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Sample records for nocturnal melatonin elevation

  1. Simulation of migratory flight and stopover affects night levels of melatonin in a nocturnal migrant.

    OpenAIRE

    Fusani, Leonida; Gwinner, Eberhard

    2004-01-01

    Several species of diurnal birds are nocturnal migrants. The activation of nocturnal activity requires major physiological changes, which are essentially unknown. Previous work has shown that during migratory periods nocturnal migrants have reduced night-time levels of melatonin. Since this hormone is involved in the modulation of day-night rhythms, it is a good candidate regulator of nocturnal migratory activity. We studied whether melatonin levels change when nocturnally active blackcaps (S...

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

    Directory of Open Access Journals (Sweden)

    Grossman E

    2011-09-01

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

  3. Indirect blue light does not suppress nocturnal salivary melatonin in humans in an automobile setting.

    Science.gov (United States)

    Lerchl, Alexander; Schindler, Carina; Eichhorn, Karsten; Kley, Franziska; Erren, Thomas C

    2009-09-01

    In 2007, the International Agency for Research on Cancer (IARC) classified shift work that involves circadian disruption as being probably carcinogenic to humans (Group 2A). In this context, light exposure during the night plays a key role because it can suppress nocturnal melatonin levels when exposures exceed a certain threshold. Blue light around 464 nm is most effective in suppressing melatonin because of the spectral sensitivity of melanopsin, a recently discovered photopigment in retinal ganglion cells; the axons of these cells project to the suprachiasmatic nucleus, a circadian master clock in the brain. Due to advances in light technologies, normal tungsten light bulbs are being replaced by light-emitting diodes which produce quasi-monochromatic or white light. The objective of this study was to assess whether the light-melanopsin-melatonin axis might be affected in automobiles at night which employ the new generation diodes. To this end, we have tested in an experimental automobile setting whether indirect blue light (lambda(max) = 465 nm) at an intensity of 0.22 or 1.25 lx can suppress salivary melatonin levels in 12 male volunteers (age range 17-27 years) who served as their own controls. Daytime levels were low (2.7 +/- 0.5 pg/mL), and night-time levels without light exposure were high (14.5 +/- 1.1 pg/mL), as expected. Low-intensity light exposures had no significant effect on melatonin levels (0.22 lx: 17.2 +/- 2.8 pg/mL; P > 0.05; 1.25 lx: 12.6 +/- 2.0 pg/mL; P > 0.05). It is concluded that indirect blue light exposures in automobiles up to 1.25 lx do not cause unintentional chronodisruption via melatonin suppression. PMID:19555449

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

    Science.gov (United States)

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

    2013-10-18

    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

  5. Melatonin

    Science.gov (United States)

    ... might increase or decrease melatonin levels in the body. When taken together with melatonin supplements, caffeine seems to increase melatonin levels.EchinaceaTaking echinacea together with melatonin might have negative effects on immune function.Herbs and supplements that might ...

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

    Directory of Open Access Journals (Sweden)

    C. Pérez-Rico

    2009-05-01

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

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

    Scientific Electronic Library Online (English)

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

    2009-05-01

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

  8. Melatonin

    Science.gov (United States)

    ... by a part of the brain called the pineal (say: "pie-nee-all") gland. Melatonin may help ... synthetic (manmade). Natural melatonin is made from the pineal gland of animals. This form could be contaminated ...

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2013-08-01

    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

  11. A personal light-treatment device for possibly improving sleep quality in the elderly: Dynamics of nocturnal melatonin suppression at two exposure levels

    OpenAIRE

    Figueiro, Mariana G.; Bierman, Andrew; Bullough, John D.; Rea, Mark S.

    2009-01-01

    Light treatment has been used as a non-pharmacological tool to help mitigate poor sleep quality frequently found in the older people. In order to increase compliance to non-pharmacological light treatments, new, more efficacious light-delivery systems need to be developed. A prototype personal light-treatment device equipped with low brightness blue light-emitting diodes (LEDs) (peak wavelength near 470 nm) was tested for its effectiveness in suppressing nocturnal melatonin, a measure of circ...

  12. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression

    Science.gov (United States)

    Zeitzer, J. M.; Dijk, D. J.; Kronauer, R.; Brown, E.; Czeisler, C.

    2000-01-01

    Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.

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

    OpenAIRE

    Grossman E; Laudon M; Zisapel N

    2011-01-01

    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...

  14. URINARY MELATONIN IN DEPRESSION

    OpenAIRE

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

    1983-01-01

    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...

  15. 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

    OpenAIRE

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

    2007-01-01

    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...

  16. Melatonin in animal models

    OpenAIRE

    Pévet, Paul

    2003-01-01

    Melatonin is a hormone synthesized and secreted during the night by the pineal gland. Its production is mainly driven by the Orcadian clock, which, in mammals, is situated in the suprachiasmatic nucleus of the hypothalamus. The melatonin production and release displays characteristic daily (nocturnal) and seasonal patterns (changes in duration proportional to the length of the night) of secretion. These rhythms in circulating melatonin are strong synchronizers for the expression of numerous p...

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

    OpenAIRE

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

    2012-01-01

    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 ...

  18. Morning and nocturnal serum melatonin rhythm levels in patients with major depressive disorder: an analytical cross-sectional study / Medir los niveles del ritmo de melatonina día-noche entre los pacientes con trastorno depresivo mayor: un estudio analítico transversal

    Scientific Electronic Library Online (English)

    Shahnaz, Khaleghipour; Mohsen, Masjedi; Hassan, Ahade; Meersalahodin, Enayate; Gholamreza, Pasha; Farah, Nadery; Gholamhossein, Ahmadzade.

    Full Text Available CONTEXTO Y OBJETIVO: La glándula pineal actúa precisamente regulando los ritmos biológicos de melatonina de hemostasia cerebral, como un órgano adaptativo. La modificación del ritmo de melatonina puede ser el motivo probable del trastorno depresivo. Este estudio se realizó con el objetivo de medir l [...] os niveles de melatonina entre los pacientes con trastorno depresivo mayor y los sanos. DISEÑO Y ESPACIO: Estudio analítico transversal-la unidad medicina laboral de empresa de Zob Ahan de Isfahán-Irán. MÉTODO: Los niveles de melatonina en suero día-noche se midó entre dos grupos (pacientes y sanos) utilizando el método de ELISA (Ensayo por inmunoabsorción ligado a enzimas). Todos los datos se hizo utilizando el análisis de la varianza. RESULTADOS: El nivel de melatonina en suero día-noche era distinto entre los deprimidos y los saludables (P Abstract in english CONTEXT AND OBJECTIVE: The pineal gland is an adaptive organ that precisely regulates the biological rhythms of melatonin brain hemostasis. Variation in the regulation of melatonin rhythms is a likely cause of depressive disorder. The purpose of this study was to measure serum melatonin levels in pa [...] tients with major depressive disorder (MDD) and normal control subjects. DESIGN AND SETTING: Analytical cross-sectional study at the industrial medical unit of the Iron Smelting Company of Isfahan, Iran. METHODS: The morning and nocturnal serum melatonin levels of patients and controls were measured using the enzyme-linked immunosorbent assay (ELISA) method. All data were assessed using variance analysis. RESULTS: The morning and nocturnal serum melatonin levels of depressed and healthy subjects differed (P

  19. Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    EkelØf, Sarah V; Halladin, Natalie L

    2014-01-01

    Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia-reperfusion injury. Melatonin, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma levels of high-sensitive troponin T were assessed repeatedly. The experimenters were blinded with regard to treatmentregimen. Melatonin did not significantly increase myocardial salvage index compared with placebo [melatonin 21.8 % (16.1; 24.8) vs. placebo 20.2 % (16.9; 27.0), p = 1.00]. The extent of microvascular obstruction was similar between the groups [melatonin 3.8 % (2.7; 7.1) vs. placebo 3.7 % (1.3; 7.7), p = 0.96]. The area under the curve for high-sensitive troponin T release was insignificantly reduced by 32 % in the melatonin group [AUC melatonin 12,343.9 (6,889.2; 20,147.4) ng h/L vs. AUC placebo 18,285.3 (5,180.4; 23,716.8) ng h/L, p = 0.82]. Combined intracoronary and intravenous treatment with melatonin did not reduce myocardial reperfusion injury. The lack of a positive effect could be due to an ineffective dose of melatonin, a type II error or the timing of administration.

  20. Average diurnal changes in melatonin levels are associated with hourly incidence of bereavement apparitions: support for the hypothesis of temporal (limbic) lobe microseizuring.

    Science.gov (United States)

    Persinger, M A

    1993-04-01

    Transient suppressions of nocturnal melatonin levels due to enhanced geomagnetic activity have been suggested as the precipitating source of experiences of postmortem (bereavement) apparitions when the brain has been sensitized (grief) by elevations of the epileptogenic neuropeptide, corticotrophin-releasing factor. Although the hourly incidence of subjective experiences of telepathy, precognition, and bereavement apparitions were all significantly correlated with published indices of hourly melatonin levels, only the significant association between melatonin levels and apparitions was not changed when the other two classes of psi experiences were held constant. PMID:8387181

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

    Scientific Electronic Library Online (English)

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

    2007-05-01

    Full Text Available 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

  2. The effect of clonidine and bright light on plasma melatonin

    OpenAIRE

    Grasby, PM; Cowen, PJ

    1988-01-01

    We studied the effect of ?2-adrenoceptor agonist, clonidine, and bright artificial light (> 2500 lux) on the nocturnal increase in plasma melatonin in normal subjects. Clonidine (1.5 ?g/kg, intravenously) was without effect on plasma melatonin concentration. In contrast, bright light treatment abolished the increase in night-time melatonin. Bright light is a simple and effective means of altering melatonin secretion in humans.

  3. 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)

    LC. Reis

    2007-05-01

    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.

  4. 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 ...

  5. Melatonin profiles and sleep characteristics in boys with fragile X syndrome: a preliminary study.

    Science.gov (United States)

    Gould, E L; Loesch, D Z; Martin, M J; Hagerman, R J; Armstrong, S M; Huggins, R M

    2000-12-11

    Sleep patterns and endogenous melatonin profiles in 13 fragile X boys between the age of 4.7 and 11.0 years were compared to those of 8 age-matched, normal control boys. Parents recorded sleep patterns on a Sleep Diary Chart for 14 consecutive days. Twelve saliva samples were obtained from 8 fragile X participants and all of the controls over 48 hours for the assessment of salivary melatonin profiles. The results showed greater variability in total sleep time and difficulty in sleep maintenance in fragile X boys compared with the control participants. Nocturnal melatonin production, expressed as both peak level and area under the concentration-time curve between 20:00 h and 08:00 h, were found to be significantly larger in fragile X boys than in controls. Additionally, the mean of the minimum daytime melatonin levels recorded was significantly higher for the fragile X group. Elevated levels in some fragile X boys relative to the range seen in controls, occurring either during the day or at night, or in both segments of the secretory profile for some individuals, may be due in part to overactivity of the sympathetic nervous system. Alternative molecular mechanisms leading to changes in melatonin profiles in fragile X are also discussed. PMID:11186882

  6. Endogenous melatonin and oxidatively damaged guanine in DNA

    OpenAIRE

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

    2009-01-01

    Abstract Background A significant body of literature indicates that melatonin, a hormone primarily produced nocturnally by the pineal gland, is an important scavenger of hydroxyl radicals and other reactive oxygen species. Melatonin may also lower the rate of DNA base damage resulting from hydroxyl radical attack and increase the rate of repair of that damage. This paper reports the results of a study relating the level of overnight melatonin production to the overnight excretion of the two p...

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

    OpenAIRE

    Galli-carminati, Giuliana Mariangela; Deriaz, Nicolas; Bertschy, Gilles

    2009-01-01

    BACKGROUND: Melatonin may be used to treat sleep disorders in both children and adults with intellectual disability. The evidence for its efficacy, potential adverse effects and drug interactions are reviewed in the context of prescription of melatonin to patients with autism. METHODS: This study presents the use of melatonin to treat severe circadian sleep-wake disturbances in 6 adults with autism. Melatonin was initiated at a daily dose of 3 mg at nocturnal bedtime. If this proved ineffecti...

  8. Dietary factors and fluctuating levels of melatonin

    Directory of Open Access Journals (Sweden)

    Katri Peuhkuri

    2012-07-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jack M.

    1992-06-01

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

  10. Nocturnal enuresis

    OpenAIRE

    Kiddoo, Darcie

    2011-01-01

    Nocturnal enuresis affects 15% to 20% of 5-year-old children, 5% of 10-year-old children, and 1% to 2% of people aged 15 years and over. Without treatment, 15% of affected children will become dry each year. Nocturnal enuresis is not diagnosed in children aged

  11. Nocturnal enuresis

    OpenAIRE

    Kiddoo, Darcie

    2007-01-01

    Nocturnal enuresis affects 15?20% of 5-year-old children, 5% of 10-year-old children, and 1?2% of people aged 15 years and over. Without treatment, 15% of affected children will become dry each year. Nocturnal enuresis is not diagnosed in children younger than 5 years, and treatment may be inappropriate for children younger than 7 years.

  12. 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

  13. Melatonin in plants and other phototrophs: advances and gaps concerning the diversity of functions.

    Science.gov (United States)

    Hardeland, Rüdiger

    2015-02-01

    Melatonin is synthesized in Alphaproteobacteria, Cyanobacteria, Dinoflagellata, Euglenoidea, Rhodophyta, Phae ophyta, and Viridiplantae. The biosynthetic pathways have been identified in dinoflagellates and plants. Other than in dinoflagellates and animals, tryptophan is not 5-hydroxylated in plants but is first decarboxylated. Serotonin is formed by 5-hydroxylation of tryptamine. Serotonin N-acetyltransferase is localized in plastids and lacks homology to the vertebrate aralkylamine N-acetyltransferase. Melatonin content varies considerably among species, from a few picograms to several micrograms per gram, a strong hint for different actions of this indoleamine. At elevated levels, the common and presumably ancient property as an antioxidant may prevail. Although melatonin exhibits nocturnal maxima in some phototrophs, it is not generally a mediator of the signal 'darkness'. In various plants, its formation is upregulated by visible and/or UV light. Increases are often induced by high or low temperature and several other stressors including drought, salinity, and chemical toxins. In Arabidopsis, melatonin induces cold- and stress-responsive genes. It has been shown to support cold resistance and to delay experimental leaf senescence. Transcriptome data from Arabidopsis indicate upregulation of genes related to ethylene, abscisic acid, jasmonic acid, and salicylic acid. Auxin-like actions have been reported concerning root growth and inhibition, and hypocotyl or coleoptile lengthening, but effects caused by melatonin and auxins can be dissected. Assumptions on roles in flower morphogenesis and fruit ripening are based mainly on concentration changes. Whether or not melatonin will find a place in the phytohormone network depends especially on the identification of molecular signals regulating its synthesis, high-affinity binding sites, and signal transduction pathways. PMID:25240067

  14. MELATONIN: POTENTIAL UTILITY FOR IMPROVING PUBLIC HEALTH

    Directory of Open Access Journals (Sweden)

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

    2006-04-01

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

  15. Nocturnal hemodialysis

    OpenAIRE

    Ranganathan, D.; John, G. T.

    2012-01-01

    Patients receiving conventional hemodialysis have high hospitalisation rates, poor quality of life and survival compared to the general population. Many centres around the world are providing longer hours of hemodialysis - short daily hemodialysis and nocturnal hemodialysis - with a view to improving patient survival and quality of life. Studies have shown that nocturnal haemodiaysis is more effective than conventional hemodialysis in clearing most small, middle and larger molecule toxins and...

  16. Plastic oscillators and fixed rhythms: changes in the phase of clock-gene rhythms in the PVN are not reflected in the phase of the melatonin rhythm of grass rats.

    Science.gov (United States)

    Martin-Fairey, C A; Ramanathan, C; Stowie, A; Walaszczyk, E; Smale, L; Nunez, A A

    2015-03-12

    The same clock-genes, including Period (PER) 1 and 2, that show rhythmic expression in the suprachiasmatic nucleus (SCN) are also rhythmically expressed in other brain regions that serve as extra-SCN oscillators. Outside the hypothalamus, the phase of these extra-SCN oscillators appears to be reversed when diurnal and nocturnal mammals are compared. Based on mRNA data, PER1 protein is expected to peak in the late night in the paraventricular nucleus of the hypothalamus (PVN) of nocturnal laboratory rats, but comparable data are not available for a diurnal species. Here we use the diurnal grass rat (Arvicanthis niloticus) to describe rhythms of PER1 and 2 proteins in the PVN of animals that either show the species-typical day-active (DA) profile, or that adopt a night-active (NA) profile when given access to running wheels. For DA animals housed with or without wheels, significant rhythms of PER1 or PER2 protein expression featured peaks in the late morning; NA animals showed patterns similar to those expected from nocturnal laboratory rats. Since the PVN is part of the circuit that controls pineal rhythms, we also measured circulating levels of melatonin during the day and night in DA animals with and without wheels and in NA wheel runners. All three groups showed elevated levels of melatonin at night, with higher levels during both the day and night being associated with the levels of activity displayed by each group. The differential phase of rhythms in the clock-gene protein in the PVN of diurnal and nocturnal animals presents a possible mechanism for explaining species differences in the phase of autonomic rhythms controlled, in part, by the PVN. The present study suggests that the phase of the oscillator of the PVN does not determine that of the melatonin rhythm in diurnal and nocturnal species or in diurnal and nocturnal chronotypes within a species. PMID:25575946

  17. Melatonin Promotes Superovulation in Sika Deer (Cervus nippon)

    OpenAIRE

    Liang; Wang; Zhi-Yong Zhuo; Wen-Qing Shi; Dun-Xian Tan; Chao Gao; Xiu-Zhi Tian; Lu Zhang; Guang-Bin Zhou; Shi-En Zhu; Peng Yun; Guo-Shi Liu

    2014-01-01

    In this study, the effects of melatonin (MT) on superovulation and reproductive hormones (melatonin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and PRL) were investigated in female sika deer. Different doses (40 or 80 mg/animal) of melatonin were subcutaneously implanted into deer before the breeding season. Exogenous melatonin administration significantly elevated the serum FSH levels at the time of insemination compared with levels in control animals. During superovulation...

  18. Nocturnal Animals

    Science.gov (United States)

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

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

    OpenAIRE

    Hardeland, R.

    2008-01-01

    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...

  20. Use of Transdermal Melatonin Delivery to Improve Sleep Maintenance during Daytime

    OpenAIRE

    Aeschbach, D; Lockyer, BJ; Dijk, D-J; Lockley, SW; Nuwayser, ES; Nichols, LD; Czeisler, CA

    2009-01-01

    Oral melatonin can improve daytime sleep, but the hormone's short elimination half-life limits its use as a hypnotic in shift workers, jet-lag and other situations. Here we show in healthy subjects that transdermal delivery of melatonin during the daytime can elevate plasma melatonin and reduce waking after sleep onset by promoting sleep in the latter part of an 8-hour sleep opportunity. Thus, transdermal melatonin may have advantages over fast-release oral melatonin in improving sleep mainte...

  1. Photic and circadian regulation of retinal melatonin in mammals

    Science.gov (United States)

    Tosini, G.; Fukuhara, C.

    2003-01-01

    Several studies have established that melatonin synthesis occurs in the retina of vertebrates, including mammals. In mammals, a subpopulation of photoreceptors (probably the cones) synthesize melatonin. Melatonin synthesis in the retina is elevated at night and reduced during the day in a fashion similar to events in the pineal gland. Both the MT1 and MT2 melatonin receptors are present in the retina and retinal melatonin does not contribute to circulating levels, suggesting that retinal melatonin acts locally as a neurohormone and/or neuromodulator. Melatonin synthesis in the retina of mammals is under the control of a circadian oscillator, and circadian rhythms in melatonin synthesis and/or release have been described for several species of mammals. These rhythms are present in vivo, persist in vitro, are entrained by light and are temperature compensated. The cloning of the gene responsible for the synthesis of the enzyme arylalkylamine N-acetyltransferase (the key enzyme in the melatonin biosynthetic pathway) has allowed studies of the molecular mechanisms responsible for the generation of retinal melatonin rhythmicity. The present review focuses on the cellular and molecular mechanisms that regulate melatonin synthesis. In particular, we discuss how the photic environment and the circadian clock interact in determining melatonin levels, in addition to the role that melatonin plays in retinal physiology.

  2. Endogenous melatonin and oxidatively damaged guanine in DNA

    DEFF Research Database (Denmark)

    Davanipour, Zoreh; Poulsen, Henrik E

    2009-01-01

    A significant body of literature indicates that melatonin, a hormone primarily produced nocturnally by the pineal gland, is an important scavenger of hydroxyl radicals and other reactive oxygen species. Melatonin may also lower the rate of DNA base damage resulting from hydroxyl radical attack and increase the rate of repair of that damage. This paper reports the results of a study relating the level of overnight melatonin production to the overnight excretion of the two primary urinary metabolites of the repair of oxidatively damaged guanine in DNA.

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

    Directory of Open Access Journals (Sweden)

    Guillaume Bronsard

    2013-10-01

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

  4. Clinical aspects of melatonin.

    OpenAIRE

    Reiter, Russel J.; Ahmet Korkmaz

    2008-01-01

    ABSTRACT Melatonin is produced in the human pineal gland, particularly at night, with the circadian rhythm of blood melatonin levels closely paralleling its production within the pineal gland. Light exposure at night, or rapid transmeridian travel severely compromises the circadian production of melatonin. The disturbed melatonin rhythm contributes to jet lag and sleep inefficiency, both of which are improved by melatonin administration. Melatonin is also a highly effective direct free rad...

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

    OpenAIRE

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

    1996-01-01

    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...

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

    OpenAIRE

    Vigo DE; Mf, Vidal; Dp, Cardinali

    2012-01-01

    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...

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

    OpenAIRE

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

    1994-01-01

    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 ...

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

    Science.gov (United States)

    Lee, Jack Monroe, Jr.

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

  9. Melatonin’s Effect in Febrile Seizures and Epilepsy

    Directory of Open Access Journals (Sweden)

    Abolfazl MAHYAR

    2014-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE FA How to Cite This Article: Mahyar A, Ayazi P, Dalirani R, Gholami N, Daneshi-Kohan MM, Mohammadi N, Ahmadi MM, Sahmani AA. Melatonin’s Effect in Febrile Seizures and Epilepsy Iran J Child Neurol. 2014 Summer;8(3: 24-29. AbstractObjectiveRecognition of risk factors for febrile seizures (FS and epilepsy is essential. Studies regarding the role of melatonin in these convulsive disorders are limited.This study determines the relationship between serum melatonin levels and FS and epilepsy in children.Materials & MethodsA population of 111 children with simple FS, complex FS, and epilepsy (37 children per group, respectively were included as case groups. In addition, 37 febrile children without seizures comprised the control group. Serum melatonin levels were measured and compared between all groups.ResultsThe serum melatonin levels in the simple, complex FSs, and epilepsy groups were 2, 2.4, and 2 pg/ml, respectively. The serum melatonin level in the control group was 2.1pg/ml.Moreover, there were no significant differences observed while comparing the case groups.ConclusionThe present study reveals that there is no association between serum melatonin level and simple or complex FS and epilepsy. It appears that melatonin plays no significant role in these convulsive disorders. ReferencesBanerjee TK, Hazra A, Biswas A, Ray Jet al. Neurological disorders in children and adolescents. Indian J Pediatr2009; 76:139-46.Salehi Omran MR, Khalilian E, Mehdipour E, Ghabeli JA. Febrile seizures in North Iranian children: Epidemiology and clinical feature, Journal of Pediatric Neurology2008, 6: 39-43.Shinnar S, O’Dell C. Febrile Seizures, Pediatr Ann 2004, 33: 394-402.Millar JS. The child with febrile seizure, Pediatrics for parents 2006.24:12-14.Fetvei A. Assessment of febrile seizures in children, Eur J Pediatr2008, 167:17-27.Mikati MA. Seizures in Childhood In: Kliegman RM, Stanton BF, Schor NF, St. Geme III JW, Behrman RE. Nelson textbook of pediatrics. 19th ed. Phila: Saunders, 2011:2013-2039.Camfield PR, Canfield CS. Epilepsy. In: Swaiman KF, Ashwal S, Ferriero DM, editors. Pediatric neurology: principles and practice. 4th ed. Philadelphia: Mosby, 2006:981-8.Chang BS, Lowenstein DH. Epilepsy, N Eng J Med 2003, 13:1257-1266.Aydin A, Ergor A, Ergor G, Dirik E. The prevalence of epilepsy amongst school children in Izmir, Turkey, Seizure 2002; 11: 392–396.10.Jan MM, Girvin JP. Febrile seizures. Update and controversies. Neurosciences (Riyadh 2004; 9:235-42.French JA. Febrile seizures: possible outcomes. Neurology2012; 28; 79:e80-2.Guo JF,Yao JF. Serum melatonin levels in children with epilepsy or FS, Zhongguo Dang Dai Er Ke Za Zhi2009, 11:288-90 (Medline.Reiter RJ. Melatonin: clinical relevance, Best Pract. Res Clin Endocrinol Metab 2003, 17: 273-285.Seithikurippu R, Perumal P, Trakh I, Srinivasan V, Spence DW, Maestroni GJM, Zisapel N, Cardinali DP. Physiological effects of melatonin Role of melatonin receptors and signal transduction pathways, Prog Neurobiol 85, 2008: 335-353.Ardura J, Andres J, Garmendia JR, Ardura F. Melatonin in epilepsy and FS.J Child Neurol 2010; 25:888-91.Ganesh R, Janakiraman L, Meenakshi B. Serum zinc levels are low in children with simple FS compared with those in children with epileptic seizures and controls.Ann Trop Paediatr 2011; 31:345-9.Bazil CW, Short D, Crispin D, Zheng W. Patients with intractable epilepsy have low melatonin, which increases following seizures. Neurology 2000; 55:1746-8.Yalyn O, Arman F, Erdogan F, Kula M. A comparison of the circadian rhythmsand the levels of melatonin in patients with diurnal and nocturnal complexpartial seizures. Epilepsy Behav 2006;8:542-6.Schapel GJ, Beran RG, Kennaway DL, McLoughney J, Matthews CD. Melatonin response in active epilepsy. Epilepsia 1995; 36:75-8.Ekmekcioglu C. Melatonin receptors in humans: biological role and clinical relevance,Biomedicine and Pharmacotherapy 2006,60: 97-108.Tan DX, Manchester LC, Hardeland R, Lopez-Burillo S, et al. Melatonin: a hormone, a tissue fa

  10. Nocturnal increase in plasma cGMP levels in humans.

    Science.gov (United States)

    Zhdanova, I V; Simmons, M; Marcus, J N; Busza, A C; Leclair, O U; Taylor, J A

    1999-08-01

    The circadian dynamics of responses to cyclic guanosine 3',5'-monophosphate (cGMP) in in vitro experiments and the stimulating effects of the pineal hormone melatonin on cGMP levels both in vitro and in vivo provoked an investigation into the diurnal pattern of occurrence of this second messenger in human plasma and its correlation with plasma melatonin levels. Plasma cGMP levels were measured in 9 normal human subjects who were over 50 years of age. Samples were obtained hourly through a 20-h period (11 a.m. to 7 a.m.) that included the subjects' habitual hours of nocturnal sleep; physical activity was kept to a minimum during the daylight hours. The area under the time-plasma cGMP concentration curve showed a significant increase during the period of nocturnal sleep compared to that observed during the period of daytime wakefulness. The individual temporal pattern of the nocturnal rise in plasma cGMP differed among the subjects; however, the initial increase typically was observed soon after bedtime. No significant correlation was observed between individual nocturnal plasma melatonin levels and cGMP levels. PMID:10447311

  11. The internal time-giver role of melatonin. A key for our health.

    Science.gov (United States)

    Pévet, P

    2014-11-01

    Daily rhythms in physiological and behavioural processes are controlled by a network of circadian clocks. In mammals, at the top of the network is a master clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The nocturnal synthesis and release of melatonin by the pineal gland are tightly controlled by the SCN clock. Several roles of melatonin in the circadian system have been identified. As a major hormonal output, melatonin distributes temporal cues generated by the SCN to the multitude of tissues expressing melatonin receptors. In some target tissues, these melatonin signals can drive daily rhythmicity that would otherwise be lacking. In other target structures, melatonin signals are used for the synchronization (i.e., adjustment of the timing of existing oscillations) of peripheral oscillators. Due to the expression of melatonin receptors in the SCN, endogenous melatonin is also able to feedback onto the master clock. Of note, pharmacological treatment with exogenous melatonin can synchronize the SCN clock. From a clinical point of view, provided that the subject is not exposed to light at night, the daily profile of circulating melatonin provides a reliable estimate of the timing of the human SCN. During the past decade, a number of melatonin agonists have been developed. These drugs may target the SCN for improving circadian timing or act indirectly at some downstream level of the circadian network to restore proper internal synchronization. PMID:25287733

  12. Melatonin, a natural programmed cell death inducer in cancer.

    Science.gov (United States)

    Sánchez-Hidalgo, M; Guerrero, J M; Villegas, I; Packham, G; de la Lastra, C A

    2012-01-01

    Melatonin, an indolamine derived from the amino-acid tryptophan, participates in diverse physiological functions and has great functional versatility related to the regulation of circadian rhythms and seasonal behaviour, sexual development, retinal physiology, tumour inhibition, as an antioxidant, immunomodulatory and anti-aging properties. In relation to its oncostatic properties, there is evidence that tumor initiation, promotion or progression may be restrained by the night-time physiological surge of melatonin in the blood or extracellular fluid. In addition, depressed nocturnal melatonin concentrations or nocturnal excretion of the main melatonin metabolite, 6-sulfatoxymelatonin, were found in individuals with various tumor types. In the majority of studies, melatonin was shown to inhibit development and/or growth of various experimental animal tumors and some human cell lines in vitro. Many tumors do not respond to drug treatment due to their resistance to undergo apoptosis thereby contributing to the development of cancer. Thus, given the importance of the apoptotic program in cancer treatment, the role of melatonin in influencing apoptosis in tumor cells attracted attention because it seems that it actually promotes apoptosis in most tumor cells, in contrast to the obvious inhibition of apoptotic processes in normal cells. Thus, this paper is also intended to provide to the reader an up-date of all the researches that have been carried out to date, which investigate the proapoptotic effects of melatonin in experimental preclinical models of cancer (in vitro and in vivo) and the underlying proposed action mechanism of this effects. If melatonin uniformly induces apoptosis in cancer cells, the findings could have important clinical implications to improve the quality of live while preventing the appearance of cancer. PMID:22612707

  13. Melatonin-induced glycosaminoglycans augmentation in myocardium remote to infarction.

    Science.gov (United States)

    Drobnik, J; Tosik, D; Piera, L; Szczepanowska, A; Olczak, S; Zielinska, A; Liberski, P P; Ciosek, J

    2013-12-01

    Elevated levels of collagen as well as transient increases of glycosaminoglycans (GAG) have been shown in the myocardium remote to the infarction. The aim of the study is to observe the effect of melatonin on the accumulation of collagen and GAG in the left ventricle wall, remote to the infarction. A second aim is to determine whether the effect of the pineal indole is mediated by the membrane melatonin receptors of heart fibroblasts. Rats with myocardial infarction induced by ligation of the left coronary artery were treated with melatonin at a dose of 60 ?g/100 g b.w. or vehicle (2% ethanol in 0.9% NaCl). The results were compared with an untreated control. In the second part of the study, the fibroblasts from the non-infarcted part of myocardium were isolated and cultured. Melatonin at a range of concentrations from 10(-8) M to 10(-6) M was applied to the fibroblast cultures. In the final part of the study, the influence of luzindole (10(-6) M), the melatonin membrane receptor inhibitor, on melatonin-induced GAG augmentation was investigated. Both collagen and GAG content were measured in the experiment. Melatonin elevated GAG content in the myocardium remote to the infarcted heart. Collagen level was not changed by pineal indoleamine. Fibroblasts isolated from the myocardium varied in shape from fusiform to spindle-shaped. Moreover, the pineal hormone (10(-7)M and 10(-6)M) increased GAG accumulation in the fibroblast culture. Luzindole inhibited melatonin-induced elevation of GAG content at 10(-6)M. Melatonin increased GAG content in the myocardium remote to infarction. This effect was dependent on the direct influence of the pineal indole on the heart fibroblasts. The melatonin-induced GAG elevation is blocked by luzindole, the melatonin membrane receptors inhibitor, indicating a direct effect of this indole. PMID:24388888

  14. Secondary Nocturnal Enuresis

    Science.gov (United States)

    ... Contact Us You are here Home » Secondary Nocturnal Enuresis Some children have always wet the bed at ... for a variable period of time. Secondary nocturnal enuresis (SNE) is bedwetting that develops after at least ...

  15. Adrenaline and nocturnal asthma.

    OpenAIRE

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

    1990-01-01

    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...

  16. Selective protection of the cerebellum against intracerebroventricular LPS is mediated by local melatonin synthesis.

    Science.gov (United States)

    Pinato, Luciana; da Silveira Cruz-Machado, Sanseray; Franco, Daiane G; Campos, Leila M G; Cecon, Erika; Fernandes, Pedro A C M; Bittencourt, Jackson C; Markus, Regina P

    2015-03-01

    Although melatonin is mainly produced by the pineal gland, an increasing number of extra-pineal sites of melatonin synthesis have been described. We previously demonstrated the existence of bidirectional communication between the pineal gland and the immune system that drives a switch in melatonin production from the pineal gland to peripheral organs during the mounting of an innate immune response. In the present study, we show that acute neuroinflammation induced by lipopolysaccharide (LPS) injected directly into the lateral ventricles of adult rats reduces the nocturnal peak of melatonin in the plasma and induces its synthesis in the cerebellum, though not in the cortex or hippocampus. This increase in cerebellar melatonin content requires the activation of nuclear factor kappa B (NF-?B), which positively regulates the expression of the key enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AA-NAT). Interestingly, LPS treatment led to neuronal death in the hippocampus and cortex, but not in the cerebellum. This privileged protection of cerebellar cells was abrogated when G-protein-coupled melatonin receptors were blocked by the melatonin antagonist luzindole, suggesting that the local production of melatonin protects cerebellar neurons from LPS toxicity. This is the first demonstration of a switch between pineal and extra-pineal melatonin production in the central nervous system following a neuroinflammatory response. These results have direct implications concerning the differential susceptibility of specific brain areas to neuronal death. PMID:24363121

  17. Melatonin prolonged release: in the treatment of insomnia in patients aged ?55 years.

    Science.gov (United States)

    Lyseng-Williamson, Katherine A

    2012-11-01

    Melatonin prolonged release (PR) 2 mg is approved for the treatment of primary insomnia characterized by poor sleep quality in patients aged ?55 years in the EU and elsewhere. Patients may receive treatment with melatonin PR for up to 13 weeks. Production of endogenous nocturnal melatonin, which helps regulate circadian rhythm, may be decreased in older adults. Administration of melatonin PR 2 mg 1-2 h before bedtime mimics the natural secretion pattern of melatonin, thereby leading to improvements in the circadian regulation of the sleep-wake cycle. In older adults, melatonin PR 2 mg 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 10 mg alone or in combination with melatonin PR 2 mg. In 3-week and 6-month, randomized, double-blind clinical trials in patients with primary insomnia aged ?55 years, melatonin PR 2 mg 1-2 h before bedtime was associated with significant improvements relative to placebo in many sleep and daytime parameters, including sleep quality and latency, morning alertness and health-related quality of life. Melatonin PR 2 mg was very well tolerated in clinical trials in older patients, with a tolerability profile that was similar to that of placebo. Short- or longer-term treatment with melatonin PR 2 mg was not associated with dependence, tolerance, rebound insomnia or withdrawal symptoms. PMID:23044640

  18. The Melatonin Receptor Agonist Ramelteon Effectively Treats Insomnia and Behavioral Symptoms in Autistic Disorder

    OpenAIRE

    Kentaro Kawabe; Fumie Horiuchi; Yasunori Oka; Shu-ichi Ueno

    2014-01-01

    Children with autism spectrum disorders (ASD), including autistic disorder, frequently suffer from comorbid sleep problems. An altered melatonin rhythm is considered to underlie the impairment in sleep onset and maintenance in ASD. We report three cases with autistic disorder in whom nocturnal symptoms improved with ramelteon, a selective melatonin receptor agonist. Insomnia and behavior, assessed using the Clinical Global Impression-Improvement Scale, improved in two cases with 2?mg ramelt...

  19. Melatonin treatment in an institutionalised child with psychomotor retardation and an irregular sleep-wake pattern

    OpenAIRE

    Pillar, G.; Etzioni, A.; Shahar, E.; Lavie, P.

    1998-01-01

    An institutionalised 13 year old girl with psychomotor retardation suffered from an irregular sleep-wake pattern. Multiple measurements of urinary sulphatoxymelatonin (aMT6) concentrations were abnormally low, without any significant day-night differences. Administration of exogenous melatonin (3 mg) at 18:00 resulted in increased nocturnal urinary aMT6 concentrations and improvements in her sleep-wake pattern. Melatonin may help disabled children suffering from sleep disorders.?...

  20. Effects of time of L-ornithine administration on the diurnal rhythms of plasma growth hormone, melatonin, and corticosterone levels in mice.

    Science.gov (United States)

    Matsuo, Haruka; Iwamoto, Ayaka; Otsuka, Tsuyoshi; Hishida, Yukihiro; Akiduki, Saori; Aoki, Mami; Furuse, Mitsuhiro; Yasuo, Shinobu

    2015-03-01

    The synthesis and secretion of many hormones such as growth hormone (GH), melatonin, and corticosterone, exhibit temporal variations over each day and night. Oral administration of several nutritional factors, including L-ornithine, modulates these hormonal secretions and induces an acute increase in plasma GH levels. However, the impact of L-ornithine on the diurnal rhythms of hormone secretion remains unclear. In this study, we evaluated whether the diurnal rhythms of plasma GH, melatonin, and corticosterone secretion were altered by the daily administration of L-ornithine as well as the timing of the administration, in CBA/N mice. Our results showed that the plasma GH levels that peaked at light phase were amplified by L-ornithine (500?mg/kg) administered at Zeitgeber time (ZT) 22, but not at ZT10. Additionally, L-ornithine (1000?mg/kg) administered at ZT22 advanced the onset of the nocturnal rise of melatonin, which resulted in the elongation of the melatonin peak. On the other hand, L-ornithine (500 and 1000?mg/kg) administered at ZT10, but not at ZT22, suppressed the diurnal rhythm peaks of plasma corticosterone. The effects of L-ornithine on plasma GH rhythms lasted for at least 2 days after cessation of the daily administration. Running wheel activity during the active phase was slightly elevated by L-ornithine administration at ZT22, but the overall patterns were only slightly affected. L-Ornithine levels in the plasma and hypophysis after a single administration of L-ornithine at ZT22 were lower than those after administration at ZT10, suggesting that the metabolic rate of L-ornithine differs between day and night. In conclusion, our data suggest that a daily administration of L-ornithine regulates the diurnal rhythms of GH, melatonin, and corticosterone in a manner dependent on administration time, which might be related to the diurnal rhythms of L-ornithine metabolism. PMID:25286138

  1. Melatonin and the skeleton

    DEFF Research Database (Denmark)

    Amstrup, A K; Sikjaer, T

    2013-01-01

    Melatonin may affect bone metabolism through bone anabolic as well as antiresorptive effects. An age-related decrease in peak melatonin levels at nighttime is well documented, which may increase bone resorption and bone loss in the elderly. In vitro, melatonin reduces oxidative stress on bone cells by acting as an antioxidant. Furthermore, melatonin improves bone formation by promoting differentiation of human mesenchymal stem cell (hMSC) into the osteoblastic cell linage. Bone resorption is reduced by increased synthesis of osteoprogeterin (OPG), a decoy receptor that prevents receptor activator of NK-?B ligand (RANKL) in binding to its receptor. Moreover, melatonin is believed to reduce the synthesis of RANKL preventing further bone resorption. In ovariectomized as well as nonovariectomized rodents, melatonin has shown beneficial effects on bone as assessed by biochemical bone turnover markers, DXA, and ?CT scans. Furthermore, in pinealectomized animals, bone mineral density (BMD) is significantly 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.

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

    Directory of Open Access Journals (Sweden)

    Vigo DE

    2012-10-01

    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

  3. Possible Role of Exogenous Melatonin and Melatonin-Receptor-Agonists in the Treatment of Menopause?Associated Sleep Disturbances

    OpenAIRE

    Amnon Brzezinski

    2014-01-01

    One of the core symptoms of the menopausal transition is sleep disturbance. Peri-menopausal women often complain of difficulties initiating and/or maintaining sleep with frequent nocturnal and early morning awakenings. Factors that may play a role in this type of insomnia include vasomotor symptoms and changing reproductive hormone levels, circadian rhythm abnormalities, primary insomnia, mood disorders, coexistent medical conditions, and lifestyle. Exogenous melatonin ...

  4. Postnatal development of female sheep pineal gland under natural inhibitory photoperiods: an immunocytochemical and physiological (melatonin concentration) study

    OpenAIRE

    Redondo, E.; Regodo?n, S.; Masot, A. J.; Ga?zquez, A.; Franco, A.

    2003-01-01

    The purpose of this study was to determine structural and immunocytochemical changes taking place during the day and at night in developing sheep pineal gland under natural non-stimulatory photoperiods (summer solstice). Additionally, the diurnal cycle of plasma melatonin levels was charted and differences between diurnal and nocturnal pineal melatonin concentrations were analyzed. 36 ewes of three different ages were examined: infants (1-6 months old), puberta...

  5. Melatonin Promotes Superovulation in Sika Deer (Cervus nippon

    Directory of Open Access Journals (Sweden)

    Liang Wang

    2014-07-01

    Full Text Available In this study, the effects of melatonin (MT on superovulation and reproductive hormones (melatonin, follicle-stimulating hormone (FSH, luteinizing hormone (LH and PRL were investigated in female sika deer. Different doses (40 or 80 mg/animal of melatonin were subcutaneously implanted into deer before the breeding season. Exogenous melatonin administration significantly elevated the serum FSH levels at the time of insemination compared with levels in control animals. During superovulation, the serum LH levels in donor sika deer reached their highest values (7.1 ± 2.04 ng/mL at the point of insemination, compared with the baseline levels (4.98 ± 0.07 ng/mL in control animals. This high level of LH was sustained until the day of embryo recovery. In contrast, the serum levels of PRL in the 80 mg of melatonin-treated group were significantly lower than those of control deer. The average number of corpora lutea in melatonin-treated deer was significantly higher than that of the control (p < 0.05. The average number of embryos in the deer treated with 40 mg of melatonin was higher than that of the control; however, this increase did not reach significant difference (p > 0.05, which may be related to the relatively small sample size. In addition, embryonic development in melatonin-treated groups was delayed.

  6. Radioimmunoassay for Melatonin

    International Nuclear Information System (INIS)

    A radioimmunoassay for melatonin has been developed and used to measure the level of melatonin of male and post-menopausal female patients coming to operation for benign and malignant conditions. The amount of melatonin in the serum of the females was considerably lower than that in males. No difference could be found between patients suffering from benign and malignant conditions. A patient with a non-parenchymatous pineal tumour had considerably lower levels in the serum at three months after surgery and radiotherapy. A further month later melatonin could not be found in samples of serum taken over a 24-hour period. (author)

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

    OpenAIRE

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

    2011-01-01

    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.

  8. Melatonin feedback on clock genes: a theory involving the proteasome.

    Science.gov (United States)

    Vriend, Jerry; Reiter, Russel J

    2015-01-01

    The expression of 'clock' genes occurs in all tissues, but especially in the suprachiasmatic nuclei (SCN) of the hypothalamus, groups of neurons in the brain that regulate circadian rhythms. Melatonin is secreted by the pineal gland in a circadian manner as influenced by the SCN. There is also considerable evidence that melatonin, in turn, acts on the SCN directly influencing the circadian 'clock' mechanisms. The most direct route by which melatonin could reach the SCN would be via the cerebrospinal fluid of the third ventricle. Melatonin could also reach the pars tuberalis (PT) of the pituitary, another melatonin-sensitive tissue, via this route. The major 'clock' genes include the period genes, Per1 and Per2, the cryptochrome genes, Cry1 and Cry2, the clock (circadian locomotor output cycles kaput) gene, and the Bmal1 (aryl hydrocarbon receptor nuclear translocator-like) gene. Clock and Bmal1 heterodimers act on E-box components of the promoters of the Per and Cry genes to stimulate transcription. A negative feedback loop between the cryptochrome proteins and the nucleus allows the Cry and Per proteins to regulate their own transcription. A cycle of ubiquitination and deubiquitination controls the levels of CRY protein degraded by the proteasome and, hence, the amount of protein available for feedback. Thus, it provides a post-translational component to the circadian clock mechanism. BMAL1 also stimulates transcription of REV-ERB? and, in turn, is also partially regulated by negative feedback by REV-ERB?. In the 'black widow' model of transcription, proteasomes destroy transcription factors that are needed only for a particular period of time. In the model proposed herein, the interaction of melatonin and the proteasome is required to adjust the SCN clock to changes in the environmental photoperiod. In particular, we predict that melatonin inhibition of the proteasome interferes with negative feedback loops (CRY/PER and REV-ERB?) on Bmal1 transcription genes in both the SCN and PT. Melatonin inhibition of the proteasome would also tend to stabilize BMAL1 protein itself in the SCN, particularly at night when melatonin is naturally elevated. Melatonin inhibition of the proteasome could account for the effects of melatonin on circadian rhythms associated with molecular timing genes. The interaction of melatonin with the proteasome in the hypothalamus also provides a model for explaining the dramatic 'time of day' effect of melatonin injections on reproductive status of seasonal breeders. Finally, the model predicts that a proteasome inhibitor such as bortezomib would modify circadian rhythms in a manner similar to melatonin. PMID:25369242

  9. Timely administration of melatonin accelerates reentrainment to phase-shifted light-dark cycles in the field mouse Mus booduga.

    Science.gov (United States)

    Sharma, V K; Singaravel, M; Subbaraj, R; Chandrashekaran, M K

    1999-03-01

    The effect of melatonin on the rate of reentrainment after a 6 h phase delay and a 6 h phase advance in the light-dark (LD) cycle was assayed in the nocturnal field mouse Mus booduga. After a phase delay of 6 h in the LD cycle, a single dose of melatonin (1 mg/kg) was administered for three consecutive days at about CT4 (circadian time 4). After a phase advance of 6 h in the LD cycle, melatonin was administered for three consecutive days at about CT22. Melatonin was found to accelerate reentrainment in both cases. Melatonin-treated animals took significantly fewer cycles to reentrain compared to vehicle-treated (50% dimethylsulfoxide [DMSO]) and nontreated control animals. PMID:10219488

  10. Melatonin-related genes expressed in the mouse uterus during early gestation promote embryo implantation.

    Science.gov (United States)

    He, Changjiu; Wang, Jing; Li, Yu; Zhu, Kuanfeng; Xu, Zhiyuan; Song, Yile; Song, Yukun; Liu, Guoshi

    2015-04-01

    Melatonin, a superior antioxidant, is an important molecule which regulates female reproduction due to its receptor-mediated and receptor-independent antioxidant actions. In this study, we investigated the effect of melatonin on early gestation in a mouse model. During early gestation, the expression of the melatonin's rate-limiting enzyme, AANAT, gradually increased - in the uterus while the MT2 melatonin receptor was only expressed at day 2 of gestation and no MT1 was detected. Based on these findings, we conducted a melatonin injection experiment which demonstrated that 15 mg/kg melatonin significantly improved the number of implantation sites and the litter size. Also, the blastocyst and uterus were collected to identify the local action of melatonin. In the melatonin-treated mice, the endometrium was thicker than in the control mice; melatonin also caused an increase in density of uterine glands, and the uterine gland index (UGI) was significantly elevated over that of the control. Serum steroid hormone measurements revealed that at day 6 of gestation (postimplantation), melatonin significantly downregulated the E2 level, with no obvious effects on progesterone. Gene expression assay revealed that melatonin significantly upregulated expression of HB-EGF, a crucial gene involved in implantation as well as its receptor ErbB1 in the blastocyst. In addition, PRA, an important gene which influences the decidual response and luminal cell differentiation, p53, which regulates uterine through leukaemia inhibitory factor (LIF), were both increased after melatonin treatment. These data suggest that melatonin and its MT2 receptor influence early gestation. Exogenous melatonin treatment can improve mouse embryo implantation and litter size, which may have important applications in human reproductive health and animal husbandry. PMID:25689975

  11. Melatonin promotes superovulation in sika deer (Cervus nippon).

    Science.gov (United States)

    Wang, Liang; Zhuo, Zhi-Yong; Shi, Wen-Qing; Tan, Dun-Xian; Gao, Chao; Tian, Xiu-Zhi; Zhang, Lu; Zhou, Guang-Bin; Zhu, Shi-En; Yun, Peng; Liu, Guo-Shi

    2014-01-01

    In this study, the effects of melatonin (MT) on superovulation and reproductive hormones (melatonin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and PRL) were investigated in female sika deer. Different doses (40 or 80 mg/animal) of melatonin were subcutaneously implanted into deer before the breeding season. Exogenous melatonin administration significantly elevated the serum FSH levels at the time of insemination compared with levels in control animals. During superovulation, the serum LH levels in donor sika deer reached their highest values (7.1±2.04 ng/mL) at the point of insemination, compared with the baseline levels (4.98±0.07 ng/mL) in control animals. This high level of LH was sustained until the day of embryo recovery. In contrast, the serum levels of PRL in the 80 mg of melatonin-treated group were significantly lower than those of control deer. The average number of corpora lutea in melatonin-treated deer was significantly higher than that of the control (p0.05), which may be related to the relatively small sample size. In addition, embryonic development in melatonin-treated groups was delayed. PMID:25007067

  12. Is pineal melatonin released in the third ventricle in humans? A study in movement disorders.

    Science.gov (United States)

    Leston, J; Harthé, C; Mottolese, C; Mertens, P; Sindou, M; Claustrat, B

    2015-01-01

    In order to determine sources and metabolism of melatonin in human cerebrospinal fluid (CSF), melatonin and 6-sulfatoxymelatonin (aMT6S) concentrations were measured in CSF sampled during neurosurgery in both lateral and third ventricles in patients displaying movement disorder (Parkinson's disease, essential tremor, dystonia or dyskinesia) and compared with their plasma levels. Previous determinations in nocturnal urine had showed that the patients displayed melatonin excretion in the normal range, compared with healthy controls matched according to age. A significant difference in melatonin concentration was observed between lateral and third ventricles, with the highest levels in the third ventricle (8.75±2.75pg/mL vs. 3.20±0.33pg/mL, P=0.01). CSF aMT6s levels were similar in both ventricles and of low magnitude, less than 5pg/mL. They were not correlated with melatonin levels or influenced by the area of sampling. Melatonin levels were significantly higher in third ventricle than in the plasma, whereas there was no difference between plasma and lateral ventricle levels. These findings show that melatonin may enter directly the CSF through the pineal recess in humans. The physiological meaning of these data remains to be elucidated. PMID:24975205

  13. A Multicenter, Placebo-controlled Trial of Melatonin for Sleep Disturbance in Alzheimer’s Disease

    Science.gov (United States)

    Singer, Clifford; Tractenberg, Rochelle E.; Kaye, Jeffrey; Schafer, Kim; Gamst, Anthony; Grundman, Michael; Thomas, Ronald; Thal, Leon J.

