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Sample records for nocturnal melatonin elevation

  1. Nocturnal melatonin secretion in multiple sclerosis patients with affective disorders.

    Science.gov (United States)

    Sandyk, R; Awerbuch, G I

    1993-02-01

    The pineal gland has been implicated recently in the pathogenesis of multiple sclerosis (MS), a chronic demyelinating disease of CNS. Since nocturnal melatonin secretion is low in some groups of patients with mental depression, we predicted lower melatonin secretion in MS patients with history of affective illness compared to those without psychiatric disorders. To test this hypothesis, we studied single nocturnal plasma melatonin levels and the incidence of pineal calcification (PC) on CT scan in a cohort of 25 MS patients (4 men, 21 women; mean age = 39.4 years, SD = 9.3), 15 of whom had a history of coexisting psychiatric disorders with predominant affective symptomatology. Other factors that may be related to depression such as vitamin B12, folic acid, zinc, magnesium, and homocysteine, were also included in the analysis. Neither any of the metabolic factors surveyed nor the incidence of PC distinguished the psychiatric from the control group. However, the mean melatonin level in the psychiatric patients was significantly lower than in the control group. Since low melatonin secretion in patients with depression may be related to a phase-advance of the circadian oscillator regulating the offset of melatonin secretion, we propose that the depression of MS likewise may reflect the presence of dampened circadian oscillators. Furthermore, since exacerbation of motor symptoms in MS patients may be temporally related to worsening of depression, we propose that circadian phase lability may also underlie the relapsing-remitting course of the disease. Consequently, pharmacological agents such as lithium or bright light therapy, which have been shown to phase-delay circadian rhythms, might be effective in the treatment of affective symptoms in MS as well as preventing motor exacerbation and hastening a remission from an acute attack. PMID:8063528

  2. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance

    Science.gov (United States)

    Dollins, A. B.; Zhdanova, I. V.; Wurtman, R. J.; Lynch, H. J.; Deng, M. H.

    1994-01-01

    We examined effects of very low doses of melatonin (0.1-10 mg, orally) or placebo, administered at 1145 h, on sleep latency and duration, mood, performance, oral temperature, and changes in serum melatonin levels in 20 healthy male volunteers. A repeated-measure double-blind Latin square design was used. Subjects completed a battery of tests designed to assess mood and performance between 0930 and 1730 h. The sedative-like effects of melatonin were assessed by a simple sleep test: at 1330 h subjects were asked to hold a positive pressure switch in each hand and to relax with eyes closed while reclining in a quiet darkened room. Latency and duration of switch release, indicators of sleep, were measured. Areas under the time-melatonin concentration curve varied in proportion to the different melatonin doses ingested, and the 0.1- and 0.3-mg doses generated peak serum melatonin levels that were within the normal range of nocturnal melatonin levels in untreated people. All melatonin doses tested significantly increased sleep duration, as well as self-reported sleepiness and fatigue, relative to placebo. Moreover, all of the doses significantly decreased sleep-onset latency, oral temperature, and the number of correct responses on the Wilkinson auditory vigilance task. These data indicate that orally administered melatonin can be a highly potent hypnotic agent; they also suggest that the physiological increase in serum melatonin levels, which occurs around 2100 h daily, may constitute a signal initiating normal sleep onset.

  3. Nocturnal Melatonin Profiles in Patients with Delayed Sleep-Wake Phase Disorder and Control Sleepers.

    Science.gov (United States)

    Micic, Gorica; Lovato, Nicole; Gradisar, Michael; Burgess, Helen J; Ferguson, Sally A; Kennaway, David J; Lack, Leon

    2015-10-01

    A significant delay in the timing of endogenous circadian rhythms has been associated with delayed sleep phase disorder (DSPD). More recently, other mechanisms have also been proposed to account for this disorder. To further explore the etiology of DSPD, the present study compared nocturnal melatonin profiles of 26 DSPD patients (18 males, 8 females; age, 21.73 ± 4.98 years) and 17 normally timed good sleepers (10 males, 7 females; age, 23.82 ± 5.23 years) in a time-free, dim-light (sleep opportunities and 40 min of enforced wakefulness was used to measure the endogenous melatonin circadian rhythm. Salivary melatonin was sampled half-hourly from 1820 h to 0020 h and then hourly from 0120 h to 1620 h. DSPD patients had significantly later timed melatonin profiles that were delayed by approximately 3 h compared to normal sleepers, and there were no notable differences in the relative duration of secretion between groups. However, melatonin secretion between dim-light melatonin onset (DLMO) and acrophase was less prominent in DSPD patients compared to good sleepers, who showed a more acute initial surge of melatonin following the DLMO. Although the regulatory role of melatonin is unknown, abnormal melatonin profiles have been linked to psychiatric and neurological disorders (e.g., major depression, obsessive compulsive disorder, Parkinson disease). These results therefore suggest that in addition to a delayed endogenous circadian rhythm, a diminished initial surge of melatonin secretion following DLMO may contribute to the etiology of DSPD. PMID:26149168

  4. 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).

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-02-01

    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.

  7. 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

  8. Melatonin

    Science.gov (United States)

    ... their bodies to start with. There is some interest in finding out whether melatonin might help with “ ... people, particularly children with multiple neurological disorders. In theory, taking melatonin might decrease the effectiveness of medications ...

  9. 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...

  10. Melatonin

    Science.gov (United States)

    ... to be more effective. Stomach ulcers caused by H. pylori infection. Evidence suggests that taking melatonin together with ... improves healing in people with ulcers caused by H. pylori infection. Irritable bowel syndrome (IBS). Early research suggests ...

  11. Variations in the light-induced suppression of nocturnal melatonin with special reference to variations in the pupillary light reflex in humans.

    Science.gov (United States)

    Yasukouchi, Akira; Hazama, Tadaaki; Kozaki, Tomoaki

    2007-03-01

    The purpose of the present study was to elucidate the existence of individual differences of pupil response to light stimulation, and to confirm the reproducibility of this phenomenon. Furthermore, the relationship between the individual differences in nocturnal melatonin suppression induced by lighting and the individual differences of pupillary light response (PLR) was examined. The pupil diameter and salivary melatonin content of 20 male students were measured at the same period of time (00:00-02:30 hr) on different days, accordingly. Illumination (530 nm) produced by a monochromatic light-emitting diode (LED) was employed as the light stimulation: pupil diameter was measured with 4 different levels of illuminance of 1, 3, 30 and 600 lux and melatonin levels were measured at 30 and 600 lux (respective controls were taken at 0 lux). Oral temperature, blood pressure and subjective index of sleepiness were taken in experiments where melatonin levels were measured. Changes of the pupil diameter in response to light were expressed as PLR and light-induced melatonin suppression was expressed as a control-adjusted melatonin suppression score (control-adjusted MSS), which was compared to the melatonin level measured at 0 lux. In the PLR, the coefficients of variation obtained at 30 lux or less were large (51.5, 45.0, 28.4 and 6.2% at 1, 3, 30 and 600 lux, respectively). Correlations of illuminance of any combination at 30 lux or less were statistically significant at less than 1% level (1 vs. 3 lux: r=0.68; 1 vs. 30 lux: r=0.64; 3 vs. 30 lux: r=0.73), which showed the reproducibility of individual differences. The control-adjusted MSS at 600 lux (-1.14+/-1.16) was significantly (p<0.05) lower than that registered at 30 lux (-0.22+/-2.12). PLR values measured at 30 and 600 lux were then correlated with control-adjusted MSS; neither indicated a significant linear relationship. However, the control-adjusted MSS showed around 0 under any of the illuminance conditions in subjects with high PLR. In control-adjusted MSS of low values (i.e., melatonin secretions were easily suppressed), subjects indicated typically low PLR. In subjects with low control-adjusted MSS (n=3), characteristic changes in the autonomic nervous system, such as body temperature and blood pressure, were noted in subjects exposed to low illuminance of 30 lux. The fact that the relationship between PLR and control-adjusted MSS portray a similar pattern even under different luminance conditions suggests that MSS may not be affected in those with high PLR at low illuminance, regardless of the illuminance condition. PMID:17435353

  12. 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...

  13. Nocturnal Elevated Convection Initiation Leading to a Daytime Surface-Based Squall Line during 13 June IHOP_2002

    Science.gov (United States)

    Marsham, J.; Trier, S. B.; Davis, C. A.; Weckwerth, T. M.; Wilson, J. W.; Ahijevych, D. A.

    2012-04-01

    In the summertime Great Plains of the USA the nocturnal maximum in precipitation is influenced by both mesoscale convective systems (MCSs) moving into the region, as well as local nocturnal initiation. During the morning, the majority of MCSs tend to dissipate, but a significant minority intensity. The greater contribution of elevated convection at night contributes to the poor forecasts of nocturnal storms (we refer to convection where the conditionally unstable source air is located above the boundary layer as "elevated" and storms fed from the boundary layer as "surface based"). Despite their importance, there are very few studies of elevated nocturnal systems leading to surface-based daytime MCSs. During the International H2O Project, the elevated nocturnal initiation of an MCS, which developed into a surface-based squall-line was observed. The elevated initiation occurred in northwest-southeast-oriented lines where a southerly nocturnal low-level jet (LLJ) terminated, with waves also observed to trigger initiation. During the morning, the structure and orientation of the MCS evolved to a southwest-northeast-oriented squall line, which built a cold-pool outflow. Convection-permitting simulations demonstrate the importance of environmental preconditioning on MCS reorganisation; the development of the SW-NE rainband is facilitated by a zone of antecedent mesoscale upward motion. Consistent with the observations, the modelled MCS develops a surface cold pool and evolves into an squall-type system. The cold pool is not necessary for the reorganisation and maintenance of the MCS. However, the latent cooling does influence the MCS strength, structure, and motion by early in the post-sunrise stage.

  14. 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...

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

    Science.gov (United States)

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

    2013-08-01

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

  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. 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

  18. Added impact of obesity and insulin resistance in nocturnal blood pressure elevation in children and adolescents.

    Science.gov (United States)

    Lurbe, Empar; Torro, Isabel; Aguilar, Francisco; Alvarez, Julio; Alcon, Jose; Pascual, Jose Maria; Redon, Josep

    2008-03-01

    The aim of the present study was to analyze the relationship between insulin resistance and the ambulatory blood pressure components in obese children and adolescents. Eighty-seven overweight and obese white children and adolescents of both sexes, of European origin from 6 to 18 years of age (mean age: 10.9+/-2.7 years), were selected. Obesity was defined on the basis of a threshold body mass index z score >2 (Cole's least mean square method) and overweight with a body mass index from the 85th to 97th percentile. A validated oscillometric method was used to measure ambulatory BP (Spacelabs 90207) during 24 hours. Fasting glucose and insulin were measured, and the homeostasis model assessment index was calculated. Subjects were grouped into tertiles of homeostasis model assessment index. No significant differences in terms of age, sex, and body mass index z score distribution were observed among groups. When adjusted by age, sex, and height, nocturnal systolic blood pressure and heart rate were significantly higher in subjects in the highest homeostasis model assessment index tertile (>4.7) as compared with those of the other groups, whereas no differences were observed for awake systolic blood pressure or heart rate. Whereas body mass index z score was more closely related with blood pressure and heart rate values, waist circumference was strongly related with insulin resistance. Moreover, both waist circumference and insulin resistance were mainly associated with higher nocturnal but not with awake blood pressure. The early increment of nocturnal blood pressure and heart rate associated with hyperinsulinemia may be a harbinger of hypertension-related insulin resistance and may contribute to heightened cardiovascular risk associated with this condition. PMID:18195166

  19. 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

  20. Antioxidative protection in a high-melatonin organism: the dinoflagellate Gonyaulax polyedra is rescued from lethal oxidative stress by strongly elevated, but physiologically possible concentrations of melatonin.

    Science.gov (United States)

    Antolín, I; Obst, B; Burkhardt, S; Hardeland, R

    1997-11-01

    Lethal oxidative stress was investigated in the dinoflagellate Gonyaulax polyedra by measuring the dying-peak of bioluminescence during circadian phases of low physiological light emission, low bioluminescence capacity, and low sensitivity to stimulatory agents. Measurements were carried out in constant darkness after transfer of cells from light at CT 6 (circadian time, 0600 hr). H2O2 (0.08 mM), when administered 1 hr after transfer of cells, led to a multifold, long-lasting enhancement of light emission, which is typical for lethal cell damage. At the circadian phases of investigation, melatonin did not substantially stimulate bioluminescence up to concentrations of 0.5 mM. At this concentration, addition of melatonin prevented the dying-peak and reduced bioluminescence to almost basal values. The high concentration of melatonin applied is not unphysiological in Gonyaulax, because the indoleamine can increase to levels of several millimolar, e.g., in response to temperature signals. These protective effects of melatonin seem to be caused mainly by the direct action of melatonin as an antioxidant, because the major enzymes of antioxidative protection were not stimulated by melatonin, although some of them responded to H2O2. The activities of neither superoxide dismutase, hemoperoxidase/catalase, glutathione peroxidase, nor haloperoxidase were enhanced under the influence of melatonin; glutathione S-transferase activity increased only slightly. PMID:9462850

  1. Melatonin attenuates Leishmania (L.) amazonensis infection by modulating arginine metabolism.

    Science.gov (United States)

    Laranjeira-Silva, Maria Fernanda; Zampieri, Ricardo A; Muxel, Sandra M; Floeter-Winter, Lucile Maria; Markus, Regina P

    2015-11-01

    Acute inflammatory responses induced by bacteria or fungi block nocturnal melatonin synthesis by rodent pineal glands. Here, we show Leishmania infection does not impair daily melatonin rhythm in hamsters. Remarkably, the attenuated parasite burden and lesion progression in hamsters infected at nighttime was impaired by blockage of melatonin receptors with luzindole, whereas melatonin treatment during the light phase attenuated Leishmania infection. In vitro studies corroborated in vivo observations. Melatonin treatment reduced macrophage expression of Cat-2b, Cat1, and ArgI, genes involved in arginine uptake and polyamine synthesis. Indeed, melatonin reduced macrophage arginine uptake by 40%. Putrescine supplementation reverted the attenuation of infectivity by melatonin indicating that its effect was due to the arrest of parasite replication. This study shows that the Leishmania/host interaction varies in a circadian manner according to nocturnal melatonin pineal synthesis. Our results provide new data regarding Leishmania infectiveness and show new approaches for applying agonists of melatonin receptors in Leishmaniasis therapy. PMID:26383232

  2. Melatonin Induces Follicle Maturation in Danio rerio

    OpenAIRE

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

    2011-01-01

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

  3. Changes of sleep architecture, spectral composition of sleep EEG, the nocturnal secretion of cortisol, ACTH, GH, prolactin, melatonin, ghrelin, and leptin, and the DEX-CRH test in depressed patients during treatment with mirtazapine.

    Science.gov (United States)

    Schmid, Dagmar A; Wichniak, Adam; Uhr, Manfred; Ising, Marcus; Brunner, Hans; Held, Katja; Weikel, Jutta C; Sonntag, Annette; Steiger, Axel

    2006-04-01

    The noradrenergic and specific serotoninergic antidepressant mirtazapine improves sleep, modulates hormone secretion including blunting of hypothalamic-pituitary-adrenocortical (HPA) activity, and may prompt increased appetite and weight gain. The simultaneous investigation of sleep electroencephalogram (EEG) and hormone secretion during antidepressive treatment helps to further elucidate these effects. We examined sleep EEG (for later conventional and quantitative analyses) and the nocturnal concentrations of cortisol, adrenocorticotropin (ACTH), growth hormone (GH), prolactin, melatonin and the key factors of energy balance, ghrelin, and leptin before and after 28 days of treatment of depressed patients (seven women, three men, mean age 39.9+/-4.2 years) with mirtazapine. In addition, a sleep EEG was recorded at day 2 and the dexamethasone-corticotropin-releasing hormone (DEX-CRH) test was performed to assess HPA activity at days -3 and 26. Psychometry and mirtazapine plasma concentrations were measured weekly. Already at day 2, sleep continuity was improved. This effect persisted at day 28, when slow-wave sleep, low-delta, theta and alpha activity, leptin and (0300-0700) melatonin increased, and cortisol and ghrelin decreased. ACTH and prolactin remained unchanged. The first two specimens of GH collected after the start of quantitative EEG analysis were reduced at day 28. The DEX-CRH test showed, at day 26, a blunting of the overshoot of ACTH and cortisol found at day -3. The Hamilton Depression score decreased from 32.1+/-7.3 to 15.5+/-6.7 between days -1 and 28. A weight gain of approximately 3 kg was observed. This unique profile of changes is compatible with the action of mirtazapine at 5-HT-2 receptors, at presynaptic adrenergic alpha 2 receptors, at the HPA system, and on ghrelin and leptin. PMID:16237393

  4. 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.

  5. Posttranscriptional regulation of pineal melatonin synthesis in Octodon degus

    OpenAIRE

    Lee, Soo Jung; Liu, Tiecheng; Chattoraj, Asamanja; Zhang, Samantha L.; Wang, lijun; Lee, Theresa M.; Wang, Michael M.; Borjigin, Jimo

    2009-01-01

    Small laboratory animals have provided significant information about melatonin regulation, yet most of these organisms are nocturnal and regulate melatonin synthesis by mechanisms that diverge from those of humans. For example, in all rodents examined, melatonin secretion occurs with a time lag of several hours after the onset of darkness; in addition, arylalkylamine N-acetyltransferase (AANAT), the key enzyme in melatonin synthesis, displays dynamic transcriptional activation specifically at...

  6. 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.

  7. Nocturnal Asthma

    Science.gov (United States)

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

  8. Melatonin: Physiological effects in humans.

    Science.gov (United States)

    Claustrat, B; Leston, J

    2015-01-01

    Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland at night under normal light/dark conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained to the light/dark cycle. Light is able to either suppress or synchronize melatonin production according to the light schedule. The nycthohemeral rhythm of this hormone can be evaluated by repeated measurement of plasma or saliva melatonin or urine sulfatoxymelatonin, the main hepatic metabolite. The primary physiological function of melatonin, whose secretion adjusts to night length, is to convey information concerning the daily cycle of light and darkness to body structures. This information is used for the organisation of functions, which respond to changes in the photoperiod such as the seasonal rhythms. Seasonal rhythmicity of physiological functions in humans related to possible alteration of the melatonin message remains, however, of limited evidence in temperate areas under field conditions. Also, the daily melatonin secretion, which is a very robust biochemical signal of night, can be used for the organisation of circadian rhythms. Although functions of this hormone in humans are mainly based on correlations between clinical observations and melatonin secretion, there is some evidence that melatonin stabilises and strengthens coupling of circadian rhythms, especially of core temperature and sleep-wake rhythms. The circadian organisation of other physiological functions depend also on the melatonin signal, for instance immune, antioxidant defences, haemostasis and glucose regulation. The difference between physiological and pharmacological effects of melatonin is not always clear but is based upon consideration of dose and not of duration of the hormone message. It is admitted that a "physiological" dose provides plasma melatonin levels in the same order of magnitude as a nocturnal peak. Since the regulating system of melatonin secretion is complex, following central and autonomic pathways, there are many pathophysiological situations where melatonin secretion can be disturbed. The resulting alteration could increase the predisposition to disease, add to the severity of symptoms or modify the course and outcome of the disorder. Since melatonin receptors display a very wide distribution in the body, putative therapeutic indications of this compound are multiple. Great advances in this field could be achieved by developing multicentre trials in a large series of patients, in order to establish efficacy of melatonin and absence of long-term toxicity. PMID:25908646

  9. Non-vertebrate melatonin.

    Science.gov (United States)

    Hardeland, Rüdiger; Poeggeler, Burkhard

    2003-05-01

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

  10. 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...

  11. Homeobox genes and melatonin synthesis

    DEFF Research Database (Denmark)

    Rohde, Kristian; Møller, Morten; Rath, Martin Fredensborg

    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, ...

  12. 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.

  13. 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

  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. Posttranscriptional regulation of pineal melatonin synthesis in Octodon degus

    Science.gov (United States)

    Lee, Soo Jung; Liu, Tiecheng; Chattoraj, Asamanja; Zhang, Samantha L.; Wang, Lijun; Lee, Theresa M.; Wang, Michael M.; Borjigin, Jimo

    2010-01-01

    Small laboratory animals have provided significant information about melatonin regulation, yet most of these organisms are nocturnal and regulate melatonin synthesis by mechanisms that diverge from those of humans. For example, in all rodents examined, melatonin secretion occurs with a time lag of several hours after the onset of darkness; in addition, arylalkylamine N-acetyltransferase (AANAT), the key enzyme in melatonin synthesis, displays dynamic transcriptional activation specifically at night in all rodents studied to date. In ungulates and primates including humans, on the other hand, melatonin secretion occurs immediately during the early night and is controlled by circadian posttranscriptional regulation of AANAT. We hypothesize that the diurnal Octodon degus (an Hystricognath rodent) could serve as an improved experimental model for studies of human melatonin regulation. To test this, we monitored melatonin production in degus using pineal microdialysis and characterized the regulation of melatonin synthesis by analyzing degu Aanat. Degu pineal melatonin rises with little latency at night, as in ungulates and primates. In addition, degu Aanat mRNA expression displays no detectable diurnal variation, suggesting that, like ungulates and primates, melatonin in this species is regulated by a posttranscriptional mechanism. Compared with AANAT from all rodents examined to date, the predicted amino acid sequence of degu AANAT is phylogenetically more closely related to ungulate and primate AANAT. These data suggest that Octodon degus may provide an ideal model system for laboratory investigation of mechanisms of melatonin synthesis and secretion in diurnal mammals. PMID:19538336

  16. Intake of melatonin increases tryptophan hydroxylase type 1 activity in aged rats: Preliminary study.

    Science.gov (United States)

    Moranta, D; Barceló, P; Aparicio, S; Garau, C; Sarubbo, F; Ramis, M; Nicolau, C; Esteban, S

    2014-01-01

    Pineal melatonin is important not only for synchronization of biological rhythms, but also in the ageing process as a potential drug to relieve oxidative damage. During ageing, the nocturnal melatonin production decreases resulting in an increased incidence of disorders. Present in vivo experiments were performed to study the effects of exogenous melatonin chronically administered to old rats on the pineal biosynthesis of melatonin and the precursor serotonin (5-HT) mediated by tryptophan hydroxylase type 1 (TPH-1). Accumulation of 5-hydroxytryptophan (5-HTP) after decarboxylase inhibition was used as a measure of the TPH-1 activity. 5-HT and its metabolite 5-HIAA were also quantified by HPLC-ED. As expected, ageing resulted in worsening of different neurochemical parameters. However, chronic intake of melatonin (1mg/kg/day, diluted in drinking water, 4 weeks) increased TPH-1 activity and significantly improved the age-induced deficits in nocturnal melatonin content in the pineal gland. Results suggest that melatonin intake (or melatonin rich foods) may contribute to recover the pineal function preventing the nocturnal descent of 5-HT and melatonin biosynthesis that normally occur in pineal gland as a consequence of ageing. PMID:24189046

  17. 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.

  18. 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...

  19. 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...

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

    OpenAIRE

    Vigo DE; Vidal MF; Cardinali DP

    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...

  1. 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 ...

  2. 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.

  3. 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

  4. Sleep-anticipating effects of melatonin in the human brain.

    Science.gov (United States)

    Gorfine, Tali; Assaf, Yaniv; Goshen-Gottstein, Yonatan; Yeshurun, Yaara; Zisapel, Nava

    2006-05-15

    Melatonin, the hormone produced nocturnally by the pineal gland, is an endogenous regulator of the sleep-wake cycle. The effects of melatonin on brain activities and their relation to induction of sleepiness were studied in a randomized, double-blind, placebo controlled functional magnetic resonance imaging (fMRI) study. Melatonin, but not placebo, reduced task-related activity in the rostro-medial aspect of the occipital cortex during a visual-search task and in the auditory cortex during a music task. These effects correlated with subjective measurements of fatigue. In addition, melatonin enhanced the activation in the left parahippocampus in an autobiographic memory task. Results demonstrate that melatonin modulates brain activity in a manner resembling actual sleep although subjects are fully awake. Furthermore, the fatigue inducing effect of melatonin on brain activity is essentially different from that of sleep deprivation thus revealing differences between fatigues related to the circadian sleep regulation as opposed to increased homeostatic sleep need. Our findings highlight the role of melatonin in priming sleep-associated brain activation patterns in anticipation of sleep. PMID:16427787

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

    OpenAIRE

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

    2008-01-01

    Disturbed sleep is common in chronic obstructive pulmonary disease (COPD). Conventional hypnotics worsen nocturnal hypoxemia and, in severe cases, can lead to respiratory failure. Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions. This randomized, double-blind, placebo-controlled study was carried out to determine the effects of melatonin on sleep in COPD. Thirty consecutive patients with moderate to very severe COPD were ini...

