiation-induced elevations in MDA and PC levels in the liver tissue and significantly restored hepatic GSH content, GST, CAT and MPO activities. Post-irradiation treatment with melatonin showed significant higher hepatic DNA and RNA contents than irradiated rats. The activities of AST, ALP, and GGT in serum were significantly ameliorated when melatonin was administrated after irradiation. Conclusion: Melatonin has effective mitigating effects against gamma- radiation induced oxidative stress and liver injury.

2011-01-01

107

Melatonin synthesis in the human pineal gland  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Poster presentation: The mammalian pineal organ is a peripheral oscillator, depending on afferent information from the so-called master clock in the suprachiasmatic nuclei of the hypothalamus. One of the best studied outputs of the pineal gland is the small and hydrophobic molecule melatonin. In all vertebrates, melatonin is synthesized rhythmically with high levels at night, signalling the body the duration of the dark period. Changes or disruptions of melatonin rhythms in humans are related...

Ackermann Katrin; Bux Roman; Rüb Udo; Kauert Gerold; Stehle Jörg H

2007-01-01

108

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

1999-08-01

109

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 SciELO Brazil | Language: English 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 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.

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

110

Amelioration of melatonin on oxidative stress and genotoxic effects induced by cisplatin in vitro.  

Science.gov (United States)

In this study, we made an effort to evaluate the possible protective actions of melatonin on cisplatin-induced oxidative damage in mice brain homogenate and genotoxic effects in human lymphocytes under in vitro conditions. The tissue homogenate was divided into three parts. The first portion was kept as control treated with dimethyl sulphoxide (DMSO) (group 1) while the second and third portion were treated with 24 µg/g tissue cisplatin alone (group 2) and 24 µg/g tissue cisplatin in combination with 3 mM melatonin (group 3), respectively. We measured the oxidative stress biomarkers such as lipid peroxidation, 8-hydroxy 2' deoxyguanosine (8-OHdG) and antioxidant parameters such as reduced glutathione, superoxide dismutase, glutathione peroxidase, and glutathione reductase in brain homogenate. Likewise peripheral venous blood was collected from healthy donors and human lymphocyte culture was done using karyotyping medium. Cultures were divided into three groups. Group 1 was the control i.e. lymphocytes treated with DMSO 5 µg/mL. In group 2, lymphocytes were treated with 2 µg/mL cisplatin and group 3 with a combination of 2 µg/mL cisplatin and 0.3 mM melatonin. Incubation of tissue homogenates with cisplatin elevated the malondialdehyde and 8-OHdG levels which were then reversed by melatonin. Reduction in antioxidant parameters with respect to corresponding controls were also restored by melatonin treatment. Furthermore, supplementation of melatonin was found to modulate the chromosome damage elicited by cisplatin which was determined using Giemsa (GTG) banding and karyotyping. These findings suggest that melatonin improves the cellular function and helps them to survive in the belligerent environment created by free radicals. PMID:22889322

Surendran, Divya; Geetha, C S; Mohanan, P V

2012-10-01

111

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

112

Airway inflammation in nocturnal asthma  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In Chapter 2.1-2.4 some methodological problems of obtaining, processing and evaluating bronchial biopsies were described. In chapter 3-5 the inflammatory data of our study on bronchial biopsies in nocturnal asthma were presented. Finally in chapter 6-7 markers of inflammation in other body compartments were described, t.e. in exhaled air serum and BAL fluid. ... Zie: Summary, discussion, conclusions and perspectives

Hacken, Nicolaas Hubertus Theodorus Ten

1998-01-01

113

[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; Šottner, O; Hanuš, T; Martan, A; Hor?i?ka, L; Feyereisl, J; Halaška, M; Švabík, K; Krofta, L

2013-08-01

114

[Anti-inflammatory potential of melatonin].  

Science.gov (United States)

The summary of anti-inflammatory properties, cellular and systemic mechanisms of action of epiphyseal melatonin is presented. Dual effect of interaction between melatonin and non-steroidal anti-inflammatory agents is discussed with reference to enhancement of their specific activity and prevention of side effects. PMID:24437164

Arushanian, É B; Naumov, S S

2013-01-01

115

Melatonin and aging: prospects for human treatment.  

Science.gov (United States)

Human life span, with or without modern medicine is around 85-95 years. All living creatures have their inner clock that measures their daily (circadian) and their seasonal (circannual) time. These time changes are mediated by the alteration of levels of melatonin, an evolutionary ancient hormone, which is produced in many body tissues, including the pineal gland, retina and the gastrointestinal tract (GIT). Light is blocking the production of melatonin in the pineal gland, darkness is stimulating it. So, the diurnal changes of light intensity of melatonin, provide a "daily clock" and the seasonal changes provide a "seasonal clock". Finally, the reduction of melatonin observed with aging, may indicate the presence of an "age clock". Melatonin is a strong antioxidant (often it is called scavenger of free radicals), which protects the body from the effects of noxious compounds. Therefore it was hypothesized that the reduction of melatonin levels with age contributes to the aging process. So far, the only remedy to extend the life span was a 40% reduction in caloric intake, which prolonged the life in mice, rats, dogs and monkeys by 30-50%. A large group of people imitate these experiments performed on animals, but the results of these experiments will not be known for several decades. How is being hungry prolonging the life span? There is a connection between caloric reduction and melatonin levels in GIT. Several experiments indicate that fasting in animals substantially increased their production of GIT melatonin. Therefore, instead of being permanently hungry, a prolongation of human life could be achieved by a replacement melatonin therapy. A daily intake of melatonin before bed time might achieve the same effect as fasting e.g. an increase of body melatonin levels, which will protect the individual from the ravages of old age. That includes Parkinson's disease and Alzheimer's disease. There is a large group of people taking melatonin daily who believe that melatonin is the "fountain of youth". Those are the subjects which will one day provide an experimental evidence of the efficacy of melatonin. PMID:21451205

Bubenik, G A; Konturek, S J

2011-02-01

116

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

117

Neurobiology, Pathophysiology, and Treatment of Melatonin Deficiency and Dysfunction  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Melatonin is a highly pleiotropic signaling molecule, which is released as a hormone of the pineal gland predominantly during night. Melatonin secretion decreases during aging. Reduced melatonin levels are also observed in various diseases, such as types of dementia, some mood disorders, severe pain, cancer, and diabetes type 2. Melatonin dysfunction is frequently related to deviations in amplitudes, phasing, and coupling of circadian rhythms. Gene polymorphisms of melatonin receptors and cir...

Hardeland, Ru?diger

2012-01-01

118

The early response of pineal N-acetyltransferase activity, melatonin and catecholamine levels in rats irradiated with gamma rays  

International Nuclear Information System (INIS)

Male Wistar rats adapted to an artificial light-dark regimen were whole-body gamma-irradiated with a dose of 14.35 Gy. Irradiation, sham-irradiation and decapitation 30, 60 and 120 min after the exposure were performed between 2000 h and 0100 h in the darkness. The serotonin N-acetyltransferase activity (NAT), the concentration of melatonin and corticosterone were also determined. Ionizing radiation did not change the activity of NAT, the key enzyme of melatonin synthesis; however, it decreased the concentration of pineal melatonin. The concentration of pineal dopamine and norepinephrine decreased 30 and 120 min after exposure, while the concentration of epinephrine was elevated 30 min after irradiation, though later it was markedly decreased. The serum melatonin level was not changed but an increase in corticosterone level was observed. In the early period after exposure a decrease in pineal melatonin occurred, accompanied by a decrease in pineal catecholamines. On the contrary, in the phase of developed radiation injury the signs of increased melatonin synthesis were observed on days 3 and 4 after the exposure. (author) 6 figs., 25 refs

1995-10-01

119

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

120

Utility of melatonin to treat surgical stress after major vascular surgery--a safety study.  

DEFF Research Database (Denmark)

Surgery for abdominal aortic aneurysm is associated with elevated oxidative stress. As an antioxidant in animal and human studies, melatonin has the potential of ameliorating some of this oxidative stress, but melatonin has never been administered to adults during surgery for the purpose of reducing oxidative damage. The aim of this pilot study was to evaluate the safety of various doses of melatonin administered during or after surgery and to monitor the changes in biomarkers of oxidative stress and inflammation during the pre-, intra-, and postoperative period. Six patients undergoing aortic surgery received 10 (n = 2), 30 (n = 2) or 60 (n = 2) mg melatonin intravenously in the intraoperative phase and 10 mg orally for three nights after surgery. Patients were monitored for hemodynamic parameters during and after surgery. Any unexpected events during the hospitalization were registered. Blood samples were collected preoperatively and at 5 min, 6 hr and 24 hr after clamp removal or after re-circulation of the first leg and the samples were analyzed for malondialdehyde (MDA), ascorbic acid (AA), dehydroascorbic acid (DHA), and interleukin-6 (IL-6). Troponin I (TpI) and C-reactive protein (CRP) were also measured for 4 days after surgery. Melatonin administration did not change hemodynamic parameters (mean arterial pressure or pulse rate) during surgery (P = 0.499 and 0.149, respectively), but oxidative stress parameters (MDA and AA) decreased significantly (P = 0.014 and 0.001, respectively). There was a significant increase in the inflammatory parameters (IL-6 and CRP) (P = 0.001 and 0.001, respectively) and an increase in TpI (P = 0.009) as a consequence of surgery. These were not influenced by melatonin treatment. Treatment of patients undergoing major aortic surgery with melatonin intravenously up to 60 mg in the intraoperative phase was safe and without complications. Melatonin may decrease oxidative damage resulting from surgery, but randomized clinical trials are required before definitive conclusions can be drawn regarding the clinical benefit of melatonin in surgical situations.

Kücükakin, Bülent; Lykkesfeldt, Jens

2008-01-01

 
 
 
 
121

Utility of melatonin to treat surgical stress after major vascular surgery - a safety study  

DEFF Research Database (Denmark)

Surgery for abdominal aortic aneurysm is associated with elevated oxidative stress. As an antioxidant in animal and human studies, melatonin has the potential of ameliorating some of this oxidative stress, but melatonin has never been administered to adults during surgery for the purpose of reducing oxidative damage. The aim of this pilot study was to evaluate the safety of various doses of melatonin administered during or after surgery and to monitor the changes in biomarkers of oxidative stress and inflammation during the pre-, intra- and postoperative period. Six patients undergoing aortic surgery received 10 (n=2), 30 (n=2) or 60 (n=2) mg melatonin intravenously in the intraoperative phase and 10 mg orally for three nights after surgery. Patients were monitored for hemodynamic parameters during and after surgery. Any unexpected events during the hospitalization were registered. Blood samples were collected preoperatively and at 5 min, 6 hrs and 24 hrs after clamp removal or after re-circulation of the first leg and the samples were analysed for malondialdehyde (MDA), ascorbic acid (AA), dehydroascorbic acid (DHA) and interleukin-6 (IL-6). Troponin I (TpI) and C-reactive protein (CRP) were also measured for four days after surgery. Melatonin administration did not change hemodynamic parameters (mean arterial pressure or pulse rate) during surgery (P=0.499 and 0.149, respectively), but oxidative stress parameters (MDA and AA) decreased significantly (P=0.014 and 0.001, respectively). There was a significant increase in the inflammatory parameters (IL-6 and CRP) (P=0.001 and 0.001, respectively) and an increase in TpI (P=0.009) as a consequence of surgery. These were not influenced by melatonin treatment. Treatment of patients undergoing major aortic surgery with melatonin intravenously up to 60 mg in the intraoperative phase was safe and without complications. Melatonin may decrease oxidative damage resulting from surgery, but randomized clinical trials are required before definitive conclusions can be drawn regarding the clinical benefit of melatonin in surgical situations.

Kücükakin, Bülent; Lykkesfeldt, Jens

2008-01-01

122

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 25"0C during summer and about 20"0C 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

123

Duration of Nocturnal Hypoglycemia Before Seizures  

Science.gov (United States)

OBJECTIVE—Despite a high incidence of nocturnal hypoglycemia documented by the use of continuous glucose monitoring (CGM), there are no reports in the literature of nocturnal hypoglycemic seizures while a patient is wearing a CGM device. RESEARCH DESIGN AND METHODS—In this article, we describe four such cases and assess the duration of nocturnal hypoglycemia before the seizure. RESULTS—In the cases where patients had a nocturnal hypoglycemic seizure while wearing a CGM device, sensor hypoglycemia (<60 mg/dl) was documented on the CGM record for 2.25–4 h before seizure activity. CONCLUSIONS—Even with a subcutaneous glucose lag of 18 min when compared with blood glucose measurements, glucose sensors have time to provide clinically meaningful alarms. Current nocturnal hypoglycemic alarms need to be improved, however, since patients can sleep through the current alarm systems.

Buckingham, Bruce; Wilson, Darrell M.; Lecher, Todd; Hanas, Ragnar; Kaiserman, Kevin; Cameron, Fergus

2008-01-01

124

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

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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 organ...

Rüdiger Hardeland

2013-01-01

125

Role of melatonin in neurodegenerative diseases.  

Science.gov (United States)

The pineal product melatonin has remarkable antioxidant properties. It scavenges hydroxyl, carbonate and various organic radicals, peroxynitrite and other reactive nitrogen species. Melatonyl radicals formed by scavenging combine with and, thereby, detoxify superoxide anions in processes terminating the radical reaction chains. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes like superoxide dismutase, glutathione peroxidase and glutathione reductase, and by augmenting glutathione levels. 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, e.g., Alzheimer's disease. Melatonin has been shown to be effective in arresting neurodegenerative phenomena seen in experimental models of Alzheimer's disease, Parkinsonism and ischemic stroke. Melatonin preserves mitochondrial homeostasis, reduces free radical generation, e.g., by enhancing mitochondrial glutathione levels, and safeguards proton potential and ATP synthesis by stimulating complex I and IV activities. Therapeutic trials with melatonin have been effective in slowing the progression of Alzheimer's disease but not of Parkinson's disease. Melatonin's efficacy in combating free radical damage in the brain suggests that it may be a valuable therapeutic agent in the treatment of cerebral edema after traumatic brain injury. PMID:16179266

Srinivasan, V; Pandi-Perumal, S R; Maestroni, G Jm; Esquifino, A I; Hardeland, R; Cardinali, D P

2005-01-01

126

Melatonin as a radioprotective agent: a review  

International Nuclear Information System (INIS)

Melatonin (N-acetyl-5-methoxytryptamine), the chief secretory product of the pineal gland in the brain, is well known for its functional versatility. In hundreds of investigations, melatonin has been documented as a direct free radical scavenger and an indirect antioxidant, as well as an important immunomodulatory agent. The radical scavenging ability of melatonin is believed to work via electron donation to detoxify a variety of reactive oxygen and nitrogen species, including the highly toxic hydroxyl radical. It has long been recognized that the damaging effects of ionizing radiation are brought about by both direct and indirect mechanisms. The direct action produces disruption of sensitive molecules in the cells, whereas the indirect effects (?70%) result from its interaction with water molecules, which results in the production of highly reactive free radicals such as ·OH, ·H, and eaq- and their subsequent action on subcellular structures. The hydroxyl radical scavenging ability of melatonin was used as a rationale to determine its radioprotective efficiency. Indeed, the results from many in vitro and in vivo investigations have confirmed that melatonin protects mammalian cells from the toxic effects of ionizing radiation. Furthermore, several clinical reports indicate that melatonin administration, either alone or in combination with traditional radiotherapy, results in a favorable efficacy:toxicity ratio during the treatment of human cancers. This article reviews the literature from laboratory investigations that document the ability of melatonin to scavenge a variety of free radicals (including the hydroxyl radical induced by ionizing radiation) and summarizes the evidence that should be used to design larger translational research-based clinical trials using melatonin as a radioprotector and also in cancer radiotherapy. The potential use of melatonin for protecting individuals from radiation terrorism is also considered

2004-07-01

127

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

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

Franey, C.; Aldhous, M.; Burton, S.; Checkley, S.; Arendt, J.

1986-01-01

128

Neuromodulatory role of melatonin in retinal information processing.  

Science.gov (United States)

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. PMID:22986412

Huang, Hai; Wang, Zhongfeng; Weng, Shi-Jun; Sun, Xing-Huai; Yang, Xiong-Li

2013-01-01

129

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

International Nuclear Information System (INIS)

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

1990-01-01

130

Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling.  

Science.gov (United States)

Evidence is accumulating regarding the importance of circadian core oscillators, several associated factors, and melatonin signaling in the maintenance of health. Dysfunction of endogenous clocks, melatonin receptor polymorphisms, age- and disease-associated declines of melatonin likely contribute to numerous diseases including cancer, metabolic syndrome, diabetes type 2, hypertension, and several mood and cognitive disorders. Consequences of gene silencing, overexpression, gene polymorphisms, and deviant expression levels in diseases are summarized. The circadian system is a complex network of central and peripheral oscillators, some of them being relatively independent of the pacemaker, the suprachiasmatic nucleus. Actions of melatonin on peripheral oscillators are poorly understood. Various lines of evidence indicate that these clocks are also influenced or phase-reset by melatonin. This includes phase differences of core oscillator gene expression under impaired melatonin signaling, effects of melatonin and melatonin receptor knockouts on oscillator mRNAs or proteins. Cross-connections between melatonin signaling pathways and oscillator proteins, including associated factors, are discussed in this review. The high complexity of the multioscillator system comprises alternate or parallel oscillators based on orthologs and paralogs of the core components and a high number of associated factors with varying tissue-specific importance, which offers numerous possibilities for interactions with melatonin. It is an aim of this review to stimulate research on melatonin signaling in peripheral tissues. This should not be restricted to primary signal molecules but rather include various secondarily connected pathways and discriminate between direct effects of the pineal indoleamine at the target organ and others mediated by modulation of oscillators. PMID:22034907

Hardeland, Rüdiger; Madrid, Juan Antonio; Tan, Dun-Xian; Reiter, Russel J

2012-03-01

131

Role of melatonin in upper gastrointestinal tract.  

Science.gov (United States)

Melatonin, an indole formed enzymatically from L-tryptophan, is the most versatile and ubiquitous hormone molecule produced not only in all animals but also in some plants. This review focuses on the role of melatonin in upper portion of gastrointestinal tract (GIT), including oral cavity, esophagus, stomach and duodenum, where this indole is generated and released into the GIT lumen and into the portal circulation to be uptaken, metabolized by liver and released with bile into the duodenum. The biosynthetic steps of melatonin with two major rate limiting enzymes, arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), transforming tryptophan to melatonin, originally identified in pinealocytes have been also detected in entero-endocrine (EE) cells of GIT wall, where this indole may act via endocrine, paracrine and/or luminal pathway through G-protein coupled receptors. Melatonin in GIT was shown to be generated in about 500 times larger amounts than it is produced in pineal gland. The production of melatonin by pineal gland shows circadian rhythm with high night-time peak, especially at younger age, followed by the fall during the day-light time. As a highly lipophilic substance, melatonin reaches all body cells within minutes, to serve as a convenient circadian timing signal for alteration of numerous body functions.. Following pinealectomy, the light/dark cycle of plasma melatonin levels disappears, while its day-time blood concentrations are attenuated but sustained mainly due to its release from the GIT. After oral application of tryptophan, the plasma melatonin increases in dose-dependent manner both in intact and pinealectomized animals, indicating that extrapineal sources such as GIT rather than pineal gland are the major producers of this indole. In the upper portion of GIT, melatonin exhibits a wide spectrum of activities such as circadian entrainment, free radicals scavenging activity, protection of mucosa against various irritants and healing of various GIT lesions such as stomatitis, esophagitis, gastritis and peptic ulcer. This review concentrates on the generation and pathophysiological implication of melatonin in upper GIT. PMID:18212399

Konturek, S J; Konturek, P C; Brzozowski, T; Bubenik, G A

2007-12-01

132

Loss of Response to Melatonin Treatment Is Associated with Slow Melatonin Metabolism  

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Background: In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to melatonin is yet unknown. We hypothesise that this…

Braam, W.; van Geijlswijk, I.; Keijzer, Henry; Smits, Marcel G.; Didden, Robert; Curfs, Leopold M. G.

2010-01-01

133

Testicular function and semen characteristics of Awassi rams treated with melatonin out of the breeding season.  

Science.gov (United States)

The objective of this study was to evaluate the effect of long-term melatonin treatment applied during the non-breeding season on semen characteristics, endocrine function of testicles and baseline level of insulin-like growth factor-I (IGF-I) in Awassi rams kept in the temperate continental zone of Europe and used as semen donors in an artificial insemination (AI) programme. On 23 February (day 0), slow-release melatonin implants were inserted subcutaneously into rams (n = 8). Control animals (n = 8) received no treatment. In both groups, basic semen parameters (concentration, total motility, fast and slow forward motility, morphology), GnRH-induced testosterone response and basal IGF-I concentration were evaluated on days 0, 47 and 71. No differences were found in concentration of spermatozoa, total motility, and numbers of spermatozoa with fast and slow progressive motility and normal/abnormal morphology between the melatonin-treated and the control group. However, in melatonin-treated animals, basal and GnRH-induced testosterone levels were slightly elevated on day 47 and became significantly higher on day 71 (P semen characteristics and the IGF-I level of semen donor Awassi rams used in an AI programme and kept in the temperate continental zone of Europe. PMID:19897457

Faigl, Vera; Keresztes, Mónika; Kulcsár, Margit; Nagy, Sándor; Keresztes, Zsuzsanna; Amiridis, Georgios S; Solti, László; Huszenicza, Gyula; Cseh, Sándor

2009-12-01

134

Melatonin prevents gestational hyperhomocysteinemia-associated alterations in neurobehavioral developments in rats.  

Science.gov (United States)

Chronic hyperhomocysteinemia is a risk factor in cardiovascular diseases and neurodegeneration. Among the putative mechanisms of homocysteine-induced neurotoxicity, an increased production of reactive oxygen species has been suggested. However, elevated homocysteine levels might disturb neurogenesis during brain development and lead to persistent congenital malformations in the fetus. In this study, we examined whether administration of melatonin inhibits maternal hyperhomocysteinemia-induced cognitive deficits in offspring. Hyperhomocysteinemia was induced in female rats by administration of methionine during pregnancy at a dose of 1 g/kg body weight dissolved in drinking water. Some animals received methionine plus 10 mg/kg/day melatonin subcutaneously throughout pregnancy. The levels of glial fibrillary acidic protein, S100B protein, and neural cell adhesion molecules were determined in the brain tissue from the pups. Learning and memory performances of the young-adult offspring were tested using the Morris water maze test. There were significant reductions in the expression of glial fibrillary acidic protein and S100 B protein in the brains of pups from hyperhomocysteinemic rat dams. Furthermore, maternal hyperhomocysteinemia altered the expression pattern of neural cell adhesion molecules in the fetal brain. In addition, maternal hyperhomocysteinemia significantly reduced learning abilities in offspring. Treatment with melatonin during pregnancy improved learning deficits and prevented the reduction of glial and neuronal markers induced by hyperhomocysteinemia. In conclusion, administration of melatonin throughout pregnancy reduces the effects of hyperhomocysteinemia on the development of fetal brain; therefore, it might be beneficial in preventing persistent congenital malformations. PMID:18289170

Baydas, Giyasettin; Koz, Sema T; Tuzcu, Mehmet; Nedzvetsky, Viktor S

2008-03-01

135

Melatonin membrane receptors in peripheral tissues: distribution and functions.  

Science.gov (United States)

Many of melatonin's actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the ROR?/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the ROR?/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, reproductive and cardiovascular functions, modulation of skin pigmentation, hair growth, cancerogenesis, and aging. Melatonin receptor agonists and antagonists have an exciting future since they could define multiple mechanisms by which melatonin modulates the complexity of such a wide variety of physiological and pathological processes. PMID:22245784

Slominski, Radomir M; Reiter, Russel J; Schlabritz-Loutsevitch, Natalia; Ostrom, Rennolds S; Slominski, Andrzej T

2012-04-01

136

Green Light for Nocturnally Migrating Birds  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 during migration as a result of encountering artificial light sources. This happens, for instance, in the North Sea, where large numbers of nocturnally migrating birds are attracted to the many offsh...

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

2008-01-01

137

Role of melatonin in the induction and maintenance of sleep  

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Pharmacokinetic studies of melatonin in young and elderly human volunteers, and the measurement of hypnotic effects in chicks under alternate light-dark or permanent light conditions, show that melatonin is a bioprecursor of hypnotic acetyl metabolites produced by the enzymatic acetylation of both melatonin and 2-oxomelatonin under the control of serotonin N-acetyltransferases (NATs), which are present in the pineal gland. The acetyl metabolite of melatonin, which we call carbo2, is an N-acet...

Fourtillan, Jean B.

2002-01-01

138

Melatonin differentially affects vascular blood flow in humans  

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Melatonin is synthesized and released into the circulation by the pineal gland in a circadian rhythm. Melatonin has been demonstrated to differentially alter blood flow to assorted vascular beds by the activation of different melatonin receptors in animal models. The purpose of the present study was to determine the effect of melatonin on blood flow to various vascular beds in humans. Renal (Doppler ultrasound), forearm (venous occlusion plethysmography), and cerebral blood flow (transcranial...

Cook, Jonathan S.; Sauder, Charity L.; Ray, Chester A.

2011-01-01

139

Chronotypology and melatonin alterations in minimal hepatic encephalopathy  

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Abstract Background "Minimal (subclinical) hepatic encephalopathy" is a term that describes impairment of every day life activities in cirrhosis patients without clinical neurologic abnormalities. Melatonin diurnal pattern disruption and metabolic changes due to liver insufficiency can affect the human biologic clock. Our study was conducted to measure plasma melatonin levels in an attempt to correlate plasma melatonin abnormalities with liver insufficiency severity, and desc...

Velissaris Dimitrios; Karamouzos Vasilis; Polychronopoulos Panagiotis; Karanikolas Menelaos

2009-01-01

140

Extracellular serotonin promotes melatonin release from cultured rat pinealocytes: evidence for an S2-type receptor-mediated autocrine feedback.  

Science.gov (United States)

Recent evidence points to the secretion of serotonin from the rat pineal gland both in vivo and in vitro. In view of the fact that adrenergic stimulation of cultured pinealocytes leads to rapid serotonin release well in advance of melatonin production, the question arises as to the physiological significance of serotonin secretion. The present studies examined the impact of ketanserine, a specific serotonin type 2 receptor antagonist, on the cyclic AMP and melatonin response of cultured rat pinealocytes to adrenergic stimuli. Whereas the beta-adrenergic agonist isoproterenol (1 microM) stimulated cAMP accumulation as well as melatonin release significantly, the presence of ketanserine inhibited these responses in a dose dependent manner. Since the same inhibitory effect of ketanserine was seen in cells stimulated by dibutyryl-cAMP (which acts post-adrenergic receptor to elevate melatonin synthesis), the mechanism for serotonin's feedback actions does not appear to involve changes in adrenergic receptor/cAMP coupling. These results indicate that extracellular serotonin may be important for the full activation of melatonin secretion following adrenergic stimulation. PMID:8032911

Olcese, J; Münker, M

1994-04-18

 
 
 
 
141

[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

142

Melatonin Plays a Protective Role in Postburn Rodent Gut Pathophysiology  

Directory of Open Access Journals (Sweden)

Full Text Available 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 understanding in vivo melatonin mechanisms in control and inflamed tissues will improve our understanding of its potential as a safe anti-inflammatory/antioxidant therapeutic alternative. Towards this end, we tested the hypothesis that the gut is both a source and a target for melatonin and that mesenteric melatonin plays an anti-inflammatory role following major thermal injury in rats with 3rd degree hot water scald over 30% TBSA. Our methods for assessing the gut as a source of melatonin included plasma melatonin ELISA measurements in systemic and mesenteric circulation as well as rtPCR measurement of jejunum and terminal ileum expression of the melatonin synthesizing enzymes arylalkylamine N-acetyltransferase (AA-NAT and 5-hydroxyindole-O-methyltransferase (HIOMT in sham versus day-3 postburn rats. Our melatonin ELISA results revealed that mesenteric circulation has much higher melatonin than systemic circulation and that both mesenteric and systemic melatonin levels are increased three days following major thermal injury. Our rtPCR results complemented the ELISA data in showing that the melatonin synthesizing enzymes AA-NAT and HIOMT are expressed in the ileum and jejunum and that this expression is increased three days following major thermal injury. Interestingly, the rtPCR data also revealed negative feedback by melatonin as exogenous melatonin supplementation at a dose of 7.43 mg (32 ?mole/kg, but not 1.86 mg/kg (8 ?mole/kg drastically suppressed AA-NAT mRNA expression. Our methods also included an assessment of the gut as a target for melatonin utilizing computerized immunohistochemical measurements to quantify the effects of exogenous melatonin supplementation on postburn gut mucosa barrier inflammatory profiles. Here, our results revealed that daily postburn intraperitoneal melatonin administration at a dose of 1.86 mg/kg (8 ?mole/kg significantly suppressed both neutrophil infiltration and tyrosine nitrosylation as revealed by Gr-1 and nitrotyrosine immunohistochemistry, respectively. In conclusion, our results provide support for high mesenteric melatonin levels and dynamic de novo gut melatonin production, both of which increase endogenously in response to major thermal injury, but appear to fall short of abrogating the excessive postburn hyper-inflammation. Moreover, supplementation by exogenous melatonin significantly suppresses gut inflammation, thus confirming that melatonin is protective against postburn inflammation.

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

2010-01-01

143

Melatonin plays a protective role in postburn rodent gut pathophysiology.  

Science.gov (United States)

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 understanding in vivo melatonin mechanisms in control and inflamed tissues will improve our understanding of its potential as a safe anti-inflammatory/antioxidant therapeutic alternative. Towards this end, we tested the hypothesis that the gut is both a source and a target for melatonin and that mesenteric melatonin plays an anti-inflammatory role following major thermal injury in rats with 3rd degree hot water scald over 30% TBSA. Our methods for assessing the gut as a source of melatonin included plasma melatonin ELISA measurements in systemic and mesenteric circulation as well as rtPCR measurement of jejunum and terminal ileum expression of the melatonin synthesizing enzymes arylalkylamine N-acetyltransferase (AA-NAT) and 5-hydroxyindole-O-methyltransferase (HIOMT) in sham versus day-3 postburn rats. Our melatonin ELISA results revealed that mesenteric circulation has much higher melatonin than systemic circulation and that both mesenteric and systemic melatonin levels are increased three days following major thermal injury. Our rtPCR results complemented the ELISA data in showing that the melatonin synthesizing enzymes AA-NAT and HIOMT are expressed in the ileum and jejunum and that this expression is increased three days following major thermal injury. Interestingly, the rtPCR data also revealed negative feedback by melatonin as exogenous melatonin supplementation at a dose of 7.43 mg (32 micromole/kg), but not 1.86 mg/kg (8 micromole/kg) drastically suppressed AA-NAT mRNA expression. Our methods also included an assessment of the gut as a target for melatonin utilizing computerized immunohistochemical measurements to quantify the effects of exogenous melatonin supplementation on postburn gut mucosa barrier inflammatory profiles. Here, our results revealed that daily postburn intraperitoneal melatonin administration at a dose of 1.86 mg/kg (8 micromole/kg) significantly suppressed both neutrophil infiltration and tyrosine nitrosylation as revealed by Gr-1 and nitrotyrosine immunohistochemistry, respectively. In conclusion, our results provide support for high mesenteric melatonin levels and dynamic de novo gut melatonin production, both of which increase endogenously in response to major thermal injury, but appear to fall short of abrogating the excessive postburn hyper-inflammation. Moreover, supplementation by exogenous melatonin significantly suppresses gut inflammation, thus confirming that melatonin is protective against postburn inflammation. PMID:20567497

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

2010-01-01

144

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 product

Kamperis, Konstantinos; Hagstrøm, Søren

2005-01-01

145

Localization, physiological significance and possible clinical implication of gastrointestinal melatonin.  