    2015-01-01

    Objectives To determine the safety and efficacy of 2 dose formulations of melatonin for the treatment of insomnia in patients with Alzheimer’s disease. Design A multicenter, randomized, placebo-controlled clinical trial of 2 dose formulations of oral melatonin coordinated by the National Institute of Aging-funded Alzheimer’s Disease Cooperative Study. Subjects with Alzheimer’s disease and nighttime sleep disturbance were randomly assigned to 1 of 3 treatment groups: placebo, 2.5-mg slow-release melatonin, or 10-mg melatonin. Setting Private homes and long-term care facilities. Participants 157 individuals were recruited by 36 Alzheimer’s disease research centers. Subjects with a diagnosis of Alzheimer’s disease were eligible if they averaged less than 7 hours of sleep per night (as documented by wrist actigraphy) and had 2 or more episodes per week of nighttime awakenings reported by the caregiver. Measurements Nocturnal total sleep time, sleep efficiency, wake-time after sleep onset, and day-night sleep ratio during 2- to 3-week baseline and 2-month treatment periods. Sleep was defined by an automated algorithmic analysis of wrist actigraph data. Results No statistically significant differences in objective sleep measures were seen between baseline and treatment periods for the any of the 3 groups. Nonsignificant trends for increased nocturnal total sleep time and decreased wake after sleep onset were observed in the melatonin groups relative to placebo. Trends for a greater percentage of subjects having more than a 30-minute increase in nocturnal total sleep time in the 10-mg melatonin group and for a decline in the day-night sleep ratio in the 2.5-mg sustained-release melatonin group, compared to placebo, were also seen. On subjective measures, caregiver ratings of sleep quality showed improvement in the 2.5-mg sustained-release melatonin group relative to placebo. There were no significant differences in the number or seriousness of adverse events between the placebo and melatonin groups. Conclusions Based on actigraphy as an objective measure of sleep time, melatonin is not an effective soporific agent in people with Alzheimer’s disease. PMID:14655926

  14. Nocturnal panic attacks

    Directory of Open Access Journals (Sweden)

    Lopes Fabiana L.

    2002-01-01

    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.

  15. Nocturn and Aubade

    OpenAIRE

    Morteza Dehghani

    2012-01-01

    Nocturne After such a meandering historyOf ramblingAlong water and up the stepsAnd steps and down the treesAnd trees and across the waterAnd round and round the waterfall and fountainAnd kaleidoscopic...

  16. Nocturnal intermittent hemodialysis.

    Science.gov (United States)

    Thumfart, Julia; Müller, Dominik

    2015-05-01

    Preemptive renal transplantation is the method of choice for end stage renal disease in childhood and adolescence. However, without preemptive transplantation, waiting time for kidney transplantation might exceed several years. The poor quality of life and the extremely high morbidity and mortality rates of dialysis patients have led to the development of intensified hemodialysis programs in which the modes of dialysis (short daily, nocturnal intermittent or daily nocturnal) are different. Such programs have been shown to significantly improve several uremia-associated parameters, such as blood pressure, phosphate control, anemia and growth retardation, in both adult and pediatric (children and adolescents) patients and lead to a reduction in medications, including phosphate binders, erythropoietin and antihypertensive agents. Fluid limitations and dietary restrictions can also be lifted. With respect to psychosocial rehabilitation and quality of life, nocturnal intermittent dialysis programs provide a reasonable compromise of all forms of intensified programs. Experiences and practical approaches of our own in-center nocturnal intermittent hemodialysis program in the light of the recent publications are described in this review. PMID:25103600

  17. Role of melatonin on diabetes-related metabolic disorders

    Directory of Open Access Journals (Sweden)

    Javier Espino

    2011-01-01

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

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

    Science.gov (United States)

    Gooneratne, Nalaka S; Edwards, Alena Y Z; Zhou, Chen; Cuellar, Norma; Grandner, Michael A; Barrett, Jeffrey S

    2012-05-01

    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 (2mg) melatonin in a combined immediate release/controlled release dose, especially in older adults who may also exhibit altered melatonin disposition. To assess this, we conducted a randomized, double-blind, placebo-controlled study of low-dose (0.4mg) and high-dose (4.0mg) melatonin (25% immediate release+75% controlled release) in 27 older adults with insomnia complaints and low endogenous melatonin levels to determine whether melatonin pharmacokinetic properties differ between these two doses. The time to maximum level (1.3hrs versus 1.5hrs), elimination half-life (1.8hrs versus 2.1hrs), and apparent total clearance (379L/hr versus 478L/hr) did not differ significantly between the low- and high-dose arms, respectively. The maximum concentration was 405?±93pg/mL for the low-dose arm and 3999±700pg/mL for the high-dose arm, both of which are substantially higher than physiologic melatonin levels for this age group. In addition, subjects in the high-dose arm maintained melatonin levels >50pg/mL for an average of 10hrs, which could result in elevated melatonin levels beyond the typical sleep period. Renal and liver function parameters remained stable after 6wks of treatment. The linear pharmacokinetic behavior of melatonin observed in the elderly can form the basis for future studies exploring a wider range of dosing scenarios to establish exposure-response relationships for melatonin-mediated sleep outcomes. PMID:22348451

  19. Melatonin protection from chronic, low-level ionizing radiation.

    Science.gov (United States)

    Reiter, Russel J; Korkmaz, Ahmet; Ma, Shuran; Rosales-Corral, Sergio; Tan, Dun-Xian

    2011-12-15

    In the current survey, we summarize the published literature which supports the use of melatonin, an endogenously produced molecule, as a protective agent against chronic, low-level ionizing radiation. Under in vitro conditions, melatonin uniformly was found to protect cellular DNA and plasmid super coiled DNA from ionizing radiation damage due to Cs(137) or X-radiation exposure. Likewise, in an in vivo/in vitro study in which humans were given melatonin orally and then their blood lymphocytes were collected and exposed to Cs(137) ionizing radiation, nuclear DNA from the cells of those individuals who consumed melatonin (and had elevated blood levels) was less damaged than that from control individuals. In in vivo studies as well, melatonin given to animals prevented DNA and lipid damage (including limiting membrane rigidity) and reduced the percentage of animals that died when they had been exposed to Cs(137) or Co(60) radiation. Melatonin's ability to protect macromolecules from the damage inflicted by ionizing radiation likely stems from its high efficacy as a direct free radical scavenger and possibly also due to its ability to stimulate antioxidative enzymes. Melatonin is readily absorbed when taken orally or via any other route. Melatonin's ease of self administration and its virtual absence of toxicity or side effects, even when consumed over very long periods of time, are essential when large populations are exposed to lingering radioactive contamination such as occurs as a result of an inadvertent nuclear accident, an intentional nuclear explosion or the detonation of a radiological dispersion device, i.e., a "dirty" bomb. PMID:22185900

  20. Disruption of melatonin circadian rhythm production is related to multiple sclerosis severity: A preliminary study.

    Science.gov (United States)

    Damasceno, Alfredo; Moraes, Adriel Santos; Farias, Alessandro; Damasceno, Benito Pereira; Dos Santos, Leonilda Maria Barbosa; Cendes, Fernando

    2015-06-15

    Sunlight can influence the immune system independently of vitamin D, such as through melatonin production in the pineal gland. Inflammatory disorders can suppress nocturnal melatonin production, but only a few studies have investigated melatonin status in multiple sclerosis (MS). We aimed to study melatonin production in association with clinical and immunological data in MS patients. Eleven treated relapsing-remitting MS (RRMS) patients and eight controls underwent neurological examination and were assessed for fatigue severity and depressive symptoms. Inflammatory cytokines were analyzed in blood samples and concentration of 6-sulfatoxymelatonin (6-SMT) was determined in 24h urine. Patients with an abnormal proportion of overnight 6-SMT (n=8, 72.7%) had higher disability and fatigue severity (p<0.05). Overnight 6-SMT was inversely related with fatigue severity (p=0.016), number of relapses in the previous 12months (p=0.010) and EDSS scores (p=0.049). In conclusion, disruption of melatonin circadian rhythm production is frequent among RRMS patients and seemingly related to higher disability and fatigue scores. Future studies with larger sample size are necessary to establish melatonin status as a biomarker of disease severity in MS. PMID:25930714

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

    DEFF Research Database (Denmark)

    Ucar, Ebru; Lehtinen, Emilia K

    2012-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Fooladsaz K

    2004-06-01

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

  3. Melatonin labelled by hydrogen isotopes

    International Nuclear Information System (INIS)

    Isotope exchange of melatonin with deuterium (D2O) and tritium (HTO) oxides under different conditions is studied. Simplicity of isotope exchange of hydrogens of the indole ring of melatonin in the acidic medium decreases in series H4>H2>H6>>H7, that permits to suggest the way of melatonin preparation labelled by hydrogen isotopes in positions 4,6 and 2 of the indole ring. The way of melatonin preparation labelled by hydrogen isotopes in position 2 according to the reaction of desulfation 2-(2,4-dinitrophenylsulphenyl) melatonin at catalyst Ni(Re)(D) is suggested

  4. Melatonin phase advances circadian rhythm.

    OpenAIRE

    Attenburrow, ME; Dowling, BA; Sargent, PA; Sharpley, AL; Cowen, PJ

    1995-01-01

    We studied the effect of acute (1 day) and subacute (7 days) treatment with melatonin (0.5 mg) on the endogenous rhythms of melatonin secretion in 12 healthy male volunteers, using a placebo-controlled, double-blind, cross-over design. Melatonin given at 1700 h for 7 days significantly advanced the onset of endogenous melatonin secretion, while a single dose was without effect. These data are consistent with the hypothesis that melatonin plays a role in the organisation of circadian rhythms i...

  5. Melatonin labeled with hydrogen isotopes

    International Nuclear Information System (INIS)

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

  6. Melatonin for the newborn

    Directory of Open Access Journals (Sweden)

    Lucia Marseglia

    2014-06-01

    Full Text Available Reactive oxygen species play an important role in the pathogenesis of several diseases during the perinatal and neonatal period. Melatonin, an effective direct free-radical scavenger and indirect antioxidant agent, diffuses through biological membranes easily and exerts pleiotropic actions on every cell. Several studies have tested the efficacy of melatonin to counteract oxidative damage in diseases of newborn such as chronic lung disease, perinatal brain injury, necrotizing enterocolitis and sepsis, giving promising results. The peculiar perinatal susceptibility to oxidative stress indicates that prophylactic use of antioxidants as melatonin could help to prevent or at least reduce oxidative stress related diseases in newborns. However, more studies are needed to confirm these beneficial effects. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  7. Paroxysmal nocturnal hemoglobinuria.

    Science.gov (United States)

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

    2005-01-01

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

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

    Scientific Electronic Library Online (English)

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

    2008-10-01

    Full Text Available Disturbed sleep is common in chronic obstructive pulmonary disease (COPD). Conventional hypnotics worsen nocturnal hypoxemia and, in severe cases, can lead to respiratory failure. Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions. 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.

  9. Antitumour activity of melatonin in a mouse model of human prostate cancer: relationship with hypoxia signalling.

    Science.gov (United States)

    Paroni, Rita; Terraneo, Laura; Bonomini, Francesca; Finati, Elena; Virgili, Eleonora; Bianciardi, Paola; Favero, Gaia; Fraschini, Franco; Reiter, Russel J; Rezzani, Rita; Samaja, Michele

    2014-08-01

    Melatonin is known to exert antitumour activity in several types of human cancers, but the underlying mechanisms as well as the efficacy of different doses of melatonin are not well defined. Here, we test the hypothesis whether melatonin in the nanomolar range is effective in exerting antitumour activity in vivo and examine the correlation with the hypoxia signalling mechanism, which may be a major molecular mechanism by which melatonin antagonizes cancer. To test this hypothesis, LNCaP human prostate cancer cells were xenografted into seven-wk-old Foxn1nu/nu male mice that were treated with melatonin (18 i.p. injections of 1 mg/kg in 41 days). Saline-treated mice served as control. We found that the melatonin levels in plasma and xenografted tissue were 4× and 60× higher, respectively, than in control samples. Melatonin tended to restore the redox imbalance by increasing expression of Nrf2. As part of the phenotypic response to these perturbations, xenograft microvessel density was less in melatonin-treated animals, indicative of lower angiogenesis, and the xenograft growth rate was slower (P < 0.0001). These changes were accompanied by a reduced expression of Ki67, elevated expression of HIF-1? and increased phosphorylation of Akt in melatonin than saline-treated mice. We conclude that the beneficial effect of melatonin in reducing cancer growth in vivo was evident at melatonin plasma levels as low as 4 nm and was associated with decreased angiogenesis. Higher HIF-1? expression in xenograft tissue indicates that the antitumour effect cannot be due to a postulated antihypoxic effect, but may stem from lower angiogenesis potential. PMID:24786921

  10. Endogenous melatonin and oxidatively damaged guanine in DNA

    Directory of Open Access Journals (Sweden)

    Poulsen Henrik E

    2009-10-01

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

  11. Modulation of antioxidant status, carbohydrate and lipid metabolism by melatonin on streptozotocin induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Mirunalini Sankaran*

    2012-08-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Melatonin, “synchronizer of the biological clock” is major hormones secreted from the pineal gland have various therapeutic effects. The present study was designed to explore the modulatory effect of melatonin on antioxidant status, glucose and lipid metabolism in streptozotocin (STZ induced diabetic rats. Male Wistar rats weighing 180-200 g were made diabetic by administration of streptozotocin (STZ (40 mg/kg body weight intraperitoneally. Melatonin was administered intraperitoneally at a dose of 2 mg/kg body weight to STZ-induced diabetic rats for 30 days. Body weight, blood glucose, carbohydrate metabolic enzyme, lipid profile, antioxidant and lipid peroxidation status were assessed. The level of the blood glucose, carbohydrate metabolic enzymes (glucose-6-phosphatase and fructose-1,6-bisphosphatase and lipid peroxidative marker (TBARS were increased in STZ induced diabetic rats while the melatonin treatment revert back to the near normal condition. In contrast, administered melatonin resulted in an increased in body weight and insulin secretion in diabetic rats. The enzymatic antioxidants (SOD, CAT and GPX and non-enzymatic antioxidants (GSH, vitamin C and vitamin E were also increased by melatonin treatment. The cholesterol and phospholipids which were elevated in diabetic rats were normalized by the melatonin administration. Hence these findings indicate that melatonin protects against STZ induced oxidative stress and thus explain its use in treatment of diabetes by modulating lipid and glucose metabolism.

  12. Melatonin: Buffering the Immune System

    Directory of Open Access Journals (Sweden)

    Juan M. Guerrero

    2013-04-01

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

  13. Melatonin Poisoning: A Case Report

    Directory of Open Access Journals (Sweden)

    Mehmet Gül

    2012-10-01

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

  14. Role of Melatonin in Schizophrenia

    OpenAIRE

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

    2013-01-01

    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...

  15. Behavioral Treatment for Nocturnal Enuresis

    Science.gov (United States)

    Friman, Patrick C.; Jones, Kevin M.

    2005-01-01

    Nocturnal enuresis is one of the most prevalent and distressing of all childhood problems. The treatment of nocturnal enuresis has shifted in the past few decades from a strictly psychopathological perspective to a biobehavioral perspective. Although the primary clinical features of this disorder are medical/organic, there is currently strong…

  16. Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

    Directory of Open Access Journals (Sweden)

    Maria Angeles Bonmati-Carrion

    2014-12-01

    Full Text Available Currently, in developed countries, nights are excessively illuminated (light at night, whereas daytime is mainly spent indoors, and thus people are exposed to much lower light intensities than under natural conditions. In spite of the positive impact of artificial light, we pay a price for the easy access to light during the night: disorganization of our circadian system or chronodisruption (CD, including perturbations in melatonin rhythm. Epidemiological studies show that CD is associated with an increased incidence of diabetes, obesity, heart disease, cognitive and affective impairment, premature aging and some types of cancer. Knowledge of retinal photoreceptors and the discovery of melanopsin in some ganglion cells demonstrate that light intensity, timing and spectrum must be considered to keep the biological clock properly entrained. Importantly, not all wavelengths of light are equally chronodisrupting. Blue light, which is particularly beneficial during the daytime, seems to be more disruptive at night, and induces the strongest melatonin inhibition. Nocturnal blue light exposure is currently increasing, due to the proliferation of energy-efficient lighting (LEDs and electronic devices. Thus, the development of lighting systems that preserve the melatonin rhythm could reduce the health risks induced by chronodisruption. This review addresses the state of the art regarding the crosstalk between light and the circadian system.

  17. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

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

  18. Hepatoprotective actions of melatonin: Possible mediation by melatonin receptors

    Directory of Open Access Journals (Sweden)

    Alexander M Mathes

    2010-12-01

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

  19. The function of nocturnal transpiration

    Science.gov (United States)

    Pfautsch, Sebastian; Resco de Dios, Víctor; Loik, Michael; Tissue, David

    2014-05-01

    Nocturnal transpiration is an important source of water loss, accounting for up to 25% of daytime transpiration in some species. Nocturnal water losses cannot be explained under the prevailing 'paradigm' of optimizing carbon gain while minimizing water loss because carbon fixation does not occur at night. Alternative explanations regarding the function and potential evolutionary advantage of nocturnal transpiration have been proposed, such as enhanced nutrient uptake and transport or delivery of O2 to parenchyma cells for respiration. However, recent evidence suggests that the role of nocturnal transpiration in supplementing the overall plant nutrient budget is relatively small, and the O2 hypothesis is difficult to test experimentally. Here, we propose that the main function of nocturnal transpiration (and water transport) is to prevent catastrophic xylem failure by restoring depleted stem 'capacitors' and enhancing early morning CO2 uptake, as stomata 'prepare' for daytime conditions. Nocturnal sap flux was highest in Eucalyptus grandis trees in the field following a heat wave (reaching 47C with VPDs > 8kPa in the daytime) generating maximal daytime water losses compared with cooler and lower VPD periods, indicating the importance of nocturnal stomatal conductance for stem refilling. Moreover, we observed that the time for stomata to respond to light early in the morning (dawn) across 25 different genotypes of E. camaldulensis in a glasshouse was shortest in those genotypes with highest nocturnal stomatal conductance, which was also correlated with higher daytime photosynthesis. This observation is consistent with previous observations that nocturnal stomatal conductance is partially controlled by the clock, which is utilised to anticipate daytime conditions. Data from the literature suggests that eucalypts respond similarly to other C3 species, suggesting that mechanisms regulating night-time transpiration may be universal.

  20. Nocturnal Seizures” in Idiopathic Pulmonary Arterial Hypertension

    OpenAIRE

    Izzo, Anthony; Mcsweeney, Julia; Kulik, Thomas; Khatwa, Umakanth; Kothare, Sanjeev V.

    2013-01-01

    The usual differential diagnoses of nocturnal events in children include parasomnias, nocturnal seizures, nocturnal reflux (Sandifer syndrome), hypnic jerks, periodic limb movements of sleep, and sleep disordered breathing. We report a previously healthy young girl who presented to the sleep clinic for evaluation of nocturnal events which were diagnosed as medically refractory nocturnal seizures. It was not until a syncopal event occurred in the daytime, which prompted referral for cardiac ev...

  1. MELATONIN: A PLEIOTROPIC MOLECULE REGULATING INFLAMMATION

    OpenAIRE

    Radogna, Flavia; Diederich, Marc; Ghibelli, Lina

    2010-01-01

    Abstract Melatonin is a neurohormone produced by the pineal gland that regulates sleep and circadian functions. Melatonin also regulates inflammatory and immune processes acting as both an activator and inhibitor of these responses. Melatonin demonstrates endocrine, but also paracrine and autocrine effects in the leukocyte compartment: on one side, leukocytes respond to melatonin in a circadian fashion; on the other side, leukocytes are able to synthesize melatonin by themselves. W...

  2. Homeobox Genes and Melatonin Synthesis: Regulatory Roles of the Cone-Rod Homeobox Transcription Factor in the Rodent Pineal Gland

    OpenAIRE

    Kristian Rohde; Xf Ller, Morten M.; Martin Fredensborg Rath

    2014-01-01

    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processe...

  3. Myocardial infarction and nocturnal hypoxaemia

    Directory of Open Access Journals (Sweden)

    Pen?i? Biljana

    2007-01-01

    Full Text Available 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 pulse oximetry and 24-hour electrocardiography. Patients were divided into two groups according to nocturnal hypoxaemia. Total number of ventricular premature complex (VPC; maximal VPC/h; incidence of VPC Lown class>2 and occurrence of ST-segment depression were analyzed for nocturnal (10 PM to 6 AM, daytime (6 AM to 22 PM periods and for the entire 24 hours. Results. Both groups were similar in age, gender, standard risk factors, myocardial infarction size and did not differ in VPC during the analyzed periods. The number of nocturnal maximal VPC/h was insignificantly greater in group 1 (with hypoxaemia compared to group 2 (without hypoxaemia, (p=0.084. Maximal VPC/h did not differ significantly either for daytime or for 24 hours among the groups. Nocturnal VPC Lown>2 were significantly more frequent in group 1 (25% vs 0%, p=0.002. The incidence of VPC Lown>2 was similar during the daytime, and during 24 hrs in both groups. Occurrence of ST-segment depression did not differ between groups 1 and 2. Conclusion. Nocturnal hypoxaemia was associated with complex nocturnal ventricular arrhythmias in patients with MI. .

  4. Distinct Expression Profiles of Three Melatonin Receptors during Early Development and Metamorphosis in the Flatfish Solea senegalensis

    Science.gov (United States)

    Lan-Chow-Wing, Olivier; Confente, Francesca; Herrera-Pérez, Patricia; Isorna, Esther; Chereguini, Olvido; Rendón, Maria del Carmen; Falcón, Jack; Muñoz-Cueto, José A.

    2014-01-01

    Melatonin actions are mediated through G protein-coupled transmembrane receptors. Recently, mt1, mt2, and mel1c melatonin receptors were cloned in the Senegalese sole. Here, their day-night and developmental expressions were analyzed by quantitative PCR. These results revealed distinct expression patterns of each receptor through development. mel1c transcripts were more abundant in unfertilized ovulated oocytes and declined during embryonic development. mt1 and mt2 expression was higher at the earliest stages (2–6 days post-fertilization), decreasing before (mt2) or during (mt1) metamorphosis. Only mt1 and mel1c expression exhibited day-night variations, with higher nocturnal mRNA levels. These results suggest different roles and transcriptional regulation of these melatonin receptors during flatfish development and metamorphosis. PMID:25402642

  5. Monosymptomatic nocturnal enuresis

    Directory of Open Access Journals (Sweden)

    Bertan Karabo?a

    2012-03-01

    Full Text Available Enuresis Nocturna is the most common urologic problemin childhood. There is not a consensus about terminology.Terminology identified by The International Children’sContinence Society (ICCS is recommended. Bed-wettingat night during sleep (incontinence in children above 5years of age who don’t have congenital or acquired centralnervous system defect is defined as enuresis nocturna.There are two groups monosymptomatic (simpleand non-monosymptomatic (complicated. Monosymptomaticenuresis nocturna (MNE has no symptoms otherthan bed-wetting at night during sleep. Various theoriesconcerning etiology of MNE has been suggested; one ormore of genetic, hormonal, bladder associated and sleepdisorders are stated to play a role. Self-improvement canbe achieved each year by 15% increasing maturity. Underpinning treatment and in addition to this unique treatmentmust be done by considering the factors in the pathophysiology.The success of the treatment and roadmapto be followed must be arrange with child and family. Thepurpose of this eclectic is; evaluation of correct diagnosis,differential diagnosis, patient follow-up and treatment optionsof the cases applicant with nocturnal enuresis basedon the current knowledge of ICCS and Turkey EnuresisTreatment Guide.

  6. Mood Disorders, Circadian Rhythms, Melatonin and Melatonin Agonists

    OpenAIRE

    M.A. Quera Salva; Hartley, S.

    2012-01-01

    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...

  7. Hepatoprotective actions of melatonin: Possible mediation by melatonin receptors

    OpenAIRE

    Alexander M Mathes

    2010-01-01

    Melatonin, the hormone of darkness and messenger of the photoperiod, is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone’s intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo, a...

  8. Monosymptomatic nocturnal enuresis is associated with abnormal nocturnal bladder emptying

    DEFF Research Database (Denmark)

    HagstrØm, SØren; Kamperis, K

    2004-01-01

    PURPOSE: We investigate the nature of enuresis episodes in monosymptomatic nocturnal enuresis using a fluid provocation model. MATERIALS AND METHODS: The study included 18 children 7 to 13 years old with monosymptomatic nocturnal enuresis. Based on basal home recordings patients were subgrouped into those with a normal nocturnal urine output and those with nocturnal polyuria (mean nocturnal urine production on wet nights exceeding 130% of functional bladder capacity, normal functional bladder capacity for age provided). Children were admitted to the hospital for 4 consecutive nights. After an adaptation night all children received orally 25 ml/kg water, 30 minutes before bedtime on the remaining 3 nights. A cordless alarm device enabled registration of enuretic episodes from another room and diapers allowed the measurement of enuresis volumes. Post-void residual volumes were measured by ultrasound. Pelvic floor electromyography was continuously recorded throughout the night, and its association to bladder emptying was investigated. RESULTS: A total of 95 enuresis and 14 nocturia episodes were recorded. Significantly more enuresis episodes were registered on nights with oral fluid load, whereas no increase in number of nocturia episodes was seen. Of the enuresis episodes 46 were associated with incomplete bladder emptying (post-void residual volume greater than 10% of total bladder volume at time of enuresis). No difference between patient groups regarding post-void residual volume was seen. Abnormal bursts of electromyography activity were associated with incomplete micturitions. CONCLUSIONS: Enuresis nocturna episodes in polyuric and nonpolyuric patients are frequently incomplete micturitions. The present findings question the definition of nocturnal enuresis episode as normal complete voiding.

  9. Melatonin in pathogenesis and therapy of cancer

    Directory of Open Access Journals (Sweden)

    Ravindra T

    2006-12-01

    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.

  10. Nocturnal aircraft noise effects.

    Science.gov (United States)

    Basner, M; Samel, A

    2004-01-01

    Noise protection associated with the construction and extension of airports in the Federal Republic of Germany has been regulated by the law for protection against aircraft noise since 1971. This legislation is due for revision because of different aspects. One aspect is the growth of air traffic which has led many airports to the limits of their capacity and in search of new ways of adaptation to the increasing demand for flight services. Another aspect is the increasing concern of the population about noise effects which has to be addressed by better protection against the effects of aircraft noise. The framework conditions of policy in terms of society as a whole, its health and economic environment need to be put into effect by political action. Science can contribute to this goal by performing noise effects research and by providing recommendations to the political body. However, it remains controversial, what measures are necessary or adequate to assure effective protection of the population against aircraft noise. This is particularly true for the protection of rest and sleep at night. The problem of finding a common basis for adequate recommendations is associated with (1) the low number of primary studies, which also exhibited highly variable results and assessments, (2) the handling of acoustic or psycho-acoustic dimensions for quantifying psychological or physiological reactions, and (3) the conception of how far preventive measures have to go to prove effective. With this in mind, the DLR Institute for Aerospace Medicine is conducting a large-scale, multi-stage study for investigating the acute effects of nocturnal aircraft noise on human sleep. This enterprise is implemented in the framework of the HGF/DLR project "Quiet Air Traffic" for developing sustainable assessment criteria for human-specific effects of aircraft noise at night. PMID:15070533

  11. Multi-Modal Treatment of Nocturnal Enuresis.

    Science.gov (United States)

    Mohr, Caroline; Sharpley, Christopher F.

    1988-01-01

    The article reports a multimodal treatment of nocturnal enuresis and anxious behavior in a mildly mentally retarded woman. Behavioral treatment and removal of caffeine from the subject's diet eliminated both nocturnal enuresis and anxious behavior. (Author/DB)

  12. The Angiotensin-Melatonin Axis

    OpenAIRE

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

    2013-01-01

    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 ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-03-15

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

  14. The role of melatonin in radiation induced biochemical disturbances in brain and thyroid gland in adult male albino rats

    International Nuclear Information System (INIS)

    Radiation induced changes in adult male albino male rats before and after melatonin administration were monitored to detect some biochemical changes in brain and thyroid gland. The parameters monitored were dopamine (DA), norepinephdne (NE) and gamma aminobutyric acid (GABA) in brain and triiodothyronine (T3) thyroxine (T4) and thyroid stimulating hormone (TSH) in serum of irradiated adult male albino rats before and after intraperitoneal injection of melatonin. Results indicated that 6.0 Gy whole body ?-irradiated rats showed gradual and significant decrease in DA, NE and GABA contents in different brain areas under investigation (cerebellum, pons+medulla oblongata, corpus striatum, cerebral cortex, hypothalamus, midbrain and hippocampus). The maximum effect of whole body ?-irradiation was observed after 21 days. Moreover, gradual and significant decrease in serum T3 and T4 levels were recorded after ?-irradiation. However, TSH level showed significant elevation throughout the experimental period. Melatonin at a dose level of 15 mg/kg b.wt. was intraperitoneally injected daily 30 minutes after 6.0 Gy whole body ?-irradiation, ameliorated DA, NE and GABA contents in different brain areas compared to those measured in irradiated rats. Moreover, melatonin gradually attenuated the effect of ?-irradiation on serum T3 and T4 levels to reach nearly the control level at day 21 after melatonin injection. Ht day 21 after melatonin injection. However, melatonin ameliorated the elevated TSH level induced by ?-irradiation to reach its corresponding control value at day 21

  15. Melatonin: new places in therapy.

    Science.gov (United States)

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

    2007-12-01

    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

  16. Tritiation of melatonin by several methods

    International Nuclear Information System (INIS)

    The hormone melatonin acts at several G protein-linked receptors to cause a myriad of significant physiological effects. The tritiation of melatonin at high specific activity and characterization of it with tritium NMR for biological testing is reported. (author)

  17. Protective Effect of Melatonin on Acute Pancreatitis

    OpenAIRE

    Jaworek, Jolanta; Szklarczyk, Joanna; Jaworek, Andrzej K.; Nawrot-pora?bka, Katarzyna; Leja-szpak, Anna; Bonior, Joanna; Kot, Michalina

    2012-01-01

    Melatonin, a product of the pineal gland, is released from the gut mucosa in response to food ingestion. Specific receptors for melatonin have been detected in many gastrointestinal tissues including the pancreas. Melatonin as well as its precursor, L-tryptophan, attenuates the severity of acute pancreatitis and protects the pancreatic tissue from the damage caused by acute inflammation. The beneficial effect of melatonin on acute pancreatitis, which has been reported in many experimental stu...

  18. Melatonin Metabolism in the Central Nervous System

    OpenAIRE

    Hardeland, Ru?diger

    2010-01-01

    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...

  19. Melatonin in pathogenesis and therapy of cancer

    OpenAIRE

    Ravindra T; Lakshmi N; Ahuja Y

    2006-01-01

    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, ...

  20. Melatonin formation in mammals: In vivo perspectives

    OpenAIRE

    Chattoraj, Asamanja; Liu, Tiecheng; Zhang, Liang Samantha; Huang, Zheping; Borjigin, Jimo

    2009-01-01

    Melatonin is a hormone secreted from the pineal gland specifically at night and contributes to a wide array of physiological functions in mammals. Melatonin is one of the most well understood output of the circadian clock located in the suprachiasmatic nucleus. Melatonin synthesis is controlled distally via the circadian clock located in the suprachiasmatic nucleus and proximally regulated by norepinephrine released in response to the circadian clock signals. To understand melatonin synthesis...

  1. Melatonin: a possible link between the presence of artificial light at night and reductions in biological fitness.

    Science.gov (United States)

    Jones, Therésa M; Durrant, Joanna; Michaelides, Ellie B; Green, Mark P

    2015-05-01

    The mechanisms underpinning the ecological impacts of the presence of artificial night lighting remain elusive. One suspected underlying cause is that the presence of light at night (LAN) supresses nocturnal production of melatonin, a key driver of biological rhythm and a potent antioxidant with a proposed role in immune function. Here, we briefly review the evidence for melatonin as the link between LAN and changes in behaviour and physiology. We then present preliminary data supporting the potential for melatonin to act as a recovery agent mitigating the negative effects of LAN in an invertebrate. Adult crickets (Teleogryllus commodus), exposed to constant illumination, were provided with dietary melatonin (concentrations: 0, 10 or 100 µg ml(-1)) in their drinking water. We then compared survival, lifetime fecundity and, over a 4-week period, immune function (haemocyte concentration, lysozyme-like and phenoloxidase (PO) activity). Melatonin supplementation was able only partially to mitigate the detrimental effects of LAN: it did not improve survival or fecundity or PO activity, but it had a largely dose-dependent positive effect on haemocyte concentration and lysozyme-like activity. We discuss the implications of these relationships, as well as the usefulness of invertebrates as model species for future studies that explore the effects of LAN. PMID:25780235

  2. Short-wavelength enrichment of polychromatic light enhances human melatonin suppression potency.

    Science.gov (United States)

    Brainard, George C; Hanifin, John P; Warfield, Benjamin; Stone, Marielle K; James, Mary E; Ayers, Melissa; Kubey, Alan; Byrne, Brenda; Rollag, Mark

    2015-04-01

    The basic goal of this research is to determine the best combination of light wavelengths for use as a lighting countermeasure for circadian and sleep disruption during space exploration, as well as for individuals living on Earth. Action spectra employing monochromatic light and selected monochromatic wavelength comparisons have shown that short-wavelength visible light in the blue-appearing portion of the spectrum is most potent for neuroendocrine, circadian, and neurobehavioral regulation. The studies presented here tested the hypothesis that broad spectrum, polychromatic fluorescent light enriched in the short-wavelength portion of the visible spectrum is more potent for pineal melatonin suppression in healthy men and women. A total of 24 subjects were tested across three separate experiments. Each experiment used a within-subjects study design that tested eight volunteers to establish the full-range fluence-response relationship between corneal light irradiance and nocturnal plasma melatonin suppression. Each experiment tested one of the three types of fluorescent lamps that differed in their relative emission of light in the short-wavelength end of the visible spectrum between 400 and 500 nm. A hazard analysis, based on national and international eye safety criteria, determined that all light exposures used in this study were safe. Each fluence-response curve demonstrated that increasing corneal irradiances of light evoked progressively increasing suppression of nocturnal melatonin. Comparison of these fluence-response curves supports the hypothesis that polychromatic fluorescent light is more potent for melatonin regulation when enriched in the short-wavelength spectrum. PMID:25726691

  3. Electric power, melatonin, and breast cancer

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

    Halladin, Natalie L; Busch, Sarah EkelØf

    2014-01-01

    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.

  5. Melatonin regulates splenocytes proliferation via IP3-dependent intracellular Ca2+ release in seasonally breeding bird, Perdicula asiatica.

    Science.gov (United States)

    Kumar Yadav, Sanjeev; Haldar, Chandana; Kumar Singh, Sunil; Dash, Debabrata

    2014-08-01

    Melatonin plays an important role in the immune regulation of birds. Both endogenous and exogenous melatonin modulates lymphocyte proliferation via its speci?c membrane receptors, Mel(1a), Mel(1b) and Mel(1c), though the mechanisms behind this process are poorly understood. We investigated the di?erences in melatonin membrane receptor Mel(1a), Mel(1b) and Mel(1c) expression by western blot and reverse transcription reaction and the in vitro e?ect of melatonin on the intracellular Ca(2+) concentration ([Ca2+]i) in splenocytes of the Indian Jungle Bush Quail, Perdicula asiatica. We used a non-selective melatonin receptor antagonist for Mel(1a) and Mel(1b), luzindole, and the selective Mel(1b) blocker, 4P-PDOT to check the specific role of melatonin receptor on ([Ca2+]i). The expression of Mel(1a), Mel(1b) and Mel(1c) receptors mRNA and protein was upregulated by melatonin (10(-7)?M) with a significant high rise in ([Ca2+]i), which was differentially blocked by supplementation of antagonist, luzindole (10(-7)?M) and 4P-PDOT (10(-7)?M). Furthermore, we noted in vitro effect of melatonin and 2-aminoethoxydiphenyl borate (2-APB), a cell-permeable antagonist of inositol 1, 4, 5-trisphosphate (IP3) receptor to check the rise in ([Ca2+]i) through the IP3 pathway. Significantly low ([Ca2+]i) was noted in melatonin and 2-APB pretreated splenocytes when compared with splenocytes where 2-APB was absent. Thus, our data suggest that melatonin through its membrane receptor induced the elevation of ([Ca2+]i) via IP(3)-dependent pathway for splenocyte proliferation in P. asiatica. PMID:24512472

  6. Treatment of nocturnal eating disorders.

    Science.gov (United States)

    Howell, Michael J; Schenck, Carlos H

    2009-09-01

    Identifying abnormal nocturnal eating is critically important for patient care and public health. Obesity is a global pandemic and a leading cause of preventable mortality in the United States, with more than 100,000 deaths annually. Normally, nighttime energy homeostasis is maintained, despite an absence of food intake, through appetite suppression and alterations in glucose metabolism that result in stable energy stores. Two conditions break this nighttime fast and are associated with weight gain as well as medical and neuropsychiatric comorbidities. Sleep-related eating disorder (SRED) is characterized by isolated nocturnal eating, whereas the night-eating syndrome (NES) is a circadian delay in meal timing leading to evening hyperphagia, nocturnal eating, and morning anorexia. Recently, SRED has been associated with the benzodiazepine receptor agonist zolpidem. Both SRED and NES are treatable and represent potentially reversible forms of obesity. In SRED, the antiseizure medication topiramate and dopaminergics have both demonstrated promising results. Nocturnal eating associated with NES has responded well to sertraline. PMID:19744399

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

    Directory of Open Access Journals (Sweden)

    José Antonio Muñoz-Cueto

    2013-04-01

    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.

  8. Radioimmunoassay for melatonin in human serum

    International Nuclear Information System (INIS)

    Goat antisera raised against N-acetyl-5-methoxytryptophan conjugated to bovine thyroglobulin by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide is utilized in a radioimmunoassay for melatonin. The raised antibodies are coupled to Sepharose 4B and melatonin in human serum is isolated by affinity chromatography, thereby avoiding the time-consuming extractions by organic solvents. A detection limit of 1.9 pg (8.2x10-15 mol)melatonin is achieved. The antibody specificity has been analysed and none of the common melatonin analogues influence this method of melatonin measurement. (Auth.)

  9. Melatonin, immune function and aging

    Directory of Open Access Journals (Sweden)

    Perumal SR Pandi

    2005-11-01

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

  10. Melatonin Anticancer Effects: Review

    Directory of Open Access Journals (Sweden)

    Luigi Di Bella

    2013-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Eckhard Mühlbauer

    2013-03-01

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

  12. Effect of indomethacin on desmopressin resistant nocturnal polyuria and nocturnal enuresis

    DEFF Research Database (Denmark)

    Kamperis, Konstantinos; Rittig, SØren

    2012-01-01

    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.

  13. Pharmacology and function of melatonin receptors

    International Nuclear Information System (INIS)

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

  14. Nocturnal Enuresis and its Impact on Growth

    OpenAIRE

    AmirAli Ghahramani; Mahdi Basirymoghadam; Mohammad Ghahramani

    2008-01-01

    Objective: Nocturnal enuresis is a common developmental-behavioral problem in children. The present study was conducted to estimate the prevalence of primary nocturnal enuresis and to determine its impact on physical growth of the first grade elementary school children. Material & Methods: This is a cross-sectional study carried out on 350 first-grade children (6 to 6.5 yr old) elementary schools in Gonabad through random stratified sampling. All children had primary nocturnal enuresis. A que...

  15. Fundamental Issues Related to the Origin of Melatonin and Melatonin Isomers during Evolution: Relation to Their Biological Functions

    OpenAIRE

    Dun-Xian Tan; Xiaodong Zheng; Jin Kong; Manchester, Lucien C.; Ruediger Hardeland; Seok Joong Kim; Xiaoying Xu; Reiter, Russel J.

    2014-01-01

    Melatonin and melatonin isomers exist and/or coexist in living organisms including yeasts, bacteria and plants. The levels of melatonin isomers are significantly higher than that of melatonin in some plants and in several fermented products such as in wine and bread. Currently, there are no reports documenting the presence of melatonin isomers in vertebrates. From an evolutionary point of view, it is unlikely that melatonin isomers do not exist in vertebrates. On the other hand, large quantit...

  16. Melatonin Improves mitochondrial function by promoting MT1/SIRT1/PGC-1 alpha-dependent mitochondrial biogenesis in cadmium-induced hepatotoxicity in vitro.

    Science.gov (United States)

    Guo, Pan; Pi, Huifeng; Xu, Shangcheng; Zhang, Lei; Li, Yuming; Li, Min; Cao, Zhengwang; Tian, Li; Xie, Jia; Li, Renyan; He, Mindi; Lu, Yonghui; Liu, Chuan; Duan, Weixia; Yu, Zhengping; Zhou, Zhou

    2014-11-01

    Melatonin is an indolamine synthesized in the pineal gland that has a wide range of physiological functions, and it has been under clinical investigation for expanded applications. Increasing evidence demonstrates that melatonin can ameliorate cadmium-induced hepatotoxicity. However, the potentially protective effects of melatonin against cadmium-induced hepatotoxicity and the underlying mechanisms of this protection remain unclear. This study investigates the protective effects of melatonin pretreatment on cadmium-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. We exposed HepG2 cells to different concentrations of cadmium chloride (2.5, 5, and 10 ?M) for 12 h. We found that Cd stimulated cytotoxicity, disrupted the mitochondrial membrane potential, increased reactive oxygen species production, and decreased mitochondrial mass and mitochondrial DNA content. Consistent with this finding, Cd exposure was associated with decreased Sirtuin 1 (SIRT1) protein expression and activity, thus promoted acetylation of PGC-1 alpha, a key enzyme involved in mitochondrial biogenesis and function, although Cd did not disrupt the interaction between SIRT1 and PGC-1 alpha. However, all cadmium-induced mitochondrial oxidative injuries were efficiently attenuated by melatonin pretreatment. Moreover, Sirtinol and SIRT1 siRNA each blocked the melatonin-mediated elevation in mitochondrial function by inhibiting SIRT1/ PGC-1 alpha signaling. Luzindole, a melatonin receptor antagonist, was found to partially block the ability of melatonin to promote SIRT1/ PGC-1 alpha signaling. In summary, our results indicate that SIRT1 plays an essential role in the ability of moderate melatonin to stimulate PGC-1 alpha and improve mitochondrial biogenesis and function at least partially through melatonin receptors in cadmium-induced hepatotoxicity. PMID:25159133

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

    Science.gov (United States)

    Cavalcanti, Paula Regina Aguiar

    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; p<.01). Actigraphic analysis during the wake phase demonstrated that diabetic subjects showed lower levels of activity (p=.02). Additionally, there was a significant difference decrease in sleep 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.

  18. 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)

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

    1039-10-01

    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.

  19. The Impact of Melatonin on Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    Zeynep Arzu Ye?in

    2009-12-01

    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

  20. Melatonin Attenuates Intermittent Hypoxia-Induced Lipid Peroxidation and Local Inflammation in Rat Adrenal Medulla

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2014-10-01

    Full Text Available Chronic intermittent hypoxia (CIH induces lipid peroxidation and leads to cardiovascular dysfunction, in which impaired activities of the adrenal medulla are involved. This may be caused by CIH-induced injury in the adrenal medulla, for which the mechanism is currently undefined. We tested the hypothesis that melatonin ameliorates the CIH-induced lipid peroxidation, local inflammation and cellular injury in rat adrenal medulla. Adult Sprague–Dawley rats were exposed to air (normoxic control or hypoxia mimicking a severe recurrent sleep apnoeic condition for 14 days. The injection of melatonin (10 mg/kg or vehicle was given before the daily hypoxic treatment. We found that levels of malondialdehyde and nitrotyrosine were significantly increased in the vehicle-treated hypoxic group, when compared with the normoxic control or hypoxic group treated with melatonin. Also, the protein levels of antioxidant enzymes (superoxide dismutase (SOD-1 and SOD-2 were significantly lowered in the hypoxic group treated with vehicle but not in the melatonin group. In addition, the level of macrophage infiltration and the expression of inflammatory cytokines (tumor necrosis factor (TNF-?, interleukin (IL-1? and IL-6 and mediators (inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (COX-2 were elevated in the vehicle-treated hypoxic group, but were significantly ameliorated by the melatonin treatment. Moreover, the amount of apoptotic cells in the hypoxic groups was significantly less in the melatonin-treated group. In conclusion, CIH-induced lipid peroxidation causes local inflammation and cellular injury in the adrenal medulla. The antioxidant and anti-inflammatory actions of melatonin are indicative of a protective agent against adrenal damage in patients with severe obstructive sleep apnea syndrome.

  1. The Impact of Melatonin on Glucose Homeostasis

    OpenAIRE

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

    2009-01-01

    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 ti...

  2. Dietary factors and fluctuating levels of melatonin

    OpenAIRE

    Katri Peuhkuri; Nora Sihvola; Riitta Korpela

    2012-01-01

    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 l...

  3. Nocturnal drainage wind characteristics in two converging air sheds

    International Nuclear Information System (INIS)

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

  4. Melatonin receptors: Current status, facts, and hypothesis

    International Nuclear Information System (INIS)

    Great progress has been made in the identification of melatonin binding sites, commonly identified as melatonin receptors by many authors, in recent years. The bulk of these studies have investigated the sites using either autoradiographic and biochemical techniques with the majority of the experiments being done on the rat, Djungarian and Syrian hamster, and sheep, although human tissue has also been employed. Many of the studies have identified melatonin binding in the central nervous system with either tritium- or iodine-labelled ligands. The latter ligand seems to provide the most reproducible and consistent data. Of the central neural tissues examined, the suprachiasmatic nuclei are most frequently mentioned as a location for melatonin binding sites although binding seems to be widespread in the brain. The other tissue that has been prominently mentioned as a site for melatonin binding is the pars tuberalis of the anterior pituitary gland. There may be time-dependent variations in melatonin binding densities in both neural and pituitary gland tissue. Very few attempts have been made to identify melatonin binding outside of the central nervous system despite the widespread actions of melatonin. Preliminary experiments have been carried out on the intracellular second messengers which mediate the actions of melatonin

  5. Homeobox genes and melatonin synthesis : regulatory roles of the cone-rod homeobox transcription factor in the rodent pineal gland

    DEFF Research Database (Denmark)

    Rohde, Kristian; MØller, Morten

    2014-01-01

    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX) transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating cAMP response element-based circadian melatonin production.