  6. The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes.

    Science.gov (United States)

    Leonardo-Mendonça, Roberto C; Martinez-Nicolas, Antonio; de Teresa Galván, Carlos; Ocaña-Wilhelmi, Javier; Rusanova, Iryna; Guerra-Hernández, Eduardo; Escames, Germaine; Acuña-Castroviejo, Darío

    2015-10-01

    Exercise can induce circadian phase shifts depending on the duration, intensity and frequency. These modifications are of special meaning in athletes during training and competition. Melatonin, which is produced by the pineal gland in a circadian manner, behaves as an endogenous rhythms synchronizer, and it is used as a supplement to promote resynchronization of altered circadian rhythms. In this study, we tested the effect of melatonin administration on the circadian system in athletes. Two groups of athletes were treated with 100?mg?day(-1) of melatonin or placebo 30?min before bed for four weeks. Daily rhythm of salivary melatonin was measured before and after melatonin administration. Moreover, circadian variables, including wrist temperature (WT), motor activity and body position rhythmicity, were recorded during seven days before and seven days after melatonin or placebo treatment with the aid of specific sensors placed in the wrist and arm of each athlete. Before treatment, the athletes showed a phase-shift delay of the melatonin circadian rhythm, with an acrophase at 05:00?h. Exercise induced a phase advance of the melatonin rhythm, restoring its acrophase accordingly to the chronotype of the athletes. Melatonin, but not placebo treatment, changed daily waveforms of WT, activity and position. These changes included a one-hour phase advance in the WT rhythm before bedtime, with a longer nocturnal steady state and a smaller reduction when arising at morning than the placebo group. Melatonin, but not placebo, also reduced the nocturnal activity and the activity and position during lunch/nap time. Together, these data reflect the beneficial effect of melatonin to modulate the circadian components of the sleep-wake cycle, improving sleep efficiency. PMID:26361788

  7. Melatonin and the skeleton

    DEFF Research Database (Denmark)

    Amstrup, A K; Sikjaer, T; Mosekilde, L; Rejnmark, L; Rejnmark, Lars

    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 red...

  8. 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.

  9. Nocturnal light pollution and underexposure to daytime sunlight: Complementary mechanisms of circadian disruption and related diseases.

    Science.gov (United States)

    Smolensky, Michael H; Sackett-Lundeen, Linda L; Portaluppi, Francesco

    2015-10-01

    Routine exposure to artificial light at night (ALAN) in work, home, and community settings is linked with increased risk of breast and prostate cancer (BC, PC) in normally sighted women and men, the hypothesized biological rhythm mechanisms being frequent nocturnal melatonin synthesis suppression, circadian time structure (CTS) desynchronization, and sleep/wake cycle disruption with sleep deprivation. ALAN-induced perturbation of the CTS melatonin synchronizer signal is communicated maternally at the very onset of life and after birth via breast or artificial formula feedings. Nighttime use of personal computers, mobile phones, electronic tablets, televisions, and the like - now epidemic in adolescents and adults and highly prevalent in pre-school and school-aged children - is a new source of ALAN. However, ALAN exposure occurs concomitantly with almost complete absence of daytime sunlight, whose blue-violet (446-484?nm ?) spectrum synchronizes the CTS and whose UV-B (290-315?nm ?) spectrum stimulates vitamin D synthesis. Under natural conditions and clear skies, day/night and annual cycles of UV-B irradiation drive corresponding periodicities in vitamin D synthesis and numerous bioprocesses regulated by active metabolites augment and strengthen the biological time structure. Vitamin D insufficiency and deficiency are widespread in children and adults in developed and developing countries as a consequence of inadequate sunlight exposure. Past epidemiologic studies have focused either on exposure to too little daytime UV-B or too much ALAN, respectively, on vitamin D deficiency/insufficiency or melatonin suppression in relation to risk of cancer and other, e.g., psychiatric, hypertensive, cardiac, and vascular, so-called, diseases of civilization. The observed elevated incidence of medical conditions the two are alleged to influence through many complementary bioprocesses of cells, tissues, and organs led us to examine effects of the totality of the artificial light environment in which humans reside today. Never have chronobiologic or epidemiologic investigations comprehensively researched the potentially deleterious consequences of the combination of suppressed vitamin D plus melatonin synthesis due to life in today's man-made artificial light environment, which in our opinion is long overdue. PMID:26374931

  10. Nocturnal panic attacks

    OpenAIRE

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

    2002-01-01

    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 sle...

  11. 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

  12. 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.

  13. Methylphenidate Ameliorates Depressive Comorbidity in ADHD Children without any Modification on Differences in Serum Melatonin Concentration between ADHD Subtypes

    OpenAIRE

    Isabel Cubero-Millán; Antonio Molina-Carballo; Irene Machado-Casas; Luisa Fernández-López; Sylvia Martínez-Serrano; Pilar Tortosa-Pinto; Aida Ruiz-López; Juan-de-Dios Luna-del-Castillo; José Uberos; Antonio Muñoz-Hoyos

    2014-01-01

    The vast majority of Attention-deficit/hyperactivity disorder (ADHD) patients have other associated pathologies, with depressive symptoms as one of the most prevalent. Among the mediators that may participate in ADHD, melatonin is thought to regulate circadian rhythms, neurological function and stress response. To determine (1) the serum baseline daily variations and nocturnal excretion of melatonin in ADHD subtypes and (2) the effect of chronic administration of methylphenidate, as well as ...

  14. Effect of melatonin on circadian rhythm, locomotor activity and body temperature in the intact house sparrow, Japanese quail and owl.

    Science.gov (United States)

    Murakami, N; Kawano, T; Nakahara, K; Nasu, T; Shiota, K

    2001-01-19

    We compared the effect of melatonin on circadian rhythm, body temperature, and locomotion in the intact house sparrow, Japanese quail and owl. Daily treatment with melatonin at a fixed time did not entrain the free-running rhythm of locomotor activity in the house sparrow and the disrupted rhythm in Japanese quail under constant dim light. However, melatonin clearly inhibited movement for several hours after treatment. The duration of resting after injection of melatonin was dose-dependent. Body temperature was significantly decreased after melatonin treatment, the effect being more potent during the active phase than in the resting phase. Although this effect of melatonin on body temperature was also dose-dependent, the magnitude of the decrease in body temperature after injection of melatonin was greater in the house sparrow than in the Japanese quail. On the other hand, melatonin induced a further large decrease of body temperature in a nocturnal bird, the owl, whose pineal gland is degenerate. The decrease of body temperature was larger in the active phase than in the resting phase, and melatonin did not prevent movement in spite of the decrease in body temperature. These results suggest that the effects of melatonin on circadian rhythm, locomotor activity and body temperature differ among avian species, and that these mechanisms may not be linked to each other. PMID:11166707

  15. 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.

  16. 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)

  17. Melatonin, Chronobiology, and Cancer

    Science.gov (United States)

    The NCI Office of Cancer Complementary and Alternative Medicine Invited Speaker Series Melatonin, Chronobiology, and Cancer CONTENTS Introduction...................................................................... 1 Presentation Summaries.................................................. 3 Speaker Biographies and Abstracts.

  18. 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...

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

    DEFF Research Database (Denmark)

    Kücükakin, Bülent; Lykkesfeldt, Jens; Nielsen, Hans Jørgen; Reiter, Russel J.; Rosenberg, Jacob; Gögenür, Ismayil

    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 stres...

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

    DEFF Research Database (Denmark)

    Kücükakin, Bülent; Lykkesfeldt, Jens; Nielsen, Hans Jørgen; Reiter, Russel J; Rosenberg, Jacob; Gögenur, Ismail

    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 stres...

  1. Melatonin: a multitasking molecule.

    Science.gov (United States)

    Reiter, Russel J; Tan, Dun-Xian; Fuentes-Broto, Lorena

    2010-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) has revealed itself as an ubiquitously distributed and functionally diverse molecule. The mechanisms that control its synthesis within the pineal gland have been well characterized and the retinal and biological clock processes that modulate the circadian production of melatonin in the pineal gland are rapidly being unravelled. A feature that characterizes melatonin is the variety of mechanisms it employs to modulate the physiology and molecular biology of cells. While many of these actions are mediated by well-characterized, G-protein coupled melatonin receptors in cellular membranes, other actions of the indole seem to involve its interaction with orphan nuclear receptors and with molecules, for example calmodulin, in the cytosol. Additionally, by virtue of its ability to detoxify free radicals and related oxygen derivatives, melatonin influences the molecular physiology of cells via receptor-independent means. These uncommonly complex processes often make it difficult to determine specifically how melatonin functions to exert its obvious actions. What is apparent, however, is that the actions of melatonin contribute to improved cellular and organismal physiology. In view of this and its virtual absence of toxicity, melatonin may well find applications in both human and veterinary medicine. PMID:20478436

  2. 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

  3. 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…

  4. 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.

  5. Melatonin improves oxidative stress parameters measured in the blood of elderly type 2 diabetic patients.

    Science.gov (United States)

    Kedziora-Kornatowska, Kornelia; Szewczyk-Golec, Karolina; Kozakiewicz, Mariusz; Pawluk, Hanna; Czuczejko, Jolanta; Kornatowski, Tomasz; Bartosz, Grzegorz; Kedziora, Józef

    2009-04-01

    An elevated oxidative status in the aging organism may be involved in the development of non-insulin dependent diabetes mellitus (NIDDM). Melatonin, a potent antioxidant agent, is essential for glucose homeostasis and regulation. The aim of this study was to determine the influence of melatonin supplementation on the oxidative stress parameters in elderly NIDDM patients. The malondialdehyde (MDA) concentration, Cu-Zn superoxide dismutase (SOD-1) activity in erythrocytes, the level of nitrate/nitrite in plasma and morning melatonin concentration and oxidase activity of ceruloplasmin (Cp) in serum in 15 elderly NIDDM patients at baseline and after the 30 days of melatonin supplementation (5 mg daily) in comparison with levels in 15 healthy elderly volunteers were determined. A significant increase of MDA level and decrease of SOD-1 activity and melatonin concentration were observed in NIDDM patients. Cp oxidase activity and nitrate/nitrite level were similar in both examined groups. Melatonin administration in NIDDM patients resulted in a significant increase in the morning melatonin concentration and SOD-1 activity, and a reduction in the MDA level and Cp oxidase activity. Statistically significant alterations in nitrate/nitrite levels were not observed. These results indicate an improvement of antioxidative defense after melatonin supplementation in the NIDDM individuals and suggest melatonin supplementation as an additional treatment for the control of diabetic complications. PMID:19317795

  6. 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

    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.

  7. Role of Melatonin in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Armando L. Morera-Fumero

    2013-04-01

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

  8. Role of Melatonin in Schizophrenia

    Science.gov (United States)

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

    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 approach deals with the clinical applications of melatonin as a drug treatment. In this paper, both aspects of melatonin application are reviewed. Its clinical use in schizophrenia is emphasized. PMID:23698762

  9. 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...

  10. 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

  11. 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)

  12. 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.

  13. Melatonin modulates M4-type ganglion-cell photoreceptors.

    Science.gov (United States)

    Pack, W; Hill, D D; Wong, K Y

    2015-09-10

    In the retina, melatonin is secreted at night by rod/cone photoreceptors and serves as a dark-adaptive signal. Melatonin receptors have been found in many retinal neurons including melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), suggesting it could modulate the physiology of these inner retinal photoreceptors. Here, we investigated whether melatonin modulates the alpha-like M4-type ipRGCs, which are believed to mediate image-forming vision as well as non-image-forming photoresponses. Applying melatonin during daytime (when endogenous melatonin secretion is low) caused whole-cell-recorded M4 cells' rod/cone-driven depolarizing photoresponses to become broader and larger, whereas the associated elevation in spike rate was reduced. Melanopsin-based light responses were not affected significantly. Nighttime application of the melatonin receptor antagonist luzindole also altered M4 cells' rod/cone-driven light responses but in the opposite ways: the duration and amplitude of the graded depolarization were reduced, whereas the accompanying spiking increase was enhanced. These luzindole-induced changes confirmed that M4 cells are modulated by endogenous melatonin. Melatonin could induce the above effects by acting directly on M4 cells because immunohistochemistry detected MT1 receptors in these cells, although it could also act presynaptically. Interestingly, the daytime and nighttime recordings showed significant differences in resting membrane potential, spontaneous spike rate and rod/cone-driven light responses, suggesting that M4 cells are under circadian control. This is the first report of a circadian variation in ipRGCs' resting properties and synaptic input, and of melatoninergic modulation of ipRGCs. PMID:26141846

  14. Morning and evening physical exercise differentially regulate the autonomic nervous system during nocturnal sleep in humans.

    Science.gov (United States)

    Yamanaka, Yujiro; Hashimoto, Satoko; Takasu, Nana N; Tanahashi, Yusuke; Nishide, Shin-Ya; Honma, Sato; Honma, Ken-Ichi

    2015-11-01

    Effects of daily physical exercise in the morning or in the evening were examined on circadian rhythms in plasma melatonin and core body temperature of healthy young males who stayed in an experimental facility for 7 days under dim light conditions (plasma melatonin rhythm was delayed by 1.1 h without exercise. Phase-delay shifts of a similar extent were detected by morning and evening exercise. But the falling phase shifted only after evening exercise by 1.0 h. The sleep PSG did not change after morning exercise, while Stage 1+2 sleep significantly decreased by 13.0% without exercise, and RE sleep decreased by 10.5% after evening exercise. The nocturnal decline of rectal temperature was attenuated by evening exercise, but not by morning exercise. HRV during sleep changed differentially. Very low frequency (VLF) waves increased without exercise. VLF, low frequency (LF), and high frequency (HF) waves increased after morning exercise, whereas HR increased after evening exercise. Morning exercise eventually enhanced the parasympathetic activity, as indicated by HRV, while evening exercise activated the sympathetic activity, as indicated by increase in heart rate in the following nocturnal sleep. These findings indicated differential effects of morning and evening exercise on the circadian melatonin rhythm, PSG, and HRV. PMID:26333783

  15. 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. .

  16. 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.

  17. Melatonin Anticancer Effects: Review

    OpenAIRE

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

    2013-01-01

    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 prope...

  18. 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.

  19. 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.

  20. Protecting the melatonin rhythm through circadian healthy light exposure.

    Science.gov (United States)

    Bonmati-Carrion, Maria Angeles; Arguelles-Prieto, Raquel; Martinez-Madrid, Maria Jose; Reiter, Russel; Hardeland, Ruediger; Rol, Maria Angeles; Madrid, Juan Antonio

    2014-01-01

    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. PMID:25526564

  1. 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.

  2. Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

    Science.gov (United States)

    Bonmati-Carrion, Maria Angeles; Arguelles-Prieto, Raquel; Martinez-Madrid, Maria Jose; Reiter, Russel; Hardeland, Ruediger; Rol, Maria Angeles; Madrid, Juan Antonio

    2014-01-01

    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. PMID:25526564

  3. 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.

  4. 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 app...

  5. Melatonin promotes adipogenesis and mitochondrial biogenesis in 3T3-L1 preadipocytes.

    Science.gov (United States)

    Kato, Hisashi; Tanaka, Goki; Masuda, Shinya; Ogasawara, Junetsu; Sakurai, Takuya; Kizaki, Takako; Ohno, Hideki; Izawa, Tetsuya

    2015-09-01

    Melatonin is synthesized in the pineal gland, but elicits a wide range of physiological responses in peripheral target tissues. Recent advances suggest that melatonin controls adiposity, resulting in changes in body weight. The aim of this study was to investigate the effect of melatonin on adipogenesis and mitochondrial biogenesis in 3T3-L1 mouse embryo fibroblasts. Melatonin significantly increased the expression of peroxisome proliferator-activated receptor-? (PPAR-?), a master regulator of adipogenesis, and promoted differentiation into adipocytes. Melatonin-treated cells also formed smaller lipid droplets and abundantly expressed several molecules associated with lipolysis, including adipose triglyceride lipase, perilipin, and comparative gene identification-58. Moreover, the hormone promoted biogenesis of mitochondria, as indicated by fluorescent staining, elevated the citrate synthase activity, and upregulated the expression of PPAR-? coactivator 1 ?, nuclear respiratory factor-1, and transcription factor A. The expression of uncoupling protein 1 was also observable both at mRNA and at protein level in melatonin-treated cells. Finally, adiponectin secretion and the expression of adiponectin receptors were enhanced. These results suggest that melatonin promotes adipogenesis, lipolysis, mitochondrial biogenesis, and adiponectin secretion. Thus, melatonin has potential as an anti-obesity agent that may reverse obesity-related disorders. PMID:26123001

  6. Nocturnal polyuria in monosymptomatic nocturnal enuresis refractory to desmopressin treatment

    DEFF Research Database (Denmark)

    Kamperis, K; Rittig, S

    2006-01-01

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

  7. Melatonin, immune function and cancer.

    Science.gov (United States)

    Srinivasan, Venkatramanujam; Pandi-Perumal, Seithikurippu R; Brzezinski, Amnon; Bhatnagar, Kunwar P; Cardinali, Daniel P

    2011-05-01

    Melatonin is a natural substance ubiquitous in distribution and present in almost all species ranging from unicellular organisms to humans. In mammals, melatonin is synthesized not only in the pineal gland but also in many other parts of the body, including the eyes, bone marrow, gastrointestinal tract, skin and lymphocytes. Melatonin influences almost every cell and can be traced in membrane, cytoplasmic, mitochondrial and nuclear compartments of the cell. The decline in the production of melatonin with age has been suggested as one of the major contributors to immunosenescence and development of neoplastic diseases. Melatonin is a natural antioxidant with immunoenhancing properties. T-helper cells play an important role for protection against malignancy and melatonin has been shown to enhance T-helper cell response by releasing interleukin-2, interleukin-10 and interferon-?. Melatonin is effective in suppressing neoplastic growth in a variety of tumors like melanoma, breast and prostate cancer, and ovarian and colorectal cancer. As an adjuvant therapy, melatonin can be beneficial in treating patients suffering from breast cancer, hepatocellular carcinoma or melanoma. In this paper, a brief review of recent patents on melatonin and cancer has also been presented. PMID:22074586

  8. 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.

  9. 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.

  10. Melatonin: comprehensive profile.

    Science.gov (United States)

    Al-Omary, Fatmah A M

    2013-01-01

    This chapter includes the aspects of melatonin. The drug is synthesized in the pineal gland starting from tryptophane or synthetically by using indole as starting material. Melatonin has been used as an adjunct to interleukin-2 therapy for malignant neoplasms, as contraceptive, in the management of various forms of insomnia, to alleviate jet lag following long flights, and finally as free radical scavenger and hence as an antioxidant and an anti-inflammatory. The chapter discusses the drug metabolism and pharmacokinetics and presents various method of analysis of this drug such as biological analysis, spectroscopic analysis, and chromatographic techniques of separation. It also discusses its physical properties such as solubility characteristics, X-ray powder diffraction pattern, and thermal methods of analysis. The chapter is concluded with a discussion on its biological properties such as activity, toxicity, and safety. PMID:23668405

  11. 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; psleep duration (p=.03), efficiency (p=.02); and higher activity counts during the sleep phase (p=.02) in the diabetic group. Sleep efficiency was significantly correlated with melatonin collected two hours before bed time (rho=.61; p=.047). Additionally, there were significant inverse relationships between melatonin collected at two hours before bed time and latency (rho=-.87; p=.001), wake after sleep onset (rho=-.69; p=.02) and nocturnal activity (rho=-.67; p=.03). Latency was inversely correlated with melatonin collected at bed time (rho=-.69; p=.02). These findings suggest that T2DM presents disturbances in the homeostatic and circadian drives, mainly characterized by less consistency across days of the daily circadian signal, higher rhythm fragmentation and lower rhythm amplitude. In addition to the lower melatonin levels, the decrease in the amplitude of the activity rhythm may also be involved in circadian alterations of the sleep-wake cycle.

  12. Clinical pharmacokinetics of melatonin

    DEFF Research Database (Denmark)

    Harpsøe, Nathja Groth; Andersen, Lars Peter Holst; Gögenur, Ismail; Rosenberg, Jacob

    2015-01-01

    PURPOSE: The aim of the review was to provide an overview of studies investigating the pharmacokinetics of exogenous melatonin in humans and if possible, to provide recommendations for clinical use. METHODS: The review was conducted in accordance to PRISMA guidelines. A systematic literature search was performed in PubMed and Embase databases. The pharmacokinetic variables included maximal plasma/serum concentration (Cmax), time to maximal plasma/serum concentration (Tmax), elimination half-life...

  13. The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders

    OpenAIRE

    Pagan, C; Delorme, R.; Callebert, J.; Goubran-Botros, H; Amsellem, F; Drouot, X; Boudebesse, C; Le Dudal, K; Ngo-Nguyen, N; Laouamri, H; Gillberg, C; Leboyer, M.; Bourgeron, T.; Launay, J-M

    2014-01-01

    Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melat...

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

    OpenAIRE

    Kristian Rohde; Morten Møller; 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...

  15. Melatonin in the mammalian olfactory bulb

    OpenAIRE

    Corthell, J. T.; Olcese, J.; Trombley, P. Q.

    2013-01-01

    Melatonin is a neurohormone associated with circadian rhythms. A diurnal rhythm in olfactory sensitivity has been previously reported and melatonin receptor mRNAs have been observed in the olfactory bulb, but the effects of melatonin in the olfactory bulb have not been explored. First, we corroborated data from a previous study that identified melatonin receptor messenger RNAs in the olfactory bulb. We then investigated whether melatonin treatment would affect cells in the olfactory bulbs of ...

  16. 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...

  17. First-Morning Urinary Melatonin and Breast Cancer Risk in the Guernsey Study

    Science.gov (United States)

    Wang, Xiao-Si; Tipper, Sarah; Appleby, Paul N.; Allen, Naomi E.; Key, Timothy J.; Travis, Ruth C.

    2014-01-01

    It has been hypothesized that suppressed nocturnal melatonin production is associated with an increased risk of breast cancer, but results from several small prospective studies of the association have been inconclusive. We examined the association between nocturnal melatonin and breast cancer risk in a case-control study nested within the Guernsey III Study, a British prospective cohort study (1977–2009). Concentrations of 6-sulfatoxymelatonin were measured in prediagnostic first-morning urine samples from 251 breast cancer cases and 727 matched controls. Conditional logistic regression models were used to calculate odds ratios for breast cancer in relation to 6-sulfatoxymelatonin level. No significant association was found between 6-sulfatoxymelatonin level and breast cancer risk, either overall (for highest third vs. lowest, multivariable-adjusted odds ratio = 0.90, 95% confidence interval: 0.61, 1.33) or by menopausal status. However, in a meta-analysis of all published prospective data, including 1,113 cases from 5 studies, higher 6-sulfatoxymelatonin levels were associated with lower breast cancer risk (for highest fourth vs. lowest, odds ratio = 0.81, 95% confidence interval: 0.66, 0.99). In summary, we found no evidence that 6-sulfatoxymelatonin level in a first-morning urine sample was associated with breast cancer risk among British women. However, overall the published data suggest a modest inverse association between melatonin levels and breast cancer risk. Further data are needed to confirm this association. PMID:24418683

  18. 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.

  19. Methylphenidate Ameliorates Depressive Comorbidity in ADHD Children without any Modification on Differences in Serum Melatonin Concentration between ADHD Subtypes

    Directory of Open Access Journals (Sweden)

    Isabel Cubero-Millán

    2014-09-01

    Full Text Available The vast majority of Attention-deficit/hyperactivity disorder (ADHD patients have other associated pathologies, with depressive symptoms as one of the most prevalent. Among the mediators that may participate in ADHD, melatonin is thought to regulate circadian rhythms, neurological function and stress response. To determine (1 the serum baseline daily variations and nocturnal excretion of melatonin in ADHD subtypes and (2 the effect of chronic administration of methylphenidate, as well as the effects on symptomatology, 136 children with ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR criteria were divided into subgroups using the “Children’s Depression Inventory” (CDI. Blood samples were drawn at 20:00 and 09:00 h, and urine was collected between 21:00 and 09:00 h, at inclusion and after 4.61 ± 2.29 months of treatment. Melatonin and its urine metabolite were measured by radioimmunoassay RIA. Factorial analysis was performed using STATA 12.0. Melatonin was higher predominantly in hyperactive-impulsive/conduct disordered children (PHI/CD of the ADHD subtype, without the influence of comorbid depressive symptoms. Methylphenidate ameliorated this comorbidity without induction of any changes in the serum melatonin profile, but treatment with it was associated with a decrease in 6-s-melatonin excretion in both ADHD subtypes. Conclusions: In untreated children, partial homeostatic restoration of disrupted neuroendocrine equilibrium most likely led to an increased serum melatonin in PHI/CD children. A differential cerebral melatonin metabolization after methylphenidate may underlie some of the clinical benefit.