Science.gov (United States)

The gastrointestinal tract (GIT) is a major source of extrapineal melatonin. In some animals, tissue concentrations of melatonin in the GIT surpass blood levels by 10-100 times and the digestive tract contributes significantly to melatonin concentrations in the peripheral blood, particularly during the day. Some melatonin found in the GIT may originate from the pineal gland, as the organs of the digestive system contain binding sites, which in some species exhibit circadian variation. Unlike the production of pineal melatonin, which is under the photoperiodic control, release of GI melatonin seems to be related to periodicity of food intake. Melatonin and melatonin binding sites were localized in all GI tissues of mammalian and avian embryos. Postnatally, melatonin was localized in the GIT of newborn mice and rats. Phylogenetically, melatonin and melatonin binding sites were detected in GIT of numerous mammals, birds and lower vertebrates. Melatonin is probably produced in the serotonin-rich enterochromaffin cells (EC) of the GI mucosa and can be released into the portal vein postprandially. In addition, melatonin can act as an autocrine or a paracrine hormone affecting the function of GI epithelium, lymphatic tissues of the immune system and the smooth muscles of the digestive tube. Finally, melatonin may act as a luminal hormone, synchronizing the sequential digestive processes. Higher peripheral and tissue levels of melatonin were observed not only after food intake but also after a long-term food deprivation. Such melatonin release may have a direct effect on the various GI tissues but may also act indirectly via the CNS; such action might be mediated by sympathetic or parasympathetic nerves. Melatonin can protect GI mucosa from ulceration by its antioxidant action, stimulation of the immune system and by fostering microcirculation and epithelial regeneration. Melatonin may reduce the secretion of pepsin and the hydrochloric acid and influence the activity of the myoelectric complexes of the gut via its action in the CNS. Tissue or blood levels of melatonin may serve as a marker of GI lesions or tumors. Clinically, melatonin has a potential for a prevention or treatment of colorectal cancer, ulcerative colitis, irritable bowel syndrome, children colic and diarrhea. PMID:11721091

Bubenik, G A

2001-01-01

146

Aging and oxygen toxicity: Relation to changes in melatonin  

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Melatonin (N-acetyl-5-methoxytryptamine) is a chemical mediator produced in the pineal gland and other sites in the body. The melatonin found in the blood is derived almost exclusively from the pineal gland. Since the pineal synthesizes melatonin primarily at night, blood levels of the indole are also higher at night (5–15 fold) than during the day. Some individuals on a nightly basis produce twice as much melatonin as others of the same age. Throughout life, the melatonin rhythm gradually ...

Reiter, Russel J.

1997-01-01

147

Melatonin--a pleiotropic, orchestrating regulator molecule.  

Science.gov (United States)

Melatonin, the neurohormone of the pineal gland, is also produced by various other tissues and cells. It acts via G protein-coupled receptors expressed in various areas of the central nervous system and in peripheral tissues. Parallel signaling mechanisms lead to cell-specific control and recruitment of downstream factors, including various kinases, transcription factors and ion channels. Additional actions via nuclear receptors and other binding sites are likely. By virtue of high receptor density in the circadian pacemaker, melatonin is involved in the phasing of circadian rhythms and sleep promotion. Additionally, it exerts effects on peripheral oscillators, including phase coupling of parallel cellular clocks based on alternate use of core oscillator proteins. Direct central and peripheral actions concern the up- or downregulation of various proteins, among which inducible and neuronal NO synthases seem to be of particular importance for antagonizing inflammation and excitotoxicity. The methoxyindole is also synthesized in several peripheral tissues, so that the total content of tissue melatonin exceeds by far the amounts in the circulation. Emerging fields in melatonin research concern receptor polymorphism in relation to various diseases, the control of sleep, the metabolic syndrome, weight control, diabetes type 2 and insulin resistance, and mitochondrial effects. Control of electron flux, prevention of bottlenecks in the respiratory chain and electron leakage contribute to the avoidance of damage by free radicals and seem to be important in neuroprotection, inflammatory diseases and, presumably, aging. Newly discovered influences on sirtuins and downstream factors indicate that melatonin has a role in mitochondrial biogenesis. PMID:21193011

Hardeland, Rüdiger; Cardinali, Daniel P; Srinivasan, Venkatramanujam; Spence, D Warren; Brown, Gregory M; Pandi-Perumal, Seithikurippu R

2011-03-01

148

Melatonin  

Science.gov (United States)

... in the ears, depression, chronic fatigue syndrome (CFS), fibromyalgia, migraine and other headaches, irritable bowel syndrome (IBS), ... CFS). Osteoporosis. Irritable bowel syndrome (IBS). Birth control. Fibromyalgia. Aging. Other conditions. More evidence is needed to ...

149

Unlike the synchronous Plasmodium falciparum and P. chabaudi infection, the P. berghei and P. yoelii asynchronous infections are not affected by melatonin  

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Full Text Available Piero Bagnaresi1, Eduardo Alves1, Henrique Borges da Silva1, Sabrina Epiphanio2, Maria M Mota2, Célia RS Garcia11Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil; 2Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, PortugalAbstract: We have previously reported that Plasmodium chabaudi and P. falciparum sense the hormone melatonin and this could be responsible for the synchrony of malaria infection. In P. chabaudi and P. falciparum, melatonin induces calcium release from internal stores, and this response is abolished by U73122, a phospholipase C inhibitor, and luzindole, a melatoninreceptor competitive antagonist. Here we show that, in vitro, melatonin is not able to modulate cell cycle, nor to elicit an elevation in intracellular calcium concentration of the intraerythrocytic forms of P. berghei or P. yoelii, two rodent parasites that show an asynchrononous development in vivo. Interestingly, melatonin and its receptor do not seem to play a role during hepatic infection by P. berghei sporozoites either. These data strengthen the hypothesis that hostderived melatonin does not synchronize malaria infection caused by P. berghei and P. yoelii. Moreover, these data explain why infections by these parasites are asynchronous, contrary to what is observed in P. falciparum and P. chabaudi infections.Keywords: malaria, calcium, melatonin, cell cycle, rhythm, sporozoite

Piero Bagnaresi

2009-04-01

150

The role of melatonin as an antioxidant in the follicle  

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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

2012-01-01

151

Expression of melatonin receptors in arteries involved in thermoregulation  

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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

152

Expression of melatonin receptors in arteries involved in thermoregulation  

International Nuclear Information System (INIS)

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

1990-01-01

153

Genetics Home Reference: Autosomal dominant nocturnal frontal lobe epilepsy  

Science.gov (United States)

... disorder catalog Conditions > Autosomal dominant nocturnal frontal lobe epilepsy (often shortened to ADNFLE ) On this page: Description ... What is ADNFLE? Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon form of epilepsy that ...

154

Thirty four years since the discovery of gastrointestinal melatonin.  

Science.gov (United States)

After the discovery of melatonin in the pineal gland by Lerner and co-workers in 1958, melatonin was also detected in the retina and the human appendix. Later, melatonin was confirmed immunohistologically in all segments of the gastrointestinal tract (GIT), in the guts of bovine embryos and in the GIT of low vertebrates. Melatonin was also confirmed in the pancreas and the hepatobiliary system. Melatonin is produced in the enteroendocrine cells of the GIT mucosa. The concentrations of melatonin in the GIT are 10-100x higher than in the plasma and the total amount of melatonin in the GIT is around 400x higher than the amount of melatonin in the pineal gland. Similar to pineal melatonin, GIT melatonin is a multifunctional compound which exhibits some general as well as some specific effects, depending on the organ and the location of GIT tissue. In the GIT, melatonin exhibits endocrine, paracrine, autocrine and luminal actions. Generally, the episodic secretion of melatonin from the GIT is related to the intake and digestion of food and to the prevention of tissue damage caused by hydrochloric acid and digestive enzymes. Some actions, such as the scavenging of hydroxyl free radicals, immunoenhancement and antioxidant effects are of general nature, whereas others, such as an increase of mucosal blood flow, the reduction of peristalsis and the regulation of fecal water content, are specific to the tubular GIT. Generally, melatonin actions oppose those of serotonin. Laboratory and clinical studies indicate that the utilization of melatonin can prevent or treat pathological conditions such as esophageal and gastric ulcers, pancreatitis, colitis, irritable bowel disease, and colon cancer. PMID:18812627

Bubenik, G A

2008-08-01

155

Nocturnal life of young songbirds well before migration  

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In songbirds, nocturnal activity is believed to be a characteristic feature of migration. However, unlike experimental conditions where the onset of nocturnal restlessness is defined as a shift of activity leading up to the dark period, this behaviour has, until now, not been observed in natural conditions. Here we studied the nocturnal behaviour of radio-tagged juvenile Eurasian reed warblers (Acrocephalus scirpaceus) during the pre-migratory period. The birds started nocturnal flights at th...

Mukhin, Andrey; Kosarev, Vlad; Ktitorov, Pavel

2005-01-01

156

Testicular dysfunction in experimental chronic renal insufficiency: a deficiency of nocturnal pineal N-acetyltransferase activity.  

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Biochemical correlates of neuroendocrine/gonadal function and nocturnal levels of serotonin N-acetyltransferase (NAT) activity were determined in partially nephrectomized (PNx), male, Long Evans rats following a 5-week period of chronic renal insufficiency (CRI). PNx animals demonstrated two to four-fold elevations in urea nitrogen and three to four-fold reductions (P less than 0.02) in plasma total testosterone concentrations as compared to sham-operated controls. The pituitary LH contents o...

Holmes, E. W.; Hojvat, S. A.; Kahn, S. E.; Bermes, E. W.

1989-01-01

157

The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial  

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Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/Vurea, a 1.74-fold higher average number of treatments per week, and a 2.45-fol...

Rocco, Michael V.; Lockridge, Robert S.; Beck, Gerald J.; Eggers, Paul W.; Gassman, Jennifer J.; Greene, Tom; Larive, Brett; Chan, Christopher T.; Chertow, Glenn M.; Copland, Michael; Hoy, Christopher D.; Lindsay, Robert M.; Levin, Nathan W.; Ornt, Daniel B.; Pierratos, Andreas

2011-01-01

158

Nocturnal acid breakthrough: consequences and confronting  

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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

2007-03-01

159

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

2007-03-01

160

Paroxysmal nocturnal hemoglobinuria in systemic lupus erythematosus: a case report  

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Abstract Introduction Paroxysmal nocturnal hemoglobinuria is an acquired disorder of hemopoiesis and is characterized by recurrent episodes of intravascular hemolysis due to an increased sensitivity to complement-mediated hemolysis. Systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. We report a case of paroxysmal nocturnal hemoglobinuria that developed in a patient with systemic lupus erythematosus and lupus nephritis. Case presentation...

Nakamura Norio; Sugawara Toshiyuki; Shirato Ken-ichi; Kumasaka Ryuichiro; Nakamura Masayuki; Shimada Michiko; Fujita Takeshi; Murakami Reiichi; Shimaya Yuko; Osawa Hiroshi; Yamabe Hideaki; Okumura Ken

2011-01-01

 
 
 
 
161

The Influence of Gonadectomy on Anxiolytic and Antidepressant Effects of Melatonin in Male and Female Wistar Rats: A Possible Implication of Sex Hormones  

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Full Text Available The main objective of this study was to analyze the effects of sex, ovariectomy (Ovx and orchidectomy (Orx on antidepressant and anxiolytic effect of melatonin in forced swimming test, open field test and elevated plus maze test. Initially, 4 mg/kg of melatonin was daily administered, at 4:00 pm, to intact male and female rats during 8 weeks. Our results have shown that the effect of chronic injection of Mel is sex dependent in the three behaviors tests. Females rats have responded better than males in behavior test study after administration of melatonin, this difference between the sexes may be related to the action of sex hormones (androgens and estrogens on behavior in males as well as in females. Secondly, to determine the possible interaction between Melatonin and steroid hormones, Ovx/sham female received Mel at dose of 4mg/kg alone or NaCl (0.9% alone, and Orx/sham male received Mel at dose of 4 mg/kg alone or NaCl (0.9% alone daily and during 8 weeks of treatment at 4:00 pm. All animals were tested in the open-field test, elevated plus maze test for anxiety behavior study, and forced swimming test for depression behavior study. Results revealed that Mel exerts an anxiolytic and antidepressant effects in the orchidectomized males and in intact females, confirming that the suppression of androgens by orchidectomy improved anxiolytic and antidepressant effects of melatonin in males. However in females, the suppression of estrogen by ovariectomy masked the antidepressant and anxiolytic effects of melatonin. Our results confirmed that the antidepressant and anxiolytic effects of melatonin are linked to sex hormones.

Ouichou Ali

2012-06-01

162

Neurobiology, Pathophysiology, and Treatment of Melatonin Deficiency and Dysfunction  

Science.gov (United States)

Melatonin is a highly pleiotropic signaling molecule, which is released as a hormone of the pineal gland predominantly during night. Melatonin secretion decreases during aging. Reduced melatonin levels are also observed in various diseases, such as types of dementia, some mood disorders, severe pain, cancer, and diabetes type 2. Melatonin dysfunction is frequently related to deviations in amplitudes, phasing, and coupling of circadian rhythms. Gene polymorphisms of melatonin receptors and circadian oscillator proteins bear risks for several of the diseases mentioned. A common symptom of insufficient melatonin signaling is sleep disturbances. It is necessary to distinguish between symptoms that are curable by short melatonergic actions and others that require extended actions during night. Melatonin immediate release is already effective, at moderate doses, for reducing difficulties of falling asleep or improving symptoms associated with poorly coupled circadian rhythms, including seasonal affective and bipolar disorders. For purposes of a replacement therapy based on longer-lasting melatonergic actions, melatonin prolonged release and synthetic agonists have been developed. Therapies with melatonin or synthetic melatonergic drugs have to consider that these agents do not only act on the SCN, but also on numerous organs and cells in which melatonin receptors are also expressed.

Hardeland, Rudiger

2012-01-01

163

Neurobiology, pathophysiology, and treatment of melatonin deficiency and dysfunction.  

Science.gov (United States)

Melatonin is a highly pleiotropic signaling molecule, which is released as a hormone of the pineal gland predominantly during night. Melatonin secretion decreases during aging. Reduced melatonin levels are also observed in various diseases, such as types of dementia, some mood disorders, severe pain, cancer, and diabetes type 2. Melatonin dysfunction is frequently related to deviations in amplitudes, phasing, and coupling of circadian rhythms. Gene polymorphisms of melatonin receptors and circadian oscillator proteins bear risks for several of the diseases mentioned. A common symptom of insufficient melatonin signaling is sleep disturbances. It is necessary to distinguish between symptoms that are curable by short melatonergic actions and others that require extended actions during night. Melatonin immediate release is already effective, at moderate doses, for reducing difficulties of falling asleep or improving symptoms associated with poorly coupled circadian rhythms, including seasonal affective and bipolar disorders. For purposes of a replacement therapy based on longer-lasting melatonergic actions, melatonin prolonged release and synthetic agonists have been developed. Therapies with melatonin or synthetic melatonergic drugs have to consider that these agents do not only act on the SCN, but also on numerous organs and cells in which melatonin receptors are also expressed. PMID:22629173

Hardeland, Rüdiger

2012-01-01

164

[Nocturnal enuresis in children. II--Diagnosis and treatment of nocturnal enuresis].  

Science.gov (United States)

The classification of the various types of urination disorders among children as well as the latest theories explaining the causes of nocturnal enuresis were presented in the first part of the article entitled "Nocturnal Enuresis in Children" (in "Medycyna Wieku Rozwojowego" 1998, II, 1 pp. 55-69). The second part of this article concentrates on the differential diagnostics of urination disorders amongst patients seeking help for nocturnal enuresis. The diagnostic model developed by the Urodynamic Unit at the Department of Paediatric Surgery, National Research Institute of Mother and Child can be applied in an outpatient clinic. Hospitalization of the patient is not necessary to carry out the study, meaning that the child is spared any additional stress. Currently applied methods for treating nocturnal enuresis by non-pharmacological methods are also discussed in this text. PMID:10910655

Paruszkiewicz, G

1999-01-01

165

Nocturnal faecal soiling and anal masturbation.  

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Two cases of late onset faecal soiling as a result of anal masturbation in children who were neither mentally handicapped nor psychotic were studied. The role of soiling in aiding the young person and his family to avoid separating and maturing is highlighted. We suggest that the association of anal masturbation and resistant nocturnal soiling may be unrecognised.

Clark, A. F.; Tayler, P. J.; Bhate, S. R.

1990-01-01

166

Melatonin implantátumok hatása a juhok ivarzására  

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A dolgozat a melatonin implantátumok hatását vizsgálja a juhok ivarzására. Vizsgálja a progeszteron szintet, és a született bárányokat. Az implantátumok mennyivel tudják el?bbre hozni az ivari ciklust. A bárány létszám jelent?s különbséget mutat a melatoninnal + ivarzászinkronizált anayákban, mint a csak ivarzás szinkronizáltak esetén. A BHB szintet és a NEFA szintet is vizsgálja, bár ezek különbsége nem szignifikáns.

2012-01-01

167

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

2009-01-01

168

Genetic variation of melatonin productivity in laboratory mice under domestication  

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Melatonin is a pineal hormone produced at night; however, many strains of laboratory mice are deficient in melatonin. Strangely enough, the gene encoding HIOMT enzyme (also known as ASMT) that catalyzes the last step of melatonin synthesis is still unidentified in the house mouse (Mus musculus) despite the completion of the genome sequence. Here we report the identification of the mouse Hiomt gene, which was mapped to the pseudoautosomal region (PAR) of sex chromosomes. The gene was highly po...

Kasahara, Takaoki; Abe, Kuniya; Mekada, Kazuyuki; Yoshiki, Atsushi; Kato, Tadafumi

2010-01-01

169

Melatonin delays clutch initiation in a wild songbird  

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The hormone melatonin is known to play an important role in regulating many seasonal changes in physiology, morphology and behaviour. In birds, unlike in mammals, melatonin has thus far been thought to play little role in timing seasonal reproductive processes. This view is mainly derived from laboratory experiments on male birds. This study tests whether melatonin is capable of influencing the timing of clutch initiation in wild female songbirds. Free-living female great tits (Parus major) t...

Greives, Timothy J.; Kingma, Sjouke A.; Beltrami, Giulia; Hau, Michaela

2012-01-01

170

Impact of oral melatonin on the electroretinogram cone response.  

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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 ...

Gagne?, Anne-marie; Danilenko, Konstantin; Rosolen, Serge; He?bert, Marc

2009-01-01

171

Melatonin Supplementation in Patients with Complete Tetraplegia and Poor Sleep  

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People with complete tetraplegia have interrupted melatonin production and commonly report poor sleep. Whether the two are related is unclear. This pilot study investigated whether nightly supplementation of 3?mg melatonin would improve objective and subjective sleep in tetraplegia. Five participants with motor and sensory complete tetraplegia ingested 3?mg melatonin (capsule) two hours prior to usual sleep time for two weeks. Full portable sleep studies were conducted in participants' ho...

Spong, Jo; Kennedy, Gerard A.; Brown, Douglas J.; Armstrong, Stuart M.; Berlowitz, David J.

2013-01-01

172

Impact of oral melatonin on the electroretinogram cone response  

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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 o...

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

2009-01-01

173

Treatment with beta-adrenoceptor blockers reduces plasma melatonin concentration.  

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In treated hypertensive patients plasma melatonin levels were lower in subjects receiving beta-adrenoceptor blockers than those treated with diuretics. Melatonin concentrations in middle-aged and young control subjects were similar to each other and to those of the diuretic-treated patients. The results suggest that treatment with beta-adrenoceptor blockers causes a persistent reduction in plasma melatonin but it is unclear if this finding has clinical implications.

1985-01-01

174

Measurement of melatonin in body fluids: Standards, protocols and procedures  

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The circadian rhythm of melatonin in saliva or plasma, or of the melatonin metabolite 6-sulfatoxymelatonin (a6MTs) in urine, is a defining feature of suprachiasmatic nucleus (SCN) function, the body’s endogenous oscillatory pacemaker. The primary objective of this review is to ascertain the clinical benefits and limitations of current methodologies employed for detection and quantification of melatonin in biological fluids and tissues.A search of the English-language literature (Medline) an...

Almeida, Eduardo; Mascio, Paolo; Harumi, Tatsuo; Warren Spence, D.; Moscovitch, Adam; Hardeland, Ru?diger; Cardinali, Daniel; Brown, Gregory M.; Pandi-perumal, S. R.

2010-01-01

175

Melatonin Plays a Protective Role in Postburn Rodent Gut Pathophysiology  

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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 understanding in vivo melatonin mechanisms in control and inflamed tissues will improve our understanding of its potential as a safe anti-inflammatory/antioxidant therapeutic alternative. Towards this end,...

Al-ghoul, Walid M.; Abu-shaqra, Steven; Park, Byeong Gyu; Fazal, Nadeem

2010-01-01

176

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

177

Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.  

Science.gov (United States)

This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8-arms maze' tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS). PMID:24727051

Allagui, M S; Feriani, A; Saoudi, M; Badraoui, R; Bouoni, Z; Nciri, R; Murat, J C; Elfeki, A

2014-08-01

178

Interactions between melatonin and nicotinamide nucleotide: NADH preservation in cells and in cell-free systems by melatonin.  

Science.gov (United States)

Interactions of melatonin and nicotinamide adenine dinucleotide (NADH) have been studied in different experimental models including NADH-promoted oxyhemoglobin oxidation, vanadate-induced NADH oxidation and paraquat-induced NADH depletion in cultured PC12 cells. Our findings indicate that melatonin preserves NADH levels under oxidative stress both in cell-free systems and in cultured PC12 cells. These interactions likely involve electron donation by melatonin and reduction of the NAD radical. As a result, the NAD radical is recycled to NADH and melatonin is oxidized to N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK). NADH is a central molecule at the crossroads between energy metabolism and the antioxidant defense system in organisms. Recycling of NADH by melatonin might improve the efficiency of NADH as an energy carrier and as an antioxidant. Interactions between melatonin and NADH may be implicated in mitochondrial metabolism. PMID:16098097

Tan, Dun-Xian; Manchester, Lucien C; Sainz, Rosa M; Mayo, Juan C; Leon, Josefa; Hardeland, Ruediger; Poeggeler, Burkhard; Reiter, Russel J

2005-09-01

179

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

2013-10-01

180

Maternal and placental melatonin: actions and implication for successful pregnancies.  

Science.gov (United States)

Melatonin is one of the main sources of mitochondrial protection and its protective effects are equal or even better if compared with several consecrated antioxidants. Furthermore, the activation of specific melatonin receptors triggers several cellular pathways that improve the oxidoreduction and inflammatory cellular state. The discovery of the melatoninergic machinery in placental cells was the first step to understand the effects of this indoleamine during pregnancy. In critical points of pregnancy, melatonin has been pointed as a protagonist and its beneficial effects have been shown as essential for the control of trophoblastic function and development. On the contrary of the plasmatic melatonin (produced in pineal gland), placental melatonin does not vary according to the circadian cycle and acts as an autocrine, paracrine, intracrine, and endocrine hormone. The important effects of melatonin in placenta have been demonstrated in the physiopathology of pre-eclampsia with alterations in the levels of melatonin and in the expression of its receptors and synthetizing enzymes. Some authors suggested melatonin as a biomarker of pre-eclampsia and as a possible treatment for this disease and other obstetric pathologies associated with placental defect and increases in oxidative stress. This review will approach the beneficial effects of melatonin on placenta homeostasis and consequently on pregnancy and fetal health. PMID:24971781

Sagrillo-Fagundes, L; Soliman, A; Vaillancourt, C

2014-06-01

 
 
 
 
181

Melatonin reduces dimethylnitrosamine-induced liver fibrosis in rats.  

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Increased deposition of the extracellular matrix components, particularly collagen, is a central phenomenon in liver fibrosis. Stellate cells, the central mediators in the pathogenesis of fibrosis are activated by free radicals, and synthesize collagen. Melatonin is a potent physiological scavenger of hydroxyl radicals. Melatonin has also been shown to be involved in the inhibitory regulation of collagen content in tissues. At present, no effective treatment of liver fibrosis is available for clinical use. We aimed to test the effects of melatonin on dimethylnitrosamine (DMN)-induced liver damage in rats. Wistar albino rats were injected with DMN intraperitoneally. Following a single dose of 40 mg/kg DMN, either saline (DMN) or 100 mg/kg daily melatonin was administered for 14 days. In other rats, physiologic saline or melatonin were injected for 14 days, following a single injection of saline as control. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) levels were evaluated in blood and tissue homogenates. DMN caused hepatic fibrotic changes, whereas melatonin suppressed these changes in five of 14 rats (P < 0.05). DMN administration resulted in increased hydroxyproline and MDA levels, and decreased GSH and SOD levels, whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin functions as a potent fibrosuppressant and antioxidant, and may be a therapeutic choice. PMID:15298665

Tahan, Veysel; Ozaras, Resat; Canbakan, Billur; Uzun, Hafize; Aydin, Seval; Yildirim, Beytullah; Aytekin, Huseyin; Ozbay, Gulsen; Mert, Ali; Senturk, Hakan

2004-09-01

182

Role of melatonin in alleviating cold stress in Arabidopsis thaliana.  

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Melatonin (N-acetyl-5-methoxytryptamine) has been implicated in abiotic and biotic stress tolerance in plants. However, information on the effects of melatonin in cold-stress tolerance in vivo is limited. In this study, the effect of melatonin was investigated in the model plant Arabidopsis thaliana challenged with a cold stress at 4?C for 72 and 120 hr. Melatonin-treated plants (10 and 30 ?m) had significantly higher fresh weight, primary root length, and shoot height compared with the nontreated plants. To aid in the understanding of the role of melatonin in alleviating cold stress, we investigated the effects of melatonin treatment on the expression of cold-related genes. Melatonin up-regulated the expression of C-repeat-binding factors (CBFs)/Drought Response Element Binding factors (DREBs), a cold-responsive gene, COR15a, a transcription factor involved in freezing and drought-stress tolerance CAMTA1 and transcription activators of reactive oxygen species (ROS)-related antioxidant genes, ZAT10 and ZAT12, following cold stress. The up-regulation of cold signaling genes by melatonin may stimulate the biosynthesis of cold-protecting compounds and contribute to the increased growth of plants treated with exogenous melatonin under cold stress. PMID:24350934

Bajwa, Vikramjit S; Shukla, Mukund R; Sherif, Sherif M; Murch, Susan J; Saxena, Praveen K

2014-04-01

183

Effects of melatonin on sleep and neurochemistry in the rat.  

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1 The effects of intraperitoneally administered melatonin on sleep and brain neurochemistry in the rat were studied by use of EEG recording and standard fluorescence techniques. 2 Melatonin, 10 mg/kg, reduced time to sleep onset and time spent awake but increased both slow wave and paradoxical sleep. Qualitatively similar but smaller effects were produced by a dose of 2.5 mg/kg. 3 Neither dose of melatonin altered normal EEG patterns or disrupted normal sleep behaviour. 4 Melatonin, 20 mg/Kg,...

Holmes, S. W.; Sugden, D.

1982-01-01

184

Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids  

International Nuclear Information System (INIS)

In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p 4 displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl4, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage. Highlights: ? After 30-day chronic CCl4 intoxication mitochondria displayed considerable changes. ? The functional parameters of mitochondria were similar to the control values. ? Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ? The above complex enhanced regenerative processes in the liver.

2012-06-15

185

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

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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,...

2013-01-01

186

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). Citation: Kansagra S; Walter R; Vaughn B. Nocturnal temazepam in the treatment of narcolepsy. J Clin Sleep Med 2013;9(5):499-500.

Kansagra, Sujay; Walter, Robert; Vaughn, Bradley

2013-01-01

187

Melatonin in Alzheimer's disease and other neurodegenerative disorders  

Science.gov (United States)

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

188

Melatonin in Alzheimer's disease and other neurodegenerative disorders.  

Science.gov (United States)

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-beta 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. PMID:16674804

Srinivasan, V; Pandi-Perumal, S R; Cardinali, D P; Poeggeler, B; Hardeland, R

2006-01-01

189

Paroxysmal Nocturnal Hemoglobinuria from Bench to Bedside  

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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease that presents with protean manifestations. Clinical and laboratory investigation over the past 25 years have uncovered most of the basic science underpinnings of PNH and have led to the development of a highly effective targeted therapy. PNH originates from a multipotent hematopoietic stem cell (HSC) that acquires a somatic mutation in a gene called phosphatidylinositol glycan anchor biosynthesis, class A (PIG-A). The PIG...

Pu, Jeffrey J.; Brodsky, Robert A.

2011-01-01

190

How I treat paroxysmal nocturnal hemoglobinuria  

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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal blood disorder that manifests with hemolytic anemia, bone marrow failure, and thrombosis. Many of the clinical manifestations of the disease result from complement-mediated intravascular hemolysis. Allogeneic bone marrow transplantation is the only curative therapy for PNH. Eculizumab, a monoclonal antibody that blocks terminal complement activation, is highly effective in reducing hemolysis, improving quality of life, and reducing th...

Brodsky, Robert A.

2009-01-01

191

Antidiuretic hormone regulation in patients with primary nocturnal enuresis.  

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Treatment of primary nocturnal enuresis using DDAVP is based upon the hypothesis that antidiuretic hormone (ADH) secretion is insufficient at night. The known efficacy of the treatment on the one hand, and persisting doubts about its theoretical basis on the other, formed the background of the present study. Ten children (mean age 10.5 years) with primary nocturnal enuresis were compared with a corresponding control group of eight patients. Diurnal and nocturnal urine production, ADH secretio...

Eggert, P.; Ku?hn, B.

1995-01-01

192

Visual cues and parental favouritism in a nocturnal bird  

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Visual signals are crucial for parent–offspring communication, although their functioning has been neglected for nocturnal birds. Here, we investigated parental preference for nestling coloration in nocturnal conditions—a question hitherto unexplored—in a nocturnal raptor, the scops owl (Otus scops). We assessed how parents allocated food during the night in relation to a manipulation of ultraviolet (UV) reflectance of the cere (skin above the beak) of their offspring. Reflectance of th...

Parejo, Deseada; Avile?s, Jesu?s M.; Rodri?guez, Juan

2010-01-01

193

Is there any correlation between hypercalciuria and nocturnal enuresis?  