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

    International Nuclear Information System (INIS)

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

  7. Sleep and psychological disturbance in nocturnal asthma

    OpenAIRE

    Stores, G.; Ellis, A.; Wiggs, L.; Crawford, C.; Thomson, A.

    1998-01-01

    Subjective and objective sleep disturbance was studied in children with nocturnal asthma. Relations between such disturbance and daytime psychological function were also explored, including possible changes in learning and behaviour associated with improvements in nocturnal asthma and sleep. Assessments included home polysomnography, parental questionnaires concerning sleep disturbance, behaviour, and mood and cognitive testing. Compared with matched controls, children with ...

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

    Scientific Electronic Library Online (English)

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

    2000-10-01

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

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

    OpenAIRE

    Eckhard Mühlbauer; Ina Bähr; Elmar Peschke

    2013-01-01

    The pineal hormone melatonin exerts its influence in the periphery through activation of two specific trans-membrane receptors: MT1 and MT2. Both isoforms are expressed in the islet of Langerhans and are involved in the modulation of insulin secretion from ?-cells and in glucagon secretion from ?-cells. De-synchrony of receptor signaling may lead to the development of type 2 diabetes. This notion has recently been supported by genome-wide association studies identifying particularly the MT2...

  10. Melatonin improves experimental colitis with sleep deprivation.

    Science.gov (United States)

    Park, Young-Sook; Chung, Sook-Hee; Lee, Seong-Kyu; Kim, Ja-Hyun; Kim, Jun-Bong; Kim, Tae-Kyun; Kim, Dong-Shin; Baik, Haing-Woon

    2015-04-01

    Sleep deprivation (SD) is an epidemic phenomenon in modern countries, and its harmful effects are well known. SD acts as an aggravating factor in inflammatory bowel disease. Melatonin is a sleep-related neurohormone, also known to have antioxidant and anti-inflammatory effects in the gastrointestinal tract; however, the effects of melatonin on colitis have been poorly characterized. Thus, in this study, we assessed the measurable effects of SD on experimental colitis and the protective effects of melatonin. For this purpose, male imprinting control region (ICR) mice (n = 24) were used; the mice were divided into 4 experimental groups as follows: the control, colitis, colitis with SD and colitis with SD and melatonin groups. Colitis was induced by the administration of 5% dextran sulfate sodium (DSS) in the drinking water for 6 days. The mice were sleep-deprived for 3 days. Changes in body weight, histological analyses of colon tissues and the expression levels of pro-inflammatory cytokines and genes were evaluated. SD aggravated inflammation and these effects were reversed by melatonin in the mice with colitis. In addition, weight loss in the mice with colitis with SD was significantly reduced by the injection of melatonin. Treatment with melatonin led to high survival rates in the mice, in spite of colitis with SD. The levels of pro-inflammatory cytokines, such as interleukin (IL)-1?, IL-6, IL-17, interferon-? and tumor necrosis factor-?, in the serum of mice were significantly increased by SD and reduced by melatonin treatment. The melatonin-treated group showed a histological improvement of inflammation. Upon gene analysis, the expression of the inflammatory genes, protein kinase C? (PKC?) and calmodulin 3 (CALM3), was increased by SD, and the levels decreased following treatment with melatonin. The expression levels of the apoptosis-related inducible nitric oxide synthase (iNOS) and wingless-type MMTV integration site family, member 5A (Wnt5a) genes was decreased by SD, but increased following treatment with melatonin. Treatment with melatonin reduced weight loss and prolonged survival in mice with colitis with SD. Melatonin exerted systemic anti-inflammatory effects. Gene analysis revealed a possible mechanism of action of melatonin in inflammation and sleep disturbance. Thus, melatonin may be clinically applicable for patients with inflammatory bowel disease, particularly those suffering from sleep disturbances. PMID:25625560

  11. 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

  12. Comparative analysis of the protective effects of melatonin and caffeic acid phenethyl ester (CAPE) on mobile phone-induced renal impairment in rat.

    Science.gov (United States)

    Ozguner, Fehmi; Oktem, Faruk; Armagan, Abdullah; Yilmaz, Ramazan; Koyu, Ahmet; Demirel, Reha; Vural, Huseyin; Uz, Efkan

    2005-08-01

    Melatonin and caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, were recently found to be potent free radical scavengers and antioxidants. There are a number of reports on the effects induced by electromagnetic radiation (EMR) in various cellular systems. Mechanisms of adverse effects of EMR indicate that reactive oxygen species may play a role in the biological effects of this radiation. The present study was carried out to compare the protective effects of melatonin and CAPE against 900 MHz EMR emitted mobile phone-induced renal tubular injury. Melatonin was administered whereas CAPE was given for 10 days before the exposure. Urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury) and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of oxidative stress-induced renal impairment in rats exposed to EMR. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Urinary NAG and renal MDA were increased in EMR exposed rats while both melatonin and CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD and GSH-Px activities were decreased in EMR exposed animals while melatonin caused a significant increase in the activities of these antioxidant enzymes but CAPE did not. Melatonin caused a significant decrease in urinary NAG activity and MDA levels which were increased because of EMR exposure. CAPE also reduced elevated MDA levels in EMR exposed renal tissue, but the effect of melatonin was more potent than that of CAPE. Furthermore, treatment of EMR exposed rats with melatonin increased activities of SOD and GSH-Px to higher levels than those of control rats. In conclusion, melatonin and CAPE prevent renal tubular injury by reducing oxidative stress and protect the kidney from oxidative damage induced by 900 MHz mobile phone. Nevertheless, melatonin seems to be a more potent antioxidant compared with CAPE in kidney. PMID:16132682

  13. Melatonin attenuates neutrophil inflammation and mucus secretion in cigarette smoke-induced chronic obstructive pulmonary diseases via the suppression of Erk-Sp1 signaling.

    Science.gov (United States)

    Shin, In-Sik; Shin, Na-Rae; Park, Ji-Won; Jeon, Chan-Mi; Hong, Ju-Mi; Kwon, Ok-Kyoung; Kim, Joong-Sun; Lee, In-Chul; Kim, Jong-Choon; Oh, Sei-Ryang; Ahn, Kyung-Seop

    2015-01-01

    The incidence of chronic obstructive pulmonary disease (COPD) has substantially increased in recent decade. Cigarette smoke (CS) is the most important risk factor in the development of COPD. In this study, we investigated the effects of melatonin on the development of COPD using a CS and lipopolysaccharide (LPS)-induced COPD model and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells, a human mucoepidermoid carcinoma cell. On day 4, the mice were treated intranasally with LPS. The mice were exposed to CS for 1 hr per day (8 cigarettes per day) from day 1 to day 7. Melatonin (10 or 20 mg/kg) was injected intraperitoneally 1 hr before CS exposure. Melatonin markedly decreased the neutrophil count in the BALF, with reduction in the proinflammatory mediators and MUC5AC. Melatonin inhibited Erk phosphorylation and Sp1 expression induced by CS and LPS treatment. Additionally, melatonin decreased airway inflammation with a reduction in myeloperoxidase expression in lung tissue. In in vitro experiments, melatonin suppressed the elevated expression of proinflammatory mediators induced by CSC treatment. Melatonin reduced Erk phosphorylation and Sp1 expression in CSC-stimulated H292 cells. In addition, cotreatment of melatonin and Erk inhibitors significantly limited the proinflammatory mediators with greater reductions in Erk phosphorylation and Sp1 expression than that observed in H292 cells treated with Erk inhibitor alone. Taken together, melatonin effectively inhibited the neutrophil airway inflammation induced by CS and LPS treatment, which was closely related to downregulation of Erk phosphorylation. These findings suggest that melatonin has a therapeutic potential for the treatment of COPD. PMID:25388990

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

    Science.gov (United States)

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

    2013-09-01

    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.

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

    DEFF Research Database (Denmark)

    Kücükakin, Bülent; Lykkesfeldt, Jens

    2008-01-01

    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.

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

    DEFF Research Database (Denmark)

    Kücükakin, Bülent; Lykkesfeldt, Jens

    2008-01-01

    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.

  17. Role of melatonin in embryo fetal development.

    Science.gov (United States)

    Voiculescu, S E; Zygouropoulos, N; Zahiu, C D; Zagrean, A M

    2014-01-01

    Melatonin is an indoleamine produced by the pineal gland and secreted in a circadian manner. In the past few decades, research over this topic has been enhanced. Melatonin has many important roles in the human physiology: regulator of the circadian rhythms, sleep inducer, antioxidant, anticarcinogenic. This paper reviews the involvement of melatonin in embryo fetal development. The pineal gland develops completely postpartum, so both the embryo and the fetus are dependent on the maternal melatonin provided transplacentally. Melatonin appears to be involved in the normal outcome of pregnancy beginning with the oocyte quality and finishing with the parturition. Its pregnancy night-time concentrations increase after 24 weeks of gestation, with significantly high levels after 32 weeks. Melatonin receptors are widespread in the embryo and fetus since early stages. There is solid evidence that melatonin is neuroprotective and has a positive effect on the outcome of the compromised pregnancies. In addition, chronodisruption leads to a reproductive dysfunction. Thus, the influence of melatonin on the developing human fetus may not be limited to the entertaining of circadian rhythmicity, but further studies are needed. PMID:25713608

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

    DEFF Research Database (Denmark)

    Ansel, L; Bolborea, M

    2010-01-01

    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.

  19. Therapeutic actions of melatonin on gastrointestinal cancer development and progression

    OpenAIRE

    Glenister, Rachael; McDaniel, Kelly; Francis, Heather; Venter, Julie; Jensen, Kendal; DUSIO, GIUSEPPINA; Gaudio, Eugenio; Glaser, Shannon; Meng, Fanyin; Alpini, Gianfranco

    2013-01-01

    Melatonin exerts a multitude of physiological functions including the regulation of the sleep cycle and circadian rhythm. Although the synthesis of melatonin in the pineal gland is regulated by changes in the light/dark cycle, the release of melatonin in the gastrointestinal tract is related to food consumption. Melatonin regulates antioxidative processes and it improves T-helper cell response by stimulating the production of specific cytokines. Melatonin is directly involved in preventing tu...

  20. Neurobiology, Pathophysiology, and Treatment of Melatonin Deficiency and Dysfunction

    OpenAIRE

    Hardeland, Rüdiger

    2012-01-01

    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...

  1. Melatonin-Based Therapeutics for Neuroprotection in Stroke

    OpenAIRE

    Borlongan, Cesar V.; Meaghan Staples; Kazutaka Shinozuka

    2013-01-01

    The present review paper supports the approach to deliver melatonin and to target melatonin receptors for neuroprotection in stroke. We discuss laboratory evidence demonstrating neuroprotective effects of exogenous melatonin treatment and transplantation of melatonin-secreting cells in stroke. In addition, we describe a novel mechanism of action underlying the therapeutic benefits of stem cell therapy in stroke, implicating the role of melatonin receptors. As we envision the clinical entry of...

  2. Novel non-indolic melatonin receptor agonists differentially entrain endogenous melatonin rhythm and increase its amplitude.

    Science.gov (United States)

    Drijfhout, W J; de Vries, J B; Homan, E J; Brons, H F; Copinga, S; Gruppen, G; Beresford, I J; Hagan, R M; Grol, C J; Westerink, B H

    1999-10-15

    In this study we have examined the ability of melatonin and four synthetic melatonin receptor agonists to entrain endogenous melatonin secretion in rats, free running in constant darkness. The circadian melatonin profile was measured by trans-pineal microdialysis, which not only reveals the time of onset and end of production (phase), but also the amplitude of the rhythm. Exogenous melatonin given at the onset of subjective darkness (clock time 12 h) was effective to entrain endogenous melatonin production. Only one agonist, 2-chloroacetamido-8-methoxytetralin (AH-017), mimicked this action. Two other agonists, 4-methoxy-2-(methylene propylamide)indan (GG-012) and N-[2-[2,3,7,8-tetrahydro-1H-furo(2, 3-g)indol-1-yl]ethyl]acetamide (GR196429), induced a phase-delay under free running conditions, possibly by increasing tau (tau) period. One agonist, 2-acetamido-8-methoxytetralin (AH-001) did not show any phase effect on the free running rhythm. Unexpectedly, all melatonin receptor agonists increased the amplitude of melatonin secretion. The amount of the increase varied from just below the level of significance (AH-001) to an approximately 2-fold increase (GG-012 and GR196429). This is in clear contrast to entrainment with melatonin, which significantly decreased the amplitude. It is hypothesized that entrainment and effects on amplitude of melatonin secretion are mediated by different mechanisms which can be differentially modulated using specific ligands. PMID:10556666

  3. Effects of exercise intensity and duration on nocturnal heart rate variability and sleep quality.

    Science.gov (United States)

    Myllymäki, Tero; Rusko, Heikki; Syväoja, Heidi; Juuti, Tanja; Kinnunen, Marja-Liisa; Kyröläinen, Heikki

    2012-03-01

    Acute physical exercise may affect cardiac autonomic modulation hours or even days during the recovery phase. Although sleep is an essential recovery period, the information on nocturnal autonomic modulation indicated by heart rate variability (HRV) after different exercises is mostly lacking. Therefore, this study investigated the effects of exercise intensity and duration on nocturnal HR, HRV, HR, and HRV-based relaxation, as well as on actigraphic and subjective sleep quality. Fourteen healthy male subjects (age 36 ± 4 years, maximal oxygen uptake 49 ± 4 ml/kg/min) performed five different running exercises on separate occasions starting at 6 p.m. with HR guidance at home. The effect of intensity was studied with 30 min of exercises at intensities corresponding to HR level at 45% (easy), 60% (moderate) and 75% (vigorous) of their maximal oxygen uptake. The effect of duration was studied with 30, 60, and 90 min of moderate exercises. Increased exercise intensity elevated nocturnal HR compared to control day (p sleep quality. The results suggest that increased exercise intensity and/or duration cause delayed recovery of nocturnal cardiac autonomic modulation, although long exercise duration was needed to induce changes in nocturnal HRV. Increased exercise intensity or duration does not seem to disrupt sleep quality. PMID:21667290

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

    Directory of Open Access Journals (Sweden)

    Terry PD

    2013-03-01

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

  5. Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

    Science.gov (United States)

    Ho Mien, Ivan; Chua, Eric Chern-Pin; Lau, Pauline; Tan, Luuan-Chin; Lee, Ivan Tian-Guang; Yeo, Sing-Chen; Tan, Sara Shuhui; Gooley, Joshua J

    2014-01-01

    Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n?=?24, 21-28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2) s(-1)), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n?=?8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P?=?0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light. PMID:24797245

  6. Melatonin agonists in primary insomnia and depression-associated insomnia: are they superior to sedative-hypnotics?

    Science.gov (United States)

    Srinivasan, Venkatramanujan; Brzezinski, Amnon; Pandi-Perumal, Seithikurippu R; Spence, D Warren; Cardinali, Daniel P; Brown, Gregory M

    2011-06-01

    Current pharmacological treatment of insomnia involves the use of sedative-hypnotic benzodiazepine and non-benzodiazepine drugs. Although benzodiazepines improve sleep, their multiple adverse effects hamper their application. Adverse effects include impairment of memory and cognitive functions, next-day hangover and dependence. Non-benzodiazepines are effective for initiating sleep but are not as effective as benzodiazepines for improving sleep quality or efficiency. Furthermore, their prolonged use produces adverse effects similar to those observed with benzodiazepines. Inasmuch as insomnia may be associated with decreased nocturnal melatonin, administration of melatonin is a strategy that has been increasingly used for treating insomnia. Melatonin can be effective for improving sleep quality without the adverse effects associated with hypnotic-sedatives. Ramelteon, a synthetic analog of melatonin which has a longer half life and a stronger affinity for MT1 and MT2 melatonergic receptors, has been reportedly effective for initiating and improving sleep in both adult and elderly insomniacs without showing hangover, dependence, or cognitive impairment. Insomnia is also a major complaint among patients suffering from depressive disorders and is often aggravated by conventional antidepressants especially the specific serotonin reuptake inhibitors. The novel antidepressant agomelatine, a dual action agent with affinity for melatonin MT1 and MT2 receptors and 5-HT2c antagonistic properties, constitutes a new approach to the treatment of major depressive disorders. Agomelatine ameliorates the symptoms of depression and improves the quality and efficiency of sleep. Taken together, the evidence indicates that MT1/MT2 receptor agonists like ramelteon or agomelatine may be valuable pharmacological tools for insomnia and for depression-associated insomnia. PMID:21453740

  7. 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 th 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

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

    OpenAIRE

    Rüdiger Hardeland

    2013-01-01

    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 a...

  9. Melatonin in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Jian-Zhi Wang

    2013-07-01

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

  10. Green Light for Nocturnally Migrating Birds

    OpenAIRE

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

    2008-01-01

    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...

  11. 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 theble 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

  12. MT1 melatonin receptors and their role in the oncostatic action of melatonin

    Directory of Open Access Journals (Sweden)

    Karolina Danielczyk

    2009-09-01

    Full Text Available Melatonin, the main hormone produced by the pineal gland, strongly inhibits the growth of cancer cells [i]in vitro[/i] and [i]in vivo[/i]. Some publications indicate that the addition of melatonin to culture medium slows the proliferation of some cancer cell lines. It is also suggested that melatonin used as an adjuvant benefits the effectiveness and tolerance of chemotherapy. The mechanisms of this are not fully understood, but melatonin receptors might be one of the most important elements. Two distinct types of membrane-bound melatonin receptors have been identified in humans: MT1 (Mel1a and MT2 (Mel1b receptors. These subtypes are 60?0homologous at the amino-acid level. MT1 receptors are G-protein-coupled receptors. Through the ? subunit of G protein, melatonin receptors stimulate an adenylate cyclase and decrease the level of cAMP. This has a significant influence on cell proliferation and has been confirmed in many tests on different cell lines, such as S-19, B-16 murine melanoma cells, and breast cancer cells. It seems that expression of the MT1 melatonin receptors benefits the efficacy of melatonin treatment. Melatonin and its receptors may provide a promising way to establish new alternative therapeutic approaches in human cancer prevention.

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

    OpenAIRE

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

    1986-01-01

    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...

  14. Induction of ecdysteroidogenesis, methyl farnesoate synthesis and expression of ecdysteroid receptor and retinoid X receptor in the hepatopancreas and ovary of the giant mud crab, Scylla serrata by melatonin.

    Science.gov (United States)

    Girish, B P; Swetha, Ch; Reddy, P Sreenivasula

    2015-01-01

    Melatonin, a chronobiotic molecule, is known to modulate several physiological functions in crustaceans including reproduction, molting and glucose homeostasis. In our earlier studies (Sainath and Reddy, 2010a), we observed hyperglycemia in crabs after melatonin administration and concluded that melatonin is another crustacean hyperglycemic hormone. In the current study, we have further examined the role of melatonin in regulating the levels of methyl farnesoate and ecdysteroid in the giant mud crab Scylla serrata and determined that melatonin indeed is a reproductive hormone. Further, we have determined partial nucleotide sequences of retinoid X receptor (RXR) and ecdysone receptor (EcR) in S. serrata and also studied the effect of melatonin on expression of these genes. Cloned RXR and EcR possess high sequence similarity with other Brachyuran genes. Administration of melatonin elevated circulatory methyl farnesoate (MF) and ecdysteroid levels in crabs. Since MF and ecdysteroid act through RXR and EcR respectively and these receptors are involved in the regulation of reproduction in crustaceans, we measured the expression levels of RXR and EcR in hepatopancreas and ovary after melatonin administration. The expression levels of both RXR and EcR increased significantly in the hepatopancreas and ovary of melatonin injected crabs when compared to the controls. In vitro culture of mandibular organ (MO) and Y-organ (YO) in the presence of melatonin resulted in a significant increase in the secretion of methyl farnesoate and ecdysteroid respectively. From the above studies it is clear that melatonin stimulates YO and MO, resulting in increased synthesis of ecdysteroids and methyl farnesoate, and thereby inducing reproduction in S. serrata. PMID:25989476

  15. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects.

    Science.gov (United States)

    Lemoine, Patrick; Nir, Tali; Laudon, Moshe; Zisapel, Nava

    2007-12-01

    Melatonin, secreted nocturnally by the pineal gland, is an endogenous sleep regulator. Impaired melatonin production and complaints on poor quality of sleep are common among the elderly. Non-restorative sleep (perceived poor quality of sleep) and subsequently poor daytime functioning are increasingly recognized as a leading syndrome in the diagnostic and therapeutic process of insomnia complaints. The effects of 3-weeks prolonged-release melatonin 2 mg (PR-melatonin) versus placebo treatment were assessed in a multi-center randomized placebo-controlled study in 170 primary insomnia outpatients aged > or =55 years. Improvements in quality of sleep (QOS) the night before and morning alertness (BFW) were assessed using the Leeds Sleep Evaluation Questionnaire and changes in sleep quality (QON) reported on five categorical unit scales. Rebound insomnia and withdrawal effects following discontinuation were also evaluated. PR-melatonin significantly improved QOS (-22.5 versus -16.5 mm, P = 0.047), QON (0.89 versus 0.46 units; P = 0.003) and BFW (-15.7 versus -6.8 mm; P = 0.002) compared with placebo. The improvements in QOS and BFW were strongly correlated (Rval = 0.77, P treatment effect on the restorative value of sleep. These results were confirmed in a subgroup of patients with a greater symptom severity. There was no evidence of rebound insomnia or withdrawal effects following treatment discontinuation. The incidence of adverse events was low and most side-effects were judged to be of minor severity. PR-melatonin is the first drug shown to significantly improve quality of sleep and morning alertness in primary insomnia patients aged 55 years and older-suggesting more restorative sleep, and without withdrawal symptoms upon discontinuation. PMID:18036082

  16. Nocturnal worsening of asthma and sleep-disordered breathing.

    Science.gov (United States)

    Bohadana, Abraham B; Hannhart, Bernard; Teculescu, Dan B

    2002-04-01

    Asthma has a tendency, to destabilize and get worse at night, probably due to a nocturnal increase in airiway inflammation and bronchial responsiveness. Nocturnal airway narrowing in asthma is often associated with sleep disorders, such as episodes of nocturnal and early morning awakening, difficulty in maintaining sleep, and day time sleepiness. On the other hand, an association has been documented between nocturnal sleep-disordered breathing and asthma. This review highlights the causes of nocturnal worsening of asthma and examines the evidence pointing toward a causal relationship between nocturnal asthma and sleep-disordered breathing. PMID:11990234

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

    Science.gov (United States)

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

    2012-03-01

    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

  18. Age dependent nitro-oxidative load and melatonin receptor expression in the spleen and immunity of goat Capra hircus.

    Science.gov (United States)

    Singh, Amaresh Kumar; Haldar, Chandana

    2014-12-01

    The decline in the plasma level of melatonin has been associated with increased oxidative stress in the physiological system while aging. The increased levels of oxidants are known to augment the nitro-oxidative stress, which induces the apoptotic factors in lymphoid organs leading to age dependent immunosenescence. There are no reports to date that can suggest how the age dependent nitro-oxidative stress can influence the melatonin membrane MT1/MT2R expression and immune status of any small ruminant. In the present study, we noted the expression of melatonin receptors MT1R and MT2R and inducible nitric oxide synthase (iNOS) along with the apoptotic markers (viz. Bcl-2, Bax and Pro-caspase-3) in the spleen of young, middle-aged and old-aged Indian goat Capra hircus. The lymphocyte proliferation was also recorded along with the total nitrite and nitrate ion concentration (NOx) in the spleen and plasma. An age dependent decline in MT1R and MT2R expressions and lymphocyte proliferation with increased level of reactive nitrogen species (RNS) and iNOS expression was noted. An increased Bax/Bcl-2 ratio and a decreased Pro-caspase-3 expression were observed in the spleen of goat with an age dependent decline in the peripheral melatonin level. This decline in melatonin along with reduced melatonin receptor (MT1/MT2) expression and elevated RNS level in the spleen with aging might have an important role in the regulation of immune function of goats. Our observations suggest that the age-associated immunosenescence observed in goats can be a consequence of declining melatonin and its receptor expression and induction of apoptotic factors influenced by the increased RNS level that deteriorates the proper functioning of the spleen. PMID:25281807

  19. Melatonin: a "Higgs boson" in human reproduction.

    Science.gov (United States)

    Dragojevic Dikic, Svetlana; Jovanovic, Ana Mitrovic; Dikic, Srdjan; Jovanovic, Tomislav; Jurisic, Aleksandar; Dobrosavljevic, Aleksandar

    2015-02-01

    As the Higgs boson could be a key to unlocking mysteries regarding our Universe, melatonin, a somewhat mysterious substance secreted by the pineal gland primarily at night, might be a crucial factor in regulating numerous processes in human reproduction. Melatonin is a powerful antioxidant which has an essential role in controlling several physiological reactions, as well as biological rhythms throughout human reproductive life. Melatonin, which is referred to as a hormone, but also as an autocoid, a chronobiotic, a hypnotic, an immunomodulator and a biological modifier, plays a crucial part in establishing homeostatic, neurohumoral balance and circadian rhythm in the body through synergic actions with other hormones and neuropeptides. This paper aims to analyze the effects of melatonin on the reproductive function, as well as to shed light on immunological and oncostatic properties of one of the most powerful hormones. PMID:25377724

  20. Melatonin in Plants: More Studies are Necessary

    OpenAIRE

    Arnao, Marino B; Hernández-Ruiz, Josefa

    2007-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is a biogenic indoleamine structurally related with other important substances such as tryptophan, serotonin, indole-3-acetic acid (IAA). In mammals, birds, reptiles and fish melatonin is a biological modulator of several timing (circadian) processes such as mood, sleep, sexual behavior, immunological status, etc. Since its discovery in plants in 1995 several physiological roles, including a possible role in flowering, circadian rhythms and photoperiod...

  1. Clinical Uses of Melatonin in Pediatrics

    OpenAIRE

    Emilio J. Sánchez-Barceló; Mediavilla, Maria D.; Reiter, Russel J.

    2011-01-01

    This study analyzes the results of clinical trials of treatments with melatonin conducted in children, mostly focused on sleep disorders of different origin. Melatonin is beneficial not only in the treatment of dyssomnias, especially delayed sleep phase syndrome, but also on sleep disorders present in children with attention-deficit hyperactivity, autism spectrum disorders, and, in general, in all sleep disturbances associated with mental, neurologic, or other medical disorders. Sedative prop...

  2. A potential multiple resonance mechanism by which weak magnetic fields affect molecules and medical problems: the example of melatonin and experimental "multiple sclerosis".

    Science.gov (United States)

    Persinger, Michael A

    2006-01-01

    A biophysical hypothesis to explain the powerful ameliorating effects of weak (nanoTesla range) magnetic fields on melatonin-related diseases is presented. The effects are dependent upon the molarity of the melatonin within specific organ spaces. The optimal ameliorating effects upon experimental allergic encephalomyelitis for both the derived intensities (about 35 and 70 nT) and the frequency (7 Hz) were congruent with the empirical observations from previously published and unpublished experiments with rats involving about 1-5000 nT strengths of either 0.5, 7, 40, or 60 Hz magnetic fields. The hypothesis predicts that weaker magnetic fields within the nanoTesla to picoTesla range would optimally affect concentrations of melatonin (in this situation) within the micromolar range and that neurological states (epilepsy) or conditions (ethanol, antidepressants, sleep deprivation) that affect nocturnal melatonin levels in human beings would determine the optimal effective intensity within the 7 Hz range. The resonance solution also suggests that mitochondrial proton gradients may be critical to the process. The model offers an alternative explanation to the variations of Faraday's Law and the Boltzmann constant that have been employed to explain and to dismiss biological effects from weak magnetic fields. PMID:16321472

  3. The effect of sleep on nocturnal urine output

    DEFF Research Database (Denmark)

    Kamperis, Konstantinos; HagstrØm, SØren

    2005-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

    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…

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

    Directory of Open Access Journals (Sweden)

    Ebaid Hossam

    2013-02-01

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

  6. Putative melatonin receptors in a human biological clock

    International Nuclear Information System (INIS)

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

  7. Can nocturnal hypertension predict cardiovascular risk?

    Directory of Open Access Journals (Sweden)

    Oded Friedman

    2009-09-01

    Full Text Available Oded Friedman1, Alexander G Logan21Samuel Lunenfeld Research Institute, Division of Nephrology, Mount Sinai Hospital, 2Mount Sinai Hospital and University Health Network and Department of Medicine, University of Toronto, Toronto, CanadaAbstract: Nocturnal hypertension and non-dipping of blood pressure during sleep are distinct entities that often occur together and are regarded as important harbingers of poor cardiovascular prognosis. This review addresses several aspects related to these blood pressure abnormalities including definitions, diagnostic limitations, pathogenesis and associated patient profiles, prognostic significance, and therapeutic strategies. Taken together, persistent nocturnal hypertension and non-dipping blood pressure pattern, perhaps secondary to abnormal renal sodium handling and/or altered nocturnal sympathovagal balance, are strongly associated with deaths, cardiovascular events, and progressive loss of renal function, independent of daytime and 24-hour blood pressure. Several pharmacological and non-pharmacological approaches may restore nocturnal blood pressure and circadian blood pressure rhythm to normal; however, whether this translates to a clinically meaningful reduction in unfavorable cardiovascular and renal consequences remains to be seen.Keywords: blood pressure, sleep, nocturnal hypertension

  8. Potassium hexacyanoferrate(III)-mediated fluorometric determination of melatonin.

    Science.gov (United States)

    Iizuka, Hideaki; Yajima, Takehiko

    2003-01-01

    This paper describes the development of a novel, simple and sensitive high-performance liquid chromatographic method for the determination of melatonin using precolumn fluorometric derivatization. A strong fluorescence was induced when alkaline solution of melatonin was heated in the presence of potassium hexacyanoferrate (III). This fluorescent reaction was used for the precolumn derivatization of melatonin. Solid phase extraction was used for concentrating melatonin below a level of detection limit. PMID:15206777

  9. Role of melatonin in the induction and maintenance of sleep

    OpenAIRE

    Fourtillan, Jean B.

    2002-01-01

    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...

  10. Melatonin improves spermatogonial stem cells transplantation efficiency in azoospermic mice

    OpenAIRE

    Gholami, Mohammadreza; Saki, Ghasem; Hemadi, Masoud; Khodadadi, Ali; Mohammadi-Asl, Javad

    2014-01-01

    Objective(s): Transplantation quality improvement and reduction of cellular damage are important goals that are now considered by researchers. Melatonin is secreted from the pineal gland and some organs such as testes. According to beneficial effects of melatonin (such as its antioxidant and antiapoptotic properties), researchers have proposed that the use of melatonin may improve transplantation quality. The aim of this study was to investigate the effects of melatonin on the spermatogonial ...

  11. Iatrogenic nocturnal eneuresis – an overlooked side effect of anti histamines?

    Science.gov (United States)

    Italiano, D; Italiano, F; Genovese, C; Calabrò, R S

    2015-01-01

    Nocturnal enuresis is a common disorder in childhood, but its pathophysiological mechanisms have not been fully elucidated. Iatrogenic nocturnal enuresis has been described following treatment with several psychotropic medications. Herein, we describe a 6-year-old child who experienced nocturnal enuresis during treatment with the antihistamine cetirizine. Drug rechallenge was positive. Several neurotransmitters are implicated in the pathogenesis of nocturnal enuresis, including noradrenaline, serotonin and dopamine. Antihistamine treatment may provoke functional imbalance of these pathways resulting in incontinence. PMID:25766344

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

    OpenAIRE

    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

    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...

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

    OpenAIRE

    Lemoine P; Ag, Wade; Katz A; Nir T; Zisapel N

    2012-01-01

    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 pati...

  14. Melatonin Induces Akt Phosphorylation through Melatonin Receptor- and PI3K-Dependent Pathways in Primary Astrocytes

    OpenAIRE

    Kong, Pil-Jae; Byun, Jong-Seon; Lim, So-Young; Lee, Jae-Jun; Hong, Sung-Jun; Kwon, Kwang-Jun; Kim, Sung-Soo

    2008-01-01

    Melatonin has been reported to protect neurons from a variety of neurotoxicity. However, the underlying mechanism by which melatonin exerts its neuroprotective property has not yet been clearly understood. We previously demonstrated that melatonin protected kainic acid-induced neuronal cell death in mouse hippocampus, accompanied by sustained activation of Akt, a critical mediator of neuronal survival. To further elucidate the neuroprotective action of melatonin, we examined in the present st...

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

    Directory of Open Access Journals (Sweden)

    Piero Bagnaresi

    2009-04-01

    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

  16. Exercise elicits phase shifts and acute alterations of melatonin that vary with circadian phase.

    Science.gov (United States)

    Buxton, Orfeu M; Lee, Calvin W; L'Hermite-Baleriaux, Mireille; Turek, Fred W; Van Cauter, Eve

    2003-03-01

    To examine the immediate phase-shifting effects of high-intensity exercise of a practical duration (1 h) on human circadian phase, five groups of healthy men 20-30 yr of age participated in studies involving no exercise or exposure to morning, afternoon, evening, or nocturnal exercise. Except during scheduled sleep/dark and exercise periods, subjects remained under modified constant routine conditions allowing a sleep period and including constant posture, knowledge of clock time, and exposure to dim light intensities averaging (+/-SD) 42 +/- 19 lx. The nocturnal onset of plasma melatonin secretion was used as a marker of circadian phase. A phase response curve was used to summarize the phase-shifting effects of exercise as a function of the timing of exercise. A significant effect of time of day on circadian phase shifts was observed (P phase-shifting of the human circadian system and that 2) early evening exercise of high intensity may induce phase advances relevant for nonphotic entrainment of the human circadian system. PMID:12571075

  17. 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 me 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.

  18. Melatonin regulates carbohydrate metabolism and defenses against Pseudomonas syringae pv. tomato DC3000 infection in Arabidopsis thaliana.

    Science.gov (United States)

    Zhao, Hongbo; Xu, Lingfei; Su, Tao; Jiang, Yang; Hu, Lingyu; Ma, Fengwang

    2015-08-01

    Melatonin has been reported to promote plant growth and development. Our experiments with Arabidopsis thaliana showed that exogenous applications of this molecule mediated invertase inhibitor (C/VIF)-regulated invertase activity and enhanced sucrose metabolism. Hexoses were accumulated in response to elevated activities by cell wall invertase (CWI) and vacuolar invertase (VI). Analyses of sugar metabolism-related genes revealed differential expression during plant development that was modulated by melatonin. In particular, C/VIF1 and C/VIF2 were strongly down-regulated by exogenous feeding. We also found the elevated CWI activity in melatonin-treated Arabidopsis improved the factors (cellulose, xylose, and galactose) for cell wall reinforcement and callose deposition during Pseudomonas syringae pv. tomato DC3000 infection, therefore, partially induced the pathogen resistance. However, CWI did not involve in salicylic acid (SA)-regulated defense pathway. Taken together, this study reveals that melatonin plays an important role in invertase-related carbohydrate metabolism, plant growth, and pathogen defense. PMID:25958775

  19. Aging and oxygen toxicity: Relation to changes in melatonin

    OpenAIRE

    Reiter, Russel J.

    1997-01-01

    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 ...

  20. The Behavioral Treatment of Childhood Nocturnal Enuresis.

    Science.gov (United States)

    Wagner, William G.

    1987-01-01

    Notes that of the treatments attempted for nocturnal enuresis, pharmacotherapy, individual psychotherapy, and behavioral conditioning, the most effective is behavioral conditioning with a urine alarm. Reviews the enuresis literature and provides recommendations for use of the urine alarm approach. (Author/ABB)

  1. Nocturnal activity and the enuresis alarm device.

    OpenAIRE

    Crisp, A. H.; Sireling, L. I.; Faizey, J.

    1984-01-01

    The effect on nocturnal activity of the wire mesh element within the 'buzzer and pad' enuresis alarm device was studied using healthy adult volunteers in a single or double cross-over design. On the nights when the mesh was in the bed there was less activity, supporting the finding of improved polygraphic sleep on the mesh and suggesting an unexpected therapeutic mechanism.

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

    Directory of Open Access Journals (Sweden)

    Ouichou Ali

    2012-06-01

    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.

  3. The role of melatonin as an antioxidant in the follicle

    Directory of Open Access Journals (Sweden)

    Tamura Hiroshi

    2012-01-01

    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.

  4. Transcriptional regulation of programmed hypertension by melatonin: an epigenetic perspective.

    Science.gov (United States)

    Tain, You-Lin; Huang, Li-Tung; Chan, Julie Y H

    2014-01-01

    Melatonin is an endogenously produced indoleamine and secreted by the pineal gland. Melatonin has pleiotropic bioactivities and is involved in epigenetic regulation. Suboptimal conditions during maternal and perinatal phases can elicit epigenetic regulation of genes for nephrogenesis and reset physiological responses to develop programmed hypertension. This review discusses the early utility of melatonin to prevent programmed hypertension in later life by epigenetic regulation in the kidney, with an emphasis on: (1) the role of melatonin in epigenetic regulation; (2) the beneficial effects of melatonin on programmed hypertension; (3) epigenetic regulation of maternal melatonin therapy in different developmental windows of offspring kidneys analyzed by whole-genome RNA next-generation sequencing; and (4) current blocks in the application of melatonin in preventing programmed hypertension. PMID:25318052

  5. Melatonin and its precursors scavenge nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-12-01

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

  6. Melatonin prevents oxidative damage induced by maternal ethanol administration and reduces homocysteine in the cerebellum of rat pups.

    Science.gov (United States)

    Bagheri, Farzaneh; Goudarzi, Iran; Lashkarbolouki, Taghi; Elahdadi Salmani, Mahmoud

    2015-07-01

    Chronic alcoholism leads to elevated plasma and brain homocysteine (Hcy) levels, as demonstrated by animal experiments. This study was designed to evaluate the alterations in offspring rat cerebellum following increase of plasma Hcy level induced by maternal exposure to ethanol and to investigate the possible protective role of melatonin administration upon cerebellar ethanol-induced neurotoxicity. The adult female rats were divided randomly into 4 groups, including one control and three experimental groups, after vaginal plagues. Group I received normal saline, group II received ethanol (4g/kg), group III received ethanol+melatonin (10mg/kg) and group IV received melatonin on day 6 of gestation until weaning. 21 days after birth, plasma Hcy level, level of lipid peroxidation, the activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and levels of bcl-2 and bax mRNA expression in cerebellum were determined. Our results demonstrated that ethanol could induce lipid peroxidation, and decrease antioxidants activities and increase plasma total Hcy level. We also observed that ethanol impaired performance on the rotarod and locomotor activities of rats. However, treatment with melatonin significantly attenuated motoric impairment, the lipid peroxidation process and restored the levels of antioxidant activities and significantly reduced plasma total Hcy levels. Moreover, melatonin reduced bax/bcl-2 ratio in the presence of ethanol. We conclude that these results provide evidence that ethanol neurotoxicity in part is related to increase of plasma Hcy levels and melatonin with reducing of plasma Hcy level has neuroprotective effects against ethanol toxicity in cerebellum. PMID:25797213

  7. Melatonin administration reduces inflammatory pain in rats

    Directory of Open Access Journals (Sweden)

    Laste G

    2012-09-01

    Full Text Available Gabriela Laste,1–3 Isabel Cristina de Macedo,1,3 Joanna Ripoll Rozisky,1–3 Fernanda Ribeiro da Silva,1,3 Wolnei Caumo,1,2 Iraci LS Torres1–31Laboratório de Farmacologia da Dor, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, 2Programa de Pós-Graduação em Medicina, Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 3Unidade de Experimentação Animal e Grupo de Pesquisa e Pós-Graduação, Hospital de Clínicas de Porto Alegre, Porto Alegre, BrazilAbstract: In view of the broad range of effects attributed to melatonin, this study evaluated its analgesic effect on inflammatory pain induced by complete Freund's adjuvant (CFA in Wistar rats. Inflammation was induced by intradermal CFA injection in the hind paw of all animals, which were then divided into two groups that received either 60 mg/kg of melatonin or vehicle (1% alcohol in saline, intraperitoneally, for three days. The analgesic effect of melatonin was assessed by the hot-plate test, immediately and thereafter at 30, 60, 90, and 120 minutes after the first administration and 24 hours after once-daily administration for 2 more days. After CFA injection, melatonin administration increased withdrawal latency at 60 minutes after the first dose. After the end of treatment, melatonin showed a significant analgesic effect on inflammatory pain. This study paves the way for exploration of how brief courses of treatment could improve this analgesic effect in the late phases of inflammatory pain.Keywords: analgesic response, complete Freund's adjuvant, hot-plate test, inflammation, melatonin, nociception

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

    Science.gov (United States)

    Dwyer, Ross G; Bearhop, Stuart; Campbell, Hamish A; Bryant, David M

    2013-03-01

    Intertidal habitats provide important feeding areas for migratory shorebirds. Anthropogenic developments along coasts can increase ambient light levels at night across adjacent inter-tidal zones. Here, we report the effects of elevated nocturnal light levels upon the foraging strategy of a migratory shorebird (common redshank Tringa totanus) overwintering on an industrialised estuary in Northern Europe. To monitor behaviour across the full intertidal area, individuals were located by day and night using VHF transmitters, and foraging behaviour was inferred from inbuilt posture sensors. Natural light was scored using moon-phase and cloud cover information and nocturnal artificial light levels were obtained using geo-referenced DMSP/OLS night-time satellite imagery at a 1-km resolution. Under high illumination levels, the commonest and apparently preferred foraging behaviour was sight-based. Conversely, birds feeding in areas with low levels of artificial light had an elevated foraging time and fed by touch, but switched to visual rather than tactile foraging behaviour on bright moonlit nights in the absence of cloud cover. Individuals occupying areas which were illuminated continuously by lighting from a large petrochemical complex invariably exhibited a visually based foraging behaviour independently of lunar phase and cloud cover. We show that ambient light levels affect the timing and distribution of foraging opportunities for redshank. We argue that light emitted from an industrial complex improved nocturnal visibility. This allowed sight-based foraging in place of tactile foraging, implying both a preference for sight-feeding and enhanced night-time foraging opportunities under these conditions. The study highlights the value of integrating remotely sensed data and telemetry techniques to assess the effect of anthropogenic change upon nocturnal behaviour and habitat use. PMID:23190422

  9. Amyloid ? peptide directly impairs pineal gland melatonin synthesis and melatonin receptor signaling through the ERK pathway.

    Science.gov (United States)

    Cecon, Erika; Chen, Min; Marçola, Marina; Fernandes, Pedro A C; Jockers, Ralf; Markus, Regina P

    2015-06-01

    Melatonin is the hormone produced by the pineal gland known to regulate physiologic rhythms and to display immunomodulatory and neuroprotective properties. It has been reported that Alzheimer disease patients show impaired melatonin production and altered expression of the 2 G protein-coupled melatonin receptors (MTRs), MT1 and MT2, but the underlying mechanisms are not known. Here we evaluated whether this dysfunction of the melatonergic system is directly caused by amyloid ? peptides (A?1-40 and A?1-42). A? treatment of rat pineal glands elicited an inflammatory response within the gland, evidenced by the up-regulation of 52 inflammatory genes, and decreased the production of melatonin up to 75% compared to vehicle-treated glands. Blocking NF-?B activity prevented this effect. Exposure of HEK293 cells stably expressing recombinant MT1 or MT2 receptors to A? lead to a 40% reduction in [(125)I]iodomelatonin binding to MT1. ERK1/2 activation triggered by MTRs, but not by the ?2-adrenergic receptor, was markedly impaired by A? in HEK293 transfected cells, as well as in primary rat endothelial cells expressing endogenous MTRs. Our data reveal the melatonergic system as a new target of A?, opening new perspectives to Alzheimer disease diagnosis and therapeutic intervention.-Cecon, E., Chen, M., Marçola, M., Fernandes, P. A. C., Jockers, R., Markus, R. P. Amyloid ? peptide directly impairs pineal gland melatonin synthesis and melatonin receptor signaling through the ERK pathway. PMID:25757565

  10. The research of melatonin in hypoxic-ischemic encephalopathy

    International Nuclear Information System (INIS)

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

  11. Melatonin as a potential antihypertensive treatment.

    Czech Academy of Sciences Publication Activity Database

    Šimko, F.; Paulis, ?udovít

    2007-01-01

    Ro?. 42, ?. 4 (2007), s. 319-322. ISSN 0742-3098 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : antioxidants * hypertension * melatonin Subject RIV: ED - Physiology Impact factor: 4.098, year: 2007

  12. Isolation of melatonin by immunoaffinity chromatography.

    Czech Academy of Sciences Publication Activity Database

    Rol?ík, Jakub; Lenobel, René; Siglerová, V?ra; Strnad, Miroslav

    2002-01-01

    Ro?. 25, ?. 1 (2002), s. 9-15. ISSN 0378-4347 R&D Projects: GA MŠk OC 844.10; GA ?R GA301/02/0475 Institutional research plan: CEZ:AV0Z5038910 Keywords : Melatonin Subject RIV: CE - Biochemistry Impact factor: 1.913, year: 2002

  13. Therapeutic implications of melatonin in cerebral edema.

    Science.gov (United States)

    Rathnasamy, Gurugirijha; Ling, Eng-Ang; Kaur, Charanjit

    2014-12-01

    Cerebral edema/brain edema refers to the accumulation of fluid in the brain and is one of the fatal conditions that require immediate medical attention. Cerebral edema develops as a consequence of cerebral trauma, cerebral infarction, hemorrhages, abscess, tumor, hypoxia, and other toxic or metabolic factors. Based on the causative factors cerebral edema is differentiated into cytotoxic cerebral edema, vasogenic cerebral edema, osmotic and interstitial cerebral edema. Treatment of cerebral edema depends on timely diagnosis and medical assistance. Pragmatic treatment strategies such as antihypertensive medications, nonsteroidal anti-inflammatory drugs, barbiturates, steroids, glutamate and N-methyl-D-aspartate receptor antagonists and trometamol are used in clinical practice. Although the above mentioned treatment approaches are being used, owing to the complexity of the mechanisms involved in cerebral edema, a single therapeutic strategy which could ameliorate cerebral edema is yet to be identified. However, recent experimental studies have suggested that melatonin, a neurohormone produced by the pineal gland, could be an effective alternative for treating cerebral edema. In animal models of stroke, melatonin was not only shown to reduce cerebral edema but also preserved the blood brain barrier. Melatonin's beneficial effects were attributed to its properties, such as being a potent anti-oxidant, and its ability to cross the blood brain barrier within minutes after its administration. This review summarizes the beneficial effects of melatonin when used for treating cerebral edema. PMID:24876075

  14. Nocturnal enuresis in sickle cell haemoglobinopathies.

    OpenAIRE

    Readett, D. R.; Morris, J. S.; Serjeant, G. R.

    1990-01-01

    The prevalence of nocturnal enuresis (wet at least two nights a week) was investigated in children, aged 8, who were being followed up as part of a prospective cohort study. There were 175 children with homozygous sickle cell disease, 106 with sickle cell haemoglobin C disease, and 150 controls with a normal haemoglobin genotype. In homozygous sickle cell disease, 48 boys (52%) and 31 girls (38%) were enuretic, a significantly higher prevalence than in those with sickle cell haemoglobin C dis...

  15. Ipratropium bromide in patients with nocturnal asthma.

    OpenAIRE

    Cox, I. D.; Hughes, D. T.; Mcdonnell, K. A.

    1984-01-01

    Fourteen patients with nocturnal asthma were recruited to a two period crossover trial which compared a run-in period on nightly salbutamol (200 micrograms) with a period on nightly ipratropium bromide (160 micrograms) and a period on nightly salbutamol plus ipratropium at night. Morning dipping, as assessed by the fall in peak flow overnight, was significantly reduced in the periods when ipratropium bromide was taken. Peak flow in the morning and also at night was improved when taking ipratr...

  16. Nocturnal asthma: a study in general practice.

    OpenAIRE

    Turner-warwick, M.

    1989-01-01

    Symptoms of nocturnal asthma were studied using questionnaires returned by 1199 general practitioners throughout the United Kingdom. Of 7729 asthmatic patients seen consecutively and prescribed a bronchodilator aerosol, 73% woke with asthma at least once a week and 39% woke nightly. The percentage of asthmatics waking at night at least once a week in this population, where 48% were prescribed corticosteroid aerosols, was very similar to the 74% found to have asthma attacks at night in an earl...

  17. Bat predation on nocturnally migrating birds

    OpenAIRE

    Ibáñez, Carlos; Juste, Javier; García-Mudarra, Juan L.; Agirre-Mendi, Pablo T.

    2001-01-01

    Bat predation on birds is a very rare phenomenon in nature. Most documented reports of bird-eating bats refer to tropical bats that occasionally capture resting birds. Millions of small birds concentrate and cross over the world's temperate regions during migration, mainly at night, but no nocturnal predators are known to benefit from this enormous food resource. An analysis of 14,000 fecal pellets of the greater noctule bat (Nyctalus lasiopterus) reveals that this...

  18. Unrecognised nocturnal hypoglycaemia masquerading as senile dementia.

    OpenAIRE

    Ramasamy, R.