  20. The potential physiological crosstalk and interrelationship between two sovereign endogenous amines, melatonin and homocysteine.

    Science.gov (United States)

    Paul, Rajib; Borah, Anupom

    2015-10-15

    The antioxidant melatonin and the non-proteinogenic excitotoxic amino acid homocysteine (Hcy) are very distinct but related reciprocally to each other in their mode of action. The elevated Hcy level has been implicated in several disease pathologies ranging from cardio- and cerebro-vascular diseases to neurodegeneration owing largely to its free radical generating potency. Interestingly, melatonin administration potentially normalizes the elevated Hcy level, thereby protecting the cells from the undesired Hcy-induced excitotoxicity and cell death. However, the exact mechanism and between them remain obscure. Through literature survey we have found an indistinct but a vital link between melatonin and Hcy i.e., the existence of reciprocal regulation between them, and this aspect has been thoroughly described herein. In this review, we focus on all the possibilities of co-regulation of melatonin and Hcy at the level of their production and metabolism both in basal and in pathological conditions, and appraised the potential of melatonin in ameliorating homocysteinemia-induced cellular stresses. Also, we have summarized the differential mode of action of melatonin and Hcy on health and disease states. PMID:26281918

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

    OpenAIRE

    Mathes, Alexander M.

    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, and...

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

    OpenAIRE

    Quera Salva, M.A.; 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...

  3. Melatonin as a preventive and curative therapy against pulmonary hypertension.

    Science.gov (United States)

    Maarman, Gerald; Blackhurst, Dee; Thienemann, Friedrich; Blauwet, Lori; Butrous, Ghazwan; Davies, Neil; Sliwa, Karen; Lecour, Sandrine

    2015-10-01

    Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure, which leads to right ventricular (RV) hypertrophy and failure. The pathophysiological mechanisms of PH remain unclear but oxidative stress is believed to contribute to RV dysfunction. Melatonin is a powerful antioxidant and is cardioprotective against ischemia-reperfusion injury and hypertension. Therefore, we hypothesized that a chronic treatment with melatonin, given as a curative or preventive therapy, may confer cardiovascular benefits in PH. PH was induced in Long Evans rats (n ? 6 per group), with a single subcutaneous injection of monocrotaline (MCT, 80 mg/kg). Melatonin was given daily in the drinking water, with the treatment starting either on the day of the injection of MCT (dose testing: melatonin 75 ng/L and 6 mg/kg), 14 days after the injection of MCT (curative treatment: 6 mg/kg), or 5 days before the injection (preventive treatment: 6 mg/kg). The development of PH was assessed by measuring RV hypertrophy, RV function, cardiac interstitial fibrosis, and plasma oxidative stress. Compared with controls, MCT-treated rats displayed RV hypertrophy and dysfunction, increased interstitial fibrosis, and elevated plasma oxidative stress. A chronic melatonin treatment (75 ng/L or 6 mg/kg) reduced RV hypertrophy, improved RV function and reduced plasma oxidative stress. Curative and preventive treatment improved RV functional and plasma oxidative stress parameters and reduced cardiac interstitial fibrosis. Our data demonstrate that melatonin confers cardioprotection in this model of PH. As melatonin is an inexpensive and safe drug, we propose that clinical investigation of the effects of melatonin on RV function in patients with PH should be considered. PMID:26201290

  4. 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.

  5. The organization of melatonin in lipid membranes.

    Science.gov (United States)

    Dies, Hannah; Cheung, Bonnie; Tang, Jennifer; Rheinstädter, Maikel C

    2015-04-01

    Melatonin is a hormone that has been shown to have protective effects in several diseases that are associated with cholesterol dysregulation, including cardiovascular disease, Alzheimer's disease, and certain types of cancers. We studied the interaction of melatonin with model membranes made of dimyristoylphosphatidylcholine (DMPC) at melatonin concentrations ranging from 0.5mol% to 30mol%. From 2-dimensional X-ray diffraction measurements, we find that melatonin induces a re-ordering of the lipid membrane that is strongly dependent on the melatonin concentration. At low melatonin concentrations, we observe the presence of melatonin-enriched patches in the membrane, which are significantly thinner than the lipid bilayer. The melatonin molecules were found to align parallel to the lipid tails in these patches. At high melatonin concentrations of 30mol%, we observe a highly ordered melatonin structure that is uniform throughout the membrane, where the melatonin molecules align parallel to the bilayers and one melatonin molecule associates with 2 lipid molecules. Understanding the organization and interactions of melatonin in membranes, and how these are dependent on the concentration, may shed light into its anti-amyloidogenic, antioxidative and photoprotective properties and help develop a structural basis for these properties. PMID:25602914

  6. 21 CFR 522.1350 - Melatonin implant.

    Science.gov (United States)

    2010-04-01

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

  7. 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...

  8. 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, ...

  9. 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

  10. 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 ...

  11. 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.

  12. Impact of different colours of artificial light at night on melatonin rhythm and gene expression of gonadotropins in European perch.

    Science.gov (United States)

    Brüning, Anika; Hölker, Franz; Franke, Steffen; Kleiner, Wibke; Kloas, Werner

    2016-02-01

    The distribution and intensity of artificial light at night, commonly referred to as light pollution, is consequently rising and progressively also ecological implications come to light. Low intensity light is known to suppress nocturnal melatonin production in several fish species. This study aims to examine the least suppressive light colour for melatonin excreted into the holding water and the influence of different light qualities and quantities in the night on gene expression of gonadotropins in fish. European perch (Perca fluviatilis) were exposed to light of different wavelengths during the night (blue, green, and red). Melatonin concentrations were measured from water samples every 3h during a 24h period. Gene expression of gonadotropins was measured in perch exposed to different light colours and was additionally examined for perch subjected to different intensities of white light (0lx, 1lx, 10lx, 100lx) during the night. All different light colours caused a significant drop of melatonin concentration; however, blue light was least suppressive. Gene expression of gonadotropins was not influenced by nocturnal light of different light colours, but in female perch gonadotropin expression was significantly reduced by white light already at the lowest level (1lx). We conclude that artificial light with shorter wavelengths at night is less effective in disturbing biological rhythms of perch than longer wavelengths, coinciding with the light situation in freshwater habitats inhabited by perch. Different light colours in the night showed no significant effect on gonadotropin expression, but white light in the night can disturb reproductive traits already at very low light intensities. These findings indicate that light pollution has not only the potential to disturb the melatonin cycle but also the reproductive rhythm and may therefore have implications on whole species communities. PMID:26584071

  13. Role of Carnosine and Melatonin in Ameliorating Cardiotoxicity of Titanium Dioxide Nanoparticles in the Rats

    Directory of Open Access Journals (Sweden)

    Nouf Al-Rasheed

    2015-08-01

    Full Text Available The aim of this work was to study the possible cardiotoxicity of two different doses of 50 nm nano titanium dioxide (n-TiO2 and the possible modulating effects of the use of two natural antioxidants carnosine and melatonin. The results showed that TiO2- NPs produced deleterious effects on rat cardiac tissue as confirmed by the increased levels of serum myoglobin, troponin-T and CK-MB. Increased levels of serum Inflammatory markers represented by the tumor necrosis factor alpha (TNF-? and Interleukin-6 (IL-6 was also noticed. Caspase3 and IGg were elevated compared to the control group in a dose dependant manner. treatment of the rats with Carnosine or melatonin. along with TiO2- NPs administration significantly improved most of the elevated biochemical markers. It was concluded that the use of Carnosine or melatonin could play a beneficial role against deleterious effects of TiO2- NPs

  14. 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.

  15. Sertraline and venlafaxine-induced nocturnal enuresis

    Directory of Open Access Journals (Sweden)

    inci meltem atay

    2015-01-01

    Full Text Available Nocturnal enuresis is defined as the involuntary discharge of urine after the age of expected continence that occurs during sleep at night. Although there are a few reports in adults for nocturnal enuresis associated with serotonin reuptake inhibitors (SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs, the mechanism or frequency of this side effect have not been identified yet. We report here a case of nocturnal enuresis associated with both sertraline and venlafaxine in different major depressive episodes in an adult patient that resolves after the discontinuation of the medications and continuation with escitalopram. To our knowledge, in literature there have been no reports about nocturnal enuresis caused by those two agents in the same patient. This case is discussed in detail for the recurrence of nocturnal enuresis, the importance of detailed assessment of even rare side effects and for their possible mechanisms.

  16. 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.

  17. 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.)

  18. Melatonin lowers edema after spinal cord injury

    OpenAIRE

    Li, Cheng; Chen, Xiao; Qiao, Suchi; Liu, Xinwei; Liu, Chang; Zhu, Degang; Su, Jiacan; Wang, Zhiwei

    2014-01-01

    Melatonin has been shown to diminish edema in rats. Melatonin can be used to treat spinal cord injury. This study presumed that melatonin could relieve spinal cord edema and examined how it might act. Our experiments found that melatonin (100 mg/kg, i.p.) could reduce the water content of the spinal cord, and suppress the expression of aquaporin-4 and glial fibrillary acidic protein after spinal cord injury. This suggests that the mechanism by which melatonin alleviates the damage to the spin...

  19. Melatonin, environmental light, and breast cancer.

    Science.gov (United States)

    Srinivasan, V; Spence, D W; Pandi-Perumal, S R; Trakht, I; Esquifino, A I; Cardinali, D P; Maestroni, G J

    2008-04-01

    Although many factors have been suggested as causes for breast cancer, the increased incidence of the disease seen in women working in night shifts led to the hypothesis that the suppression of melatonin by light or melatonin deficiency plays a major role in cancer development. Studies on the 7,12-dimethylbenz[a]anthracene and N-methyl-N-nitrosourea experimental models of human breast cancer indicate that melatonin is effective in reducing cancer development. In vitro studies in MCF-7 human breast cancer cell line have shown that melatonin exerts its anticarcinogenic actions through a variety of mechanisms, and that it is most effective in estrogen receptor (ER) alpha-positive breast cancer cells. Melatonin suppresses ER gene, modulates several estrogen dependent regulatory proteins and pro-oncogenes, inhibits cell proliferation, and impairs the metastatic capacity of MCF-7 human breast cancer cells. The anticarcinogenic action on MCF-7 cells has been demonstrated at the physiological concentrations of melatonin attained at night, suggesting thereby that melatonin acts like an endogenous antiestrogen. Melatonin also decreases the formation of estrogens from androgens via aromatase inhibition. Circulating melatonin levels are abnormally low in ER-positive breast cancer patients thereby supporting the melatonin hypothesis for breast cancer in shift working women. It has been postulated that enhanced endogenous melatonin secretion is responsible for the beneficial effects of meditation as a form of psychosocial intervention that helps breast cancer patients. PMID:17541739

  20. Extrapineal melatonin: sources, regulation, and potential functions.

    Science.gov (United States)

    Acuña-Castroviejo, Darío; Escames, Germaine; Venegas, Carmen; Díaz-Casado, María E; Lima-Cabello, Elena; López, Luis C; Rosales-Corral, Sergio; Tan, Dun-Xian; Reiter, Russel J

    2014-08-01

    Endogenous melatonin is synthesized from tryptophan via 5-hydroxytryptamine. It is considered an indoleamine from a biochemical point of view because the melatonin molecule contains a substituted indolic ring with an amino group. The circadian production of melatonin by the pineal gland explains its chronobiotic influence on organismal activity, including the endocrine and non-endocrine rhythms. Other functions of melatonin, including its antioxidant and anti-inflammatory properties, its genomic effects, and its capacity to modulate mitochondrial homeostasis, are linked to the redox status of cells and tissues. With the aid of specific melatonin antibodies, the presence of melatonin has been detected in multiple extrapineal tissues including the brain, retina, lens, cochlea, Harderian gland, airway epithelium, skin, gastrointestinal tract, liver, kidney, thyroid, pancreas, thymus, spleen, immune system cells, carotid body, reproductive tract, and endothelial cells. In most of these tissues, the melatonin-synthesizing enzymes have been identified. Melatonin is present in essentially all biological fluids including cerebrospinal fluid, saliva, bile, synovial fluid, amniotic fluid, and breast milk. In several of these fluids, melatonin concentrations exceed those in the blood. The importance of the continual availability of melatonin at the cellular level is important for its physiological regulation of cell homeostasis, and may be relevant to its therapeutic applications. Because of this, it is essential to compile information related to its peripheral production and regulation of this ubiquitously acting indoleamine. Thus, this review emphasizes the presence of melatonin in extrapineal organs, tissues, and fluids of mammals including humans. PMID:24554058

  1. 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.

  2. Melatonin Anticancer Effects: Review

    Science.gov (United States)

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

    2013-01-01

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

  3. Treatment of paroxysmal nocturnal hemoglobinuria

    Directory of Open Access Journals (Sweden)

    I. A. Lisukov

    2014-07-01

    Full Text Available Paroxysmal nocturnal hemoglobinuria (PNH is a rare, life?threatening clonal hematological disorder caused by an acquired mutation in the phosphatidylinositol glucan (PIG-A gene. PNH is characterized by chronic intravascular hemolysis, marrow failure, thrombophilia and other severe clinical syndromes. Until recently, the treatment of PNH has been symptomatic with blood transfusions, anticoagulation and supplementation with folic acid or iron. The only potentially curative treatment is allogeneic stem cell transplantation, but this has severe complications with high mortality rates. A new targeted treatment strategy is the inhibition of the terminal complement cascade with anti?C5 monoclonal antibody (eculizumab. Eculizumab has shown significant efficacy in controlling of intravascular hemolysis resulting in improving quality of life and survival.

  4. The cause of ischaemic nocturnal rest pain

    DEFF Research Database (Denmark)

    Jelnes, Rolf; Bülow, J

    1988-01-01

    Adipose tissue blood flow in the forefoot was measured simultaneously with mean systemic arterial blood pressure over 24 hours in 8 patients (15 feet) with different degrees of arterial insufficiency. Mean systemic arterial pressure decreased by 19 +/- 9% during sleep, irrespective of symptomatology. In two limbs, with a normal peripheral circulation, blood flow decreased by 8 +/- 7%. In five limbs with arterial insufficiency, but no rest pain, blood flow decreased by 16 +/- 8% and in eight limbs with ischaemic nocturnal rest pain blood flow was reduced by 32 +/- 12% during sleep. It is concluded that nocturnal hypotension is a major factor in the production of nocturnal ischaemic rest pain.

  5. 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. However, melatonin ameliorated the elevated TSH level induced by ?-irradiation to reach its corresponding control value at day 21

  6. Melatonin action in neonatal gonadotrophs.

    Czech Academy of Sciences Publication Activity Database

    Balík, Aleš; Kretschmannová, Karla; Mazna, Petr; Svobodová, Irena; Zemková, Hana

    2004-01-01

    Ro?. 53, Suppl. 1 (2004), s. S153-S166. ISSN 0862-8408 R&D Projects: GA ?R GA309/02/1519; GA AV ?R IAA5011103; GA AV ?R IAA5011408 Institutional research plan: CEZ:AV0Z5011922 Keywords : melatonin * gonadotrophs * GnRH Subject RIV: ED - Physiology Impact factor: 1.140, year: 2004

  7. 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; Lucien C. Manchester; 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...

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

    Science.gov (United States)

    Harada, Tetsuo

    2004-08-11

    BACKGROUND: In a previous study, when adult subjects were exposed to a level of 400 lux light for more than 30 min or a level of 300 lux light for more than 2 hours, salivary melatonin concentration during the night dropped lower than when the subjects were exposed to dim illumination. It was suggested that such light exposure in adolescents or children during the first half of subjective night in normal life might decrease the melatonin level and prevent the falling into sleep. However, there has been no actual study on the effects of light exposure in adolescents. METHODS: Effects of exposure to the bright light (2000 lux) from fluorescent light bulbs during a period of three hours from 19:30 to 22:30 in one evening were examined on evening salivary melatonin concentrations from 19:45 to 23:40. The control group was exposed to dim light (60 lux) during these three hours. Both the dim light control group [DLCG] and the bright light experimental group [BLEG] consisted of two female and three male adolescent participants aged 14-15 y. RESULTS: The salivary melatonin level increased rapidly from 3.00 pg/ml at 21:45 to 9.18 pg/ml at 23:40 in DLCG, whereas it remained at less than 1.3 pg/ml for the three hours in BLEG. Melatonin concentration by BLEG at 22:30 of the experimental day was lower than that at the same time on the day before the experimental day, whereas it was significantly higher in the experimental day than on the day before the experimental day in DLCG. CONCLUSIONS: Bright lights of 2000 lux and even moderate lights of 200-300 lux from fluorescent light bulbs can inhibit nocturnal melatonin concentration in adolescents. Ancient Japanese lighting from a traditional Japanese hearth, oil lamp or candle (20-30 lux) could be healthier for children and adolescents because rapid and clear increase in melatonin concentration in blood seems to occur at night under such dim light, thus facilitating a smooth falling into night sleep. PMID:15304196

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

    Directory of Open Access Journals (Sweden)

    Zago W.M.

    1999-01-01

    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.

  10. 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.

    1999-08-01

    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.

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

    International Nuclear Information System (INIS)

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

  12. Green Light for Nocturnally Migrating Birds

    OpenAIRE

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

    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...

  13. Nocturnal panic attacks Ataques de pânico noturno

    OpenAIRE

    FABIANA L. LOPES; Nardi, Antonio E; Isabella Nascimento; Valença, Alexandre M.; Walter A Zin

    2002-01-01

    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 sle...

  14. Inhibition of hippocampal neurogenesis by sleep deprivation is independent of circadian disruption and melatonin suppression.

    Science.gov (United States)

    Mueller, A D; Mear, R J; Mistlberger, R E

    2011-10-13

    Procedures that restrict or fragment sleep can inhibit neurogenesis in the hippocampus of adult rodents, although the underlying mechanism is unknown. We showed that rapid-eye-movement (REM) sleep deprivation (RSD) by the platform-over-water method inhibits hippocampal cell proliferation in adrenalectomized rats with low-dose corticosterone clamp. This procedure also greatly disrupts daily behavioral rhythms. Given recent evidence for circadian clock regulation of cell proliferation, we asked whether disruption of circadian rhythms might play a role in the anti-neurogenic effects of sleep loss. Male Sprague-Dawley rats were subjected to a 4-day RSD procedure or were exposed to constant bright light (LL) for 4 days or 10 weeks, a non-invasive procedure for eliminating circadian rhythms of behavior and physiology in this species. Proliferating cells in the granule cell layer of the dentate gyrus were identified by immunolabeling for the thymidine analogue 5-bromo-2-deoxyuridine. Consistent with our previous results, the RSD procedure suppressed cell proliferation by ?50%. By contrast, although LL attenuated or eliminated daily rhythms of activity and sleep-wake without affecting daily amounts of REM sleep, cell proliferation was not affected. Melatonin, a nocturnally secreted neurohormone that is inhibited by light, has been shown to promote survival of new neurons. We found that 3-weeks of LL eliminated daily rhythms and decreased plasma melatonin by 88% but did not significantly affect either total cell survival or survival of new neurons (doublecortin+). Finally, we measured cell proliferation rates at the beginning and near the end of the daily light period in rats entrained to a 12:12 light/lark (LD) cycle, but did not detect a daily rhythm. These results indicate that the antineurogenic effect of RSD is not secondary to disruption of circadian rhythms, and provide no evidence that hippocampal cell proliferation and survival are regulated by the circadian system or by nocturnal secretion of pineal melatonin. PMID:21771640

  15. Pineal melatonin is a circadian time-giver for leptin rhythm in Syrian hamsters.

    Science.gov (United States)

    Chakir, Ibtissam; Dumont, Stéphanie; Pévet, Paul; Ouarour, Ali; Challet, Etienne; Vuillez, Patrick

    2015-01-01

    Nocturnal secretion of melatonin from the pineal gland may affect central and peripheral timing, in addition to its well-known involvement in the control of seasonal physiology. The Syrian hamster is a photoperiodic species, which displays gonadal atrophy and increased adiposity when adapted to short (winter-like) photoperiods. Here we investigated whether pineal melatonin secreted at night can impact daily rhythmicity of metabolic hormones and glucose in that seasonal species. For that purpose, daily variations of plasma leptin, cortisol, insulin and glucose were analyzed in pinealectomized hamsters, as compared to sham-operated controls kept under very long (16 h light/08 h dark) or short photoperiods (08 h light/16 h dark). Daily rhythms of leptin under both long and short photoperiods were blunted by pinealectomy. Furthermore, the phase of cortisol rhythm under a short photoperiod was advanced by 5.6 h after pinealectomy. Neither plasma insulin, nor blood glucose displays robust daily rhythmicity, even in sham-operated hamsters. Pinealectomy, however, totally reversed the decreased levels of insulin under short days and the photoperiodic variations in mean levels of blood glucose (i.e., reduction and increase in long and short days, respectively). Together, these findings in Syrian hamsters show that circulating melatonin at night drives the daily rhythmicity of plasma leptin, participates in the phase control of cortisol rhythm and modulates glucose homeostasis according to photoperiod-dependent metabolic state. PMID:26074760

  16. 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.

  17. Melatonin synthesis in the human pineal gland

    OpenAIRE

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

    2007-01-01

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

  18. 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...

  19. 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...

  20. 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

  1. Effect of Light and Melatonin and Other Melatonin Receptor Agonists on Human Circadian Physiology.

    Science.gov (United States)

    Emens, Jonathan S; Burgess, Helen J

    2015-12-01

    Circadian (body clock) timing has a profound influence on mental health, physical health, and health behaviors. This review focuses on how light, melatonin, and other melatonin receptor agonist drugs can be used to shift circadian timing in patients with misaligned circadian rhythms. A brief overview of the human circadian system is provided, followed by a discussion of patient characteristics and safety considerations that can influence the treatment of choice. The important features of light treatment, light avoidance, exogenous melatonin, and other melatonin receptor agonists are reviewed, along with some of the practical aspects of light and melatonin treatment. PMID:26568121

  2. Some implications of melatonin use in chronopharmacology of insomnia.

    Science.gov (United States)

    Golombek, Diego A; Pandi-Perumal, Seithikurippu R; Brown, Gregory M; Cardinali, Daniel P

    2015-09-01

    The last decade has witnessed the emergence of new chronopharmacological perspectives. In the case of sleep disorders, the accumulating evidence suggests that even a minor dysfunction in the biological clock can impact broadly upon body physiology causing increases in sleep onset latency, phase delays or advances in sleep initiation, frequent nocturnal awakenings, reduced sleep efficiency, delayed and shortened rapid eye movement sleep and increased periodic leg movements, among others. Thus, restoration of the adequate circadian pattern of proper sleep hygiene, targeted exposure to light and the use of chronobiotic drugs, such as melatonin, which affect the output phase of clock-controlled circadian rhythms, can help to recover the sleep-wake cycle. The optimization of drug effects and/or minimization of toxicity by timing medications with regard to biological rhythms is known as chronotherapeutics. While chronotherapeutical approaches have been particularly successful in the treatment of hypertension, allergies and some forms of cancer, a time-dependent pharmacological approach can be also effective when dealing with sleep disruptions like insomnia. A large proportion of patients under benzodiazepine (BZD)/Z drug treatment fail to achieve a complete and sustained recovery and are left with residual symptoms, like tolerance or dependency, that make relapse or recurrence more likely, and poorer quality of life a reality. Thus the chronic and extensive use of BZD/Z drugs has become a public health issue and has led to multiple campaigns to reduce both prescription and consumption of BZD/Z-drugs. This short review discusses available data on the efficacy of melatonin to reduce chronic BZD use in insomnia patients. PMID:26004526

  3. 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 a...

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    P.S.R. Mattos

    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.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.

  6. Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals.