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Nocturnal enuresis is a common problem among children. Hypercalciuria has been proposed as an important etiology of bedwetting. We investigated the incidence of hypercalciuria among children with nocturnal enuresis and age- and sex-matched healthy controls. In this case–control study 118 children with nocturnal enuresis and 100 age-, sex-, and educational district-matched healthy controls were recruited. Urine samples were obtained from each subject twice: immediately after awakening and 2 ...

Nikibakhsh, A.; Poostindooz, H.; Mahmoodzadeh, H.; Karamyyar, M.; Ghareaghaji, R. Rasoul; Sepehrvand, N.

2012-01-01

194

Effect of sleep deprivation on overnight bronchoconstriction in nocturnal asthma.  

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Nocturnal cough and wheeze are common in asthma. The cause of nocturnal asthma is unknown and there is conflicting evidence on whether sleep is a factor. Twelve adult asthmatic subjects with nocturnal wheeze were studied on two occasions: on one night subjects were allowed to sleep and on the other they were kept awake all night, wakefulness being confirmed by electroencephalogram. Every patient developed bronchoconstriction overnight both on the asleep night, when peak expiratory flow (PEF) ...

Catterall, J. R.; Rhind, G. B.; Stewart, I. C.; Whyte, K. F.; Shapiro, C. M.; Douglas, N. J.

1986-01-01

195

Melatonin inhibits cholangiocyte hyperplasia in cholestatic rats by interaction with MT1 but not MT2 melatonin receptors.  

Science.gov (United States)

In bile duct-ligated (BDL) rats, large cholangiocytes proliferate by activation of cAMP-dependent signaling. Melatonin, which is secreted from pineal gland as well as extrapineal tissues, regulates cell mitosis by interacting with melatonin receptors (MT1 and MT2) modulating cAMP and clock genes. In the liver, melatonin suppresses oxidative damage and ameliorates fibrosis. No information exists regarding the role of melatonin in the regulation of biliary hyperplasia. We evaluated the mechanisms of action by which melatonin regulates the growth of cholangiocytes. In normal and BDL rats, we determined the hepatic distribution of MT1, MT2, and the clock genes, CLOCK, BMAL1, CRY1, and PER1. Normal and BDL (immediately after BDL) rats were treated in vivo with melatonin before evaluating 1) serum levels of melatonin, bilirubin, and transaminases; 2) intrahepatic bile duct mass (IBDM) in liver sections; and 3) the expression of MT1 and MT2, clock genes, and PKA phosphorylation. In vitro, large cholangiocytes were stimulated with melatonin in the absence/presence of luzindole (MT1/MT2 antagonist) and 4-phenyl-2-propionamidotetralin (MT2 antagonist) before evaluating cell proliferation, cAMP levels, and PKA phosphorylation. Cholangiocytes express MT1 and MT2, CLOCK, BMAL1, CRY1, and PER1 that were all upregulated following BDL. Administration of melatonin to BDL rats decreased IBDM, serum bilirubin and transaminases levels, the expression of all clock genes, cAMP levels, and PKA phosphorylation in cholangiocytes. In vitro, melatonin decreased the proliferation, cAMP levels, and PKA phosphorylation, decreases that were blocked by luzindole. Melatonin may be important in the management of biliary hyperplasia in human cholangiopathies. PMID:21757639

Renzi, Anastasia; Glaser, Shannon; Demorrow, Sharon; Mancinelli, Romina; Meng, Fanyin; Franchitto, Antonio; Venter, Julie; White, Mellanie; Francis, Heather; Han, Yuyan; Alvaro, Domenico; Gaudio, Eugenio; Carpino, Guido; Ueno, Yoshiyuki; Onori, Paolo; Alpini, Gianfranco

2011-10-01

196

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

2012-09-01

197

Renal clearance of melatonin Renale opruiming van melatonien  

Directory of Open Access Journals (Sweden)

Full Text Available Only two publications exist in which actual values for the renal clearance of intact melatonin in man is described. The melatonin clearance values were, however, obtained either after the oral intake of melatonin, or by applying different techniques for the determination of melatonin in urine and plasma. In this study, renal clearance of melatonin was determined during the hours where melatonin concentrations are relatively constant. Melatonin levels in plasma and urine respectively were each deter­mined by three analytical techniques, i.e. the Fraser, NID and WHB methods. The results show renal clearance of melatonin to be under 2 ml/min and that higher values are obtained with analytical techniques which bypass the extraction process.Slegs twee publikasies bestaan waarin die omvang van die renale opruiming van melatonien in mense beskryf word. Die melatonienopruimingswaardes is egter verkry na óf orale toediening van melatonien óf deur verskillende tegnieke te gebruik vir die bepaling van melatonien in die plasma en urien onderskeidelik. In hierdie studie is melatonienopruiming bepaal oor 'n tyd van die dag wanneer die plasmavlakke relatief konstant bly, en is die melatonienvlakke in plasma en urien elk onderskeidelik met die Fraser-, NID- en WHB-metodes bepaal. Die resultate toon dat melatonienopruiming onder 2 ml/min is en dat hoër waardes verkry word wanneer van metodes gebruik gemaak word wat die ekstraksieprosedures omseil.

Editorial Office

1996-07-01

198

Melatonin, a potential effective protector in whole body ?-irradiated rats  

International Nuclear Information System (INIS)

Melatonin (N-acetyl-5-methoxytryptamine), the chief hormone of pineal gland, is widely distributed in animal kingdom. It is claimed for its antioxidant and free radical properties. The present study aimed to examine the radio protective potentiality and efficacy of melatonin against damages induced in whole body ?-irradiated rats. Animals received melatonin (10 mg/ kg body wt/ day) for 10 successive days pre-exposure to 3 Gy of ?-radiation (acute dose). Rats sacrificed at 10 and 20 days post the irradiation time. The results revealed that the prolonged administration of melatonin has ameliorated the radiation- induced depletion in brain, testis and serum glutathione (GSH) level and a decrease in serum glutathione peroxidase (GPX) activity when compared with their matched values in irradiated rats. In addition, remarkable decreases in the concentration of lipid peroxidation (LPO) product; malondialdhyde (MDA) was observed in brain, testis and serum of rats received melatonin pre-radiation exposure. As well as, significant decreases in disulphide glutathione (GSSG) were observed in serum.Histopathological examination of brain and testis showed that administration of melatonin pre-irradiation according to the present regimen has attenuated radiation induced tissue damages and improved tissue architecture. Cytogenetically, the chromosomal aberration (CA) assay in bone marrow pointed out a significant difference between rats received melatonin pre-irradiation and ?-irradiated rats in most CA types. Accordingly, it could be postulated the tissue diversity and cytogenetic impact of the administrated melatonin against acute ion syndrome in rat model.

2010-01-01

199

Melatonin in higher plants: occurrence and possible functions.  

Science.gov (United States)

Melatonin may be ubiquitous in the plant kingdom. This review considers the evaluation of methods of melatonin determination in plant material and possible melatonin functions in plants. Concerning the determination methods, the only reliable techniques are liquid chromatography--mass spectrometry or gas chromatography--mass spectrometry after some purification steps of the extract. Melatonin was shown to delay flower induction in some photoperiodic plants and in the dinoflagellate Lingulodinium it replaces, in part, the requirement of darkness for cyst formation. Melatonin may also have a function as an antioxidant and it may possess some auxin-like effects. Finally, it may act as a signal for interaction of plants with herbivores and pests. Further research is needed to clarify these potential functions. PMID:16207287

Kolár, Jan; Machácková, Ivana

2005-11-01

200

Radioprotective effects of melatonin on radiation-induced cataract  

International Nuclear Information System (INIS)

One of the mechanisms proposed to explain lens opacification is the oxidation of crystallins, either by radiation or reactive oxygen species (ROS). It has been shown that melatonin has both an anti-peroxidative effect on several tissues and a scavenger effect on ROS. The purpose of this study was to determine the antioxidant role of melatonin (5 mg/kg/day) against radiation-induced cataract in the lens after total-cranium irradiation of rats with a single dose of 5 Gy. Sprague-Dawley rats were divided into four groups. Control group received neither melatonin nor irradiation. Irradiated rats (IR) and melatonin+irradiated rats (IR+Mel) groups were exposed to total cranium irradiation of 5 Gy in a single dose by using a cobalt-60 teletherapy unit. IR+Mel and melatonin (Mel) groups were administered 5 mg/kg melatonin daily by intraperitoneal injections during ten days. Chylack's cataract classification was used in this study. At the end of the 10th day, the rats were killed and their eyes were enucleated to measure the antioxidant enzymes i.e. the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and lipid peroxidation level (malondialdehyde (MDA)). Irradiation significantly increased the MDA level, as an end product of lipid peroxidation, and also significantly decreased SOD and GSH-Px activity, emphasizing the generation of increased oxidative stress. Rats injected with melatonin only did not cause cataract formation. Melatonin supplementation with irradiation significantly increased the activity of SOD and GSH-Px enzymes and significantly decreased the MDA level. Total cranium irradiation of 5 Gy in a single dose enhanced cataract formation, and melatonin supplementation protected the lenses from radiation-induced cataract formation. Our results suggest that supplementing cancer patients with adjuvant therapy of melatonin may reduce patients suffering from toxic therapeutic regimens such as chemotherapy and/or radiotherapy and may provide an alleviation of the symptoms due to radiation-induced organ injuries. (author)

2005-06-01

 
 
 
 
201

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

Science.gov (United States)

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. PMID:23171152

Vitalini, Sara; Gardana, Claudio; Simonetti, Paolo; Fico, Gelsomina; Iriti, Marcello

2013-04-01

202

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

Ahmet Korkmaz

2011-02-01

203

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

204

Green Light for Nocturnally Migrating Birds  

Directory of Open Access Journals (Sweden)

Full Text Available 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 during migration as a result of encountering artificial light sources. This happens, for instance, in the North Sea, where large numbers of nocturnally migrating birds are attracted to the many offshore platforms. Our aim is to develop bird-friendly artificial lighting that meets human demands for safety but does not attract and disorient birds. Our current working hypothesis is that artificial light interferes with the magnetic compass of the birds, one of several orientation mechanisms and especially important during overcast nights. Laboratory experiments have shown the magnetic compass to be wavelength dependent: migratory birds require light from the blue-green part of the spectrum for magnetic compass orientation, whereas red light (visible long-wavelength disrupts magnetic orientation. We designed a field study to test if and how changing light color influenced migrating birds under field conditions. We found that nocturnally migrating birds were disoriented and attracted by red and white light (containing visible long-wavelength radiation, whereas they were clearly less disoriented by blue and green light (containing less or no visible long-wavelength radiation. This was especially the case on overcast nights. Our results clearly open perspective for the development of bird-friendly artificial lighting by manipulating wavelength characteristics. Preliminary results with an experimentally developed bird-friendly light source on an offshore platform are promising. What needs to be investigated is the impact of bird-friendly light on other organisms than birds.

Marcel R. Wernand

2008-12-01

205

Early dinner reduces nocturnal gastric acidity.  

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This study examines whether eating food at different times has differential effects on intragastric pH. Experiments were done in 23 healthy volunteers (12 men). Intragastric acidity was monitored by ambulatory 22 hour pH-metry. Composition of meals was standardised: breakfast and lunch at 7 am and 12 noon respectively, and dinner at 6 or 9 pm, in random order. The time of going to bed and getting up was also standardised. With early dinner nocturnal pH was higher, than with late dinner (pH me...

Duroux, P.; Bauerfeind, P.; Emde, C.; Koelz, H. R.; Blum, A. L.

1989-01-01

206

HLA antigens in paroxysmal nocturnal hemoglobinuria.  

Science.gov (United States)

10 patients with paroxysmal nocturnal hemoglobinuria were studied taking 109 normal subjects of the Cuban population as control group. 26 HLA antigens corresponding to loci A and B were studied in both groups. Phenotypical frequency of both groups were compared. No statistically significant increase was found for any of the studied antigens, though there was a nonsignificant increase for antigens HLA-B7 and BW-21. These results might be influenced by the small number of patients studied due to the rareness of the disease. PMID:6768210

Ustariz, C R; Arce, S; Hernández, P; Almaguer, M; Pérez, S; Ballester, J M

1980-01-01

207

Paroxysmal nocturnal hemoglobinuria presenting as moyamoya syndrome.  

Science.gov (United States)

We report an 11-year-old girl who has paroxysmal nocturnal hemoglobinuria (PNH) and was admitted because of recurrent cerebrovascular accidents (CVA) and intermittent hemoglobinuria. Internal carotid angiography revealed bilateral typical moyamoya patterns. Although CVA due to arterial thrombosis may occur in PNH, the basal moyamoya vessels were never mentioned in case reports yet. The moyamoya syndrome has been reported in a variety of diseases and represents the nonspecific response to an impairment of arterial flow at specific sites in the brain. Our case discloses that PNH may present as moyamoya syndrome. PMID:8733912

Lin, H C; Chen, R L; Wang, P J

1996-01-01

208

Melatonin affects the temporal pattern of vocal signatures in birds.  

Science.gov (United States)

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. PMID:22506964

Derégnaucourt, Sébastien; Saar, Sigal; Gahr, Manfred

2012-10-01

209

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

2013-09-01

210

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

Science.gov (United States)

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. PMID:22739839

Pandi-Perumal, Seithikurippu R; BaHammam, Ahmed S; Brown, Gregory M; Spence, D Warren; Bharti, Vijay K; Kaur, Charanjit; Hardeland, Rüdiger; Cardinali, Daniel P

2013-04-01

211

Artificial light and nocturnal activity in gammarids.  

Science.gov (United States)

Artificial light is gaining attention as a potential stressor to aquatic ecosystems. Artificial lights located near streams increase light levels experienced by stream invertebrates and we hypothesized light would depress night drift rates. We also hypothesized that the effect of light on drift rates would decrease over time as the invertebrates acclimated to the new light level over the course of one month's exposure. These hypotheses were tested by placing Gammarus spp. in eight, 75 m × 1 m artificial flumes. One flume was exposed to strong (416 lx) artificial light at night. This strong light created a gradient between 4.19 and 0.04 lx over the neighboring six artificial flumes, while a control flume was completely covered with black plastic at night. Night-time light measurements taken in the Berlin area confirm that half the flumes were at light levels experienced by urban aquatic invertebrates. Surprisingly, no light treatment affected gammarid drift rates. In contrast, physical activity measurements of in situ individually caged G. roeseli showed they increased short-term activity levels in nights of complete darkness and decreased activity levels in brightly lit flumes. Both nocturnal and diurnal drift increased, and day drift rates were unexpectadly higher than nocturnal drift. PMID:24688857

Perkin, Elizabeth K; Hölker, Franz; Heller, Stefan; Berghahn, Rüdiger

2014-01-01

212

Nocturnal panic attacks / Ataques de pânico noturno  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese 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. Abstract in english 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 a [...] ttacks, 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.

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

213

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)

2005-12-01

214

Urinary Melatonin Levels and Skin Malignancy  

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Full Text Available Melatonin inhibits tumor genesis in a variety of in vivo and in vitro experimental models of neoplasia. In industrialized societies, light at night, by suppressing melatonin production, poses a new risk for the development of a variety of cancers such as breast cancer. This effect on skin has been previously studied only in animals and not in humans. Our goal was to examine the relationship between 24-hour 6-sulphatoxymelatonin levels and skin cancer in a case-control study of 70 patients with skin cancer and 70 healthy individuals. The level of 6-sulfatoxymelatonin was measured in 24-hour urine by the ELISA method. In the case group, 55 (78% patients had basal cell carcinoma and 15 (22% had squamous cell carcinoma. The mean level of 24-hour urine 6-sulfatoxymelatonin was significantly higher in the control group (P<0.001. Also, sleep duration had a significant difference between the two groups (P=0.001. It seems that a low level of 24-hour urinary 6-sulfatoxymelatonin renders human beings prone to skin cancer. This association, however, requires further investigation.

Reza Ghaderi

2014-01-01

215

Nocturnal panic attack: is it an another subtype?  

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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.

Sezgin Erdiman

2011-01-01

216

Melatonin and 5-methoxytryptamine in non-metazoans.  

Science.gov (United States)

Melatonin seems to be an almost ubiquitous substance, which has been detected not only in metazoans, but also in all major non-metazoan taxa investigated, including bacteria, dinoflagellates, euglenoids, trypanosomids, fungi, rhodophyceans, pheophyceans, chlorophyceans and angiosperms. Despite its vast abundance, little is known to date about its functions. Its presence is not necessarily associated with circadian rhythmicity, which is evident in yeast. Circadian rhythms of melatonin have been reported in non-metazoans only for several unicellular organisms and in one angiosperm. In dinoflagellates, which have been studied in the most detail, the effects on enzyme activities and on phase shifting are known, but the most spectacular actions concerning the stimulation of bioluminescence, changes in cytoplasmic pH and induction of resting stages, can be related to a metabolite of melatonin, the 5-methoxytryptamine; therefore, melatonin should also be considered as a source of other agonists. PMID:10420441

Hardeland, R

1999-01-01

217

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.

2002-01-01

218

Melatonin distribution reveals clues to its biological significance in basal metazoans.  

Science.gov (United States)

Although nearly ubiquitous in nature, the precise biological significance of endogenous melatonin is poorly understood in phylogenetically basal taxa. In the present work, we describe insights into the functional role of melatonin at the most "basal" level of metazoan evolution. Hitherto unknown morphological determinants of melatonin distribution were evaluated in Nematostella vectensis by detecting melatonin immunoreactivity and examining the spatial gene expression patterns of putative melatonin biosynthetic and receptor elements that are located at opposing ends of the melatonin signaling pathway. Immuno-melatonin profiling indicated an elaborate interaction with reproductive tissues, reinforcing previous conjectures of a melatonin-responsive component in anthozoan reproduction. In situ hybridization (ISH) to putative melatonin receptor elements highlighted the possibility that the bioregulatory effects of melatonin in anthozoan reproduction may be mediated by interactions with membrane receptors, as in higher vertebrates. Another intriguing finding of the present study pertains to the prevalence of melatonin in centralized nervous structures. This pattern may be of great significance given that it 1) identifies an ancestral association between melatonin and key neuronal components and 2) potentially implies that certain effects of melatonin in basal species may be spread widely by regionalized nerve centers. PMID:23300630

Roopin, Modi; Levy, Oren

2012-01-01

219

Melatonin in Alzheimer's disease and other neurodegenerative disorders  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 regula...

Srinivasan, V.; Pandi-perumal, Sr; Cardinali, Dp; Poeggeler, B.; Hardeland, R.

2006-01-01

220

Melatonin in Alzheimer's disease and other neurodegenerative disorders  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 ...

Srinivasan V; Sr, Pandi-perumal; Dp, Cardinali; Poeggeler B; Hardeland R

2006-01-01

 
 
 
 
221

Melatonin agonists for treatment of sleep and depressive disorders  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Melatonin the hormone secreted by the pineal gland has been effective in improving sleep both in normal sleepers and insomniacs and has been used successfully in treating sleep and circadian rhythm sleep disorders. The lack of consistency in the reports published by the authors is attributed to the differential bioavailabilty and short half-life of melatonin. Sleep disturbances are also prominent features of depressive disorders. To overcome this problem, melatonergic agonists with sleep prom...

Venkataramanujan Srinivasan; Cardinali, Daniel P.; Pandi-perumal, Seithikurippu R.; Brown, Gregory M.

2011-01-01

222

Melatonin: A Novel Indolamine in Oral Health and Disease  

Digital Repository Infrastructure Vision for European Research (DRIVER)

This paper attempts to summarise the findings accumulated within the last few years concerning the hormone of darkness “melatonin.” Based on its origin, from the pineal gland until recently it was portrayed exclusively as a hormone. Due to its lipophilic nature, it is accessible to every cell. Thus, in the classic sense it is a cell protector rather than a hormone. Recent studies, by Claustrat et al. (2005), detected few extrapineal sources of melatonin like retina, gastrointestinal tract...

Chava, V. K.; Sirisha, K.

2012-01-01

223

Chemiluminometric evaluation of melatonin and selected melatonin precursors' interaction with reactive oxygen and nitrogen species.  

Science.gov (United States)

Melatonin is a hormone, a derivative of tryptophan, that possesses a potent scavenging capacity for the most reactive and dangerous free radicals, being an important protection against oxidative stress. In this work, an automated flow-based procedure for assessment of melatonin, tryptophan, and 5-hydroxytryptophan scavenging capacity was developed. The presented methodology involved a multi-pumping flow system and exploited the ability of selected compounds to inhibit the chemiluminescence reaction of luminol with hydrogen peroxide, hydroxyl radical, and peroxynitrite anion. The system was based on the use of several solenoid actuated micro-pumps as the only active components of the flow manifold. This enabled the reproducible insertion and efficient mixing of very low volumes of sample and reagents as well as the transportation of the sample zone toward detection for monitoring the chemiluminometric response. Furthermore, the high versatility of the proposed multi-pumping flow system allowed the implementation of distinct reactions for the in-line generation of the different reactive species assayed without requiring physical reconfiguration. The results obtained demonstrated that 5-hydroxytryptophan is the most potent scavenger, followed by melatonin and tryptophan. The developed multi-pumping flow system exhibited good measurement precision (relative standard deviations typically <2%, n=10), low operational costs, and low reagent consumption. PMID:21964500

Harasimowicz, Joanna; Marques, Karine L; Silva, Ana F T; Costa, Renata C B; Prior, João A V; Rodrigues, S Sofia M; Santos, João L M

2012-01-01

224

[The treatment of nocturnal enuresis in children].  

Science.gov (United States)

367 children with nocturnal enuresis (NE) were divided into randomly selected groups. Two groups were treated with amitriptylin (the 1st group) or imipramine (the 2nd one). In the third group the treatment was differentiated and depended on coexist clinical sleep disturbances. In such cases there were used according to indications amitriptylin (including in combination with cyclodol), imipramine, diazepam. Additionally nootropic drugs (pyracetam, pantogam) were also administrated. In 3 month after the treatment 68.3% of the patients of the 3rd group still had complete remission. These results were better then in the 1st (20.9%) and in the 2nd (45.6%) groups of patients in which the treatment of NE was not depended on coexist disturbances. PMID:9343478

Gruzman, A V

1997-01-01

225

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

2013-01-01

226

Early dinner reduces nocturnal gastric acidity.  

Science.gov (United States)

This study examines whether eating food at different times has differential effects on intragastric pH. Experiments were done in 23 healthy volunteers (12 men). Intragastric acidity was monitored by ambulatory 22 hour pH-metry. Composition of meals was standardised: breakfast and lunch at 7 am and 12 noon respectively, and dinner at 6 or 9 pm, in random order. The time of going to bed and getting up was also standardised. With early dinner nocturnal pH was higher, than with late dinner (pH median: 1.67 and 1.39, p less than 0.001). During the remaining time periods, pH values were similar. Thus early dinner may be helpful in conditions where low intragastric acidity is desirable. PMID:2767502

Duroux, P; Bauerfeind, P; Emde, C; Koelz, H R; Blum, A L

1989-08-01

227

Clinical correlation between hypercalciuria and nocturnal enuresis.  

Science.gov (United States)

Hypercalciuria may present with dysuria, urinary incontinence and nocturnal enuresis (NE). To determine the frequency of hypercalciuria in NE patients and normally continent children, we studied 122 consecutive pre- school children with NE referred to our nephrology clinic during two years, from September 2007 to August 2009. We measured the 24- hour urinary calcium. Furthermore, we compared the response to nasal desmopressin in hypercalciuric and normocalciuric patients. Hypercalciuria was found in 26 (21.3 %) of the NE patients as compared with five (4.5%) of 110 continent children [(P 0.05). The response to desmopressin above 90% occurred within one month of therapy without a significant change in the levels of hypercalciuria. We conclude that these results suggest that hypercalciuria has a significant association with NE and does not interfere with the desmopressin therapy. PMID:21912028

Valavi, Ehsan; Ahmadzadeh, Ali; Hooman, Nakisa; Aminzadeh, Majid

2011-09-01

228

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

1990-05-13

229

Effect of Melatonin on Bone Mineral Density of Irradiated Rats  

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Full Text Available Objective: Melatonin is a powerful endogenous antioxidant and it may play a role in preventionof radiation-induced damage. The aim of this study was to investigate the effect ofmelatonin on bone mineral density in rats receiving radiation.Materials and Methods: Sprague Dawley rats were divided into four groups. Group 1(control group received neither melatonin nor radiation (control group. Group 2 (Melgroup was administered intraperitoneal injections of 5mg/kg melatonin daily for ten days.Group 3 (RT group and Group 4 were exposed to total cranium radiation of 5 Gy in a singledose by using a cobalt-60 teletherapy unit. In addition to irradiation, group 4 (RT + Melgroup was administered 5mg/kg of melatonin intraperitoneally. At the end of the 10th day,the rats' cranium and vertebrae bone mineral densities (BMDs were measured.Results: When cranial BMDs were evaluated, statistically more significant BMD increaseswere seen in the Mel group and the RT + Mel groups than in the control group. No significantdifference was seen in the Mel group versus the RT + Mel group; however, there wasa significant difference between RT and RT + Mel groups. When vertebral BMDs wereevaluated, the only significant difference was found between the control and Mel groups.Conclusion: We think that melatonin is a radioprotective agent. However, we would liketo emphasize that further studies are needed before clinical trials with melatonin are initiated.

Zerrin Orbak

2011-01-01

230

Immune stimulation by exogenous melatonin during experimental endotoxemia.  

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Melatonin has been shown to enhance the immune response under immune-compromised conditions. However, its immune-modulatory effects under inflammatory conditions are unclear at present. Both pro- and anti-inflammation has been reported. To study time-dependent effects of melatonin on the general immune response during endotoxemia in more detail, we used two models in male rats: per-acute endotoxemia was induced by lipopolysaccharide (LPS) bolus injection (2.5 mg/kg), sub-acute endotoxemia by LPS infusion (2.5 mg/kg × h). Melatonin was applied directly before and 2 h after LPS administration (3 mg/kg, each). The LPS-induced formation of the pro-inflammatory cytokines tumor necrosis factor alpha, interferon-gamma, interleukin (IL)-1?/?, IL-5, and IL-6 and of the anti-inflammatory cytokine IL-10 was further amplified by melatonin, although it was only significant during per-acute endotoxemia. In both models, melatonin had no effect on the LPS-induced nitric oxide release. These findings show that exogenous melatonin is capable of enhancing the general immune response under inflammatory conditions. PMID:24385237

Effenberger-Neidnicht, Katharina; Brencher, Lisa; Broecker-Preuss, Martina; Hamburger, Tim; Petrat, Frank; de Groot, Herbert

2014-06-01

231

Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography-mass spectrometry  

International Nuclear Information System (INIS)

Melatonin, the chief hormone of the pineal gland in vertebrates, is widely distributed in the animal kingdom. Among many functions, melatonin synchronizes circadian and circannual rhythms, stimulates immune function, may increase life span, inhibits growth of cancer cells in vitro and cancer progression and promotion in vivo, and was recently shown to be a potent hydroxyl radical scavenger and antioxidant. Hydroxyl radicals are highly toxic by-products of oxygen metabolism that damage cellular DNA and other macromolecules. Herein we report that melatonin, in varying concentrations, is also found in a variety of plants. Melatonin concentrations, measured in nine different plants by radioimmunoassay, ranged from 0 to 862 pg melatonin/mg protein. The presence of melatonin was verified by gas chromatography/mass spectrometry. Our findings suggest that the consumption of plant materials that contain high levels of melatonin could alter blood melatonin levels of the indole as well as provide protection of macromolecules against oxidative damage. (au) 30 refs

1995-01-01

232

Ontogenesis of Corneal Surface Ultrastructure in Nocturnal Lepidoptera.  

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The morphogenesis of epicorneal structures in nocturnal Lepidoptera was studied with light and electron microscopy. The main ultrastructural events involved in the formation of the corneal nipples during the ontogenetic development of the distal parts of ...

G. Gemne

1971-01-01

233

Nocturnal frontal lobe epilepsy presenting as excessive daytime sleepiness.  

Science.gov (United States)

Excessive daytime sleepiness (EDS) is common in the general population. Etiologies include insufficient sleep and primary sleep disorders. Due to its high prevalence, physicians often overlook EDS as a significant problem. However, EDS may also be the presenting symptom of seizures, in particular Nocturnal Frontal Lobe Epilepsy (NFLE). Due to the clinical similarity between the nocturnal behaviors of NFLE and parasomnias, and poor patient-related history, NFLE remains a challenging diagnosis. We report the case of a patient with NFLE who presented with a primary complaint of EDS, and discuss the differential diagnosis and evaluation of patients with EDS associated with nocturnal behaviors. In the context of a patient presenting with EDS and stereotyped nocturnal events, clinical suspicion should be high for NFLE. PMID:24479058

Cheng, Jocelyn Y; Wallace, Douglas M; Lopez, Maria R; Carrazana, Enrique J

2013-01-01

234

Do wintering Harlequin Ducks forage nocturnally at high latitudes?  

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We monitored radio-tagged Harlequin Ducks (Histrionicus histrionicus) to determine whether nocturnal feeding was part of their foraging strategy during winter in south-central Alaska. Despite attributes of our study site (low ambient temperatures, harsh weather, short day length) and study species (small body size, high daytime foraging rates) that would be expected to favor nocturnal foraging, we found no evidence of nocturnal dive-feeding. Signals from eight radio-tagged Harlequin Ducks never exhibited signal loss due to diving during a total of 780 minutes of nocturnal monitoring. In contrast, the same eight birds exhibited signal loss during 62 ?? 7% (SE) of 5-minute diurnal monitoring periods (total of 365 minutes of monitoring). Our results suggest that Harlequin Ducks in south-central Alaska face a stringent time constraint on daytime foraging during midwinter. Harlequin Ducks wintering at high latitudes, therefore, may be particularly sensitive to factors that increase foraging requirements or decrease foraging efficiency.

Rizzolo, D. J.; Esler, D.; Roby, D. D.; Jarvis, R. L.

2005-01-01

235

Distribution, function and physiological role of melatonin in the lower gut  

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Melatonin is a hormone with endocrine, paracrine and autocrine actions. It is involved in the regulation of multiple functions, including the control of the gastrointestinal (GI) system under physiological and pathophysiological conditions. Since the gut contains at least 400 times more melatonin than the pineal gland, a review of the functional importance of melatonin in the gut seems useful, especially in the context of recent clinical trials. Melatonin exerts its physiological effects thro...

Chun-Qiu Chen; Jakub Fichna; Mohammad Bashashati; Yong-Yu Li; Martin Storr

2011-01-01

236

Melatonin pharmacokinetics following two different oral surge-sustained release doses in older adults  

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Melatonin is increasingly used for the treatment of sleep disorders. Surge-sustained formulations consisting of combined immediate release and controlled release dosing may mimic the endogenous melatonin physiologic profile. However, relatively little is known about the pharmacokinetic properties of low dose (2 mg) melatonin in a combined immediate release/controlled release dose, especially in older adults who may also exhibit altered melatonin disposition. To assess...

2012-01-01

237

Hearing is not necessarily believing in nocturnal anurans  

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The recent discovery of the use of visual cues for mate choice by nocturnal acoustic species raises the important, and to date unaddressed, question of how these signals affect the outcome of mate choice predicted by female preference for male calls. In order to address this question, we presented female Hyla arborea tree frogs with a series of choices between combinations of acoustic and visual cues of varying quality in nocturnal conditions. While females exhibited the expected preference f...