    1983-01-01

    A 70-year-old woman with insulin dependent diabetes mellitus presented with symptoms suggestive of senile dementia. Outpatient assessment failed to reveal poor diabetic control with frequent nocturnal hypoglycaemia. Eventual appreciation of the poor control resulted in several failed attempts at improving therapy with various subcutaneous insulin regimes. Intramuscular and intravenous routes produced acceptable blood glucose levels with striking reversal of the patient's symptoms. The possibl...

  19. Melatonin ameliorates neural function by promoting endogenous neurogenesis through the MT2 melatonin receptor in ischemic-stroke mice.

    Science.gov (United States)

    Chern, Chang-Ming; Liao, Jyh-Fei; Wang, Yea-Hwey; Shen, Yuh-Chiang

    2012-05-01

    Melatonin has many protective effects against ischemic stroke, but the underlying neuroprotective mechanisms are not fully understood. Our aim was to explore the relationship between melatonin's neuroprotective effects and activation of the MT2 melatonin receptor in a murine ischemic-stroke model. Male ICR mice were subjected to a transient middle cerebral ischemic/reperfusional injury, and melatonin (5 and 10 mg/kg, ip) was administrated once daily starting 2 h after ischemia. More than 80% of the mice died within 5 days after stroke without treatment. Melatonin treatment significantly improved the survival rates and neural functioning with modestly prolonged life span of the stroke mice by preserving blood-brain barrier (BBB) integrity via a reduction in the enormous amount of stroke-induced free radical production and significant gp91(phox) cell infiltration. These protective effects of melatonin were reversed by pretreatment with MT2 melatonin receptor antagonists (4-phenyl-2-propionamidotetralin (4P-PDOT) and luzindole). Moreover, treatment with melatonin after stroke dramatically enhanced endogenous neurogenesis (doublecortin positive) and cell proliferation (ki67 positive) in the peri-infarct regions. Most ki67-positive cells were nestin-positive and NG2-positive neural stem/progenitor cells that coexpressed two neurodevelopmental proteins (adam11 and adamts20) and the MT2 melatonin receptor. RT-PCR revealed that the gene expression levels of doublecortin, ki67, adamts20, and adam11 are markedly reduced by stroke, but are restored by melatonin treatment; furthermore, pretreatment with 4P-PDOT and luzindole antagonized melatonin's restorative effect. Our results support the hypothesis that melatonin is able to protect mice against stroke by activating MT2 melatonin receptors, which reduces oxidative/inflammatory stress. This results in the preservation of BBB integrity and enhances endogenous neurogenesis by upregulating neurodevelopmental gene/protein expression. PMID:22330064

  20. 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.

  1. Melatonin protects against behavioural dysfunctions and dendritic spine damage in 3-nitropropionic acid-induced rat model of Huntington's disease.

    Science.gov (United States)

    Chakraborty, J; Nthenge-Ngumbau, D N; Rajamma, U; Mohanakumar, K P

    2014-05-01

    Huntington's disease (HD), an autosomal dominant neurodegenerative movement disorder in which striatal and cortical neurons are mostly affected, has no effective cure existing. A fungal neurotoxin and a potent inhibitor of mitochondrial electron transport chain complex II inhibitor, 3-nitropropionic acid (3-NP) is known to cause HD pathology, including lesions in the striatum and the cortex, and several behavioural syndromes in experimental animals. In the present study we examined the effect of melatonin on motor activities, neuronal morphology as revealed by Nissl and rapid Golgi staining, as well as GABA, glutamate and biogenic amine neurotransmitter levels in 3-NP-induced HD in rats. We found that melatonin (10, 20mg/kg, i.p.) administered 1h prior to 3-NP dose (20mg/kg; daily for 4 days) restored motor coordination ability as shown in gait, beam balancing, swim ability and performance on rotarod. However it failed to reduce 3-NP-induced striatal lesion core area, neuronal damage and the elevated levels of striatal dopamine. Melatonin administration partially restored 3-NP-induced loss of dendritic spines in the striatum and the cortex, and the reduction in cerebellar granule cell, but not hippocampal CA1 neuronal arborization. These findings collectively suggest that melatonin offers beneficial effects in correction of learning related fine motor adjustments, but not in behaviours unrelated to learning, by the restoration of striatal and cortical spines, and cerebellar granule cell arborization. PMID:24509309

  2. Paroxysmal nocturnal hemoglobinuria in systemic lupus erythematosus: a case report

    OpenAIRE

    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

    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...

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

    OpenAIRE

    De Almeida, Eduardo; Mascio, Paolo; Harumi, Tatsuo; Warren Spence, D.; Moscovitch, Adam; Hardeland, Rüdiger; Cardinali, Daniel; Gregory M. Brown; Pandi-Perumal, S. R.

    2010-01-01

    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) and ...

  4. ARE THE MELATONIN SUPPLEMENTS POTENTIAL TREATMENT OPTIONS? A SYSTEMATIC REVIEW

    OpenAIRE

    Subhranil Saha, Munmun Koley And Sandip Patra

    2013-01-01

    Introduction: Melatonin is a neuro-hormone secreted from the pineal gland and involved in various regulatory activities in body. Ever-increasing use of melatonin supplements and enlarging research evidences make the authors undertook the review to arrive at a qualitative conclusion whether melatonin supplements can act as potential treatment options or not.Methodology: A comprehensive search was undertaken in different electronic databases using various search terms. A total of 225 studies we...

  5. Melatonin enhances chondrogenic differentiation of human mesenchymal stem cells.

    Science.gov (United States)

    Gao, Wenjie; Lin, Mianlong; Liang, Anjing; Zhang, Liangming; Chen, Changhua; Liang, Guoyan; Xu, Caixia; Peng, Yan; Chen, Chong; Huang, Dongsheng; Su, Peiqiang

    2014-01-01

    Intramembranous ossification and endochondral ossification are two ways through which bone formation and fracture healing occur. Accumulating amounts of evidence suggests that melatonin affects osteoblast differentiation, but little is known about the effects of melatonin on the process of chondrogenic differentiation. In this study, the effects of melatonin on human mesenchymal stem cells (MSCs) undergoing chondrogenic differentiation were investigated. Cells were induced along chondrogenic differentiation via high-density micromass culture in chondrogenic medium containing vehicle or 50 nm melatonin. Histological study and quantitative analysis of glycosaminoglycan (GAG) showed induced cartilage tissues to be larger and richer in GAG, collagen type II and collagen type X in the melatonin group than in the untreated controls. Real-time RT-PCR analysis demonstrated that melatonin treatment significantly up-regulated the expression of the genes involved in chondrogenic differentiation, including aggrecan (ACAN), collagen type II (COL2A1), collagen type X (COL10A1), SRY (sex-determining region Y)-box 9 (SOX9), runt-related transcription factor 2 (RUNX2) and the potent inducer of chondrogenic differentiation, bone morphogenetic protein 2 (BMP2). And the expression of melatonin membrane receptors (MT) MT1 and MT2 were detected in the chondrogenic-induced-MSCs by immunofluorescence staining. Luzindole, a melatonin receptor antagonist, was found to partially block the ability of melatonin to increase the size and GAG synthesis of the induced cartilage tissues, as well as to completely reverse the effect of melatonin on the gene expression of ACAN, COL2A1, COL10A1, SOX9 and BMP2 after 7 days of differentiation. These findings demonstrate that melatonin enhances chondrogenic differentiation of human MSCs at least partially through melatonin receptors. PMID:24117903

  6. Melatonin Effects on Hard Tissues: Bone and Tooth

    OpenAIRE

    Hong-Wen He; Fang Huang; Jie Liu

    2013-01-01

    Melatonin is an endogenous hormone rhythmically produced in the pineal gland under the control of the suprachiasmatic nucleus (SCN) and the light/dark cycle. This indole plays an important role in many physiological processes including circadian entrainment, blood pressure regulation, seasonal reproduction, ovarian physiology, immune function, etc. Recently, the investigation and applications of melatonin in the hard tissues bone and tooth have received great attention. Melatonin has been inv...

  7. Melatonin Plays a Protective Role in Postburn Rodent Gut Pathophysiology

    OpenAIRE

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

    2010-01-01

    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,...

  8. Transcriptional Regulation of Programmed Hypertension by Melatonin: An Epigenetic Perspective

    OpenAIRE

    You-Lin Tain; Li-Tung Huang; Chan, Julie Y. H.

    2014-01-01

    Melatonin is an endogenously produced indoleamine and secreted by the pineal gland. Melatonin has pleiotropic bioactivities and is involved in epigenetic regulation. Suboptimal conditions during maternal and perinatal phases can elicit epigenetic regulation of genes for nephrogenesis and reset physiological responses to develop programmed hypertension. This review discusses the early utility of melatonin to prevent programmed hypertension in later life by epigenetic regulation in the kidney, ...

  9. The role of melatonin as an antioxidant in the follicle

    OpenAIRE

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

    2012-01-01

    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 radica...

  10. Treatment with beta-adrenoceptor blockers reduces plasma melatonin concentration.

    OpenAIRE

    Cowen, PJ; Bevan, JS; GOSDEN, B; Elliott, SA

    1985-01-01

    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.

  11. Genetic variation of melatonin productivity in laboratory mice under domestication

    OpenAIRE

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

    2010-01-01

    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...

  12. Melatonin and its use in atherosclerosis and dyslipidemia

    Directory of Open Access Journals (Sweden)

    Danilenko KV

    2013-03-01

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

  13. Melatonin as a proteasome inhibitor. Is there any clinical evidence?

    Science.gov (United States)

    Vriend, Jerry; Reiter, Russel J

    2014-10-12

    Proteasome inhibitors and melatonin are both intimately involved in the regulation of major signal transduction proteins including p53, cyclin p27, transcription factor NF-?B, apoptotic factors Bax and Bim, caspase 3, caspase 9, anti-apoptotic factor Bcl-2, TRAIL, NRF2 and transcription factor beta-catenin. The fact that these factors are shared targets of the proteasome inhibitor bortezomib and melatonin suggests the working hypothesis that melatonin is a proteasome inhibitor. Supporting this hypothesis is the fact that melatonin shares with bortezomib a selective pro-apoptotic action in cancer cells. Furthermore, both bortezomib and melatonin increase the sensitivity of human glioma cells to TRAIL-induced apoptosis. Direct evidence for melatonin inhibition of the proteasome was recently found in human renal cancer cells. We raise the issue whether melatonin should be investigated in combination with proteasome inhibitors to reduce toxicity, to reduce drug resistance, and to enhance efficacy. This may be particularly valid for hematological malignancies in which proteasome inhibitors have been shown to be useful. Further studies are necessary to determine whether the actions of melatonin on cellular signaling pathways are due to a direct inhibitory effect on the catalytic core of the proteasome, due to an inhibitory action on the regulatory particle of the proteasome, or due to an indirect effect of melatonin on phosphorylation of signal transducing factors. PMID:25219883

  14. 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 ?-irraed 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.

  15. Detection of melatonin receptor mRNA in human muscle

    International Nuclear Information System (INIS)

    To verify the expression of melatonin receptor mRNA in human, muscle, muscle beside vertebrae was collected to obtain total RNA and the mRNA of melatonin receptor was detected by RT-PCR method. The electrophoretic results of RT-PCR products by mt1 and MT2 primer were all positive and the sequence is corresponding with human melatonin receptor cDNA. It suggests that melatonin may act on the muscle beside vertebrae directly and regulate its growth and development. (authors)

  16. Melatonin: An Underappreciated Player in Retinal Physiology and Pathophysiology

    OpenAIRE

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

    2012-01-01

    In the vertebrate retina, melatonin is synthesized by the photoreceptors with high levels of melatonin at night and lower levels during the day. Melatonin exerts its influence by interacting with a family of G-protein-coupled receptors that are negatively coupled with adenylyl cyclase. Melatonin receptors belonging to the subtypes MT1 and MT2 have been identified in the mammalian retina. MT1 and MT2 receptors are found in all layers of the neural retina and in the retinal pigmented epithelium...

  17. Adherence to Bergmann's rule by lizards may depend on thermoregulatory mode: support from a nocturnal gecko.

    Science.gov (United States)

    Penniket, Sophie; Cree, Alison

    2015-06-01

    Bergmann's rule predicts an increase in body size with decreasing environmental temperature; however, the converse pattern has been found in the majority of lizards studied to date. For these ectotherms, small body size may provide thermal benefits (rapid heat uptake when basking), which would be highly advantageous in cold environments. Yet such an advantage may not exist in nocturnal lizards (which do not avidly bask), in which Bergmann's rule has not been closely studied. We have examined whether the body size of a primarily nocturnal gecko, Woodworthia "Otago/Southland" changed with elevation and operative temperature (determined using physical copper models). In a laboratory study, we investigated whether thermoregulatory mode (heliothermy or thigmothermy) alters the effect of body size on heating and cooling rates. This gecko followed Bergmann's rule, thereby showing the opposite of the dominant pattern in diurnal lizards. Size at maturity, maximum size of adults and size at birth were larger at higher elevations and at lower operative temperatures. Using physical models, we found that large body size can confer thermal benefits for nocturnal lizards that remain within diurnal retreats. Bergmann's rule should not be dismissed for all lizards. Our results clearly support Bergmann's rule for at least one thigmothermic species, for which large body size may provide thermal benefits. Future studies on Bergmann's rule in lizards should consider thermoregulatory mode. We advocate that this ecogeographic rule be examined in relation to operative temperature measured at field sites. Finally, we predict that climate warming may weaken the relationship between body size and elevation in this gecko. PMID:25663371

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

    International Nuclear Information System (INIS)

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

  19. Melatonin suppression by light in humans is maximal when the nasal part of the retina is illuminated.

    Science.gov (United States)

    Visser, E K; Beersma, D G; Daan, S

    1999-04-01

    This study investigated whether sensitivity of the nocturnal melatonin suppression response to light depends on the area of the retina exposed. The reason to suspect uneven spatial sensitivity distribution stems from animal work that revealed that retinal ganglion cells projecting to the suprachiasmatic nuclei (SCN) are unequally distributed in several species of mammals. Four distinct areas of the retinas of 8 volunteers were selectively exposed to 500 lux between 1:30 a.m. and 3:30 a.m. Saliva samples were taken before, during, and after light exposure in 1-h intervals. A significant difference in sensitivity was found between exposure of the lateral and nasal parts of the retinas, showing that melatonin suppression is maximal on exposure of the nasal part of the retina. The results imply that artificial manipulation of the circadian pacemaker to alleviate jet lag, to improve alertness in shift workers, and possibly to treat patients suffering from seasonal affective disorder should encompass light exposure of the nasal retina. PMID:10194647

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

    DEFF Research Database (Denmark)

    Radvanska, E; Kamperis, Konstantinos

    2011-01-01

    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.

  1. 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 inries, may cause circulatory adjustments in these arteries, which are believed to be involved in thermoregulation

  2. Exogenous Melatonin for Sleep Problems in Individuals with Intellectual Disability: A Meta-Analysis

    Science.gov (United States)

    Braam, Wiebe; Smits, Marcel G.; Didden, Robert; Korzilius, Hubert; van Geijlswijk, Ingeborg M.; Curfs, Leopold M. G.

    2009-01-01

    Recent meta-analyses on melatonin has raised doubts as to whether melatonin is effective in treating sleep problems in people without intellectual disabilities. This is in contrast to results of several trials on melatonin in treating sleep problems in individuals with intellectual disabilities. To investigate the efficacy of melatonin in treating…

  3. An update on the use of melatonin as a stroke therapeutic.

    Science.gov (United States)

    Gonzales-Portillo, G S; Lozano, D; Aguirre, D; Reyes, S; Borlongan, C V; Tajiri, N; Kaneko, Y

    2015-06-01

    Delivery of melatonin and targeting melatonin receptors pose as neuroprotective strategies for stroke therapy. The potential of melatonin-based therapeutics for clinical application in stroke patients requires translational research to guide the conduct of clinical trials. We review recent preclinical and clinical data that support the use of melatonin for stroke. PMID:25000217

  4. Green Light for Nocturnally Migrating Birds

    Directory of Open Access Journals (Sweden)

    Marcel R. Wernand

    2008-12-01

    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.

  5. Microorganisms for the production of melatonin

    DEFF Research Database (Denmark)

    Knight, Eric Michael Technical University of Denmark,

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

  6. Melatonin in Alzheimer’s Disease

    OpenAIRE

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

    2013-01-01

    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 pa...

  7. Fundamental Issues Related to the Origin of Melatonin and Melatonin Isomers during Evolution: Relation to Their Biological Functions

    Directory of Open Access Journals (Sweden)

    Dun-Xian Tan

    2014-09-01

    Full Text Available Melatonin and melatonin isomers exist and/or coexist in living organisms including yeasts, bacteria and plants. The levels of melatonin isomers are significantly higher than that of melatonin in some plants and in several fermented products such as in wine and bread. Currently, there are no reports documenting the presence of melatonin isomers in vertebrates. From an evolutionary point of view, it is unlikely that melatonin isomers do not exist in vertebrates. On the other hand, large quantities of the microbial flora exist in the gut of the vertebrates. These microorganisms frequently exchange materials with the host. Melatonin isomers, which are produced by these organisms inevitably enter the host’s system. The origins of melatonin and its isomers can be traced back to photosynthetic bacteria and other primitive unicellular organisms. Since some of these bacteria are believed to be the precursors of mitochondria and chloroplasts these cellular organelles may be the primary sites of melatonin production in animals or in plants, respectively. Phylogenic analysis based on its rate-limiting synthetic enzyme, serotonin N-acetyltransferase (SNAT, indicates its multiple origins during evolution. Therefore, it is likely that melatonin and its isomer are also present in the domain of archaea, which perhaps require these molecules to protect them against hostile environments including extremely high or low temperature. Evidence indicates that the initial and primary function of melatonin and its isomers was to serve as the first-line of defence against oxidative stress and all other functions were acquired during evolution either by the process of adoption or by the extension of its antioxidative capacity.

  8. In the rat, exogenous melatonin increases the amplitude of pineal melatonin secretion by a direct action on the circadian clock.

    Science.gov (United States)

    Bothorel, Béatrice; Barassin, Stéphane; Saboureau, Michel; Perreau, Stéphanie; Vivien-Roels, Berthe; Malan, André; Pévet, Paul

    2002-09-01

    The effect of exogenous melatonin on pineal melatonin synthesis was studied in the rat in vivo. Daily melatonin profiles were measured by transpineal microdialysis over 4 consecutive days in rats maintained on a 12-h light : 12-h dark schedule (LD 12 : 12). Curve-fitting was used to determine the amplitude of the peak of melatonin production, and the times of its onset (IT50) and offset (DT50). A subcutaneous injection of melatonin (1 mg/kg) at the onset of darkness (ZT12) induced an advance of IT50 on the second day after the treatment, in 50% of the animals kept in LD. When the animals were switched to constant darkness, the treatment caused no detectable advance of IT50, while 70% of individuals showed a significant delay in DT50 2 days after the injection. Locally infusing the drug by reverse microdialysis into the suprachiasmatic nuclei (SCN) failed to enhance the shift in melatonin onset. Following subcutaneous melatonin injection, a significant increase ( approximately 100%) in melatonin peak amplitude was observed. This increase persisted over 2 days and occurred only when the melatonin was applied at ZT12, but not at ZT6, 17 or 22. The effect was also observed when the drug was infused directly into the SCN, but not into the pineal. Thus, the SCN are the target site for the effect of exogenous melatonin on the amplitude of the endogenous melatonin rhythm, with a similar window of sensitivity as its phase-shifting effect on the pacemaker. PMID:12383238

  9. Melatonin as a treatment for gastrointestinal cancer: a review.

    Science.gov (United States)

    Xin, Zhenlong; Jiang, Shuai; Jiang, Peng; Yan, Xiaolong; Fan, Chongxi; Di, Shouyin; Wu, Guiling; Yang, Yang; Reiter, Russel J; Ji, Gang

    2015-05-01

    Gastrointestinal cancer is a disease that affects the population worldwide with high morbidity and mortality. Melatonin, an endogenously produced molecule, may provide a defense against a variety of cancer types. In particular, the ability of melatonin to inhibit gastrointestinal cancer is substantial. In this review, we first clarify the relationship between the disruption of the melatonin rhythm and gastrointestinal cancer (based on epidemiologic surveys and animal and human studies) and summarize the preventive effect of melatonin on carcinogenesis. Thereafter, the mechanisms through which melatonin exerts its anti-gastrointestinal cancer actions are explained, including inhibition of proliferation, invasion, metastasis, and angiogenesis, and promotion of apoptosis and cancer immunity. Moreover, we discuss the drug synergy effects and the role of melatonin receptors involved in the growth-inhibitory effects on gastrointestinal cancer. Taken together, the information compiled here serves as a comprehensive reference for the anti-gastrointestinal cancer actions of melatonin that have been identified to date and will hopefully aid in the design of further experimental and clinical studies and increase the awareness of melatonin as a therapeutic agent in cancers of the gastrointestinal tract. PMID:25752643

  10. Melatonin improves spatial navigation memory in male diabetic rats

    Directory of Open Access Journals (Sweden)

    Farrin Babaei-Balderlou

    2012-09-01

    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.

  11. Melatonin modulates the fetal cardiovascular defense response to acute hypoxia.

    Science.gov (United States)

    Thakor, Avnesh S; Allison, Beth J; Niu, Youguo; Botting, Kimberley J; Serón-Ferré, Maria; Herrera, Emilio A; Giussani, Dino A

    2015-08-01

    Experimental studies in animal models supporting protective effects on the fetus of melatonin in adverse pregnancy have prompted clinical trials in human pregnancy complicated by fetal growth restriction. However, the effects of melatonin on the fetal defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested the hypothesis, in vivo, that melatonin modulates the fetal cardiometabolic defense responses to acute hypoxia in chronically instrumented late gestation fetal sheep via alterations in fetal nitric oxide (NO) bioavailability. Under anesthesia, 6 fetal sheep at 0.85 gestation were instrumented with vascular catheters and a Transonic flow probe around a femoral artery. Five days later, fetuses were exposed to acute hypoxia with or without melatonin treatment. Fetal blood was taken to determine blood gas and metabolic status and plasma catecholamine concentrations. Hypoxia during melatonin treatment was repeated during in vivo NO blockade with the NO clamp. This technique permits blockade of de novo synthesis of NO while compensating for the tonic production of the gas, thereby maintaining basal cardiovascular function. Melatonin suppressed the redistribution of blood flow away from peripheral circulations and the glycemic and plasma catecholamine responses to acute hypoxia. These are important components of the fetal brain sparing response to acute hypoxia. The effects of melatonin involved NO-dependent mechanisms as the responses were reverted by fetal treatment with the NO clamp. Melatonin modulates the in vivo fetal cardiometabolic responses to acute hypoxia by increasing NO bioavailability. PMID:25908097

  12. Use of Melatonin in Young Children for Sleep Disorders.

    Science.gov (United States)

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

    2002-01-01

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

  13. Promising Role of Melatonin as Neuroprotectant in Neurodegenerative Pathology.

    Science.gov (United States)

    Joshi, Neeraj; Biswas, Joyshree; Nath, C; Singh, Sarika

    2014-08-27

    Melatonin treatment showed a potent neuroprotective action in experimental models and in clinical studies. However, the entire disease prevention is not observed with melatonin treatment. Therefore, findings have suggested its future use in combination therapies for neurological diseases. Several studies have showed its free radical scavenging, antioxidant property, antiapoptotic activity, and its action towards enhanced mitochondrial function. It has direct and indirect effects on mitochondrial functions. Neurodegenerative disease pathology includes the impaired mitochondrial functions and apoptotic death of neurons due to energy crisis which could be prevented with antiapoptotic activity of melatonin. However, for the therapeutic use of melatonin, researchers also need to pay attention towards the various intermediary events taking place in apoptotic death of neurons during disease pathology. Age-related neurological diseases include the decreased level of melatonin in neuronal death. Therefore, it is worthwhile to discuss about the different functions of melatonin in aspect of its antioxidative property, its role in the enhancement of mitochondrial function, and its antiapoptotic attributes. This review summarizes the reports to date showing the potent role of melatonin in experimental models and clinical trials and discussing the employment of melatonin as future potent neuroprotective agent. PMID:25159482

  14. Nocturnal hypertension and impaired sympathovagal tone in Turner syndrome

    DEFF Research Database (Denmark)

    Gravholt, Claus HØjbjerg; Hansen, Klavs Würgler

    2006-01-01

    OBJECTIVE: Increased blood pressure (BP), night: day BP ratio, and heart rate is seen in Turner syndrome (TS), and an increased risk of ischaemic heart disease and type 2 diabetes, as well as aortic dilatation and dissection. We hypothesized that altered heart rate variability is present in TS in comparison with controls, and can be influenced by hormonal replacement therapy (HRT). MATERIAL AND METHODS: We examined the impact of HRT on sympathovagal control of heart rate variability. Patients (n = 8, aged 29.5 +/- 5.3 years; no treatment or HRT) and controls (n = 8, aged 28.5 +/- 4.2 years; no treatment) were examined by short-term spectral analysis (supine-standing), bedside neuropathy tests, and 24-h ambulatory BP. N-terminal pro-brain natriuretic peptide (BNP), renin, aldosterone and urinary albumin excretion was determined. The interaction between position and status (TS or control) was examined for data from spectral analysis. RESULTS: Low-frequency (LF) power, coefficient of component variation of LF (both measures of sympathetic and vagal activity), and the LF: high-frequency (HF) power ratio (a measure of sympathovagal balance) were diminished in TS compared with controls, especially during standing. Systolic and diastolic night ambulatory BP (both P = 0.03), and systolic and diastolic night: day ratio (P = 0.01; P = 0.004) was increased in TS. During HRT diastolic day (P = 0.05) and 24-h diastolic ambulatory BP (P = 0.08) decreased. N-terminal pro-BNP was elevated in TS. CONCLUSION: Decreased sympathovagal balance or tone and nocturnal hypertension is present in TS, and N-terminal pro-BNP is elevated. HRT did not modulate the sympathovagal tone, but decreased BP. These changes may be linked to the increased cardiovascular risk and possibly the increased risk of aortic dilatation in TS.

  15. A Mathematical Model of the Circadian Phase-Shifting Effects of Exogenous Melatonin

    OpenAIRE

    Breslow, Emily R.; Phillips, Andrew J. K.; Huang, Jean M.; St Hilaire, Melissa A.; Klerman, Elizabeth B.

    2013-01-01

    Melatonin is endogenously produced and released in humans during nighttime darkness and is suppressed by ocular light exposure. Exogenous melatonin is used to induce circadian phase shifts and sleep. The circadian phase-shifting ability of a stimulus (e.g., melatonin or light) relative to its timing may be displayed as a phase response curve (PRC). Published PRCs to exogenous melatonin show a transition from phase advances to delays approximately 1 h after dim light melatonin onset. A previou...

  16. Artificial light and nocturnal activity in gammarids

    Directory of Open Access Journals (Sweden)

    Elizabeth K. Perkin

    2014-03-01

    Full Text Available 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.

  17. Nocturnal panic attacks / Ataques de pânico noturno

    Scientific Electronic Library Online (English)

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

    2002-09-01

    Full Text Available 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.

  18. Ambient Light Intensity, Actigraphy, Sleep and Respiration, Circadian Temperature and Melatonin Rhythms and Daytime Performance of Crew Members During Space Flight on STS-90 and STS-95 Missions

    Science.gov (United States)

    Czeisler, Charles A.; Dijk, D.-J.; Neri, D. F.; Hughes, R. J.; Ronda, J. M.; Wyatt, J. K.; West, J. B.; Prisk, G. K.; Elliott, A. R.; Young, L. R.

    1999-01-01

    Sleep disruption and associated waking sleepiness and fatigue are common during space flight. A survey of 58 crew members from nine space shuttle missions revealed that most suffered from sleep disruption, and reportedly slept an average of only 6.1 hours per day of flight as compared to an average of 7.9 hours per day on the ground. Nineteen percent of crewmembers on single shift missions and 50 percent of the crewmembers in dual shift operations reported sleeping pill usage (benzodiazepines) during their missions. Benzodiazepines are effective as hypnotics, however, not without adverse side effects including carryover sedation and performance impairment, anterograde amnesia, and alterations in sleep EEG. Our preliminary ground-based data suggest that pre-sleep administration of 0.3 mg of the pineal hormone melatonin may have the acute hypnotic properties needed for treating the sleep disruption of space flight without producing the adverse side effects associated with benzodiazepines. We hypothesize that pre-sleep administration of melatonin will result in decreased sleep latency, reduced nocturnal sleep disruption, improved sleep efficiency, and enhanced next-day alertness and cognitive performance both in ground-based simulations and during the space shuttle missions. Specifically, we have carried out experiments in which: (1) ambient light intensity aboard the space shuttle is assessed during flight; (2) the impact of space flight on sleep (assessed polysomnographically and actigraphically), respiration during sleep, circadian temperature and melatonin rhythms, waking neurobehavioral alertness and performance is assessed in crew members of the Neurolab and STS-95 missions; (3) the effectiveness of melatonin as a hypnotic is assessed independently of its effects on the phase of the endogenous circadian pacemaker in ground-based studies, using a powerful experimental model of the dyssomnia of space flight; (4) the effectiveness of melatonin as a hypnotic is assessed during the STS-90 (Neurolab) and STS-95 missions in a double-blind placebo-controlled trial. In both flight-based experiments, the effects of melatonin on sleep stages and spectral composition of the EEG during sleep will be determined as well as its effects on daytime alertness and performance; (5) the impact of space flight on sleep and waking neurobehavioral alertness and performance in 30-45-year-old astronauts is compared with its impact in a 77-year-old astronaut. This case study is the first to assess the effects of space flight on an older individual. Because the investigators are still blind to the treatment in this double-blind, placebo-controlled trial, preliminary results will be presented independent of the drug condition.

  19. Can melatonin help us in radiation oncology treatments?

    Science.gov (United States)

    Mihandoost, Ehsan; Shirazi, Alireza; Mahdavi, Seied Rabie; Aliasgharzadeh, Akbar

    2014-01-01

    Nowadays, radiotherapy has become an integral part of the treatment regimen in various malignancies for curative or palliative purposes. Ionizing radiation interacts with biological systems to produce free radicals, which attack various cellular components. Radioprotectors act as prophylactic agents that are administered to shield normal cells and tissues from the harmful effects of radiation. Melatonin has been shown to be both a direct free radical scavenger and an indirect antioxidant by stimulating antioxidant enzymes and suppressing prooxidative enzymes activity. In addition to its antioxidant property, there have also been reports implicating antiapoptotic function for melatonin in normal cells. Furthermore, through its antitumor and radiosensitizing properties, treatment with melatonin may prevent tumor progression. Therefore, addition of melatonin to radiation therapy could lower the damage inflicted to the normal tissue, leading to a more efficient tumor control by use of higher doses of irradiation during radiotherapy. Thus, it seems that, in the future, melatonin may improve the therapeutic gain in radiation oncology treatments. PMID:24900972

  20. [Melatonin as a regulator of human sleep and circadian systems].

    Science.gov (United States)

    Mishima, Kazuo

    2012-07-01

    Melatonin(N-acetyl-5-methoxytryptamine) is synthesized from tryptophan and is intensively secreted into the blood only in darkness (nighttime) by the pineal gland. Melatonin is not only the most reliable marker of internal circadian phase but also a potent sleep-promoting and circadian phase regulatory agent in humans. There is evidence that daytime administered melatonin is able to exhibit short-acting hypnagogic effect and phase-shifting of the circadian rhythms such that sleep timing and associated various physiological functions realign at a new desired phase. Under favor of these properties, melatonin and melatonin receptor agonists have been shown to be potent therapeutic agents for the treatment of circadian rhythm sleep disorders and some type of insomnia. PMID:22844795

  1. High levels of melatonin generated during the brewing process.

    Science.gov (United States)

    Garcia-Moreno, H; Calvo, J R; Maldonado, M D

    2013-08-01

    Beer is a beverage consumed worldwide. It is produced from cereals (barley or wheat) and contains a wide array of bioactive phytochemicals and nutraceutical compounds. Specifically, high melatonin concentrations have been found in beer. Beers with high alcohol content are those that present the greatest concentrations of melatonin and vice versa. In this study, gel filtration chromatography and ELISA were combined for melatonin determination. We brewed beer to determine, for the first time, the beer production steps in which melatonin appears. We conclude that the barley, which is malted and ground in the early process, and the yeast, during the second fermentation, are the largest contributors to the enrichment of the beer with melatonin. PMID:23607887

  2. Coordinated regulation of melatonin synthesis and degradation genes in rice leaves in response to cadmium treatment.

    Science.gov (United States)

    Byeon, Yeong; Lee, Hyoung Yool; Hwang, Ok Jin; Lee, Hye-Jung; Lee, Kyungjin; Back, Kyoungwhan

    2015-05-01

    We investigated the expression patterns of genes involved in melatonin synthesis and degradation in rice leaves upon cadmium (Cd) treatment and the subcellular localization sites of melatonin 2-hydroxylase (M2H) proteins. The Cd-induced synthesis of melatonin coincided with the increased expression of melatonin biosynthetic genes including tryptophan decarboxylase (TDC), tryptamine 5-hydroxylase (T5H), and N-acetylserotonin methyltransferase (ASMT). However, the expression of serotonin N-acetyltransferase (SNAT), the penultimate gene in melatonin biosynthesis, was downregulated, suggesting that melatonin synthesis was counter-regulated by SNAT. Notably, the induction of melatonin biosynthetic gene expression was coupled with the induction of four M2H genes involved in melatonin degradation, which suggests that genes for melatonin synthesis and degradation are coordinately regulated. The induced M2H gene expression was correlated with enhanced M2H enzyme activity. Three of the M2H proteins were localized to the cytoplasm and one M2H protein was localized to chloroplasts, indicating that melatonin degradation occurs both in the cytoplasm and in chloroplasts. The biological activity of 2-hydroxymelatonin in the induction of the plant defense gene expression was 50% less than that of melatonin, which indicates that 2-hydroxymelatonin may be a metabolite of melatonin. Overall, our data demonstrate that melatonin synthesis occurs in parallel with melatonin degradation in both chloroplasts and cytoplasm, and the resulting melatonin metabolite 2-hydroxymelatonin also acts as a signaling molecule for defense gene induction. PMID:25783167

  3. Melatonin and its analogs in insomnia and depression.

    Science.gov (United States)

    Cardinali, Daniel P; Srinivasan, Venkataramanujan; Brzezinski, Amnon; Brown, Gregory M

    2012-05-01

    Benzodiazepine sedative-hypnotic drugs are widely used for the treatment of insomnia. Nevertheless, their adverse effects, such as next-day hangover, dependence and impairment of memory, make them unsuitable for long-term treatment. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause hangover or show any addictive potential. However, there is a lack of consistency on its therapeutic value (partly because of its short half-life and the small quantities of melatonin employed). 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. The MT(1) and MT(2) melatonergic receptor ramelteon was effective in increasing total sleep time and sleep efficiency, as well as in reducing sleep latency, in insomnia patients. The melatonergic antidepressant agomelatine, displaying potent MT(1) and MT(2) melatonergic agonism and relatively weak serotonin 5HT(2C) receptor antagonism, was found effective in the treatment of depressed patients. However, long-term safety studies are lacking for both melatonin agonists, particularly considering the pharmacological activity of their metabolites. In view of the higher binding affinities, longest half-life and relative higher potencies of the different melatonin agonists, studies using 2 or 3mg/day of melatonin are probably unsuitable to give appropriate comparison of the effects of the natural compound. Hence, clinical trials employing melatonin doses in the range of 50-100mg/day are warranted before the relative merits of the melatonin analogs versus melatonin can be settled. PMID:21951153

  4. Melatonin for pre- and postoperative anxiety in adults

    DEFF Research Database (Denmark)

    Hansen, Melissa V; Halladin, Natalie L

    2015-01-01

    BACKGROUND: Anxiety in relation to surgery is a well-known problem. Melatonin offers an atoxic alternative to benzodiazepines in ameliorating this condition in the pre- and postoperative period. OBJECTIVES: To assess the effect of melatonin on pre- and postoperative anxiety in adults when comparing melatonin with placebo or when comparing melatonin with benzodiazepines. SEARCH METHODS: The following databases were searched on 19 April 2013: CENTRAL, MEDLINE, EMBASE, CINAHL and Web of Science. For ongoing trials and protocols we searched clinicaltrials.gov, Current Controlled Trials and the World Health Organization (WHO) International Clinical Trials Registry Platform. We reran the search in October 2014. We will deal with any studies of interest when we update the review. SELECTION CRITERIA: Randomized, placebo-controlled or standard treatment-controlled, or both, studies that evaluated the effect of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patientsof both genders (15 to 90 years of age) undergoing any kind of surgical procedure in which it was necessary to use general, regional or topical anaesthesia. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two review authors. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimen, preoperative anxiety outcome measures and postoperative anxiety outcome measures. MAIN RESULTS: This systematic review identified 12 randomized controlled trials (RCTs) including 774 patients that assessed melatonin for treating preoperative anxiety, postoperative anxiety or both. Four of the 12 studies compared melatonin, placebo and midazolam, whereas the remaining eight studies compared melatonin and placebo only.The quality of the evidence for our primary outcome (melatonin versus placebo for preoperative anxiety) was high. More than half of the included studies had a low risk of selection bias and at least 75% of the included studies had a low risk of attrition, performance and detection bias. Most of the included studies had an unclear risk of reporting bias.Eight out the 10 studies that assessed the effect of melatonin on preoperative anxiety using a visual analogue scale (VAS) (ranging from 0 to 100 mm, higher scores indicate greater anxiety) showed a reduction compared to placebo. The reported estimate of effect (relative effect -13.36, 95% confidence interval (CI) -16.13 to -10.58; high quality evidence) was based on a meta-analysis of seven studies. Two studies did not show any difference between melatonin and placebo. Two studies comparing melatonin with midazolam using a VAS found no evidence of a difference in preoperative anxiety between the two groups (relative effect -1.18, 95% CI -2.59 to 0.23; low quality evidence).Eight studies assessed the effect of melatonin on postoperative anxiety. Four of these studies measuring postoperative anxiety 90 minutes postoperatively using a VAS did not find any evidence of a difference between melatonin and placebo (relative effect -3.71, 95% CI -9.26 to 1.84). Conversely, two studies showed a reduction of postoperative anxiety measured six hours after surgery using the State-Trait Anxiety Inventory (STAI) when comparing melatonin with placebo (relative effect -5.31, 95% CI -8.78 to -1.84; moderate quality evidence). Two studies comparing melatonin with midazolam using a VAS did not find any evidence of a difference between the two groups in postoperative anxiety (relative effect -2.02, 95% CI -5.82 to 1.78). AUTHORS' CONCLUSIONS: When compared to placebo, melatonin given as premedication (tablets or sublingually) can reduce preoperative anxiety in adults (measured 50 to 100 minutes after administration). Melatonin may be equally as effective as standard treatment with midazolam in reducing preoperative anxiety in adults (measured 50 to 100 minutes after administration). The effect of melatonin on postoperative anxiety (measured 90minutes

  5. Nocturnal panic attack: is it an another subtype?

    Directory of Open Access Journals (Sweden)

    Sezgin Erdiman

    2011-01-01

    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.

  6. 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 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)

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

    Directory of Open Access Journals (Sweden)

    Lemoine P

    2011-07-01

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

  8. Nocturnal frontal lobe epilepsy in mucopolysaccharidosis.

    Science.gov (United States)

    Bonanni, Paolo; Volzone, Anna; Randazzo, Giovanna; Antoniazzi, Lisa; Rampazzo, Angelica; Scarpa, Maurizio; Nobili, Lino

    2014-10-01

    Nocturnal frontal lobe epilepsy (NFLE) is an epileptic syndrome that is primarily characterized by seizures with motor signs occurring almost exclusively during sleep. We describe 2 children with mucopolysaccharidosis (MPS) who were referred for significant sleep disturbance. Long term video-EEG monitoring (LT-VEEGM) demonstrated sleep-related hypermotor seizures consistent with NFLE. No case of sleep-related hypermotor seizures has ever been reported to date in MPS. However, differential diagnosis with parasomnias has been previously discussed. The high frequency of frontal lobe seizures causes sleep fragmentation, which may result in sleep disturbances observed in at least a small percentage of MPS patients. We suggest monitoring individuals with MPS using periodic LT-VEEGM, particularly when sleep disorder is present. Moreover, our cases confirm that NFLE in lysosomal storage diseases may occur, and this finding extends the etiologic spectrum of NFLE. PMID:24447995

  9. Behavioral alarm treatment for nocturnal enuresis

    Directory of Open Access Journals (Sweden)

    Rodrigo F. Pereira

    2010-06-01

    Full Text Available PURPOSES: To investigate the efficacy of alarm treatment in a sample of Brazilian children and adolescents with nocturnal enuresis and relate treatment success to age and type of clinical support. MATERIALS AND METHODS: During 32 weeks, 84 children and adolescents received alarm treatment together with weekly psychological support sessions for individual families or groups of 5 to 10 families. RESULTS: 71% of the participants achieved success, defined as 14 consecutive dry nights. The result was similar for children and adolescents and for individual or group support. The time until success was shorter for participants missing fewer support sessions. CONCLUSIONS: Alarm treatment was effective for the present sample, regardless of age or type of support. Missing a higher number of support sessions, which may reflect low motivation for treatment, increased the risk of failure.

  10. Behavioral alarm treatment for nocturnal enuresis

    Scientific Electronic Library Online (English)

    Rodrigo F., Pereira; Edwiges F. M., Silvares; Paula F., Braga.

    2010-06-01

    Full Text Available PURPOSES: To investigate the efficacy of alarm treatment in a sample of Brazilian children and adolescents with nocturnal enuresis and relate treatment success to age and type of clinical support. MATERIALS AND METHODS: During 32 weeks, 84 children and adolescents received alarm treatment together w [...] ith weekly psychological support sessions for individual families or groups of 5 to 10 families. RESULTS: 71% of the participants achieved success, defined as 14 consecutive dry nights. The result was similar for children and adolescents and for individual or group support. The time until success was shorter for participants missing fewer support sessions. CONCLUSIONS: Alarm treatment was effective for the present sample, regardless of age or type of support. Missing a higher number of support sessions, which may reflect low motivation for treatment, increased the risk of failure.

  11. A conceptual view on inertial oscillations and nocturnal low-level jets

    OpenAIRE

    Wiel, B.J.H., van de; Moene, A.F.; Steeneveld, G. J.; Baas, P.; Bosveld, F.C.; Holtslag, A.A.M.

    2010-01-01

    In the present work Blackadar's concept on nocturnal inertial oscillations is extended. Blackadar's concept describes frictionless inertial oscillations above the nocturnal inversion layer. The current work includes frictional effects within the nocturnal boundary layer. As a result it is shown that the nocturnal wind speed profile describes an oscillation around the nocturnal equilibrium wind vector, rather than around the geostrophic wind vector (as in the Blackadar case). By using this per...

  12. Effect of Melatonin on Human Dental Papilla Cells

    Directory of Open Access Journals (Sweden)

    Ryusuke Tachibana

    2014-09-01

    Full Text Available Melatonin regulates a variety of biological processes, which are the control of circadian rhythms, regulation of seasonal reproductive function and body temperature, free radical scavenging and so on. Our previous studies have shown that various cells exist in human and mouse tooth germs that express the melatonin 1a receptor (Mel1aR. However, little is known about the effects of melatonin on tooth development and growth. The present study was performed to examine the possibility that melatonin might exert its influence on tooth development. DP-805 cells, a human dental papilla cell line, were shown to express Mel1aR. Expression levels of mRNA for Mel1aR in DP-805 cells increased until 3 days after reaching confluence and decreased thereafter. Real-time reverse transcription-polymerase chain reaction showed that melatonin increased the expression of mRNAs for osteopontin (OPN, osteocalcin (OCN, bone sialoprotein (BSP, dentin matrix protein-1 (DMP-1 and dentin sialophosphoprotin (DSPP. Melatonin also enhanced the mineralized matrix formation in DP-805 cell cultures in a dose-dependent manner. These results strongly suggest that melatonin may play a physiological role in tooth development/growth by regulating the cellular function of odontogenic cells in tooth germs.

  13. Melatonin and Atopy: Role in Atopic Dermatitis and Asthma

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    Lucia Marseglia

    2014-08-01

    Full Text Available Melatonin may have important immunostimulatory actions in allergic diseases, in addition to its well-known antioxidant and cytoprotective effects in several inflammatory conditions. The activation of the immune system leads to free radical production associated with decreased melatonin levels and depressed antioxidant enzyme activities in several inflammatory diseases. Many skin disorders, including atopic dermatitis, are accompanied by infiltration and activation of mast cells, which release vasoactive and proinflammatory mediators. Experimental data suggest that melatonin inhibits development of atopic eczema and reduces serum total IgE and IL-4. Allergic asthma is a condition characterized by bronchial hyperresponsiveness and the presence of IgE antibodies in response to inhaled allergens; often there is also enhanced total serum IgE levels. Melatonin regulates smooth muscle tone and influences the immune response. Melatonin may, however, act as a pro-inflammatory agent in asthma leading to bronchial constriction. The safety of melatonin as a sleep-inducing agent has been confirmed in asthmatic subjects, but its routine use is not recommended in bronchial asthma. This review summarizes what is known about the role of melatonin as an immunomodulatory agent in asthma and atopic eczema.

  14. Solubilization and purification of melatonin receptors from lizard brain

    International Nuclear Information System (INIS)

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

  15. Melatonin reduces 3H-nitrendipine binding in the heart.

    Science.gov (United States)

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

    1994-10-01

    The effect of melatonin on cardiac and brain voltage-sensitive calcium channels, as measured by 3H-nitrendipine binding, was examined in rats 3 hr after melatonin administration (either 0.5 or 1.0 mg/kg given subcutaneously). Scatchard analysis of the data on specific binding of 3H-nitrendipine with crude cardiac membranes from melatonin treated rats revealed significant decreases (P < 0.05 and P < 0.01 for the 0.5 and 1.0 mg/kg melatonin doses, respectively) in the density of Ca2+ channels without a change in their affinity for the ligand. At doses of 0.5 and 1.0 mg/kg of melatonin, Bmax values were 157 and 142 fmoles/mg protein, respectively, compared with a control value of 199 fmoles/mg protein in crude cardiac membranes. In brain, melatonin treatment did not statistically significantly influence either 3H-nitrendipine binding or its affinity when compared with control animals. These results suggest that melatonin modulates the functional status of voltage sensitive calcium channels in the heart, changes that may have implications for normal cardiac physiology and for the pharmacological manipulation of the heart. PMID:7938033

  16. A radiobiological review on melatonin. A novel radioprotector

    International Nuclear Information System (INIS)

    Complete text of publication follows. For the sake of improvement in radiation therapy, radiobiology plays a crucial role through explaining observed phenomena, and suggesting improvements to existing therapies. Due to the damaging effects of ionizing radiation, radiobiologists have long been interested in identifying novel, nontoxic, effective, and convenient compounds to protect humans against radiation induced normal tissue injuries. Melatonin (N-acetyl-5-methoxytryptamine), the chief secretory product of the pineal gland in the brain, has been documented to ameliorate the oxidative injuries due to ionizing radiation. This article reviews different features that make melatonin a potentially useful radioprotector. Moreover, based on radiobiological models we hypothesize that melatonin may postpone the saturation of repair enzymes which leads to repairing more induced damage by repair system and more importantly allows the use of higher doses of radiation during radiotherapy to get a better therapeutic ratio. The implications of the accumulated observations suggest by virtue of melatonin's radioprotective and anticancer effects; it is time to use it as a radioprotector both for radiation workers and patients suffering from cancer either alone for cancer inhibition or in combination with traditional radiotherapy for getting a favorable efficacy/toxicity ratio during the treatment. Although compelling evidence suggests that melatonin may be effective for a variety of datonin may be effective for a variety of disorders, the optimum dose of melatonin for human radioprotection is yet to be determined by further research. We propose that, in the future melatonin improve therapeutic ratio in radiation oncology.

  17. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

    OpenAIRE

    Dubocovich, Margarita L.; Delagrange, Philippe; Krause, Diana N.; Sugden, David; Cardinali, Daniel P.; Olcese, James

    2010-01-01

    The hormone melatonin (5-methoxy-N-acetyltryptamine) is synthesized primarily in the pineal gland and retina, and in 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. Melatonin receptors receive and translate melatonin's message to influence daily and seasonal rhythms of physiology and behavior. The melatonin message is transla...