    Science.gov (United States)

    Kumar Jha, Pawan; Challet, Etienne; Kalsbeek, Andries

    2015-12-15

    Most aspects of energy metabolism display clear variations during day and night. This daily rhythmicity of metabolic functions, including hormone release, is governed by a circadian system that consists of the master clock in the suprachiasmatic nuclei of the hypothalamus (SCN) and many secondary clocks in the brain and peripheral organs. The SCN control peripheral timing via the autonomic and neuroendocrine system, as well as via behavioral outputs. The sleep-wake cycle, the feeding/fasting rhythm and most hormonal rhythms, including that of leptin, ghrelin and glucocorticoids, usually show an opposite phase (relative to the light-dark cycle) in diurnal and nocturnal species. By contrast, the SCN clock is most active at the same astronomical times in these two categories of mammals. Moreover, in both species, pineal melatonin is secreted only at night. In this review we describe the current knowledge on the regulation of glucose and lipid metabolism by central and peripheral clock mechanisms. Most experimental knowledge comes from studies in nocturnal laboratory rodents. Nevertheless, we will also mention some relevant findings in diurnal mammals, including humans. It will become clear that as a consequence of the tight connections between the circadian clock system and energy metabolism, circadian clock impairments (e.g., mutations or knock-out of clock genes) and circadian clock misalignments (such as during shift work and chronic jet-lag) have an adverse effect on energy metabolism, that may trigger or enhancing obese and diabetic symptoms. PMID:25662277

  7. Nocturnal antihypertensive treatment in patients with type 1 diabetes with autonomic neuropathy and non-dipping of blood pressure during night time

    DEFF Research Database (Denmark)

    Hjortkær, Henrik; Jensen, Tonny; Kofoed, Klaus; Mogensen, Ulrik; Køber, Lars; Hilsted, Karen Lisa; Corinth, Helle; Theilade, Simone; Hilsted, Jannik

    2014-01-01

    INTRODUCTION: Cardiac autonomic neuropathy (CAN) and elevated nocturnal blood pressure are independent risk factors for cardiovascular disease in patients with diabetes. Previously, associations between CAN, non-dipping of nocturnal blood pressure and coronary artery calcification have been demonstrated. The present protocol describes a trial to test the efficacy of bedtime dosing of the ACE inhibitor enalapril on night time blood pressure and left ventricular mass in patients with type 1 diabet...

  8. Melatonin-Based Therapeutics for Neuroprotection in Stroke

    Directory of Open Access Journals (Sweden)

    Cesar V. Borlongan

    2013-04-01

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

  9. Role of melatonin in cancer treatment.

    Science.gov (United States)

    Cutando, Antonio; López-Valverde, Antonio; Arias-Santiago, Salvador; DE Vicente, Joaquin; DE Diego, Rafael Gómez

    2012-07-01

    Melatonin has revealed itself to be a pleiotropic and multitasking molecule. The mechanisms that control its synthesis and the biological clock processes that modulate the circadian production of melatonin in the pineal gland have been well-characterized. A feature that characterizes melatonin is the variety of mechanisms it employs to modulate the physiology and molecular biology of cells. Research has implicated the pineal gland and melatonin in the processes of both aging and age-related diseases. The decline in the production of melatonin with age is thought to contribute to immunosenescence and potential development of neoplastic diseases. Melatonin has been shown to inhibit growth of different tumors under both in vitro and in vivo conditions. There is evidence that the administration of melatonin alone or in combination with interleukin-2 in conjunction with chemoradiotherapy and/or supportive care in cancer patients with advanced solid tumors, has been associated with improved outcomes of tumor regression and survival. Moreover, chemotherapy has been shown to be better tolerated in patients treated with melatonin. PMID:22753734

  10. 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

  11. 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.

  12. 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

  13. Melatonin-Based Therapeutics for Neuroprotection in Stroke

    OpenAIRE

    Cesar V. Borlongan; 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...

  14. 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...

  15. 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...

  16. Nocturnal acid breakthrough: consequences and confronting

    Directory of Open Access Journals (Sweden)

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

    2007-03-01

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

  17. Nocturnal acid breakthrough: consequences and confronting

    Directory of Open Access Journals (Sweden)

    K. Triantafillidis, Maria Mylonaki, F. Georgopoulos

    2007-03-01

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

  18. Melatonin in experimental seizures and epilepsy.

    Science.gov (United States)

    Banach, Monika; Gurdziel, Elwira; J?drych, Marian; Borowicz, Kinga K

    2011-01-01

    Although melatonin is approved only for the treatment of jet-lag syndrome and some types of insomnia, clinical data suggest that it is effective in the adjunctive therapy of osteoporosis, cataract, sepsis, neurodegenerative diseases, hypertension, and even cancer. Melatonin also modulates the electrical activity of neurons by reducing glutamatergic and enhancing GABA-ergic neurotransmission. The indoleamine may also be metabolized to kynurenic acid, an endogenous anticonvulsant. Finally, the hormone and its metabolites act as free radical scavengers and antioxidants. The vast majority of experimental data indicates anticonvulsant properties of the hormone. Melatonin inhibited audiogenic and electrical seizures, as well as reduced convulsions induced by pentetrazole, pilocarpine, L-cysteine and kainate. Only a few studies have shown direct or indirect proconvulsant effects of melatonin. For instance, melatonin enhanced low Mg2+-induced epileptiform activity in the hippocampus, whereas melatonin antagonists delayed the onset of pilocarpine-induced seizures. However, the relatively high doses of melatonin required to inhibit experimental seizures can induce some undesired effects (e.g., cognitive and motor impairment and decreased body temperature). In humans, melatonin may attenuate seizures, and it is most effective in the treatment of juvenile intractable epilepsy. Its additional benefits include improved physical, emotional, cognitive, and social functions. On the other hand, melatonin has been shown to induce electroencephalographic abnormalities in patients with temporal lobe epilepsy and increase seizure activity in neurologically disabled children. The hormone showed very low toxicity in clinical practice. The reported adverse effects (nightmares, hypotension, and sleep disorders) were rare and mild. However, more placebo-controlled, double-blind randomized clinical trials are needed to establish the usefulness of melatonin in the adjunctive treatment of epilepsy. PMID:21441606

  19. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-12-01

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

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

    International Nuclear Information System (INIS)

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

  2. 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 almost all organ...

  3. Functions of melatonin in plants: a review.

    Science.gov (United States)

    Arnao, Marino B; Hernández-Ruiz, Josefa

    2015-09-01

    The number of studies on melatonin in plants has increased significantly in recent years. This molecule, with a large set of functions in animals, has also shown great potential in plant physiology. This review outlines the main functions of melatonin in the physiology of higher plants. Its role as antistress agent against abiotic stressors, such as drought, salinity, low and high ambient temperatures, UV radiation and toxic chemicals, is analyzed. The latest data on their role in plant-pathogen interactions are also discussed. Both abiotic and biotic stresses produce a significant increase in endogenous melatonin levels, indicating its possible role as effector in these situations. The existence of endogenous circadian rhythms in melatonin levels has been demonstrated in some species, and the data, although limited, suggest a central role of this molecule in the day/night cycles in plants. Finally, another aspect that has led to a large volume of research is the involvement of melatonin in aspects of plant development regulation. Although its role as a plant hormone is still far of from being fully established, its involvement in processes such as growth, rhizogenesis, and photosynthesis seems evident. The multiple changes in gene expression caused by melatonin point to its role as a multiregulatory molecule capable of coordinating many aspects of plant development. This last aspect, together with its role as an alleviating-stressor agent, suggests that melatonin is an excellent prospect for crop improvement. PMID:26094813

  4. Pulse radiolysis studies of melatonin and chloromelatonin.

    Science.gov (United States)

    Roberts, J E; Hu, D N; Wishart, J F

    1998-02-01

    The endogenous indole melatonin and the melatonin receptor agonist 6-chloromelatonin block the proliferation of both dermal and uveal melanoma cells by mechanisms that may involve redox reactions. The interactions of hydrated electrons, the azide radical, hydroxyl radicals and superoxide with melatonin and its 6-chloro analogue have been studied using the technique of pulse radiolysis. The reaction rate constants of eaq- and N3 x with these compounds were found to be dependent on substitution at the sixth position. The rate constants for reaction of 6-chloromelatonin and melatonin with solvated electrons are 4.5 x 10(9) M-1 s-1 and 4.2 x 10(8) M-1 s-1, respectively. The reaction rate constants of N3 x with malatonin and chloromelatonin are 9.8 x 10(9) M-1 s-1 and 3.5 x 10(9) M-1 s-1 and 3.5 x 10(9) M-1 s-1, respectively. Melatonin and 6-chloromelatonin react with hydroxyl radicals at near diffusion controlled rates (1.3 x 10(10) M-1 s-1, 8.2 x 10(9) M-1 s-1). Melatonin and 6-chloromelatonin did not react with superoxide radicals and we calculate an upper limit of 1.0 x 10(4) M-1 s-1 for the rate constant for reaction of melatonin and 6-chloromelatonin with superoxide ion. PMID:9540219

  5. Melatonin stimulates the release of growth hormone and prolactin by a possible induction of the expression of frog growth hormone-releasing peptide and its related peptide-2 in the amphibian hypothalamus.

    Science.gov (United States)

    Chowdhury, Vishwajit S; Yamamoto, Kazutoshi; Saeki, Izumi; Hasunuma, Itaru; Shimura, Taichi; Tsutsui, Kazuyoshi

    2008-03-01

    We recently identified a novel hypothalamic neuropeptide stimulating GH release in bullfrogs and termed it frog GH-releasing peptide (fGRP). The fGRP precursor encodes fGRP and its related peptides (fGRP-RP-1, -RP-2, and -RP-3), and fGRP-RP-2 also stimulates GH and prolactin (PRL) release. Cell bodies and terminals containing these neuropeptides are localized in the suprachiasmatic nucleus (SCN) and median eminence, respectively. To understand the physiological role of fGRP and fGRP-RP-2, we investigated the mechanisms that regulate the expression of these neuropeptides. This study shows that melatonin induces the expression of fGRP and fGRP-RPs in bullfrogs. Orbital enucleation combined with pinealectomy (Ex plus Px) decreased the expression of fGRP precursor mRNA and content of mature fGRP and fGRP-RPs in the diencephalon including the SCN and median eminence. Conversely, melatonin administration to Ex plus Px bullfrogs increased dose-dependently their expressions. The expression of fGRP precursor mRNA was photoperiodically controlled and increased under short-day photoperiods, when the nocturnal duration of melatonin secretion increases. To clarify the mode of melatonin action on the induction of fGRP and fGRP-RPs, we further demonstrated the expression of Mel(1b), a melatonin receptor subtype, in SCN neurons expressing fGRP precursor mRNA. Finally, we investigated circulating GH and PRL levels after melatonin manipulation because fGRP and fGRP-RP-2 stimulate the release of GH and GH/PRL, respectively. Ex plus Px decreased plasma GH and PRL concentrations, whereas melatonin administration increased these hormone levels. These results suggest that melatonin induces the expression of fGRP and fGRP-RP-2, thus stimulating the release of GH and PRL in bullfrogs. PMID:18063680

  6. Melatonin: General Features and its Role in Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Murat Erdem

    2013-06-01

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

  7. Melatonin as a radioprotective agent: a review

    International Nuclear Information System (INIS)

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

  8. 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...

  9. 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.

  10. Abnormal melatonin synthesis in autism spectrum disorders

    OpenAIRE

    Melke, Jonas; Goubran-Botros, Hany; Chaste, Pauline; Betancur, Catalina; Nygren, Gudrun; Anckarsäter, Henrik; Rastam, Maria; Ståhlberg, Ola; Gillberg, I. Carina; Delorme, Richard; Chabane, Nadia; Mouren-Simeoni, Marie-Christine; Fauchereau, Fabien; Durand, Christelle; Chevalier, Fabien

    2007-01-01

    Melatonin is produced in the dark by the pineal gland and is a key regulator of circadian and seasonal rhythms. A low melatonin level has been reported in individuals with autism spectrum disorders (ASD), but the underlying cause of this deficit was unknown. The ASMT gene, encoding the last enzyme of melatonin synthesis, is located on the pseudo-autosomal region 1 of the sex chromosomes, deleted in several individuals with ASD. In this study, we sequenced all ASMT exons and promoters in indiv...

  11. 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 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)

  12. The use of melatonin to combat mustard toxicity. REVIEW.

    Science.gov (United States)

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

    2008-10-01

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

  13. Nocturnal Hypertension and Attenuated Nocturnal Blood Pressure Dipping is Common in Pediatric Lupus [version 2; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    J. Fallon Campbell

    2015-11-01

    Full Text Available Hypertension is an important manifestation of systemic lupus erythematosus (SLE but reports of prevalence vary between 20-70% in published reports of adult and pediatric patients. For both children and adults with SLE, the clinical diagnosis and management of hypertension has traditionally been based on guidelines developed for the general population. In clinical trials, the criteria used for defining participants with hypertension are mostly undefined. As a first step towards formally assessing the blood pressure (BP patterns of children diagnosed with SLE, 24-hr ambulatory BP monitoring data was analyzed on clinic patients who presented with prehypertension or stage I hypertension. In this pediatric SLE cohort (n=10, 20% met daytime criteria for a diagnosis of hypertension. Patterns of BP elevation varied widely with white coat, masked, isolated systolic, and diastolic nocturnal hypertension all identified. Nocturnal hypertension was detected in 60% and attenuated nocturnal BP dipping in 90% of both hypertensive and normotensive SLE patients. In SLE patients, the median nighttime systolic and diastolic loads were 25% and 15.5% compared with median daily loads of 12.5% and 11.5%. Daytime and nighttime systolic and diastolic BP load and nocturnal dipping was compared to a control population consisting of 85 non-SLE patients under 21 years old with prehypertension or stage 1 hypertension presenting to hypertension clinic. Median systolic BP dipped 5.3 mmHg in SLE patients compared to 11.9 mmHg in non-lupus (p-value = 0.001. Median diastolic BP dipped 12.9 mmHg versus 18.5 mmHg in non-lupus (p-value = 0.003. Patterns of BP dysregulation in pediatric SLE merit further exploration. Children with or without SLE displaying prehypertensive or stage 1 casual BP measurements had similar rates of hypertension by ambulatory BP monitoring. However, regardless of BP diagnosis, and independent of kidney involvement, there was an increased proportion with attenuated nocturnal dipping and nocturnal hypertension in SLE patients.

  14. Consequences of nocturnal water loss: a synthesis of regulating factors and implications for capacitance, embolism and use in models.

    Science.gov (United States)

    Zeppel, M J B; Lewis, J D; Phillips, N G; Tissue, D T

    2014-10-01

    Total daily water use is a key factor influencing the growth of many terrestrial plants, and reflects both day-time and nocturnal water fluxes. However, while nocturnal sap flow (En) and stomatal conductance (gs,n) have been reported across a range of species, ecosystems and microclimatic conditions, the regulation of these fluxes remains poorly understood. Here, we present a framework describing the role of abiotic and biotic factors in regulating En and gs,n highlighting recent developments in this field. Across ecosystems, En and gs,n generally increased with increasing soil water content and vapor pressure deficit, but the interactive effects of these factors and the potential roles of wind speed and other abiotic factors remain unclear. On average, gs,n and En are higher in broad-leaved compared with needle-leaved plants, in C3 compared with C4 plants, and in tropical compared with temperate species. We discuss the impacts of leaf age, elevated [CO2] and refilling of capacitance on night-time water loss, and how nocturnal gs,n may be included in vegetation models. Younger leaves may have higher gs,n than older leaves. Embolism refilling and recharge of capacitance may affect sap flow such that total plant water loss at night may be less than estimated solely from En measurements. Our estimates of gs,n for typical plant functional types, based on the published literature, suggest that nocturnal water loss may be a significant fraction (10-25%) of total daily water loss. Counter-intuitively, elevated [CO2] may increase nocturnal water loss. Assumptions in process-based ecophysiological models and dynamic global vegetation models that gs is zero when solar radiation is zero are likely to be incorrect. Consequently, failure to adequately consider nocturnal water loss may lead to substantial under-estimation of total plant water use and inaccurate estimation of ecosystem level water balance. PMID:25413023

  15. 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

  16. Melatonin in psychiatric disorders - subtyping affective disorder.

    Science.gov (United States)

    Wahlund, B

    1999-01-01

    Altered diurnal secretory patterns, i.e. altered phase and/or amplitude of melatonin have been reported in sleep and affective disorders. The alteration may depend on environmental factors which in vulnerable individuals may cause sleep and/or affective disorders. Early stress in conjunction with development of resistance to corticotropin-releasing hormone may be linked to the low melatonin syndrome in subgroups of depressed patients. Also the seasonal variation in melatonin as well as serotonin may be linked to the seasonal pattern seen in subgroups of affective disorders. Melatonin may be used as a combined marker for proneness to develop affective disorders especially in latent carriers of bipolar disorders. PMID:10085473

  17. Melatonin: Bone Metabolism in Oral Cavity

    OpenAIRE

    Fanny López-Martínez; Patricia N. Olivares Ponce; Miriam Guerra Rodríguez; Ricardo Martínez Pedraza

    2012-01-01

    Throughout life, bone tissue undergoes a continuous process of resorption and formation. Melatonin, with its antioxidant properties and its ability to detoxify free radicals, as suggested by Conconi et al. (2000) may interfere in the osteoclast function and thereby inhibit bone resorption, as suggested by Schroeder et al. (1981). Inhibition of bone resorption may be enhanced by a reaction of indoleamine in osteoclastogenesis. That it has been observed melatonin, at pharmacological doses, decr...

  18. Melatonin in perioperative medicine: Current perspective

    OpenAIRE

    Maitra, Souvik; Baidya, Dalim Kumar; Khanna, Puneet

    2013-01-01

    Melatonin, a new addition to the armamentarium of anesthesiologist, has some unique properties that are highly desirable in routine peri-operative care. Available clinical data show that preoperative melatonin is as effective as benzodiazepines in reducing preoperative anxiety with minimal action on psychomotor performance and sleep wake cycle. It may be considered as a safe and effective alternative of benzodiazepines as preoperative anxiolytic. It may have opioid sparing effect, may reduce ...

  19. 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...

  20. 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…

  1. 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

  2. Body position and late postoperative nocturnal hypoxaemia

    DEFF Research Database (Denmark)

    Rosenberg-Adamsen, S; Stausholm, K; Edvardsen, L; Zwarts, M; Kehlet, H; Rosenberg, J

    1997-01-01

    Thirteen patients were monitored for nocturnal body position (supine vs. side) and arterial oxygen saturation pre-operatively and on the second postoperative night after major abdominal surgery. The number of positional changes were significantly decreased after operation (p < 0.05) with a trend towards more time spent in the supine position (p = 0.1). Individual mean arterial oxygen saturation decreased postoperatively (p < 0.05) but without a difference between the supine and side positions (p...

  3. 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...

  4. 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.

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

    Science.gov (United States)

    Atherino, Victoria Fairbanks; Lima, Larissa de Sá; Moutinho, Anderson Augusto; do Amaral, Fernanda Gaspar; Peres, Rafael; Martins de Lima, Thais; Torrão, Andréa da Silva; Cipolla-Neto, José; Scavone, Cristóforo; Afeche, Solange Castro

    2013-01-01

    The glutamatergic modulation of melatonin synthesis is well known, along with the importance of astrocytes in mediating glutamatergic signaling in the central nervous system. Pinealocytes and astrocytes are the main cell types in the pineal gland. The objective of this work was to investigate the interactions between astrocytes and pinealocytes as a part of the glutamate inhibitory effect on melatonin synthesis. Rat pinealocytes isolated or in coculture with astrocytes were incubated with glutamate in the presence of norepinephrine, and the melatonin content, was quantified. The expression of glutamate receptors, the intracellular calcium content and the NF-?B activation were analyzed in astrocytes and pinealocytes. TNF-?'s possible mediation of the effect of glutamate was also investigated. The results showed that glutamate's inhibitory effect on melatonin synthesis involves interactions between astrocytes and pinealocytes, possibly through the release of TNF-?. Moreover, the activation of the astrocytic NF-?B seems to be a necessary step. In astrocytes and pinealocytes, AMPA, NMDA, and group I metabotropic glutamate receptors were observed, as well as the intracellular calcium elevation. In conclusion, there is evidence that the modulation of melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through the activation of the astrocytic NF-?B transcription factor and possibly by subsequent TNF-? release. PMID:23984387

  6. 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; Wade AG; 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...

  7. Melatonin for pre- and postoperative anxiety in adults

    DEFF Research Database (Denmark)

    Hansen, Melissa V; Halladin, Natalie L; Rosenberg, Jacob; Gögenur, Ismail; Møller, Ann Merete

    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. Fo...

  8. Melatonin differentially affects vascular blood flow in humans

    OpenAIRE

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

    2010-01-01

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

  9. 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 ...

  10. Short-term air temperature on a regional scale and its estimation with a nocturnal cooling model

    International Nuclear Information System (INIS)

    Accuracy of spatial estimation of air temperatures can be very poor for a short term temperature. The objective of this paper is to study feasibility of the regional estimation of air temperatures with a nocturnal cooling model, which was proposed by Kondo & Mori (1982) to describe nocturnal cooling rate with wind speed and site-specific parameters. First, relationships between elevation and air temperatures within diurnal cycles were addressed at 27 monitoring points across a region of 110km×100km in central Japan. The weather data were obtained from the Automated Meteorological Data Acquisition System. The results showed that air temperature in the evenings was linearly related to the elevation above sea level with little perturbations from the weather, wind speed and topography. In contrast, minimum air temperature in the mornings and nocturnal cooling rate were greatly influenced by the above factors. Furthermore, in a complex terrain, the morning air temperature and cooling rate were unrelated to those at nearby points. Therefore, the two temperature traits may not be accurately estimated by using spatial interpolation. Second, two parameters (a & b) of the nocturnal cooling model were determined for each of the 27 monitoring points, and were related to topographical features of the points. Indexes of surface flatness (Sidx), cubical measure by a concavo-convex space (Cidx) and steepness (Ridx) on the level surface at observation were defined and calculated for each point using elevations of the grid points of the Digital National Land Information. The parameter b, which represents thermal conditions and accumulation of cold air, was related to Sidx and Cidx. The parameter a, which represents the extent of air mixing, was related to Ridx. The short-term air temperatures could therefore be estimated on a regional basis with the nocturnal cooling model, whose parameters are determined with the topographical indexes. (author)

  11. Evaluation of nocturnal bronchoconstriction by all night tracheal sound monitoring.

    OpenAIRE

    Lenclud, C; Cuttitta, G.; Van Gansbeke, D.; Visconti, A.; Van Muylem, A.; Bellia, V.; Yernault, J. C.

    1996-01-01

    BACKGROUND: A study was undertaken to evaluate the reliability of a digital tracheal sound analyser (ELENS-DSA) in predicting nocturnal changes in airways resistance in asthmatic patients. This device allows continuous measurement of the proportion of the time occupied by wheezing (Wh%). METHODS: Nocturnal polygraphic studies with simultaneous continuous monitoring of tracheal sounds and airways resistance were performed in seven patients with nocturnal asthma. In order to evaluate the possib...

  12. 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...

  13. 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 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)

  14. Protective Effect of Melatonin on Damage in the Sperm Parameters of Mice Exposed to Diazinon Efecto Protector de la Melatonina sobre el Daño en los Parámetros Espermáticos de Ratones Expuestos a Diazinón

    OpenAIRE

    L. Sarabia; O Espinoza-Navarro; Maurer, I.; C Ponce; E. Bustos-Obregón

    2011-01-01

    Since normal sperm parameters can be altered by organophosphorous pesticides, this study intended to determine if melatonin is able to prevent the damage on sperm quality after an acute exposure to diazinon. Adult male mice were injected intraperitoneally with melatonin, diazinon (1/3 or 2/3 LD50) or both, and sperm parameters were evaluated on days 1 or 32 post injection. Groups treated with diazinon showed elevated lipid peroxidation levels on day 1 post treatment, while groups pretreated w...