Richardson, Christina; Gomez, Doris; Durieux, Romain; The?ry, Marc; Joly, Pierre; Le?na, Jean-paul; Ple?net, Sandrine; Lengagne, Thierry

2010-01-01

238

Working for Food Shifts Nocturnal Mouse Activity into the Day  

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Nocturnal rodents show diurnal food anticipatory activity when food access is restricted to a few hours in daytime. Timed food access also results in reduced food intake, but the role of food intake in circadian organization per se has not been described. By simulating natural food shortage in mice that work for food we show that reduced food intake alone shifts the activity phase from the night into the day and eventually causes nocturnal torpor (natural hypothermia). Release into continuous...

Hut, Roelof A.; Pilorz, Violetta; Boerema, Ate S.; Strijkstra, Arjen M.; Daan, Serge

2011-01-01

239

Melatonin and synthetic analogs as antioxidants.  

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Recent studies suggest that overproduction of reactive oxygen and nitrogen species (ROS/RNS), lowered antioxidant defense of the body. Oxidative stress is damaging to DNA, lipids, proteins and many more vital macromolecules. Consequences of oxidative stress thought to contribute to the development of a wide range of diseases including Alzheimer's disease, Parkinson's disease, diabetes, rheumatoid arthritis, neurodegeneration in motor neuron diseases and many cancer types. Melatonin (MLT) is a powerful antioxidant with a particular role in the protection of nuclear and mitochondrial DNA. To find an improved antioxidant activity, developments of novel synthetic analogues are under investigation. These studies may offer a new progress and approach in antioxidant drug development as well as antioxidant chemistry. Therefore, we have been synthesizing novel MLT derivatives and investigating their antioxidant capacities. This review gives a brief knowledge about the MLT based analogue indole derivatives as potential antioxidants. PMID:22998047

Suzen, Sibel

2013-02-01

240

Melatonin, But not auxin, affects postnatal reproductive development in the marsh rice rat (Oryzomys palustris).  

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Melatonin and the plant hormone auxin (indole-3-acetic acid) have some structural similarity and, may thus exert comparable physiological effects on reproduction and growth. To test this possibility, I examined the effects of melatonin and auxin administration on reproductive and non-reproductive organ development in an animal model, the marsh rice rat Oryzomys palustris. Juvenile males housed under 14L:10D conditions were injected daily for four weeks with saline, melatonin, auxin, or melatonin and auxin, and the development of the testes and other organs was assessed. Melatonin alone significantly inhibited the development of the testes, seminal vesicles, Harderian glands, and overall somatic growth, but not the spleen. Auxin did not affect any endpoint measured. When melatonin was administered simultaneously with auxin, the melatonin effects dominated in suppressing reproduction and growth. The administration of melatonin or auxin in the drinking water produced results similar to the effects of melatonin and auxin injections reported herein. Lastly, both melatonin and auxin in the drinking water failed to alter any short photoperiod-induced reproductive inhibition. These data suggest that structural similarities between melatonin and auxin do not result in similar postnatal effects on reproductive and non-reproductive organ development on a long photoperiod and further suggest that melatonin and auxin do not operate through a common physiological mechanism. PMID:23721467

Edmonds, Kent E

2013-06-01

 
 
 
 
241

Melatonina y deficiencia de hormona de crecimiento: contribucin a la evaluacin de los desrdenes neuroendocrinos / Melatonin and growth hormone deficiency: a contribution to the evaluation of neuroendocrine disorders  

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Full Text Available SciELO Argentina | Language: Spanish Abstract in spanish La melatonina constituye un integrante fundamental del denominado "reloj biolgico" y las alteraciones hormonales sueo-dependientes. Siendo la secrecin fisiolgica de GH, predominantemente nocturna, evaluamos en un grupo de nios y adultos deficitarios de GH (GHD) sin y con tratamiento sustitutivo, la [...] secrecin nocturna de melatonina. Estudiamos 44 pacientes GHD: Grupo a (Ga): Nios sin tratamiento; Grupo b (Gb): Nios con tratamiento con GH (0.16 mg/Kg/semana, dosis estable por mnimo de 6 meses); Grupo c (Gc): Adultos sin tratamiento y Grupo d (Gd): Adultos con tratamiento con GH (0.1- 0.8 mg/da, para mantener IGF1 entre 0 y +2 SDS, dosis estable por mnimo de 6 meses). Todos los pacientes con dficits hormonales asociados estaban adecuadamente sustituidos. La produccin de melatonina fue evaluada a travs de la medicin de su principal metabolito urinario: 6-Sulfatoximelatonina (6-SM), dosado por radioinmunoensayo, en muestras nocturnas (6PM a 8AM). Los niveles de 6-SM nocturna expresados como ?g/unidad de tiempo fueron (media SEM) para el grupo peditrico: Ga = 6.50 ( 5.10) y Gb = 8.21 ( 5.31) (Test de Mann-Whitney, p = 0.82). Para los adultos fueron: Gc = 2.99 ( 1.17) y Gd = 6.60 ( 2.00) (Test de Mann-Whitney, p = 0.35). En algunas alteraciones hipotlamo-hipofisarias han sido descriptas modificaciones del patrn secretorio de melatonina, pero no se han caracterizado en forma completa an, las posibles variaciones en pacientes con GHD. Si bien en las condiciones de este estudio, no hallamos diferencias en la excrecin nocturna de 6-SM entre los GHD no tratados y los tratados en ambos grupos, ello no invalida la existencia de posibles diferencias que podran detectarse estudiando la secrecin diurna de melatonina y su diferencia con la secrecin nocturna. Todo ello podr contribuir al conocimiento de los posibles desrdenes cronobiolgicos involucrados en la deficiencia de GH. Abstract in english Melatonin, a hormone secreted by the pineal gland, constitutes a landmark in neuroendocrine integration. The relationship between melatonin and different pituitary hormones and sex steroids has been studied; however, the relationship between growth hormone (GH) and melatonin remains unclear. Conside [...] ring that melatonin is an essential component of the so-called "biological clock", related to circadian rhythm, day-night cycle, and sleep-dependent hormonal alterations, and knowing that physiological GH secretion occurs predominantly at night, we decided to evaluate nocturnal melatonin secretion in a group of GH-deficient children and adults on and off replacement therapy. Patients and Methods: We studied 44 patients with GH deficiency (GHD), duly confirmed by pharmacological tests, divided into 4 groups: Group a (Ga ): untreated GHD children; Group b (Gb): GHD children on GH replacement therapy (0.16 mg/Kg/week, stable dose for at least 6 months); Group c (Gc): untreated GHD adults and Group d (Gd): GHD adults on GH replacement therapy (0.1- 0.8 mg/day, to maintain IGF1 between 0 and +2 SDS, stable dose for at least 6 months). All associated hormonal deficits were adequately replaced. Melatonin production was evaluated by measuring the excretion of its major urinary metabolite: 6-Sulphatoxymelatonin (6-SM). Urinary 6-SM was measured (radioimmunoassay, Stockgrand Ltd, Guildford, UK) in nocturnal samples (6PM to 8AM) in all patients. Results: Nocturnal 6-SM levels expressed as ?g/unit of time were (mean SEM) for the pediatric group: Ga = 6.50 ( 5.10) and Gb = 8.21 ( 5.31) (Mann Whitney test, p = 0.82). For adults: Gc = 2.99 ( 1.17) and Gd = 6.60 ( 2.00) (Mann Whitney test, p = 0.35). Discussion and Conclusions: It is difficult to characterize the relationship between melatonin and GH in healthy individuals; however, the administration of intravenous melatonin stimulates GH secretion in normal adults. In some hypothalamic-pituitary alterations, changes in the secretory pattern of melatonin have been reported, but possible variations in GHD patients have n

Fideleff, G; Surez, M; Boquete, HR; Azaretzky, M; Sobrado, P; Brunetto, O; Fideleff, HL.

242

Original paper Nocturnal Electrobioimpedance Volumetric Assessment (NEVA®: an alternative for determining the quality of nocturnal erections  

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Full Text Available Objectives: The NEVA® device (Urometrics, Inc measures changes in penile blood flow during nocturnal erections and enables one to make the diagnosis of either arterial insufficiency or venous leakage. The RigiScan® (Osbon Medical Systems determines the quality of nocturnal erections to establish the organic or psychogenic nature of erectile dysfunction (ED without indicating the nature of the impotence. This study compares both devices and tries to answer two questions. Does NEVA® give information on nocturnal erections comparable to that provided by the RigiScan®? What is the diagnostic capacity of NEVA® when compared to a comprehensive approach including laboratory examinations, psychological evaluation, intra-cavernous injection, and Duplex Doppler?Material and methods: Twenty-five men with complaints of ED were enrolled in our study. Each of them had a complete work-up. This included the use of the RigiScan® for two consecutive nights. Then the NEVA® and RigiScan® devices were used simultaneously for the third night. The dynamic data provided by the NEVA® system were compared to the conventional nocturnal penile tumescence testing by means of the RigiScan®.Results: An analysis of all sessions shows that all night recordings are comparable. The mean number of erections/night (2.80±0.34 vs 2.76±0.31 does not differ statistically significantly between NEVA® and RigiScan® assessments. Also the mean duration of events (30.66±1.92 minutes vs 25.63±1.62 minutes does not differ. Normal axial rigidity by NEVA® (>200% change over baseline correlates with all grade III erections by RigiScan®. The analysis of NEVA® data gives in 84% of the cases the same diagnosis of ED as that made after a complete work-up.Conclusions: The present study demonstrates that electrobioimpedance registration has a good correlation with conventional penile tumescence testing. The analysis of data obtained with the NEVA® device seems to be an important and easy method for predicting the etiology of ED. For the assessment of the performance of the male partner during a sexual intercourse the registration of axial rigidity is a more important parameter than radial rigidity.

Dirk P.J. Michielsen

2005-09-01

243

Paroxysmal nocturnal hemoglobinuria: a red clot syndrome.  

Science.gov (United States)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, nonmalignant disorder of hematopoietic stem cells characterized by hemolysis, diminished hematopoiesis, and thrombophilia. We describe a 65-year-old woman with known PNH and peripheral arterial disease who presented with critical limb ischemia and a nonhealing left foot ulcer. She underwent surgical bypass of a diffusely diseased left superficial femoral artery with autologous reversed saphenous vein graft. Her postoperative course was complicated by wound sepsis and PNH exacerbation with resultant graft thrombosis requiring an above-knee amputation. This case highlights several key concepts relevant to the management of vascular surgery patients with PNH: (1) their predisposition for arterial and venous thrombosis; (2) hypercoagulability despite standard anticoagulation regimens; (3) the role of eculizumab (a monoclonal antibody that inhibits complement activation used to treat PNH) in reducing thrombotic complications and hemolysis; and (4) complications associated with the immunosuppressive effects of eculizumab. We recommend careful monitoring of hemolysis and immunosuppression, aggressive anticoagulation, frequent graft surveillance, and early consultation with hematology. PMID:24200143

Crawford, Jeffrey D; Wong, Victor W; Deloughery, Thomas G; Mitchell, Erica L; Liem, Timothy K; Landry, Gregory J; Azarbal, Amir F; Moneta, Gregory L

2014-01-01

244

Laboratory tests for paroxysmal nocturnal hemoglobinuria.  

Science.gov (United States)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder that is often suspected in a patient presenting with non-immune hemolytic anemia associated with pancytopenia or venous thrombosis. This disorder is a consequence of acquired somatic mutations in the phosphatidylinositol glycan class A (PIG-A) gene in the hematopoietic stem cells (HSC) of patients. The presence of these mutations leads to production of blood cells with decreased glycosyl phosphatidylinositol-anchored cell surface proteins, making red blood cells derived from the clone more sensitive to complement mediated hemolysis. The diagnosis of PNH may be difficult in some cases due a low proportion of PNH cells in the blood and occasionally due to difficulties in selecting the most appropriate diagnostic studies. The latest generation of tests allow for detection of very small populations of PNH cells, for following the natural course and response to therapy of the disease, and for helping to decide when to initiate therapy with monoclonal antibody targeting the terminal complement protein C5 (Eculizumab), anticoagulation, and in some cases allogeneic HSC transplant. In this article, we review the different diagnostic tests available to clinicians for PNH diagnosis. PMID:24127129

Preis, Meir; Lowrey, Christopher H

2014-03-01

245

PACAP – Melatonin Interaction in Mouse Suprachiasmatic Nucleus Slice Cultures  

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Full Text Available The pineal indoleamine-hormone melatonin elicits a wide variety of physiological actions across vertebrate species. Mouse suprachiasmatic nucleus (SCN has high density of melatonin receptors that plays important role in the entrainment of the circadian pacemaker. SCN of the mammalian hypothalamus serves as the central biological clock, controlling circadian rhythms that are synchronized with the external light/dark cycle by retinal photoreception and transmission of light information via the retinohypothalamic tract (RHT. RHT has recently been shown to contain pituitary adenylate cyclase-activating polypeptide (PACAP as neurotransmitter/neuromodulator. In the present study we cultured hypothalamic brain slices that included the region of the SCN on multi-microelectrode arrays to study in long-duration recordings simultaneously the electrical activity of SCN neurons and their possible target neurons in the hypothalamus. The extracellular recordings from the acute and ? or organotypic hypothalamic slices mainly exhibited multi-unit activity often without the possibility to discriminate single unit activity. Application of melatonin (1nM for 50 min at CT 10 shifted served the circadian rhythm in the firing rate and caused a phase-advance of 4 hours. Application of PACAP (100nM for 25 min at CT6 evoked phase-advance of 2-3 hours while application of PACAP at CT10 had no effect on the circadian rhythm. Co-application of PACAP together with melatonin at CT 10 completely blocked the phase-advance normally induced by melatonin.

Ehab TOUSSON

2010-09-01

246

Formation of melatonin and its isomer during bread dough fermentation and effect of baking.  

Science.gov (United States)

Melatonin is produced mainly by the pineal gland in vertebrates. Also, melatonin and its isomer are found in foods. Investigating the formation of melatonin and its isomer is of importance during bread dough fermentation and its degradation during baking since bread is widely consumed in high amounts. Formation of melatonin was not significant during dough fermentation. The melatonin isomer content of nonfermented dough was found to be 4.02 ng/g and increased up to 16.71 ng/g during fermentation. Lower amounts of isomer in crumb and crust than dough showed that the thermal process caused a remarkable degree of degradation in melatonin isomer. At the end of the 180 min fermentation Trp decreased by 58%. The results revealed for the first time the formation of a melatonin isomer in bread dough during yeast fermentation. PMID:24611648

Y?lmaz, Cemile; Kocada?l?, Tolgahan; Gökmen, Vural

2014-04-01

247

Which is the best choice for gastroesophageal disorders: Melatonin or proton pump inhibitors?  

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Full Text Available Melatonin is used in many countries to improve sleep disorders. Melatonin is a hormone produced by the pineal gland and enterochromaffin cells which control sleep and gastrointestinal motility. Low levels of melatonin lead to gastroesophageal reflux disease (GERD. Most of patients with GERD have a sleep disorder. So, low melatonin levels is the main cause of insomnia. Beyond this, it has an inhibitory action on gastric acid secretion and seems to control the lower esophageal sphincter. Proton pump inhibitors (PPIs are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. Omeprazole (one of the PPIs and melatonin have similarities in their chemical structures. Therefore, we could consider omeprazole as a rough copy of melatonin. In this paper, we compare the advantages and disadvantages of the clinical use of melatonin and PPIs.

Joanna Dulce Favacho de Oliveira Torres

2010-10-01

248

Testicular dysfunction in experimental chronic renal insufficiency: a deficiency of nocturnal pineal N-acetyltransferase activity.  

Science.gov (United States)

Biochemical correlates of neuroendocrine/gonadal function and nocturnal levels of serotonin N-acetyltransferase (NAT) activity were determined in partially nephrectomized (PNx), male, Long Evans rats following a 5-week period of chronic renal insufficiency (CRI). PNx animals demonstrated two to four-fold elevations in urea nitrogen and three to four-fold reductions (P less than 0.02) in plasma total testosterone concentrations as compared to sham-operated controls. The pituitary LH contents of PNx rats were decreased to approximately 60% of the control value (P less than 0.05). There were no differences in plasma prolactin levels between the control and PNx groups either at mid-day or in the middle of the night. Nocturnal pineal NAT activity in PNx rats was markedly reduced to approximately 20% of the control value (P less than 0.001). Similar evidence of gonadal dysfunction (reduced plasma total testosterone and testes testosterone content) and a significant decrease in night-time levels of pineal NAT activity were also observed after 13 weeks of CRI in PNx rats of the Sprague-Dawley strain that were housed under a different photoperiod. These results suggest that pineal gland dysfunction is a feature of CRI in the PNx model. Such an abnormality might contribute to the pathogenesis of gonadal dysfunction in CRI.

Holmes, E. W.; Hojvat, S. A.; Kahn, S. E.; Bermes, E. W.

1989-01-01

249

Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids  

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In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage. Highlights: ? After 30-day chronic CCl{sub 4} intoxication mitochondria displayed considerable changes. ? The functional parameters of mitochondria were similar to the control values. ? Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ? The above complex enhanced regenerative processes in the liver.

Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

2012-06-15

250

Nocturnal asthma in school children of south punjab, pakistan  

International Nuclear Information System (INIS)

At the present time, the epidemiology of the childhood asthma is of considerable interest. There is an understandable concern that changes in the geographical area, lifestyle, and environment. This study was conducted to find the prevalence of nocturnal asthma, in school children of south Punjab, Pakistan. It was a cross sectional, questionnaire based, descriptive survey of the children aged 3-18 years, in randomly selected primary and secondary schools, from October 2002 to March 2003. The data was analysed with Statistical Analysis System (SAS). Of 6120 questionnaire sent to the parents/guardians, we received 3180 back (52%). Of the 3180 respondents, 1767 (56%) were for boys and 1413 (44%) were for girls. The median age was 8.25 years. Around 71% of children were between 4 to 11 years of age. The parents reported nocturnal asthma in 177 (6%) of their children with an equal prevalence in boys and girls, i.e., (3% each, rounded off to nearest whole number). Of these 177 children with nocturnal asthma, 99 (56%) were boys and 78 (44%) were girls. Of the 1767 boys and 1413 girls, the nocturnal asthma reported by parents was 6% each (99 and 78 respectively). The nocturnal asthma was not reported in 14-18 years age group of females. The asthma is taken as a stigma in our society and as such is not reported or disclosed rather denied. An extensive educational media campaign is required for awareness of the masses. (author)

2008-01-01

251

Paroxysmal nocturnal hemoglobinuria in systemic lupus erythematosus: a case report  

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Full Text Available Abstract Introduction Paroxysmal nocturnal hemoglobinuria is an acquired disorder of hemopoiesis and is characterized by recurrent episodes of intravascular hemolysis due to an increased sensitivity to complement-mediated hemolysis. Systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. We report a case of paroxysmal nocturnal hemoglobinuria that developed in a patient with systemic lupus erythematosus and lupus nephritis. Case presentation A 29-year-old Mongolian woman had systemic lupus erythematosus, which manifested only as skin lesions when she was 12 years old. She had leg edema and proteinuria when she was 23 years old, and a renal biopsy revealed lupus nephritis (World Health Organization type IV. She had been treated with steroids and immunosuppressant therapy. At 29, she had headaches, nausea, general fatigue, and severe pancytopenia and was admitted to our hospital. A laboratory evaluation showed hemolytic anemia. Further examination showed a neutrophil alkaline phosphatase score of 46 points, a CD55 value of 18%, and a CD59 value of 78.6%. The results of Ham test and sugar water tests were positive. The constellation of symptoms throughout the clinical course and the laboratory findings suggested paroxysmal nocturnal hemoglobinuria. Conclusions To the best of our knowledge, systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. Clinicians should be aware of the association between autoimmune and hematological diseases.

Nakamura Norio

2011-11-01

252

Melatonin and ulcerative colitis: evidence, biological mechanisms, and future research.  

Science.gov (United States)

Ulcerative colitis (UC) is an inflammatory bowel disease that afflicts up to 1 million people in the US. Current treatments for UC are mostly nonspecific, not always effective, and often accompanied by serious side effects. Therefore, there is considerable interest in finding alternative and more tolerable treatments for this disease. Physiologic data suggest that melatonin is an important regulator of both inflammation and motility in the gastrointestinal tract, and data from in vitro studies, animal experiments, and limited studies in humans suggest that supplemental melatonin may have an ameliorative effect on colitis. In this review we summarize the evidence regarding melatonin as a possible therapeutic agent in UC and discuss possible biological mechanisms and directions for future research. PMID:18626968

Terry, Paul D; Villinger, Francois; Bubenik, George A; Sitaraman, Shanti V

2009-01-01

253

Search for seasonal rhythmicity of pineal melatonin production in rats under constant laboratory conditions: spectral chronobiological analysis, and relation to solar and geomagnetic variables.  

Science.gov (United States)

Earlier we reported that in a number of experiments pineal melatonin production in rats under constant laboratory conditions displayed seasonal rhythms but subsequently were not always able to confirm this. Since there was no indication under which conditions such rhythms may be present, we performed four consecutive identical experiments with untreated female Sprague-Dawley rats within the same animal room during 1997-2006. Nocturnal urine samples (19-23, 23-3, 3-7 h) were collected at monthly intervals over 494-658 d with 12 animals each in experiments I and II (1997-1999, 1999-2000), 30 animals in experiment III (2002-2004), and 15 in experiment IV (2005-2006). 6-Sulfatoxymelatonin (aMT6s) was measured by ELISA. The excreted aMT6s at each time interval as well as total nocturnal aMT6s-excretion (19-7 h) was submitted to standard statistical analyses as well as to a spectral chronobiological analysis to determine the period lengths of the components involved which was followed by processing with the single cosinor method. Seasonal rhythm components (circannual period length: 360 ± 60 d) were detected in experiment III (2002-2004) for the overall nocturnal excretion as well as for two sub-intervals (23-3 and 3-7 h) and in one night interval of experiment II (23-3 h). Multiple components with mostly short period lengths of around 100 d and some long ones of 500-650 d were found in the other experiments. Systematic MESOR and amplitude variations were observed during the experiments, being highest in experiment II (19-7 h, also 23-3 h and 3-7 h) and lowest in experiments I and IV. These results illustrate that seasonal melatonin rhythms are not a general phenomenon in female laboratory rats indicating an involvement of unknown environmental cues. As an extension of our earlier hypothesis regarding a seasonal Zeitgeber function of the horizontal intensity H of the geomagnetic field showing circannual variations, we assume further modulation by the 11-yrs' sunspot cycle which leads to geomagnetic disturbances and could facilitate seasonal aMT6s rhythmicity during specific years. PMID:22971170

Bartsch, Hella; Mecke, Dieter; Probst, Hansgeorg; Küpper, Heinz; Seebald, Eckard; Salewski, Lothar; Stehle, Thilo; Bartsch, Christian

2012-10-01

254

Relationship between melatonin rhythms and visual loss in the blind  

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Melatonin rhythms were assessed in 49 registered blind individuals by measurement of the urinary metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s). Subjects had different causes of visual loss and were classified as having light perception or better (LP; n 5 19) or having no perception of light (NPL; n 5 30). Subjects collected four-hourly urine samples (eight-hourly overnight) for 48 h at weekly intervals for 3–5 weeks. The majority of LP subjects (14 of 19) had normally entrained aMT6...

Lockley, Sw; Skene, Dj; Arendt, J.; Tabandeh, H.; Bird, Ac; Defrance, R.

1997-01-01

255

Interactions of the platelets in paroxysmal nocturnal hemoglobinuria with complement. Relationship to defects in the regulation of complement and to platelet survival in vivo.  

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The blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) have abnormal interactions with complement. The activity of the alternative pathway C3 convertase on the platelets of 9 out of 19 patients with PNH was elevated. 10 patients had C3 convertase activity within the normal range even though 80-95% of their platelets lacked the complement regulatory protein decay accelerating factor (DAF) that is absent from the affected blood cells in PNH. PNH and normal platelets released...

Devine, D. V.; Siegel, R. S.; Rosse, W. F.

1987-01-01

256

Recurrent and progressive abdominal pain and enteritis in a Japanese patient with paroxysmal nocturnal hemoglobinuria.  

Science.gov (United States)

This case report describes a young male patient with recurrent abdominal pain persisting for more than 16 months. Clinical investigations showed signs of inflammation and pancytopenia. A diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) was made 9 months after the onset of the abdominal pain, following endoscopic examinations that revealed evidence of a previously unknown hemorrhage. Regular monitoring indicated that the abdominal pain was associated with elevations in lactate dehydrogenase, C-reactive proteins, and D-dimer levels. The patient started treatment with the complement inhibitor eculizumab shortly after it was approved for use in Japanese PNH patients with hemolysis. Resolution of the abdominal pain and normalization of clinical parameters were noted within 3 weeks from treatment initiation. PMID:24587926

Hino, Akihisa; Yamashita, Yukiko; Yamaguchi, Mitsuhiro; Azenishi, Yasuhiko

2014-01-01

257

Detection and quantification of the antioxidant melatonin in Montmorency and Balaton tart cherries (Prunus cerasus).  

Science.gov (United States)

The antioxidant melatonin was recently identified in a variety of edible plants and seeds in high concentrations. In plants, as in animals, melatonin is believed to function as a free radical scavenger and possibly in photoperiodism. In this study, melatonin was detected and quantified in fresh-frozen Balaton and Montmorency tart cherries (Prunus cerasus) using high-performance liquid chromatography. Both cherry species contain high levels of melatonin compared to the melatonin concentrations in the blood of mammals. Montmorency cherries (13.46 +/- 1.10 ng/g) contain approximately 6 times more melatonin than do Balaton cherries (2.06 +/- 0.17 ng/g). Neither the orchard of origin nor the time of harvest influenced the amount of melatonin in fresh cherries. The implication of the current findings is that consuming cherries could be an important source of dietary melatonin inasmuch as melatonin is readily absorbed when taken orally. Also, previously published data and the results presented here show that melatonin is not only endogenously produced but also present in the diet. PMID:11600041

Burkhardt, S; Tan, D X; Manchester, L C; Hardeland, R; Reiter, R J

2001-10-01

258

Influence of melatonin receptor signalling on parameters involved in blood glucose regulation.  

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The pineal hormone melatonin is known to influence insulin secretion via the G-protein-coupled receptor isoforms MT1 and MT2. The present study was aimed to further elucide the impact of melatonin on blood glucose regulation. To this end, mouse lines were used, in which one of the two or both melatonin receptors were deleted. In comparison with wild-type mice of the same age (8-12 months old), increased plasma insulin and melatonin levels and decreased blood glucose levels and body weights were detected in the MT1- and double-knockout lines. The elimination of melatonin receptor signalling also altered blood glucose concentrations, body weight and melatonin and insulin levels when comparing wild-type and receptor knockout mice of different ages (6 wk and 8-12 months old); such changes, however, were dependent on the type of receptor deleted. Furthermore, reverse transcription polymerase chain reaction results provided evidence that melatonin receptor deficiency has an impact on transcript levels of pancreatic islet hormones as well as on pancreatic and hepatic glucose transporters (Glut1 and 2). Under stimulated insulin secretion in the presence of melatonin in the rat insulinoma ?-cells INS-1, the Glut1 transcript level was decreased. In conclusion, the present findings demonstrate that melatonin receptor knockout types affect blood glucose levels, body weight, plasma levels of melatonin and insulin, as well as pancreatic hormone and Glut1 expression in significantly different manners. PMID:24117965

Bazwinsky-Wutschke, Ivonne; Bieseke, Lars; Mühlbauer, Eckhard; Peschke, Elmar

2014-01-01

259

Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats.  

Science.gov (United States)

Melatonin limits obesity in rodents without affecting food intake and activity, suggesting a thermogenic effect. Identification of brown fat (beige/brite) in white adipose tissue (WAT) prompted us to investigate whether melatonin is a brown-fat inducer. We used Zücker diabetic fatty (ZDF) rats, a model of obesity-related type 2 diabetes and a strain in which melatonin reduces obesity and improves their metabolic profiles. At 5 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control and those treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk. Melatonin induced browning of inguinal WAT in both ZDF and ZL rats. Hematoxylin-eosin staining showed patches of brown-like adipocytes in inguinal WAT in ZDF rats and also increased the amounts in ZL animals. Inguinal skin temperature was similar in untreated lean and obese rats. Melatonin increased inguinal temperature by 1.36 ± 0.02°C in ZL and by 0.55 ± 0.04°C in ZDF rats and sensitized the thermogenic effect of acute cold exposure in both groups. Melatonin increased the amounts of thermogenic proteins, uncoupling protein 1 (UCP1) (by ~2-fold, P irisin levels were not affected by melatonin. These results demonstrate that chronic oral melatonin drives WAT into a brown-fat-like function in ZDF rats. This may contribute to melatonin's control of body weight and its metabolic benefits. PMID:24007241

Jiménez-Aranda, Aroa; Fernández-Vázquez, Gumersindo; Campos, Daniel; Tassi, Mohamed; Velasco-Perez, Lourdes; Tan, Dun-Xian; Reiter, Russel J; Agil, Ahmad

2013-11-01

260

Effectiveness of melatonin in tardive dyskinesia.  

Science.gov (United States)

Tardive Dyskinesia (TD) is a movement disorder associated with the clinical administration of antipsychotics. It is believed that TD is due, among other factors, to an increase in the oxidative damage produced by free radicals. Antioxidants, like vitamin E, have been used in the treatment of TD but there is no evidence of their effectiveness. Melatonin (MEL) is 6 to 10 times more effective, as an antioxidant, than vitamin E and it has been used with an apparent higher effectiveness in the treatment of TD, although the results have not been conclusive. A randomized, double blind, placebo controlled design was used to determine the effectiveness of MEL (20 mg/day) during 12 weeks in 7 patients with TD. Six patients with TD were treated with placebo. The Abnormal Involuntary Movement Scale (AIMS) was chosen to assess the severity of TD initially and after 4, 8 and 12 weeks. The psychiatric evaluation was done following the Brief Psychiatric Rating Scale. In two patients treated with MEL a significant improvement (more than 60%) of the values of AIMS was detected. In the remainder five, as well as in the patients treated with placebo, no difference was observed during the 12 weeks. When compared the AIMS score in all the MEL-treated patients with the values in the placebo-treated patients, no significant differences were detected during the 12 weeks of the study. However, the significant clinical improvement observed in two patients must be considered before reaching a final conclusion on the usefulness of MEL in TD. PMID:21950196

Castro, Fernando; Carrizo, Edgardo; Prieto de Rincón, Dexy; Rincón, Ciro Alberto; Asián, Triana; Medina-Leendertz, Shirley; Bonilla, Ernesto

2011-09-01

 
 
 
 
261

Melatonin and the theories of aging: a critical appraisal of melatonin's role in antiaging mechanisms.  