  18. Melatonin, human aging, and age-related diseases.

    Science.gov (United States)

    Karasek, M

    2004-01-01

    The worldwide prolongation of the mean life expectancy has resulted in a rapid increase of the size of the elderly population (over the age of 60), both in numbers and as a proportion of the whole. As a consequence, increasing the number of potential beneficiaries of health and pension funds, mainly those aged 65 and over raises many social and economic problems since they are supported by a relatively smaller number of potential contributors, i.e. those in the economically active ages between 18 and 64. Therefore, there is a search for any therapeutic agent improving quality of life in the elderly. A role for melatonin as such a compound was recently suggested. In this survey, data on the possible role of melatonin in human aging and age-related diseases are briefly presented. Undoubtedly the aging process is multi-factorial, and no single factor has been identified which satisfactorily explains the phenomenon. Although many theories relating the pineal gland and its secretory product melatonin to aging have been proposed, the role of this agent in the aging process is still unclear. However, for several reasons it seems reasonable to postulate a role for melatonin in this process. Melatonin levels decline gradually over the life-span and may be related to lowered sleep efficacy, very often associated with advancing age, as well as to deterioration of many circadian rhythms. Melatonin exhibits immunomodulatory properties, and a remodeling of immune system function is an integral part of aging. Finally, because melatonin is a potent free radical scavenger, its deficiency may result in reduced antioxidant protection in the elderly which may have significance not only for aging per se but also may contribute to the incidence or severity of some age-related diseases. Presently available data do not allow us to conclude that melatonin may have a role in extending normal longevity. However, although melatonin cannot be recognized as 'rejuvenating' agent, some of its actions may be beneficial for the aging process. Administration of melatonin may improve temporal organization in advanced age. Moreover, it has beneficial effects on sleep as well as age-related diseases. Although recommendations of melatonin supplementation in elderly should be considered, there is a need for extensive studies on the use of melatonin in order to improve the quality of life in advanced age. PMID:15582288

  19. Diurnal rhythm of melatonin binding in the rat suprachiasmatic nucleus

    International Nuclear Information System (INIS)

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

  20. Reactions of melatonin with radicals in deoxygenated aqueous solution

    International Nuclear Information System (INIS)

    Reactions of melatonin (N-acetyl-5-methoxytryptamine) with radiolytically generated radicals were studied. Reaction of melatonin with OH radicals is diffusion-controlled (k=1.2 x 1010 dm3 mol-1 x s-1), the main (but not the only one) intermediate being the indolyl-type radical, while the rate constant for the reaction with hydrated electrons is k=4.3 x 108 dm3 x mol-1 x s-1. Melatonin is capable of scavenging tert-butanol radicals, while its reactivity towards polymer radicals of poly(acrylic acid) and poly(vinyl pyrrolidone) is very low. (author)

  1. Effectiveness of Psychological and Pharmacological Treatments for Nocturnal Enuresis.

    Science.gov (United States)

    Houts, Arthur C.; And Others

    1994-01-01

    Assesses overall effectiveness of psychological and pharmacological treatments, relative effectiveness of specific treatments, and moderators of treatment effectiveness for nocturnal enuretic children via quantitative integration of research. Findings confirm that more children benefit from psychological than from pharmacological interventions and…

  2. Sickle Cell Anemia: Iron Availability and Nocturnal Oximetry

    OpenAIRE

    Cox, SE; L'Esperance, V; Makani, J.; Soka, D; Prentice, AM; Hill, CM; Kirkham, FJ

    2012-01-01

    STUDY OBJECTIVE: To test the hypothesis that low iron availability, measured as transferrin saturation, is associated with low nocturnal hemoglobin oxygen saturation (SpO(2)) in children with homozygous sickle cell anemia (SCA; hemoglobin SS). METHODS: This was a cross-sectional study of Tanzanian children with SCA who were not receiving regular blood transfusions. Thirty-two children (16 boys) with SCA (mean age 8.0, range 3.6-15.3 years) underwent motion-resistant nocturnal oximetry (Masimo...

  3. Nocturnal sleep pattern in native Brazilian Terena adults

    OpenAIRE

    REIMÃO RUBENS; SOUZA JOSÉ CARLOS; GAUDIOSO CARLOS EDUARDO VILELA; GUERRA HELLEN DA COSTA; ALVES ANDREA DAS CHAGAS; OLIVEIRA JOLENE CRISTINA FERREIRA; GNOBIE NILTON CEZAR ANTONIO; SILVÉRIO DESIRÉE CORREA GUERRA

    2000-01-01

    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 ...

  4. Nocturnal Frontal Lobe Epilepsy Presenting as Excessive Daytime Sleepiness

    OpenAIRE

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

    2013-01-01

    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....

  5. 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 transmission may be, however, involved in mediating the effects of Mel on the osmotically-activated OT and PRL release. (author). 48 refs, 3 figs

  6. Melatonin signaling in mouse cerebellar granule cells with variable native MT1 and MT2 melatonin receptors

    OpenAIRE

    Imbesi, Marta; Uz, Tolga; Dzitoyeva, Svetlana; Giusti, Pietro; Manev, Hari

    2008-01-01

    Although G protein-coupled MT1 and MT2 melatonin receptors are expressed in neurons of the mammalian brain including in humans, relatively little is known about the influence of native MT1 and MT2 melatonin receptors on neuronal melatonin signaling. Whereas human cerebellar granule cells (CGC) express only MT1 receptors, mouse CGC express both MT1 and MT2. To study the effects of altered neuronal MT1/MT2 receptors, we used CGC cultures prepared from immature cerebella of wild-type mice (MT1/M...

  7. Sustained delivery of exogenous melatonin influences biomarkers of oxidative stress and total antioxidant capacity in summer-stressed anestrous water buffalo (Bubalus bubalis).

    Science.gov (United States)

    Kumar, Ashok; Mehrotra, S; Singh, G; Narayanan, K; Das, G K; Soni, Y K; Singh, Mahak; Mahla, A S; Srivastava, N; Verma, M R

    2015-06-01

    High ambient temperature during summer in tropical and subtropical countries predisposes water buffaloes (Bubalus bubalis) to develop oxidative stress having antigonadotropic and antisteroidogenic actions. Melatonin is a regulator of seasonal reproduction in photoperiodic species and highly effective antioxidant and free radical scavenger. Therefore, a study was designed to evaluate the effect of sustained-release melatonin on biomarkers of oxidative stress i.e., the serum malondialdehyde (MDA) and nitric oxide (NO), and the total antioxidant capacity (TAC). For the study, postpartum buffaloes diagnosed as summer anestrus (absence of overt signs of estrus, concurrent rectal examination, and RIA for serum progesterone) were grouped as treated (single subcutaneous injection of melatonin at 18 mg/50 kg body weight dissolved in sterilized corn oil as vehicle, n = 20) and untreated (subcutaneous sterilized corn oil, n = 8). Blood sampling for estimation of serum TAC and MDA (mmol/L) and NO (?mol/L) was carried out at 4 days of interval from 8 days before treatment till 28 days after treatment or for the ensuing entire cycle length. Results showed serum TAC concentration was higher in the treatment group with a significant (P melatonin has a protective effect by elevating antioxidant status and reducing oxidative stress resulting in the induction of cyclicity in summer-stressed anestrous buffaloes. PMID:25805692

  8. Melatonin in higher plants: occurrence and possible functions.

    Czech Academy of Sciences Publication Activity Database

    Kolá?, Jan; Machá?ková, Ivana

    2005-01-01

    Ro?. 39, - (2005), s. 333-341. ISSN 0742-3098 Institutional research plan: CEZ:AV0Z50380511 Keywords : Melatonin * Lingulodinium * auxin-like effects Subject RIV: ED - Physiology Impact factor: 5.025, year: 2005

  9. Melatonin is required for the circadian regulation of sleep.

    Science.gov (United States)

    Gandhi, Avni V; Mosser, Eric A; Oikonomou, Grigorios; Prober, David A

    2015-03-18

    Sleep is an evolutionarily conserved behavioral state whose regulation is poorly understood. A classical model posits that sleep is regulated by homeostatic and circadian mechanisms. Several factors have been implicated in mediating the homeostatic regulation of sleep, but molecules underlying the circadian mechanism are unknown. Here we use animals lacking melatonin due to mutation of arylalkylamine N-acetyltransferase 2 (aanat2) to show that melatonin is required for circadian regulation of sleep in zebrafish. Sleep is dramatically reduced at night in aanat2 mutants maintained in light/dark conditions, and the circadian regulation of sleep is abolished in free-running conditions. We find that melatonin promotes sleep downstream of the circadian clock as it is not required to initiate or maintain circadian rhythms. Additionally, we provide evidence that melatonin may induce sleep in part by promoting adenosine signaling, thus potentially linking circadian and homeostatic control of sleep. PMID:25754820

  10. Melatonin improves spermatogonial stem cells transplantation efficiency in azoospermic mice

    Directory of Open Access Journals (Sweden)

    Mohammadreza Gholami

    2014-02-01

    Conclusion: Administration of melatonin (20 mg/kg simultaneously with transplantation of spermatogonial stem cells in azoospermia mouse testis increases the efficiency of transplantation and improves structural properties of the testes tissue.

  11. New actions of melatonin and their relevance to biometeorology

    Science.gov (United States)

    Hardeland, Rüdiger

    Melatonin is not only produced by the pineal gland, retina and parietal but also by various other tissues and cells from vertebrates, invertebrates, fungi, plants, multicellular algae and by unicells. In plants, many invertebrates and unicells, its concentration often exceeds that found in vertebrate blood by several orders of magnitude. The action of melatonin is highly pleiotropic. It involves firstly, direct effects, via specific binding sites in various peripheral tissues and cells of vertebrates, including immunomodulation; secondly, systemic influences on the cytoskeleton and nitric oxide formation, mediated by calmodulin; and thirdly, antioxidative protection, perhaps also in the context of photoprotection in plants and unicells. In some dinoflagellates, melatonin conveys temperature signals. On the basis of these comparisons, melatonin appears to mediate and modulate influences from several major environmental factors, such as the photoperiod, radiation intensity and temperature.

  12. The effect of melatonin on bovine in vitro embryo development

    Directory of Open Access Journals (Sweden)

    B. Gasparrini

    2010-04-01

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

  13. Expression of melatonin and serotonin in human prostate tumors.

    Science.gov (United States)

    Filippov, S V

    2008-02-01

    We present the results of immunohistochemical study demonstrating possible variants of neuroimmunoendocrine regulation of prostate tumor growth with serotonin, melatonin, and other hormones produced by neuroendocrine cells via paracrine and autocrine secretory mechanisms. PMID:19023983

  14. Roles of Melatonin in Fetal Programming in Compromised Pregnancies

    Directory of Open Access Journals (Sweden)

    Yu-Chieh Chen

    2013-03-01

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

  15. Melatonin: a protective and detoxifying agent in paraquat toxicity

    International Nuclear Information System (INIS)

    The ability of melatonin as a protective and detoxifying agent against paraquat-induced oxidative damage in rat lungs and liver was examined. Changes in reduced glutathione (OSH) concentration and malonaldehyde (MDA) level were measured. Pathological examination to lungs and liver was done. Paraquat in 2 doses (20,70 mg/kg) was injected I.P. into rats with melatonin (10 mg/kg) I. P. either before and after paraquat intoxication or only after it. Melatonin proved its protective role when given before and after paraquat intoxication more than its detoxifying effect when given only after paraquat. The biochemical improvement following melatonin therapy was more evident than the histopathological one. (author)

  16. Presence and effects of melatonin in Trypanosoma cruzi.

    Science.gov (United States)

    Macías, M; Rodríguez-Cabezas, M N; Reiter, R J; Osuna, A; Acuña-Castroviejo, D

    1999-09-01

    The unicellular organism Trypanosoma cruzi is an eukaryote whose cell cycle mainly occurs under darkness in the insect gut. The unique external phase corresponds to the metacyclic forms, the forms that are able to infect humans, which appear within the insect deyections. Thus, light may be a powerful stressor in this unicell. Epimastigote forms (the parasite forms that grow and transform to metacyclic forms in the insect gut) of Trypanosoma cruzi grow normally when cultured in a LD cycle of 0:24 hr, reaching exponential growth by the 7th day. A pulse of 2 hr of light (LD 2:22) was enough to block the growth of the epimastigotes, an effect that was correlated with the expression of heat-shock proteins during the first 120 min of light exposure. Thereafter, protein synthesis decreased. Light exposure of metacyclic forms also inhibits the parasitization ability. It is known that light regulates the production of melatonin in most animal species studied, including other unicells such as dinoflagellates. T. cruzi contains and synthesizes melatonin and, thus, light-mediated events on the parasite biological cycle could be mediated by light-induced changes in melatonin produced by this unicell. Epimastigotes cultured under continuous darkness produce melatonin over the 24 hr period in a biphasic manner. Coinciding with the melatonin peaks, there was high melatonin efflux from the parasite into the medium. Epimastigotes cultured for 7 days under a LD cycle of 2:22 hr showed a 55% reduction in melatonin content, although this reduction seems not to be related with the growth delay. In fact, incubation of epimastigotes with exogenous melatonin (1 pM) did not affect parasite growth, but significantly reduced their transformation into metacyclic forms by the 7-8th day of treatment. Thus, the light-dependent decrease in melatonin production by the unicell may be responsible, at least partially, for the light-induce parasitization inhibition. Moreover, melatonin production is highest in the metacyclic forms. These data support a link between light, melatonin production and parasitization ability of T. cruzi and suggest the participation of the indoleamine in its biological cycle. PMID:10496144

  17. 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 suppt 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)

  18. Efectos de la melatonina sobre la macro-arquitectura del sueño en pacientes con demencia tipo Alzheimer / Melatonin effects on macro arquitecture sleep in Alzheimer's disease patients

    Scientific Electronic Library Online (English)

    Manuel Alejandro, Cruz-Aguilar; Ignacio, Ramírez-Salado; Carlos, Cruz-Ulloa; Gloria, Benítez-King.

    2013-08-01

    Full Text Available El objetivo del presente estudio fue determinar los efectos de 5 mg. de melatonina de liberación inmediata sobre la macro-arquitectura del sueño en ocho pacientes con diagnóstico de Demencia Tipo Alzheimer (DTA) de media a moderada. Utilizando la técnica polisomnográfica (PSG) se realizó un estudio [...] simple ciego, no aleatorio, controlado con placebo. Los registros PSG se llevaron a cabo de la siguiente manera: Noche 1: administración de placebo; noche 2 y 3: administración continua de melatonina (5 mg). Observamos que el tratamiento con melatonina durante la primera noche de administración disminuyó significativamente la latencia de la fase 2, del sueño de ondas delta y el sueño de MOR al ser comparadas con el placebo (P ?.05). No se observaron diferencias significativas en el tiempo total de cada fase de sueño; tampoco se observaron diferencias en la eficiencia del sueño en presencia de la melatonina. Sin embargo se observó una tendencia a la disminución del tiempo total de vigilia y un aumento del tiempo total de sueño, principalmente durante la segunda noche de tratamiento. Concluimos que la melatonina puede mejorar el sueño en pacientes con DTA de media a moderada. Abstract in english The objective of the present study was to evaluate the 5 mg. melatonin effects on the sleep macro-architecture in eight patients with middle to moderate Alzheimer's disease (DTA). Using the polysomnography technique (PSG), we made a simple-blind, non-randomized, controlled with placebo study. The PS [...] G was carried out according to the following order: night 1: placebo administration; night 2 and 3: continues melatonin administration. In the first night with melatonin treatment, the sleep latency to the first episode of Stage 2, Delta and REM sleep, was significantly diminished as compared with placebo (?.05). No significant difference in total time of each sleep stage and sleep efficiency was observed. Nevertheless, a tendency to diminish the total time of nocturnal wake and increase of the total sleep time in the second night with melatonin treatment was observed. We conclude that melatonin can improve sleep in patients with middle to moderate DTA.

  19. Melatonin agonists for treatment of sleep and depressive disorders

    OpenAIRE

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

    2011-01-01

    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...

  20. Melatonin Acts as Antioxidant and Improves Sleep in MS Patients

    OpenAIRE

    Adamczyk-sowa, Monika; Pierzchala, Krystyna; Sowa, Pawel; Mucha, Sebastian; Sadowska-bartosz, Izabela; Adamczyk, Jowita; Hartel, Marcin

    2014-01-01

    The relationship between the prevalence of multiple sclerosis (MS) and sunlight’s ultraviolet radiation was proved. Oxidative stress plays a role in the pathogenic traits of MS. Melatonin possesses antioxidative properties and regulates circadian rhythms. Sleep disturbances in MS patients are common and contribute to daytime fatigue. The aim of study was to evaluate 5 mg daily melatonin supplementation over 90 days on serum total oxidant status (TOS), total antioxidant capacity (TAC) and ...

  1. Heteromeric MT1/MT2 Melatonin Receptors Modulate Photoreceptor Function

    OpenAIRE

    Baba, Kenkichi; Benleulmi-Chaachoua, Abla; Journé, Anne-Sophie; Kamal, Maud; Guillaume, Jean-Luc; Dussaud, Sébastien; Gbahou, Florence; Yettou, Katia; Liu, Cuimei; Contreras-Alcantara, Susana; Jockers, Ralf; Tosini, Gianluca

    2013-01-01

    The formation of G protein-coupled receptor (GPCR) heteromers elicits signaling diversification and holds great promise for improved drug selectivity. Most studies have been conducted in heterologous expression systems; however, in vivo validation is missing from most cases thus questioning the physiological significance of GPCR heteromerization. Melatonin MT1 and MT2 receptors have been shown to exist as homo- and heteromers in vitro. We show here that the effect of melatonin on rod photorec...

  2. Pharmacological actions of melatonin in oxygen radical pathophysiology.

    Science.gov (United States)

    Reiter, R; Tang, L; Garcia, J J; Muñoz-Hoyos, A

    1997-01-01

    Melatonin, the chief secretory product of the pineal gland, was recently found to be a free radical scavenger and antioxidant. This review briefly summarizes the published reports supporting this conclusion. Melatonin is believed to work via electron donation to directly detoxify free radicals such as the highly toxic hydroxyl radical. Additionally, in both in vitro and in vivo experiments, melatonin has been found to protect cells, tissues and organs against oxidative damage induced by a variety of free radical generating agents and processes, e.g., the carcinogen safrole, lipopolysaccharide, kainic acid, Fenton reagents, potassium cyanide, L-cysteine, excessive exercise, glutathione depletion, carbon tetrachloride, ischemia-reperfusion, MPTP, amyloid beta (25-35 amino acid residue) protein, and ionizing radiation. Melatonin as an antioxidant is effective in protecting nuclear DNA, membrane lipids and possibly cytosolic proteins from oxidative damage. Also, melatonin has been reported to alter the activities of enzymes which improve the total antioxidative defense capacity of the organism, i.e., superoxide dimutase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and nitric oxide synthase. Most studies have used pharmacological concentrations or doses of melatonin to protect against free radical damage; in a few studies physiological levels of the indole have been shown to be beneficial against oxidative stress. Melatonin's function as a free radical scavenger and antioxidant is likely assisted by the ease with which it crosses morphophysiological barriers, e.g., the blood-brain barrier, and enters cells and subcellular compartments. Whether the quantity of melatonin produced in vertebrate species is sufficient to significantly influence the total antioxidative defense capacity of the organism remains unknown, but its pharmacological benefits seem assured considering the low toxicity of the molecule. PMID:9194681

  3. Melatonin and its use in atherosclerosis and dyslipidemia

    OpenAIRE

    Danilenko KV; Ragino YI.

    2013-01-01

    Konstantin V Danilenko, Yulia I Ragino Institute of Internal Medicine, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Russia Abstract: A review of pineal melatonin synthesis, regulation, and physiological effects indicates that not only does melatonin act as a hormonal signal of darkness, but also that it possesses antioxidant and anti-inflammatory properties. Although oxidation and inflammation play a pivotal role in atherogenesis, no studies have investigated admin...

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

    International Nuclear Information System (INIS)

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

  5. Melatonin and Atopy: Role in Atopic Dermatitis and Asthma

    OpenAIRE

    Lucia Marseglia; Gabriella D'Angelo; Sara Manti; Carmelo Salpietro; Teresa Arrigo; Ignazio Barberi; Reiter, Russel J.; Eloisa Gitto

    2014-01-01

    Melatonin may have important immunostimulatory actions in allergic diseases, in addition to its well-known antioxidant and cytoprotective effects in several inflammatory conditions. The activation of the immune system leads to free radical production associated with decreased melatonin levels and depressed antioxidant enzyme activities in several inflammatory diseases. Many skin disorders, including atopic dermatitis, are accompanied by infiltration and activation of mast cells, which release...

  6. Peripheral and Central Effects of Melatonin on Blood Pressure Regulation

    Directory of Open Access Journals (Sweden)

    Olga Pechanova

    2014-10-01

    Full Text Available The pineal hormone, melatonin (N-acetyl-5-methoxytryptamine, shows potent receptor-dependent and -independent actions, which participate in blood pressure regulation. The antihypertensive effect of melatonin was demonstrated in experimental and clinical hypertension. Receptor-dependent effects are mediated predominantly through MT1 and MT2 G-protein coupled receptors. The pleiotropic receptor-independent effects of melatonin with a possible impact on blood pressure involve the reactive oxygen species (ROS scavenging nature, activation and over-expression of several antioxidant enzymes or their protection from oxidative damage and the ability to increase the efficiency of the mitochondrial electron transport chain. Besides the interaction with the vascular system, this indolamine may exert part of its antihypertensive action through its interaction with the central nervous system (CNS. The imbalance between the sympathetic and parasympathetic vegetative system is an important pathophysiological disorder and therapeutic target in hypertension. Melatonin is protective in CNS on several different levels: It reduces free radical burden, improves endothelial dysfunction, reduces inflammation and shifts the balance between the sympathetic and parasympathetic system in favor of the parasympathetic system. The increased level of serum melatonin observed in some types of hypertension may be a counter-regulatory adaptive mechanism against the sympathetic overstimulation. Since melatonin acts favorably on different levels of hypertension, including organ protection and with minimal side effects, it could become regularly involved in the struggle against this widespread cardiovascular pathology.

  7. Pineal melatonin synthesis in Syrian hamsters: A summary

    Science.gov (United States)

    Rollag, M. D.

    1982-12-01

    During the past decade there has been ample documentation of the proposition that the pineal gland mediates photoperiodic influences upon reproductive behavior of hamsters. It is commonly hypothesized that the pineal gland expresses its activity by transformation of photoperiodic information into an hormonal output, that hormone being melatonin. If this hypothesis is correct, there must be some essential diffrence in melatonin's output when hamsters are exposed to different photoperiodic environments. The experiments summarized in this communication analyze pineal melatonin contents in Syrian hamsters maintained in a variety of photoperiodic conditions during different physiological states. The results demonstrate that adult hamsters have a daily surge in pineal melatonin content throughout their lifetime when exposed to simulated annual photoperiodic cycles. There is some fluctuation in the amount of pineal melatonin produced during different physiological states and photoperiodic environments, but these fluctuations seem small when compared to those normally found for other regulatory hormones. When hamsters are exposed to different photoperiodic regimens, the daily melatonin surge maintains a relatively constant phase relationship with respect to the onset of daily activity. There is a concomitant change in its phase relationship with respect to light-dark transitions.

  8. Effect of Melatonin on Bone Mineral Density of Irradiated Rats

    Directory of Open Access Journals (Sweden)

    Zerrin Orbak

    2011-01-01

    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.

  9. Serum levels of melatonin and cytokines in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Naser Farhadi

    2014-04-01

    Full Text Available Cytokines are important factors of the immune system in autoimmune diseases such as multiple sclerosis (MS in which damage caused by oxidants plays a major role in the pathology. Melatonin secreted by the pineal gland has recently been considered as an antioxidant. The purpose of this study was to determine the relationship between melatonin and cytokines in patients with MS. Thirty patients with MS and 30 healthy controls were selected. Serum levels of melatonin and cytokines, including interleukin-4, interferon-?, and tumor necrosis factor alpha (TNF-?, were detected in all participants by the enzyme-linked immunosorbent assay (ELISA method. There was a significant difference between patient and control groups in the levels of melatonin and TNF-?. Also, no significant correlation between the serum levels of melatonin and cytokines in both patient and control groups was seen. We concluded that decrease of melatonin and subsequent increase of pro-inflammatory cytokine, TNF-?, could be a factor in the inflammatory reactions in the pathologic process of MS.

  10. Multiple sclerosis: the role of melatonin and N-acetylserotonin.

    Science.gov (United States)

    Anderson, George; Rodriguez, Moses

    2015-03-01

    Multiple sclerosis (MS) is an immune mediated disorder that is under intensive investigation in an attempt to improve on available treatments. Many of the changes occurring in MS, including increased mitochondrial dysfunction, pain reporting and depression may be partly mediated by increased indoleamine 2,3-dioxygenase, which drives tryptophan to the production of neuroregulatory tryptophan catabolites and away from serotonin, N-acetylserotonin and melatonin production. The consequences of decreased melatonin have classically been attributed to circadian changes following its release from the pineal gland. However, recent data shows that melatonin may be produced by all mitochondria containing cells to some degree, including astrocytes and immune cells, thereby providing another important MS treatment target. As well as being a powerful antioxidant, anti-inflammatory and antinociceptive, melatonin improves mitochondrial functioning, partly via increased oxidative phosphorylation. Melatonin also inhibits demyelination and increases remyelination, suggesting that its local regulation in white matter astrocytes by serotonin availability and apolipoprotein E4, among other potential factors, will be important in the etiology, course and treatment of MS. Here we review the role of local melatonin and its precursors, N-acetylserotonin and serotonin, in MS. PMID:25787187

  11. Wound healing and the effect of pineal gland and melatonin

    Directory of Open Access Journals (Sweden)

    Jacek Drobnik

    2012-02-01

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

  12. Melatonin protects rat liver against irradiation-induced oxidative injury

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the antioxidant roles of different doses of melatonin (5 and 10 mg kg-1) against ?-irradiation-caused oxidative damage in liver tissue after total body irradiation (TBI) with a single dose of 6.0 Gy. Fifty adult rats were divided into 5 equal groups, 10 rats each. Groups I and II were injected with 5 and 10 mg kg-1 of melatonin, and group III was injected with an isotonic NaCl solution. Group IV was injected with only 5 mg kg-1 of melatonin. Group V was reserved as a sham control. Following a 30-min-period, 6.0 Gy TBI was given to groups 1, 2 and 3 in a single fraction. The liver malondialdehyde (MDA) levels, super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured in all groups. TBI resulted in a significant increase in the liver tissue MDA levels and a decrease of SOD and GSH-Px activities. The results demonstrated that the liver tissue MDA levels in irradiated rats that were pretreated with melatonin (5 or 10 mg kg-1) were significantly decreased, while the SOD and GSH-Px activities were significantly increased. Decreasing the MDA levels by melatonin was dose dependent, but the liver tissue SOD and GSH activities were not. The data obtained in this study suggest that melatonin administration prior to irradiation may prevent liver damage by irradiation. (author)

  13. How significant is nocturnal sap flow?

    Science.gov (United States)

    Forster, Michael A

    2014-07-01

    Nocturnal sap flow (Qn) has been found to occur across many taxa, seasons and biomes. There is no general understanding as to how much Qn occurs and whether it is a significant contribution to total daily sap flow (Q). A synthesis of the literature and unpublished data was made to determine how significant is Qn, as a proportion of Q (%Qn), across seasons, biomes, phylogenetic groups and different thermometric sap flow methods. A total of 98 species were analysed to find that %Qn, on average, was 12.03% with the highest average dataset of 69.00%. There was significantly less %Qn in winter than in other temperate seasons, and significantly less %Qn in the wet season than in the dry season. The equatorial and tropical biomes had significantly higher %Qn than the warm temperate and nemoral biomes. The heat ratio method (HRM) and the thermal dissipation (TDP) method had significantly higher %Qn than the heat balance method. Additional analysis between HRM and TDP found HRM to have significantly higher %Qn in winter, wet season and various biomes. In all but one out of 246 cases Qn occurred, demonstrating that Qn is significant and needs to be carefully considered in sap flow and related studies. PMID:24990866

  14. Melatonin suppresses markers of inflammation and oxidative damage in a human daytime endotoxemia model

    DEFF Research Database (Denmark)

    Alamili, Mahdi; Bendtzen, Klaus

    2014-01-01

    Melatonin used as an exogenous drug has been documented to have potent antioxidant and anti-inflammatory effects in animal model. We aimed to examine the effect of melatonin in an experimental human sepsis model.

  15. A one step synthesis of ring labelled melatonin-3H with high specific activity

    International Nuclear Information System (INIS)

    A mixture of brominated melatonin derivatives has been synthesized for use as starting material for preparation of ring tritium labelled melatonin by catalytic hydrogenolysis. The high specific activity obtained makes this product useful in radioimmunoassay studies. (author)

  16. 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

  17. Diurnal Profiles of Melatonin Synthesis-Related Indoles, Catecholamines and Their Metabolites in the Duck Pineal Organ

    Directory of Open Access Journals (Sweden)

    Bogdan Lewczuk

    2014-07-01

    Full Text Available This study characterizes the diurnal profiles of ten melatonin synthesis-related indoles, the quantitative relations between these compounds, and daily variations in the contents of catecholamines and their metabolites in the domestic duck pineal organ. Fourteen-week-old birds, which were reared under a 12L:12D cycle, were killed at two-hour intervals. The indole contents were measured using HPLC with fluorescence detection, whereas the levels of catecholamines and their metabolites were measured using HPLC with electrochemical detection. All indole contents, except for tryptophan, showed significant diurnal variations. The 5-hydroxytryptophan level was approximately two-fold higher during the scotophase than during the photophase. The serotonin content increased during the first half of the photophase, remained elevated for approximately 10 h and then rapidly decreased in the middle of the scotophase. N-acetylserotonin showed the most prominent changes, with a more than 15-fold increase at night. The melatonin cycle demonstrated only an approximately 5-fold difference between the peak and nadir. The 5-methoxytryptamine content was markedly elevated during the scotophase. The 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid and 5-methoxytryptophol profiles were analogous to the serotonin rhythm. The norepinephrine and dopamine contents showed no significant changes. The DOPA, DOPAC and homovanillic acid levels were higher during the scotophase than during the photophase. Vanillylmandelic acid showed the opposite rhythm, with an elevated level during the daytime.

  18. Diurnal profiles of melatonin synthesis-related indoles, catecholamines and their metabolites in the duck pineal organ.

    Science.gov (United States)

    Lewczuk, Bogdan; Zió?kowska, Natalia; Prusik, Magdalena; Przybylska-Gornowicz, Barbara

    2014-01-01

    This study characterizes the diurnal profiles of ten melatonin synthesis-related indoles, the quantitative relations between these compounds, and daily variations in the contents of catecholamines and their metabolites in the domestic duck pineal organ. Fourteen-week-old birds, which were reared under a 12L:12D cycle, were killed at two-hour intervals. The indole contents were measured using HPLC with fluorescence detection, whereas the levels of catecholamines and their metabolites were measured using HPLC with electrochemical detection. All indole contents, except for tryptophan, showed significant diurnal variations. The 5-hydroxytryptophan level was approximately two-fold higher during the scotophase than during the photophase. The serotonin content increased during the first half of the photophase, remained elevated for approximately 10 h and then rapidly decreased in the middle of the scotophase. N-acetylserotonin showed the most prominent changes, with a more than 15-fold increase at night. The melatonin cycle demonstrated only an approximately 5-fold difference between the peak and nadir. The 5-methoxytryptamine content was markedly elevated during the scotophase. The 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid and 5-methoxytryptophol profiles were analogous to the serotonin rhythm. The norepinephrine and dopamine contents showed no significant changes. The DOPA, DOPAC and homovanillic acid levels were higher during the scotophase than during the photophase. Vanillylmandelic acid showed the opposite rhythm, with an elevated level during the daytime. PMID:25032843

  19. Effects of melatonin administration on daytime sleep after simulated night shift work

    OpenAIRE

    Sharkey, Katherine M.; Fogg, Louis F.; Eastman, Charmane I.

    2001-01-01

    Disturbed sleep and on-the-job sleepiness are widespread problems among night shift workers. The pineal hormone melatonin may prove to be a useful treatment because it has both sleep-promoting and circadian phase-shifting effects. This study was designed to isolate melatonin’s sleep-promoting effects, and to determine whether melatonin could improve daytime sleep and thus improve night time alertness and performance during the night shift. The study utilized a placebo-controlled, double-bli...

  20. Electron Microscopic Study on the Effects of Melatonin on Early Spermatids in the Rat Testis

    OpenAIRE

    El-alfy, Sherif H.; Rashed, Rashed-morad A.; Mohamed, Ihab K.

    2011-01-01

    Melatonin is a neuroendocrine hormone secreted principally at night by pineal gland and regulates biological rhythms. Exogenous melatonin is used as a potential treatment for insomnia, sleep disorders and depression. The present investigation was undertaken to characterize the morphological defects in spermatids during early phases of spermiogenesis in melatonin-treated rats using electron microscopy. A single melatonin dose of either 0.05 or 0.1 mg kg-1 body weight was orally administrated t...

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

    OpenAIRE

    Gooneratne, Nalaka S.; Edwards, Alena Y. Z.; Zhou, Chen; Cuellar, Norma; Grandner, Michael A.; Barrett, Jeffrey S.

    2012-01-01

    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 this, we conducted a ran...

  2. Melatonin Distribution Reveals Clues to Its Biological Significance in Basal Metazoans

    OpenAIRE

    Roopin, Modi; Levy, Oren

    2012-01-01

    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...

  3. Evaluation of the combined treatment with cisplatin and melatonin on neuroblastoma cell viability and antioxidant capacity

    OpenAIRE

    Adem KARA; YUCEL, Atakan; YUCEL, Nermin; Ozcan, Halil; SELLI, Jale; ÜNAL, Deniz

    2014-01-01

    In this study, we investigated the cell viability and antioxidant effects of melatonin both with and without cisplatin (CDDP) on the cultured neuroblastoma cancer cell line. Neuroblastoma cancer cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) at 37°C with 5% CO2 to examine the cytotoxic effect of melatonin; cells were cultured both CDDP with and without melatonin and thereafter counted in a 48-well microplate. To examine the effect of melatonin and CDDP, cells were di...

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

    OpenAIRE

    Fernie, K J; Bird, D. M.; Petitclerc, D

    1999-01-01

    Birds reproduce within electromagnetic fields (EMFs) from transmission lines. Melatonin influences physiologic and behavioral processes that are critical to survival, and melatonin has been equivocally suppressed by EMFs in mammalian species. We examined whether EMFs affect photophasic plasma melatonin in reproducing adult and fledgling American kestrels (Falco sparverius), and whether melatonin was correlated with body mass to explain previously reported results. Captive kestrel pairs were b...

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

    OpenAIRE

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

    2011-01-01

    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...

  6. The role of mitochondrial complex III in melatonin induced ROS production in cultured mesangial cells

    OpenAIRE

    ZHANG, HONG-MEI; Zhang, Yi-Qiang; Zhang, Bin-Xian

    2010-01-01

    Melatonin is a potent scavenger of reactive oxygen (ROS) and reactive nitrogen species (RNS). At pharmacological concentrations, however, melatonin is documented to cause ROS/RNS production, especially in cultured cancerous cells. Currently, the mechanism responsible for melatonin-induced ROS generation remains elusive. In this study, we provide evidence that melatonin, at micromolar concentrations induced rapid ROS generation by a mitochondrial dependent mechanism in primary human mesangial ...

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

    OpenAIRE

    Joanna Dulce Favacho de Oliveira Torres; Ricardo de Souza Pereira

    2010-01-01

    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. Proto...

  8. Melatonin receptor and KATP channel modulation in experimental vascular dementia.

    Science.gov (United States)

    Singh, Prabhat; Gupta, Surbhi; Sharma, Bhupesh

    2015-04-01

    Cerebrovascular and cardiovascular diseases are stated as important risk factors of vascular dementia (VaD) and other cognitive disorders. In the central nervous system, melatonin (MT1/MT2) as well as serotonin subtype 2C (5-HT2C) receptors is pharmacologically associated with various neurological disorders. Brain mitochondrial potassium channels have been reported for their role in neuroprotection. This study has been structured to investigate the role of agomelatine, a melatonergic MT1/MT2 agonist and nicorandil, a selective ATP sensitive potassium (KATP) channel opener in renal artery ligation (two-kidney-one-clip: 2K1C) hypertension induced endothelial dysfunction, brain damage and VaD. 2K1C-renovascular hypertension has increased mean arterial blood pressure (MABP), impaired memory (elevated plus maze and Morris water maze), endothelial function, reduced serum nitrite/nitrate and increased brain damage (TTC staining of brain sections). Furthermore, 2K1C animals have shown high levels of oxidative stress in serum (increased thiobarbituric acid reactive species-TBARS with decreased levels of glutathione-GSH, superoxide dismutase-SOD and catalase-CAT), in the aorta (increased aortic superoxide anion) and in the brain (increased TBARS with decreased GSH, SOD and CAT). 2K1C has also induced a significant increase in brain inflammation (myeloperoxidase-MPO levels), acetylcholinesterase activity (AChE) and calcium levels. Impairment in mitochondrial complexes like NADH dehydrogenase (complex-I), succinate dehydrogenase (complex-II) and cytochrome oxidase (complex-IV) was also noted in 2K1C animals. Administration of agomelatine, nicorandil and donepezil significantly attenuated 2K1C-hypertension induced impairments in memory, endothelial function, nitrosative stress, mitochondrial dysfunction, inflammation and brain damage. Therefore, modulators of MT1/MT2 receptors and KATP channels may be considered as potential agents for the management of renovascular hypertension induced VaD. PMID:25659733

  9. Identification of melatonin-regulated genes in the ovine pituitary pars tuberalis, a target site for seasonal hormone control.

    Science.gov (United States)

    Dupré, Sandrine M; Burt, Dave W; Talbot, Richard; Downing, Alison; Mouzaki, Daphne; Waddington, David; Malpaux, Benoit; Davis, Julian R E; Lincoln, Gerald A; Loudon, Andrew S I

    2008-11-01

    The pars tuberalis (PT) of the pituitary gland expresses a high density of melatonin (MEL) receptors and is believed to regulate seasonal physiology by decoding changes in nocturnal melatonin secretion. Circadian clock genes are known to be expressed in the PT in response to the decline (Per1) and onset (Cry1) of MEL secretion, but to date little is known of other molecular changes in this key MEL target site. To identify transcriptional pathways that may be involved in the diurnal and photoperiod-transduction mechanism, we performed a whole genome transcriptome analysis using PT RNA isolated from sheep culled at three time points over the 24-h cycle under either long or short photoperiods. Our results reveal 153 transcripts where expression differs between photoperiods at the light-dark transition and 54 transcripts where expression level was more globally altered by photoperiod (all time points combined). Cry1 induction at night was associated with up-regulation of genes coding for NeuroD1 (neurogenic differentiation factor 1), Pbef / Nampt (nicotinamide phosphoribosyltransferase), Hif1alpha (hypoxia-inducible factor-1alpha), and Kcnq5 (K+ channel) and down-regulation of Rorbeta, a key clock gene regulator. Using in situ hybridization, we confirmed day-night differences in expression for Pbef / Nampt, NeuroD1, and Rorbeta in the PT. Treatment of sheep with MEL increased PT expression for Cry1, Pbef / Nampt, NeuroD1, and Hif1alpha, but not Kcnq5. Our data thus reveal a cluster of Cry1-associated genes that are acutely responsive to MEL and novel transcriptional pathways involved in MEL action in the PT. PMID:18669596

  10. Melatonin in Children with Autism Spectrum Disorders: Endogenous and Pharmacokinetic Profiles in Relation to Sleep

    Science.gov (United States)

    Goldman, Suzanne E.; Adkins, Karen W.; Calcutt, M. Wade; Carter, Melissa D.; Goodpaster, Robert L.; Wang, Lily; Shi, Yaping; Burgess, Helen J.; Hachey, David L.; Malow, Beth A.

    2014-01-01

    Supplemental melatonin has been used to treat sleep onset insomnia in children with autism spectrum disorders (ASD), although the mechanism of action is uncertain. We assessed endogenous and supplemental melatonin profiles in relation to sleep in nine children with ASD. In endogenous samples, maximal melatonin concentration (C[subscript max]) and…

  11. Direct fluorination of melatonin and 5-hydroxy-L-tryptophan with [18F]F2

    International Nuclear Information System (INIS)

    In order that melatonin receptors may be studied in man with positron emission tomography, melatonin labelled with a positron emitting isotope is needed. The preparation of 6-fluoro-melatonin labelled with F-18 is described. Using the same fluorination method, 5-hydroxy-6-(F-18)fluorotryptophan and 4-(F-18)fluoro-5-hydroxy-tryptophan were also prepared. (UK)

  12. 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)

  13. Melatonin and adjustment to phase shift.

    Science.gov (United States)

    Arendt; Deacon; English; Hampton; Morgan

    1995-12-01

    The pineal hormone melatonin has clear circadian phase-shifting effects in humans which have recently been formalized as a phase response curve. Its potential use in circadian rhythm disorders has been investigated in field studies of jet lag and shift work and in simulated phase shift. A substantial amount of information indicates that in the majority of subjects it hastens adaptation of both subjective and objective measures to forced shifts in time cues with few reported side-effects. Field studies of its use in adaptation to shift work are sparse and preliminary but the first indications are positive. In some blind subjects with sleep disturbance it can stabilize sleep onset time without necessarily entraining all circadian rhythms and it can advance sleep timing in delayed sleep-phase insomnia. Acute suppression of core body temperature may be an integral part of the phase-shifting mechanism. PMID:10607217

  14. [Melatonin, aging and tumors of the prostate].

    Science.gov (United States)

    Kniaz'kin, I V

    2008-01-01

    Morphological changes that take place in the epiphysis in the course of age involution are inseparably associated with a drastic decrease in the synthesis of melatonin (MT) - the main hormone of the pineal gland that coordinates biorhythms of the body at all system levels. The pineal gland is not the only organ able producing MT Multiple research have proved that the extrapineal MT is also widely present in human and animal organism. In this paper we present the results of our own research upon whose analysis we can base a hypothesis that MT and serotonin can play an important role in the mechanisms of the prostate aging. On the one hand, they both can perform regulatory function for the prostate's normal work; on the other, these agents in one form or another can take part in the pathogenesis of such disfunctions as cancer and benign prostate hyperplasia. PMID:18546827

  15. Exogenous melatonin's phase-shifting effects on the endogenous melatonin profile in sighted humans: a brief review and critique of the literature.

    Science.gov (United States)

    Lewy, A J; Sack, R L

    1997-12-01

    Melatonin's phase-shifting effects in humans are thought by some investigators to be subtle, particularly in comparison to those achieved with appropriately timed bright light exposure. The initial study in sighted people was only intermittently successful in phase advancing the endogenous melatonin profile. The study of free-running blind people showed statistically significant phase advances the day after melatonin administration. When holding the light-dark cycle constant, consistent phase advances the day after melatonin administration in sighted people were first shown in the course of describing the melatonin phase response curve (PRC), which also provided the first evidence that melatonin could cause phase delays. More recent studies have replicated the PRC and shown that phase shifts can occur in response to physiological doses within 1 day. This article reviews this literature and attempts to reconcile some of the results from differing studies. If the timing of melatonin administration is optimized according to the melatonin PRC, then consistent phase advances and delays can be achieved. If a reliable and sensitive circadian phase marker (e.g., the highly resolved dim light melatonin onset) is used, then phase shifts can be demonstrated consistently--even a small shift the day after a single physiological dose. The present authors predict that in the near future, melatonin administration will become as useful as bright light exposure in the treatment of circadian phase disorders. PMID:9406034

  16. 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

    Directory of Open Access Journals (Sweden)

    G Fideleff

    2011-10-01

    Full Text Available 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.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. Considering 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 not been thoroughly characterized yet. This led us to evaluate 6-SM concentrations in GH deficient children and adults on and

  17. 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

    Scientific Electronic Library Online (English)

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

    2011-10-01

    Full Text Available 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 not been thoroughly characterized yet. This led us to evaluate 6-S

  18. A radiobiological review on melatonin. A novel radioprotector

    International Nuclear Information System (INIS)

    In spite of the fact that radiotherapy is a common and effective tool for cancer treatment; the radio sensitivity of normal tissues adjacent to the tumor which are unavoidably exposed to radiation limits therapeutic gain. For the sake of improvement in radiation therapy, radiobiology- the study of the action of ionizing radiation on living things- plays a crucial role through explaining observed phenomena, and suggesting improvements to existing therapies. Due to the damaging effects of ionizing radiation, radiobiologists have long been interested in identifying novel, nontoxic, effective, and convenient compounds to protect humans against radiation induced normal tissue injuries. In hundreds of investigations, melatonin (N-acetyl-5-methoxytryptamine), the chief secretory product of the pineal gland in the brain, has been documented to ameliorate the oxidative injuries due to ionizing radiation. This article reviews different features that make melatonin a potentially useful radioprotector. Moreover, based on radiobiological models we can hypothesize that melatonin may postpone the saturation of repair enzymes which leads to repairing more induced damage by repair system and more importantly allows the use of higher doses of radiation during radiotherapy to get a better therapeutic ratio. The implications of the accumulated observations suggest by virtue of melatonin's radioprotective and anticancer effects; it is time to use it as a radioprotector both for radiation it as a radioprotector both for radiation workers and patients suffering from cancer either alone for cancer inhibition or in combination with traditional radiotherapy for getting a favorable efficacy/toxicity ratio during the treatment. Although compelling evidence suggests that melatonin may be effective for a variety of disorders, the optimum dose of melatonin for human radioprotection is yet to be determined. We propose that, in the future, melatonin improve the therapeutic ratio in radiation oncology. (author)

  19. Is eucalyptol the cause of nocturnal events observed in Australia?

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, I. K.; Suni, T.; Groenholm, T.; Boy, M.; Vehkamaeki, H.; Kulmala, M. (Division of Atmospheric Sciences, Dept. of Physics, Univ. of Helsinki (Finland)); Hakola, H.; Hellen, H. (Finnish Meteorological Institute, Air Chemistry Laboratory, Helsinki (Finland)); Valmari, T.; Arvela, H. (STUK - Radiation and nuclear safety authority, Helsinki (Finland))

    2009-07-01

    Nocturnal nucleation events were observed from July 2005 to October 2006 in Tumbarumba in New South Wales, Australia. These events were observed on one third of the nights and they were often much more intense than normal daytime events. One of the main features found in this environment was the abundance of eucalyptol among the volatile organic compounds (VOC) emitted by the local Eucalypt forest. In contrast, in most other forest environments, such as Hyytiaelae in southern Finland, eucalyptol is a minor component of VOC emissions. Therefore, the objective of this study was to evaluate the role of eucalyptol in the nocturnal nucleation events. For this purpose, a series of experiments and quantum mechanical calculations were performed. Both approaches showed that the role of eucalyptol in the nocturnal events can be ruled out. (orig.)

  20. Sickle Cell Anemia: Iron Availability and Nocturnal Oximetry

    Science.gov (United States)

    Cox, Sharon E.; L'Esperance, Veline; Makani, Julie; Soka, Deogratius; Prentice, Andrew M.; Hill, Catherine M.; Kirkham, Fenella J.