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

    Science.gov (United States)

    Bagnaresi, Piero; Alves, Eduardo; da Silva, Henrique Borges; Epiphanio, Sabrina; Mota, Maria M; Garcia, Célia Rs

    2009-01-01

    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 melatonin-receptor 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 host-derived 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. PMID:20360886

  17. Melatonin increases oestradiol-induced bone formation in ovariectomized rats.

    Science.gov (United States)

    Ladizesky, Marta G; Boggio, Verónica; Albornoz, Liliana E; Castrillón, Patricia O; Mautalen, Carlos; Cardinali, Daniel P

    2003-03-01

    To assess the effect of melatonin on bone metabolism in ovariectomized rats, receiving oestradiol therapy or not, melatonin was administered in the drinking water (25 microg/mL water) and oestradiol (10 microg/kg body weight) or vehicle was given subcutaneously 5 days/week for up to 60 days after surgery. Urinary deoxypyridinoline (a marker of bone resorption) and circulating levels of bone alkaline phosphatase activity (a marker of bone formation), as well as serum calcium and phosphorus levels, were measured every 15 days. Bone area (BA), bone mineral content (BMC), bone mineral density (BMD) and total body fat (expressed as 100 g body weight) were measured by dual-energy X-ray absorptiometry at the end of the experiment. Body weight and total body fat were augmented after ovariectomy, and decreased after melatonin or oestradiol treatment. The effect of melatonin on body weight was seen in sham-operated rats only. Ovariectomy augmented, and melatonin or oestradiol lowered, urinary deoxypyridinoline excretion. This effect of melatonin and oestradiol was seen mainly in ovariectomized rats. The efficacy of oestradiol to counteract ovariectomy-induced bone resorption was increased by melatonin. Melatonin or oestradiol lowered serum bone alkaline phosphatase activity. Melatonin inhibition was seen mainly on the increase of bone alkaline phosphatase activity that followed ovariectomy. Serum phosphorus levels decreased after melatonin administration and were augmented after oestradiol injection; overall, melatonin impaired the increase of serum phosphorus caused by oestradiol. Ovariectomy decreased, and oestradiol increased, serum calcium levels while melatonin augmented serum calcium in sham-operated rats only. On day 60 after surgery, BMD and content decreased after ovariectomy and were increased after oestradiol injection. Melatonin augmented BA of spine and BMC of whole of the skeleton and tibia. The highest values observed were those of rats treated concurrently with oestradiol and melatonin. The present results indicate that: (i) melatonin treatment restrained bone remodelling after ovariectomy; (ii) the effect of melatonin required adequate concentrations of oestradiol; (iii) melatonin augmented oestradiol effects on bone in ovariectomized rats; (iv) a counter-regulation by melatonin of the increase in body fat caused by ovariectomy was uncovered. The melatonin doses employed were pharmacological in terms of circulating melatonin levels but not necessarily for some other fluids or tissues. PMID:12562506

  18. 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 wa...

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

    DEFF Research Database (Denmark)

    Radvanska, E; Kamperis, Konstantinos; Kleif, A; Kovács, L; Rittig, S

    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.

  20. 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.

  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 in these arteries, which are believed to be involved in thermoregulation

  2. 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.

  3. Early dinner reduces nocturnal gastric acidity.

    OpenAIRE

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

    1989-01-01

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

  4. Extended Driving Impairs Nocturnal Driving Performances

    OpenAIRE

    Sagaspe, Patricia; Taillard, Jacques; Åkerstedt, Torbjorn; Bayon, Virginie; Espié, Stéphane; Chaumet, Guillaume; Bioulac, Bernard; Philip, Pierre

    2008-01-01

    Though fatigue and sleepiness at the wheel are well-known risk factors for traffic accidents, many drivers combine extended driving and sleep deprivation. Fatigue-related accidents occur mainly at night but there is no experimental data available to determine if the duration of prior driving affects driving performance at night. Participants drove in 3 nocturnal driving sessions (3–5am, 1–5am and 9pm–5am) on open highway. Fourteen young healthy men (mean age [±SD]?=?23.4 [±1.7] years) partici...

  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: an ancient molecule that makes oxygen metabolically tolerable.

    Science.gov (United States)

    Manchester, Lucien C; Coto-Montes, Ana; Boga, Jose Antonio; Andersen, Lars Peter H; Zhou, Zhou; Galano, Annia; Vriend, Jerry; Tan, Dun-Xian; Reiter, Russel J

    2015-11-01

    Melatonin is remarkably functionally diverse with actions as a free radical scavenger and antioxidant, circadian rhythm regulator, anti-inflammatory and immunoregulating molecule, and as an oncostatic agent. We hypothesize that the initial and primary function of melatonin in photosynthetic cyanobacteria, which appeared on Earth 3.5-3.2 billion years ago, was as an antioxidant. The evolution of melatonin as an antioxidant by this organism was necessary as photosynthesis is associated with the generation of toxic-free radicals. The other secondary functions of melatonin came about much later in evolution. We also surmise that mitochondria and chloroplasts may be primary sites of melatonin synthesis in all eukaryotic cells that possess these organelles. This prediction is made on the basis that mitochondria and chloroplasts of eukaryotes developed from purple nonsulfur bacteria (which also produce melatonin) and cyanobacteria when they were engulfed by early eukaryotes. Thus, we speculate that the melatonin-synthesizing actions of the engulfed bacteria were retained when these organelles became mitochondria and chloroplasts, respectively. That mitochondria are likely sites of melatonin formation is supported by the observation that this organelle contains high levels of melatonin that are not impacted by blood melatonin concentrations. Melatonin has a remarkable array of means by which it thwarts oxidative damage. It, as well as its metabolites, is differentially effective in scavenging a variety of reactive oxygen and reactive nitrogen species. Moreover, melatonin and its metabolites modulate a large number of antioxidative and pro-oxidative enzymes, leading to a reduction in oxidative damage. The actions of melatonin on radical metabolizing/producing enzymes may be mediated by the Keap1-Nrf2-ARE pathway. Beyond its direct free radical scavenging and indirect antioxidant effects, melatonin has a variety of physiological and metabolic advantages that may enhance its ability to limit oxidative stress. PMID:26272235

  7. Deficient nocturnal surge of thyrotropin in central hypothyroidism.

    Science.gov (United States)

    Caron, P J; Nieman, L K; Rose, S R; Nisula, B C

    1986-05-01

    In normal individuals, serum TSH concentrations have a circadian pattern characterized by a nocturnal surge which begins in the late afternoon and reaches its peak after midnight. We assessed the nocturnal surge of TSH in 16 patients with pituitary and/or hypothalamic diseases, 6 of whom were judged to be hypothyroid. To assess the magnitude of the nocturnal surge in individual patients, TSH was measured in 5 serum samples obtained during the normal time of the TSH nadir in the late afternoon and in 5 samples obtained during the normal time of the peak of serum TSH after midnight. A significant nocturnal surge of TSH was defined as a significantly greater mean nighttime TSH level than the mean daytime TSH concentration. The nocturnal TSH surge was absent in the 6 patients with central hypothyroidism, while it was present in the 10 euthyroid patients with central lesions. In 6 hypothyroid patients who did not have pituitary or hypothalamic lesions, the nocturnal TSH surge was intact, indicating that hypothyroidism per se does not account for the deficient nocturnal TSH surge in central hypothyroidism. We conclude that central hypothyroidism is characterized by a deficient nocturnal surge of TSH, and accordingly, we suggest that evaluation of the circadian pattern of TSH may be a useful adjunct in making the diagnosis of hypothyroidism in patients with diseases involving the pituitary or hypothalamus. PMID:3958131

  8. 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

  9. 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.

  10. Predominance of 2-hydroxymelatonin over melatonin in plants.

    Science.gov (United States)

    Byeon, Yeong; Tan, Dun-Xian; Reiter, Russel J; Back, Kyoungwhan

    2015-11-01

    The cloning of the gene encoding melatonin 2-hydroxylase (M2H), which is responsible for the synthesis of 2-hydroxymelatonin, has expanded the study of melatonin metabolism in plants. Kinetic analysis of M2H enzymatic activity demonstrated that the catalytic efficiency of M2H is much higher than those of other melatonin biosynthetic enzymes such as serotonin N-acetyltransferase (SNAT) and N-acetylserotonin O-methyltransferase (ASMT), suggesting that melatonin metabolism is rapid in plants. To test this prediction, we selected 24 plant species belonging to 16 families and quantified the levels of melatonin and 2-hydroxymelatonin using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The melatonin levels in most of the species were melatonin in plants was approximately 368:1, indicating that the accumulation of 2-hydroxymelatonin predominates over that of melatonin. These data were consistent with previous results on the kinetics of the corresponding enzymes, as well as with in vivo melatonin conversion data. Among several melatonin metabolites in plants, the most abundant metabolite was found to be 2-hydroxymelatonin (99%) followed by 4-hydroxymelatonin (0.05%), but 6-hydroxymelatonin was not detected in rice seedlings. PMID:26331804

  11. 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)

  12. Melatonin differentially affects vascular blood flow in humans.

    Science.gov (United States)

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

    2011-02-01

    Melatonin is synthesized and released into the circulation by the pineal gland in a circadian rhythm. Melatonin has been demonstrated to differentially alter blood flow to assorted vascular beds by the activation of different melatonin receptors in animal models. The purpose of the present study was to determine the effect of melatonin on blood flow to various vascular beds in humans. Renal (Doppler ultrasound), forearm (venous occlusion plethysmography), and cerebral blood flow (transcranial Doppler), arterial blood pressure, and heart rate were measured in 10 healthy subjects (29±1 yr; 5 men and 5 women) in the supine position for 3 min. The protocol began 45 min after the ingestion of either melatonin (3 mg) or placebo (sucrose). Subjects returned at least 2 days later at the same time of day to repeat the trial after ingesting the other substance. Melatonin did not alter heart rate and mean arterial pressure. Renal blood flow velocity (RBFV) and renal vascular conductance (RVC) were lower during the melatonin trial compared with placebo (RBFV, 40.5±2.9 vs. 45.4±1.5 cm/s; and RVC, 0.47±0.02 vs. 0.54±0.01 cm·s(-1)·mmHg(-1), respectively). In contrast, forearm blood flow (FBF) and forearm vascular conductance (FVC) were greater with melatonin compared with placebo (FBF, 2.4±0.2 vs. 1.9±0.1 ml·100 ml(-1)·min(-1); and FVC, 0.029±0.003 vs. 0.023±0.002 arbitrary units, respectively). Melatonin did not alter cerebral blood flow measurements compared with placebo. Additionally, phentolamine (5-mg bolus) after melatonin reversed the decrease in RVC, suggesting that melatonin increases sympathetic outflow to the kidney to mediate renal vasoconstriction. In summary, exogenous melatonin differentially alters vascular blood flow in humans. These data suggest the complex nature of melatonin on the vasculature in humans. PMID:21148765

  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. 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

  15. 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

  16. Melatonin in Chagas´ disease: Possible therapeutic value

    Directory of Open Access Journals (Sweden)

    Daniel P. Cardinali

    2011-10-01

    Full Text Available Chagas' disease is a severe health problem in Latin America, causing approximately 50 000 deaths a year, with approximately 18 million infected people. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. The protective response against T. cruzi depends on both innate and acquired immunity involving macrophages, natural killer cells, T and B lymphocytes, and the production of proinflammatory Th-1 cytokines. In addition, an increased nitric oxide (NO production in macrophages leading to effective microbicidal action is needed to control parasitemia. Melatonin is detectable in T. cruzi and may play a role in promoting infection whereas, when administered in high doses during the acute phase of T. cruzi infection, it can decrease parasitemia while reducing NO production. During chronic disease progression, the sustained oxidative stress concomitant to myocardial damage could be reduced by administering melatonin. It is hypothesized that the coordinated administration of a melatonin agonist like the MT1/MT2 agonist ramelteon, that lacks antioxidant activity and may not affect NO production during the acute phase, and of melatonin in doses high enough to decrease oxidative damage, to preserve mitochondrial and to prevent cardiomyopathy during the chronic phase, could be a novel add-on treatment of Chagas´ disease.

  17. Raconter Accident nocturne de Patrick Modiano Raconter Accident nocturne de Patrick Modiano

    Directory of Open Access Journals (Sweden)

    Jurate Kaminskas

    2012-10-01

    Full Text Available Modiano affirme que chaque roman marque un pas en avant dans la réalisation de son oeuvre. « J’ai l’impression qu’à chaque livre je me suis débarrassé d’un truc pour essayer d’accéder à d'autres choses », explique-t-il dans un entretien avec Laurence Liban. Qu’en est-il donc pour Accident nocturne ?Modiano affirme que chaque roman marque un pas en avant dans la réalisation de son oeuvre. « J’ai l’impression qu’à chaque livre je me suis débarrassé d’un truc pour essayer d’accéder à autre chose », explique-t-il dans un entretien avec Laurence Liban. Qu’en est-il donc pour Accident nocturne ?

  18. 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.

  19. Interleukin-1 ? Modulates Melatonin Secretion in Ovine Pineal Gland: Ex Vivo Study.

    Science.gov (United States)

    Herman, A P; Bochenek, J; Skipor, J; Król, K; Krawczy?ska, A; Antushevich, H; Pawlina, B; Marciniak, E; Tomaszewska-Zaremba, D

    2015-01-01

    The study was designed to determine the effect of proinflammatory cytokine, interleukin- (IL-) 1?, on melatonin release and expression enzymes essential for this hormone synthesis: arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) in ovine pineal gland, taking into account the immune status of animals before sacrificing. Ewes were injected by lipopolysaccharide (LPS; 400?ng/kg) or saline, two hours after sunset during short day period (December). Animals were euthanized three hours after the injection. Next, the pineal glands were collected and divided into four explants. The explants were incubated with (1) medium 199 (control explants), (2) norepinephrine (NE; 10?µM), (3) IL-1? (75?pg/mL), or (4) NE + IL-1?. It was found that IL-1? abolished (P < 0.05) NE-induced increase in melatonin release. Treatment with IL-1? also reduced (P < 0.05) expression of AA-NAT enzyme compared to NE-treated explants. There was no effect of NE or IL-1? treatment on gene expression of HIOMT; however, the pineal fragments isolated from LPS-treated animals were characterized by elevated (P < 0.05) expression of HIOMT mRNA and protein compared to the explants from saline-treated ewes. Our study proves that IL-1? suppresses melatonin secretion and its action seems to be targeted on the reduction of pineal AA-NAT protein expression. PMID:26339621

  20. Nocturnal flow on a western Colorado slope

    International Nuclear Information System (INIS)

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

  1. 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.

  2. On the Role of Melatonin in Skin Physiology and Pathology

    OpenAIRE

    Slominski, A; Fischer, T. W.; Zmijewski, M. A.; Wortsman, J.; Semak, I.; ZBYTEK, B.; Slominski, R.M.; Tobin, D. J.

    2005-01-01

    Melatonin has been experimentally implicated in skin functions such as hair growth cycling, fur pigmentation, and melanoma control, and melatonin receptors are expressed in several skin cells including normal and malignant keratinocytes, melanocytes, and fibroblasts. Melatonin is also able to suppress ultraviolet (UV)-induced damage to skin cells and shows strong antioxidant activity in UV exposed cells. Moreover, we recently uncovered expression in the skin of the biochemical machinery invol...

  3. 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...

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

    OpenAIRE

    Jacek Drobnik

    2012-01-01

    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 infl...

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

    OpenAIRE

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

    1987-01-01

    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 counterac...

  6. No effect of melatonin on oxidative stress after laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Kücükakin, B.; Klein, M.; Lykkesfeldt, Jens; Reiter, R.J.; Rosenberg, J.; Gögenür, I.

    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 pr...

  7. Melatonin attenuates the skin sympathetic nerve response to mental stress

    OpenAIRE

    Muller, Matthew D.; Sauder, Charity L.; Ray, Chester A.

    2013-01-01

    Melatonin attenuates muscle sympathetic nerve responses to sympathoexcitatory stimuli, but it is unknown whether melatonin similarly attenuates reflex changes in skin sympathetic nerve activity (SSNA). In this double-blind, placebo-controlled, crossover study, we tested the hypothesis that melatonin (3 mg) would attenuate the SSNA response to mental stress (mental arithmetic). Twelve healthy subjects underwent experimental testing on two separate days. Three minutes of mental stress occurred ...

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

    OpenAIRE

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

    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. 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,...

  10. 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...

  11. 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...

  12. 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...

  13. Peripheral Reproductive Organ Health and Melatonin: Ready for Prime Time

    Directory of Open Access Journals (Sweden)

    Russel J. Reiter

    2013-04-01

    Full Text Available Melatonin has a wide variety of beneficial actions at the level of the gonads and their adnexa. Some actions are mediated via its classic membrane melatonin receptors while others seem to be receptor-independent. This review summarizes many of the published reports which confirm that melatonin, which is produced in the ovary, aids in advancing follicular maturation and preserving the integrity of the ovum prior to and at the time of ovulation. Likewise, when ova are collected for in vitro fertilization-embryo transfer, treating them with melatonin improves implantation and pregnancy rates. Melatonin synthesis as well as its receptors have also been identified in the placenta. In this organ, melatonin seems to be of particular importance for the maintenance of the optimal turnover of cells in the villous trophoblast via its ability to regulate apoptosis. For male gametes, melatonin has also proven useful in protecting them from oxidative damage and preserving their viability. Incubation of ejaculated animal sperm improves their motility and prolongs their viability. For human sperm as well, melatonin is also a valuable agent for protecting them from free radical damage. In general, the direct actions of melatonin on the gonads and adnexa of mammals indicate it is an important agent for maintaining optimal reproductive physiology.

  14. 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...

  15. Melatonin attenuates the skin sympathetic nerve response to mental stress.

    Science.gov (United States)

    Muller, Matthew D; Sauder, Charity L; Ray, Chester A

    2013-11-01

    Melatonin attenuates muscle sympathetic nerve responses to sympathoexcitatory stimuli, but it is unknown whether melatonin similarly attenuates reflex changes in skin sympathetic nerve activity (SSNA). In this double-blind, placebo-controlled, crossover study, we tested the hypothesis that melatonin (3 mg) would attenuate the SSNA response to mental stress (mental arithmetic). Twelve healthy subjects underwent experimental testing on two separate days. Three minutes of mental stress occurred before and 45 min after ingestion of melatonin (3 mg) or placebo. Skin temperature was maintained at 34°C. Reflex increases in SSNA (peroneal nerve), mean arterial pressure, and heart rate (HR) to mental stress before and after melatonin were determined. Melatonin lowered HR (pre, 66 ± 3 beats/min; and post, 62 ± 3 beats/min, P = 0.046) and SSNA (pre, 14,282 ± 3,706 arbitrary units; and post, 9,571 ± 2,609 arbitrary units, P = 0.034) at rest. In response to mental stress, SSNA increases were significantly attenuated following melatonin ingestion (second minute, 114 ± 30 vs. 74 ± 14%; and third minute, 111 ± 29 vs. 54 ± 12%, both P melatonin. In summary, exogenous melatonin attenuates the SSNA response to mental stress. PMID:23997106

  16. 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)

  17. Visual cues and parental favouritism in a nocturnal bird.

    Science.gov (United States)

    Parejo, Deseada; Avilés, Jesús M; Rodríguez, Juan

    2010-04-23

    Visual signals are crucial for parent-offspring communication, although their functioning has been neglected for nocturnal birds. Here, we investigated parental preference for nestling coloration in nocturnal conditions--a question hitherto unexplored--in a nocturnal raptor, the scops owl (Otus scops). We assessed how parents allocated food during the night in relation to a manipulation of ultraviolet (UV) reflectance of the cere (skin above the beak) of their offspring. Reflectance of the cere shows a marked peak in the UV part of the spectrum, and location of the UV peak is related to nestling body mass (i.e. heavier nestlings have a UV peak at lower wavelengths). We found evidence of parental bias in favour of lighter offspring: UV-reduced nestlings gained more weight during the night than their control siblings. This study provides the first experimental evidence of the use of visual cues for parent-offspring communication in a nocturnal bird. PMID:19864276

  18. Eye shape and the nocturnal bottleneck of mammals

    OpenAIRE

    Hall, Margaret I.; Kamilar, Jason M.; Kirk, E. Christopher

    2012-01-01

    Most vertebrate groups exhibit eye shapes that vary predictably with activity pattern. Nocturnal vertebrates typically have large corneas relative to eye size as an adaptation for increased visual sensitivity. Conversely, diurnal vertebrates generally demonstrate smaller corneas relative to eye size as an adaptation for increased visual acuity. By contrast, several studies have concluded that many mammals exhibit typical nocturnal eye shapes, regardless of activity pattern. However, a recent ...

  19. The effect of sleep on nocturnal urine output

    DEFF Research Database (Denmark)

    Kamperis, Konstantinos; Hagstrøm, Søren; Rittig, Søren; Radvanska, Eva; Djurhuus, Jens Christian

    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 adm...

  20. Melatonin treatment following stroke induction modulates L-arginine metabolism.

    Science.gov (United States)

    Nair, Shiva M; Rahman, Rosanna M A; Clarkson, Andrew N; Sutherland, Brad A; Taurin, Sebastien; Sammut, Ivan A; Appleton, Ian

    2011-10-01

    The efficacy of melatonin treatment in experimental stroke has been established. Some of the neuroprotective properties have been attributed to its anti-oxidant and anti-inflammatory effects. Nitric oxide synthases (NOS) and cyclooxygenases (COX) are considered to have a significant role in the inflammatory milieu occurring in acute stroke. While previous reports have shown that pretreatment with melatonin in a stroke model can modulate NOS isoforms, the effect of post-treatment with melatonin on l-arginine metabolism has not been investigated. This study initially examined the effect of melatonin (1 nm-1 mm) on l-arginine metabolism pathways in human fibrosarcoma fibroblasts (HT-1080) fibroblasts. Evidence of neuroprotection with melatonin was evaluated in rats subjected to middle cerebral artery occlusion (MCAO). Animals were treated with three daily doses of 5 mg/kg i.p., starting 1 hr after the onset of ischemia. Constitutive NOS activity but not expression was significantly increased by in vitro exposure (72 hr) to melatonin. In addition, melatonin treatment increased arginase activity by increasing arginase II expression. In vivo studies showed that melatonin treatment after MCAO significantly inhibited inducible NOS activity and attenuated expression of the inducible isoform, resulting in decreased total NOS activity and tissue nitrite levels. COX activity was significantly reduced with melatonin treatment. The neuroprotective anti-inflammatory effects of melatonin were consistent with the substantial reduction in infarct volume throughout the cortex and striatum and recovery of mitochondrial enzyme activities. The evidence presented here suggests that modulation of l-arginine metabolism by melatonin make it a valuable neuroprotective therapy for stroke. PMID:21605165

  1. 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…

  2. 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.

  3. 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 patien...

  4. Melatonin given in the morning prevents the suppressive action on the reproductive system of melatonin given in late afternoon.

    Science.gov (United States)

    Chen, H J; Brainard, G C; Reiter, R J

    1980-08-01

    Melatonin administered to female hamsters kept under light:dark cycles of 14:10 (in hours) normally suppresses reproductive processes only if the indoleamine is administered later than 6.5 h after the beginning of the photoperiod. In the present study, we investigated the influence of morning (11.00 h) injections of melatonin on the reproductive inhibitory effects of afternoon (17.00 h) melatonin injections. Adult female hamsters were exposed to light daily from 06.00 to 20.00 h. The animals were divided into the following experimental groups: group 1, injected with vehicle at both 11.00 and 17.00 h; group 2, injected with vehicle at 11.00 h and 25 microgram melatonin at 17.00 h; group 3, injected with 1 mg melatonin at 11.00 h and 25 microgram melatonin at 17.00 h; group 4, injected with 1 mg melatonin at 11.00 h and vehicle at 17.00 h. Control animals injected with vehicle at both 11.00 and 17.00 h had normal 4-day estrous cycles throughout the 8 weeks of the experiment. 100% of the animals injected with vehicle in the morning and melatonin in the afternoon became acyclic within 7 weeks. However, if the afternoon injections of melatonin were preceded by morning injections of the indoleamine, the animals continued to exhibit normal estrous cycles. Also, hamsters injected with melatonin at 11.00 h and vehicle at 15.00 h had normal estrous cycles throughout the study. At the conclusion of the experiment, the uterine weights and plasma prolactin levels in the animals that received vehicle at 11.00 h and malatonin at 17.00 h were depressed compared to those in the vehicle-vehicle injected controls. Again, the morning injections of melatonin prevented the afternoon injections of melatonin from decreasing either the uterine weights or the plasma prolactin levels. It is concluded that the morning injections of melatonin either down-regulated the melatonin receptors or decreased their number and thereby rendered afternoon injections of melatonin incapable of inhibiting reproductive processes. PMID:7190229

  5. 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.