Science.gov (United States)

The classic theories of aging such as the free radical theory, including its mitochondria-related versions, have largely focused on a few specific processes of senescence. Meanwhile, numerous interconnections have become apparent between age-dependent changes previously thought to proceed more or less independently. Increased damage by free radicals is not only linked to impairments of mitochondrial function, but also to inflammaging as it occurs during immune remodeling and by release of proinflammatory cytokines from mitotically arrested, DNA-damaged cells that exhibit the senescence-associated secretory phenotype (SASP). Among other effects, SASP can cause mutations in stem cells that reduce the capacity for tissue regeneration or, in worst case, lead to cancer stem cells. Oxidative stress has also been shown to promote telomere attrition. Moreover, damage by free radicals is connected to impaired circadian rhythmicity. Another nexus exists between cellular oscillators and metabolic sensing, in particular to the aging-suppressor SIRT1, which acts as an accessory clock protein. Melatonin, being a highly pleiotropic regulator molecule, interacts directly or indirectly with all the processes mentioned. These influences are critically reviewed, with emphasis on data from aged organisms and senescence-accelerated animals. The sometimes-controversial findings obtained either in a nongerontological context or in comparisons of tumor with nontumor cells are discussed in light of evidence obtained in senescent organisms. Although, in mammals, lifetime extension by melatonin has been rarely documented in a fully conclusive way, a support of healthy aging has been observed in rodents and is highly likely in humans. PMID:24112071

Hardeland, Rüdiger

2013-11-01

262

Paroxysmal nocturnal haemoglobinuria and Budd-Chiari syndrome.  

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An 11 year old boy developed pancytopenia, haemolysis, and Budd-Chiari syndrome. The venous thrombosis extended to involve other intra-abdominal vessels before paroxysmal nocturnal haemoglobinuria was recognised as the underlying haematological abnormality. Earlier diagnosis would have made curative bone marrow transplantation a possibility.

Wyatt, H. A.; Mowat, A. P.; Layton, M.

1995-01-01

263

Renal and hepatic scintigraphy in paroxysmal nocturnal hemoglobinuria (PNH)  

International Nuclear Information System (INIS)

Scintigraphic findings in paroxysmal nocturnal hemoglobinuria (PNH) have been presented. To summarize, a focal hot spot on liver imaging was better seen on the IDA scan, showing resolution following a satisfactory portacaval anastomosis. PNH is another cause of hot kidneys on bone imaging

1985-01-01

264

Effects of Geminid meteor showers on nocturnal LF amplitude  

International Nuclear Information System (INIS)

Evidence that Geminid meteor showers of December 1972 and 1973 affect the nocturnal LF amplitude is presented. The observations clearly show high attenuation of the signal with an increase in fading frequency, pronouncedly on December 14, the peak activity day of Geminids, for both years. The fading frequency appears to be deeper and faster when it is associated with higher magnetic activity

1976-07-01

265

Transient pancytopenia associated with parvovirus infection in paroxysmal nocturnal haemoglobinuria.  

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A 25 year old woman with a 15-year history of paroxysmal nocturnal haemoglobinuria developed transient pancytopenia following infection with human parvovirus B19. This is the first report of transient pancytopenia in a patient with an acquired haemolytic anaemia due to parvovirus. The possible mechanism of pancytopenia in such a case is discussed.

1987-01-01

266

Melatonin inhibits oxidative modification of human low-density lipoprotein.  

Science.gov (United States)

An important property of melatonin is that it is a free-radical scavenger or antioxidant. Since free radicals can induce oxidative modification of low-density lipoprotein (LDL), a process believed to be involved in atherogenesis, we were prompted to evaluate the capacity of melatonin to prevent oxidative modification of LDL. To induce oxidation, human LDL (0.4 mg protein/ml) was incubated at 37 degrees C with either 10 microM cupric chloride or 10 mM 2,2'-azo-bis-(2-amidinopropane) dihydrochloride (AAPH) for 3 hr or 24 hr, respectively. Several assays were then performed to unequivocally determine the extent of LDL oxidation. Compared to native LDL, oxidized LDL had increased agarose gel electrophoretic mobility and weaker immunoreactivity with a murine monoclonal antibody to human apolipoprotein B-100. Measurement of thiobarbituric acid-reactive substances (TBARS) revealed that native LDL contained 1.8 +/- 0.6 nmoles TBARS/mg protein, whereas copper-oxidized LDL contained 53 +/- 4 nmoles TBARS/mg protein. However, when present during incubation, melatonin (0.125-4 mM) inhibited in a concentration-dependent manner the increase in electrophoretic mobility, decrease in immunoreactivity of LDL, and increase in formation of TBARS caused by either copper or AAPH. In a fourth assay, phospholipid analysis of LDL was performed. Native LDL contained 420 +/- 9 nmoles phosphatidylcholine (PC)/mg LDL protein and 30 +/- 20 nmoles lysophosphatidylcholine (LysPC)/mg LDL protein. LDL incubated with copper had a decreased PC content (276 +/- 48 nmoles PC/mg LDL protein) and increased LysPC content (76 +/- 22 nmoles LysPC/mg LDL protein). But when present during the incubation of LDL with copper, melatonin attenuated in a concentration-dependent manner the degradation of PC to LysPC. Therefore, we conclude that melatonin can inhibit oxidative modification of LDL in vitro. PMID:9247205

Kelly, M R; Loo, G

1997-05-01

267

Determination Melatonin in Serum of Kurdish Horses by HPLC in Kermanshah Region at Breeding Season  

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Full Text Available The objective of this study was to evaluate changes in serum concentration of melatonin of Kurdish horses Kermanshah region at breeding season (February to June of 2010. Blood samples from jugular vein of 40 Kurdish horses were collected. Serum was harvested from these blood samples by centrifugation. After preparation and derivation of serums for HPLC assay, samples were injected to HPLC column and melatonin was measured by area under curve based on standard curve of melatonin. The mean (±S.E of serum melatonin was determined 63.23±9.51 pg/mL. The concentration of serum melatonin of mares was nearly 2 times than stallions and significantly differed (p = 0.01. Thus serum melatonin related to breed of horses and may affect reproductive activity in different breed and geographical region.

Afsaneh Arabi

2012-06-01

268

Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin.  

Science.gov (United States)

Melatonin, a derivative of an essential amino acid, tryptophan, was first identified in bovine pineal tissue and subsequently it has been portrayed exclusively as a hormone. Recently accumulated evidence has challenged this concept. Melatonin is present in the earliest life forms and is found in all organisms including bacteria, algae, fungi, plants, insects, and vertebrates including humans. Several characteristics of melatonin distinguish it from a classic hormone such as its direct, non-receptor-mediated free radical scavenging activity. As melatonin is also ingested in foodstuffs such as vegetables, fruits, rice, wheat and herbal medicines, from the nutritional point of view, melatonin can also be classified as a vitamin. It seems likely that melatonin initially evolved as an antioxidant, becoming a vitamin in the food chain, and in multicellular organisms, where it is produced, it has acquired autocoid, paracoid and hormonal properties. PMID:12485375

Tan, Dun-Xian; Manchester, Lucien C; Hardeland, Rüdiger; Lopez-Burillo, Silvia; Mayo, Juan C; Sainz, Rosa M; Reiter, Russel J

2003-01-01

269

Melatonin mitigate cerebral vasospasm after experimental subarachnoid hemorrhage: a study of synchrotron radiation angiography  

International Nuclear Information System (INIS)

Cerebral vasospasm (CV) after subarachnoid hemorrhage (SAH) is a devastating and unsolved clinical issue. In this study, the rat models, which had been induced SAH by prechiasmatic cistern injection, were treated with melatonin. Synchrotron radiation angiography (SRA) was employed to detect and evaluate CV of animal models. Neurological scoring and histological examinations were used to assess the neurological deficits and CV as well. Using SRA techniques and histological analyses, the anterior cerebral artery diameters of SAH rats with melatonin administration were larger than those without melatonin treatment (p < 0.05). The neurological deficits of SAH rats treated with melatonin were less than those without melatonin treatment (p < 0.05). We concluded that SRA was a precise and in vivo tool to observe and evaluate CV of SAH rats; intraperitoneally administration of melatonin could mitigate CV after experimental SAH.

2013-06-01

270

A carnivore species (Canis familiaris) expresses circadian melatonin rhythm in the peripheral blood and melatonin receptors in the brain  

International Nuclear Information System (INIS)

Dogs kept under controlled photoperiodic conditions of 12h light and 12h dark expressed a clear diurnal melatonin rhythm in the peripheral blood, with a swift peak restricted to the late part of the scotophase. The highest density of high-affinity, G-protein-linked 2-["1"2"5I]iodomelatonin binding sites was found in the pars tuberalis of the pituitary gland. Binding sites were found also in the pars distalis, and light microscopy/high-resolution autoradiography showed that binding was located exclusively over the chromophobe and basophilic cells forming the adenopituitary zona tuberalis, well developed in the species, and extending into the gland as a continuation of pars tuberalis. Cords of basophilic cells located in the pars distalis proper also expressed high receptor density. Quantitative autoradiography inhibition experiments revealed that the apparent melatonin inhibitory constant in all those areas was around 0.1 nmol/l, which is a physiologically appropriate value considering the peripheral blood melatonin levels. Co-incubation with guanosine 3-thiotriphosphate led to a consequential decrease in the binding density. Collectively, these data show that the dog possesses all the prerequisites for an efficient network adapted to photoperiodic time measurements. A circadian melatonin signal in the peripheral blood and an apparently functional readout receptor system located in key positions within the brain are both present in this species. 43 refs. 6 figs., 1 tabs

1994-08-01

271

Protective effect of maternal prenatal melatonin administration on rat pups born to mothers submitted to constant light during gestation  

Directory of Open Access Journals (Sweden)

Full Text Available We studied the effects of adverse conditions such as constant light (LL on the circadian rhythm of malate (MDH, EC 1.1.1.37 and lactate (LDH, EC 1.1.1.27 dehydrogenase activities of the testes of male Wistar rats on postnatal day 28 (PN28, anxiety-like behavior (elevated plus-maze test at PN60 and sexual behavior at PN120. The rats were assigned to mother groups on day 10 of pregnancy: control (12-h light/dark, LL (light from day 10 to 21 of pregnancy, and LL+Mel (LL and sc injection to the mothers of a daily dose of melatonin, 1 mg/kg body weight at circadian time 12, from day 17 to 21 of pregnancy. LL offspring did not show circadian rhythms of MDH (N = 62 and LDH (N = 63 activities (cosinor and ANOVA-LSD Fisher. They presented a 44.7% decrease in open-arm entries and a 67.9% decrease in time (plus-maze test, N = 15, P < 0.001, Mann-Whitney U-test and Kruskal-Wallis test, an increase in mounting (94.4%, intromission (94.5% and ejaculation (56.6% latencies (N = 12, P < 0.01, Mann-Whitney U-test and Kruskal-Wallis test and lower numbers of these events (61, 59 and 73%, respectively; P < 0.01, N = 12 compared to controls. The offspring of the LL+Mel group presented MDH and LDH circadian rhythms (P < 0.05, N = 50, cosinor and ANOVA-LSD Fisher, anxiety-like and sexual behaviors similar to control. These findings supported the importance of the melatonin signal and provide evidence for the protective effects of hormones on maternal programming during gestation. This protective action of melatonin is probably related to its entrainment capacity, favoring internal coupling of the fetal multioscillatory system.

C.D. Cisternas

2010-09-01

272

Beneficial Effects of Melatonin Combined with Exercise on Endogenous Neural Stem/Progenitor Cells Proliferation after Spinal Cord Injury  

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Full Text Available Endogenous neural stem/progenitor cells (eNSPCs proliferate and differentiate into neurons and glial cells after spinal cord injury (SCI. We have previously shown that melatonin (MT plus exercise (Ex had a synergistic effect on functional recovery after SCI. Thus, we hypothesized that combined therapy including melatonin and exercise might exert a beneficial effect on eNSPCs after SCI. Melatonin was administered twice a day and exercise was performed on a treadmill for 15 min, six days per week for 3 weeks after SCI. Immunohistochemistry and RT-PCR analysis were used to determine cell population for late response, in conjunction with histological examination and motor function test. There was marked improvement in hindlimb function in SCI+MT+Ex group at day 14 and 21 after injury, as documented by the reduced size of the spinal lesion and a higher density of dendritic spines and axons; such functional improvements were associated with increased numbers of BrdU-positive cells. Furthermore, MAP2 was increased in the injured thoracic segment, while GFAP was increased in the cervical segment, along with elevated numbers of BrdU-positive nestin-expressing eNSPCs in the SCI+MT+Ex group. The dendritic spine density was augmented markedly in SCI+MT and SCI+MT+Ex groups.These results suggest a synergistic effect of SCI+MT+Ex might create a microenvironment to facilitate proliferation of eNSPCs to effectively replace injured cells and to improve regeneration in SCI.

Youngjeon Lee

2014-01-01

273

Light exposure at night and rotating night shift associated with circadian disruption of 6- sulfatoxy melatonin  

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Background: Alterations in the sleep-wake cycle leads to decreased melatonin secretion and it may be associated with sleep disorders and cancer risk. Exposure of light at night and rotating night shift decrease the melatonin production due to acute suppression of pineal melatonin secretion during night work has been suggested to increases cancer risks. Aims & Objectives: The objectives of the present study were to investigate the effect of light exposure at night on circadian pattern of 6-Sul...

2013-01-01

274

Analysis Method and Experimental Conditions Affect Computed Circadian Phase from Melatonin Data  

Science.gov (United States)

Accurate determination of circadian phase is necessary for research and clinical purposes because of the influence of the master circadian pacemaker on multiple physiologic functions. Melatonin is presently the most accurate marker of the activity of the human circadian pacemaker. Current methods of analyzing the plasma melatonin rhythm can be grouped into three categories: curve-fitting, threshold-based and physiologically-based linear differential equations. To determine which method provides the most accurate assessment of circadian phase, we compared the ability to fit the data and the variability of phase estimates for seventeen different markers of melatonin phase derived from these methodological categories. We used data from three experimental conditions under which circadian rhythms - and therefore calculated melatonin phase - were expected to remain constant or progress uniformly. Melatonin profiles from older subjects and subjects with lower melatonin amplitude were less likely to be fit by all analysis methods. When circadian drift over multiple study days was algebraically removed, there were no significant differences between analysis methods of melatonin onsets (P?=?0.57), but there were significant differences between those of melatonin offsets (P<0.0001). For a subset of phase assessment methods, we also examined the effects of data loss on variability of phase estimates by systematically removing data in 2-hour segments. Data loss near onset of melatonin secretion differentially affected phase estimates from the methods, with some methods incorrectly assigning phases too early while other methods assigning phases too late; missing data at other times did not affect analyses of the melatonin profile. We conclude that melatonin data set characteristics, including amplitude and completeness of data collection, differentially affect the results depending on the melatonin analysis method used.

Klerman, Hadassa; St. Hilaire, Melissa A.; Kronauer, Richard E.; Gooley, Joshua J.; Gronfier, Claude; Hull, Joseph T.; Lockley, Steven W.; Santhi, Nayantara; Wang, Wei; Klerman, Elizabeth B.

2012-01-01

275

Plasma melatonin profiles in mrigal carp (Cirrhinus mrigala) kept under natural and manipulated photoperiods  

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One major challenge in Asian aquaculture is the limited availability of carp fries. In order to establish out of season supply of fries, knowledge about the pineal melatonin clock and calendar function, and its influence on the reproductive system, is needed. Three experiments were carried out to examine pineal melatonin dynamics of mrigal carp (Cirrhinus mrigala), under natural outdoor, and manipulated photoperiods. Plasma melatonin profile of the mrigal carp kept under natural outdoor photo...

2012-01-01

276

Bimodal circadian secretion of melatonin from the pineal gland in a living CBA mouse  

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Circadian melatonin secretion is the best-known output signal from the circadian pacemaker in the suprachiasmatic nucleus that indicates internal conditions of the body. We have established a system that enables long-term monitoring of melatonin secretion by implanting a transverse microdialysis probe in or near the pineal gland in a freely moving mouse. This in vivo method enabled continuous measurement of melatonin secretion over a period of >20 days in individual CB...

Nakahara, Daiichiro; Nakamura, Masato; Iigo, Masayuki; Okamura, Hitoshi

2003-01-01

277

Effects of melatonin on the proliferation and differentiation of rat adipose-derived stem cells  

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Background: Osteogenesis driven by adipose-derived stem cells (ADSCs) is regulated by physiological and pathological factors. Accumulating evidence from in vitro and in vivo experiments suggests that melatonin may have an influence on bone formation. However, little is known about the effects of melatonin on osteogenesis, which thus remains to be elucidated. This study was performed to determine whether melatonin at physiological concentrations (0.01-10 nM) could aff...

2008-01-01

278

Hemoglobinuria paroxística nocturna: Actualización Paroxysmal nocturnal haemoglobinuria  

Directory of Open Access Journals (Sweden)

Full Text Available La hemoglobinuria paroxística nocturna (HPN es una enfermedad clonal y adquirida causada por una mutación somática en el gen PIG-A que se encuentra en el cromosoma X y codifica una proteina involucrada en la síntesis del glicosilfosfatidilinositol (GPI, el cual le sirve como anclaje a muchas proteínas de la membrana celular. La mutación ocurre en el stem cell hematopoyético y da lugar a una deficiencia parcial o total de la proteína PIG-A con la consecuente alteración en la síntesis del GPI de anclaje; como resultado, una parte de las células sanguíneas serán deficientes de todas las proteínas ligadas al GPI. La ausencia de estas proteinas en la HPN explica algunos de los síntomas clínicos de la enfermedad, como la hemólisis intravascular mediada por el complemento, la trombosis venosa, el déficit de la hematopoyesis, etc; pero no el mecanismo mediante el cual el clon HPN se expande en la médula ósea. Varios estudios han demostrado que la inactivación del gen PIG- A por sí sola, no confiere una ventaja proliferativa al stem cell mutado, uno o más factores ambientales externos son necesarios para la expansión de este clon mutado, los cuales ejercen una presión selectiva a favor del clon HPN. La causa por el cual el clon HPN se estimula a proliferar podría ser un daño selectivo a la hematopoyesis normal. En el tratamiento de esta enfermedad se han utilizado varios agentes terapéuticos, pero el único tratamiento curativo es el trasplante de progenitores hematopoyéticosThe paroxysmal nocturnal haemoglobinuria (PNH is a clonal acquired disease caused by a somatic mutation in the PIG-A gene that is located in the chromosome X and codifies a protein involved in the synthesis of glycosil phosphatidylinositol (GPI, which serves as an anchor for many proetins of the cellular membrane. The mutations occurs in the hematopoietic stem cell and gives rise to a partial or total deficiency of the protein PIG-A with the subsequent alteration in the synthesis of the anchored GPI. As a result, a part of the blood cells will be lacking all the proteins bound to the GPI. The absence of these proteins in the NPH explains some of the clinical symptoms of the disease, such as the intravascular hemolysis mediated by the complement, the venous thrombosis, the deficit of hematopoiesis, etc., but not the mechanism by which the NPH clone expands into the bone marrow. Some studies have proved that the inactivation of the GPI-A gene does not confer a proliferative advantage to the mutated stem cell. One or more external environmental factors are needed for the expansion of this mutated clone. These factors exert a selective pressure in favor of the NPH clone. The cause for which the NPH clone is estimulated to proliferate may be a selective damage to the normal hematopoiesis. Several therapeutic agents have been used in the treatment of this disease, but the only curative treatment is the transplantation of hematopoietic progenitors

María Teresa Milanés Roldán

2003-04-01

279

Preliminary evidence that light through the eyelids can suppress melatonin and phase shift dim light melatonin onset  

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Full Text Available Abstract Background A previous study reported a method for measuring the spectral transmittance of individual human eyelids. A prototype light mask using narrow-band “green” light (?max?=?527 nm was used to deliver light through closed eyelids in two within-subjects studies. The first study investigated whether an individual-specific light dose could suppress melatonin by 40% through the closed eyelid without disrupting sleep. The light doses were delivered at three times during the night: 1 beginning (while subjects were awake, 2 middle (during rapid eye movement (REM sleep, and 3 end (during non-REM sleep. The second study investigated whether two individual-specific light doses expected to suppress melatonin by 30% and 60% and delivered through subjects’ closed eyelids before the time of their predicted minimum core body temperature would phase delay the timing of their dim light melatonin onset (DLMO. Findings Compared to a dark control night, light delivered through eyelids suppressed melatonin by 36% (p?=?0.01 after 60-minute light exposure at the beginning, 45% (p?=?0.01 at the middle, and 56% (p p?=?0.03 and by 45% (p?=?0.009 and circadian phase, as measured by DLMO, was delayed by 17 minutes (p?=?0.03 and 71 minutes (ns after 60-minute exposures to light levels 1 and 2, respectively. Conclusions These studies demonstrate that individual-specific doses of light delivered through closed eyelids can suppress melatonin and phase shift DLMO and may be used to treat circadian sleep disorders.

Figueiro Mariana G

2012-05-01

280

Determination of melatonin content in traditional Thai herbal remedies used as sleeping aids  

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Background Melatonin content was screened in leaves of seven edible herbs used as sleeping aids in Thai traditional medicine. These plants are Piper nigrum L, Sesbania glandiflora (L.) Desv., Sesbania sesban (L.) Merr., Senna tora (L.) Roxb., Moringa oleifera Lam., Momordica charantia L. and Baccaurea ramiflora Lour. Dried leaves were extracted by sonication in methanol for six hours at room temperature, and then melatonin was purified by C18 solid phase extraction (SPE). Melatonin was then quantified by a validated RP-C18 HPLC method with fluorescent detection. Findings Melatonin contents in extracts of B. ramiflora,?S. glandiflora,?M. charantia,?S. tora and S. sesban were 43.2, 26.3, 21.4, 10.5 and 8.7 ng/g of dry sample weight, respectively. The highest melatonin content was from P. nigrum extract (1092.7 ng/g of dry sample weight). Melatonin was not detected in the extract of M. oleifera. Melatonin identification was confirmed by ELISA. Conclusions Melatonin was found in six of the seven herbs in the traditional Thai sleeping recipe. One of these, P. nigrum, exhibited an encouragingly high amount of melatonin.

2014-01-01

 
 
 
 
281

Melatonin synthesized by T lymphocytes as a ligand of the retinoic acid-related orphan receptor.  

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Melatonin modulates a wide array of physiological events with pleiotropic effects on the immune system. While the relevance of specific melatonin membrane receptors has been well established for several biological functions, retinoic acid-related orphan receptor alpha (ROR?) has been suggested as a mediator of nuclear melatonin signalling by results obtained from pharmacological approaches. However, a melatonin-mediated downstream effect cannot be ruled out, and further evidence is needed to support a direct interaction between melatonin and ROR?. Here, we show that ROR? is mainly located in human Jurkat T-cell nucleus, and it is co-immunoprecipitated with melatonin. Moreover, immunocytochemistry studies confirmed the co-localization of melatonin and ROR?. Melatonin promoted a time-dependent decrease in nuclear ROR? levels, suggesting a role in the ROR? transcriptional activity. Interestingly, ROR? acts as a molecular switch implicated in the mutually exclusive generation of Th17 and Treg cells, both involved in the harm/protection balance of immune conditions such as autoimmunity or acute transplant rejection. Therefore, the identification of melatonin as a natural modulator of ROR? gives it a tremendous therapeutic potential for a variety of clinical disorders. PMID:21736617

Lardone, Patricia J; Guerrero, Juan M; Fernández-Santos, José M; Rubio, Amalia; Martín-Lacave, Inés; Carrillo-Vico, Antonio

2011-11-01

282

Functional roles of melatonin in plants, and perspectives in nutritional and agricultural science.  

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The presence of melatonin in plants is universal. Evidence has confirmed that a major portion of the melatonin is synthesized by plants themselves even though a homologue of the classic arylalkylamine N-acetyltransferase (AANAT) has not been identified as yet in plants. Thus, the serotonin N-acetylating enzyme in plants may differ greatly from the animal AANAT with regard to sequence and structure. This would imply multiple evolutionary origins of enzymes with these catalytic properties. A primary function of melatonin in plants is to serve as the first line of defence against internal and environmental oxidative stressors. The much higher melatonin levels in plants compared with those found in animals are thought to be a compensatory response by plants which lack means of mobility, unlike animals, as a means of coping with harsh environments. Importantly, remarkably high melatonin concentrations have been measured in popular beverages (coffee, tea, wine, and beer) and crops (corn, rice, wheat, barley, and oats). Billions of people worldwide consume these products daily. The beneficial effects of melatonin on human health derived from the consumption of these products must be considered. Evidence also indicates that melatonin has an ability to increase the production of crops. The mechanisms may involve the roles of melatonin in preservation of chlorophyll, promotion of photosynthesis, and stimulation of root development. Transgenic plants with enhanced melatonin content could probably lead to breakthroughs to increase crop production in agriculture and to improve the general health of humans. PMID:22016420

Tan, Dun-Xian; Hardeland, Rudiger; Manchester, Lucien C; Korkmaz, Ahmet; Ma, Shuran; Rosales-Corral, Sergio; Reiter, Russel J

2012-01-01

283

Melatonin phase shifts human circadian rhythms in a placebo-controlled simulated night-work study  

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There has been scant evidence for a phase-shifting effect of melatonin in shift-work or jet-lag protocols. This study tested whether melatonin can facilitate phase shifts in a simulated night-work protocol. Subjects (n = 32) slept in the afternoons/evenings before night work (a 7-h advance of the sleep schedule). They took melatonin (0.5 mg or 3.0 mg) or placebo before the first four of eight afternoon/evening sleep episodes at a time when melatonin has been shown to phase advance the circadi...

Sharkey, Katherine M.; Eastman, Charmane I.

2002-01-01

284

Melatonin: an overlooked factor in schizophrenia and in the inhibition of anti-psychotic side effects.  

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This paper reviews melatonin as an overlooked factor in the developmental etiology and maintenance of schizophrenia; the neuroimmune and oxidative pathophysiology of schizophrenia; specific symptoms in schizophrenia, including sleep disturbance; circadian rhythms; and side effects of antipsychotics, including tardive dyskinesia and metabolic syndrome. Electronic databases, i.e. PUBMED, Scopus and Google Scholar were used as sources for this review using keywords: schizophrenia, psychosis, tardive dyskinesia, antipsychotics, metabolic syndrome, drug side effects and melatonin. Articles were selected on the basis of relevance to the etiology, course and treatment of schizophrenia. Melatonin levels and melatonin circadian rhythm are significantly decreased in schizophrenic patients. The adjunctive use of melatonin in schizophrenia may augment the efficacy of antipsychotics through its anti-inflammatory and antioxidative effects. Further, melatonin would be expected to improve sleep disorders in schizophrenia and side effects of anti-psychotics, such as tardive dyskinesia, metaboilic syndrome and hypertension. It is proposed that melatonin also impacts on the tryptophan catabolic pathway via its effect on stress response and cortisol secretion, thereby impacting on cortex associated cognition, amygdala associated affect and striatal motivational processing. The secretion of melatonin is decreased in schizophrenia, contributing to its etiology, pathophysiology and management. Melatonin is likely to have impacts on the metabolic side effects of anti-psychotics that contribute to subsequent decreases in life-expectancy. PMID:22527998

Anderson, George; Maes, Michael

2012-06-01

285

Protective effects of chronic melatonin treatment against renal injury in streptozotocin-induced diabetic rats.  

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The aim of this study was to investigate the effects of melatonin as an antioxidant, on prevention and treatment of streptozotocin (STZ)-induced diabetic renal injury in rats. Male Wistar rats were divided into four groups: (1) untreated, (2) melatonin-treated, (3) untreated diabetic (UD), (4) melatonin-treated diabetic (MD). Experimental diabetes was induced by single dose (60 mg/kg, i.p.) STZ injection. For 3 days prior to administration of STZ, melatonin was injected (200 microg/kg/day, i.p.); these injections were continued until the end of the study (4 weeks). Malondialdehyde (MDA) levels as a marker of lipid peroxidation were significantly increased in the renal homogenates of UD animals and decreased after melatonin administration. The activity of the antioxidative enzyme glutathione peroxidase (GSH-Px) was significantly reduced in UD rats. Melatonin treatment reversed STZ-induced reduction of GSH-Px activity without having an effect on blood glucose. Upon histopathological examination, it was observed that the melatonin treatment prevented the renal morphological damage caused by diabetes. Upon immunohistochemical investigation, glomerular anti-laminin beta1 staining decreased in MD rats. Additionally, no tubular anti-IGF-1 staining was observed in melatonin-treated rats. In conclusion, chronically administered melatonin reduced renal injury in STZ-induced diabetic rats and thus it may provide a useful therapeutic option in humans to reduce oxidative stress and the associated renal injury in patients with diabetes mellitus. PMID:12932206

Cam, Meryem; Yavuz, Ozlem; Guven, Aysel; Ercan, Feriha; Bukan, Neslihan; Ustündag, Nil

2003-10-01

286

Characterization of melatonin binding sites in the Harderian gland and median eminence of the rat  

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The characterization of specific melatonin binding sites in the Harderian gland (HG) and median eminence (ME) of the rat was studied using [125I]melatonin. Binding of melatonin to membrane crude preparations of both tissues was dependent on time and temperature. Thus, maximal binding was obtained at 37 degree C after 30-60 min incubation. Binding was also dependent on protein concentration. The specific binding of [125I]melatonin was saturable, exhibiting only the class of binding sites in both tissues. The dissociation constants (Kd) were 170 and 190 pM for ME and HG, respectively. The concentration of the binding sites in ME was 8 fmol/mg protein, and in the HG 4 fmol/mg protein. In competition studies, binding of [125I]melatonin to ME or HG was inhibited by increasing concentration of native melatonin; 50% inhibition was observed at about 702 and 422 nM for ME and HG, respectively. Additionally, the [125I]melatonin binding to the crude membranes was not affected by the addition of different drugs such as norepinephrine, isoproterenol, phenylephrine, propranolol, or prazosin. The results confirm the presence of melatonin binding sites in median eminence and show, for the first time, the existence of melatonin binding sites in the Harderian gland

1991-01-01

287

Characterization of melatonin binding sites in the Harderian gland and median eminence of the rat  

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The characterization of specific melatonin binding sites in the Harderian gland (HG) and median eminence (ME) of the rat was studied using ({sup 125}I)melatonin. Binding of melatonin to membrane crude preparations of both tissues was dependent on time and temperature. Thus, maximal binding was obtained at 37{degree}C after 30-60 min incubation. Binding was also dependent on protein concentration. The specific binding of ({sup 125}I)melatonin was saturable, exhibiting only the class of binding sites in both tissues. The dissociation constants (Kd) were 170 and 190 pM for ME and HG, respectively. The concentration of the binding sites in ME was 8 fmol/mg protein, and in the HG 4 fmol/mg protein. In competition studies, binding of ({sup 125}I)melatonin to ME or HG was inhibited by increasing concentration of native melatonin; 50% inhibition was observed at about 702 and 422 nM for ME and HG, respectively. Additionally, the ({sup 125}I)melatonin binding to the crude membranes was not affected by the addition of different drugs such as norepinephrine, isoproterenol, phenylephrine, propranolol, or prazosin. The results confirm the presence of melatonin binding sites in median eminence and show, for the first time, the existence of melatonin binding sites in the Harderian gland.