    2012-01-01

    Study Objective: To test the hypothesis that low iron availability, measured as transferrin saturation, is associated with low nocturnal hemoglobin oxygen saturation (SpO2) in children with homozygous sickle cell anemia (SCA; hemoglobin SS). Methods: This was a cross-sectional study of Tanzanian children with SCA who were not receiving regular blood transfusions. Thirty-two children (16 boys) with SCA (mean age 8.0, range 3.6-15.3 years) underwent motion-resistant nocturnal oximetry (Masimo Radical) and had steady state serum transferrin saturation and hematological indices assessed. Results: Higher transferrin saturation, adjusted for age and ?-thalassemia deletion, was associated with lower nocturnal mean SpO2 (p = 0.013, r2 = 0.41), number of SpO2 dips/h > 3% from baseline (p = 0.008, r2 = 0.19) and with min/h with SpO2 < 90% (p = 0.026 r2 = 0.16). Transferrin saturation < 16% (indicative of iron deficiency) was associated with a 2.2% higher nocturnal mean SpO2. Conclusions: Contrary to our hypothesis, higher iron availability, assessed by transferrin saturation, is associated with nocturnal chronic and intermittent hemoglobin oxygen desaturation in SCA. Whether these associations are causal and are driven by hypoxia-inducible factor and hepcidin-mediated upregulation of demand for iron warrants further investigation. Citation: Cox SE; L'Esperance V; Makani J; Soka D; Prentice AM; Hill CM; Kirkham FJ. Sickle cell anemia: iron availability and nocturnal oximetry. J Clin Sleep Med 2012;8(5):541-545. PMID:23066366

  1. Ocellar optics in nocturnal and diurnal bees and wasps.

    Science.gov (United States)

    Warrant, Eric J; Kelber, Almut; Wallén, Rita; Wcislo, William T

    2006-12-01

    Nocturnal bees, wasps and ants have considerably larger ocelli than their diurnal relatives, suggesting an active role in vision at night. In a first step to understanding what this role might be, the morphology and physiological optics of ocelli were investigated in three tropical rainforest species - the nocturnal sweat bee Megalopta genalis, the nocturnal paper wasp Apoica pallens and the diurnal paper wasp Polistes occidentalis - using hanging-drop techniques and standard histological methods. Ocellar image quality, in addition to lens focal length and back focal distance, was determined in all three species. During flight, the ocellar receptive fields of both nocturnal species are centred very dorsally, possibly in order to maximise sensitivity to the narrow dorsal field of light that enters through gaps in the rainforest canopy. Since all ocelli investigated had a slightly oval shape, images were found to be astigmatic: images formed by the major axis of the ocellus were located further from the proximal surface of the lens than images formed by the minor axis. Despite being astigmatic, images formed at either focal plane were reasonably sharp in all ocelli investigated. When compared to the position of the retina below the lens, measurements of back focal distance reveal that the ocelli of Megalopta are highly underfocused and unable to resolve spatial detail. This together with their very large and tightly packed rhabdoms suggests a role in making sensitive measurements of ambient light intensity. In contrast, the ocelli of the two wasps form images near the proximal boundary of the retina, suggesting the potential for modest resolving power. In light of these results, possible roles for ocelli in nocturnal bees and wasps are discussed, including the hypothesis that they might be involved in nocturnal homing and navigation, using two main cues: the spatial pattern of bright patches of daylight visible through the rainforest canopy, and compass information obtained from polarised skylight (from the setting sun or the moon) that penetrates these patches. PMID:18089077

  2. A train of blue light pulses delivered through closed eyelids suppresses melatonin and phase shifts the human circadian system

    Directory of Open Access Journals (Sweden)

    Figueiro MG

    2013-10-01

    Full Text Available Mariana G Figueiro, Andrew Bierman, Mark S ReaLighting Research Center, Rensselaer Polytechnic Institute, Troy, NY, USAAbstract: A model of circadian phototransduction was published in 2005 to predict the spectral sensitivity of the human circadian system to narrow-band and polychromatic light sources by combining responses to light from the spectral-opponent “blue” versus “yellow” cone bipolar pathway with direct responses to light by the intrinsically photosensitive retinal ganglion cells. In the model, depolarizing “blue” responses, but not hyperpolarizing “yellow” responses, from the “blue” versus “yellow” pathway are combined with the intrinsically photosensitive retinal ganglion cell responses. Intrinsically photosensitive retinal ganglion cell neurons are known to be much slower to respond to light than the cone pathway, so an implication of the model is that periodic flashes of “blue” light, but not “yellow” light, would be effective for stimulating the circadian system. A within-subjects study was designed to test the implications of the model regarding retinal exposures to brief flashes of light. The study was also aimed at broadening the foundation for clinical treatment of circadian sleep disorders by delivering flashing light through closed eyelids while people were asleep. In addition to a dark control night, the eyelids of 16 subjects were exposed to three light-stimulus conditions in the phase delay portion of the phase response curve while they were asleep: (1 2-second flashes of 111 W/m2 of blue (?max ? 480 nm light once every minute for 1 hour, (2 131 W/m2 of green (?max ? 527 nm light, continuously on for 1 hour, and (3 2-second flashes of the same green light once every minute for 1 hour. Inferential statistics showed that the blue flash light-stimulus condition significantly delayed circadian phase and significantly suppressed nocturnal melatonin. The results of this study further our basic understanding of circadian phototransduction and broaden the technical foundations for delivering light through closed eyelids during sleep for treating circadian sleep disorders.Keywords: melatonin, dim light melatonin onset, eyelids, flashing blue light, circadian rhythms, sleep

  3. Presence of melatonin in various cat brainstem nuclei determined by radioimmunoassay

    International Nuclear Information System (INIS)

    Microdissected samples of juvenile cat brain tissue were assayed for melatonin content using a double antibody radioimmunoassay. Immunoreactive melatonin was consistently detected, albeit in variable amounts, in pineal, habenula, the region of the nucleus gracilis, gigantocellular reticular formation of the pons and medulla oblongata. Among the negative areas were raphe nuclei, substantia nigra dn locus caeruleus. These findings suggest that melatonin may play a role in some structures of the central nervous system outside the pineal-hypothalamo-pituitary axis. This immunoreactive melatonin could reflect a local synthesis, or a tissular uptake of melatonin from blood or cerebrospinal fluid. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    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

    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.

  5. Melatonin regulates the rhythmic migration of neutrophils in live zebrafish.

    Science.gov (United States)

    Ren, Da-long; Li, Ya-juan; Hu, Bing-bing; Wang, Han; Hu, Bing

    2015-05-01

    The circadian clock plays a vital role in physiology and behavior such as the sleep-wake cycle and blood pressure and hormone levels. Immune responses also display circadian rhythmicity and particularly pineal melatonin contributes to immunological processes. Little attention, however, is given to mechanisms underlying rhythmic neutrophil responses to the injury. Here, we used a transgenic Tg(lyz:EGFP) zebrafish tail fin transection model to investigate whether the recruitment of neutrophils toward the injured site is regulated by the circadian clock. We found that migrating neutrophils display robust rhythmicity, peaking at darkness. Melatonin positively regulates rhythmic neutrophil migration, as evidenced that treatment with melatonin at low dosage can significantly enhance neutrophil recruitment toward the injured site, which is attenuated by luzindole treatment and in pinealectomized fish. Furthermore, using a transgenic zebrafish eyeball model, we observed that melatonin enhances secretion of two cytokines, TNF-? and IL-8, both of which markedly enhance neutrophil migration. Taken together, these results highlight a positive role of melatonin in rhythmic neutrophil migration and help obtain a better understanding of circadian regulation in immunology. PMID:25763660

  6. PACAP – Melatonin Interaction in Mouse Suprachiasmatic Nucleus Slice Cultures

    Directory of Open Access Journals (Sweden)

    Ehab TOUSSON

    2010-09-01

    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.

  7. Melatonin, a possible promising panacea for premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Ting Guo

    2011-04-01

    Full Text Available Premature ovarian failure (POF is characterized by impairment of ovarian function unrelated to elevatedfollicle-stimulating hormone (FSH before the age of 40. The consequence of POF is severe and distinctive, presentingfrom infertility to symptoms caused by hormone deprivation. The mechanism of POF remains unclearand current treatments are therefore ineffective. Melatonin (N-acetyl-5-methoxytryptamine is a neuroendocrinalhormone chiefly secreted by the pineal body. Melatonin exerts extensive physiological and pharmacologicaleffects on the biological rhythm, oxidative stress, reproduction, autoimmune and tumourigenesis. However,current researches have not yet brought melatonin into the study of POF. In the present review, we have involvedstate-of-the-art research progress of melatonin in ovary with regard to oxidation, follicle formation and function,and ovarian autoimmune disorders since these aspects mainly dispose to POF development. The features thatmelatonin scavenges reactive oxygen species (ROS, directly and indirectly induces follicle maturation, ovulationand inhibits apoptosis, and modulates autoimmune derangements in the ovaries are highly indicative that melatonincan effect in combating POF. Also, in this respect we have discussed the possibility of applying melatoninin the treatment of POF and have listed evidence of studies in vitro and in vivo. Vacant research directions aresubsequently suggested and the future application of melatonin in POF treatment is prospected.

  8. Melatonin protects uterus and oviduct exposed to nicotine in mice

    Directory of Open Access Journals (Sweden)

    Seyed Saadat Seyedeh Nazanin

    2014-03-01

    Full Text Available Smoking is associated with higher infertility risk. The aim of this study was to evaluate protective effects of melatonin on the uterus and oviduct in mice exposed to nicotine. Adult female mice (n=32 were divided into four groups. Group A: control animals received normal saline, Group B: injected with nicotine 40 ?g/kg, Group C: injected with melatonin 10 ?g, Group D: injected with nicotine 40 ?g/kg and melatonin 10 ?g. All animals were treated over 15 days intraperitoneally. On the 16th day, animals in the estrus phase were dissected and their uterus and oviducts were removed. Immunohistochemistry was recruited for studying apoptosis and for detection of estrogen receptor (ER alpha in luminal epithelium of the uterus and oviduct. Enzyme-linked immunosorbent assay was used for serum estradiol level determination. Nicotine in group B decreased estradiol level and ERalpha numbers both in the uterus and oviduct (p<0.05. Co-administration of melatonin-nicotine in Group D ameliorated the histology of the uterus and oviduct, increased ERalpha numbers and reduced apoptosis in the uterus and oviduct compared with the nicotine Group B (p<0.05. This study indicates that nicotine impairs the histology of the uterus and oviduct and co-administration of melatonin-nicotine ameliorates these findings, partly through alteration in ERalpha numbers and reduction of apoptosis

  9. Melatonin prevents hyperglycemia in a model of sleep apnea

    Scientific Electronic Library Online (English)

    Renata Schenkel Rivera, Kaminski; Denis, Martinez; Micheli, Fagundes; Emerson Ferreira, Martins; Carolina Caruccio, Montanari; Darlan Pase, Rosa; Cintia Zappe, Fiori; Norma Possa, Marroni.

    2015-02-01

    Full Text Available Objective Obstructive sleep apnea is a common disorder associated with aging and obesity. Apneas cause repeated arousals, intermittent hypoxia, and oxidative stress. Changes in glucolipidic profile occur in apnea patients, independently of obesity. Animal models of sleep apnea induce hyperglycemia. [...] This study aims to evaluate the effect of the antioxidants melatonin and N-acetylcysteine on glucose, triglyceride, and cholesterol levels in animals exposed to intermittent hypoxia. Materials and methods Two groups of Balb/c mice were exposed to intermittent hypoxia (n = 36) or sham intermittent hypoxia (n = 36) for 35 days. The intermittent hypoxia group underwent a total of 480 cycles of 30 seconds reducing the inspired oxygen fraction from 21% to 7 ± 1% followed by 30 seconds of normoxia, during 8 hours daily. Melatonin or N-acetylcysteine were injected intraperitonially daily from day 21 on. Results At day 35, glucose levels were significantly higher in the intermittent hypoxia group than in the control group. The intermittent hypoxia groups receiving N-acetylcysteine and vehicle showed higher glucose levels than the group receiving melatonin. The lipid profile was not affected by intermittent hypoxia or antioxidant administration. Conclusions The present results suggest that melatonin prevents the well-recognized increase in glucose levels that usually follows exposure to intermittent hypoxia. Further exploration of the role of melatonin in sleep apnea is warranted. Arch Endocrinol Metab. 2015;59(1):66-70

  10. Melatonin receptors in diabetes: a potential new therapeutical target?

    Science.gov (United States)

    She, Meihua; Laudon, Moshe; Yin, Weidong

    2014-12-01

    Melatonin is synthesized and secreted mainly by the pineal gland in a circadian fashion, and it thus mediates endogenous circadian rhythms and influences other physiological functions. Both the G-protein coupled receptors MT1 (encoded by MTNR1A) and MT2 (encoded by MTNR1B) in mammals mediate the actions of melatonin. Evidence from in vivo and in vitro studies proved a key role of melatonin in the regulation of glucose metabolism and the pathogenesis of diabetes, as further confirmed by the recent studies of human genetic variants of MTNR1B. Remarkably, it was also suggested that genetic variations within MTNR1B disordered ?-cells function directly, i.e. insulin secretion. This indicated the functional link between MT2 and T2D risk at the protein level, and it may represent the prevailing pathomechanism for how impaired melatonin signaling causes metabolic disorders and increases the T2D risk. It is speculated that melatonin and its receptors may be a new therapeutic avenue in diabetes. PMID:25160745

  11. ARE THE MELATONIN SUPPLEMENTS POTENTIAL TREATMENT OPTIONS? A SYSTEMATIC REVIEW

    Directory of Open Access Journals (Sweden)

    Subhranil Saha*, Munmun Koley and Sandip Patra

    2013-10-01

    Full Text Available Introduction: Melatonin is a neuro-hormone secreted from the pineal gland and involved in various regulatory activities in body. Ever-increasing use of melatonin supplements and enlarging research evidences make the authors undertook the review to arrive at a qualitative conclusion whether melatonin supplements can act as potential treatment options or not.Methodology: A comprehensive search was undertaken in different electronic databases using various search terms. A total of 225 studies were identified including clinical research studies and basic experiments. Data were extracted individually from the studies and compiled in the end.Results: Melatonin has been used successfully in chronic insomnia and as an anti-oxidant in cancer and other age-related neuro-degenerative disorders, especially Alzheimer’s disease and Autistic disorders. Its evidences of use in other conditions remained insufficient and inconclusive.Conclusion: Melatonin therapy may be considered as efficacious and safe in insomnia and as an anti-oxidant; however, other roles needs to be evaluated in further studies.

  12. Effects of melatonin on liver of rats with experimental hyperthyroid

    Directory of Open Access Journals (Sweden)

    Oner J.

    2005-01-01

    Full Text Available The aim of this study was to investigate the structural changes that occurred in the liver of rats with experimental hyperthyroidism and the possible effects of melatonin on these changes. The animals were designated as control group (group I, 3,3', 5-Triiodo-I-Thyronine (T3 injected group (group II and T3+ melatonin injected group (group III. At the end of study, tissue specimens were examined for changes in structure. In the T3 injected group dilatation in sinusoids and pale cytoplasm were observed, as well as an increased number of the Kupffer cells and an increased amount of glycogen. In T3 + melatonin injected group, the amount of glycogen was similar to the T3 injected groups while the number of Kupffer cells increased but sinusoid largeness and hepatocyte structure were similar to the control. On electron microscopic examination the mitochondria of T3 injected group were slightly larger than those of the control group. In T3 + melatonin injected group enlargement in the spaces of Disse, increased number of lipid vacuoles of Ito cells and increased number of microvilli of hepatocytes were observed. Kupffer cells were more active in this group. The results of this study indicate that T3 injection causes structural changes in the liver, and melatonin hormone has a small, if any, protective effect on the liver of rats with hyperthyroid.

  13. Immunohistochemical distribution of leptin in kidney tissues of melatonin treated diabetic rats.

    Science.gov (United States)

    Elis Yildiz, S; Deprem, T; Karadag Sari, E; Bingol, S A; Koral Tasci, S; Aslan, S; Nur, G; Sozmen, M

    2015-05-01

    We examined using immunohistochemistry the distribution of leptin in kidney tissues of melatonin treated, streptozotocin (STZ) diabetic rats. The animals were divided into five groups: control, sham, melatonin-treated, diabetic and melatonin-treated diabetic. Kidney sections were prepared and stained with hematoxylin and eosin, and Crossman's triple staining for histological examination. The immunohistochemical localization of leptin in the kidney tissue was determined using the streptavidin-biotin-peroxidase method. We determined that on days 7 and 14, the leptin immunoreactivity of the diabetic and melatonin-treated diabetic groups was weaker than for the other groups. Weak immunoreactivity was found in the proximal and distal tubules of the kidney in the diabetic and melatonin-treated diabetic groups on days 7 and 14, and strong immunoreactivity was found in the control, sham and melatonin groups. Melatonin application had no significant effect on leptin production in the kidney tissues of diabetic rats. PMID:25539049

  14. Diurnal melatonin patterns in children: ready to apply in clinical practice?

    Science.gov (United States)

    Praninskien?, R?ta; Dumalakien?, Irena; Kemežys, Robertas; Mauricas, Mykolas; Ju?ait?, Aurelija

    2012-02-01

    Experimental and clinical studies suggest that endogenous melatonin plays an important role in pediatric sleep regulation. This finding led to the introduction of exogenous melatonin to treat sleep disturbances. Optimizing the treatment algorithm involves a review of melatonin measurements and interpretations in clinical practice. Diurnal patterns of salivary melatonin and urinary metabolite 6-sulfatoxymelatonin were investigated in 29 children and adolescents (age, 5.5-17.3 years) by measuring concentrations every 3 hours. Relationships between melatonin parameters (peak concentrations and area under the time curve) and anthropometric measures (height, weight, and body mass index), age, and sleep scores (Sleep Disturbance Scale for Children) were investigated. High interindividual variability was evident in melatonin diurnal profiles. Melatonin production (adjusted to body weight) decreased with age and sexual maturation (P needed. PMID:22264699

  15. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety

    OpenAIRE

    Wade Alan G; Ford Ian; Crawford Gordon; McConnachie Alex; Nir Tali; Laudon Moshe; Zisapel Nava

    2010-01-01

    Abstract Background Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also ma...

  16. Synthesis of 2-iodo- and 2-phenyl-[{sup 11}C]melatonin: potential PET tracers for melatonin binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Chen Jiajun; Fiehn-Schulze, Brita; Firnau, Guenter [Section of Radiology and Nuclear Medicine, Hamilton Health Sciences Corporation, McMaster University Medical Centre, Hamilton, ON (Canada); Brough, Paul A.; Snieckus, Victor [Department of Chemistry, University of Waterloo, Waterloo, ON (Canada)

    1998-12-01

    Two {sup 11}C-labelled melatonin derivatives, 2-iodo-[{sup 11}C]melatonin (2-iodo-5-methoxy-N[{sup 11}C-acetyl]-tryptamine, an agonist) and 2-phenyl-[{sup 11}C]melatonin (2-phenyl-5-methoxy-N[{sup 11}C-acetyl]tryptamine, a putative antagonist) were synthesized from [{sup 11}C]carbon dioxide. The reaction sequence was common to both compounds and consisted of three steps: (i) carbonylation of methyl magnesium bromide with [{sup 11}C]carbon dioxide, (ii) conversion of the adduct to [{sup 11}C]acetyl chloride, (iii) acetylation of the amine precursors (2-iodo-5-methoxy-tryptamine or 2-phenyl-5-methoxy-tryptamine) with [{sup 11}C]acetyl chloride. The precursors were especially prepared. The radiochemical yield was 19% for 2-iodomelatonin and 32% for 2-phenymelatonin, based on [{sup 11}C]carbon dioxide; the specific activity ranged from 300 to 600 mCi/{mu}mol. Both labelled 2-substituted-melatonins are intended to be used as radiotracers to study melatonin binding sites in man with positron emission tomography.

  17. Synthesis of 2-iodo- and 2-phenyl-[11C]melatonin: potential PET tracers for melatonin binding sites

    International Nuclear Information System (INIS)

    Two 11C-labelled melatonin derivatives, 2-iodo-[11C]melatonin (2-iodo-5-methoxy-N[11C-acetyl]-tryptamine, an agonist) and 2-phenyl-[11C]melatonin (2-phenyl-5-methoxy-N[11C-acetyl]tryptamine, a putative antagonist) were synthesized from [11C]carbon dioxide. The reaction sequence was common to both compounds and consisted of three steps: (i) carbonylation of methyl magnesium bromide with [11C]carbon dioxide, (ii) conversion of the adduct to [11C]acetyl chloride, (iii) acetylation of the amine precursors (2-iodo-5-methoxy-tryptamine or 2-phenyl-5-methoxy-tryptamine) with [11C]acetyl chloride. The precursors were especially prepared. The radiochemical yield was 19% for 2-iodomelatonin and 32% for 2-phenymelatonin, based on [11C]carbon dioxide; the specific activity ranged from 300 to 600 mCi/?mol. Both labelled 2-substituted-melatonins are intended to be used as radiotracers to study melatonin binding sites in man with positron emission tomography

  18. The pineal neurohormone melatonin and its physiologic opiatergic immunoregulatory role

    Directory of Open Access Journals (Sweden)

    Georges J. M. Maestroni

    1987-01-01

    Full Text Available The pineal gland functions as a neuroendocrine transducer that coordinate the organism response to changing environmental stimuli such as light and temperature. The main and best known pineal neurohormone is melatonin that is synthesized and released in a circadian fashion with a peak during the night darkness hours. We have recently reported that melatonin exerts important immuno regulatory functions. Here we describe the astonishing property of exogenous melatonin which is able to counteract completely the depressive effect of anxiety-restraint stress and/or of corticosterone on thymus weight, andibody production and antiviral responses. This effect seems to be mediated by antigen-activated T cells via an opiatergic mechanism.

  19. The pineal neurohormone melatonin and its physiologic opiatergic immunoregulatory role

    Scientific Electronic Library Online (English)

    Georges J. M., Maestroni; Ario, Conti; Walter, Pierpaoli.

    Full Text Available The pineal gland functions as a neuroendocrine transducer that coordinate the organism response to changing environmental stimuli such as light and temperature. The main and best known pineal neurohormone is melatonin that is synthesized and released in a circadian fashion with a peak during the nig [...] ht darkness hours. We have recently reported that melatonin exerts important immuno regulatory functions. Here we describe the astonishing property of exogenous melatonin which is able to counteract completely the depressive effect of anxiety-restraint stress and/or of corticosterone on thymus weight, andibody production and antiviral responses. This effect seems to be mediated by antigen-activated T cells via an opiatergic mechanism.

  20. Theoretical insight into the antioxidant properties of melatonin and derivatives.

    Science.gov (United States)

    Johns, Jeffrey R; Platts, James A

    2014-10-21

    Density functional theory calculations on melatonin, metabolites and synthetic derivatives thereof, and a range of other biological antioxidant molecules are presented, with a view to understanding the antioxidant ability of these molecules. After testing of the necessary calculations, we show that melatonin lies close to vitamin E on a donor-acceptor map, indicating that it should be an excellent electron donor but a poor acceptor. The neutral radical metabolite of melatonin is predicted to be an even better donor, whereas other metabolites and synthetic derivatives should retain antioxidant ability but are less powerful than the parent. QSAR models of antioxidant activity, measured in two different assays, are presented. We show that octanol-water partition coefficient is an excellent predictor of activity in lipophilic media, while properties related to electron donor/acceptor power give good fits against activity in aqueous media. PMID:25164170

  1. A systematic review of peri-operative melatonin

    DEFF Research Database (Denmark)

    Andersen, L P H; Werner, M U

    2014-01-01

    We systematically reviewed randomised controlled trials of peri-operative melatonin. We included 24 studies of 1794 participants that reported eight peri-operative outcomes: anxiety; analgesia; sleep quality; oxidative stress; emergence behaviour; anaesthetic requirements; steal induction; and safety. Compared with placebo, melatonin reduced the standardised mean difference (95% CI) pre-operative anxiety score by 0.88 (0.44-1.33) and postoperative pain score by 1.06 (0.23-1.88). The magnitude of effect was unreliable due to substantial statistical heterogeneity, with I(2) 87% and 94%, respectively. Qualitative reviews suggested the melatonin improved sleep quality and emergence behaviour, and might be capable of reducing oxidative stress and anaesthetic requirements.

  2. Identification and characteristic of melatonin receptor in human stomach

    International Nuclear Information System (INIS)

    To determine whether melatonin receptors (MR) exist in human stomach, specific binding of melatonin receptor i human stomach was measured by radioligand binding assay. The maximum binding capacity (Bmax) of MR was 0.48 +- 0.11 fmol/mg protein. Equilibrium dissociation constant (Kd) of MR was 51 +- 17 pmol/L. Standard criteria of binding sites-saturability, reversibility, specificity and high affinity were observed in this assay to determine melatonin binding sites. The following was the subcellular distribution of MR in human stomach in an descending order: nuclear, mitochondrial, microsomal and cytosol. Specific binding of MR could be inhibited by GTPrS. Conclusion: MRs are present in the human stomach and the above findings suggested that MR may be coupled with Gi protein system

  3. Hormone melatonin influence on cell to cell information transfer

    International Nuclear Information System (INIS)

    The radiation-induced bystander effect is a phenomenon whereby cellular damage is expressed in unirradiated neighboring cells, connected or not to an irradiated cell or cells. The influence of melatonin on bystander effect has been studied, using the colony-forming and micronuclei assay in cultured human cells. It was shown that donor medium transfer to unirradiated cells caused bystander effect. Irradiated culture medium itself (without cells) does not able to induce bystander effect. Melatonin increased the colony-forming ability of bystander recipient cells and reduced micronucleus rate, when it was added into culture medium after irradiation of donor cells. The received results indicate that melatonin reduces transfer of bystander signals from irradiated cells to unirradiated ones. It's important for bystander mechanism study as well as for radiation risk assessment and cancer radiotherapy. (authors)

  4. Sleep board review question: nocturnal hypoxemia in COPD

    Directory of Open Access Journals (Sweden)

    Poongkunran C

    2013-01-01

    Full Text Available No abstract available. Article truncated at end of question. Question: Which of the following is the strongest predictor of nocturnal hypoxemia in patients with chronic obstructive pulmonary disease (COPD?1.Forced expiratory volume in 1 second (FEV12.Age3.Daytime Oxygen Saturation4.Radiological severity of COPD…

  5. Sleep board review question: nocturnal hypoxemia in COPD

    OpenAIRE

    Poongkunran C; Budhiraja R

    2013-01-01

    No abstract available. Article truncated at end of question. Question: Which of the following is the strongest predictor of nocturnal hypoxemia in patients with chronic obstructive pulmonary disease (COPD)?1.Forced expiratory volume in 1 second (FEV1)2.Age3.Daytime Oxygen Saturation4.Radiological severity of COPD…

  6. Transient pancytopenia associated with parvovirus infection in paroxysmal nocturnal haemoglobinuria.

    OpenAIRE

    Lakhani, A K; Malkovska, V.; Bevan, D. H.; Anderson, M J

    1987-01-01

    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.

  7. Successful Use of the Nocturnal Urine Alarm for Diurnal Enuresis.

    Science.gov (United States)

    Friman, Patrick C.; Vollmer, Dennis

    1995-01-01

    A urine alarm, typically used to treat nocturnal enuresis, was effectively used to treat diurnal enuresis in a 15-year-old female with depression, attention deficit hyperactivity disorder, and conduct disorder. The study indicated that the alarm eliminated wetting in both treatment phases and that continence was maintained at three-month and…

  8. Primary Nocturnal Enuresis: A Structural and Strategic Family Systems Approach.

    Science.gov (United States)

    Fletcher, Teresa B.

    2000-01-01

    Exploration of the literature regarding primary nocturnal enuresis suggests there are various causes including genetic, biological, physiological, and psychological explanations. Treatments typically consist of medication and behavioral intervention. However, it was believed that this enuretic case was caused by psychological trauma. A series of…

  9. Successful use of the nocturnal urine alarm for diurnal enuresis.

    OpenAIRE

    Friman, P. C.; Vollmer, D.

    1995-01-01

    We report the effects of using a urine alarm, typically employed for nocturnal enuresis, to treat chronic diurnal enuresis in a 15-year-old female resident at Boys' Town. The results of an ABAB reversal design indicate that the alarm eliminated wetting in both treatment phases and that continence was maintained at 3- and 6-month follow-up.

  10. Nocturnal Fog and Stratus Over the Northern Plains

    Science.gov (United States)

    The Cooperative Institute for Meteorological Satellite Studies (CIMSS) at the University of Wisconsin-Madison has provided GOES satellite imagery of the nocturnal fog and stratus formed over the Northern Plains for the overnight hours of November 2, 1998. In addition, descriptions of the GOES satellite imagery and an image of the topography of the region are also available.

  11. Does petroleum development affect burrowing owl nocturnal space-use?

    Energy Technology Data Exchange (ETDEWEB)

    Scobie, Corey; Wellicome, Troy; Bayne, Erin [Department of Biological Sciences, University of Alberta (Canada)], email: cscobie@ualberta.ca, email: tiw@ualberta.ca, email: bayne@ualberta.ca

    2011-07-01

    Decline all over Canada in the population of burrowing owls, a federally listed endangered species, has raised concerns about the possible influence of petroleum infrastructure development on owl nocturnal space-use while foraging. Roads, wells, pipelines and sound-producing facilities related to petroleum development change the landscape and can influence the owls' mortality risk. For 3 years, 27 breeding adult male burrowing owls with nests close to different petroleum infrastructures were captured and fitted with a miniature GPS datalogger in order to track their nocturnal foraging. Data from these GPS devices were fed into a geographical information system and showed that pipelines and wells did not alter the foraging habits of the owls. Dirt and gravel roads, with little traffic, were preferentially selected by the owls, conceivably because of higher owl mortality risk along paved roads. Sound-producing facilities did not change owls' foraging behaviour, implying that sound may not affect their nocturnal space-use. Traffic data and sound power measurements will be used in further studies in an effort to better understand burrowing owls' nocturnal foraging habits.

  12. Photosynthetic overcompensation under nocturnal warming enhances grassland carbon sequestration.

    Science.gov (United States)

    Wan, Shiqiang; Xia, Jianyang; Liu, Weixing; Niu, Shuli

    2009-10-01

    A mechanistic understanding of the carbon (C) cycle-climate change feedback is essential for projecting future states of climate and ecosystems. Here we report a novel field mechanism and evidence supporting the hypothesis that nocturnal warming in a temperate steppe ecosystem in northern China can result in a minor C sink instead of a C source as models have predicted. Nocturnal warming increased leaf respiration of two dominant grass species by 36.3%, enhanced consumption of carbohydrates in the leaves (72.2% and 60.5% for sugar and starch, respectively), and consequently stimulated plant photosynthesis by 19.8% in the subsequent days. Our experimental findings confirm previous observations of nocturnal warming stimulating plant photosynthesis through increased draw-down of leaf carbohydrates at night. The enhancement of plant photosynthesis overcompensated the increased C loss via plant respiration under nocturnal warming and shifted the steppe ecosystem from a minor C source (1.87 g C x m(-2) x yr(-1)) to a C sink (21.72 g C x m(-2) x yr(-1)) across the three growing seasons from 2006 to 2008. Given greater increases in daily minimum than maximum temperature in many regions, plant photosynthetic overcompensation may partially serve as a negative feedback mechanism for terrestrial biosphere to climate warming. PMID:19886480

  13. Melatonin acts as antioxidant and improves sleep in MS patients.

    Science.gov (United States)

    Adamczyk-Sowa, Monika; Pierzchala, Krystyna; Sowa, Pawel; Mucha, Sebastian; Sadowska-Bartosz, Izabela; Adamczyk, Jowita; Hartel, Marcin

    2014-08-01

    The relationship between the prevalence of multiple sclerosis (MS) and sunlight's ultraviolet radiation was proved. Oxidative stress plays a role in the pathogenic traits of MS. Melatonin possesses antioxidative properties and regulates circadian rhythms. Sleep disturbances in MS patients are common and contribute to daytime fatigue. The aim of study was to evaluate 5 mg daily melatonin supplementation over 90 days on serum total oxidant status (TOS), total antioxidant capacity (TAC) and its influence on sleep quality and depression level of MS patients. A case-control prospective study was performed on 102 MS patients and 20 controls matched for age and sex. The Kurtzke's Expanded Disability Status Scale, magnetic resonance imaging examinations, Athens Insomnia Scale (AIS), Beck Depression Inventory questionnaires were completed. Serum TOS and TAC levels were measured. We observed higher serum levels of TOS in all MS groups, while after melatonin treatment the TOS levels significantly decreased. The TAC level was significantly lower only in mitoxantrone-treated group and it increased after melatonin supplementation. A strong positive correlation between T1Gd(+) number lesions and TAC level in interferon-beta-1A group was observed. AIS group mean score above 6 defining insomnia were observed in interferon-beta-1B-group, glatiramer acetate-group and mitoxantrone-group: 6.62 ± 2.88, 8.45 ± 2.07, 11.1 ± 3.25, respectively. After melatonin treatment the AIS mean scores decrease in glatiramer acetate-group and mitoxantrone-group achieving 5.25 ± 1.14 and 7.08 ± 2.39, respectively (p melatonin can act as an antioxidant and improves reduced sleep quality in MS patients. PMID:24974099

  14. Melatonin combats molecular terrorism at the mitochondrial level.

    Science.gov (United States)

    Reiter, Russel J; Paredes, Sergio D; Korkmaz, Ahmet; Jou, Mei-Jie; Tan, Dun-Xian

    2008-09-01

    The intracellular environmental is a hostile one. Free radicals and related oxygen and nitrogen-based oxidizing agents persistently pulverize and damage molecules in the vicinity of where they are formed. The mitochondria especially are subjected to frequent and abundant oxidative abuse. The carnage that is left in the wake of these oxygen and nitrogen-related reactants is referred to as oxidative damage or oxidative stress. When mitochondrial electron transport complex inhibitors are used, e.g., rotenone, 1-methyl-1-phenyl-1,2,3,6-tetrahydropyridine, 3-nitropropionic acid or cyanide, pandemonium breaks loose within mitochondria as electron leakage leads to the generation of massive amounts of free radicals and related toxicants. The resulting oxidative stress initiates a series of events that leads to cellular apoptosis. To alleviate mitochondrial destruction and the associated cellular implosion, the cell has at its disposal a variety of free radical scavengers and antioxidants. Among these are melatonin and its metabolites. While melatonin stimulates several antioxidative enzymes it, as well as its metabolites (cyclic 3-hydroxymelatonin, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine and N(1)-acetyl-5-methoxykynuramine), likewise effectively neutralize free radicals. The resulting cascade of reactions greatly magnifies melatonin's efficacy in reducing oxidative stress and apoptosis even in the presence of mitochondrial electron transport inhibitors. The actions of melatonin at the mitochondrial level are a consequence of melatonin and/or any of its metabolites. Thus, the molecular terrorism meted out by reactive oxygen and nitrogen species is held in check by melatonin and its derivatives. PMID:21218104

  15. Yeast contribution to melatonin, melatonin isomers and tryptophan ethyl ester during alcoholic fermentation of grape musts.

    Science.gov (United States)

    Vigentini, Ileana; Gardana, Claudio; Fracassetti, Daniela; Gabrielli, Mario; Foschino, Roberto; Simonetti, Paolo; Tirelli, Antonio; Iriti, Marcello

    2015-05-01

    Melatonin (MEL) has been found in some medicinal and food plants, including grapevine, a commodity of particular interest for the production of wine, a beverage of economic relevance. It has also been suggested that MEL in wine may, at least in part, contribute to the health-promoting properties attributed to this beverage and, possibly, to other traditional Mediterranean foodstuffs. After a preliminary screening of 9 yeast strains in laboratory medium, three selected strains (Saccharomyces cerevisiae EC1118, Torulaspora delbrueckii CBS1146(T) and Zygosaccharomyces bailii ATCC36947(T) ) were inoculated in experimental musts obtained from 2 white (Moscato and Chardonnay) and 2 red (Croatina and Merlot) grape varieties. The production of MEL, melatonin isomers (MIs) and tryptophan ethyl ester (TEE) was monitored during the alcoholic fermentation. The screening showed that the three investigated strains produced the highest concentrations of MEL and two MIs in optimal growth conditions. However, MEL and MIs were not produced in oenological conditions, but the three strains synthesized high concentrations of a new MI and TEE in musts. PMID:25726850

  16. Enurese noturna monossintomática / Monosymptomatic nocturnal enuresis

    Scientific Electronic Library Online (English)

    Rejane de P., Meneses.

    2001-06-01

    Full Text Available OBJETIVO: a enurese noturna monossintomática (ENM) ocupa papel de destaque na prática pediátrica, pela alta freqüência, pelo impacto psicossocial e por ser assunto controverso em relação à etiologia e ao tratamento. O principal interesse deste trabalho é mostrar que a ENM é uma entidade clínica bem [...] individualizada. A enurese noturna pode ser sintoma de distúrbio miccional cuja abordagem terapêutica é completamente diferente. MÉTODOS: Encontramos na literatura uma enorme quantidade de publicações, mas procuramos selecionar, para esta revisão, as publicações clássicas e as mais recentes, de autores internacionalmente reconhecidos como estudiosos neste tema; além disso, trazemos a experiência acumulada ao longo de 13 anos no Centro de Nefrologia Pediátrica do Paraná - Unidade de Distúrbios Miccionais. RESULTADOS: A falta de consenso internacional bem definido quanto a conceituação, terminologia e classificação dificulta a avaliação dos inúmeros estudos publicados na literatura. A individualização da entidade clínica ENM é o ponto de partida fundamental para uma orientação adequada do paciente. A enurese não é um mal da civilização moderna e encontra-se presente na maioria das sociedades, dando oportunidade às mais diversas interpretações e propostas de tratamento (1). Há consenso em relação ao prejuízo da auto-estima em crianças enuréticas e, portanto, em relação ao benefício de seu tratamento. CONCLUSÕES: A enurese noturna continua sendo um grande segredo de família, e muitas crianças permanecem sem orientação e tratamento, sofrendo por falta de compreensão e tendo sua auto-estima atingida. A ENM deve ser ativamente pesquisada na ocasião da consulta pediátrica. Um interrogatório detalhado sobre hábitos e qualidade da micção, antecedentes de infecção urinária e exame físico minucioso, permite descartar outros diagnósticos. A ENM é um problema médico, merecedor de atenção dos profissionais e familiares. Abstract in english OBJECTIVES: Monosymptomatic nocturnal enuresis (MNE) plays a very important role in the practice of pediatrics due to its high prevalence, its psychosocial impact, and its controversial etiology and treatment. Our objective was to show that MNE can be a well-defined clinical entity (monosymptomatic) [...] , but it can also be a symptom of urinary disorder, thus requiring a completely different therapeutic approach. METHODS: The literature presents numerous publications related to the matter of MNE, thus we tried to select, for this review, the classical and the most recent publications from internationally recognized authors; in addition, we also have a 13-year work experience at the Unit for Urinary Disorders of the Pediatric Nephrology Center of the state of Paraná (Unidade de Distúrbios Miccionais - Centro de Nefrologia Pediatrica do Paraná). RESULTS: The lack of a well-defined, international consensus on the concept, terminology, and classification of MNE is an obstacle for the assessment of the numerous studies found in the literature. The individualization of the MNE clinical entity is the fundamental starting point for providing appropriate guidance for patients. Enuresis can be found in most societies and, thus, it gives way to several interpretations and forms of treatment. There is a consensus, however, on the damage to the self-esteem of enuretic children, and consequently, on the advantage of proper treatment. CONCLUSIONS: In most cases, MNE is kept as a family secret while children remain without proper guidance and treatment and suffering with the lack of understanding and damage to their self-esteem. Doctors should survey patients extensively for MNE during pediatric appointments. It is possible to discard other diagnoses with a detailed survey of habits, quality of the urination, and history of urinary infection and a meticulous physical examination. MNE should be faced as a medical problem worthy of the attention of professionals and patients' families.

  17. Enurese noturna monossintomática Monosymptomatic nocturnal enuresis

    Directory of Open Access Journals (Sweden)

    Rejane de P. Meneses

    2001-06-01

    Full Text Available OBJETIVO: a enurese noturna monossintomática (ENM ocupa papel de destaque na prática pediátrica, pela alta freqüência, pelo impacto psicossocial e por ser assunto controverso em relação à etiologia e ao tratamento. O principal interesse deste trabalho é mostrar que a ENM é uma entidade clínica bem individualizada. A enurese noturna pode ser sintoma de distúrbio miccional cuja abordagem terapêutica é completamente diferente. MÉTODOS: Encontramos na literatura uma enorme quantidade de publicações, mas procuramos selecionar, para esta revisão, as publicações clássicas e as mais recentes, de autores internacionalmente reconhecidos como estudiosos neste tema; além disso, trazemos a experiência acumulada ao longo de 13 anos no Centro de Nefrologia Pediátrica do Paraná - Unidade de Distúrbios Miccionais. RESULTADOS: A falta de consenso internacional bem definido quanto a conceituação, terminologia e classificação dificulta a avaliação dos inúmeros estudos publicados na literatura. A individualização da entidade clínica ENM é o ponto de partida fundamental para uma orientação adequada do paciente. A enurese não é um mal da civilização moderna e encontra-se presente na maioria das sociedades, dando oportunidade às mais diversas interpretações e propostas de tratamento (1. Há consenso em relação ao prejuízo da auto-estima em crianças enuréticas e, portanto, em relação ao benefício de seu tratamento. CONCLUSÕES: A enurese noturna continua sendo um grande segredo de família, e muitas crianças permanecem sem orientação e tratamento, sofrendo por falta de compreensão e tendo sua auto-estima atingida. A ENM deve ser ativamente pesquisada na ocasião da consulta pediátrica. Um interrogatório detalhado sobre hábitos e qualidade da micção, antecedentes de infecção urinária e exame físico minucioso, permite descartar outros diagnósticos. A ENM é um problema médico, merecedor de atenção dos profissionais e familiares.OBJECTIVES: Monosymptomatic nocturnal enuresis (MNE plays a very important role in the practice of pediatrics due to its high prevalence, its psychosocial impact, and its controversial etiology and treatment. Our objective was to show that MNE can be a well-defined clinical entity (monosymptomatic, but it can also be a symptom of urinary disorder, thus requiring a completely different therapeutic approach. METHODS: The literature presents numerous publications related to the matter of MNE, thus we tried to select, for this review, the classical and the most recent publications from internationally recognized authors; in addition, we also have a 13-year work experience at the Unit for Urinary Disorders of the Pediatric Nephrology Center of the state of Paraná (Unidade de Distúrbios Miccionais - Centro de Nefrologia Pediatrica do Paraná. RESULTS: The lack of a well-defined, international consensus on the concept, terminology, and classification of MNE is an obstacle for the assessment of the numerous studies found in the literature. The individualization of the MNE clinical entity is the fundamental starting point for providing appropriate guidance for patients. Enuresis can be found in most societies and, thus, it gives way to several interpretations and forms of treatment. There is a consensus, however, on the damage to the self-esteem of enuretic children, and consequently, on the advantage of proper treatment. CONCLUSIONS: In most cases, MNE is kept as a family secret while children remain without proper guidance and treatment and suffering with the lack of understanding and damage to their self-esteem. Doctors should survey patients extensively for MNE during pediatric appointments. It is possible to discard other diagnoses with a detailed survey of habits, quality of the urination, and history of urinary infection and a meticulous physical examination. MNE should be faced as a medical problem worthy of the attention of professionals and patients' families.

  18. Hemoglobinuria paroxística nocturna: Actualización / Paroxysmal nocturnal haemoglobinuria

    Scientific Electronic Library Online (English)

    María Teresa, Milanés Roldán; Norma, Fernández Delgado; Teresa, Fundora Sarraff; Juan Carlos, Jaime Facundo; Porfirio, Hernández Ramírez.

    2003-04-01

    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 prote [...] ínas 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 hematopoyéticos Abstract in english The 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 c [...] ellular 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

  19. Hemoglobinuria paroxística nocturna: Actualización Paroxysmal nocturnal haemoglobinuria

    Directory of Open Access Journals (Sweden)

    María Teresa Milanés Roldán

    2003-04-01

    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

  20. Sleep Apnea and Nocturnal Cardiac Arrhythmia: A Populational Study.

    Science.gov (United States)

    Cintra, Fatima Dumas; Leite, Renata Pimentel; Storti, Luciana Julio; Bittencourt, Lia Azeredo; Poyares, Dalva; Castro, Laura de Siqueira; Tufik, Sergio; Paola, Angelo de

    2014-11-01

    Background: The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. The authors hypothesized that nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea. Objective: To analyze the relationship between obstructive sleep apnea and abnormal heart rhythm during sleep in a population sample. Methods: Cross-sectional study with 1,101 volunteers, who form a representative sample of the city of São Paulo. The overnight polysomnography was performed using an EMBLA® S7000 digital system during the regular sleep schedule of the individual. The electrocardiogram channel was extracted, duplicated, and then analyzed using a Holter (Cardio Smart®) system. Results: A total of 767 participants (461 men) with a mean age of 42.00 ± 0.53 years, were included in the analysis. At least one type of nocturnal cardiac rhythm disturbance (atrial/ventricular arrhythmia or beat) was observed in 62.7% of the sample. The occurrence of nocturnal cardiac arrhythmias was more frequent with increased disease severity. Rhythm disturbance was observed in 53.3% of the sample without breathing sleep disorders, whereas 92.3% of patients with severe obstructive sleep apnea showed cardiac arrhythmia. Isolated atrial and ventricular ectopy was more frequent in patients with moderate/severe obstructive sleep apnea when compared to controls (p < 0.001). After controlling for potential confounding factors, age, sex and apnea-hypopnea index were associated with nocturnal cardiac arrhythmia. Conclusion: Nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea and the prevalence increases with disease severity. Age, sex, and the Apnea-hypopnea index were predictors of arrhythmia in this sample. PMID:25252161

  1. Pulsed Led’s Light at 650 nm Promote and at 470 nm Suppress Melatonin’s Secretion

    Directory of Open Access Journals (Sweden)

    F. Ferro Milone

    2015-02-01

    Full Text Available In a previous research we have studied the effect of the stimulation of the retina, by pulsed LED’s light of different wavelength, on the spectral density of the alpha rhythms of the electroencephalogram [1] [2]. In conformity to our results and the recent discovery of a nonvisual pathway of light from the retina to the brain, we are induced to search for the effect of stimulation of the retina, with different wavelength, on the melatonin’s secretion. We have, therefore, stimulated the retina with blue LED’s light 470 nm and red LED’s light 650 nm, and measured the melatonin’s secretion in saliva by means of High Pressure Liquid Chromatography (HPLC. The results show that melatonin values are higher with long wavelength stimulation (red, 650 nm to be confronted with short wavelength stimulation where the values are lower (blue, 470 nm, the difference being significant (***. Action spectrum of short wavelength, producing melatonin suppression, was already evidenced in vivo; it was also demonstrated that blue LED’s light differentially modulated cell’s survival and growth, inducing mitochondrial suppression in vitro. We speculate, therefore, that long wavelength light (red produces photobiomodulation effect at the level of the retina and that this effect is the opposite of the effect produced by the short wavelength (blue. The molecular mechanism underlying both effects may be, we suppose, the activation (red or depression (blue of the mitochondrial cytochrome c oxidase activity at the level of the pool of the retina’s ganglion cells.

  2. Nocturnal Diaphoresis Secondary to Mild Obstructive Sleep Apnea in a Patient with a History of Two Malignancies

    OpenAIRE

    Vorona, Robert Daniel; Szklo-coxe, Mariana; Fleming, Mark; Ware, J. Catesby

    2013-01-01

    Numerous medical disorders, including obstructive sleep apnea, may cause nocturnal diaphoresis. Previous work has associated severe obstructive sleep apnea with nocturnal diaphoresis. This case report is of import as our patient with severe nocturnal diaphoresis manifested only mild sleep apnea, and, for years, his nocturnal diaphoresis was ascribed to other causes, i.e., first prostate cancer and then follicular B-cell lymphoma. Additionally, it was the nocturnal diaphoresis and not more com...

  3. In vitro comparison of duration of action of melatonin agonists on melatonin MT1 receptor: Possible link between duration of action and dissociation rate from receptor.

    Science.gov (United States)

    Nishiyama, Keiji; Hirai, Keisuke

    2015-06-15

    Melatonin MT1 and MT2 receptors are Gi protein-coupled receptors and promising therapeutic targets for a number of diseases. A proportion of G protein-coupled receptor agonists and antagonists have been classified according to their duration of action, which influences their pharmacological efficacy. However, the duration of action of melatonin agonists remains unclear. In this study, we investigated the duration of action of melatonin agonists (melatonin, 2-iodomelatonin, ramelteon, and the ramelteon metabolite M-II) at the melatonin MT1 receptor, which is more resistant to agonist-induced desensitization than the melatonin MT2 receptor. In Chinese hamster ovary cells stably expressing the human melatonin MT1 receptor, significant differences in the duration of action were observed after 2-h pretreatment with agonists followed by washout. In contrast to melatonin and M-II, the agonist activities of ramelteon and 2-iodomelatonin were persistent (i.e. inhibition of forskolin-stimulated cAMP formation and increase in ERK 1/2 phosphorylation) even after repeated washouts. Similar activities were observed for INS-1 cells endogenously expressing the rat MT1 receptor. Further, we examined potential factors linked to the duration of action. Residual activities of melatonin agonists after washout strongly correlated with their dissociation rates from the human melatonin MT1 receptor, but not their lipophilicity or extent of desensitization. These data suggest that the in vitro duration of action significantly differs between melatonin agonists and might dictate dissociation kinetics. Characterization of these in vitro properties may facilitate further in vivo study of the duration of action. PMID:25797281

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

    Directory of Open Access Journals (Sweden)

    Chun-Qiu Chen

    2011-01-01

    Full Text Available 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 through specific membrane receptors, named melatonin-1 receptor (MT1, MT2 and MT3. These receptors can be found in the gut and their involvement in the regulation of GI motility, inflammation and pain has been reported in numerous basic and clinical studies. Stable levels of melatonin in the lower gut that are unchanged following a pinealectomy suggest local synthesis and, furthermore, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut.