  6. Receptor mechanisms involved in the anticonvulsant effect of melatonin in maximal electroshock seizures.

    Science.gov (United States)

    Ray, M; Mediratta, P K; Reeta, Kh; Mahajan, P; Sharma, K K

    2004-04-01

    The present study investigates the mechanisms involved in the anticonvulsant effect of melatonin in maximum electroshock (MES) seizures. Melatonin (25-100 mg/kg) dose-dependently decreased the duration of tonic hindlimb extension (THLE). The anticonvulsant effect of melatonin was blocked by bicuculline, a GABA(A) receptor antagonist, and luzindole, an ML(1) receptor antagonist, while prazosin, an ML(2) receptor antagonist, enhanced the anticonvulsant actions of melatonin in this seizure model. Administration of serotonergic agents, mianserin and ondansetron, along with melatonin, increased the antiseizurogenic activity of melatonin, while buspirone had no effect. Pretreating the animals with diazepam, carbamazepine or lamotrigine enhanced the anticonvulsant effect of melatonin. Melatonin thus appears to be an effective anticonvulsant, and melatonin ML(1) receptors, GABAergic and serotonergic mechanisms may play an important role in mediating the anticonvulsant activity of melatonin in electroshock seizures. PMID:15148522

  7. Melatonin Therapy in Patients with Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Daniel P. Cardinali

    2014-04-01

    Full Text Available Alzheimer’s disease (AD is a major health problem and a growing recognition exists that efforts to prevent it must be undertaken by both governmental and non-governmental organizations. In this context, the pineal product, melatonin, has a promising significance because of its chronobiotic/cytoprotective properties potentially useful for a number of aspects of AD. One of the features of advancing age is the gradual decrease in circulating melatonin levels. A limited number of therapeutic trials have indicated that melatonin has a therapeutic value as a neuroprotective drug in the treatment of AD and minimal cognitive impairment (which may evolve to AD. Both in vitro and in vivo, melatonin prevented the neurodegeneration seen in experimental models of AD. For these effects to occur, doses of melatonin about two orders of magnitude higher than those required to affect sleep and circadian rhythmicity are needed. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects, which were employed in clinical trials in sleep-disturbed or depressed patients in doses considerably higher than those employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin in the range of 50–100 mg/day are urgently needed to assess its therapeutic validity in neurodegenerative disorders such as AD.

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

    Science.gov (United States)

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

    2015-08-01

    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

  9. Relation of Melatonin to Sleep Architecture in Children with Autism

    Science.gov (United States)

    Leu, Roberta M.; Beyderman, Liya; Botzolakis, Emmanuel J.; Surdyka, Kyla; Wang, Lily; Malow, Beth A.

    2011-01-01

    Children with autism often suffer from sleep disturbances, and compared to age-matched controls, have decreased melatonin levels, as indicated by urine levels of the primary melatonin metabolite, 6-sulfatoxymelatonin (6-SM). We therefore investigated the relationship between 6-SM levels and sleep architecture in children with autism spectrum…

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Ahmet Korkmaz

    2011-02-01

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

  13. 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.

  14. 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

  15. Antiepileptic effects of melatonin in the pinealectomized Mongolian gerbil.

    Science.gov (United States)

    Rudeen, P K; Philo, R C; Symmes, S K

    1980-04-01

    Pinealectomy of the Mongolian gerbil leads to seizure activity. The pineal gland is a major source of malatonin (5-methoxy-N-acetyltryptamine) which may possess a modulatory influence upon neural activity. Melatonin administered in the form of subcutaneous beeswax implants was given to gerbils four days prior to pinealectomy or sham pinealectomy. Beeswax pellets were implanted as the vehicle agent in respective groups. Melatonin-treated pinealectomized animals exhibited fewer seizures than did pinealectomized animals that did not receive melatonin. The results indicate that melatonin has an ameliorative effect upon pinealectomy-induced seizures, but the mechanism by which pinealectomy induced the seizures, and the etiology in which melatonin reduces the seizure activity is unknown. PMID:7358040

  16. Circulating Melatonin And The Risk Of Breast And Endometrial Cancer In Women

    OpenAIRE

    Viswanathan, Akila N.; Schernhammer, Eva S.

    2008-01-01

    Several decades of observational data have accumulated to implicate a potential role for melatonin in cancer prevention. Experimental studies suggest that the antineoplastic action of melatonin arises through many different mechanisms, including melatonin’s antioxidant, antimitotic, and antiangiogenic activity, as well as its ability to modulate the immune system and alter fat metabolism. Melatonin interacts with membrane and nuclear receptors, and may be linked to the regulation of tumor gro...

  17. 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...

  18. The role of melatonin in mood disorders

    Directory of Open Access Journals (Sweden)

    De Berardis D

    2015-11-01

    Full Text Available Domenico De Berardis,1–3 Laura Orsolini,3–5 Nicola Serroni,1 Gabriella Girinelli,1–3 Felice Iasevoli,3–6 Carmine Tomasetti,3–6 Monica Mazza,3–7 Alessandro Valchera,3–8 Michele Fornaro,9 Giampaolo Perna,10–12 Monica Piersanti,13Marco Di Nicola,14 Marilde Cavuto,15 Giovanni Martinotti,2 Massimo Di Giannantonio21NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G Mazzini", Teramo, Italy; 2Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University G d'Annunzio, Chieti, Italy; 3Polyedra, Teramo, Italy; 4United Hospitals, Academic Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy; 5School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Hertfordshire, UK; 6Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine Federico II, Naples, Italy; 7Department of Health Sciences, University of L'Aquila, L'Aquila, Italy; 8Villa S Giuseppe Hospital, Hermanas Hospitalarias, Ascoli Piceno, Italy; 9Department of Scienze della Formazione, University of Catania, Catania, Italy; 10Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences, Villa San Benedetto Menni, Albese con Cassano, Como, Italy; 11Department of Psychiatry and Neuropsychology, University of Maastricht, Maastricht, the Netherlands; 12Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA; 13Hospital Pharmacy, Hospital G Mazzini, ASL 4 Teramo, Italy; 14Institute of Psychiatry and Psychology, Catholic University of Sacred Heart, Rome, Italy; 15IASM, L'Aquila, ItalyAbstract: Melatonin (N-acetyl-5-methoxytryptamine has been discovered as a hormone secreted by the pineal gland, even though it is also synthetized in various other organs, tissues, and cells. The circadian rhythm of melatonin is often used as an indicator phase position since it is a well-defined, high-amplitude rhythm controlled by the hypothalamic suprachiasmatic nuclei. Melatonin production is controlled by this endogenous circadian timing system. It peaks during the night and is suppressed by daylight. Mood spectrum disorders, including bipolar disorder (BD, major depressive disorder (MDD, and seasonal affective disorder (SAD, have been observed to be accompanied by circadian dysregulation as well as dysregulation in melatonin secretion. Simultaneously, it has also been documented that disruptions in circadian rhythms, including the sleep/wake cycle, though environmental means can produce mood-related problems in vulnerable individuals. These findings suggested that altered circadian rhythms might be biological markers of these disorders. As melatonin is considered a chronobiotic factor, ie, able to entrain the circadian rhythms of several biological functions (eg, activity/rest, sleep/wake, body temperature, endocrine rhythms, etc, its use may provide a new therapeutic approach for the treatment of affective disorders. However, the available evidence is controversial. This review summarizes the data published so far about reliable evidence on the role of melatonin in affective disorders.Keywords: melatonin, melatonergic system, mood disorders, depression, seasonal affective disorder, bipolar disorder 

  19. Relationship between Aldose reductase and superoxide dismutase inhibition capacities of indole-based analogs of melatonin derivatives

    Directory of Open Access Journals (Sweden)

    Da?-Evcimen N.

    2009-01-01

    Full Text Available Aldose reductase (AR has been implicated in the etiology of diabetic complications. Under diabetic conditions, the elevated vascular glucose level causes an increased flux through the polyol pathway, which induces functional and morphological changes associated with secondary diabetic complications such as cataract, neuropathy, and nephrop­athy. Oxidative stress, antioxidants, and the polyol pathway have recently been found to be linked in pathological states. A large number of structurally different compounds have been studied as potent in vitro AR inhibitors (ARIs. However, with few exceptions, these compounds did not show clinical benefit, and some even produced serious side effects. In view of the ARI activity of certain indole derivative compounds and antioxidant properties of melatonin, we investigated some indole-based analogs of melatonin derivatives. Antioxidant and ARI activity tests were applied to nine indole derivatives that are substituted at the third and fifth positions. Also, the relationship between ARI and antioxidant enzyme activity is discussed.

  20. Radioprotective effects of melatonin on radiation-induced cataract

    International Nuclear Information System (INIS)

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

  1. 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

  2. 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), MT? and MT?, 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 MT? or MT? receptors to A? lead to a 40% reduction in [(125)I]iodomelatonin binding to MT?. ERK1/2 activation triggered by MTRs, but not by the ??-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. PMID:25757565

  3. Human MT2 melatonin receptor and its melatonin recognition site: a structural model.

    Czech Academy of Sciences Publication Activity Database

    Luley, Ladislav; Stockner, T; Sovová, Žofie; Mazna, Petr; Ettrich, Rüdiger; Teisinger, Jan

    Ro?.272, ?.S1 (2005), s. 222-223. ISSN 1474-3833. [FEBS Congress /30./ and IUBMB Conference /9./. 02.07.2005-07.07.2005, Budapest] Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z60870520 Keywords : melatonin receptor * model * structure Subject RIV: BO - Biophysics

  4. 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)

  5. 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

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

    OpenAIRE

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

    2009-01-01

    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 e...

  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. Melatonin affects the temporal pattern of vocal signatures in birds.

    Science.gov (United States)

    Derégnaucourt, Sébastien; Saar, Sigal; Gahr, Manfred

    2012-10-01

    In humans and other animals, melatonin is involved in the control of circadian biological rhythms. Here, we show that melatonin affects the temporal pattern of behavioral sequences in a noncircadian manner. The zebra finch (Taeniopygia guttata) song and the crow of the Japanese quail (Coturnix japonica) are courtship vocalizations composed of a stereotyped sequence of syllables. The zebra finch song is learned from conspecifics during infancy, whereas the Japanese quail crow develops normally without auditory input. We recorded and analyzed the complete vocal activity of adult birds of both species kept in social isolation for several weeks. In both species, we observed a shortening of signal duration following the transfer from a light-dark (LD) cycle to constant light (LL), a condition known to abolish melatonin production and to disrupt circadian rhythmicity. This effect was reversible because signal duration increased when the photoperiod was returned to the previous LD schedule. We then tested whether this effect was directly related to melatonin by removal of the pineal gland, which is the main production site of circulating melatonin. A shortening of the song duration was observed following pinealectomy in LD. Likewise, melatonin treatment induced changes in the temporal structure of the song. In a song learning experiment, young pinealectomized finches and young finches raised in LL failed to copy the temporal pattern of their tutor's song. Taken together, these results suggest that melatonin is involved in the control of motor timing of noncircadian behavioral sequences through an evolutionary conserved neuroendocrine pathway. PMID:22506964

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Melatonin and atopy: role in atopic dermatitis and asthma.

    Science.gov (United States)

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

    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 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. PMID:25093714

  11. Therapeutic potential of melatonin in traumatic central nervous system injury.

    Science.gov (United States)

    Samantaray, Supriti; Das, Arabinda; Thakore, Nakul P; Matzelle, Denise D; Reiter, Russel J; Ray, Swapan K; Banik, Naren L

    2009-09-01

    A vast literature extolling the benefits of melatonin has accumulated during the past four decades. Melatonin was previously considered of importance to seasonal reproduction and circadian rhythmicity. Currently, it appears to be a versatile anti-oxidative and anti-nitrosative agent, a molecule with immunomodulatory actions and profound oncostatic activity, and also to play a role as a potent neuroprotectant. Nowadays, melatonin is sold as a dietary supplement with differential availability as an over-the-counter aid in different countries. There is a widespread agreement that melatonin is nontoxic and safe considering its frequent, long-term usage by humans at both physiological and pharmacological doses with no reported side effects. Endeavors toward a designated drug status for melatonin may be enormously rewarding in clinics for treatment of several forms of neurotrauma where effective pharmacological intervention has not yet been attained. This mini review consolidates the data regarding the efficacy of melatonin as an unique neuroprotective agent in traumatic central nervous system (CNS) injuries. Well-documented actions of melatonin in combating traumatic CNS damage are compiled from various clinical and experimental studies. Research on traumatic brain injury and ischemia/reperfusion are briefly outlined here as they have been recently reviewed elsewhere, whereas the studies on different animal models of the experimental spinal cord injury have been extensively covered in this mini review for the first time. PMID:19627458

  12. 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

  13. 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 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.

  14. 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.

  15. Increases in nocturnal bruxism among college students implicate stress.

    Science.gov (United States)

    Hicks, R A; Conti, P A; Bragg, H R

    1990-12-01

    While the etiology of nocturnal bruxism is unknown, three major categories of theories have been advanced to explain its cause(s), i.e., local-mechanical theories, psychological theories and systemic/neurophysiological theories. The recent report of a four-fold increase in the incidence of self-reported nocturnal bruxism in college students over the last 23-year period emphasizes the role that psychological variables may play in the development of this disorder and it is suggested that the personality traits which contribute to stress management are primary among these. PMID:2090924

  16. Melatonin Attenuates Colistin-Induced Nephrotoxicity in Rats?

    OpenAIRE

    Yousef, Jumana M.; Chen, Gong; Hill, Prue A.; Nation, Roger L; Li, Jian

    2011-01-01

    Colistin-induced nephrotoxicity is a dose-limiting adverse effect when colistin is used against Gram-negative pathogens. This study examined the nephroprotective effect of melatonin against colistin in rats. Rats (n = 7 per group) were treated intravenously twice daily with saline, colistin (at increasing doses from 0.5 to 4.0 mg/kg), melatonin (5 mg/kg), or both melatonin and colistin for 7 days. The severity of renal alteration was examined both biochemically and histologically. The effect ...

  17. Protective effect of melatonin on thrombocytopoiesis in irratiated mice

    International Nuclear Information System (INIS)

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

  18. 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)

  19. Melatonin for sleep problems in children with neurodevelopmental disorders.

    Science.gov (United States)

    2015-10-01

    Children with neurodevelopmental disorders are at risk of sleep problems, typically difficulty getting to sleep, sleep/wake rhythm disturbances and reduced duration of sleep (insomnia).(1,2) This may be associated with abnormally timed or inadequate secretion of melatonin, a naturally-occurring hormone involved in coordinating the body's sleep-wake cycle.(1,3) Previously, we reviewed the use of a melatonin product licensed for primary insomnia in adults aged over 55 years.(4) Here we review off-label and unlicensed use of melatonin in children with attention-deficit hyperactivity disorder (ADHD) or autism spectrum disorder or related neurodevelopmental disorders. PMID:26471270

  20. Nocturnal cooling in a very shallow cold air pool

    Science.gov (United States)

    Rakovec, Jože; Skok, Gregor; Žabkar, Rahela; Žagar, Nedjeljka

    2015-04-01

    Cold air pools (CAPs) may develop during nights in very shallow depressions. The depth of the stagnant air within a CAP influences the process of the cooling of nocturnal air and the resulting minimum temperature. A seven-month long field experiment was performed during winter 2013/2014 in an orchard near Kr\\vsko, Slovenia, located inside a very shallow basin only a few meters deep and approximately 500 m wide. Two locations at different elevations inside the basin were selected for measurement. The results showed that the nights (in terms of cooling) can be classified into three main categories; nights with overcast skies and weak cooling, windy nights with clear sky and strong cooling but with no difference in temperatures between locations inside the basin, and calm nights with even stronger cooling and significant temperature differences between locations inside the basin. On calm nights with clear skies, the difference at two measuring sites inside the basin can be up to 5 °C but the presence of even weak winds can cause sufficient turbulent mixing to negate any difference in temperature. To better understand the cooling process on calm, clear nights, we developed a simple 1-D thermodynamic conceptual model focusing on a very shallow CAP. The model has 5-layers (including two air layers representing air inside the CAP), and an analytical solution was obtained for the equilibrium temperatures. Sensitivity analysis of the model was performed. As expected, a larger soil heat conductivity or higher temperature in the ground increases the morning minimum temperatures. An increase in temperature of the atmosphere also increases the simulated minimum temperatures, while the temperature difference between the higher and lower locations remains almost the same. An increase in atmosphere humidity also increases the modelled equilibrium temperatures, while an increase of the humidity of the air inside the CAP results in lower equilibrium temperatures. The humidity of the air within the CAP and that of the free atmosphere strongly influence the differences in equilibrium temperatures at higher and lower locations. The more humid the air, the stronger the cooling at the lower location compared to the higher location.

  1. Role of melatonin, melatonin receptors and STAT3 in the cardioprotective effect of chronic and moderate consumption of red wine.

    Science.gov (United States)

    Lamont, Kim; Nduhirabandi, Frederic; Adam, Tasneem; Thomas, D Paul; Opie, Lionel H; Lecour, Sandrine

    2015-10-01

    We have recently discovered that melatonin, given acutely and directly to the isolated heart at the concentration found in wine, confers cardioprotection against ischemia-reperfusion (I/R). However, whether the presence of melatonin in wine contributes to the cardioprotective effect of chronic and moderate consumption of wine and its signalling mechanisms of protection are unknown. We therefore used both in vivo and in vitro models of I/R to investigate whether the presence of melatonin in red wine may contribute to the cardioprotective effect of chronic and moderate consumption of red wine. Wistar rats and C57black6 mice (WT) received drinking water supplemented daily with a moderate amount of red wine or melatonin given at the concentration found in the red wine. Rats were also pretreated with luzindole, a specific inhibitor of melatonin receptors 1 and 2 (2.3 mg/kg/day, intraperitoneally) or prazosin, a specific inhibitor of melatonin receptor type 3 (2.5 mg/kg/day, intraperitoneally). After 14 days, hearts were subjected to I/R in vivo or ex vivo. Red wine reduced the infarct size in both rats and WT mice (p < 0.001). Luzindole did not affect wine-induced cardioprotection, while prazosin reduced the infarct sparing effect of red wine (p < 0.05). Furthermore, red wine or melatonin failed to protect tumor necrosis factor alpha (TNF) receptor 2 knockout or cardiomyocyte specific signal transducer and activator of transcription 3 (STAT3) deficient mice (n.s. vs. control). Our novel findings suggest that the presence of melatonin in red wine contributes to the cardioprotective effect of chronic and moderate consumption of red wine against lethal I/R injuries. This effect is most likely mediated, at least in part, via melatonin receptor 3 and the activation of TNF and STAT3, both key players of the prosurvival and well described SAFE pathway. PMID:26296463

  2. 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...

  3. 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…

  4. Wild Chimpanzees on the Edge: Nocturnal Activities in Croplands

    Science.gov (United States)

    Krief, Sabrina; Cibot, Marie; Bortolamiol, Sarah; Seguya, Andrew; Krief, Jean-Michel; Masi, Shelly

    2014-01-01

    In a rapidly changing landscape highly impacted by anthropogenic activities, the great apes are facing new challenges to coexist with humans. For chimpanzee communities inhabiting encroached territories, not bordered by rival conspecifics but by human agricultural fields, such boundaries are risky areas. To investigate the hypothesis that they use specific strategies for incursions out of the forest into maize fields to prevent the risk of detection by humans guarding their field, we carried out video recordings of chimpanzees at the edge of the forest bordered by a maize plantation in Kibale National Park, Uganda. Contrary to our expectations, large parties are engaged in crop-raids, including vulnerable individuals such as females with clinging infants. More surprisingly chimpanzees were crop-raiding during the night. They also stayed longer in the maize field and presented few signs of vigilance and anxiety during these nocturnal crop-raids. While nocturnal activities of chimpanzees have been reported during full moon periods, this is the first record of frequent and repeated nocturnal activities after twilight, in darkness. Habitat destruction may have promoted behavioural adjustments such as nocturnal exploitation of open croplands. PMID:25338066

  5. 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.

  6. 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…

  7. 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

  8. 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.

  9. 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.

  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. 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)

  12. Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses.

    Science.gov (United States)

    Farez, Mauricio F; Mascanfroni, Ivan D; Méndez-Huergo, Santiago P; Yeste, Ada; Murugaiyan, Gopal; Garo, Lucien P; Balbuena Aguirre, María E; Patel, Bonny; Ysrraelit, María C; Zhu, Chen; Kuchroo, Vijay K; Rabinovich, Gabriel A; Quintana, Francisco J; Correale, Jorge

    2015-09-10

    Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the CNS. These epidemiological observations suggest that environmental factors influence the disease course. Here, we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans. Treatment with melatonin ameliorates disease in an experimental model of multiple sclerosis and directly interferes with the differentiation of human and mouse T cells. Melatonin induces the expression of the repressor transcription factor Nfil3, blocking the differentiation of pathogenic Th17 cells and boosts the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL-10 promoter by ROR-?. These results suggest that melatonin is another example of how environmental-driven cues can impact T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis. PMID:26359987

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. Exogenous melatonin affects photosynthesis in characeae Chara australis

    OpenAIRE

    Lazár, Dušan; Murch, Susan J; Beilby, Mary J.; Al Khazaaly, Sabah

    2013-01-01

    Melatonin was found in the fresh water characeae Chara australis. The concentrations (~4 ?g/g of tissue) were similar in photosynthesizing cells, independent of their position on the plant and rhizoids (roots) without chloroplasts. Exogenous melatonin, added at 10 ?M to the artificial pond water, increased quantum yield of photochemistry of photosystem II by 34%. The increased efficiency appears to be due to the amount of open reaction centers of photosystem II, rather than increased efficien...

  18. Melatonin and mitochondrial dysfunction in the central nervous system.

    Science.gov (United States)

    Cardinali, Daniel P; Pagano, Eleonora S; Scacchi Bernasconi, Pablo A; Reynoso, Roxana; Scacchi, Pablo

    2013-02-01

    Cell death and survival are critical events for neurodegeneration, mitochondria being increasingly seen as important determinants of both. Mitochondrial dysfunction is considered a major causative factor in Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Increased free radical generation, enhanced mitochondrial inducible nitric oxide (NO) synthase activity and NO production, and disrupted electron transport system and mitochondrial permeability transition, have all been involved in impaired mitochondrial function. Melatonin, the major secretory product of the pineal gland, is an antioxidant and an effective protector of mitochondrial bioenergetic function. Both in vitro and in vivo, melatonin was effective to prevent oxidative stress/nitrosative stress-induced mitochondrial dysfunction seen in experimental models of AD, PD and HD. These effects are seen at doses 2-3 orders of magnitude higher than those required to affect sleep and circadian rhythms, both conspicuous targets of melatonin action. Melatonin is selectively taken up by mitochondria, a function not shared by other antioxidants. A limited number of clinical studies indicate that melatonin can improve sleep and circadian rhythm disruption in PD and AD patients. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects which were employed in clinical trials in sleep-disturbed or depressed patients in doses considerably higher than those employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin in the range of 50-100mg/day are needed to assess its therapeutic validity in neurodegenerative disorders. PMID:22391273

  19. 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...

  20. Melatonin agonists for treatment of sleep and depressive disorders

    OpenAIRE

    Pandi-Perumal, Seithikurippu R; Gregory M. Brown; 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...

  1. Homology Models of Melatonin Receptors: Challenges and Recent Advances

    OpenAIRE

    Silvia Rivara; Gilberto Spadoni; Annalida Bedini; Alessio Lodola; Daniele Pala

    2013-01-01

    Melatonin exerts many of its actions through the activation of two G protein-coupled receptors (GPCRs), named MT1 and MT2. So far, a number of different MT1 and MT2 receptor homology models, built either from the prototypic structure of rhodopsin or from recently solved X-ray structures of druggable GPCRs, have been proposed. These receptor models differ in the binding modes hypothesized for melatonin and melatonergic ligands, with distinct patterns of ligand-receptor interactions and putativ...

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

    International Nuclear Information System (INIS)

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

  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. Relation of Melatonin to Sleep Architecture in Children with Autism

    OpenAIRE

    Leu, Roberta M.; Beyderman, Liya; Botzolakis, Emmanuel J; Surdyka, Kyla; Wang, Lily; Malow, Beth A

    2011-01-01

    Children with autism often suffer from sleep disturbances, and compared to age-matched controls, have decreased melatonin levels, as indicated by urine levels of the primary melatonin metabolite, 6-sulfatoxymelatonin (6-SM). We therefore investigated the relationship between 6-SM levels and sleep architecture in children with autism spectrum disorders (ASD). Twenty-three children, aged 4–10 years, completed two nights of polysomnography and one overnight urine collection for measurement of ur...