Lopez-Gonzalez, M.A.; Calvo, J.R.; Rubio, A.; Goberna, R.; Guerrero, J.M. (Univ. of Seville School of Medicine, Sevilla (Spain))

1991-01-01

288

Anxiolytisk, analgetisk og sedativ effekt af melatonin i den perioperative fase  

DEFF Research Database (Denmark)

Melatonin is a hormone mainly produced in the pineal gland. The most well known effect is a modulation of the circadian rhythm. Patients undergoing surgery often get a disruption of this rhythm. Effects of melatonin have been examined in several randomised clinical studies. In this report we briefly review evidence regarding anxiolytical, analgesic and sedative effects of melatonin in relation to surgery. Studies show an effect in favour of medication with melatonin with regards to sedation and anxiety but the effect on analgesia has yet to be clarified with further clinical studies.

Wilhelmsen, Michael; Rosenberg, Jacob

2011-01-01

289

Mechanistic and comparative studies of melatonin and classic antioxidants in terms of their interactions with the ABTS cation radical.  

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Melatonin and classic antioxidants possess the capacity to scavenge ABTSb+ with IC50s of 4, 11, 15.5, 15.5, 17 and 21 microm for melatonin, glutathione, vitamin C, trolox, NADH and NADPH, respectively. In terms of scavenging ABTSb+, melatonin exhibits a different profile than that of the classic antioxidants. Classic antioxidants scavenge one or less ABTSb+, while each melatonin molecule can scavenge more than one ABTSb+, probably with a maximum of four. Classic antioxidants do not synergize when combined in terms of scavenging ABTSb+. However, a synergistic action is observed when melatonin is combined with any of the classic antioxidants. Cyclic voltammetry indicates that melatonin donates an electron at the potential of 715 mV. The scavenging mechanism of melatonin on ABTSb+ may involve multiple-electron donations via intermediates through a stepwise process. Intermediates including the melatoninyl cation radical, the melatoninyl neutral radical and cyclic 3-hydroxymelatonin (cyclic 3-OHM) and N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) seem to participate in these reactions. More interestingly, the pH of the solution dramatically modifies the ABTSb+ scavenging capacity of melatonin while pH changes have no measurable influence on the scavenging activity of classic antioxidants. An acidic pH markedly reduces the ABTSb+ scavenging capacity of melatonin while an increased pH promotes the interaction of melatonin and ABTSb+. The major melatonin metabolites that develop when melatonin interacts with ABTSb+ are cyclic 3-OHM and AFMK. Cyclic 3-OHM is the intermediate between melatonin and AFMK, and cyclic 3-OHM also has the ability to scavenge ABTSb+. Melatonin and the metabolites which are generated via the interaction of melatonin with ABTSb+, i.e. the melatoninyl cation radical, melatoninyl neutral radical and cyclic 3-OHM, all scavenge ABTSb+. This unique cascade action of melatonin, in terms of scavenging, increases its efficiency to neutralized ABTSb+; this contrasts with the effects of the classic antioxidants. PMID:12662346

Tan, Dun-xian; Hardeland, Rüdiger; Manchester, Lucien C; Poeggeler, Burkhard; Lopez-Burillo, Silvia; Mayo, Juan C; Sainz, Rosa M; Reiter, Russel J

2003-05-01

290

Individual variations in serum melatonin levels through time: implications for epidemiologic studies.  

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Melatonin, a marker for the circadian rhythm with serum levels peaking between 2AM and 5AM, is hypothesized to possess anti-cancer properties, making it a mechanistic candidate for the probable carcinogenic effect of circadian rhythm disruption. In order to weigh epidemiologic evidence on the association of melatonin with cancer, we must first understand the laboratory and biological sources of variability in melatonin levels measured in samples. Participants for this methodological study were men enrolled in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO). We measured serum melatonin levels over a five year period in 97 individuals to test if melatonin levels are steady over time. The Pearson correlation coefficient between two measures separated by 1 year was 0.87, while the correlation between two measures separated by 5 years was to 0.70. In an additional cross-sectional study of 292 individuals, we used Analysis of Variance to identify differences in melatonin levels between different lifestyle and environmental characteristics. Serum melatonin levels were slightly higher in samples collected from 130 individuals during the winter, (6.36±0.59 pg/ml) than in samples collected from 119 individuals during the summer (4.83±0.62 pg/ml). Serum melatonin levels were lowest in current smokers (3.02±1.25 pg/ml, p?=?0.007) compared to never (6.66±0.66 pg/ml) and former (5.59±0.50 pg/ml) smokers whereas BMI did not significantly affect serum melatonin levels in this study. In conclusion, the high 5 year correlation of melatonin levels implies that single measurements may be used to detect population level associations between melatonin and risk of cancer. Furthermore, our results reiterate the need to record season of sample collection, and individual characteristics in order to maximize study power and prevent confounding. PMID:24376664

Nogueira, Leticia M; Sampson, Joshua N; Chu, Lisa W; Yu, Kai; Andriole, Gerald; Church, Timothy; Stanczyk, Frank Z; Koshiol, Jill; Hsing, Ann W

2013-01-01

291

Effect of melatonin on motor performance and brain cortex mitochondrial function during ethanol hangover.  

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Increased reactive oxygen species generation and mitochondrial dysfunction occur during ethanol hangover. The aim of this work was to study the effect of melatonin pretreatment on motor performance and mitochondrial function during ethanol hangover. Male mice received melatonin solution or its vehicle in drinking water during 7days and i.p. injection with EtOH (3.8g/kg BW) or saline at the eighth day. Motor performance and mitochondrial function were evaluated at the onset of hangover (6h after injection). Melatonin improved motor coordination in ethanol hangover mice. Malate-glutamate-dependent oxygen uptake was decreased by ethanol hangover treatment and partially prevented by melatonin pretreatment. Melatonin alone induced a decrease of 30% in state 4 succinate-dependent respiratory rate. Also, the activity of the respiratory complexes was decreased in melatonin-pretreated ethanol hangover group. Melatonin pretreatment before the hangover prevented mitochondrial membrane potential collapse and induced a 79% decrement of hydrogen peroxide production as compared with ethanol hangover group. Ethanol hangover induced a 25% decrease in NO production. Melatonin alone and as a pretreatment before ethanol hangover significantly increased NO production by nNOS and iNOS as compared with control groups. No differences were observed in nNOS protein expression, while iNOS expression was increased in the melatonin group. Increased NO production by melatonin could be involved in the decrease of succinate-dependent oxygen consumption and the inhibition of complex IV observed in our study. Melatonin seems to act as an antioxidant agent in the ethanol hangover condition but also exhibited some dual effects related to NO metabolism. PMID:24713372

Karadayian, A G; Bustamante, J; Czerniczyniec, A; Cutrera, R A; Lores-Arnaiz, S

2014-06-01

292

Melatonin attenuates prenatal dexamethasone-induced blood pressure increase in a rat model.  

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Although antenatal corticosteroid is recommended to accelerate fetal lung maturation, prenatal dexamethasone exposure results in hypertension in the adult offspring. Since melatonin is a potent antioxidant and has been known to regulate blood pressure, we examined the beneficial effects of melatonin therapy in preventing prenatal dexamethasone-induced programmed hypertension. Male offspring of Sprague-Dawley rats were assigned to four groups (n = 12/group): control, dexamethasone (DEX), control + melatonin, and DEX + melatonin. Pregnant rats received intraperitoneal dexamethasone (0.1 mg/kg) from gestational day 16 to 22. In the melatonin-treatment groups, rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Blood pressure was measured by an indirect tail-cuff method. Gene expression and protein levels were analyzed by real-time quantitative polymerase chain reaction and Western blotting, respectively. At 16 weeks of age, the DEX group developed hypertension, which was partly reversed by maternal melatonin therapy. Reduced nephron numbers due to prenatal dexamethasone exposure were prevented by melatonin therapy. Renal superoxide and NO levels were similar in all groups. Prenatal dexamethasone exposure led to increased mRNA expression of renin and prorenin receptor and up-regulated histone deacetylase (HDAC)-1 expression in the kidneys of 4-month-old offspring. Maternal melatonin therapy augmented renal Mas protein levels in DEX + melatonin group, and increased renal mRNA expression of HDAC-1, HDAC-2, and HDAC-8 in control and DEX offspring. Melatonin attenuated prenatal DEX-induced hypertension by restoring nephron numbers, altering RAS components, and modulating HDACs. PMID:24731552

Tain, You-Lin; Chen, Chih-Cheng; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Kuo, Ho-Chang; Huang, Li-Tung

2014-04-01

293

Melatonin: Action as antioxidant and potential applications in human disease and aging  

International Nuclear Information System (INIS)

This review aims at describing the beneficial properties of melatonin related to its antioxidant effects. Oxidative stress, i.e., an imbalance between the production of reactive oxygen species and antioxidant defences, is involved in several pathological conditions such as cardiovascular or neurological disease, and in aging. Therefore, research for antioxidants has developed. However, classical antioxidants often failed to exhibit beneficial effects, especially in metabolic diseases. Melatonin has been shown as a specific antioxidant due to its amphiphilic feature that allows it to cross physiological barriers, thereby reducing oxidative damage in both lipid and aqueous cell environments. Studies on the antioxidant action of melatonin are reported, with a special mention to water gamma radiolysis as a method to produce oxygen-derived free radicals, and on structure-activity relationships of melatonin derivatives. Mass spectrometry-based techniques have been developed to identify melatonin oxidation products. Besides its ability to scavenge several radical species, melatonin regulates the activity of antioxidant enzymes (indirect antioxidant properties). Efficient detection methods confirmed the presence of melatonin in several plant products. Therapeutic potential of melatonin relies either on increasing melatonin dietary intake or on supplementation with supraphysiological dosages. Clinical trials showed that melatonin could be efficient in preventing cell damage, as well under acute (sepsis, asphyxia in newborns) as under chronic (metabolic and neurodegenerative diseases, cancer, inflammation, aging). Its global action on oxidative stress, together with its rhythmicity that plays a role in several metabolic functions, lead melatonin to be of great interest for future clinical research in order to improve public health.

2010-11-28

294

Individual Variations in Serum Melatonin Levels through Time: Implications for Epidemiologic Studies  

Science.gov (United States)

Melatonin, a marker for the circadian rhythm with serum levels peaking between 2AM and 5AM, is hypothesized to possess anti-cancer properties, making it a mechanistic candidate for the probable carcinogenic effect of circadian rhythm disruption. In order to weigh epidemiologic evidence on the association of melatonin with cancer, we must first understand the laboratory and biological sources of variability in melatonin levels measured in samples. Participants for this methodological study were men enrolled in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO). We measured serum melatonin levels over a five year period in 97 individuals to test if melatonin levels are steady over time. The Pearson correlation coefficient between two measures separated by 1 year was 0.87, while the correlation between two measures separated by 5 years was to 0.70. In an additional cross-sectional study of 292 individuals, we used Analysis of Variance to identify differences in melatonin levels between different lifestyle and environmental characteristics. Serum melatonin levels were slightly higher in samples collected from 130 individuals during the winter, (6.36±0.59 pg/ml) than in samples collected from 119 individuals during the summer (4.83±0.62 pg/ml). Serum melatonin levels were lowest in current smokers (3.02±1.25 pg/ml, p?=?0.007) compared to never (6.66±0.66 pg/ml) and former (5.59±0.50 pg/ml) smokers whereas BMI did not significantly affect serum melatonin levels in this study. In conclusion, the high 5 year correlation of melatonin levels implies that single measurements may be used to detect population level associations between melatonin and risk of cancer. Furthermore, our results reiterate the need to record season of sample collection, and individual characteristics in order to maximize study power and prevent confounding.

Nogueira, Leticia M.; Sampson, Joshua N.; Chu, Lisa W.; Yu, Kai; Andriole, Gerald; Church, Timothy; Stanczyk, Frank Z.

2013-01-01

295

Anterior urethral valve in an adolescent with nocturnal enuresis.  

Science.gov (United States)

The anterior urethral valve (AUV) is a rare congenital urethral anomaly that can lead to variable urinary tract symptoms. We report on a 13-year-old boy with AUV who was referred from a primary care physician for nocturnal enuresis. AUV was disclosed by videourodynamic study and confirmed by simultaneous retrograde cystourethroscopy and antegrade urethroscopy. The AUV was ablated by neodymium:yttrium-aluminum-garnet contact laser at the 5-o'clock and 7-o'clock directions. A postoperative videourodynamic study depicted a patent urethra, a good maximal flow rate, and improved bladder capacity. His nocturnal enuresis had completely subsided at a follow-up period of longer than 24 months. PMID:18068473

Wu, Chia Chang; Yang, Stephen Shei Dei; Tsai, Yao Chou

2007-11-01

296

Melatonin concentrations in the sudden infant death syndrome  

Science.gov (United States)

To examine a possible relationship between pineal function and the sudden infant death syndrome (SIDS), samples of whole blood, ventricular cerebrospinal fluid (CSF) and/or vitreous humor (VH) were obtained at autopsy from 68 infants (45 male, 23 female) whose deaths were attributed to either SIDS (n = 32, 0.5-5.0 months of age; mean plus or minus S.E.M., 2.6 plus or minus 0.2 months) or other causes (non-SIDS, n = 36, 0.3-8.0 months of age 4.3 plus or minus 0.3 months). The melatonin concentrations were measured by radioimmunoassay. A significant correlation was observed for melatonin levels in different body fluids from the same individual. After adjusting for age differences, CSF melatonin levels were significantly lower among the SIDS infants (91 plus or minus 29 pmol/l; n = 32) than among those dying from other causes (180 plus or minus 27; n = 35, P less than 0.05). A similar, but non-significant trend was also noted in blood (97 plus or minus 23, n = 30 vs. 144 plus or minus 22 pmol/l, n = 33) and vitreous humor (68 plus or minus 21, n = 10 vs. 81 plus or minus 17 pmol/l, n = 15). These differences do not appear to be explainable in terms of the interval between death and autopsy, gender, premortem infection, or therapeutic measures instituted prior to death. Diminished melatonin production may be characteristic of SIDS and could represent an impairment in the maturation of physiologic circadian organization.

Sturner, W. Q.; Lynch, H. J.; Deng, M. H.; Gleason, R. E.; Wurtman, R. J.

1990-01-01

297

Antioxidant properties of melatonin: a pulse radiolysis study  

International Nuclear Information System (INIS)

A variety of reactive oxygen species such as OH., NO., NO2., RO., and ROO. and other one-electron oxidants such as Br2.-, N3. were scavenged by melatonin in aqueous media at pH 7 using pulse radiolysis technique. The kinetic and spectroscopic parameters were determined. One-electron reduction potential for the couple Mel./MelH was E=0.72 V. (author)

1998-01-01

298

Efficacy and safety of prolonged-release melatonin for insomnia in middle-aged and elderly patients with hypertension: a combined analysis of controlled clinical trials  

Directory of Open Access Journals (Sweden)

Full Text Available Patrick Lemoine1, Alan G Wade2, Amnon Katz3, Tali Nir3, Nava Zisapel3,41The Clinique Lyon-Lumière, Meyzieu, France; 2CPS Research, 3 Todd Campus, Glasgow, UK; 3Neurim Pharmaceuticals Ltd, Tel-Aviv, Israel; 4Department of Neurobiology Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, IsraelBackground: Add-on prolonged-release melatonin (PRM in antihypertensive therapy has been shown to ameliorate nocturnal hypertension. Hypertension is a major comorbidity among insomnia patients. The efficacy and safety of PRM for primary insomnia in patients aged 55 years and older who are treated with antihypertensive drugs were evaluated.Methods: Post hoc analysis of pooled antihypertensive drug-treated subpopulations from four randomized, double-blind trials of PRM and placebo for 3 weeks (N[PRM] = 195; N[placebo] = 197 or 28 weeks (N[PRM] = 157; N[placebo] = 40. Efficacy measurements included Leeds Sleep Evaluation Questionnaire scores of quality of sleep and alertness and behavioral integrity the following morning after 3 weeks, and sleep latency (daily sleep diary and Clinical Global Impression of Improvement (CGI-I after 6 months of treatment. Safety measures included antihypertensive drug-treated subpopulations from these four and three additional single-blind and open-label PRM studies of up to 1 year (N[PRM] = 650; N[placebo] = 632.Results: Quality of sleep and behavior following wakening improved significantly with PRM compared with placebo (P < 0.0001 and P < 0.0008, respectively. Sleep latency (P = 0.02 and CGI-I (P = 0.0003 also improved significantly. No differences were observed between PRM and placebo groups in vital signs, including daytime blood pressure at baseline and treatment phases. The rate of adverse events normalized per 100 patient-weeks was lower for PRM (3.66 than for placebo (8.53.Conclusions: The findings demonstrate substantive and sustained efficacy of PRM in primary insomnia patients treated with antihypertensive drugs. PRM appears to be safe for insomnia in patients with cardiovascular comorbidity.Keywords: prolonged-release melatonin, hypertension, nocturnal blood pressure, insomnia, cardiovascular disease, sleep quality

Lemoine P

2012-01-01

299

Intrathecal baclofen. Effects on nocturnal leg muscle spasticity.  

Science.gov (United States)

Electromyographic activity was recorded from tibialis anterior during nocturnal polysomnography in six patients with severe spasticity of spinal origin. The patients had a baclofen reservoir system implanted subcutaneously into their lumbar subarachnoid space and were studied for two nights in a double-blind, placebo controlled, crossover design. Tibialis anterior electromyographic activity per hour of sleep was reduced on the night of baclofen infusion. In particular, less electromyographic activity occurred after arousal from sleep. PMID:1739446

Kravitz, H M; Corcos, D M; Hansen, G; Penn, R D; Cartwright, R D; Gianino, J

1992-02-01

300

Behaviourally mediated crypsis in two nocturnal moths with contrasting appearance  

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The natural resting orientations of several species of nocturnal moth on tree trunks were recorded over a three-month period in eastern Ontario, Canada. Moths from certain genera exhibited resting orientation distributions that differed significantly from random, whereas others did not. In particular, Catocala spp. collectively tended to orient vertically, whereas subfamily Larentiinae representatives showed a variety of orientations that did not differ significantly from random. To understan...

Webster, Richard J.; Callahan, Alison; Godin, Jean-guy J.; Sherratt, Thomas N.

2009-01-01

 
 
 
 
301

Epidemiology and exogenous factors in nocturnal airflow limitation in children  

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The studies in this thesis add new insights to the concept on the pathophysiology of nocturnal airflow limitation in asthmatic children. Exogenous factors such as environmental tobacco smoke, the presence of pets, and high HDMA levels all independently contribute to the circadian PEF amplitude in allergic asthmatic children. Parents should not only be stressed to stop smoking during pregnancy, but also any time thereafter to improve the stability and the prognosis of their childs asthma...

Rosman-meijer, Geertruida Gerarda

1996-01-01

302

Simvastatin-induced nocturnal leg pain disappears with pravastatin substitution  

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Introduction. Statins have similar side effects that do not always occur at the same rate among the various statins. We present a case of simvastatin-induced muscle toxicity that disappeared when pravastatin was substituted for the original drug. Case Outline. A 74-year-old male, a nonsmoker, complained of severe nocturnal leg cramps. The patient also complained that similar painful cramping occurred when he walked rapidly or jogged. Because some components of his lipid panel exceeded t...

Stojakovi? Nataša; Igi? Rajko

2013-01-01

303

Paroxysmal nocturnal hemoglobinuria: a study of 17 cases.  

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Full Text Available Retrospective analysis of 17 cases of paroxysmal nocturnal hemoglobinuria (PNH was carried out. The presenting feature of anaemia and hemoglobin of less than 9 gm% were observed in all cases. Fever, jaundice and bleeding tendency were observed in 8, 8 and 7 cases respectively. Bone marrow examination revealed megaloblastic features, erythroid hyperplasia and hypocellularity in 8, 7 and 2 cases respectively. Fourteen cases were refractory to the treatment, while only 3 showed response.

Parab R

1990-01-01

304

Oxybutynin for treatment of nocturnal enuresis in children  

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Question A 7-year-old child and his parents visit my clinic owing to the child’s frequent bed-wetting. During the day, he has no problem controlling his urination. The family has tried behavioural methods but has failed to achieve dryness during the night. They ask to begin medical treatment. Is oxybutynin a safe and effective drug for treating nocturnal enuresis?

Friedman, Bat-chen; Friedman, Boris; Goldman, Ran D.

2011-01-01

305

Nocturnal oesophageal motor activity is dependent on sleep stage.  

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Simultaneous overnight oesophageal pH and manometric and sleep electroencephalographic recordings were performed in eight healthy subjects, aged 20-38 years, to test the hypothesis that the frequency of primary, swallow related contractions decreases progressively with deeper sleep stages whereas the frequency of secondary contractions remains constant throughout the night. During the nocturnal period (2300 to 0700), periods of oesophageal motor quiescence were interspersed by clusters of con...

Castiglione, F.; Emde, C.; Armstrong, D.; Schneider, C.; Bauerfeind, P.; Stacher, G.; Blum, A. L.

1993-01-01

306

The pathophysiology of paroxysmal nocturnal hemoglobinuria and treatment with eculizumab  

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Richard Kelly1, Stephen Richards1, Peter Hillmen1, Anita Hill21Institute of Oncology, St. James’s University Hospital, Leeds, UK; 2Department of Haematology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UKAbstract: Paroxysmal nocturnal hemoglobinuria is a rare disorder of hemopoietic stem cells. Affected individuals have a triad of clinical associations – intravascular hemolysis, an increased risk of thromboembolism, and bone marrow failure. Most of the symptoms exp...

Richard Kelly; Stephen Richards; Peter Hillmen; et al

2009-01-01

307

The pathophysiology of paroxysmal nocturnal hemoglobinuria and treatment with eculizumab  

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Paroxysmal nocturnal hemoglobinuria is a rare disorder of hemopoietic stem cells. Affected individuals have a triad of clinical associations – intravascular hemolysis, an increased risk of thromboembolism, and bone marrow failure. Most of the symptoms experienced in this disease occur due to the absence of complement regulatory proteins on the surface of the red blood cells. Complement activation is thus not checked and causes destruction of these cells. Eculizumab is a monoclonal antibody ...

Kelly, Richard; Richards, Stephen; Hillmen, Peter; Hill, Anita

2009-01-01

308

Comparison of desmopressin and enuresis alarm for nocturnal enuresis.  

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Fifty children with primary nocturnal enuresis were randomised for a study comparing desmopressin (DDAVP) and enuresis alarm. Forty six completed the trial, 24 of whom were treated with 20 micrograms intranasal desmopressin nightly and 22 with enuresis alarm for three months. Failures were crossed over and relapses were continued on the same treatment for a further three months. The improvement rate was 70% in the group given desmopressin and 86% in the group treated with alarm; the differenc...

Wille, S.

1986-01-01

309

Paroxysmal nocturnal hemoglobinuria: rare cause of acute renal failure  

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Paroxysmal nocturnal hemoglobinuria is a rare acquired disease, characterized by hemolytic anemia, recurrent infections, cytopenias, and vascular thrombosis. It occurs by non-malignant clonal expansion of one or more hematopoietic stem cells that acquired somatic mutations in PIG-A gene linked to chromosome X. This mutation results in lower erythrocyte expression of CD55 and CD59 surface proteins and consequently increased susceptibility to the complement system. The renal involvement i...

Vilma Takayasu; Márcia Yoshie Kanegae; Jairo Rays

2012-01-01

310

Nocturnal insects use optic flow for flight control  

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To avoid collisions when navigating through cluttered environments, flying insects must control their flight so that their sensory systems have time to detect obstacles and avoid them. To do this, day-active insects rely primarily on the pattern of apparent motion generated on the retina during flight (optic flow). However, many flying insects are active at night, when obtaining reliable visual information for flight control presents much more of a challenge. To assess whether nocturnal flyin...

Baird, Emily; Kreiss, Eva; Wcislo, William; Warrant, Eric; Dacke, Marie

2011-01-01

311

Nocturnal Homing: Learning Walks in a Wandering Spider?  

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Homing by the nocturnal Namib Desert spider Leucorchestris arenicola (Araneae: Sparassidae) is comparable to homing in diurnal bees, wasps and ants in terms of path length and layout. The spiders' homing is based on vision but their basic navigational strategy is unclear. Diurnal homing insects use memorised views of their home in snapshot matching strategies. The insects learn the visual scenery identifying their nest location during learning flights (e.g. bees and wasps) or walks (ants). Th...

Nørgaard, Thomas; Gagnon, Yakir L.; Warrant, Eric J.

2012-01-01

312

Melatonin agonists for treatment of sleep and depressive disorders  

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Full Text Available Melatonin the hormone secreted by the pineal gland has been effective in improving sleep both in normal sleepers and insomniacs and has been used successfully in treating sleep and circadian rhythm sleep disorders. The lack of consistency in the reports published by the authors is attributed to the differential bioavailabilty and short half-life of melatonin. Sleep disturbances are also prominent features of depressive disorders. To overcome this problem, melatonergic agonists with sleep promoting properties have been introduced in clinical practice. Ramelteon, the MT1/ MT2 melatonergic agonist, has been used in a large number of clinical trials involving chronic insomniacs and has been found effective in improving the total sleep time and sleep efficiency of insomniacs and has not manifested serious adverse effects. The development of another MT1/MT2 melatonergic agonist agomelatine with antagonsim to 5-HT2c serotonin receptors has been found useful not only in treating sleep problems of patients but also as a first line antidepressant with earlier onset of actions in patients with major depressive disorder. An agonist for MT3 melatonin receptor has also been found effective in animal models of depression. [J Exp Integr Med 2011; 1(3.000: 149-158

Seithikurippu R. Pandi-Perumal

2011-06-01

313

Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases  

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Full Text Available Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease.

Huey-Kang Sytwu

2013-05-01

314

Red light accelerates and melatonin retards metamorphosis of frog tadpoles  

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Full Text Available Abstract Background Earlier studies from this laboratory reported that light and its spectra influence reproduction in the Indian skipper frog Rana cyanophlyctis through both ocular and extra ocular photoreception. During the course of our ongoing studies on chromotactic behaviour of the tadpoles, we noticed that tadpoles held in red light metamorphosed earlier than those held in white or other colours of light. The focus of the present study therefore was to examine the effect of red light on metamorphosis of the tadpoles. Results Tadpoles, both intact and blind (optectomised, held in red light metamorphosed earlier than those held in white light. Addition of melatonin to aquarium water (5 micrograms/litre prevented the red light-induced acceleration of metamorphosis both in intact and blinded tadpoles. Conclusion Both ocular and extra-ocular perception of light is involved in red light-induced precocious metamorphosis. Melatonin inhibits the red light-induced acceleration of metamorphosis. The mechanism by which red light accelerates metamorphosis is not yet known. Melatonin counteracts red-light induced acceleration of metamorphosis in this tadpole.

Mohinuddin Khaja

2003-09-01

315

Malaria, anti malarial drugs and the role of melatonin.  

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Malaria, one of the most deadly diseases of our time affects more than 200 million people across the globe and is responsible for about one million deaths annually. Until recently Plasmodium falciparum has been the main cause for malarial infection in human beings but now Plasmodium knowlesi from Malaysia remains as one of the most virulent parasite spreading fast not only in Malaysia but in different parts of the world. Hence there is urgent need for the global fight to control malaria. Global malaria eradication program by use of insecticide spraying has resulted in good response in the past. Treatment of malaria infected patients with anti-malarial drugs has helped to eliminate malarial infections successfully but with increased resistance displayed by malarial parasites to these drugs there is resurgence of malaria caused both by drug resistance as well as by infection caused by new malarial species like Plasmodium knowlesi. With recent advances on molecular studies on malarial parasites it is now clear that the pineal hormone melatonin acts as a cue for growth and development of Plasmodium falciparum. Same may be true for Plasmodium knowlesi also. Hence treatment modalities that can effectively block the action of melatonin on Plasmodium species during night time by way of using either bright light therapy or use of melatonin receptor blocking can be considered as useful approaches for eliminating malarial infection in man. PMID:23082960

Srinivasan, Venkataramanujam; Mohamed, Mahaneem; Zakaria, Rahimah; Ahmad, Asma Hayati

2012-10-01

316

Nocturnal sleep pattern in native Brazilian Terena adults  

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Full Text Available Social-economic factors influence sleep habits. This research analyzes characteristics of nocturnal sleep in Brazilian Native Terena adults. Sixty-four adults (31 M; 33 F from 18 to 75 years, with a mean age of 37.0, from the Indian Reservation village of Córrego do Meio, in the central region of Mato Grosso do Sul, an agriculturally oriented group were evaluated. Nocturnal sleep characteristics were evaluated by means of a standard questionnaire applied to each individual. It was observed that reported nocturnal sleep was longer, sleep onset was earlier and wake up time was also earlier than usually described in urban populations. The mean total time in bed was 8.5 h or more, in every age bracket. The seven-day prevalence rate of insomnia was 4.6%, while the seven-day prevalence rate of hypnotic use was 1.5%, both remarkably less than described in urban populations. These findings stress the need to consider ethnic influences on sleep patterns and disorders.

REIMÃO RUBENS

2000-01-01

317

Sound imaging of nocturnal animal calls in their natural habitat.  

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We present a novel method for imaging acoustic communication between nocturnal animals. Investigating the spatio-temporal calling behavior of nocturnal animals, e.g., frogs and crickets, has been difficult because of the need to distinguish many animals' calls in noisy environments without being able to see them. Our method visualizes the spatial and temporal dynamics using dozens of sound-to-light conversion devices (called "Firefly") and an off-the-shelf video camera. The Firefly, which consists of a microphone and a light emitting diode, emits light when it captures nearby sound. Deploying dozens of Fireflies in a target area, we record calls of multiple individuals through the video camera. We conduct two experiments, one indoors and the other in the field, using Japanese tree frogs (Hyla japonica). The indoor experiment demonstrates that our method correctly visualizes Japanese tree frogs' calling behavior. It has confirmed the known behavior; two frogs call synchronously or in anti-phase synchronization. The field experiment (in a rice paddy where Japanese tree frogs live) also visualizes the same calling behavior to confirm anti-phase synchronization in the field. Experimental results confirm that our method can visualize the calling behavior of nocturnal animals in their natural habitat. PMID:21584762

Mizumoto, Takeshi; Aihara, Ikkyu; Otsuka, Takuma; Takeda, Ryu; Aihara, Kazuyuki; Okuno, Hiroshi G

2011-09-01

318

Original Design of Fluorescent Ligands by Fusing BODIPY and Melatonin Neurohormone.  

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An original design and synthesis of fluorescent ligands for melatonin receptor studies is presented and consists in the fusion of the endogenous ligand with the fluorescent BODIPY core. Probes I-IV show high affinities for MT1 and MT2 melatonin receptors and exhibit fluorescence properties compatible with cell observation. PMID:24900790

Thireau, Jérémy; Marteaux, Justine; Delagrange, Philippe; Lefoulon, Francois; Dufourny, Laurence; Guillaumet, Gérald; Suzenet, Franck

2014-02-13

319

Characterization of signaling pathways coupled to melatonin receptors in gastrointestinal smooth muscle.  