  5. Beneficial effects of melatonin in a rat model of sporadic Alzheimer's disease.

    Science.gov (United States)

    Rudnitskaya, Ekaterina A; Maksimova, Kseniya Yi; Muraleva, Natalia A; Logvinov, Sergey V; Yanshole, Lyudmila V; Kolosova, Nataliya G; Stefanova, Natalia A

    2015-06-01

    Melatonin synthesis is disordered in patients with Alzheimer's disease (AD). To determine the role of melatonin in the pathogenesis of AD, suitable animal models are needed. The OXYS rats are an experimental model of accelerated senescence that has also been proposed as a spontaneous rat model of AD-like pathology. In the present study, we demonstrate that disturbances in melatonin secretion occur in OXYS rats at 4 months of age. These disturbances occur simultaneously with manifestation of behavioral abnormalities against the background of neurodegeneration and alterations in hormonal status but before the signs of amyloid-? accumulation. We examined whether oral administration of melatonin could normalize the melatonin secretion and have beneficial effects on OXYS rats before progression to AD-like pathology. The results showed that melatonin treatment restored melatonin secretion in the pineal gland of OXYS rats as well as the serum levels of growth hormone and IGF-1, the level of BDNF in the hippocampus and the healthy state of hippocampal neurons. Additionally, melatonin treatment of OXYS rats prevented an increase in anxiety and the decline of locomotor activity, of exploratory activity, and of reference memory. Thus, melatonin may be involved in AD progression, whereas oral administration of melatonin could be a prophylactic strategy to prevent or slow down the progression of some features of AD pathology. PMID:25515660

  6. Optimization of light and melatonin to phase-shift human circadian rhythms.

    Science.gov (United States)

    Skene, D J

    2003-04-01

    Both light and melatonin, appropriately timed, have been shown to phase-shift human circadian rhythms. In addition, both light and melatonin have acute physiological and behavioural effects. Depending on the dose, melatonin can reduce core body temperature and induce sleepiness. Conversely, light at night increases body temperature and enhances alertness and performance. The acute and phase-shifting effects of light and melatonin have justified their investigation and use in the treatment of circadian rhythm sleep disorders. Melatonin is the treatment of choice for blind people with non-24 h sleep/wake disorder. Current research is directed towards optimizing these therapies with respect to time of administration, dose and formulation of melatonin, intensity, duration and spectral composition of light. Our studies in totally blind people with non-24 h sleep/wake disorder have shown that, in addition to improving sleep, daily administration of melatonin can entrain their free-running circadian rhythms. The ability of melatonin to entrain free-running rhythms depends, in part, on the time of melatonin administration relative to the subject's circadian phase. Subjects who were entrained by melatonin began their treatment in the phase advance portion (CT 6-18) of the published melatonin phase-response curves (PRCs), whereas those who failed to entrain began their melatonin treatment in the delay portion of the PRC. Whether the effect of light on the human circadian axis can be optimized by altering its spectral composition has been investigated. Recently, it was demonstrated that light-induced melatonin suppression in humans is sensitive to short wavelength light (420-480 nm; lambda(max) approximately 460 nm), a response very different to the classical scotopic and photopic visual systems. Whether other nonvisual light responses (e.g. circadian phase resetting) show a similar spectral sensitivity is currently being studied. PMID:12622847

  7. Melatonin exerts protective effect on N2a cells under hypoxia conditions through Zip1/ERK pathway.

    Science.gov (United States)

    Liu, Xin-Wei; Zi, Ying; Liu, Yun-En; Zhang, Yu-Biao; Xiang, Liang-Bi; Hou, Ming-Xiao

    2015-05-19

    Melatonin plays a neuroprotective role in different CNS injuries. However, the molecular mechanisms underlying neuroprotection by melatonin are not well understood. Here, we studied the effects of melatonin in hypoxia-induced N2a cells and our results demonstrated that melatonin not only reduced the level of ROS and MDA, induced the increase of SOD, but also increased the cell proliferation and inhibited cell apoptosis in hypoxia-induced N2a cells. Moreover, we identified that melatonin can activate the MAPK/ERK pathway via upregulating the expression of Zip1. Therefore, this study provides a new mechanism of melatonin and need our further study in detail. PMID:25864781

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

    Directory of Open Access Journals (Sweden)

    Youngjeon Lee

    2014-01-01

    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.

  9. 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)

    C.D. Cisternas

    2010-09-01

    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.

  10. Exploring the reasons why melatonin can improve tinnitus.

    Science.gov (United States)

    Pirodda, Antonio; Raimondi, Maria Chiara; Ferri, Gian Gaetano

    2010-08-01

    Melatonin has been proposed as a treatment for tinnitus, especially on the basis of its favourable effects on sleep and its vasoactive and antioxidant properties. However, to our knowledge no attempts of interpretation have been advanced through a detailed analysis of the various specific properties of melatonin possibly cooperating in a coincidental way to relieve tinnitus: among these, its modulatory effect on central nervous system resulting in a protective mechanism against an exaggerated sympathetic drive; its capacity to induce a more steady hemodynamic condition, through a multifactorial and multi-organ activity, resulting in a more regular labyrinthine perfusion; a possible action on the skeletal muscle tending to a reduction of the muscular tone, which could relieve tinnitus of muscular origin deriving from tensor tympani tonic contractions; its possible reported antidepressive effect, which could indirectly act on tinnitus; a direct regulation of inner ear immunity as proposed in literature when melatonin was reported to be present in the inner ear. All these observations seem to indicate melatonin as a tool deserving a greater attention than other antioxidants in the attempt of relieving tinnitus, justifying its application from a more precise rationale based on a series of physio-pathological aspects. PMID:20207491

  11. Production and purification of polyclonal antibody against melatonin hormone

    Directory of Open Access Journals (Sweden)

    Fooladsaz K

    1999-09-01

    Full Text Available Nowadays immunochemical techniques have played a very important and valuable role in quantitative and qualitative assays of liquid compounds of the body. Producing antibody against immunogenes is the first step to make immunochemical kits. In this study production and purification of polyclonal antibody against melatonin has been considered. This hormone which has several important functions in physiological conditions such as migraine, cirrhosis, mammary gland cancer and other diseases, is the most important pineal gland secretion. This gland is a circumventricular organ of brain and according to histological and anatomical studies, it is a high secretory organ, that secretes active biological substances like melatonin, oxytocin, serotonin and ect. In this study, melatonin has been considered as hapten and has become an immunogen by being linked to the bovine serum Albumin. Then, by the immunization of three white New Zeland rabbits that had the booster injections in regular intervals, the antibody titer was detected to be 1/2000, by using checkboard curves, and with the use of melatonin linked to penicillinase as a labeled antigen, the titer was detected 1/200. Finally an antibody with high purification rate has been obtained, which can be used in immunochemical assays like RIA, ELISA, and EIA.

  12. Circadian rhythm in salivary melatonin in narcoleptic patiens.

    Czech Academy of Sciences Publication Activity Database

    Blažejová, K.; Illnerová, Helena; Hájek, Ivan; Nevšímalová, S.

    2008-01-01

    Ro?. 437, ?. 2 (2008), s. 162-164. ISSN 0304-3940 R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : narcolepsy * circadian system * melatonin Subject RIV: FH - Neurology Impact factor: 2.200, year: 2008

  13. A novel and sensitive radioreceptor assay for serum melatonin levels

    International Nuclear Information System (INIS)

    A simple and sensitive radioreceptor assay (RRA) has been developed to measure melatonin levels in serum. The assay is based on competition between 2-[125I]iodomelatonin ([125I]MEL) and melatonin for binding to high-affinity binding sites in chick forebrain. To measure the amount of melatonin present in a serum sample, it was extracted with dichloromethane and added to the assay medium. The percentage inhibition of radioligand binding in the presence of the extracted serum was determined and compared to the percent displacement by known amounts of melatonin in a standard curve. There was little or no cross-reactivity with other structurally related compounds. The sensitivity of the assay is ?1.5pg/0.15 mL and the intra- and inter-assay variations are approximately 8%. Since the RRA results are comparable to that of an established radioimmunoassay (RIA), it provides a sensitive and rapid alternative to the more time consuming RIA

  14. The effect of melatonin on mouse jejunal crypt cell survival and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Jin Oh; Ha, Eun Young; Baik, Hyung Hwan; Cho, Yong Ho; Hong, Seong Eon [College of Medicine, Kyunghee Univ., Seoul (Korea, Republic of)

    2000-03-01

    To evaluate protective mechanism of melatonin against radiation damage and its relationship with apoptosis in mouse jejunum. 168 mice were divided into 28 groups according to radiation dose and melatonin treatment. To analysis crypt survival, microcolony survival assay was done according to Withers and Elkind's method. To analysis apoptosis, TUNEL assay was done according to Labet-Moleur's method. Radiation protection effect of melatonin was demonstrated by crypt survival assay and its effect was stronger in high radiation dose area. Apoptosis index with 8 Gy irradiation was 18.4% in control group and 16.5% in melatonin treated group. After 18 Gy, apoptosis index was 17.2%in control group and 15.4% in melatonin treated group. Apoptosis index did not show statistically significant difference between melatonin shows clear protective effect in mouse jejunum against radiation damage but its protective effect seems not to be related with apoptosis protection effect.

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

    Directory of Open Access Journals (Sweden)

    Afsaneh Arabi

    2012-06-01

    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.

  16. 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.

  17. Early prophylactic and treatment role of melatonin against certain biochemical disorders in irradiated rats

    International Nuclear Information System (INIS)

    The aim of the present study is to evaluate the possible early prophylactic and therapeutic role of melatonin on irradiated rats. The experimental animals were divided into five groups: control, injected intraperitoneally with melatonin (10 mg/ kg b.wt.), irradiated at 6 Gy, injected with melatonin before irradiation and injected with melatonin after gamma irradiation. Blood, liver and brain samples from rats were collected at three time intervals of 7, 10, 14 days after terminating all treatments. Protein content and glutathione were estimated in blood and tissues, whereas testosterone and cortisol were assayed in blood of rats after whole body gamma irradiation at 6 Gy. Administration of melatonin (10 mg/kg) before whole body gamma irradiation markedly reduced the radiation injury and controlled the changes in most of the studied parameters, but following the administration of melatonin after irradiation, there were no changes in these parameters

  18. The effect of melatonin on mouse jejunal crypt cell survival and apoptosis

    International Nuclear Information System (INIS)

    To evaluate protective mechanism of melatonin against radiation damage and its relationship with apoptosis in mouse jejunum. 168 mice were divided into 28 groups according to radiation dose and melatonin treatment. To analysis crypt survival, microcolony survival assay was done according to Withers and Elkind's method. To analysis apoptosis, TUNEL assay was done according to Labet-Moleur's method. Radiation protection effect of melatonin was demonstrated by crypt survival assay and its effect was stronger in high radiation dose area. Apoptosis index with 8 Gy irradiation was 18.4% in control group and 16.5% in melatonin treated group. After 18 Gy, apoptosis index was 17.2%in control group and 15.4% in melatonin treated group. Apoptosis index did not show statistically significant difference between melatonin shows clear protective effect in mouse jejunum against radiation damage but its protective effect seems not to be related with apoptosis protection effect

  19. Sleep-wake and melatonin pattern in craniopharyngioma patients

    DEFF Research Database (Denmark)

    Pickering, Line; Jennum, Poul

    2014-01-01

    OBJECTIVE: To assess the influence of craniopharyngioma or consequent surgery on melatonin secretion, and the association with fatigue, sleepiness, sleep pattern and sleep quality. DESIGN: Cross-sectional study. METHODS: A total of 15 craniopharyngioma patients were individually matched to healthy controls. In this study, 24-h salivary melatonin and cortisol were measured. Sleep-wake patterns were characterised by actigraphy and sleep diaries recorded for 2 weeks. Sleepiness, fatigue, sleep quality and general health were assessed by Multidimensional Fatigue Inventory, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Short-Form 36. RESULTS: Patients had increased mental fatigue, daytime dysfunction, sleep latency and lower general health (all, P?0.05), and they tended to have increased daytime sleepiness, general fatigue and impaired sleep quality compared with controls. The degree of hypothalamic injury was associated with an increased BMI and lower mental health (P=0.01). High BMI was associated with increased daytime sleepiness, daytime dysfunction, mental fatigue and lower mental health (all, P?0.01). Low midnight melatonin was associated with reduced sleep time and efficiency (P?0.03) and a tendency for increased sleepiness, impaired sleep quality and physical health. Midnight melatonin remained independently related to sleep time after adjustment for cortisol. Three different patterns of melatonin profiles were observed; normal (n=6), absent midnight peak (n=6) and phase-shifted peak (n=2). Only patients with absent midnight peak had impaired sleep quality, increased daytime sleepiness and general and mental fatigue. CONCLUSION: Craniopharyngioma patients present with changes in circadian pattern and daytime symptoms, which may be due to the influence of the craniopharyngioma or its treatment on the hypothalamic circadian and sleep regulatory nuclei.

  20. Sleep–wake and melatonin pattern in craniopharyngioma patients

    DEFF Research Database (Denmark)

    Pickering, Line; Jennum, Poul

    2014-01-01

    OBJECTIVE: To assess the influence of craniopharyngioma or consequent surgery on melatonin secretion, and the association with fatigue, sleepiness, sleep pattern and sleep quality. DESIGN: Cross-sectional study. METHODS: A total of 15 craniopharyngioma patients were individually matched to healthy controls. In this study, 24-h salivary melatonin and cortisol were measured. Sleep-wake patterns were characterised by actigraphy and sleep diaries recorded for 2 weeks. Sleepiness, fatigue, sleep quality and general health were assessed by Multidimensional Fatigue Inventory, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Short-Form 36. RESULTS: Patients had increased mental fatigue, daytime dysfunction, sleep latency and lower general health (all, P?0.05), and they tended to have increased daytime sleepiness, general fatigue and impaired sleep quality compared with controls. The degree of hypothalamic injury was associated with an increased BMI and lower mental health (P=0.01). High BMI was associated with increased daytime sleepiness, daytime dysfunction, mental fatigue and lower mental health (all, P?0.01). Low midnight melatonin was associated with reduced sleep time and efficiency (P?0.03) and a tendency for increased sleepiness, impaired sleep quality and physical health. Midnight melatonin remained independently related to sleep time after adjustment for cortisol. Three different patterns of melatonin profiles were observed; normal (n=6), absent midnight peak (n=6) and phase-shifted peak (n=2). Only patients with absent midnight peak had impaired sleep quality, increased daytime sleepiness and general and mental fatigue. CONCLUSION: Craniopharyngioma patients present with changes in circadian pattern and daytime symptoms, which may be due to the influence of the craniopharyngioma or its treatment on the hypothalamic circadian and sleep regulatory nuclei.

  1. 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-[125I]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 figsh present in this species. 43 refs. 6 figs., 1 tabs

  2. Nocturnal variations of geomagnetic horizontal field at equatorial stations

    Science.gov (United States)

    Rastogi, R. G.; Chandra, H.; James, M. E.

    The nocturnal variations of the horizontal component (H) of the geomagnetic field at equatorial stations Koror, Trivandrum, Addis-Ababa and Ibadan during any of the seasons of the period 1958-59 showed a steady decrease after sunset throughout the nighttime hours. However, at Huancayo a steady decrease after sunset to sunrise is seen only during the D-months. During the J and E months decrease is seen after sunset till about 22-23 hr and a slow and steady increase from midnight hours to sunrise. The nocturnal variations of H field at Huancayo show a remarkable similarity with the corresponding variations of the horizontal electric field in the ionosphere as determined by the Doppler shifts of backscatter echoes from the E and F layers over Jicamarca. Thus, genuine changes in the equatorial electric field and current in the ionosphere over the American sector during the nighttime hours are clearly indicated.

  3. A mathematical model of the circadian phase-shifting effects of exogenous melatonin.

    Science.gov (United States)

    Breslow, Emily R; Phillips, Andrew J K; Huang, Jean M; St Hilaire, Melissa A; Klerman, Elizabeth B

    2013-02-01

    Melatonin is endogenously produced and released in humans during nighttime darkness and is suppressed by ocular light exposure. Exogenous melatonin is used to induce circadian phase shifts and sleep. The circadian phase-shifting ability of a stimulus (e.g., melatonin or light) relative to its timing may be displayed as a phase response curve (PRC). Published PRCs to exogenous melatonin show a transition from phase advances to delays approximately 1 h after dim light melatonin onset. A previously developed mathematical model simulates endogenous production and clearance of melatonin as a function of circadian phase, light-induced suppression, and resetting of circadian phase by light. We extend this model to include the pharmacokinetics of oral exogenous melatonin and phase-shifting effects via melatonin receptors in the suprachiasmatic nucleus of the mammalian hypothalamus. Model parameters are fit using 2 data sets: (1) blood melatonin concentration following a 0.3- or 5.0-mg dose, and (2) a PRC to a 3.0-mg dose of melatonin. After fitting to the 3.0-mg PRC, the model correctly predicts that, by comparison, the 0.5-mg PRC is slightly decreased in amplitude and shifted to a later circadian phase. This model also reproduces blood concentration profiles of various melatonin preparations that differ only in absorption rate and percentage degradation by first-pass hepatic metabolism. This model can simulate experimental protocols using oral melatonin, with potential application to guide dose size and timing to optimally shift and entrain circadian rhythms. PMID:23382594

  4. Timing of sleep and its relationship with the endogenous melatonin rhythm

    OpenAIRE

    SimonVincenzi; ShanthaMRajaratnam

    2010-01-01

    While much research has investigated the effects of exogenous melatonin on sleep, less is known about the relationship between the timing of the endogenous melatonin rhythm and the sleep-wake cycle. Significant inter-individual variability in the phase relationship between sleep and melatonin rhythms has been reported although the extent to which the variability reflects intrinsic and/or environmental differences is unknown. We examined the effects of different sleeping schedules on the time ...

  5. Use of slow-release melatonin in treatment-resistant depression.

    OpenAIRE

    Dalton, E. J.; Rotondi, D.; Levitan, R. D.; Kennedy, S. H.; Brown, G. M.

    2000-01-01

    OBJECTIVE: To examine antidepressant augmentation with and hypnotic effects of slow-release melatonin (SR-melatonin) in patients with treatment-resistant depression. DESIGN: Open-label trial. SETTING: Tertiary care outpatient depression clinic. PATIENTS: Nine outpatients who had failed to respond to 2 or more 8-week trials of antidepressant medication. INTERVENTIONS: Patients received SR-melatonin 5 mg per day for the first 2 weeks and 10 mg per day for the final 2 weeks, in addition to their...

  6. Use of melatonin in circadian rhythm disorders and following phase shifts

    OpenAIRE

    Skene, Dj; Deacon, S.; Arendt, J.

    1996-01-01

    Following abrupt phase shifts (real or simulated time zone changes, night shift work) there is desynchronisation between the internal circadian rhythms (including melatonin) and the external environment with consequent disturbances in sleep, mood and performance. In humans the pineal hormone melatonin has phase-shifting and resynchronising properties with regard to a number of circadian rhythms. Suitably timed melatonin adrninstration hastened adaptation to phase shift and significantly impro...

  7. Melatonin prevents mitochondrial dysfunction and insulin resistance in rat skeletal muscle.

    Science.gov (United States)

    Teodoro, Bruno G; Baraldi, Flavia G; Sampaio, Igor H; Bomfim, Lucas H M; Queiroz, André L; Passos, Madla A; Carneiro, Everardo M; Alberici, Luciane C; Gomis, Ramon; Amaral, Fernanda G; Cipolla-Neto, José; Araújo, Michel B; Lima, Tanes; Akira Uyemura, Sérgio; Silveira, Leonardo R; Vieira, Elaine

    2014-09-01

    Melatonin has a number of beneficial metabolic actions and reduced levels of melatonin may contribute to type 2 diabetes. The present study investigated the metabolic pathways involved in the effects of melatonin on mitochondrial function and insulin resistance in rat skeletal muscle. The effect of melatonin was tested both in vitro in isolated rats skeletal muscle cells and in vivo using pinealectomized rats (PNX). Insulin resistance was induced in vitro by treating primary rat skeletal muscle cells with palmitic acid for 24 hr. Insulin-stimulated glucose uptake was reduced by palmitic acid followed by decreased phosphorylation of AKT which was prevented my melatonin. Palmitic acid reduced mitochondrial respiration, genes involved in mitochondrial biogenesis and the levels of tricarboxylic acid cycle intermediates whereas melatonin counteracted all these parameters in insulin-resistant cells. Melatonin treatment increases CAMKII and p-CREB but had no effect on p-AMPK. Silencing of CREB protein by siRNA reduced mitochondrial respiration mimicking the effect of palmitic acid and prevented melatonin-induced increase in p-AKT in palmitic acid-treated cells. PNX rats exhibited mild glucose intolerance, decreased energy expenditure and decreased p-AKT, mitochondrial respiration, and p-CREB and PGC-1 alpha levels in skeletal muscle which were restored by melatonin treatment in PNX rats. In summary, we showed that melatonin could prevent mitochondrial dysfunction and insulin resistance via activation of CREB-PGC-1 alpha pathway. Thus, the present work shows that melatonin play an important role in skeletal muscle mitochondrial function which could explain some of the beneficial effects of melatonin in insulin resistance states. PMID:24981026

  8. Melatonin in children with autistic spectrum disorders: recent and practical data

    OpenAIRE

    Doyen, C.; Mighiu, D.; Kaye, K; Colineaux, C.; Beaumanoir, C.; Mouraeff, Y.; Rieu, C.; Paubel, P.; Contejean, Y.

    2011-01-01

    Abstract Over the last 20 years, melatonin, a pineal hormone synthesized from serotonin, has been implicated in various studies on the autism spectrum disorder (ASD) and altered melatonin levels were detected in subgroups of subjects with ASD. Its effect on sleep disturbances got the attention of clinicians and several investigations were carried out to determine the usefulness and safety of melatonin administration in this disorder. Hypotheses were also raised regarding the possi...

  9. A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction

    OpenAIRE

    Han, June Hyun; Chang, In Ho; Myung, Soon Chul; Lee, Moo Yeol; Kim, Won Yong; Lee, Seo Yeon; Lee, Shin Young; Lee, Seung Wook; Kim, Kyung Do

    2012-01-01

    The aim of the present study was to elucidate the direct effects of melatonin on bladder activity and to determine the mechanisms responsible for the detrusor activity of melatonin in the isolated rat bladder. We evaluated the effects of melatonin on the contractions induced by phenylephrine (PE), acetylcholine (ACh), bethanechol (BCh), KCl, and electrical field stimulation (EFS) in 20 detrusor smooth muscle samples from Sprague-Dawley rats. To determine the mechanisms underlying the inhibito...

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

    OpenAIRE

    Næve, Ingun

    2012-01-01

    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...

  11. Targeting nocturnal hypertension in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Rossen, Niklas Blach; Knudsen, SØren Tang

    2014-01-01

    Several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular events than daytime BP. Consequently, treatment strategies to target nighttime BP have come into focus. The aim of the present study was to investigate the effect of change of administration time of antihypertensive drugs. We included 41 patients with type 2 diabetes mellitus and nocturnal hypertension (nighttime systolic BP >120 mm Hg) in an open-label, crossover study. Patients were randomized to 8 weeks of either morning or bedtime administration of all of the individual's once-daily antihypertensive drugs, followed by 8 weeks of switched dosing regimen. Bedtime administration of antihypertensive drugs resulted in a significant reduction in nighttime (7.5 mm Hg; P<0.001) and 24-hour (3.1 mm Hg; P=0.014) systolic BP, with a nonsignificant reduction in daytime (1.3 mm Hg; P=0.336) systolic BP. We did not find morning BP surge to be different between dosing regimens. Levels of C-reactive protein were significantly lower with bedtime administration, which may indicate an effect on low-grade inflammation. We found no difference in urinary albumin excretion, regardless of albuminuria status. Urinary sodium/creatinine was significantly increased and urinary osmolality significantly reduced with bedtime administration, which can be interpreted as increased nocturnal natriuresis. In patients with type 2 diabetes mellitus and nocturnal hypertension, administration of once-daily antihypertensive drugs at bedtime may be favorable. The increased nocturnal natriuresis may reflect increased effect of bedtime-administered thiazides and renin-angiotensin system inhibitors, suggesting a potential mechanism of the observed effects on BP with chronotherapeutic intervention.

  12. Nocturnal Changes in Knee Cartilage Thickness in Young Healthy Adults

    OpenAIRE

    Sitoci, K. H.; Hudelmaier, M.; Eckstein, F (Felix)

    2012-01-01

    Magnetic resonance imaging (MRI) allows one to analyze cartilage physiology in vivo. Cartilage deforms during loading, but little is known about its recovery after deformation. Here we study `nocturnal' changes in knee cartilage thickness and whether postexercise deformation differs between morning and evening. Axial magnetic resonance (MR) images were acquired in the right knees of 17 healthy volunteers (age 23.5 +/- 3.0 years) after a normal day, and then after 30 deep knee bends. Coronal i...

  13. Epidemiology and exogenous factors in nocturnal airflow limitation in children

    OpenAIRE

    Rosman-Meijer, Geertruida Gerarda,

    1996-01-01

    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...

  14. Nocturnal Homing: Learning Walks in a Wandering Spider?

    OpenAIRE

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

    2012-01-01

    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...

  15. Two Components of Nocturnal Locomotor Suppression by Light

    OpenAIRE

    Morin, Lawrence P.; Lituma, Pablo J.; Studholme, Keith M.

    2010-01-01

    In nocturnal rodents, millisecond light (“flash”) stimuli can induce both a large circadian rhythm phase shift and an associated state change from highly active to quiescence followed by behavioral sleep. Suppression of locomotion (“negative masking”) is an easily measured correlate of the state change. The present mouse studies used both flashes and longer light stimuli (“pulses”) to distinguish initiation from maintenance effects of light on locomotor suppression and to determin...

  16. Cold and hunger induce diurnality in a nocturnal mammal

    OpenAIRE

    van der Vinne, Vincent; Riede, Sjaak J.; Gorter, Jenke A.; Eijer, Willem G.; Sellix, Michael T.; Menaker, Michael; Daan, Serge; Pilorz, Violetta; Hut, Roelof A

    2014-01-01

    The circadian system drives daily rhythms in physiology and behavior. Mammals in nature can change their daily activity rhythms, but causes and consequences of this behavioral plasticity are unknown. Here we show that nocturnal mice become diurnal when challenged by cold or hunger. Negative energy balance changes hormonal, physiological and behavioral rhythms without modifying the rhythm of the circadian pacemaker in the suprachiasmatic nucleus. This response is adaptive because activity duri...

  17. Seed predation by nocturnal rodents in an African savanna ecosystem

    OpenAIRE

    Maxine F. Miller

    2012-01-01

    ENGLISH ABSTRACT: The small mammal community in Acacia savanna consists of three omnivorous nocturnal rodent species, Mastomys nataIensis, Saccostomus campestris and Aethomys chrysophilus, which eat varying proportions of seed in their diet. From a seed removal experiment, it was found that rodents preferentially selected Acacia tortilis seeds. The annual Acacia seed consumption by rodents in a South African savanna ecosystem was analysed by using estimates of rodent population densities, die...

  18. Correlations of physiological activities in nocturnal Cheyne–Stokes respiration

    OpenAIRE

    Umantsev, Alexander; Golbin, Alexander

    2011-01-01

    We have conducted a power–spectrum–density (PSD) analysis of the distinct sleep stages of a previously diagnosed nocturnal Cheyne–Stokes respiration patient (NCSR) and studied the correlations of different physiological activities. This is the first study where the correlations were analyzed separately for different sleep stages and the influence of arousals was completely eliminated. Mathematical analysis of the polysomnographical records revealed clear indicators of the disorder in th...

  19. Nocturnal enuresis: A topic review and institution experience

    OpenAIRE

    DiBianco, John Michael; Morley, Chad; Al-Omar, Osama

    2014-01-01

    The objective is to provide a review of nocturnal enuresis (NE), including its epidemiology, etiology, pathophysiology, evaluation, and current management. We also set to provide further insight on the treatment of this condition from the experience derived from patients cared for at our tertiary-care institution. NE affects approximately 15% of all children at 5-year-old, affecting boys more frequently than girls. At our large university tertiary pediatric urology center, NE and incontinence...

  20. The nocturnal water cycle in an open-canopy forest

    Science.gov (United States)

    Berkelhammer, M.; Hu, J.; Bailey, A.; Noone, D. C.; Still, C. J.; Barnard, H.; Gochis, D.; Hsiao, G. S.; Rahn, T.; Turnipseed, A.

    2013-09-01

    The movement of moisture into, out-of, and within forest ecosystems is modulated by feedbacks that stem from processes which couple plants, soil, and the atmosphere. While an understanding of these processes has been gleaned from Eddy Covariance techniques, the reliability of the method suffers at night because of weak turbulence. During the summer of 2011, continuous profiles of the isotopic composition (i.e., ?18O and ?D) of water vapor and periodic measurements of soil, leaf, and precipitation pools were measured in an open-canopy ponderosa pine forest in central Colorado to study within-canopy nocturnal water cycling. The isotopic composition of the nocturnal water vapor varies significantly based on the relative contributions of the three major hydrological processes acting on the forest: dewfall, exchange of moisture between leaf waters and canopy vapor, and periodic mixing between the canopy and background air. Dewfall proved to be surprisingly common (˜30% of the nights) and detectable on both the surface and within the canopy through the isotopic measurements. While surface dew could be observed using leaf wetness and soil moisture sensors, dew in the foliage was only measurable through isotopic analysis of the vapor and often occurred even when no dew accumulated on the surface. Nocturnal moisture cycling plays a critical role in water availability in forest ecosystems through foliar absorption and transpiration, and assessing these dynamics, as done here, is necessary for fully characterizing the hydrological controls on terrestrial productivity.

  1. Nocturnal sleep pattern in native Brazilian Terena adults

    Directory of Open Access Journals (Sweden)

    REIMÃO RUBENS

    2000-01-01

    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.

  2. Melatonin regulates Arabidopsis root system architecture likely acting independently of auxin signaling.

    Science.gov (United States)

    Pelagio-Flores, Ramón; Muñoz-Parra, Edith; Ortiz-Castro, Randy; López-Bucio, José

    2012-10-01

    Melatonin (N-acetyl-5-methoxytryptamine) is a tryptophan-derived signal with important physiological roles in mammals. Although the presence of melatonin in plants may be universal, its endogenous function in plant tissues is unknown. On the basis of its structural similarity to indole-3-acetic acid, recent studies mainly focusing on root growth in several plant species have suggested a potential auxin-like activity of melatonin. However, direct evidence about the mechanisms of action of this regulator is lacking. In this work, we used Arabidopsis thaliana seedlings as a model system to evaluate the effects of melatonin on plant growth and development. Melatonin modulated root system architecture by stimulating lateral and adventitious root formation but minimally affected primary root growth or root hair development. The auxin activity of melatonin in roots was investigated using the auxin-responsive marker constructs DR5:uidA, BA3:uidA, and HS::AXR3NT-GUS. Our results show that melatonin neither activates auxin-inducible gene expression nor induces the degradation of HS::AXR3NT-GUS, indicating that root developmental changes elicited by melatonin were independent of auxin signaling. Taken together, our results suggest that melatonin is beneficial to plants by increasing root branching and that root development processes elicited by this novel plant signal are likely independent of auxin responses. PMID:22507071

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

    Science.gov (United States)

    Anderson, George; Maes, Michael

    2012-06-01

    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

  4. Activation of MT(2) melatonin receptors in rat suprachiasmatic nucleus phase advances the circadian clock.

    Science.gov (United States)

    Hunt, A E; Al-Ghoul, W M; Gillette, M U; Dubocovich, M L

    2001-01-01

    The aim of this study was to identify the melatonin receptor type(s) (MT(1) or MT(2)) mediating circadian clock resetting by melatonin in the mammalian suprachiasmatic nucleus (SCN). Quantitative receptor autoradiography with 2-[(125)I]iodomelatonin and in situ hybridization histochemistry, with either (33)P- or digoxigenin-labeled antisense MT(1) and MT(2) melatonin receptor mRNA oligonucleotide probes, revealed specific expression of both melatonin receptor types in the SCN of inbred Long-Evans rats. The melatonin receptor type mediating phase advances of the circadian rhythm of neuronal firing rate in the SCN slice was assessed using competitive melatonin receptor antagonists, the MT(1)/MT(2) nonselective luzindole and the MT(2)-selective 4-phenyl-2-propionamidotetraline (4P-PDOT). Luzindole and 4P-PDOT (1 nM-1 microM) did not affect circadian phase on their own; however, they blocked both the phase advances (approximately 4 h) in the neuronal firing rate induced by melatonin (3 pM) at temporally distinct times of day [i.e., subjective dusk, circadian time (CT) 10; and dawn, CT 23], as well as the associated increases in protein kinase C activity. We conclude that melatonin mediates phase advances of the SCN circadian clock at both dusk and dawn via activation of MT(2) melatonin receptor signaling. PMID:11121382

  5. Transcutaneous Noninvasive Device for the Responsive Delivery of Melatonin in Microgravity. Project

    National Aeronautics and Space Administration — Our goal is develop a smart, transcutaneous device for individualized circadian (sleep) therapy by responsive release of melatonin, in microgravity. Additionally,...

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

    International Nuclear Information System (INIS)

    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

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

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Rosenberg, Jacob

    2011-01-01

    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.

  8. Analgesic effects of melatonin : a review of current evidence from experimental and clinical studies

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Amirian, Ilda

    2011-01-01

    Melatonin is an endogenous indoleamine, produced mainly by the pineal gland. Melatonin has been proven to have chronobiotic, antioxidant, antihypertensive, anxiolytic and sedative properties. There are also experimental and clinical data supporting an analgesic role of melatonin. In experimental studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid µ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby may reduce anxiety, which leads to lower levels of pain. In this paper, we review the current evidence regarding the analgesic properties of melatonin in animals and humans with chronic pain.

  9. Melatonin Induces Apoptotic Cell Death via p53 in LNCaP Cells

    OpenAIRE

    Kim, Chi Hyun; Yoo, Yeong-Min

    2010-01-01

    In this study, we examined whether melatonin promotes apoptotic cell death via p53 in prostate LNCaP cells. Melatonin treatment significantly curtailed the growth of LNCaP cells in a dose- and time-dependent manner. Melatonin treatment (0 to 3 mM) induced the fragmentation of poly(ADP-ribose) polymerase (PARP) and activation of caspase-3, caspase-8, and caspase-9. Moreover, melatonin markedly activated Bax expression and decreased Bcl-2 expression in dose increments. To investigate p53 and p2...

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

    OpenAIRE

    Sharkey, Katherine M.; Eastman, Charmane I.

    2002-01-01

    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...

  11. Melatonin improve the sperm quality in forced swimming test induced oxidative stress in nandrolone treated Wistar rats.

    Science.gov (United States)

    Minaii, Bagher; Moayeri, Ardeshir; Shokri, Saeed; Habibi Roudkenar, Mehryar; Golmohammadi, Taghi; Malek, Fatemeh; Barbarestani, Mohammad

    2014-01-01

    This study investigates the effects of melatonin on the sperm quality and testis weight after the combination of swimming exercise and nandrolone decanoate (DECA). Two groups of male Wistar rats were treated for eight weeks as follows; group A consist of CO (control), Sham, N (DECA), S (swimming) and NS (DECA plus swimming); and group B: Sham M (sham melatonin), M (melatonin), MN (melatonin plus DECA), MS (melatonin plus swimming), MNS (melatonin, DECA plus swimming). The motility of sperm was significantly improved in melatonin groups in comparison to N, S and NS groups (P?0.05).  The left testes weight was decreased in N, NS and MNS groups, and the right testes weight was decreased in N,S,NS, MS and MNS groups in compare with the control group. This study concluded that melatonin probably could improve the sperm motility and sex organs weight after the combination of DECA and exercise. PMID:25135257

  12. Epidemiology of nocturnal enuresis in basic schoolchildren in Aden Governorate, Yemen

    OpenAIRE

    Yousef Khalida; Basaleem Huda; Yahiya Mariam

    2011-01-01

    Nocturnal enuresis is a common problem among children and adolescents. Data regarding this problem in schoolchildren in Yemen are scarce. This study was aimed to determine the prevalence of nocturnal incontinence in Aden school going children, describe its severity and identify the relation between nocturnal enuresis with personal and family characteristics. The study was a cross-sectional survey conducted on the public basic schoolchildren in Aden, Yemen, in the period November 2007-April 20...

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

    OpenAIRE

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

    1994-01-01

    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...

  14. Effect of domperidone therapy on nocturnal dyspeptic symptoms of functional dyspepsia patients

    OpenAIRE

    Sheng-liang Chen, Jie-ru Ji

    2010-01-01

    AIM: To investigate the incidence of nocturnal dyspeptic symptoms in patients with functional dyspepsia (FD) and whether prokinetic drugs can alleviate them.METHODS: Eighty-five consecutive Chinese patients with FD were included in this study. One week after single-blinded placebo run-in treatment, baseline nocturnal intragastric pH, bile reflux and nocturnal dyspeptic symptoms of eligible patients, including epigastric pain or discomfort, abdominal distention and belching, were investigated ...

  15. Numerical simulation of relatively heavy nocturnal rain bands associated with nocturnal coastal fronts in the Mediterranean basin

    OpenAIRE

    Mazon, J.; Pino, D.

    2013-01-01

    Three offshore rain bands associated with nocturnal coastal fronts formed near the Israel coastline, the Gulf of Genoa and on the northeastern coast of the Iberian Peninsula are simulated by using version 3.3 of WRF–ARW mesoscale model to study the dynamics of the atmosphere in each case. A relatively large 1 h and 10 h accumulated precipitation are simulated when comparing with some other similar rain bands formed in the Mediterranean basin. According to...

  16. Plasma Melatonin Levels in Relation to the Light-Dark Cycle and Parental Background in Domestic Pigs

    Directory of Open Access Journals (Sweden)

    Andersson H

    2001-06-01

    Full Text Available To study porcine melatonin secretion in a stable environment 3 daytime (10.00 – 15.00 and 3 nighttime (22.00 – 03.00 plasma samples were collected by jugular venipuncture from 15 gilts, 16 sows, 3 boars and 48 piglets (24 females and 24 males from 8 litters and analysed for melatonin content. Nighttime melatonin concentrations were higher than daytime melatonin concentrations (p

  17. Removal of Melatonin Receptor Type 1 Increases Intraocular Pressure and Retinal Ganglion Cells Death in the Mouse

    OpenAIRE

    Alcantara-Contreras, Susana; Baba, Kenkichi; Tosini, Gianluca

    2011-01-01

    Previous studies have demonstrated that melatonin is effective in lowering intraocular pressure and that it may also protect ganglion cells. We have recently reported that, in mice lacking the melatonin receptors type 1, 25–30% ganglion cells die out by 18 months of age, suggesting that these receptors might be important for ganglion cells survival. In this study we show that the loss of ganglion cells is specific for melatonin receptors type 1 knock-out since mice lacking the melatonin rec...

  18. Modulation of immunity in young-adult and aged squirrel, Funambulus pennanti by melatonin and p-chlorophenylalanine

    OpenAIRE

    Singh Rajesh; Haldar Chandana; Rai Seema

    2009-01-01

    Abstract Background Our interest was to find out whether pineal gland and their by melatonin act as modulator of immunosenescence. Parachlorophenylalanine (PCPA) – a ? adrenergic blocker, is known to perform chemical pinealectomy (Px) by suppressing indirectly the substrate 5-hydroxytryptamine (5-HT) for melatonin synthesis and thereby melatonin itself. The role of PCPA, alone and in combination with melatonin was recorded in immunomodulation and free radical load in spleen of young adult ...

  19. Circadian variation in endotoxaemia and modulatory effects of melatonin.

    Science.gov (United States)

    Alamili, Mahdi

    2015-06-01

    The circadian rhythm in pathophysiological conditions has been known for many years. The symptoms in asthma bronchiale and the incidence of sudden cardiac death, pulmonary thromboembolism, and acute myocardial infarction all exhibit a rhythmic pattern through the day/night. In the immune system, a rhythmic cycle has also been described, and the oscillations exist both under normal, unstimulated conditions, and also when the immune system faces a challenge. The last mentioned is only examined in in vitro and ex vivo studies. Little is known about the circadian rhythm in the immune response in in vivo settings, where few studies have demonstrated that a circadian pattern might exist.  In this thesis the circadian variation in the response to an lipopolysaccharide (LPS) endotoxin challenge was investigated in rats and in humans. In rats, the response after LPS revealed a significantly higher inflammatory and oxidative response during the dark period compared with the light period of the day. We found that the cytokines levels in the blood plasma differed significantly between a day and night onset of the endotoxaemia. Also the antioxidant enzyme activity of superoxide dismutase was significantly altered. The same rhythmic pattern was confirmed in a human endotoxaemia model, except that the lipid peroxidation was higher during daytime endotoxaemia. Melatonin, an endogenous circadian synchronizer secreted from the pineal gland, has potent antioxidative and anti-inflammatory effects. In rats, we demonstrated that melatonin, both in day-time and night-time endotoxaemia, had a strong inhibiting effect on lipid peroxidation by reducing the levels of malondialdehyde, and melatonin increased the antioxidants' capacity. The effect on the inflammatory response showed great time dependence. In a human endotoxaemia model, the beneficial effect of melatonin was seen in the daytime endotoxaemia but not in night-time endotoxaemia, with respect to the inflammatory response but not the lipid peroxidation and antioxidants. Future trials should investigate whether the observed diurnal difference in the endotoxaemia effects exists in clinical settings, e.g. septic patients, and whether the difference has clinical implications with respect to morbidity and mortality. It is also of importance to study the molecular mechanisms resulting in this circadian rhythmicity. Finally, the effect of melatonin in clinical settings should be examined, taking into consideration the chronopharmalogical differences seen in the effect of melatonin. PMID:26036892

  20. Nocturnal hypoxaemia after myocardial infarction: association with nocturnal myocardial ischaemia and arrhythmias.

    DEFF Research Database (Denmark)

    Galatius-Jensen, S; Hansen, J

    1994-01-01

    OBJECTIVE--To document the trend in arterial hypoxaemia and electrocardiographic abnormalities on the second to sixth nights after acute myocardial infarction. PATIENTS--Nineteen consecutive patients with acute myocardial infarction who were monitored continuously during the night (minimum 2300-0700) with a Holter tape recorder and a pulse oximeter. Fifteen patients were monitored for five nights, one patient for four nights, one patient for three nights, and two patients for two nights. RESULTS--Five patients had > 30 episodic oxygen desaturations of > or = 5% during the nights of monitoring and many patients had episodes with oxygen desaturations to < 80% ranging from 46% to 61% (from 7/15 to 11/18 patients) during the nights of monitoring. Constant hypoxaemia was found in 11-13% (2/15) of the patients. Simultaneous episodic hypoxaemia and episodic tachycardia was seen in 9/17 (52%) patients on the second night, 11/18 (61%) on the third, 7/15 (46%) on the fourth, 8/15 (53%) on the fifth, and 5/15 (33%) on the sixth night. Simultaneous episodic hypoxaemia and ST deviation was seen in 5/17 (29%) patients on the second night, 3/18 (16%) on the third, 4/15 (26%) on the fourth, in no patients on the fifth, and in 3/5 (20%) on the sixth night. Simultaneous occurrence of episodic hypoxaemia and arrhythmias (supraventricular, ventricular ectopy, and atrioventricular blockade) was seen in 5/17 (29%) on the second night, 4/18 (22%) on the third, 4/15 (26%) on the fourth, 2/15 (14%) on the fifth, and in no patients on the sixth night. Overall, simultaneous occurrence of episodic hypoxaemia and electrocardiographic abnormalities (episodic tachycardia, ST deviations, and arrhythmias) was seen in 11/17 patients (64%) on the second night, 13/18 (72%) on the third, 10/15 (66%) on the fourth, 8/15 (53%) on the fifth, and 7/15 (46%) on the sixth night. One patient who died of cardiogenic shock had simultaneously occurring episodic hypoxaemia and nonsustained ventricular fibrillation on the night before she died. CONCLUSION--Episodic and constant hypoxaemia are common during the first week after acute myocardial infarction. Episodic hypoxaemia was associated with electrocardiographic abnormalities in most patients. Thus, episodic nocturnal hypoxaemia may be particularly detrimental to the infarcted myocardium in the early phase after infarction; special attention should therefore be directed towards oxygenation in this group of patients.

  1. 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.

  2. 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)

    Lemoine P

    2012-01-01

    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

  3. [Effects of melatonin on circadian time keeping system].

    Science.gov (United States)

    Mishima, K; Okawa, M

    1998-02-01

    This paper is intended to provide an overview of a physiological role of melatonin (MLT) in sleep-wake regulation. In human MLT studies, MLT has significantly increased sleepiness and fatigue during the daytime but not at night, which indicates time-dependent sleep-promoting effect of MLT. Op the other hand, MLT is known to have phase-shifting effect of biological clock. Phase response curve (PRC) for MLT administration was introduced in human studies. Successful melatonin treatments for circadian rhythm sleep-disorders based on PRC have been reported. MLT is known to decrease core body temperature. Effects of MLT on sleep-wake cycle may be mediated by a combination of sleep-promoting and phase-shifting actions and may involve the temperature lowering effect. PMID:9503826

  4. Light and melatonin schedule neuronal differentiation in the habenular nuclei

    OpenAIRE

    Borsetti, Nancy Hernandez; Dean, Benjamin J.; Bain, Emily J.; Clanton, Joshua A.; Taylor, Robert W.; Gamse, Joshua T.

    2011-01-01

    The formation of the embryonic brain requires the production, migration, and differentiation of neurons to be timely and coordinated. Coupling to the photoperiod could synchronize the development of neurons in the embryo. Here, we consider the effect of light and melatonin on the differentiation of embryonic neurons in zebrafish. We examine the formation of neurons in the habenular nuclei, a paired structure found near the dorsal surface of the brain adjacent to the pineal organ. Keeping embr...

  5. Chronic fluoxetine treatment increases daytime melatonin synthesis in the rodent

    OpenAIRE

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

    2009-01-01

    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 cyc...

  6. The reno-pineal axis: A novel role for melatonin

    OpenAIRE

    Kalra, Sanjay; Agrawal, Swati; Sahay, Manisha

    2012-01-01

    The pineal gland is a tiny endocrine gland whose physiologic role has been the focus of much research and much more speculation over the past century. This mini-review discusses recent findings which correlate melatonin and renal physiology, and postulates the presence of a “reno-pineal axis.” Drawing lessons from comparative endocrinology, while quoting human data, it advocates the need to study the “reno-pineal axis” in greater detail.

  7. Ramelteon: A melatonin receptor agonist for the treatment of insomnia

    OpenAIRE

    Devi V; Shankar. P

    2008-01-01

    Ramelteon is a novel MT1 and MT2 melatonin receptor selective agonist recently approved for the treatment of insomnia characterized by difficulty in sleep onset. It is a nonscheduled drug since it lacks the potential for abuse and does not interact with neurotransmitter receptors most associated with these phenomena. Although the effects of ramelteon use> 5 weeks are unknown, the available data confirms its safety and efficacy for short-term use. Clinical use and future research should un...

  8. Can Melatonin Help Us in Radiation Oncology Treatments?

    OpenAIRE

    Ehsan Mihandoost; Alireza Shirazi; Seied Rabie Mahdavi; Akbar Aliasgharzadeh

    2014-01-01

    Nowadays, radiotherapy has become an integral part of the treatment regimen in various malignancies for curative or palliative purposes. Ionizing radiation interacts with biological systems to produce free radicals, which attack various cellular components. Radioprotectors act as prophylactic agents that are administered to shield normal cells and tissues from the harmful effects of radiation. Melatonin has been shown to be both a direct free radical scavenger and an indirect antioxidant by s...

  9. 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)

    BrØns, Charlotte; LilleØre, S K

    2013-01-01

    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.

  10. Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases

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    Huey-Kang Sytwu

    2013-05-01

    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.

  11. Protective role of melatonin in mitochondrial dysfunction and related disorders.

    Science.gov (United States)

    Paradies, Giuseppe; Paradies, Valeria; Ruggiero, Francesca M; Petrosillo, Giuseppe

    2015-06-01

    Mitochondria are the powerhouse of the eukaryotic cell through their use of oxidative phosphorylation to generate ATP. Mitochondrial dysfunction is considered an important contributing factor in a variety of physiopathological situations such as aging, heart ischemia/reperfusion injury, diabetes and several neurodegenerative and cardiovascular diseases, as well as in cell death. Increased formation of reactive oxygen species, altered respiratory chain complexes activity and opening of the mitochondrial permeability transition pore have been suggested as possible factors responsible for impaired mitochondrial function. Therefore, preventing mitochondrial dysfunction could be an effective therapeutic strategy against cellular degenerative processes. Cardiolipin is a unique phospholipid located at the level of inner mitochondrial membrane where it plays an important role in mitochondrial bioenergetics, as well as in cell death. Cardiolipin abnormalities have been associated with mitochondrial dysfunction in a variety of pathological conditions and aging. Melatonin, the major secretory product of the pineal gland, is a well-known antioxidant agent and thus an effective protector of mitochondrial bioenergetic function. Melatonin was reported to prevent mitochondrial dysfunction from oxidative damage by preserving cardiolipin integrity, and this may explain, at least in part, the beneficial effect of this compound in mitochondrial physiopathology. In this article, mechanisms through which melatonin exerts its protective role in mitochondrial dysfunction and related disorders are reviewed. PMID:25690732

  12. Melatonin agonists for treatment of sleep and depressive disorders

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    Seithikurippu R. Pandi-Perumal

    2011-06-01

    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

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

    International Nuclear Information System (INIS)

    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.

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

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    Shiva Nasiraei-Moghadam

    2014-01-01

    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.