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

    Directory of Open Access Journals (Sweden)

    Fatima Dumas Cintra

    2014-11-01

    Full Text Available 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.

  6. 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

  7. 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.

  8. 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.

  9. 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)

  10. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Dubbels, R.; Klenke, E.; Schnakenberg, E.; Ehlers, C.; Schloot, W. [Univ. of Bremen, Center of Human Genetics and Genetic Counselling, Bremen (Germany); Reiter, R.J. [The Univ. of Texas Health Science Center at San Antonio, Dept. of Cellular and Structural Biology, San Antonio, Texas (United States); Goebel, A.; Schiware, H.W. [Gemeinschaftslabor Dr. Schiwara et al., Breman (Germany)

    1995-01-01

    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.

  12. 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

  13. 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

  14. 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.

  15. 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-blind...

  16. 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...

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

    OpenAIRE

    Sherif H. El-Alfy; Rashed-Morad A. Rashed; Ihab K. Mohamed

    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...

  18. Evaluation of the role of melatonin in formalin-induced pain response in mice

    OpenAIRE

    Ray M; Mediratta Pramod; Mahajan P; Sharma K

    2004-01-01

    BACKGROUND: Melatonin, the major secretory product of pineal gland has been suggested to play a regulatory role in the circadian rhythm of body activities including the pain sensitivity. Three subtypes of melatonin receptors, i.e. ML1, ML2 and ML3 have been identified. AIM: To investigate the antinociceptive activity of melatonin and to unravel the underlying receptor mechanisms involved in this action. MATERIAL AND METHODS: Effect of melatonin (25-100 mg/kg, ip) and its interaction with puta...

  19. 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...

  20. 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...

  1. 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 mel...

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

    OpenAIRE

    Kara, Adem; 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 divided...

  3. 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 ...

  4. 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...

  5. Crystal and molecular structure of melatonin

    Energy Technology Data Exchange (ETDEWEB)

    Quarles, W.G.; Templeton, D.H.; Zalkin, A.

    1974-01-01

    Crystals of melatonin (C/sub 13/H/sub 16/N/sub 2/O/sub 2/) are monoclinic, space group P2/sub 1//c; a = 7.707(2), b = 9.252(2), c = 17.077(4)A, ..beta.. = 96.78(3)/sup 0/, Z = 4, D/sub m/ = 1.272, D/sub x/ = 1.276 g cm/sup -3/. The structural model was refined to R = 0.036 for 900 independent x-ray reflections measured on an automatic diffractometer. The molecules are nearly flat with the side chain in the fully extended (trans) conformation. Molecules are connected in sheets by weak hydrogen bonds from nitrogen to oxygen, with N-O = 2.90 and 2.96 A. 3 figures, 6 tables.

  6. Plains Elevated Convection at Night (PECAN) Experiment Science Plan

    Energy Technology Data Exchange (ETDEWEB)

    Turner, D [National Oceanic and Atmospheric Administration; Parsons, D [NCAR; Geerts, B [Department of Atmospheric Science, University of Wyoming

    2015-03-01

    The Plains Elevated Convection at Night (PECAN) experiment is a large field campaign that is being supported by the National Science Foundation (NSF) with contributions from the National Oceanic and Atmospheric Administration (NOAA), the National Atmospheric and Space Administration (NASA), and the U.S. Department of Energy (DOE). The overarching goal of the PECAN experiment is to improve the understanding and simulation of the processes that initiate and maintain convection and convective precipitation at night over the central portion of the Great Plains region of the United States (Parsons et al. 2013). These goals are important because (1) a large fraction of the yearly precipitation in the Great Plains comes from nocturnal convection, (2) nocturnal convection in the Great Plains is most often decoupled from the ground and, thus, is forced by other phenomena aloft (e.g., propagating bores, frontal boundaries, low-level jets [LLJ], etc.), (3) there is a relative lack of understanding how these disturbances initiate and maintain nocturnal convection, and (4) this lack of understanding greatly hampers the ability of numerical weather and climate models to simulate nocturnal convection well. This leads to significant uncertainties in predicting the onset, location, frequency, and intensity of convective cloud systems and associated weather hazards over the Great Plains.

  7. 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

  8. 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

  9. 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…

  10. Melatonin and its correlation with testosterone in polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Priyanka Jain

    2013-01-01

    Full Text Available Context: Polycystic ovarian syndrome (PCOS is considered to be the most common endocrine disorder affecting women. Melatonin, a small lipophilic indoleamine, and reproductive hormones may be interrelated. Melatonin influences sex steroid production at different stages of ovarian follicular maturation as melatonin receptors have been demonstrated at multiple sites in ovary and in intrafollicular fluid. It plays role as an antioxidant and free radical scavanger which protects follicles from oxidative stress, rescuing them from atresia, leading to complete follicular maturation and ovulation. Aims: To study the role of melatonin in PCOS and to investigate its correlation with testosterone in patients suffering from PCOS. Settings and Design: A total of 50 women with PCOS (Rotterdam criteria, 2003 and 50 age and weight matched healthy controls were selected and serum melatonin estimation was done in both the groups and correlated with serum total testosterone levels. Materials and Methods: In a case-control study, detailed history, clinical examination and hormonal evaluation [basal levels of leutinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, insulin, total testosterone, progesterone and melatonin] were carried out in all the participants including both cases and controls. For melatonin estimation, blood samples were collected between 12:00 am and 04:00 am on day 2 nd of menstrual cycle and analyzed by using commercially available enzyme-linked immunosorbent assay kit. Statistical Analysis: Student?s t-test was used to compare the significant difference in mean values between cases and control groups. Chi-square test was used to test the significant association between the qualitative variables. Linear correlation coefficient and regression analysis were done to see the amount and direction of relationship between quantitative variables. Results: The mean melatonin level was observed to be significantly increased in patients (63.27 ? 10.97 pg/mL than in controls (32.51 ? 7.55 pg/mL. Melatonin was found to be raised in all the cases of PCOS (above cut-off value of ?45 pg/mL, P < 0.001. Total testosterone level was also raised in 72% of patients. Melatonin levels were found to be positively associated with increased testosterone (P < 0.001. In regression analysis using melatonin as dependent variable and testosterone as an independent variable, the value of R2 ? 100 (percent variation was found to be 72.1%. Conclusions: Women with PCOS have significantly raised serum melatonin levels and hyperandrogenemia along with increased number of atretic follicles. Further studies are required to establish a definite role of melatonin in PCOS cases with disturbed hormonal milieu. This could open up the way for therapeutic role of melatonin in treatment of patients suffering from PCOS.

  11. Exercise augments the nocturnal prolactin rise in exercise-trained men

    Science.gov (United States)

    Hackney, Anthony C.; Davis, Hope C.; Lane, Amy R.

    2015-01-01

    Objective: The objective of this study was to profile over a 24 h period the prolactin responses of exercise-trained men on a day involving rest with no exercise in comparison to a day involving exercise training sessions. Methods: This is a quasi-experimental design study using repeated measures determination of 24 h prolactin responses in exercise-trained men (n = 16; age = 27.3± 3.3 years (mean ± standard deviation)). Blood samples were taken hourly over a 24 h period on a day involving two intensive exercise training sessions (ED), and on a separate control day (CD) with no exercise activity. The order of the ED and CD was randomized. Physical activity and diet were controlled and replicated for the ED and CD. Blood specimens were handled, prepared and analyzed utilizing appropriate standard clinical practices. The data were analyzed with the Friedman analysis of variance and Nemenyi post hoc statistical procedure for repeated measures. Results: On the CD, prolactin displayed a typical circadian rhythm with daytime values of the hormone being less than the nocturnal rise once sleep had begun (p all other times). On the ED, prolactin responses were noticeably different from those of the CD. The morning and afternoon exercise sessions included significant increases in prolactin immediately at the end of the exercise sessions, being greater than corresponding CD time points (p exercise session. On the ED there was a displayed circadian nocturnal response in the hormone with 16:00–24:00 h being elevated above the all nonexercise effected values for that specific day (p exercise-trained men on days when they perform exercise. The mechanisms inducing this adaptive response are unclear but warrant further investigation.

  12. Circadian clock regulation of melatonin MTNR1B receptor expression in human myometrial smooth muscle cells.

    Science.gov (United States)

    Beesley, Stephen; Lee, Justin; Olcese, James

    2015-08-01

    Circadian genes are expressed in virtually all cells and tissues, and circadian rhythms influence many bodily processes, including reproductive physiology. The expression of hMTNR1B is suppressed during pregnancy until late in term (much like the oxytocin receptor), at which time it is up-regulated to allow for the nocturnal melatonin/oxytocin synergy, which promotes strong nocturnal contractions. Little is currently known about the regulation of hMNTR1b, nor about its functional significance in the myometrium. We, therefore, aimed to elucidate some of the transcription factors that regulate hMNTR1b gene expression in the human myometrium and to determine if hMNTR1b is under circadian control. In this study, we used immortalized and primary myometrial cells that were assessed for circadian gene expression rhythms using real-time bioluminometry and quantitative PCR. Chromatin immunoprecipitation examined the binding of the clock gene product brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like protein 1 (BMAL1) to the promoter of the hMTNR1B gene. Overexpression studies tested the role of circadian locomotor output cycles kaput (CLOCK) and its partner BMAL1 in regulating hMTNR1B expression. We confirmed circadian clock gene expression in both immortalized human myometrial cells and primary myometrial cell cultures. We further showed that the hBMAL1 protein binds to an E-box motif in the proximal promoter of the hMTNR1B gene. Overexpression studies demonstrated that the BMAL1/CLOCK complex activates expression of hMTNR1B leading to a circadian rhythm in phase with the E-box driven clock gene hPER2 (Period 2). These results indicate, for the first time, the presence of a functional circadian clock in the human myometrium with the hMTNR1B gene as a clock controlled target. Further investigations could open new vistas for understanding the regulation of uterine contractions and the timing of human labor. PMID:25939854

  13. 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 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)

  14. 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

  15. 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...

  16. Neuroethology of ultrasonic hearing in nocturnal butterflies (Hedyloidea)

    DEFF Research Database (Denmark)

    Yack, Jayne E.; Kalko, Elisabeth K.V.; Surlykke, Annemarie

    2007-01-01

    Nocturnal Hedyloidea butterflies possess ultrasound-sensitive ears that mediate evasive flight maneuvers. Tympanal ear morphology, auditory physiology and behavioural responses to ultrasound are described for Macrosoma heliconiaria, and evidence for hearing is described for eight other hedylid species. The ear is formed by modifications of the cubital and subcostal veins at the forewing base, where the thin (1-3 m), ovoid (520 £ 220 )mpanal membrane occurs in a cavity. The ear is innervated by n...

  17. Golden hamsters are nocturnal in captivity but diurnal in nature

    OpenAIRE

    GATTERMANN, Rolf; Johnston, Robert E; Yigit, Nuri; Fritzsche, Peter; Larimer, Samantha; Özkurt, Sakir; Neumann, Karsten; Song, Zhimin; Colak, Ercüment; Johnston, Joan; McPhee, M. Elsbeth

    2008-01-01

    Daily activity rhythms are nearly universal among animals and their specific pattern is an adaptation of each species to its ecological niche. Owing to the extremely consistent nocturnal patterns of activity shown by golden hamsters (Mesocricetus auratus) in the laboratory, this species is a prime model for studying the mechanisms controlling circadian rhythms. In contrast to laboratory data, we discovered that female hamsters in the wild were almost exclusively diurnal. These results raise m...

  18. Vision in the nocturnal wandering spider Leucorchestris arenicola (Araneae: Sparassidae)

    DEFF Research Database (Denmark)

    Nørgaard, Thomas; Nilsson, Dan-Eric; Henschel, Joh R; Garm, Anders; Wehner, Rüdiger

    2008-01-01

    At night the Namib Desert spider Leucorchestris arenicola performs long-distance homing across its sand dune habitat. By disabling all or pairs of the spiders' eight eyes we found that homing ability was severely reduced when vision was fully abolished. Vision, therefore, seems to play a key role in the nocturnal navigational performances of L. arenicola. After excluding two or three pairs of eyes, the spiders were found to be able to navigate successfully using only their lateral eyes or only t...

  19. A Climatology of Nocturnal Low-Level Jets at Cabauw

    OpenAIRE

    Baas, P.; Bosveld, F. C.; Baltink, H.K.; Holtslag, A. A. M.

    2009-01-01

    A climatology of nocturnal low-level jets (LLJs) is presented for the topographically flat measurement site at Cabauw, the Netherlands. LLJ characteristics are derived from a 7-yr half-hourly database of wind speed profiles, obtained from the 200-m mast and a wind profiler. Many LLJs at Cabauw originate from an inertial oscillation, which develops after sunset in a layer decoupled from the surface by stable stratification. The data are classified to different types of stable boundary layers b...

  20. Reduced nocturnal ACTH-driven cortisol secretion during critical illness

    OpenAIRE

    Boonen E; Meersseman P; Vervenne H; Meyfroidt G; Gu\\xefza F; Wouters PJ; VeldhuisJD; Van den Berghe G

    2014-01-01

    Recently, during critical illness, cortisol metabolism was found to be reduced. We hypothesize that such reduced cortisol breakdown may suppress pulsatile ACTH and cortisol secretion via feedback inhibition. To test this hypothesis, nocturnal ACTH and cortisol secretory profiles were constructed by deconvolution analysis from plasma concentration time series in 40 matched critically ill patients and eight healthy controls, excluding diseases or drugs that affect the hypothalamic-pituitary-adr...

  1. 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...

  2. 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.

  3. Melatonin attenuates the vestibulosympathetic but not vestibulocollic reflexes in humans: selective impairment of the utricles.

    Science.gov (United States)

    Cook, Jonathan S; Ray, Chester A

    2010-12-01

    Melatonin has been reported to decrease nerve activity of medial vestibular nuclei in the rat and is associated with attenuated muscle sympathetic nerve activity (MSNA) responses to baroreceptor unloading in humans. The purpose of this study was to determine if melatonin alters the vestibulosympathetic reflex (VSR) and vestibulocollic reflex (VCR) in humans. In study 1, MSNA, arterial blood pressure, and heart rate were measured in 12 healthy subjects (28 ± 1 yr; 6 men, 6 women) during head-down rotation (HDR) before and 45 min after ingestion of either melatonin (3 mg) or placebo (sucrose). Subjects returned at least 2 days later at the same time of day to repeat the trial after ingesting the opposite treatment (melatonin or placebo). Melatonin significantly attenuated MSNA responses during HDR compared with placebo (burst frequency ? 4 ± 1 vs. ? 7 ± 1 bursts/min, and total MSNA ? 51 ± 20 and ? 96 ± 15%, respectively; P melatonin. Melatonin did not alter the timing of the p13 and n23 peaks (pre-melatonin 13.2 ± 0.4 and 21.3 ± 0.6 ms vs. post-melatonin 13.5 ± 0.4 and 21.4 ± 0.7 ms, respectively) or the p13-n23 interpeak amplitudes [pre-melatonin 22.5 ± 4.6 arbitrary units (au) and post-melatonin 22.7 ± 4.6 au]. In summary, melatonin attenuates the VSR and supports the concept that melatonin negatively affects orthostatic tolerance. However, melatonin does not alter the VCR in humans suggesting melatonin's effect on the VSR appears to be mediated by the utricles. PMID:20829497

  4. Processes driving nocturnal transpiration and implications for estimating land evapotranspiration

    Science.gov (United States)

    de Dios, Víctor Resco; Roy, Jacques; Ferrio, Juan Pedro; Alday, Josu G.; Landais, Damien; Milcu, Alexandru; Gessler, Arthur

    2015-06-01

    Evapotranspiration is a major component of the water cycle, yet only daytime transpiration is currently considered in Earth system and agricultural sciences. This contrasts with physiological studies where 25% or more of water losses have been reported to occur occurring overnight at leaf and plant scales. This gap probably arose from limitations in techniques to measure nocturnal water fluxes at ecosystem scales, a gap we bridge here by using lysimeters under controlled environmental conditions. The magnitude of the nocturnal water losses (12-23% of daytime water losses) in row-crop monocultures of bean (annual herb) and cotton (woody shrub) would be globally an order of magnitude higher than documented responses of global evapotranspiration to climate change (51-98 vs. 7-8?mm yr-1). Contrary to daytime responses and to conventional wisdom, nocturnal transpiration was not affected by previous radiation loads or carbon uptake, and showed a temporal pattern independent of vapour pressure deficit or temperature, because of endogenous controls on stomatal conductance via circadian regulation. Our results have important implications from large-scale ecosystem modelling to crop production: homeostatic water losses justify simple empirical predictive functions, and circadian controls show a fine-tune control that minimizes water loss while potentially increasing posterior carbon uptake.

  5. Processes driving nocturnal transpiration and implications for estimating land evapotranspiration

    Science.gov (United States)

    de Dios, Víctor Resco; Roy, Jacques; Ferrio, Juan Pedro; Alday, Josu G.; Landais, Damien; Milcu, Alexandru; Gessler, Arthur

    2015-06-01

    Evapotranspiration is a major component of the water cycle, yet only daytime transpiration is currently considered in Earth system and agricultural sciences. This contrasts with physiological studies where 25% or more of water losses have been reported to occur occurring overnight at leaf and plant scales. This gap probably arose from limitations in techniques to measure nocturnal water fluxes at ecosystem scales, a gap we bridge here by using lysimeters under controlled environmental conditions. The magnitude of the nocturnal water losses (12–23% of daytime water losses) in row-crop monocultures of bean (annual herb) and cotton (woody shrub) would be globally an order of magnitude higher than documented responses of global evapotranspiration to climate change (51–98 vs. 7–8?mm yr?1). Contrary to daytime responses and to conventional wisdom, nocturnal transpiration was not affected by previous radiation loads or carbon uptake, and showed a temporal pattern independent of vapour pressure deficit or temperature, because of endogenous controls on stomatal conductance via circadian regulation. Our results have important implications from large-scale ecosystem modelling to crop production: homeostatic water losses justify simple empirical predictive functions, and circadian controls show a fine-tune control that minimizes water loss while potentially increasing posterior carbon uptake.

  6. Processes driving nocturnal transpiration and implications for estimating land evapotranspiration.

    Science.gov (United States)

    de Dios, Víctor Resco; Roy, Jacques; Ferrio, Juan Pedro; Alday, Josu G; Landais, Damien; Milcu, Alexandru; Gessler, Arthur

    2015-01-01

    Evapotranspiration is a major component of the water cycle, yet only daytime transpiration is currently considered in Earth system and agricultural sciences. This contrasts with physiological studies where 25% or more of water losses have been reported to occur occurring overnight at leaf and plant scales. This gap probably arose from limitations in techniques to measure nocturnal water fluxes at ecosystem scales, a gap we bridge here by using lysimeters under controlled environmental conditions. The magnitude of the nocturnal water losses (12-23% of daytime water losses) in row-crop monocultures of bean (annual herb) and cotton (woody shrub) would be globally an order of magnitude higher than documented responses of global evapotranspiration to climate change (51-98 vs. 7-8 mm yr(-1)). Contrary to daytime responses and to conventional wisdom, nocturnal transpiration was not affected by previous radiation loads or carbon uptake, and showed a temporal pattern independent of vapour pressure deficit or temperature, because of endogenous controls on stomatal conductance via circadian regulation. Our results have important implications from large-scale ecosystem modelling to crop production: homeostatic water losses justify simple empirical predictive functions, and circadian controls show a fine-tune control that minimizes water loss while potentially increasing posterior carbon uptake. PMID:26074373

  7. 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

  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. 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.

  10. 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.

  11. Melatonin and serotonin profiles in beans of Coffea species.

    Science.gov (United States)

    Ramakrishna, Akula; Giridhar, Parvatam; Sankar, Kadimi Udaya; Ravishankar, Gokare Aswathanarayana

    2012-05-01

    A high-performance liquid chromatography (HPLC) and an electrospray ionization mass spectrometry (LC/ESI-MS) methods were applied to quantify the profiles of melatonin and serotonin (5-HT) in green and roasted beans of Coffea canephora (robusta) and Coffea arabica (arabica). Both melatonin and 5-HT were detected in green coffee beans (5.8±0.8?g/g dry weight (DW), 10.5±0.6?g/g DW) and also in roasted beans of C. canephora (8.0±0.9?g/g DW, 7.3±0.5?g/g DW). Melatonin (3.0±0.6?g/50mL) and 5-HT (4.0±0.7?g/50mL) were detected in coffee brew. In C. arabica, 5-HT was high in green beans (12.5±0.8?g/g DW) compared with roasted beans (8.7±0.4). The levels of melatonin were higher (9.6±0.8?g/g DW) in roasted beans compared with green beans (6.8±0.4?g/g DW). Both melatonin (3.9±0.2?g/50mL) and 5-HT (7.3±0.6?g/50mL) were detected in coffee brew. Because of the relevance of indoleamines as bioactive molecules with implications for food, nutritional sciences and human health, it was of interest to explore their levels in coffee, an important universal beverage. PMID:22017393

  12. 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

  13. 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.

  14. 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.

  15. 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)

  16. 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.

  17. Acute myeloblastic leukemia in paroxysmal nocturnal hemoglobinuria. Evidence of evolution from the abnormal paroxysmal nocturnal hemoglobinuria clone.

    OpenAIRE

    Devine, D V; Gluck, W L; Rosse, W F; Weinberg, J. B.

    1987-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder in which the blood cells demonstrate aberrant interactions with serum complement. In part, this is due to the absence of the complement regulatory protein, decay accelerating factor (DAF). A small number of patients with PNH have gone on to develop acute nonlymphocytic leukemia, which is thought to arise from the injured marrow as a second hematopoietic disorder. We have studied a patient with PNH who de...

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

    OpenAIRE

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

    2011-01-01

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

  19. Efficacy and Safety O-desmethyl Quinine Compare to Quinine for Nocturnal Leg Cramp

    OpenAIRE

    Setiawan, F.; E.Y. Sukandar; I.K. Adnyana; Y. Christanti

    2013-01-01

    Quinine is an alkaloid which isolated from the bark of Cinchona sp., native plant from South America, especially in Andes Mountains. Beside the function as an anti-malaria, quinine is used as anti-pyretic, analgesic, treatment for myotonia and nocturnal leg cramps. Nocturnal leg cramps is common clinical problem seen most frequently in the elderly. Quinine therapy was reported to be effective in relieving nocturnal leg cramps. However, due to side effects that appear limited this used. ...

  20. Anatomical Specializations for Nocturnality in a Critically Endangered Parrot, the Kakapo (Strigops habroptilus)

    OpenAIRE

    Corfield, Jeremy R.; Gsell, Anna C.; Brunton, Dianne; Heesy, Christopher P.; Hall, Margaret I.; Acosta, Monica L.; Iwaniuk, Andrew N.

    2011-01-01

    The shift from a diurnal to nocturnal lifestyle in vertebrates is generally associated with either enhanced visual sensitivity or a decreased reliance on vision. Within birds, most studies have focused on differences in the visual system across all birds with respect to nocturnality-diurnality. The critically endangered Kakapo (Strigops habroptilus), a parrot endemic to New Zealand, is an example of a species that has evolved a nocturnal lifestyle in an otherwise diurnal lineage, but nothing ...

  1. Melatonin attenuates the sympathetic nerve responses to orthostatic stress in humans.

    Science.gov (United States)

    Ray, Chester A

    2003-09-15

    Previous studies have suggested that melatonin alters sympathetic outflow in humans. The purpose of the present study was to determine in humans the effect of melatonin on sympathetic nerve activity and arterial blood pressure during orthostatic stress. Fifty minutes after receiving a 3 mg tablet of melatonin or placebo (different days), muscle sympathetic nerve activity (MSNA), arterial blood pressure, heart rate, forearm blood flow and thoracic impedance were measured for 10 min at rest and during 5 min of lower body negative pressure (LBNP) at -10 and -40 mmHg (n = 11). During LBNP, MSNA responses were attenuated after melatonin at both -10 and -40 mmHg (P melatonin, respectively. However, arterial blood pressure and forearm vascular resistance responses were unchanged by melatonin during LBNP. MSNA responses were not affected by melatonin during an isometric handgrip test (30% maximum voluntary contraction) and a cold pressor test. Plasma melatonin concentration was measured at 25 min intervals for 125 min in six subjects. Melatonin concentration was 14 +/- 11 pg ml(-1) before ingestion and was significantly increased at each time point (peaking at 75 min; 1830 +/- 848 pg ml(-1)). These findings indicate that in humans, a high concentration of melatonin can attenuate the reflex sympathetic increases that occur in response to orthostatic stress. These alterations appear to be mediated by melatonin-induced changes to the baroreflexes. PMID:12869610

  2. 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...