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Melatonin, a close derivative of serotonin, is involved in physiological regulation of circadian rhythms. In the gastrointestinal (GI) system, melatonin exhibits endocrine, paracrine and autocrine actions and is implicated in the regulation of GI motility. However, it is not known whether melatonin can also act directly on GI smooth muscle cells. The aim of the present study was to determine the expression of melatonin receptors in smooth muscle and identify their signaling pathways. MT1, but not MT2 receptors are expressed in freshly dispersed and cultured gastric smooth muscle cells. Melatonin selectively activated Gq and stimulated phosphoinositide (PI) hydrolysis in freshly dispersed and cultured muscle cells. PI hydrolysis was blocked by the expression of Gq, but not Gi minigene in cultured muscle cells. Melatonin also caused rapid increase in cytosolic Ca(2+) as determined by epifluorescence microscopy in fura-2 loaded single smooth muscle cells, and induced rapid contraction. Melatonin-induced PI hydrolysis and contraction were blocked by a non-selective MT1/MT2 antagonist luzindole (1 ?M), but not by a selective MT2 antagonist 4P-PDOT (100 nM), and by the PLC inhibitor U73122. MT2 selective agonist IIK7 (100 nM) had no effect on PI hydrolysis and contraction. We conclude that rabbit gastric smooth muscle cells express melatonin MT1 receptors coupled to Gq. Activation of these receptors causes stimulation of PI hydrolysis and increase in cytosolic Ca(2+), and elicits muscle contraction. PMID:23541890

Ahmed, Rashad; Mahavadi, Sunila; Al-Shboul, Othman; Bhattacharya, Sayak; Grider, John R; Murthy, Karnam S

2013-06-10

320

Melatonin synthesis in human colostrum mononuclear cells enhances dectin-1-mediated phagocytosis by mononuclear cells.  

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Many cells in the organism besides pinealocytes, synthesize melatonin. Here, we evaluate both the mechanism of zymosan-induced melatonin synthesis and its autocrine effect in human colostral mononuclear cells. The synthesis of melatonin was induced by activation of the transcription factor nuclear factor kappa B (NF-?B), as either the blockade of the proteasome or the binding of NF-?B to DNA inhibits zymosan-induced melatonin synthesis. As observed in RAW 264.7 lineage cells, the dimer involved is RelA/c-Rel. Melatonin plays a direct role in mononuclear cell activity, increasing zymosan-induced phagocytosis by stimulating MT2 melatonin receptors and increasing the expression of dectin-1. This role was confirmed by the blockade of melatonin receptors using the competitive antagonist luzindole and the MT2 -selective partial agonist 4P-PDOT. In summary, we show that melatonin produced by immune-competent cells acts in an autocrine manner, enhancing the clearance of pathogens by increasing phagocyte efficiency. Given that these cells are present in human colostrum for 4 or 5 days after birth, this mechanism may be relevant for the protection of infant health. PMID:23745599

Pires-Lapa, Marco A; Tamura, Eduardo K; Salustiano, Eugenia M A; Markus, Regina P

2013-10-01

 
 
 
 
321

Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes.  

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Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxidant activity, showing that melatonin is able to stimulate production of intracellular reactive oxygen species (ROS). Here we show that on U937 human monocytes melatonin promotes intracellular ROS in a fast (<1 min) and transient (up to 5-6 h) way. Melatonin equally elicits its pro-radical effect on a set of normal or tumor leukocytes; intriguingly, ROS production does not lead to oxidative stress, as shown by absence of protein carbonylation, maintenance of free thiols, preservation of viability and regular proliferation rate. ROS production is independent from MT1/MT2 receptor interaction, since a) requires micromolar (as opposed to nanomolar) doses of melatonin; b) is not contrasted by the specific MT1/MT2 antagonist luzindole; c) is not mimicked by a set of MT1/MT2 high affinity melatonin analogues. Instead, chlorpromazine, the calmodulin inhibitor shown to prevent melatonin-calmodulin interaction, also prevents melatonin pro-radical effect, suggesting that the low affinity binding to calmodulin (in the micromolar range) may promote ROS production. PMID:19463840

Radogna, Flavia; Paternoster, Laura; De Nicola, Milena; Cerella, Claudia; Ammendola, Sergio; Bedini, Annalida; Tarzia, Giorgio; Aquilano, Katia; Ciriolo, Maria; Ghibelli, Lina

2009-08-15

322

Protective Effect of Melatonin against Inequality-Induced Damages on Testicular Tissue and Sperm Parameters  

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Full Text Available Background: The goals of the study are evaluation the effects of food deprivation and isolation situation as a social stress on fertility; and in the following, investigation of the improving effect of melatonin as an antioxidant component. Materials and Methods: In this experimental study, We investigated histopathological and serological effects of melatonin and social stress (food deprivation and isolation on different features of sperm and testicular tissue among 42 male rats in 7 groups including control, sham, melatonin received (M, food deprivation (FD, Food deprivation and melatonin treatment (FDM, Food deprivation and isolation situation (FDi, and Food deprivation and melatonin treatment and isolation situation (FDMi groups. Epididymal sperms of all rats were also counted. Histopathological evaluation of the testes was done under a light microscopy to determine the number of spermiogenic cells. Serological evaluation of testosterone, corticosterone, and melatonin was performed, as well. For statistical analysis, one-way ANOVA and Tukey’s post hoc test were used, and the value of p?0.05 was considered statistically significance. Results: The result showed that food deprivation increased the number of abnormal, immotile, and dead sperms, while decreased the number of normal sperms (p<0.05. Isolation could improve sperm motility and viability, while enhanced the number of spermatogenic cells. Melatonin had a protective effect on sperm count, motility, and viability, while reduced sperm abnormality. Conclusion: Our results demonstrated that melatonin treatment and isolation situation improve the parameters related to epididymal sperms and spermatogenic cells after food deprivation.

Shiva Nasiraei-Moghadam

2014-01-01

323

Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages  

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Full Text Available Hsiao-Wen Lin, E-Jian LeeNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, TaiwanAbstract: Melatonin (N-acetyl-5-methoxy-tryptamine, a naturally occurring indole produced mainly by the pineal gland, is a well known antioxidant. Stroke (cerebral ischemia is the second leading cause of death worldwide. To date, however, effective and safe treatment for stroke remains unavailable. Melatonin is both lipid- and water-soluble and readily crosses the blood–brain barrier (BBB. Increasing evidence has shown that, in animal stroke models, administering melatonin significantly reduces infarct volume, edema, and oxidative damage and improves electrophysiological and behavioral performance. Here, we reviewed studies that assess effects of melatonin on cerebral ischemia in acute, sub-acute, and chronic stages. In addition to its potent antioxidant properties, melatonin exerts antiapoptotic, antiexcitotoxic, anti-inflammatory effects and promotes mitochondrial functions in animals with cerebral ischemia. Given that melatonin shows almost no toxicity to humans and possesses multifaceted protective capacity against cerebral ischemia, it is valuable to consider using melatonin in clinical trials on patients suffering from stroke.Keywords: cerebral ischemia, melatonin, stroke, neuroprotection

Hsiao-Wen Lin

2009-03-01

324

Melatonin, hydroxyl radical-mediated oxidative damage, and aging: a hypothesis.  

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Melatonin is a very potent and efficient endogenous radical scavenger. The pineal indolamine reacts with the highly toxic hydroxyl radical and provides on-site protection against oxidative damage to biomolecules within every cellular compartment. Melatonin acts as a primary non-enzymatic antioxidative defense against the devastating actions of the extremely reactive hydroxyl radical. Melatonin and structurally related tryptophan metabolites are evolutionary conservative molecules principally involved in the prevention of oxidative stress in organisms as different as algae and rats. The rate of aging and the time of onset of age-related diseases in rodents can be retarded by the administration of melatonin or treatments that preserve the endogenous rhythm of melatonin formation. The release of excitatory amino acids such as glutamate enhances endogenous hydroxyl radical formation. The activation of central excitatory amino acid receptors suppress melatonin synthesis and is therefore accompanied by a reduced detoxification rate of hydroxyl radicals. Aged animals and humans are melatonin-deficient and more sensitive to oxidative stress. Experiments investigating the effects of endogenous excitatory amino acid antagonists and stimulants of melatonin biosynthesis such as magnesium may finally lead to novel therapeutic approaches for the prevention of degeneration and dysdifferentiation associated with diseases related to premature aging. PMID:8102180

Poeggeler, B; Reiter, R J; Tan, D X; Chen, L D; Manchester, L C

1993-05-01

325

Growing Teeth in the Dark: Circadian Rhythmic Tooth Growth Regulated by Melatonin?  

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Full Text Available Introduction: Melatonin is re-leased from the pineal gland and its release is regulated by the light. It is a well-known hormone for circadian rhythm that affects various activities of our body. In particular, melatonin has been reported to enhance the differentiation of osteoblasts in vitro and promotes bone formation in vivo. Melatonin acts on its specific receptors on the cell surface and the receptors were found to be widely distributed in many organs including the teeth, which were reported recently. Interestingly, the teeth have also been known for a long time that may grow in a rhythmic fashion. The hypothesis: Based on the aforementioned understanding on melatonin and the distribution of its receptors, we hypothesized that melatonin may be the driving force for circadian rhythmic tooth growth.Evaluation of the hypothesis: Since melatonin regulates var-ious intracellular activities via its receptor, it is possible that melatonin also affects early development of teeth and their postnatal growth. In addition, the melatonin receptors may also involve in the pathology of various dental diseases including malocclusions.

Gang Shen

2011-06-01

326

Effect of melatonin and time of administration on irradiation-induced damage to rat testes  

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Full Text Available The effect of ionizing irradiation on testes and the protective effects of melatonin were investigated by immunohistochemical and electron microscopic methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy, either to the total body or abdominopelvic region using a 60Co source at a focus of 80 cm away from the skin in the morning or evening together with vehicle (20% ethanol or melatonin administered 24 h before (10 mg/kg, immediately before (20 mg/kg and 24 h after irradiation (10 mg/kg, all ip. Caspace-3 immunoreactivity was increased in the irradiated group compared to control (P < 0.05. Melatonin-treated groups showed less apoptosis as indicated by a considerable decrease in caspace-3 immunoreactivity (P < 0.05. Electron microscopic examination showed that all spermatogenic cells, especially primary spermatocytes, displayed prominent degeneration in the groups submitted to total body and abdominopelvic irradiation. However, melatonin administration considerably inhibited these degenerative changes, especially in rats who received abdominopelvic irradiation. Total body and abdominopelvic irradiation induced identical apoptosis and testicular damage. Chronobiological assessment revealed that biologic rhythm does not alter the inductive effect of irradiation. These data indicate that melatonin protects against total body and abdominopelvic irradiation. Melatonin was more effective in the evening abdominopelvic irradiation and melatonin-treated group than in the total body irradiation and melatonin-treated group.

G. Take

2009-07-01

327

MELATONIN ENHANCES JUNCTIONAL TRANSFER IN NORMAL C3H/1OT1/2 CELLS  

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There is strong evidence that pineal melatonin is involved in controlling neoplastic processes. e have reported that physiological, but not pharmacological or subphysiological, concentrations of melatonin enhance intercellular communication in normal C3H/1OT1/2 fibroblasts. ap ju...

328

Patterns of GPS Tracks Suggest Nocturnal Foraging by Incubating Peruvian Pelicans (Pelecanus thagus)  

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Most seabirds are diurnal foragers, but some species may also feed at night. In Peruvian pelicans (Pelecanus thagus), the evidence for nocturnal foraging is sparse and anecdotal. We used GPS-dataloggers on five incubating Peruvian pelicans from Isla Lobos de Tierra, Perú, to examine their nocturnality, foraging movements and activities patterns at sea. All instrumented pelicans undertook nocturnal trips during a 5–7 day tracking period. Eighty-seven percent of these trips (n?=?13) were...

Zavalaga, Carlos B.; Omo, Giacomo; Becciu, Paolo; Yoda, Ken

2011-01-01

329

Navigational Efficiency of Nocturnal Myrmecia Ants Suffers at Low Light Levels  

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Insects face the challenge of navigating to specific goals in both bright sun-lit and dim-lit environments. Both diurnal and nocturnal insects use quite similar navigation strategies. This is despite the signal-to-noise ratio of the navigational cues being poor at low light conditions. To better understand the evolution of nocturnal life, we investigated the navigational efficiency of a nocturnal ant, Myrmecia pyriformis, at different light levels. Workers of M. pyriformis leave the nest indi...

2013-01-01

330

Role of respiratory sleep disorders in the pathogenesis of nocturnal angina and arrhythmias.  

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This report documents how respiratory sleep disorders can adversely effect ischaemic heart disease. Three male patients (aged 60-67 years) with proven ischaemic heart disease are described. They illustrate a spectrum of nocturnal cardiac dysfunction, two with nocturnal angina and one with nocturnal arrhythmias. Full sleep studies were performed in a dedicated sleep laboratory on all patients, and one patient had 48 hours of continuous Holter monitoring. Two patients were found to have obstruc...

Liston, R.; Deegan, P. C.; Mccreery, C.; Mcnicholas, W. T.

1994-01-01

331

Nocturnal eating syndrome: a case report with therapeutic response to dexfenfluramine  

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A woman with nocturnal eating syndrome responsive to dexfenfluramine (DXF) is reported. Eating consisted of nightly ingestion of large amounts of high-calorie meals and often sloppy meal consumption or preparation. Amnesia for the episodes was total. Anorexigenic medications produced partial control of her daytime carbohydrate craving and no nocturnal eating change. DXF stopped her eating behavior completely. Nocturnal eating herein meets all 4 DSM-III-R diagnostic criteria for binge eating d...

1994-01-01

332

Preliminary evidence that light through the eyelids can suppress melatonin and phase shift dim light melatonin onset  

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Abstract Background A previous study reported a method for measuring the spectral transmittance of individual human eyelids. A prototype light mask using narrow-band “green” light (?max?=?527 nm) was used to deliver light through closed eyelids in two within-subjects studies. The first study investigated whether an individual-specific light dose could suppress melatonin by 40% through the closed eyelid without disrupting sleep. The light doses were deliver...

Figueiro Mariana G; Rea Mark S

2012-01-01

333

Neurotoxins: Free Radical Mechanisms and Melatonin Protection  

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Toxins that pass through the blood-brain barrier put neurons and glia in peril. The damage inflicted is usually a consequence of the ability of these toxic agents to induce free radical generation within cells but especially at the level of the mitochondria. The elevated production of oxygen and nitrogen-based radicals and related non-radical products leads to the oxidation of essential macromolecules including lipids, proteins and DNA. The resultant damage is referred to as oxidative and nit...

Reiter, Russel J.; Manchester, Lucien C.; Tan, Dun-xian

2010-01-01

334

Melatonin inhibits glucocorticoid-dependent GR-TIF2 interaction in newborn hamster kidney (BHK) cells.  

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The antagonism exerted by melatonin on the glucocorticoid response has been well established, being strongly dependent on the cellular context. Previously, we found that melatonin inhibits glucocorticoid receptor (GR) dissociation from the chaperone hetero-complex and nuclear translocation on mouse thymocytes. Here, by performing confocal fluorescence microscopy and the Number and Brightness assay we show that in newborn hamster kidney cells (BHK21) melatonin neither affects GR nuclear translocation nor GR homodimerization. Instead, co-immunoprecipitation studies suggest that physiological concentrations of melatonin impair GR interaction with the transcriptional intermediary factor 2 (TIF2). This melatonin effect was not blocked by the MT(1)/MT(2) receptor antagonist luzindole. Curiously, luzindole behaved as an antiglucocorticoid per se by impairing the glucocorticoid-dependent MMTV-driven gene expression affecting neither GR translocation nor GR-TIF2 interaction. PMID:22079433

Presman, Diego M; Levi, Valeria; Pignataro, Omar P; Pecci, Adali

2012-02-26

335

Melatonin in aging and disease -multiple consequences of reduced secretion, options and limits of treatment.  

Science.gov (United States)

Melatonin is a pleiotropically acting regulator molecule, which influences numerous physiological functions. Its secretion by the pineal gland progressively declines by age. Strong reductions of circulating melatonin are also observed in numerous disorders and diseases, including Alzheimer's disease, various other neurological and stressful conditions, pain, cardiovascular diseases, cases of cancer, endocrine and metabolic disorders, in particular diabetes type 2. The significance of melatonergic signaling is also evident from melatonin receptor polymorphisms associated with several of these pathologies. The article outlines the mutual relationship between circadian oscillators and melatonin secretion, the possibilities for readjustment of rhythms by melatonin and its synthetic analogs, the consequences for circadian rhythm-dependent disorders concerning sleep and mood, and limits of treatment. The necessity of distinguishing between short-acting melatonergic effects, which are successful in sleep initiation and phase adjustments, and attempts of replacement strategies is emphasized. Properties of approved and some investigational melatonergic agonists are compared. PMID:22724080

Hardeland, Rüdiger

2012-04-01

336

Melatonin in Aging and Disease --Multiple Consequences of Reduced Secretion, Options and Limits of Treatment  

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Melatonin is a pleiotropically acting regulator molecule, which influences numerous physiological functions. Its secretion by the pineal gland progressively declines by age. Strong reductions of circulating melatonin are also observed in numerous disorders and diseases, including Alzheimer’s disease, various other neurological and stressful conditions, pain, cardiovascular diseases, cases of cancer, endocrine and metabolic disorders, in particular diabetes type 2. The significance of melatonergic signaling is also evident from melatonin receptor polymorphisms associated with several of these pathologies. The article outlines the mutual relationship between circadian oscillators and melatonin secretion, the possibilities for readjustment of rhythms by melatonin and its synthetic analogs, the consequences for circadian rhythm-dependent disorders concerning sleep and mood, and limits of treatment. The necessity of distinguishing between short-acting melatonergic effects, which are successful in sleep initiation and phase adjustments, and attempts of replacement strategies is emphasized. Properties of approved and some investigational melatonergic agonists are compared.

Hardeland, Rudiger

2012-01-01

337

No effect of melatonin on oxidative stress after laparoscopic cholecystectomy: a randomized placebo-controlled trial  

DEFF Research Database (Denmark)

Background Melatonin, an endogenous circadian regulator, also has antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the antioxidative effect of melatonin in patients undergoing laparoscopic cholecystectomy. Methods Patients were randomized to receive 10 mg melatonin or placebo during surgery. Blood samples for analysis of malondialdehyde (MDA), ascorbic acid (AA), total ascorbic acid (TAA) dehydroascorbic acid (DHA) and C-reactive protein (CRP) were collected pre-operatively and at 5 min, 6 h and 24 h after operation. Results Twenty patients received melatonin and 21 patients received placebo during surgery. No significant differences were observed between the groups in the oxidative stress variables MDA, TAA, AA and DHA or in the inflammatory variable CRP (repeated-measures ANOVA, P > 0.05 for all variables). Conclusions Administration of 10 mg melatonin did not reduce variables of oxidative stress in patients undergoing elective laparoscopic cholecystectomy

Kucukakin, B.; Klein, M.

2010-01-01

338

5-hydroxytryptophan is a more potent in vitro hydroxyl radical scavenger than melatonin or vitamin C.  

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Hydroxyl radicals are involved in direct damage of important biomolecules. Potent radical scavengers such as vitamin C and indoles of the tryptophan family can avert the potential damage. Melatonin and its precursor 5-hydroxytryptophan (5-HTP) were compared with water-soluble vitamin C. Different scavenger concentrations were measured in a steady-state luminol chemiluminescence system (SLCL-system) with combined Fe(II) chloride (0.1 mm) and hydrogen peroxide (1.0 mm) as hydroxyl radical generators. 5-HTP showed highest hydroxyl radical scavenging effects with a 50% inhibition concentration (IC50) of 1.8 microm. For vitamin C an IC50 of 12.7 microm was measured, whereas melatonin in pure demineralized water was much less efficient (IC50=724 microm). A comparison between melatonin in aqueous solution and melatonin in ethanol solution revealed that melatonin was significantly more effective in pure demineralized water. PMID:15617538

Keithahn, Christian; Lerchl, Alexander

2005-01-01

339

The hormonal Zeitgeber melatonin: Role as a circadian modulator in memory processing  

Directory of Open Access Journals (Sweden)

Full Text Available The neuroendocrine substance melatonin is a hormone synthesized rhythmically by the pineal gland under the influence of the circadian system and alternating light/dark cycles. Melatonin has been shown to have broad applications, and consequently becoming a molecule of great controversy. Undoubtedly, however, melatonin plays an important role as a time cue for the endogenous circadian system. This review focuses on melatonin as a regulator in the circadian modulation of memory processing. Memory processes (acquisition, consolidation and retrieval are modulated by the circadian system. However, the mechanism by which the biological clock is rhythmically influencing cognitive processes remains unknown. We also discuss, how the circadian system by generating cycling melatonin levels can implant information about daytime into memory processing, depicted as day and nighttime differences in acquisition, memory consolidation and/or retrieval.

OliverRawashdeh

2012-03-01

340

Protective Effect of Melatonin on Streptozotocin-induced Diabetes in Mice  

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Full Text Available The research work was conducted to investigate the effects of melatonin on streptozotocin (STZ-induced diabetes in mice. Mice were divided into six groups. The first two groups were STZ injected animals. The other four groups, were STZ plus melatonin injected. The melatonin doses were 50 or 500µg kg-1 respectively. Plasma glucose level, body weights and insulates were examined. The plasma glucose levels were significantly higher only in STZ-injected mice. No significant difference was seen in the plasma glucose content of STZ plus melatonin 50 and 500µg kg-1 groups. Mononuclear cell infiltration of pancreatic islets (insulates was much more intensive only in STZ injected mice.These results suggested that when melatonin is injected at the same time with STZ, it acts to prevent the development of diabetes in experimental mice.

Bulent Gunduz

2001-01-01

 
 
 
 
341

Potential therapeutic use of melatonin in migraine and other headache disorders.  

Science.gov (United States)

There is increasing evidence that headache disorders are connected with melatonin secretion and pineal function. Some headaches have a clearcut seasonal and circadian pattern, such as cluster and hypnic headaches. Melatonin levels have been found to be decreased in both migraine and cluster headaches. Melatonin mechanisms are related to headache pathophysiology in many ways, including its anti-inflammatory effect, toxic free radical scavenging, reduction of pro-inflammatory cytokine upregulation, nitric oxide synthase activity and dopamine release inhibition, membrane stabilisation, GABA and opioid analgesia potentitation, glutamate neurotoxicity protection, neurovascular regulation, 5-HT modulation and the similarity in chemical structure to indometacin. The treatment of headache disorders with melatonin and other chronobiotic agents, such as melatonin agonists (ramelteon and agomelatin), is promising and there is a great potential for their use in headache treatment. PMID:16548786

Peres, Mario F P; Masruha, Marcelo R; Zukerman, Eliova; Moreira-Filho, Carlos Alberto; Cavalheiro, Esper A

2006-04-01

342

Circadian variations in the inhibition of dopamine release from adult and newborn rat hypothalamus by melatonin.  

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The inhibitory effect of melatonin on evoked dopamine release from the hypothalamus was studied in adult male rats throughout a 24-hour period. The animals were maintained under a daily schedule of 14 h of light (0.00-14.00 h) and 10 h of darkness. The inhibition of dopamine release in vitro by 1 microM melatonin clearly exhibited a 24-hour rhythm with a peak at 5.00 h and almost no inhibition at 15.00 h. The concentrations of melatonin needed to produce this effect were similar throughout the 24-hour cycle, although the actual amount of inhibition at any given concentration of melatonin varied. Other indole derivatives, with the exception of 5-methoxy tryptophol, did not affect significantly the release of 3H-dopamine from the male rat hypothalami. The inhibition of dopamine release by melatonin was not observed in newborn rats but developed during the first week of life, reaching a plateau level between 6 and 7 days postnatally. However, the difference between the amount of inhibition by melatonin at 5.00 h and at 8.00 h existed from the time the inhibition was first observed. The change in amplitude of this difference was due not to differences in the apparent affinity towards melatonin but to increase in the maximal inhibition observed at 5.00 h. The data indicate that the hypothalamic sensitivity to melatonin exhibits a circadian rhythm, and that this develops postnatally prior to the development of circadian variations in melatonin levels, i.e. the 'melatonin rhythm'.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2983256

Zisapel, N; Egozi, Y; Laudon, M

1985-02-01

343

Melatonin treatment induces interplay of apoptosis, autophagy, and senescence in human colorectal cancer cells.  

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In Asia, the incidence of colorectal cancer has been increasing gradually due to a more Westernized lifestyle. The aim of study is to determine the interaction between melatonin-induced cell death and cellular senescence. We treated HCT116 human colorectal adenocarcinoma cells with 10 ?m melatonin and determined the levels of cell death-related proteins and evaluated cell cycle kinetics. The plasma membrane melatonin receptor, MT1, was significantly decreased by melatonin in a time-dependent manner, whereas the nuclear receptor, ROR?, was increased only after 12 hr treatment. HCT116 cells, which upregulated both pro-apoptotic Bax and anti-apoptotic Bcl-xL in the early response to melatonin treatment, activated autophagic as well as apoptotic machinery within 18 hr. Melatonin decreased the S-phase population of the cells to 57% of the control at 48 hr, which was concomitant with a reduction in BrdU-positive cells in the melatonin-treated cell population. We found not only marked attenuation of E- and A-type cyclins, but also increased expression of p16 and p-p21. Compared to the cardiotoxicity of Trichostatin A in vitro, single or cumulative melatonin treatment induced insignificant detrimental effects on neonatal cardiomyocytes. We found that 10 ?m melatonin activated cell death programs early and induced G1-phase arrest at the advanced phase. Therefore, we suggest that melatonin is a potential chemotherapeutic agent for treatment of colon cancer, the effects of which are mediated by regulation of both cell death and senescence in cancerous cells with minimized cardiotoxicity. PMID:24484372

Hong, Yunkyung; Won, Jinyoung; Lee, Youngjeon; Lee, Seunghoon; Park, Kanghui; Chang, Kyu-Tae; Hong, Yonggeun

2014-04-01

344

Proliferative effects of melatonin on Schwann cells: implication for nerve regeneration following peripheral nerve injury.  

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Activation of proliferation of Schwann cells is crucial for axonal guidance and successful nerve regeneration following peripheral nerve injury (PNI). Considering melatonin plays an important role in proliferative regulation of central glial cells, the present study determined whether melatonin can effectively promote Schwann cell proliferation and improve nerve regeneration after PNI. The spontaneous immortalized rat Schwann cell line (RSC 96 cells) was first analyzed by quantitative polymerase chain reaction (QPCR) to detect the potential existence of melatonin receptors. The melatonin receptor-mediated signaling responsible for proliferation was examined by measuring the phosphorylation of extracellular signal-regulated kinases (ERK1/2) pathway. The in vivo model of PNI was performed by the end-to-side neurorrhaphy. The quantity of Schwann cells as well as the number of re-innervated motor end plates (MEP) on target muscles was examined to represent the functional recovery of injured nerves. QPCR results indicated that MT1 is the dominant receptor in Schwann cells. Immunoblotting and proliferation assay revealed an enhanced phosphorylation of ERK1/2 and increased number of RSC 96 cells following melatonin administration. Nonselective melatonin receptor antagonist (luzindole) treatment significantly suppressed all the above findings, suggesting that the proliferative effects of melatonin were mediated by a receptor-dependent pathway. In vivo results corresponded well with in vitro findings in which melatonin effectively increased the amount of proliferated Schwann cells and re-innervated MEP on target muscles following PNI. As melatonin successfully improves nerve regeneration by promoting Schwann cell proliferation, therapeutic use of melatonin may thus serve as a promising strategy to counteract the PNI-induced neuronal disability. PMID:24499296

Chang, Hung-Ming; Liu, Chiung-Hui; Hsu, Wen-Ming; Chen, Li-You; Wang, Han-Pin; Wu, Tsung-Huan; Chen, Kuan-Ying; Ho, Wen-Hsin; Liao, Wen-Chieh

2014-04-01

345

Melatonin exerts by an autocrine loop antiproliferative effects in cholangiocarcinoma: its synthesis is reduced favoring cholangiocarcinoma growth.  

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Cholangiocarcinoma (CCA) is a devastating biliary cancer. Melatonin is synthesized in the pineal gland and peripheral organs from serotonin by two enzymes, serotonin N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT). Cholangiocytes secrete neuroendocrine factors, including serotonin-regulating CCA growth by autocrine mechanisms. Melatonin exerts its effects by interaction with melatonin receptor type 1A/1B (MT1/MT2) receptors. We propose that 1) in CCA, there is decreased expression of AANAT and ASMT and secretion of melatonin, changes that stimulate CCA growth; and 2) in vitro overexpression of AANAT decreases CCA growth. We evaluated the 1) expression of AANAT, ASMT, melatonin, and MT1/MT2 in human nonmalignant and CCA lines and control and CCA biopsy samples; 2) melatonin levels in nonmalignant and CCA lines, and bile and serum from controls and patients with intrahepatic CCA; 3) effect of melatonin on the growth and expression of AANAT/ASMT and MT1/MT2 in CCA lines implanted into nude mice; and 4) effect of AANAT overexpression on the proliferation, apoptosis, and expression of MT1/MT2 in Mz-ChA-1 cells. The expression of AANAT, ASMT, and melatonin decreased, whereas MT1/MT2 expression increased in CCA lines and biopsy samples. Melatonin secretion decreased in the supernatant of CCA lines and bile of CCA patients. Melatonin decreased xenograft CCA tumor growth in nude mice by increased AANAT/ASMT and melatonin, along with reduced MT1/MT2 expression. Overexpression of AANAT in Mz-ChA-1 cells inhibited proliferation and MT1/MT2 expression and increased apoptosis. There is dysregulation of the AANAT/ASMT/melatonin ? melatonin receptor axis in CCA, which inhibited melatonin secretion and subsequently enhanced CCA growth. PMID:21778461

Han, Yuyan; Demorrow, Sharon; Invernizzi, Pietro; Jing, Qing; Glaser, Shannon; Renzi, Anastasia; Meng, Fanyin; Venter, Julie; Bernuzzi, Francesca; White, Mellanie; Francis, Heather; Lleo, Ana; Marzioni, Marco; Onori, Paolo; Alvaro, Domenico; Torzilli, Guido; Gaudio, Eugenio; Alpini, Gianfranco

2011-10-01

346

Diurnal variation in phagocytic activity of splenic phagocytes in freshwater teleost Channa punctatus: melatonin and its signaling mechanism.  