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

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    Hsiao-Wen Lin

    2009-03-01

    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

  16. [Melatonin participates in the origin and limitation of bone pathohological processes].

    Science.gov (United States)

    Arushanian, É B

    2015-01-01

    Melatonin, a hormone produced by pineal gland and peripheral tissue cells, controls bone metabolism and is involved in various kinds of the bone pathology through specific receptors. Modern experimental data about its osteogenic activity allow melatonin to be considered as potential drug for treating bone diseases. PMID:25898547

  17. Melatonin Decreases Daytime Challenging Behaviour in Persons with Intellectual Disability and Chronic Insomnia

    Science.gov (United States)

    Braam, W.; Didden, R.; Maas, A. P. H. M.; Korzilius, H.; Smits, M. G.; Curfs, L. M. G.

    2010-01-01

    Background: Persons with intellectual disability (ID) and sleep problems exhibit more daytime challenging behaviours than persons with ID without sleep problems. Several anecdotal reports suggest that melatonin is not only effective in the treatment of insomnia, but also decreases daytime challenging behaviour. However, the effect of melatonin

  18. Melatonin Treatment in Individuals with Intellectual Disability and Chronic Insomnia: A Randomized Placebo-Controlled Study

    Science.gov (United States)

    Braam, W.; Didden, R.; Smits, M.; Curfs, L.

    2008-01-01

    Background: While several small-number or open-label studies suggest that melatonin improves sleep in individuals with intellectual disabilities (ID) with chronic sleep disturbance, a larger randomized control trial is necessary to validate these promising results. Methods: The effectiveness of melatonin for the treatment of chronic sleep…

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

    Science.gov (United States)

    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...

  20. Accompanying therapy with melatonin at radiation therapy for uterine body cancer

    International Nuclear Information System (INIS)

    The results of treatment for uterine body cancer using post-operative radiation therapy (RT) accompanied by melatonin administration are analyzed. Accompanying therapy with melatonin limited negative RT influence on hematological and immune indices and prevented aggravation of quality of life.

  1. Protective Effects of Melatonin against Cyclophosphamide-induced Oxidative Lung Toxicity in Mice.

    Science.gov (United States)

    Shokrzadeh, M; Chabra, A; Naghshvar, F; Ahmadi, A; Jafarinejhad, M; Hasani-Nourian, Y

    2015-06-01

    This study was undertaken to evaluate the protective effects of melatonin against cyclophosphamide (CP)-induced oxidative lung toxicity in mice. Mice were pre-treated with various doses of melatonin for 7 consecutive days and were then injected with CP (200?mg/kg b.?w.) 1?h after last melatonin injection. After 24?h, the mice were euthanized and their lungs were immediately harvested. Several biomarkers associated with oxidative stress in lung homogenates, such as thiobarbituric acid reactive substances (TBARs) and reduced glutathione (GSH) levels and the activity of superoxide dismutase (SOD) and catalase (CAT) were measured spectrophotometrically. A single dose of CP markedly altered the levels of these oxidative stress biomarkers in lung homogenates. However, increased lipid peroxidation, measured as TBARs, was significantly inhibited in the lung tissues of the melatonin-pretreated mice compared to the CP alone-injected group. In addition, pretreatment with melatonin also significantly restored GSH levels and SOD and CAT activities. Melatonin also effectively protected animals from CP-induced histological abnormalities in lung tissue. In conclusion, the increase in oxidative stress markers and concomitant adaptations by the antioxidant defense system indicates that oxidative stress plays an important role in CP-induced damage to the lung. Moreover, melatonin is a potent natural antioxidant that helps prevent CP-induced oxidative toxicity in mouse lung tissues. Thus, because melatonin is regarded to be a safe pineal secretory product, it may be used concomitantly as a supplement to reduce lung damage in patients undergoing chemotherapy. PMID:24668577

  2. Recurrent nocturnal asthma after exposure to grain dust.

    Science.gov (United States)

    Davies, R J; Green, M; Schofield, N M

    1976-11-01

    Bronchial provocation tests performed on two seperate occasions in a farmer with dust from his own grain led to immediate and late respiratory reactions followed, without further exposure to grain dust, by severe respiratory reactions during subsequent nights. Studies of lung function, including measurements of closing volume, suggested that both large and small airways rather than lung parenchyma were primarily involved. Examination of the grain samples together with the results of skin and serologic tests suggested that the grain mite, Glycyphagus destructor, might be an important allergen. Serum concentrations of C3 and C4 did not alter during these recurrent nocturnal asthmatic reactions. PMID:988767

  3. Melatonin modulates visual function and cell viability in the mouse retina via the MT1 melatonin receptor

    OpenAIRE

    Baba, Kenkichi; Pozdeyev, Nikita; Mazzoni, Francesca; Contreras-Alcantara, Susana; Liu, Cuimei; Kasamatsu, Manami; Martinez-Merlos, Theresa; Strettoi, Enrica; Iuvone, P. Michael; Tosini, Gianluca

    2009-01-01

    A clear demonstration of the role of melatonin and its receptors in specific retinal functions is lacking. The present study investigated the distribution of MT1 receptors within the retina, and the scotopic and photopic electroretinograms (ERG) and retinal morphology in wild-type (WT) and MT1 receptor-deficient mice. MT1 receptor transcripts were localized in photoreceptor cells and in some inner retinal neurons. A diurnal rhythm in the dark-adapted ERG responses was observed in WT mice, wit...

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

    DEFF Research Database (Denmark)

    Kucukakin, B.; Klein, M.

    2010-01-01

    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

  5. Effect of Using Melatonin Implants on Postpartum Reproductive Indices in Tigaia Sheep Breed

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    Ioan Padeanu

    2012-10-01

    Full Text Available Investigations were carried out in a commercial farm from Turnu, Arad County, on a number of 110 indigenous adultewes from the Tigaia breed. It is estimated by some authors that administration of subcutaneous melatonin implantsduring a period of 30 days, in lactating or dry ewes, would improve the reproductive performances in some sheepbreeds. Subcutaneous melatonin implants (Melovin were inserted to the ewes in doses of 18 mg. Current research,emphasized treated that from indigenous Tigaia breed, can be obtained superior reproduction indexes if the animalsare treated with melatonin implants with 35 days before the mating season, differences from the untreated groupbeing significantly (p<0.001. However, in sheep treated used melatonin implants, the lambing interval were reducedwith 40 to 50%. It seems that use of melatonin implants Melovin type near the beginning of normal breeding season,increases the reproductive performance of adult ewes from the Tigaia breed.

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

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    OliverRawashdeh

    2012-03-01

    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.

  7. Expression and putative functions of melatonin receptors in malignant cells and tissues.

    Science.gov (United States)

    Ekmekcioglu, Cem

    2014-11-01

    Melatonin, the popular hormone of the darkness, is primarily synthesized in the pineal gland, and acts classically through the G-protein coupled plasma membrane melatonin receptors MT1 and MT2, respectively. Although some of the receptor mediated functions of melatonin, especially those on the (central) circadian system, have been more or less clarified, the functional meaning of MT-receptors in various peripheral organs are still not sufficiently investigated yet. There is, however, accumulating evidence for oncostatic effects of melatonin with both, antioxidative and MT-receptor mediated mechanisms possibly playing a role. This review briefly summarizes the physiology of melatonin and MT-receptors, and discusses the expression and function of MT-receptors in human cancer cells and tissues. PMID:25023005

  8. The effects of exogenous melatonin on the morphology of thyrocytes in pinealectomized and irradiated rats

    International Nuclear Information System (INIS)

    We investigated the effects of exogenous melatonin on the thyrocytes morphology in gamma-irradiated rats under condition where the pineal gland, as a main physiological source of endogenous melatonin, was removed. Three months after pinealectomy animals were divided into two groups: one group of animals was treated with 0.5 ml of vehicle (ethanol diluted in water) and other group was injected intraperitoneally 2 mg/kg of melatonin dissolved in 0.5 ml of vehicle daily during the period of fourteen days. After this treatment all the animals were irradiated with a single dose of 8 Gy gamma rays. Ionising radiation induced apoptosis, hydropic swelling or/and necrosis in both groups of animals, however these changes were less discerned in the thyrocytes of melatonin-treated animals. Our findings demonstrate that administration of exogenous melatonin prior to irradiation reduces radiation-induced thyrocytes damage. (author)

  9. Effect of domperidone therapy on nocturnal dyspeptic symptoms of functional dyspepsia patients

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    Sheng-Liang Chen, Jie-Ru Ji, Ping Xu, Zhi-Jun Cao, Jian-Zhong Mo, Jing-Yuan Fang, Shu-Dong Xiao

    2010-02-01

    Full Text Available AIM: To investigate the incidence of nocturnal dyspeptic symptoms in patients with functional dyspepsia (FD and whether prokinetic drugs can alleviate them.METHODS: Eighty-five consecutive Chinese patients with FD were included in this study. One week after single-blinded placebo run-in treatment, baseline nocturnal intragastric pH, bile reflux and nocturnal dyspeptic symptoms of eligible patients, including epigastric pain or discomfort, abdominal distention and belching, were investigated with questionnaires. Patients exhibiting nocturnal dyspeptic symptoms were randomly and double-blindly assigned to domperidone group or placebo group. Nocturnal intragastric pH and percentage of duodenogastric bile reflux time were determined after treatment.RESULTS: Of the 85 FD patients, 2 females without nocturnal symptoms, who responded to placebo run-in treatment, were excluded from the study, 30 (36.1% exhibited nocturnal dyspeptic symptoms with increased duodenogastric bile reflux time (intragastric bilirubin absorbance > 0.14 and mean gastric pH (confirming the existence of bile reflux (P = 0.021, 0.023 at night were included in the study. Of these 30 patients, 21 (70% had overt nocturnal duodenogastric bile reflux, which was significantly higher than that of those without nocturnal symptoms (P = 0.026. The 30 patients were allocated to domperidone group or placebo group (n = 15. The nocturnal duodenogastric bile reflux and gastric pH were significantly decreased after domperidone treatment (P = 0.015, 0.021. The severity score of nocturnal dyspeptic symptoms was also significantly decreased after domperidone treatment (P = 0.010, 0.015, 0.026, which was positively correlated with the reduced nocturnal bile reflux or gastric pH (r = 0.736, 0.784, 0.753 or r = 0.679, 0.715, 0.697, P = 0.039, 0.036, 0.037 or P = 0.043, 0.039, 0.040.CONCLUSION: A subgroup of Chinese FD patients show overt nocturnal dyspeptic symptoms, which may be correlated with the excessive nocturnal duodenogastric bile reflux. Domperidone therapy can alleviate these symptoms.

  10. Nocturnal odd-oxygen budget and its implications for ozone loss in the lower troposphere

    Science.gov (United States)

    Brown, S. S.; Neuman, J. A.; Ryerson, T. B.; Trainer, M.; Dubé, W. P.; Holloway, J. S.; Warneke, C.; de Gouw, J. A.; Donnelly, S. G.; Atlas, E.; Matthew, B.; Middlebrook, A. M.; Peltier, R.; Weber, R. J.; Stohl, A.; Meagher, J. F.; Fehsenfeld, F. C.; Ravishankara, A. R.

    2006-04-01

    Nitrogen oxides are important to the regulation of ozone throughout the Earth's atmosphere. Of particular interest for regional air quality is photochemical production and nocturnal destruction of O3 in the lower troposphere in high NOx(=NO + NO2) environments. Nocturnal tropospheric odd oxygen (Ox), defined as O3 + NO2 + 2NO3 + 3N2O5, is used to assess the impact of NOx emissions on nocturnal O3 loss. Recent aircraft measurements of the components of Ox and HNO3 yield a detailed accounting of the nocturnal Ox budget in a regionally polluted environment. The analysis demonstrates the role of NO3 and N2O5 reactions in nocturnal O3 destruction and shows that multiple factors, including timing of NOx emissions, hydrocarbon and aerosol loading, seasonality and atmospheric mixing, govern the impact of NOx emissions on regional-scale air quality.

  11. Melatonin enhances the occurrence of autophagy induced by oxidative stress in Arabidopsis seedlings.

    Science.gov (United States)

    Wang, Ping; Sun, Xun; Wang, Na; Tan, Dun-Xian; Ma, Fengwang

    2015-05-01

    The beneficial effect that melatonin has against mitochondrial dysfunctioning seems to be linked to mitophagy. Roles for melatonin have been demonstrated in promoting health and preventing disease, as well as activating the process of autophagy in general. However, no reports have been made about how the application of melatonin regulates that process when plants are exposed to oxidative stress. We investigated the influence of different concentrations of melatonin (0.0, 0.5, 5.0, 10.0, or 50.0 ?m) on autophagy under methyl viologen (MV)-induced oxidative stress. Arabidopsis seedlings that were pretreated with 5 or 10 ?m melatonin underwent relatively strong induction of autophagy, as evidenced by the number of monodansylcadaverine (MDC)-stained autophagosomes in root samples. Pretreatment with 10 ?m melatonin also alleviated MV-induced photo-oxidation damage and significantly reduced the accumulation of oxidized proteins. Those responses might have been due to the strong upregulation of genes that involved in AtATG8-PE conjugation pathway, which enhanced the capacity for autophagy. Histochemical staining revealed that both O2-· and H2 O2 were highly accumulated upon MV exposure, although the response did not differ significantly between control and melatonin-pretreated seedlings. By contrast, exogenous melatonin upregulated the expression of two genes for H2 O2 -scavenging enzymes, that is, AtAPX1 and AtCATs. The activation of autophagy by melatonin without an alteration in ROS production may be part of a survival mechanism that is enhanced by melatonin after cellular damage. Therefore, it represents a second level of defense to remove damaged proteins when antioxidant activities are compromised. PMID:25788022

  12. Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Hikichi T

    2011-05-01

    Full Text Available Taiichi Hikichi1, Naohiro Tateda2, Toshiaki Miura31Department of Ophthalmology, Ohtsuka Eye Hospital, Sapporo; 2Asahikawa National College of Technology, Asahikawa; 3Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, JapanBackground: The purpose of this study was to evaluate the dynamics of plasma melatonin secretion in patients with type 2 diabetes mellitus and diabetic retinopathy.Methods: Plasma melatonin levels were measured by high-performance liquid chromatography in 56 patients. Patients were divided into a diabetic group (30 patients and a nondiabetic group (26 patients. The diabetic group was divided further into a proliferative diabetic retinopathy (PDR group (n = 14 and a nonproliferative diabetic retinopathy (NPDR group (n = 16. Plasma melatonin levels obtained at midnight and 3 am were compared between the groups.Results: Nighttime melatonin levels were significantly lower in the diabetic group than in the nondiabetic group (P < 0.03 and lower in the PDR group than in the nondiabetic and NPDR groups (P < 0.01 and P < 0.03, respectively, but no significant difference was found between the nondiabetic and NPDR groups. The daytime melatonin level did not significantly differ between the nondiabetic and diabetic groups or between the nondiabetic, NPDR, and PDR groups.Conclusion: The nighttime melatonin level is altered in patients with diabetes and PDR but not in diabetic patients without PDR. Although patients with PDR may have various dysfunctions that affect melatonin secretion more severely, advanced dysfunction of retinal light perception may cause altered melatonin secretion. Alteration of melatonin secretion may accelerate further occurrence of complications in diabetic patients.Keywords: circadian rhythm, diabetes, proliferative diabetic retinopathy, melatonin

  13. Interactions between light and melatonin on the circadian clock of mice.

    Science.gov (United States)

    Benloucif, S; Masana, M I; Yun, K; Dubocovich, M L

    1999-08-01

    Melatonin and light synchronize the biological clock and are used to treat sleep/wake disturbances in humans. However, the two treatments affect circadian rhythms differently when they are combined than when they are administered individually. To elucidate the nature of the interaction between melatonin and light, the present study assessed the effect of melatonin on circadian timing and immediate-early gene expression in the suprachiasmatic nucleus (SCN) when administered in the presence of light. Male C3H/HeN mice, housed in constant dark in cages equipped with running wheels, were treated with either melatonin (90 microg, s.c.) or vehicle (3% ethanol-saline) 5 min prior to exposure to light (15 min, 300 lux) at various times in the circadian cycle. Combined treatment resulted in lower magnitude phase delays of circadian activity rhythms than those obtained with light alone during the early subjective night and advances in phase when melatonin and light were administered during the subjective day (p light exposure measured 300 lux but not at lower light levels (p light preceded melatonin administration, the inhibition of phase delays attained significance only when the light exposure reached 1000 lux (p light-induced expression of c-fos mRNA in the SCN was modified by melatonin administration at CT 14 or CT 22. Together, these results suggest that combined administration of melatonin and light affect circadian timing in a manner not predicted by summing the two treatments given individually. Furthermore, the interaction is not likely to be due to inhibition of photic input to the clock by melatonin but might arise from a photically induced enhancement of melatonin's actions on circadian timing. PMID:10447308

  14. Nocturnal enuresis and nocturia, differences and similarities - lessons to learn?

    Science.gov (United States)

    Goessaert, A-S; Everaert, K; Hoebeke, P; Kapila, A; Walle, J Vande

    2015-04-01

    This review highlights the current views on and differences and similarities between nocturnal enuresis (NE) in children and nocturia in adults, which might be a guidance to elucidate the missing links in our knowledge. In both conditions, a genetic factor is suspected. Reduced bladder capacity and nocturnal polyuria are the main underlying lower urinary tract-related conditions. There is a link with sleep disorders, although it is not clear whether this is a cause or consequence. Physical and mental health are comprised in both conditions, however, in different ways. In NE, constipation and attention deficit disorder are the most important comorbidities and the effect on mental health and quality of life is mainly through the negative impact on self-esteem. In nocturia, cardiovascular disease and fall injuries are important comorbidities, mainly affecting the older nocturia population; personal distress and depression are consequences of the related poor sleep quality. For both conditions, treatment is often inadequate and a more individualized approach seems to be necessary. The main difference between NE and nocturia seems to be the difference in arousal to bladder stimuli, suggesting that sleep characteristics might be a key factor in these conditions. PMID:25379877

  15. Spina Bifida Occulta in Persistent Primary Nocturnal Enuresis

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    "A. Kajbafzadeh

    2004-06-01

    Full Text Available Background/Objectives: Of congenital malformations of the central nervous system 46% are abnormalities of the spinal cord, which includes spina bifida occulta (SBO. The occurrence and significance of spina bifida occulta in patients with persistent primary nocturnal enuresis (PPNE were evaluated. Materials and Methods: Between January 2000 and February 2001, 109 consecutive children who had nocturnal enuresis more than once a week after the age of 7 years for an uninterrupted period of at least 3 months, with less than 50% reduction in wet nights despite different treatments for at least 6 months, were prospectively evaluated for the presence of associated spina bifida occulta. The results were com-pared with data from a group of 40 normal children. Results: The mean age was 9.9 years in PPNE patients and 7.5 years in normal group. SBO was present in 86 (78.9% of PPNE patients and 10 (25% of normal children. This difference was statistically significant using chi-square test. (P-value < 0.001 Conclusion: Spina bifida occulta was thought to have no clinical significance but our results showed its significant higher rate among PPNE patients. There is no direct causal relation between spina bifida occulta and enuresis, apparently, but the findings suggest a common developmental etiology.

  16. The pathophysiology of paroxysmal nocturnal hemoglobinuria and treatment with eculizumab

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    Richard Kelly

    2009-11-01

    Full Text Available 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 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 treatment which specifically binds to the complement protein C5, preventing its cleavage, and so halts the complement cascade and prevents the formation of the terminal complement proteins. Eculizumab prevents intravascular hemolysis, stabilizes hemoglobin levels, reduces or stops the need for blood transfusions, and improves fatigue and patient quality of life as well as reducing pulmonary hypertension, decreasing the risk of thrombosis and protecting against worsening renal function. It is not a curative therapy but has a great benefit on those with this rare debilitating condition.Keywords: eculizumab, paroxysmal nocturnal hemoglobinuria, hemolysis

  17. Niche convergence suggests functionality of the nocturnal fovea

    Science.gov (United States)

    Moritz, Gillian L.; Melin, Amanda D.; Tuh Yit Yu, Fred; Bernard, Henry; Ong, Perry S.; Dominy, Nathaniel J.

    2014-01-01

    The fovea is a declivity of the retinal surface associated with maximum visual acuity. Foveae are widespread across vertebrates, but among mammals they are restricted to haplorhine primates (tarsiers, monkeys, apes, and humans), which are primarily diurnal. Thus primates have long contributed to the view that foveae are functional adaptations to diurnality. The foveae of tarsiers, which are nocturnal, are widely interpreted as vestigial traits and therefore evidence of a diurnal ancestry. This enduring premise is central to adaptive hypotheses on the origins of anthropoid primates; however, the question of whether tarsier foveae are functionless anachronisms or nocturnal adaptations remains open. To explore this question, we compared the diets of tarsiers (Tarsius) and scops owls (Otus), taxa united by numerous anatomical homoplasies, including foveate vision. A functional interpretation of these homoplasies predicts dietary convergence. We tested this prediction by analyzing stable isotope ratios that integrate dietary information. In Borneo and the Philippines, the stable carbon isotope compositions of Tarsius and Otus were indistinguishable, whereas the stable nitrogen isotope composition of Otus was marginally higher than that of Tarsius. Our results indicate that species in both genera consumed mainly ground-dwelling prey. Taken together, our findings support a functional interpretation of the many homoplasies shared by tarsiers and scops owls, including a retinal fovea. We suggest that the fovea might function similarly in tarsiers and scops owls by calibrating the auditory localization pathway. The integration of auditory localization and visual fixation during prey detection and acquisition might be critical at low light levels. PMID:25120441

  18. Nocturnal gastroesophageal reflux disease: issues, implications, and management strategies.

    Science.gov (United States)

    Johnson, David A; Katz, Philip O

    2008-01-01

    The consequences of nocturnal gastroesophageal reflux disease (GERD) may be greater than daytime GERD in terms of clinical complications such as increased risk of esophageal lesions and respiratory conditions, as well as issues of health-related quality of life, sleep, work productivity, and economics. Proton pump inhibitors (PPIs) are the most effective therapy for patients with GERD; however, treatment success is greater in the improvement of daytime symptoms and acid control. Acid suppression of most PPIs, which are administered once daily before breakfast, wanes during the nighttime hours. Although nighttime heartburn improves with once-daily PPI treatment, PPIs are unable to eliminate nighttime heartburn completely. Increasing the dose of a PPI provides longer acid suppression, but the benefits have not been shown to be consistently greater than standard once-daily dosing. Twice-daily dosing, with a dose given before bedtime, would extend the duration of acid suppression into the nighttime hours; however, nocturnal acid breakthrough remains an issue. As a result, improved PPIs that will more reliably control nighttime symptoms and provide on-demand relief have been developed and studied. These newer PPI formulations offer significant hope for the advancement of treatment opportunities. PMID:18641592

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

    Science.gov (United States)

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

    2008-12-01

    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

  20. Melatonin - a key to the evaluation of the effects of electric; Melatonin - Schluessel fuer die Bewertung der Wirkung elektrischer und magnetischer Felder?

    Energy Technology Data Exchange (ETDEWEB)

    Wunstorf, B.; Lichtenberg, W. [Fachhochschule Hamburg (Germany). Fachbereich Oekotrophologie; Boikat, U. [BAGS, Amt fuer Gesundheit, Hamburg (Germany)

    2000-09-01

    The human pineal gland produces melatonin in a circadian rhythm. The substance has different functions - as a hormone, as an antioxidant and as a neurotransmitter. The secretion of melatonin and its tumor inhibition function can be influenced by electric and magnetic fields. Investigations have been carried out with rodents which have a melatonin rhythm similar to humans; nevertheless, they show a high variability between the species. The present state of knowledge only allows limited use of melatonin as an indicator for the impact of electric and magnetic fields. (orig.) [German] In der Epiphyse des Menschen wird in circadianem Rhythmus Melatonin produziert und ausgeschuettet. Die Substanz hat unterschiedliche Funktionen - als Hormon, Antioxidans und Neurotransmitter. Seine Ausschuettung und seine tumorhemmende Funktion koennen durch elektrische und magnetische Felder beeinflusst werden. Anhand von Nagern, die einen dem Menschen aehnlichen Melatoninrhythmus haben, allerdings eine hohe Speziesvarianz aufweisen, wurden diese Funktionen untersucht. Nach dem jetzigen Kenntnisstand eignet sich Melatonin nur bedingt als Indikator fuer die Wirkungen elektrischer und magnetischer Felder. (orig.)

  1. A simplified radioimmunoassay for melatonin and its application to biological fluids. Preliminary observations on the half-life of plasma melatonin in man

    International Nuclear Information System (INIS)

    A simplified and rapid radioimmunoassay (RIA) for melatonin is presented. Melatonin is extracted from serum, plasma or urine and RIA is performed by using [3H]melatonin as the tracers. The standard curve covers the range 0.2-4.3 nmol/l. By increasing the sample volume the range can be extended to 0.06 nmol/l. The intra-assay variability is 7% (relative standard deviation=rsd) and the inter-assay variability is 10% (rsd). The recovery of melatonin added to calf serum is 96%. The long term variability of the assay (43 assays on aliquots of one serum sample during 6 months) is 13.5% (rsd). The serum levels in man after one oral dose of 430 ?mol melatonin have been measured. The peak value, 620 nmol/l, was noted after 0.5 h and the melatonin concentration was still above the normal range at 24 h (2.1 nmol/l). (Auth.)

  2. Melatonin against radiation induced free radicals: a study on tissues of Swiss albino mice

    International Nuclear Information System (INIS)

    Full text: Antioxidant enzymes are part of the primary cellular defense against free radicals generated by radiation. Reports on low level chronic administration of melatonin with its antiradiation influence are scanty. Although compelling logic suggests that melatonin may be effective for a variety of disorders, the mode and optimal dose of melatonin is still not clear. Most studies have used doses of supraphysiological blood levels. Present investigation reports that melatonin in relatively lower concentrations increases the mRNA of both superoxide dismutases (SODs) and glutathione peroxidase (GSH-Px) and mediates possibly through receptors. The influence of low dose chronic administration (0.10 mg/Kg body weight/day for 15 days) of melatonin was studied against radiation-induced oxidative stress in 6 to 8 weeks old mice. Just after 24 hours of the last dose in various tissues viz. brain, liver, spleen and kidney were studied for lipid peroxidation, reduced glutathione (GSH), glutathione disulphide (GSSG), glutathione peroxidase (GSH-Px), protein, RNA, DNA and serum phosphatase activity. Radiation induced augmentation in the level of lipid peroxidation, glutathione disulphide (GSSG) and acid phosphatase was significantly ameliorated by pre-irradiation treatment with melatonin. Radiation induced depletion in the level of reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and alkaline phosphatase is significantly averted by melatonin administration. Regressioned by melatonin administration. Regression analysis of survival data yielded LD50/30 as 7.16 Gy and 11Gy for control (irradiation alone) and experimental (melatonin + irradiation), respectively. Animals produced a dose reduction factor (DRF) as 1.53. Radiation induced deficit in the body and organ weight was also significantly thwarted in the melatonin pre-treated mice. Results indicate the antioxidative properties of melatonin against the gamma radiation. The findings support the results showing melatonin as a free radical scavenger, and singlet oxygen quencher and its effect on both SODs and GPx mRNA was mediated by a de novo synthesized protein. A lower dose chronic treatment of melatonin suggests that the regulation of antioxidant enzymes gene expression is likely to be receptor mediated

  3. The vertical structure of OH-HO2-RO2 chemistry in the nocturnal boundary layer: A one-dimensional model study

    Science.gov (United States)

    Geyer, Andreas; Stutz, Jochen

    2004-08-01

    Elevated OH and peroxy radical levels have recently been observed in the nocturnal boundary layer (NBL). Despite the possible importance of OH for the gas phase and particulate composition, the source of these ROx radicals at night is currently unclear. To investigate the influence of vertical mixing on nocturnal ROx chemistry, calculations with a one-dimensional chemical transport model were performed. The model predicts distinct vertical profiles for all ROx radical species during the night, with a pronounced RO2 maximum aloft and maxima of HO2 and OH closer to the ground. We conceptualize our results by distinguishing three chemical regimes in the NBL: (1) In the unreactive ground layer, which only forms at high NO emissions and strong vertical stabilities, OH chemistry is suppressed by high NO levels. (2) The upper layer, located in the upper NBL, is decoupled from the NO emissions at the ground. Ozonolysis of volatile organic compounds (VOCs) leads to the formation of ˜105 molecules cm-3 of OH. The RO2 maximum develops in the lower part of the upper layer by the elevated O3/NO3 + VOC reaction rates. (3) In the reactive mixing layer, in the height interval between the upper layer and the ground layer, RO2 and HNO4 (as HO2 reservoir) from the upper layer are mixed with NO from the ground layer. The active radical propagation chain leads to distinctive maxima of HO2 and OH (up to several 106 molecules cm-3) in this layer. The OH radicals in the reactive mixing layer can contribute up to 43% to the nocturnal VOC oxidation, illustrating that OH chemistry can be important even at night. Our model simulations show that vertical transport can redistribute ROx radicals in the NBL, acting as an important radical source in the lowest few meters of the atmosphere.

  4. Melatonin Levels in Serum and Ascitic Fluid of Patients with Hepatic Encephalopathy

    Science.gov (United States)

    Chojnacki, Cezary; Romanowski, Marek; Winczyk, Katarzyna; B?asiak, Janusz; Chojnacki, Jan

    2012-01-01

    Cirrhotic patients exhibit disturbed melatonin homeostasis, which may lead to sleep disturbances, but an influence on the hepatic encephalopathy has not been elucidated. Aim. In the present study, the association of melatonin levels in serum and ascitic fluid and ammonia concentration related to the intensity of hepatic encephalopathy (HE) was investigated. Material and Methods. The study included 90 alcoholic patients with hepatic encephalopathy and 30 healthy volunteers (C). Patients were divided in three groups according to 0–4 West-Haven Score: HE1 (n = 28), HE2 (n = 30), and HE3 (n = 32). Melatonin was measured by radioimmune assay. Results. In fasting patients with hepatic encephalopathy we noted higher melatonin serum levels [pg/mL] than in healthy subjects groups: C—11.3?±?3.9, HE1 – 34.3?±?12.2 (P < 0.01), HE2—54.8?±?23.9, and HE3—119.8?±?96.4 (P < 0.001). No correlation between melatonin and ammonia levels was found. Melatonin was detected in ascetic fluid in 24 patients of group HE2 and 27 patients of group HE2 of hepatic encephalopathy. Conclusions. Our results suggest that high blood levels of melatonin in cirrhotic liver patients may account for some of the clinical manifestations of hepatic encephalopathy, for example, daytime sleepiness, fatigue. PMID:23346104

  5. Melatonin protects the cytochrome P450 system through a novel antioxidant mechanism.

    Science.gov (United States)

    Letelier, María Eugenia; Jara-Sandoval, José; Molina-Berríos, Alfredo; Faúndez, Mario; Aracena-Parks, Paula; Aguilera, Felipe

    2010-05-14

    Melatonin, an endogenous hormone, is used as an antioxidant drug in doses quite higher than the endogenous circulating levels of this hormone. Hepatic endoplasmic reticulum contains the cytochrome P450 (CYP450) system, which catalyzes one biotransformation pathway of melatonin; this organelle is also one of the main sources of reactive oxygen species in cells. Therefore, we proposed that the antioxidant activity of this hormone may have a biological relevance in the organelle where it is biotransformed. To evaluate this postulate, we used Fe(3+)/ascorbate, an oxygen free radical generating system that leads to lipid peroxidation, loss of protein-thiol content, and activation of UDP-glucuronyltransferase in rat liver microsomes. We found that mM concentrations of melatonin prevented all these oxidative phenomena. We also found that Fe(3+)/ascorbate leads to structural alterations in the CYP450 monooxygenase, the enzyme that binds the substrate in the CYP450 system catalytic cycle, probably through direct oxidation of the protein, and also inhibited p-nitroanisole O-demethylation, a reaction catalyzed by the CYP450 system. Notably, melatonin prevented both phenomena at microM concentrations. We provide evidence suggesting that melatonin may be oxidized by oxygen free radicals. Thus, we postulate that melatonin may be acting as an oxygen free radical scavenger, and Fe(3+)/ascorbate-modified melatonin would be directly protecting the CYP450 system through an additional specific mechanism. Pharmacological relevance of this phenomenon is discussed. PMID:20302852

  6. The role of melatonin in the cells of the innate immunity: a review.

    Science.gov (United States)

    Calvo, Juan R; González-Yanes, C; Maldonado, M D

    2013-09-01

    Melatonin is the major secretory product synthesized and secreted by the pineal gland and shows both a wide distribution within phylogenetically distant organisms from bacteria to humans and a great functional versatility. In recent years, a considerable amount of experimental evidence has accumulated showing a relationship between the nervous, endocrine, and immune systems. The molecular basis of the communication between these systems is the use of a common chemical language. In this framework, currently melatonin is considered one of the members of the neuroendocrine-immunological network. A number of in vivo and in vitro studies have documented that melatonin plays a fundamental role in neuroimmunomodulation. Based on the information published, it is clear that the majority of the present data in the literature relate to lymphocytes; thus, they have been rather thoroughly investigated, and several reviews have been published related to the mechanisms of action and the effects of melatonin on lymphocytes. However, few studies concerning the effects of melatonin on cells belonging to the innate immunity have been reported. Innate immunity provides the early line of defense against microbes and consists of both cellular and biochemical mechanisms. In this review, we have focused on the role of melatonin in the innate immunity. More specifically, we summarize the effects and action mechanisms of melatonin in the different cells that belong to or participate in the innate immunity, such as monocytes-macrophages, dendritic cells, neutrophils, eosinophils, basophils, mast cells, and natural killer cells. PMID:23889107

  7. Melatonin Suppresses Hypoxia-Induced Migration of HUVECs via Inhibition of ERK/Rac1 Activation

    Directory of Open Access Journals (Sweden)

    Ling Yang

    2014-08-01

    Full Text Available Melatonin, a naturally-occurring hormone, possesses antioxidant properties and ameliorates vascular endothelial dysfunction. In this study, we evaluate the impact of melatonin on the migratory capability of human umbilical vein endothelial cells (HUVECs to hypoxia and further investigate whether ERK/Rac1 signaling is involved in this process. Here, we found that melatonin inhibited hypoxia-stimulated hypoxia-inducible factor-1? (HIF-1? expression and cell migration in a dose-dependent manner. Mechanistically, melatonin inhibited Rac1 activation and suppressed the co-localized Rac1 and F-actin on the membrane of HUVECs under hypoxic condition. In addition, the blockade of Rac1 activation with ectopic expression of an inactive mutant form of Rac1-T17N suppressed HIF-1? expression and cell migration in response to hypoxia, as well, but constitutive activation of Rac1 mutant Rac1-V12 restored HIF-1? expression, preventing the inhibition of melatonin on cell migration. Furthermore, the anti-Rac1 effect of melatonin in HUVECs appeared to be associated with its inhibition of ERK phosphorylation, but not that of the PI3k/Akt signaling pathway. Taken together, our work indicates that melatonin exerts an anti-migratory effect on hypoxic HUVECs by blocking ERK/Rac1 activation and subsequent HIF-1? upregulation.

  8. Melatonin protects against amyloid-?-induced impairments of hippocampal LTP and spatial learning in rats.

    Science.gov (United States)

    Liu, Xiao-Jie; Yuan, Li; Yang, Dong; Han, Wei-Na; Li, Qing-Shan; Yang, Wei; Liu, Qing-Song; Qi, Jin-Shun

    2013-09-01

    Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the elderly, leads to progressive loss of memory and cognitive deficits. Amyloid-? protein (A?) in the brain is thought to be the main cause of memory loss in AD. Melatonin, an indole hormone secreted by the pineal gland, has been reported to produce neuroprotective effects. We examined whether melatonin could protect A?-induced impairments of hippocampal synaptic plasticity, neuronal cooperative activity, and learning and memory. Rats received bilateral intrahippocampal injection of A?1-42 or A?31-35 followed by intraperitoneal application of melatonin for 10 days, and the effects of chronic melatonin treatment on in vivo hippocampal long-term potentiation (LTP) and theta rhythm and Morris water maze performance were examined. We showed that intrahippocampal injection of A?1-42 or A?31-35 impaired hippocampal LTP in vivo, while chronic melatonin treatment reversed A?1-42- or A?31-35-induced impairments in LTP induction. Intrahippocampal injection of A?31-35 impaired spatial learning and decreased the power of theta rhythm in the CA1 region induced by tail pinch, and these synaptic, circuit, and learning deficits were rescued by chronic melatonin treatment. These results provide evidence for the neuroprotective action of melatonin against A? insults and suggest a strategy for alleviating cognition deficits of AD. PMID:23620224

  9. The effects of melatonin on a molecular level Die effekte van melatonien op molekulêre vlak

    Directory of Open Access Journals (Sweden)

    M. Haag

    1992-07-01

    Full Text Available The indole hormone melatonin is secreted in a biphasic circadian rhythm by the pineal gland. This review presents a summary of recent results concerning — (i factors that influence melatonin synthesis; (ii the existence of melatonin receptors in brain tissue; (iii the effects of melatonin as a modulator of dopaminergic, noradrenergic, GABAergic and opioidergic neurotransmitter processes; (iv the influence of melatonin on the electric activity and metabolic rate of certain brain nuclei; and (v melatonin effects on hormone secretion in the hypothalamic-pituitary axis. A basic mechanism of melatonin action via cyclic nucleotides and thus protein phosphorylation is presented.Die indoolhormoon melatonien word volgens 'n bifasiese sirkadiese ritme deur die pineaalklier afgeskei. Hierdie oorsigartikel bied ’n opsomming van onlangse resultate oor: (i faktore wat melatoniensekresie beinvloed; (ii die bestaan van melatonienreseptore in breinweefsel; (Hi effekte van melatonien as ’n moduleerder van dopaminergiese, noradrenergiese, GABA-ergiese en opioiedergiese neuro- oordragsprosesse; (iv die invloed van melatonien op elektriese aktiwiteit en metaboliese snelheid van sekere breinkerne; asook (v melatonieneffekte op hormoonafskeiding in die hipotalamus-hipofise-as. ’n Grondliggende meganisme van melatonienwerking deur middel van sikliese nukleotiede en proteienfosforilering word verder voorgestel.

  10. The protective effect of melatonin on neural stem cell against LPS-induced inflammation.

    Science.gov (United States)

    Song, Juhyun; Kang, So Mang; Lee, Kyoung Min; Lee, Jong Eun

    2015-01-01

    Stem cell therapy for tissue regeneration has several limitations in the fact that transplanted cells could not survive for a long time. For solving these limitations, many studies have focused on the antioxidants to increase survival rate of neural stem cells (NSCs). Melatonin, an antioxidant synthesized in the pineal gland, plays multiple roles in various physiological mechanisms. Melatonin exerts neuroprotective effects in the central nervous system. To determine the effect of melatonin on NSCs which is in LPS-induced inflammatory stress state, we first investigated nitric oxide (NO) production and cytotoxicity using Griess reagent assays, LDH assay, and neurosphere counting. Also, we investigated the effect of melatonin on NSCs by measuring the mRNA levels of SOX2, TLX, and FGFR-2. In addition, western blot analyses were performed to examine the activation of PI3K/Akt/Nrf2 signaling in LPS-treated NSCs. In the present study, we suggested that melatonin inhibits NO production and protects NSCs against LPS-induced inflammatory stress. In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Based on our results, we conclude that melatonin may be an important factor for the survival and proliferation of NSCs in neuroinflammatory diseases. PMID:25705693

  11. On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK.

    Science.gov (United States)

    Galano, Annia; Tan, Dun Xian; Reiter, Russel J

    2013-04-01

    The reactions of N(1) -acetyl-N(2) -formyl-5-methoxykynuramine (AFMK) and N(1) -acetyl-5-methoxykynuramine (AMK) with (•) OH, (•) OOH, and •OOCCl3 radicals have been studied using the density functional theory. Three mechanisms of reaction have been considered: radical adduct formation (RAF), hydrogen transfer (HT), and single electron transfer (SET). Their relative importance for the free radical scavenging activity of AFMK and AMK has been assessed. It was found that AFMK and AMK react with •OH at diffusion-limited rates, regardless of the polarity of the environment, which supports their excellent •OH radical scavenging activity. Both compounds were found to be also very efficient for scavenging •OOCCl3 , but rather ineffective for scavenging •OOH. Regarding their relative activity, it was found that AFMK systematically is a poorer scavenger than AMK and melatonin. In aqueous solution, AMK was found to react faster than melatonin with all the studied free radicals, while in nonpolar environments, the relative efficiency of AMK and melatonin as free radical scavengers depends on the radical with which they are reacting. Under such conditions, melatonin is predicted to be a better •OOH and •OOCCl3 scavenger than AMK, while AMK is predicted to be slightly better than melatonin for scavenging •OH. Accordingly it seems that melatonin and its metabolite AMK constitute an efficient team of scavengers able of deactivating a wide variety of reactive oxygen species, under different conditions. Thus, the presented results support the continuous protection exerted by melatonin, through the free radical scavenging cascade. PMID:22998574

  12. 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.

  13. Validation of a direct radioimmunoassay of melatonin in the blue fox

    International Nuclear Information System (INIS)

    A direct radioimmunoassay procedure for the determination of melatonin in the blood of blue fox has been validated and applied. The assay required 50 ?l of sample and standard, 100 ?l of antiserum and 100 ?l of (3H)melatonin. After overnight incubation at 4 deg. C the antibody bound melatonin was separated from the free hormone with dextran-coated charcoal. Following centrifugation the antibody bound (3H)melatonin was determined in a beta scintillation counter. The antiserum bound 30-35 % of the (3H)melatonin at a final dilution of 1:36000. The non specific binding represented less than 5 % of the total radioactivity in all assays. The lowest detectable amount of melatonin was 2.6 fmol/tube, corresponding to 52.5 pmol/l. The inter-assay coefficient of variation at 178 and 510 pmol/l was 15.6 and 8.8 %, respectively. The precision profile, calculated from a 10-replicate standard curve, showed that the coefficient of variation decreased from 43 % at 84 pmol/l to 15 % at 336 pmol/l, and remainded at or below 10 % for concentrations exceeding 670 pmol/l. Plasma was collected from 2 male blue foxes at about hourly intervals during a 24 h period in September and assayed for melatonin. Maximum (421 pmol/l) and minimum (97 pmol/l) concentrations of the hormone were inversely related to light intensity. (author)

  14. Evaluation of melatonin treatment in primary culture of canine mammary tumors.

    Science.gov (United States)

    Lopes, Juliana Ramos; Maschio, Larissa Bazela; Jardim-Perassi, Bruna Victorasso; Moschetta, Marina Gobbe; Ferreira, Lívia Carvalho; Martins, Gustavo Rodrigues; Gelaleti, Gabriela Bottaro; De Campos Zuccari, Debora Aparecida Pires

    2015-01-01

    Mammary neoplasias are the most common tumors observed in female dogs. Identification of these tumors is valuable in order to identify beneficial therapeutic agents as alternative treatments for this tumor type. Oral administration of melatonin appears to exert an oncostatic effect on mammary neoplasia and may have a possible mechanism of action through its interaction with estrogen receptors on epithelial cells. Hence, we analyzed the potential therapeutic value of melatonin in tumors that are estrogen-dependent or -independent, and established a relationship of its action with the expression of the melatonin receptors MT1 and MT2. Furthermore, we analyzed the rate of cell proliferation and apoptosis after treatment with melatonin. Cell cultures were performed using 10 canine mammary tumor fragments and were divided into estrogen receptor (ER)-positive and ER-negative tumors. The results showed that both ER-positive and ER-negative tumors had decreased cell viability and proliferation after treatment with melatonin (ptreatment was more effective in the ER-positive tumors. Analysis of the relative expression of the MT1 and MT2 genes by quantitative PCR was performed and the data were compared with the expression of ER in 24 canine mammary tumors and the cellular response to melatonin in 10 samples. MT1 was overexpressed in ER-positive tumors (ptreatment in ER-positive tumors showed an efficient oncostatic effect by inhibiting cell viability and proliferation and inducing apoptosis. These results suggest that melatonin decreased neoplastic mammary cell proliferation and viability and induced apoptosis, with greater efficacy in ER-positive tumors that have a high expression of melatonin receptor MT1. This is a strong evidence for the use of melatonin as a therapeutic agent for estrogen-dependent canine mammary tumors. PMID:25384569

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

    Directory of Open Access Journals (Sweden)

    Alireza Shirazi

    2009-01-01

    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.

  16. Radioimmunoassay of serum concentrations of melatonin in sheep exposed to different lighting regimens

    International Nuclear Information System (INIS)

    A specific and sensitive double-antibody radioimmunoassay for melatonin (N-acetyl-5-methoxytryptamine) was developed. The least detectable concentration of melatonin standard was 10 pmolar (2.3 pg/tube) with 50 percent inhibition resulting when the concentration was 100 pmolar (23 pg/tube). Inhibition curves obtained with increasing quantities of melatonin or increasing quantities of chloroform extracts of ovine sera were parallel. Concentrations of melatonin could be accurately determined when 31 to 1000 pg were added to 1 ml ovine serum. Serum samples with melatonin concentrations of 1000 pg/ml, 500 pg/ml and 75 pg/ml had intra-assay coefficients of variation of 9.1 percent, 8.6 percent, and 17.4 percent, respectively. The respective inter-assay coefficients of variation were 22.7 percent, 18.1 percent, and 37.1 percent. Ewes exposed to a 12 h light:12 h dark lighting regimen demonstrated a circadian rhythm in serum concentrations of melatonin. Concentrations ranged from 10 to 30 pg/ml during periods of light to 100 to 300 pg/ml during periods of dark. During exposure to continuous light, the circadian rhythm was abolished and concentrations of melatonin were maintained at 10 to 50 pg/ml. When exposed to conditions of continuous dark the circadian rhythm persisted. A precipitous drop in serum concentrations of melatonin resulted when ewes experiencing peak melatonin concentrations were exposed to light. Concentrations returned to peak levels when the lights were tured to peak levels when the lights were turned off 3.5 h later

  17. Ghost protein damage by peroxynitrite and its protection by melatonin

    Scientific Electronic Library Online (English)

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

    2000-01-01

    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.

  18. Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation.

    Science.gov (United States)

    Wei, Jia-Yi; Li, Wan-Ming; Zhou, Lin-Lin; Lu, Qiu-Nan; He, Wei

    2015-05-01

    Melatonin induces apoptosis in many different cancer cell lines, including colorectal cancer. However, the precise mechanisms involved remain largely unresolved. In this study, we provide evidence to reveal a new mechanism by which melatonin induces apoptosis of colorectal cancer LoVo cells. Melatonin at pharmacological concentrations significantly suppressed cell proliferation and induced apoptosis in a dose-dependent manner. The observed apoptosis was accompanied by the melatonin-induced dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4). Pretreatment with a HDAC4-specific siRNA effectively attenuated the melatonin-induced apoptosis, indicating that nuclear localization of HDAC4 is required for melatonin-induced apoptosis. Moreover, constitutively active Ca(2+) /calmodulin-dependent protein kinase II alpha (CaMKII?) abrogated the melatonin-induced HDAC4 nuclear import and apoptosis of LoVo cells. Furthermore, melatonin decreased H3 acetylation on bcl-2 promoter, leading to a reduction of bcl-2 expression, whereas constitutively active CaMKII?(T286D) or HDAC4-specific siRNA abrogated the effect of melatonin. In conclusion, the present study provides evidence that melatonin-induced apoptosis in colorectal cancer LoVo cells largely depends on the nuclear import of HDAC4 and subsequent H3 deacetylation via the inactivation of CaMKII?. PMID:25752481

  19. Ramelteon: A melatonin receptor agonist for the treatment of insomnia

    Directory of Open Access Journals (Sweden)

    Devi V

    2008-01-01

    Full Text Available Ramelteon is a novel MT1 and MT2 melatonin receptor selective agonist recently approved for the treatment of insomnia characterized by difficulty in sleep onset. It is a nonscheduled drug since it lacks the potential for abuse and does not interact with neurotransmitter receptors most associated with these phenomena. Although the effects of ramelteon use> 5 weeks are unknown, the available data confirms its safety and efficacy for short-term use. Clinical use and future research should uncover more information about ramelteon?s properties.

  20. [Restless legs syndrome and nocturnal leg pain : Differential diagnosis and treatment].

    Science.gov (United States)

    Hornyak, M; Stiasny-Kolster, K; Evers, S; Happe, S

    2011-09-01

    Pain in the legs belongs to the five most frequent regional pain symptoms. Restless legs syndrome (RLS) presents a particular differential diagnosis for pain in the legs, which is characterized by a nocturnal urge to move the legs often associated with painful sensations in the legs. It is one of the most common neurological disorders and probably the leading cause of nocturnal pain in the legs. In this overview, the diagnosis and therapy of RLS as well as aspects of pain therapy of the disorder are presented. In addition, the differential diagnoses for exclusion of other specific causes of nocturnal pain in the legs are discussed. PMID:21717211