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The aim of the present study was to understand the rhythmic changes in innate immune response in freshwater fish Channa punctatus. Furthermore, the putative role of melatonin as the zeitgeber was explored. The phagocytic activity of splenic phagocytes assessed at 6-h intervals showed higher phagocytic activity during light phase than dark phase. The increased phagocytic activity during light phase was diminished by melatonin administration at 09:00 h. Implication of melatonin in control of diurnal variation in phagocytic activity was substantiated by administering irreversible tryptophan hydroxylase inhibitor, para-chlorophenylalanine (pCPA) at 18:00 h. pCPA abrogated the decrease of phagocytosis observed during dark phase, and the same was restored after melatonin administration. The direct involvement of melatonin in modulation of phagocytosis was demonstrated following in vitro experiments. Melatonin suppressed the phagocytic activity in a concentration-dependent manner without affecting the viability of phagocytes. The existence of functional membrane-bound melatonin receptors on fish phagocytes was pharmacologically demonstrated. Luzindole, melatonin membrane receptor antagonist, completely blocked the inhibitory effect of melatonin on phagocytosis. Further receptor-coupled adenylate cyclase-protein kinase A (PKA) pathway was implicated in transducing the melatonin effect as both adenylate cyclase and PKA inhibitor completely nullified the melatonin-induced suppression. An increased intracellular cAMP level in response to melatonin ascertained the second messenger status of cAMP for downstream signaling. However, manipulation of phospholipase C/PKC failed to influence the effect of melatonin on phagocytic activity. These observations in C. punctatus evidenced the diurnal rhythmicity in phagocytic activity that is regulated by melatonin following membrane-bound receptor-coupled cAMP-PKA pathway. PMID:18824520

Roy, Brototi; Singh, Rajeev; Kumar, Sunil; Rai, Umesh

2008-12-01

347

Protective effect of melatonin on propoxur-induced impairment of memory and oxidative stress in rats.  

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Propoxur (a carbamate pesticide) has been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. This study was designed to explore the modulation of the effects of propoxur over cognitive function by melatonin (MEL). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus, and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and reduced glutathione (GSH) levels and catalase (CAT) activity. A significant reduction in SDL and prolongation of TL was observed for the propoxur (10 mg/kg/d; p.o.) treated group at weeks 6 and 7 when compared with control. One week treatment with MEL (50 mg/kg/d; i.p.) antagonized the effect of propoxur on SDL, as well as TL. Propoxur produced a statistically significant increase in the brain MDA levels and decrease in the brain GSH levels and CAT activity. Treatment with MEL attenuated the effect of propoxur on oxidative stress. The results of the present study thus show that MEL has the potential to attenuate cognitive dysfunction and oxidative stress induced by toxicants like propoxur in the brain. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 705-713, 2014. PMID:24733834

Mehta, Kapil D; Mehta, Ashish K; Halder, Sumita; Khanna, Naresh; Tripathi, Ashok K; Sharma, Krishna K

2014-06-01

348

Increased nocturnal fat oxidation in young healthy men with low birth weight : Results from 24-h whole-body respiratory chamber measurements  

DEFF Research Database (Denmark)

OBJECTIVE: Low birth weight (LBW), a marker of disturbed fetal growth, is associated with adiposity and increased risk of type 2 diabetes (T2D). The aim of the study was to investigate whether LBW is associated with changes in 24-h energy expenditure (EE) and/or substrate utilization rates, potentially contributing to the development of adiposity and/or T2D compared to matched control subjects. MATERIALS/METHODS: Forty-six young, healthy men were included in the study; 20 with LBW (= 10th percentile) and 26 control subjects with normal birth weight (NBW) (50th-90th percentile). The subjects were fed a weight maintenance diet and 24-h energy expenditure (EE), respiratory quotient (RQ), and substrate oxidation were assessed in a respiratory chamber. RESULTS: No differences in 24-h EE, RQ or substrate oxidation were observed between LBW and controls. Interestingly, the LBW group exhibited lower nocturnal RQ compared to controls (0.81 ± 0.01 vs. 0.85 ± 0.01 (mean ± SE), P = 0.01), and hence higher nocturnal fat oxidation (2.55 ± 0.13 vs. 2.09 ± 0.12 kJ/min (mean ± SE), P = 0.02). CONCLUSIONS: Young LBW men do not exhibit reductions in 24-h EE. However, LBW subjects display increased nocturnal fat oxidation at the expense of reduced glucose oxidation. We speculate that this may be associated with insufficient capability to retain fat in subcutaneous adipose tissue after meals during day time, with an increased rate of nocturnal and morning lipolysis, and potentially with subtle elevations of gluconeogenesis and of fasting glucose levels in the LBW subjects.

Brøns, Charlotte; Lilleøre, S K

2013-01-01

349

Interaction between melatonin and follicle-stimulating hormone promotes in vitro development of caprine preantral follicles.  

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The aim of this study was to investigate the effects of melatonin and follicle-stimulating hormone (FSH) on the in vitro culture of goat preantral follicles. Ovarian fragments were cultured for 7 d in ?-minimum essential medium (?-MEM(+)) containing melatonin (100, 250, 500, or 1,000 pM), FSH (50 ng/mL), or a combination of the 2 hormones and further analyzed by histology and transmission electron and fluorescent microscopy. The results showed that after 7 d of culture, tissues cultured in ?-MEM(+) alone or supplemented with FSH alone, melatonin (500 and 1,000 pM), or the combination of FSH and melatonin (1,000 pM) maintained percentages of normal preantral follicles similar to the fresh control. In contrast to the noncultured tissues, the percentage of developing follicles was increased under all culture conditions after 7 d (P melatonin associated with FSH to the culture medium increased follicular and oocyte diameters compared with ?-MEM(+) alone after 7 d of culture (P melatonin plus FSH for 7 d. In conclusion, this study demonstrated that the interaction between melatonin and FSH maintains ultrastructural integrity and stimulates further growth of cultured caprine preantral follicles. PMID:22920266

Rocha, R M P; Lima, L F; Alves, A M C V; Celestino, J J H; Matos, M H T; Lima-Verde, I B; Bernuci, M P; Lopes, C A P; Báo, S N; Campello, C C; Rodrigues, A P R; Figueiredo, J R

2013-01-01

350

Effects of delta-aminolevulinic acid and melatonin in the harderian gland of female Syrian hamsters.  

Science.gov (United States)

Effects of delta-aminolevulinic acid (ALA) and melatonin were investigated in the female Syrian hamster Harderian gland. This is an organ physiologically exposed to strong oxidative stress due to the highest porphyrinogenic rates known in nature. Enzyme activities of porphyrin biosynthesis and of antioxidative protection, oxidative protein modification, and histological integrity were studied. In the porphyrin biosynthetic pathway, ALA and melatonin acted synergistically by downregulating ALA synthase (ALA-S) and stimulating product formation from ALA; the combination of ALA and melatonin suppressed ALA-S activity, down to about 1% of that in controls. While ALA effects on porphyrinogenesis can be interpreted in terms of homeostasis, melatonin's actions may be seen in relation to seasonality and/or reduction of oxidative stress. Among antioxidant enzymes, superoxide dismutase (SOD) and glutathione reductase (GR) activities were diminished by ALA, presumably due to the vulnerability of their active centers to free radicals, whereas melatonin moderately increased SOD. Both ALA and melatonin strongly stimulated catalase (CAT), thereby counteracting the oxidative stress induced by ALA and its metabolites. Nevertheless, exogenous ALA caused a strong net rise in protein carbonyl and considerable damage of tissue. When given together with ALA, melatonin antagonized these effects and largely protected the integrity of glandular structures. PMID:12031903

Tomás-Zapico, Cristina; Coto-Montes, Ana; Martínez-Fraga, Jorge; Rodríguez-Colunga, María Josefa; Hardeland, Rüdiger; Tolivia, Delio

2002-06-01

351

Melatonin and peripheral circuitries: insights on appetite and metabolism in Danio rerio.  

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Melatonin is a neuroendocrine transducer of circadian/circannual rhythms able to synchronize organism's physiological activity. On the basis of our recent findings on appetite regulation by melatonin in the zebrafish brain, the aim of this study was to evaluate melatonin's role in peripheral circuitries regulating food intake, growth, and lipid metabolism. For this purpose, the effect of two melatonin doses (100?nM and 1??M) administered for 10 days, via water, to adult zebrafish was evaluated at both physiological and molecular levels. The major signals controlling energy homeostasis were analyzed together. Additionally, the effect of melatonin doses on muscle metabolic resources was evaluated. The results obtained indicate that melatonin reduces food intake by stimulating molecules involved in appetite inhibition, such as leptin (LPT), in the liver and intestine and MC4R, a melanocortin system receptor, in the liver. Moreover, melatonin decreases hepatic insulin-like growth factor-I (IGF-I) gene expression, involved in growth process and other signals involved in lipid metabolism such as proliferator-activated receptors (PPAR?, ?, and ?) and sterol regulatory element-binding protein (SREBP). These results were correlated with lower levels of lipids in the muscles as evidenced by the macromolecular pools analyses. The findings obtained in this study could be of great interest for a better understanding of the molecular mechanisms as the basis of food intake control and, in turn, can be a useful tool for medical and aquaculture applications. PMID:23682835

Piccinetti, Chiara Carla; Migliarini, Beatrice; Olivotto, Ike; Simoniello, Marco Pasquale; Giorgini, Elisabetta; Carnevali, Oliana

2013-09-01

352

Melatonin enhances DNA repair capacity possibly by affecting genes involved in DNA damage responsive pathways  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Melatonin, a hormone-like substance involved in the regulation of the circadian rhythm, has been demonstrated to protect cells against oxidative DNA damage and to inhibit tumorigenesis. Results In the current study, we investigated the effect of melatonin on DNA strand breaks using the alkaline DNA comet assay in breast cancer (MCF-7 and colon cancer (HCT-15 cell lines. Our results demonstrated that cells pretreated with melatonin had significantly shorter Olive tail moments compared to non-melatonin treated cells upon mutagen (methyl methanesulfonate, MMS exposure, indicating an increased DNA repair capacity after melatonin treatment. We further examined the genome-wide gene expression in melatonin pretreated MCF-7 cells upon carcinogen exposure and detected altered expression of many genes involved in multiple DNA damage responsive pathways. Genes exhibiting altered expression were further analyzed for functional interrelatedness using network- and pathway-based bioinformatics analysis. The top functional network was defined as having relevance for “DNA Replication, Recombination, and Repair, Gene Expression, [and] Cancer”. Conclusions These findings suggest that melatonin may enhance DNA repair capacity by affecting several key genes involved in DNA damage responsive pathways.

Liu Ran

2013-01-01

353

Transient induction of melatonin biosynthesis in rice (Oryza sativa L.) during the reproductive stage.  

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The regulation of reproduction-stage inducible melatonin biosynthesis in rice (Oryza sativa cv. Dongjin) was investigated. The flag leaf and panicle (flower) were collected from field-grown rice at three different reproductive stages: the preflowering stage, flowering stage, and postflowering stage. Melatonin synthesis was induced in the panicle, whereas no induction was observed in the flag leaf during the reproductive stages. The panicle displayed a peak melatonin level of 0.4 ng/g fresh weight (fw), which was six times that found in the flag leaf. The induction of melatonin biosynthesis was paralleled by the induction of corresponding genes and proteins such as tryptophan decarboxylase, tryptamine 5-hydroxylase, and N-acetylserotonin methyltransferase. In addition, melatonin induction was preceded by the accumulation of its precursor, tryptophan, in the panicle. These results suggest that the induction of melatonin during flower development is regulated by the transcriptional control of its biosynthesis genes and that melatonin may participate in flower development. PMID:23110463

Park, Sangkyu; Le, Tieu-Ngoc Nguyen; Byeon, Yeong; Kim, Young Soon; Back, Kyoungwhan

2013-08-01

354

Lipoxygenase-mediated pro-radical effect of melatonin via stimulation of arachidonic acid metabolism  

International Nuclear Information System (INIS)

We have shown that melatonin immediately and transiently stimulates intracellular free radical production on a set of leukocytes, possibly as a consequence of calmodulin binding. We show here that melatonin-induced ROS are produced by lipoxygenase (LOX), since they are prevented by a set of LOX inhibitors, and are accompanied by increase of the 5-LOX product 5-HETE. LOX activation is accompanied by strong liberation of AA; inhibition of Ca2+-independent, but not Ca2+-dependent, phospholipase A2 (PLA2), prevents both melatonin-induced arachidonic acid and ROS production, whereas LOX inhibition only prevents ROS, indicating that PLA2 is upstream with respect to LOX, as occurs in many signaling pathways. Chlorpromazine, an inhibitor of melatonin-calmodulin interaction, inhibits both ROS and arachidonic acid production, thus possibly placing calmodulin at the origin of a melatonin-induced pro-radical pathway. Interestingly, it is known that Ca2+-independent PLA2 binds to calmodulin: our results are compatible with PLA2 being liberated by melatonin from a steady-state calmodulin sequestration, thus initiating an arachidonate signal transduction. These results delineate a novel molecular pathway through which melatonin may participate to the inflammatory response.

2009-07-15

355

Production of melatonin by Saccharomyces strains under growth and fermentation conditions.  

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Melatonin is a bioactive compound that is present in wine because it is contained in vinification grapes and synthesized by yeast during alcoholic fermentation. The purpose of this study was to determine the capacity of various Saccharomyces strains to form melatonin during its growth and alcoholic fermentation. A selection of yeasts including six S. cerevisiae (Lalvin CLOS, Lalvin ICV-D254, Enoferm QA23 Viniferm ARM, Viniferm RVA, and Viniferm TTA), one S. uvarum (Lalvin S6U) and one S. cerevisiae var. bayanus (Uvaferm BC) were tested to determine whether they produce melatonin in yeast extract peptose dextrose and synthetic must media in a variety of conditions. Two S. cerevisiae strains (ARM, and QA23), the S. uvarum and the S. cerevisiae var. bayanus, synthesized melatonin. The conditions in which they did so, however, were different: the QA23 strain produced melatonin best in a medium with a low concentration of reducing sugars and Lalvin S6U and Uvaferm BC required a synthetic must under fermentation conditions. Melatonin synthesis largely depended on the growth phase of the yeasts and the concentration of tryptophan, reducing sugars and the growth medium. These results indicate that melatonin may have a role as a yeast growth signal molecule. PMID:22515683

Rodriguez-Naranjo, María Isabel; Torija, María Jesús; Mas, Albert; Cantos-Villar, Emma; Garcia-Parrilla, María del Carmen

2012-10-01

356

Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells.  

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  Previous studies have demonstrated that apolipoprotein E (ApoE) genotype and melatonin are closely associated with Alzheimer's disease (AD). However, the relationship between ApoE genotype and melatonin remains unclear. Recently, we reported that cultured rat cortical astrocytes and glioma C6 cells synthesize melatonin. In the current study, we investigated the effect of ApoE genotype on melatonin biosynthesis. C6 cells with stable expression of ApoE isoforms (ApoE 2, 3 and 4) were established. A higher level of melatonin was demonstrated in cultured ApoE4-C6 cells than that in ApoE3-C6 cells. In addition, we found that N-acetyltransferase (NAT) protein level was up-regulated in ApoE4-C6 cells compared with ApoE3-C6 cells. Further study suggested that mRNA expression of monoamine oxidase A (MAOA) and monoamine oxidase B (MAOB) decreased in ApoE4-C6 cells. In conclusion, the increased melatonin level in ApoE4-C6 cells results from up-regulation of NAT expression, a key enzyme for melatonin synthesis, and down-regulation of MAOA and MAOB expression, the metabolic enzyme for its precursor serotonin. PMID:22225631

Liu, Ya-Jing; Meng, Fan-Tao; Wang, Li-Li; Zhang, Li-Feng; Cheng, Xin-Ping; Zhou, Jiang-Ning

2012-05-01

357

Inhibition of Calotropis procera latex-induced inflammatory hyperalgesia by oxytocin and melatonin.  

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The latex of the wild growing plant Calotropis procera produces inflammation of the skin and mucous membranes upon accidental exposure. On local administration it elicits an intense inflammatory response due to the release of histamine and prostaglandins that is associated with hyperalgesia. In the present study we have evaluated the anti-inflammatory and antinociceptive activity of oxytocin and melatonin against rat paw edema induced by dried latex (DL) of C procera and compared it with that against carrageenan-induced paw edema. Aqueous extract of DL of C procera or carrageenan (1%) was injected into the subplantar surface of the rat paw and the paw volume was measured at 0, 1, 2, 3, 4, 6, 10, and 24 hours. The associated hyperalgesic response and functional impairment were also evaluated concomitantly by dorsal flexion pain test, motility test, and stair climbing ability test. The inhibitory effect of oxytocin and melatonin on edema formation and hyperalgesic response was compared with dexamethasone. DL-induced edema formation was maximum at 2 hours and was associated with decreased pain threshold and functional impairment. Treatment with melatonin significantly attenuated the edematous response while both oxytocin and melatonin increased the pain threshold and improved functional parameters. Both oxytocin and melatonin significantly inhibited the hyperalgesia associated with DL-induced paw edema. Oxytocin was found to be as effective as melatonin in ameliorating the hyperalgesic response. However, it was found to be less effective than melatonin in attenuating edema formation. PMID:16489256

Padhy, Biswa M; Kumar, Vijay L

2005-12-14

358

Photoperiod and melatonin affect testicular growth in the marsh rice rat (Oryzomys palustris).  

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Reproduction in rice rats is subject to photoperiodic control and the pineal gland mediates this effect. We examined the effects of the pineal gland hormone melatonin on testicular weight when administered via implants, injections, and infusions. Testicular weight was modified by photoperiod and the size of the melatonin implant. Twenty-millimeter implants suppressed testicular weight in rice rats housed on 12- and 16-hr photoperiods, while those housed on a 14-hr photoperiod were more sensitive to melatonin; in these animals 10- and 20-mm implants inhibited testicular weight. Melatonin implants also prevented rice rats from responding to a change in photoperiod with the appropriate alteration of testicular growth. Melatonin injections inhibited testicular growth when administered before lights out on LD 14:10, but not on LD 16:8. Morning injections had no effect on either photoperiod. Finally, 12-hr duration melatonin infusions inhibited testicular growth in pinealectomized rice rats on LD 16:8, while 6-hr duration infusions were without effect. These data show that the pineal, through the secretion of melatonin, is a phototransducing organ intimately involved in testicular growth in rice rats. PMID:7869231

Edmonds, K E; Stetson, M H

1994-09-01

359

Pitfalls in the Measurement of the Nocturnal Blood Pressure Dip in Adolescents with Type 1 Diabetes  

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OBJECTIVE—The purpose of this study was to screen adolescents with type 1 diabetes using ambulatory blood pressure monitoring (ABPM) to 1) test the hypothesis that using a preset sleep time results in an overdiagnosis of abnormal nocturnal dipping in systolic blood pressure and 2) assess the reproducibility of an abnormal nocturnal systolic blood pressure dip.

Delaney, Angela; Pellizzari, Margaret; Speiser, Phyllis W.; Frank, Graeme R.

2009-01-01

360

Terbutaline and the Prevention of Nocturnal Hypoglycemia in Type 1 Diabetes  

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OBJECTIVE—Bedtime administration of 5.0 mg of the ?2-adrenergic agonist terbutaline prevents nocturnal hypoglycemia but causes morning hyperglycemia in type 1 diabetes. We tested the hypothesis that 2.5 mg terbutaline prevents nocturnal hypoglycemia without causing morning hyperglycemia.

Cooperberg, Benjamin A.; Breckenridge, Suzanne M.; Arbelaez, Ana Maria; Cryer, Philip E.

2008-01-01

 
 
 
 
361

Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry  

Science.gov (United States)

Paroxysmal nocturnal hemoglobinuria is a rare, acquired disease associated with hemolytic anemia, bone marrow failure, thrombosis, and, frequently, poor quality of life. The International PNH Registry is a worldwide, observational, non-interventional study collecting safety, effectiveness, and quality-of-life data from patients with a confirmed paroxysmal nocturnal hemoglobinuria diagnosis or detectable paroxysmal nocturnal hemoglobinuria clone, irrespective of treatment. In addition to evaluating the long-term safety and effectiveness of eculizumab in a global population, the registry aims to improve diagnosis, optimize patient management and outcomes, and enhance the understanding of the natural history of paroxysmal nocturnal hemoglobinuria. Here we report the characteristics of the first 1610 patients enrolled. Median disease duration was 4.6 years. Median granulocyte paroxysmal nocturnal hemoglobinuria clone size was 68.1% (range 0.01–100%). Overall, 16% of patients had a history of thrombotic events and 14% a history of impaired renal function. Therapies included anticoagulation (31%), immunosuppression (19%), and eculizumab (25%). Frequently reported symptoms included fatigue (80%), dyspnea (64%), hemoglobinuria (62%), abdominal pain (44%), and chest pain (33%). Patients suffered from poor quality of life; 23% of patients had been hospitalized due to paroxysmal nocturnal hemoglobinuria-related complications and 17% stated that paroxysmal nocturnal hemoglobinuria was the reason they were not working or were working less. This international registry will provide an ongoing, valuable resource to further the clinical understanding of paroxysmal nocturnal hemoglobinuria.

Schrezenmeier, Hubert; Muus, Petra; Socie, Gerard; Szer, Jeffrey; Urbano-Ispizua, Alvaro; Maciejewski, Jaroslaw P.; Brodsky, Robert A.; Bessler, Monica; Kanakura, Yuzuru; Rosse, Wendell; Khursigara, Gus; Bedrosian, Camille; Hillmen, Peter

2014-01-01

362

Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry.  

Science.gov (United States)

Paroxysmal nocturnal hemoglobinuria is a rare, acquired disease associated with hemolytic anemia, bone marrow failure, thrombosis, and, frequently, poor quality of life. The International PNH Registry is a worldwide, observational, non-interventional study collecting safety, effectiveness, and quality-of-life data from patients with a confirmed paroxysmal nocturnal hemoglobinuria diagnosis or detectable paroxysmal nocturnal hemoglobinuria clone, irrespective of treatment. In addition to evaluating the long-term safety and effectiveness of eculizumab in a global population, the registry aims to improve diagnosis, optimize patient management and outcomes, and enhance the understanding of the natural history of paroxysmal nocturnal hemoglobinuria. Here we report the characteristics of the first 1610 patients enrolled. Median disease duration was 4.6 years. Median granulocyte paroxysmal nocturnal hemoglobinuria clone size was 68.1% (range 0.01-100%). Overall, 16% of patients had a history of thrombotic events and 14% a history of impaired renal function. Therapies included anticoagulation (31%), immunosuppression (19%), and eculizumab (25%). Frequently reported symptoms included fatigue (80%), dyspnea (64%), hemoglobinuria (62%), abdominal pain (44%), and chest pain (33%). Patients suffered from poor quality of life; 23% of patients had been hospitalized due to paroxysmal nocturnal hemoglobinuria-related complications and 17% stated that paroxysmal nocturnal hemoglobinuria was the reason they were not working or were working less. This international registry will provide an ongoing, valuable resource to further the clinical understanding of paroxysmal nocturnal hemoglobinuria. PMID:24488565

Schrezenmeier, Hubert; Muus, Petra; Socié, Gérard; Szer, Jeffrey; Urbano-Ispizua, Alvaro; Maciejewski, Jaroslaw P; Brodsky, Robert A; Bessler, Monica; Kanakura, Yuzuru; Rosse, Wendell; Khursigara, Gus; Bedrosian, Camille; Hillmen, Peter

2014-05-01

363

Pregnancy in a patient with paroxysmal nocturnal hemoglobinuria  

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Full Text Available The occurrence of Paroxysmal Nocturnal Hemoglobinuria (PNH during pregnancy is very rare. It can cause significant fetomaternal morbidity and mortality due to associated complement mediated hemolysis and/or thrombosis. We report a case of PNH in a pregnant lady who presented to our antenatal clinic at 10th weeks of gestation. Her pregnancy was managed with multiple blood transfusions and steroid administration. During 3rd weeks postpartum period she developed sepsis with acute renal failure and posterior reversible encephalopathy syndrome requiring prolonged hospitalization. She was subsequently discharged from hospital in satisfactory condition. [Int J Reprod Contracept Obstet Gynecol 2014; 3(1.000: 285-287

Anju Singh

2014-02-01

364

Circadian Regulation of Behavior: Differences between Diurnal and Nocturnal Species  

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Full Text Available Most organisms, including humans, show daily rhythms of about 24 hoursin physiology, hormonal function, and behavior. In mammals, these rhythmsare controlled by an endogenous circadian pacemaker localized in the suprachiasmaticnucleus (SCN of the hypothalamus that determines thetemporal organization of several behaviors and physiological processes.Circadian control of daily rhythms differs in diurnal and nocturnal speciesbut many of the mechanisms that may explain these differences remain stillunknown. The aim of this review is to summarize our current knowledgeof the circadian clocks and the differences between diurnal and nocturnalspecies.

Gladys S. Martínez

2009-06-01

365

Ghost protein damage by peroxynitrite and its protection by melatonin  

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Full Text Available We have studied the effect of peroxynitrite (ONOO- on the membrane cytoskeleton of red blood cells and its protection by melatonin. Analysis of the protein fraction of the preparation by SDS-PAGE revealed a dose-dependent (0-600 µM ONOO- disappearance at pH 7.4 of the main proteins: spectrin, band 3, and actin, with the concomitant formation of high-molecular weight aggregates resistant to reduction by ß-mercaptoethanol (2% at room temperature for 20 min. These aggregates were not solubilized by 8 M urea. Incubation of the membrane cytoskeleton with ONOO- was characterized by a marked depletion of free sulfhydryl groups (50% at 250 µM ONOO-. However, a lack of effect of ß-mercaptoethanol suggests that, under our conditions, aggregate formation is not mediated only by sulfhydryl oxidation. The lack of a protective effect of the metal chelator diethylenetriaminepentaacetic acid confirmed that ONOO--induced oxidative damage does not occur only by a transition metal-dependent mechanism. However, we demonstrated a strong protection against cytoskeletal alterations by desferrioxamine, which has been described as a direct scavenger of the protonated form of peroxynitrite. Desferrioxamine (0.5 mM also inhibited the loss of tryptophan fluorescence observed when the ghosts were treated with ONOO-. Glutathione, cysteine, and Trolox® (1 mM, but not mannitol (100 mM, were able to protect the proteins against the effect of ONOO- in a dose-dependent manner. Melatonin (0-1 mM was especially efficient in reducing the loss of spectrin proteins when treated with ONOO- (90% at 500 µM melatonin. Our findings show that the cytoskeleton, and in particular spectrin, is a sensitive target for ONOO-. Specific antioxidants can protect against such alterations, which could seriously impair cell dynamics and generate morphological changes.

P. Di Mascio

2000-01-01

366

Ghost protein damage by peroxynitrite and its protection by melatonin  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english We have studied the effect of peroxynitrite (ONOO-) on the membrane cytoskeleton of red blood cells and its protection by melatonin. Analysis of the protein fraction of the preparation by SDS-PAGE revealed a dose-dependent (0-600 µM ONOO-) disappearance at pH 7.4 of the main proteins: spectrin, band [...] 3, and actin, with the concomitant formation of high-molecular weight aggregates resistant to reduction by ß-mercaptoethanol (2%) at room temperature for 20 min. These aggregates were not solubilized by 8 M urea. Incubation of the membrane cytoskeleton with ONOO- was characterized by a marked depletion of free sulfhydryl groups (50% at 250 µM ONOO-). However, a lack of effect of ß-mercaptoethanol suggests that, under our conditions, aggregate formation is not mediated only by sulfhydryl oxidation. The lack of a protective effect of the metal chelator diethylenetriaminepentaacetic acid confirmed that ONOO--induced oxidative damage does not occur only by a transition metal-dependent mechanism. However, we demonstrated a strong protection against cytoskeletal alterations by desferrioxamine, which has been described as a direct scavenger of the protonated form of peroxynitrite. Desferrioxamine (0.5 mM) also inhibited the loss of tryptophan fluorescence observed when the ghosts were treated with ONOO-. Glutathione, cysteine, and Trolox® (1 mM), but not mannitol (100 mM), were able to protect the proteins against the effect of ONOO- in a dose-dependent manner. Melatonin (0-1 mM) was especially efficient in reducing the loss of spectrin proteins when treated with ONOO- (90% at 500 µM melatonin). Our findings show that the cytoskeleton, and in particular spectrin, is a sensitive target for ONOO-. Specific antioxidants can protect against such alterations, which could seriously impair cell dynamics and generate morphological changes.

P., Di Mascio; B., Dewez; C.R.S., Garcia.

367

Evaluation of Melatonin for Prevention of Radiation Myelopathy in Irradiated Cervical Spinal Cord  

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Full Text Available Objective: Radiation myelopathy (RM is known as a serious complication of head andneck radiation therapy. Furthermore, the radioprotective roles of melatonin have beeninvestigated on different tissues. The aim of this study was to assess the radio protectiveeffects of melatonin on biochemical, histopathological and clinical manifestations of RMin the rat cervical spinal cord.Materials and Methods: Four groups of rats were investigated as follows: The controlgroup was treated with vehicle. The second group (melatonin only was intraperitoneallyinjected with 100 mg/kg melatonin. The third group's (radiation cervical spinal cord areawas irradiated with 22 Gy cobalt-60 gamma-rays. The fourth group (melatonin plus irradiationreceived 100 mg/kg melatonin intraperitoneally, and after 30 minutes their spinalcord area was irradiated with 22 Gy gamma radiation. Five animals from each group wererandomly selected. 72 hours, 8 and 22 weeks after irradiation for analysis of malondialdehyde(MDA and glutathione (GSH levels, and underwent histopathological studies.Results: The MDA levels in the irradiation group were significantly higher than in the controlgroup (p<0.001. Furthermore, the GSH levels in this group were significantly lowerthan that of those in the control group (p<0.001. Administration of melatonin markedlyreduced MDA (p<0.001 and increased GSH (p<0.05 levels in this group. Demyelinationand clinical signs of myelopathy were decreased in the melatonin plus irradiation group incomparison to the irradiated group.Conclusion: Our study confirms the radioprotective effects of melatonin at early stagesof biochemical, as well as late histological and clinical changes in the spinal cord.

Alireza Shirazi

2009-01-01

368

Obtaining fast dissolving disintegrating tablets with different doses of melatonin.  

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Fast dissolving disintegrating tablets (FDDTs) containing different dosages of melatonin have been manufactured for administration to a specific target population: pediatric patients, having potential difficulties taking other oral forms. The lower dosages (3 and 5mg) are intended for epileptic children, migraine prevention, neurodevelopmental disability, sleep disorders and blindness. Dosages of 10 and 60 mg are intended for Duchenne muscular dystrophy. Two FDDT groups have been designed, one which has excipients for direct compression and others having direct compression and effervescent excipients. Tablets have been produced having disintegration times of less than 25s and with friability and hardness values that require no special storage or packaging conditions. PMID:24699354

Muñoz, H; Castan, H; Clares, B; Ruiz, M A

2014-06-01

369

IJMS | Special Issue : Advances in the Research of Melatonin 2014  

... Despite this novel complexity, the effects of melatonin and its synthetic analogs on the circadian system continues to be of particular interest, especially as well-functioning of both central and peripheral circadian oscillators is increasingly perceived to be of significant importance to health. Phasing and coordination ...of rhythms and support of circadian amplitudes seem to represent an area in which cellular oscillations and melatonergic actions are intertwined, with mutual support and synergism in its physiological outcome. The hope is that maintenance of these time structures might overcome, to a certain degree,...

370

Chronomics reveal and quantify circadian rhythmic melatonin in duodenum of rats  

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A circadian rhythm is documented in duodenal melatonin in rats, peaking 16.8 hours after light onset.