  3. 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.

  4. 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

  5. LBA-ECO CD-03 Nocturnal Meteorological Data, Forest and Pasture Sites, Para, Brazil

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set contains measurements of nocturnal meteorological profiles collected from tethered balloon platforms during July 2001, October 2001, and November...

  6. LBA-ECO CD-03 Nocturnal Meteorological Data, Forest and Pasture Sites, Para, Brazil

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: This data set contains measurements of nocturnal meteorological profiles collected from tethered balloon platforms during July 2001, October 2001, and...

  7. 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)

  8. 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.

  9. 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.

  10. The role of melatonin in anaesthesia and critical care

    Directory of Open Access Journals (Sweden)

    Madhuri S Kurdi

    2013-01-01

    Full Text Available Melatonin is a neurohormone secreted by the pineal gland. It is widely present in both plant and animal sources. In several countries, it is sold over the counter as tablets and as food supplement or additive. Currently, it is most often used to prevent jet lag and to induce sleep. It has been and is being used in several clinical trials with different therapeutic approaches. It has sedative, analgesic, anti-inflammatory, anti-oxidative and chronobiotic effects. In the present review, the potential therapeutic benefits of melatonin in anaesthesia and critical care are presented. This article aims to review the physiological properties of melatonin and how these could prove useful for several clinical applications in perioperative management, critical care and pain medicine. The topic was handsearched from textbooks and journals and electronically from PubMed, and Google scholar using text words.

  11. 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.

  12. 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

  13. 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

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

    OpenAIRE

    Oner J.; Ozan E.

    2005-01-01

    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 pal...

  15. The inhibition of apoptosis by melatonin in VSC4.1 motoneurons exposed to oxidative stress, glutamate excitotoxicity, or TNF-alpha toxicity involves membrane melatonin receptors.

    Science.gov (United States)

    Das, Arabinda; McDowell, Misty; Pava, Matthew J; Smith, Joshua A; Reiter, Russel J; Woodward, John J; Varma, Abhay K; Ray, Swapan K; Banik, Naren L

    2010-03-01

    Loss of motoneurons may underlie some of the deficits in motor function associated with the central nervous system (CNS) injuries and diseases. We tested whether melatonin, a potent antioxidant and free radical scavenger, would prevent motoneuron apoptosis following exposure to toxins and whether this neuroprotection is mediated by melatonin receptors. Exposure of VSC4.1 motoneurons to either 50 microm H(2)O(2), 25 microm glutamate (LGA), or 50 ng/mL tumor necrosis factor-alpha (TNF-alpha) for 24 h caused significant increases in apoptosis, as determined by Wright staining and ApopTag assay. Analyses of mRNA and proteins showed increased expression and activities of stress kinases and cysteine proteases and loss of mitochondrial membrane potential during apoptosis. These insults also caused increases in intracellular free [Ca(2+)] and activities of calpain and caspases. Cells exposed to stress stimuli for 15 min were then treated with 200 nm melatonin. Post-treatment of cells with melatonin attenuated production of reactive oxygen species (ROS) and phosphorylation of p38, MAPK, and JNK1, prevented cell death, and maintained whole-cell membrane potential, indicating functional neuroprotection. Melatonin receptors (MT1 and MT2) were upregulated following treatment with melatonin. To confirm the involvement of MT1 and MT2 in providing neuroprotection, cells were post-treated (20 min) with 10 microm luzindole (melatonin receptor antagonist). Luzindole significantly attenuated melatonin-induced neuroprotection, suggesting that melatonin worked, at least in part, via its receptors to prevent VSC4.1 motoneuron apoptosis. Results suggest that neuroprotection rendered by melatonin to motoneurons is receptor mediated and melatonin may be an effective neuroprotective agent to attenuate motoneuron death in CNS injuries and diseases. PMID:20082663

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

    Science.gov (United States)

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

    2001-10-01

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

  17. Equatorial sundials as accurate nocturnals and the sidereal equation of time.

    Science.gov (United States)

    di Marzio, F.

    1993-11-01

    A sidereal equation of time is developed which enables equatorial sundials (and armillary spheres) to be employed as accurate nocturnals. An accuracy in the order of one minute can be achieved with such a sundial by simply aligning the gnomon with a bright star from behind the curved dial. This is in contrast to nocturnals which are typically in error by approximately one hour.

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

    OpenAIRE

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

    2009-01-01

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

  19. 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

  20. Oxidative stress and immunosenescence: therapeutic effects of melatonin.

    Science.gov (United States)

    Espino, Javier; Pariente, José A; Rodríguez, Ana B

    2012-01-01

    Age-associated deterioration in the immune system, which is referred to as immunosenescence, contributes to an increased susceptibility to infectious diseases, autoimmunity, and cancer in the elderly. A summary of major changes associated with aging in immune system is described in this paper. In general, immunosenescence is characterized by reduced levels of peripheral naïve T cells derived from thymus and the loss of immature B lineage cells in the bone marrow. As for macrophages and granulocytes, they show functional decline with advancing age as evidenced by their diminished phagocytic activity and impairment of superoxide generation. The indole melatonin is mainly secreted in the pineal gland although it has been also detected in many other tissues. As circulating melatonin decreases with age coinciding with the age-related decline of the immune system, much interest has been focused on melatonin's immunomodulatory effect in recent years. Here, we underlie the antioxidant and immunoenhancing actions displayed by melatonin, thereby providing evidence for the potential application of this indoleamine as a "replacement therapy" to limit or reverse some of the effects of the changes that occur during immunosenescence. PMID:23346283

  1. Melatonin as a hormone in humans: a history.

    OpenAIRE

    Wurtman, R J

    1985-01-01

    This article describes the history of melatonin's transformation, in the perception of the biomedical community, from a skin-lightening agent in amphibians to a hormone in mammals, which may also exert important behavioral--and physiological--effects in humans.

  2. 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.

  3. Melatonin and MT1 membrane receptor in rat intestine.

    Czech Academy of Sciences Publication Activity Database

    Soták, Matúš; Mrnka, Libor; Pácha, Ji?í

    Fyziologický ústav AV ?R, v. v. i.. Ro?. 55, ?. 4 (2006), 42P-42P ISSN 0862-8408. [Physiological Days /82./. 07.02.2006-09.02.2006, Prague] R&D Projects: GA ?R(CZ) GP305/03/D140 Keywords : melatonin * MT1 receptor * intestine Subject RIV: ED - Physiology

  4. 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

  5. Occurence and Possible Functions of Melatonin in Plants.

    Czech Academy of Sciences Publication Activity Database

    Kolá?, Jan; Machá?ková, Ivana

    2001-01-01

    Ro?. 14, 1/2 (2001), s. 75-84. ISSN 0256-1514 R&D Projects: GA ?R GV206/96/K188; GA MŠk LN00A081 Institutional research plan: CEZ:AV0Z5038910 Keywords : melatonin * rhythms * photoperiodism Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.200, year: 2000

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  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. Oxidative stress in paroxysmal nocturnal hemoglobinuria and other conditions of complement-mediated hemolysis.

    Science.gov (United States)

    Fibach, Eitan; Dana, Mutaz

    2015-11-01

    The complement (C') system and redox status play important roles in the physiological functioning of the body, such as the defense system, but they are also involved in various pathological conditions, including hemolytic anemia. Herein, we review the interaction between the C' and the redox systems in C'-mediated hemolytic anemias, paroxysmal nocturnal hemoglobinuria (PNH) and autoimmune hemolytic anemia, including acute hemolytic transfusion reaction. Blood cells in these diseases have been shown to have increased oxidative status, which was further elevated by interaction with activated C'. The results suggest that oxidative stress, in conjunction with activated C', may cause the underlying symptoms of these diseases, such as intra- and extravascular hemolysis and thrombotic complications. Antioxidants ameliorate oxidative stress by preventing generation of free radicals, by scavenging and preventing their accumulation, and by correcting their cellular damage. Antioxidants have been shown to reduce the oxidative stress and inhibit hemolysis as well as platelet activation mediated by activated C'. This raises the possibility that treatment with antioxidants might be considered as a potential therapeutic modality for C'-mediated hemolytic anemias. Currently, eculizumab, a humanized monoclonal antibody that specifically targets the C' protein C5, is the main treatment modality for PNH. However, because antioxidants are well tolerated and relatively inexpensive, they might be considered as potential adjuvants or an alternative therapeutic modality for PNH and other C'-mediated hemolytic anemias. PMID:25937178

  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. Monosymptomatic nocturnal enuresis caused by seasonal temperature changes

    Science.gov (United States)

    Tas, Tuncay; Cakiroglu, Basri; Hazar, Aydin Ismet; Balci, Mustafa Bahadir Can; Sinanoglu, Orhun; Nas, Yunus; Yilmazer, Fazli

    2014-01-01

    Background: Primary nocturnal enuresis is the most frequent urologic complaint among pediatric patients. Enuresis is believed to have a complex etiology involving genetic, somatic, and behavioral factors. We study the relationship between seasonal temperature changes effect and monosymptomatic nocturnal enuresis (MNE). Methods: Between 2011 and 2012, a total of 75 children with primary MNE selected from urology and pediatry clinics were included in this study. All of the children underwent physical examinations, urine analyses, urinary ultrasounds, and direct urinary graphs. We evaluated the enuresis ratio for the summer (the hot season from June to September) and winter (the cold season from December to March) months in nightly, weekly, and monthly intervals via prepared questionnaires. Results: Of the 75 study participants, 45 were boys (60%) and 30 were girls (40%). The age range was 6-16 years (mean 10.3±2.0 years). We observed a difference in the ratio of enuresis data between the summer and winter months in 29 males and 19 females, which totals 48 of the 75 MNE patients evaluated in this study. There was a statistically significant difference noted in monthly enuresis ratio in the summer and winter (p<0.0001). We observed a significant difference in quality of life, and this difference caused considerable emotional discomfort for the patients. Conclusion: In the winter months, the nightly, weekly, and monthly ratios are higher in children with MNE. This increase causes a decrease in the quality of life of these children. PMID:24955178

  12. Hypothyroidism and deficiency of the nocturnal thyrotropin surge in children with hypothalamic-pituitary disorders.

    Science.gov (United States)

    Rose, S R; Manasco, P K; Pearce, S; Nisula, B C

    1990-06-01

    The circadian pattern of serum TSH in normal children, aged 5-18 yr, is characterized by a nocturnal surge and is presumably related in some way to a biological clock within the central nervous system. To look for patients deficient in the nocturnal TSH surge, we studied 52 children with hypothalamic-pituitary disorders. Thirteen of the children were hypothyroid, as judged by subnormal serum free T4 (FT4). The hypothyroid patients had a mean nocturnal TSH surge of 22% (range, -30% to +114%), significantly less than that of normal controls (mean, 124%; 95% confidence limits, 47-300%; n = 96; P less than 0.01). Only 1 of the hypothyroid children had a value for the nocturnal TSH surge (114%) that was within the normal range. Nineteen of the 52 patients with hypothalamic-pituitary disorders had subnormal nocturnal TSH surges; their mean iodothyronine values were significantly less than those of the 33 patients with normal surges [total T4, 73 +/- 4 (mean +/- SE) vs. 109 +/- 3 nmol/L (P less than 0.01); FT4, 13 +/- 1.0 vs. 19 +/- 0.5 pmol/L (P less than 0.01)]. These data demonstrate a clear association of a deficient nocturnal TSH surge and low iodothyronine concentration in children with hypothalamic-pituitary disorders. We performed both TRH tests and nocturnal TSH surge tests in 11 of the children with central hypothyroidism; TRH was abnormal in only 2, while the nocturnal surge test was abnormal in 10 of the 11. We suggest that the nocturnal surge of TSH is important for maintenance of thyroid function and conclude that the nocturnal TSH surge is a much more sensitive test than the TSH response to TRH for the diagnosis of central hypothyroidism. PMID:2112153

  13. 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.

  14. 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.

  15. Reassessing the melatonin pharmacophore--enantiomeric resolution, pharmacological activity, structure analysis, and molecular modeling of a constrained chiral melatonin analogue.

    Science.gov (United States)

    Rivara, Silvia; Diamantini, Giuseppe; Di Giacomo, Barbara; Lamba, Doriano; Gatti, Giuseppe; Lucini, Valeria; Pannacci, Marilou; Mor, Marco; Spadoni, Gilberto; Tarzia, Giorgio

    2006-05-15

    3-(Acetylaminomethyl)-2-(ethoxycarbonyl)-6-methoxy-1,3,4,5-tetrahydrobenzo[cd]indole (2) is a rigid melatonin analogue that as a racemate displays about the same affinity and intrinsic activity of melatonin (1) in in vitro experiments. We report here the resolution of the racemate by preparative medium pressure liquid chromatography (MPLC) and the X-ray determination of the R absolute configuration of the (-)-enantiomer. The two enantiomers were separately tested as MT1 and MT2 ligands, and the (+)-(S)-2 showed a potency comparable to that of melatonin and about three orders of magnitude greater than that of its enantiomer. The information obtained by crystallographic analysis and NMR studies about the conformational preference for 2 and by the pharmacological characterization of (R)-2 and (S)-2 was employed in a molecular modeling study, aimed at reassessing the melatonin receptor pharmacophore model for agonist compounds. Chiral enantioselective agonists reported in the literature were also included in the study. PMID:16431121

  16. 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 figs., 1 tabs

  17. 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.

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

    Science.gov (United States)

    Cai, J.; He, C.; Chen, L.; Han, T.; Huang, S.; Huang, Y.; Bai, Y.; Bao, Y.; Zhang, H.; Ling, F.

    2013-06-01

    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.

  19. Development of nanocapsule suspensions and nanocapsule spray-dried powders containing melatonin

    Directory of Open Access Journals (Sweden)

    Schaffazick Scheila R.

    2006-01-01

    Full Text Available Nanocapsule suspensions containing melatonin were prepared by interfacial deposition method and characterized (size, morphological aspect and encapsulation efficiency. The formulation parameters studied were the oil nature, the type of surfactants and the type of polymer. The melatonin-encapsulation efficiency ranged between 30% and 56% and polymer nature was the parameter that more influenced the characteristics of suspensions. According to the highest encapsulation efficiency, the nanocapsules prepared with Eudragit S100® were selected to be spray-dried in order to improve the physical stability of suspension and to control the release of melatonin. The melatonin-loaded nanocapsule spray-dried powder presented encapsulation efficiency of the 93% and no morphological alterations were observed after 12 months of storage. This system showed a controlled release profile in comparison to the dissolution of the pure melatonin. The release profile was fitted to monoexponential model and the melatonin release mechanism was based on swelling and dissolution of the polymer.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. Effects of melatonin and ethanol on the heart rate of Daphnia magna

    OpenAIRE

    Rebecca Kohn; Larissa Stuckey; Elizabeth Marion; Krithika Krishnarao; Bonnie Kaas

    2009-01-01

    Melatonin, an endogenous hormone that may regulate circadian rhythms by modulating cholinergic activity, is increasing in popular use as a natural treatment for sleep disorders. However, the effects of melatonin on the human heart are not well characterized, and the consequences of combining alcohol with melatonin are unknown. The myogenic heart of the water flea Daphnia magna (D. magna) is regulated by inhibitory cholinergic neurons that modulate cardiac function, including heart rate. D. ma...

  5. Antioxidant Effect of Melatonin on the Functional Activity of Colostral Phagocytes in Diabetic Women

    OpenAIRE

    Morceli, Gliciane; Honorio-França, Adenilda C.; Fagundes, Danny L. G.; Iracema M.P. Calderon; Eduardo L. França

    2013-01-01

    Melatonin is involved in a number of physiological and oxidative processes, including functional regulation in human milk. The present study investigated the mechanisms of action of melatonin and its effects on the functional activity of colostral phagocytes in diabetic women. Colostrum samples were collected from normoglycemic (N?=?38) and diabetic (N?=?38) women. We determined melatonin concentration, superoxide release, bactericidal activity and intracellular Ca2+ release by colostral phag...

  6. Melatonin is protective against 6-hydroxydopamine-induced oxidative stress in a hemiparkinsonian rat model.

    Science.gov (United States)

    Ozsoy, O; Yildirim, F B; Ogut, E; Kaya, Y; Tanriover, G; Parlak, H; Agar, A; Aslan, M

    2015-08-01

    Melatonin is known to reduce detrimental effects of free radicals by stimulating antioxidant enzymes; however, its role has not been studied in 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease (PD). Therefore, we aimed to elucidate the effects of melatonin on motor activity and oxidative stress parameters in 6-OHDA-induced rat model of PD. Three-month-old male Wistar rats were divided into 5 groups: vehicle (V), melatonin-treated (M), 6-OHDA-injected (6-OHDA), 6-OHDA-injected + melatonin-treated (6-OHDA-Mel), and melatonin-treated + 6-OHDA-injected (Mel-6-OHDA) group. Melatonin was administered intraperitoneally at a dose of 10 mg/kg/day for 30 days in M and Mel-6-OHDA groups, for 7 days in 6-OHDA-Mel group. Rats received a unilateral stereotaxic injection of 6-OHDA into the right medial forebrain bundle. The 6-OHDA-Mel group started receiving melatonin when experimental PD was created and the treatment was continued for 7 days. In the Mel-6-OHDA group, experimental PD was created on the 23rd day of melatonin treatment and continued for the remaining 7 days. Locomotor activity decreased in 6-OHDA group compared with that in vehicle group; however, melatonin treatment did not improve this impairment. 6-OHDA injection caused an obvious reduction in tyrosine-hydroxylase-positive dopaminergic neuron viability as determined by immunohistochemistry. Melatonin supplementation decreased dopaminergic neuron death in 6-OHDA-Mel and Mel-6-OHDA groups compared with that in 6-OHDA group. Biochemical analysis confirmed the beneficial effects of melatonin displaying higher superoxide dismutase, catalase, and glutathione peroxidase activities and lower lipid peroxidation in substantia nigra samples in comparison to non-treated 6-OHDA group. Starting melatonin treatment before creating experimental PD was more effective on observed changes. PMID:25791066

  7. Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery

    DEFF Research Database (Denmark)

    Hansen, Melissa V; Andersen, Lærke T; Madsen, Michael T; Hageman, Ida; Rasmussen, Lars S; Bokmand, Susanne; Rosenberg, Jacob; Gögenür, Ismayil

    2014-01-01

    Depression, anxiety and sleep disturbances are known problems in patients with breast cancer. The effect of melatonin as an antidepressant in humans with cancer has not been investigated. We investigated whether melatonin could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery and assessed the effect of melatonin on subjective parameters: anxiety, sleep, general well-being, fatigue, pain and sleepiness. Randomized, double-blind, placebo-contr...

  8. Reduction of Melatonin Level in Patients with Type II Diabetes and Periodontal Diseases

    OpenAIRE

    Abdolsamadi, Hamidreza; Goodarzi, Mohammad Taghi; Ahmadi Motemayel, Fatemeh; Jazaeri, Mina; Feradmal, Javad; Zarabadi, Mahdiyeh; Hoseyni, Mostafa; Torkzaban, Parviz

    2014-01-01

    Background and aims. Melatonin is a circulating hormone that is mainly released from the pineal gland. It possesses antioxidant, free-radical scavenging, and immune-enhancing properties. A growing number of studies reveal a complex role for melatonin in influencing various diseases, including diabetes and periodontal diseases. The aim of this study was to examine the possible links between salivary melatonin levels and type II diabetes and periodontal diseases.

  9. MILK WITH INCREASED CONCENTRATION OF MELATONIN PACKAGING FACTORS ON CONSUMER PURCHASE INTENTION

    OpenAIRE

    Maria Patricia Milagres; Valéria Paula Rodrigues Minim; Andréa Alves Simiqueli; Ana Cristina Rocha Espeschit; Luis Antonio Minim

    2014-01-01

    The conjoint analysis of factors was used employed to develop a label for the packaging of milk with increased concentration of melatonin. Three factors were selected with three or two levels for the assembly of packaging: packaging design (“blue design with stars and pouring milk”, “white without drawing” and “blue stars with and without drawing”), name (“milk night “and” melatonin “) and informative text about getting natural melatonin by night milking, and the benefits of this compound (“w...

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

    DEFF Research Database (Denmark)

    Kucukakin, B.; Klein, M.; Lykkesfeldt, Jens; Reiter, R.J.; Rosenberg, J.; Gögenür, Ismayil

    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 pr...

  11. 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...

  12. 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...

  13. 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 possib...

  14. Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism.

    Science.gov (United States)

    Tan, Dun-Xian; Manchester, Lucien C; Esteban-Zubero, Eduardo; Zhou, Zhou; Reiter, Russel J

    2015-01-01

    Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin's synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress. PMID:26501252

  15. 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...

  16. Melatonin Supplementation During In Vitro Maturation and Development Supports the Development of Porcine Embryos.

    Science.gov (United States)

    Do, Ltk; Shibata, Y; Taniguchi, M; Nii, M; Nguyen, T V; Tanihara, F; Takagi, M; Otoi, T

    2015-12-01

    Melatonin has been reported to improve the in vitro development of embryos in some species. This study was conducted to investigate the effect of melatonin supplementation during in vitro maturation (IVM) and development culture on the development and quality of porcine embryos. In the first experiment, when the in vitro fertilized embryos were cultured with different concentrations of melatonin (0, 10, 25 and 50 ng/ml) for 8 days, the blastocyst formation rate of embryos cultured with 25 ng/ml melatonin (10.7%) was significantly increased (p IVM and development has beneficial effects on the developmental competence and quality of porcine embryos. PMID:26392209

  17. Melatonin can suppress the cytotoxic effects of chlorpyrifos on human hepG2 cell lines.

    Science.gov (United States)

    Gultekin, F; Patat, S; Akca, H; Akdogan, M; Altuntas, I

    2006-02-01

    The cytotoxic effect of chlorpyrifos (CP) on human HepG2 cell lines and the protective role of melatonin were investigated. TD50 of CP for HepGZ cells was also determined. The viability of HepGZ cells decreased with CP treatment in a dose-dependent manner (P <0.05). Preincubation with melatonin prior to CP application caused an increase in cell viability (P <0.05). TD50 of CP for HepG2 was determined as 84.5 microg/mL. A 1-hour melatonin treatment caused a decrease in TD50 from 84.5 to 34.1 microg/mL. The level of thiobarbituric acid reactive substance (TBARS) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined in cell lines with or without melatonin administration to find out the possible mechanism of melatonin. CP caused a significant decrease in SOD, GSH-Px and CAT activities and an increase in TBARS level (P <0.05). Pre-incubation of cells with melatonin prevented an increase in TBARS. Melatonin also reduced the CP-caused inhibition of the activities of GSH-Px and CAT (P <0.05). It was suggested that CP shows a cytotoxic effect on HepG2 cell lines and melatonin can suppress cytotoxicity caused by CP with its antioxidant properties. Melatonin also reduces TD50 of CP for HepG2 cell lines. PMID:16539209

  18. RGS2 is a feedback inhibitor of melatonin production in the pineal gland

    Science.gov (United States)

    Matsuo, Masahiro; Coon, Steven L.; Klein, David C.

    2014-01-01

    The 24-h rhythmic production of melatonin by the pineal gland is essential for coordinating circadian physiology. Melatonin production increases at night in response to the release of norepinephrine from sympathetic nerve processes which innervate the pineal gland. This signal is transduced through G-protein-coupled adrenergic receptors. Here, we found that the abundance of regulator of G-protein signaling 2 (RGS2) increases at night, that expression is increased by norepinephrine and that this protein has a negative feedback effect on melatonin production. These data are consistent with the conclusion that RGS2 functions on a daily basis to negatively modulate melatonin production. PMID:23523917

  19. Melatonin enhances plant growth and abiotic stress tolerance in soybean plants.

    Science.gov (United States)

    Wei, Wei; Li, Qing-Tian; Chu, Ya-Nan; Reiter, Russel J; Yu, Xiao-Min; Zhu, Dan-Hua; Zhang, Wan-Ke; Ma, Biao; Lin, Qing; Zhang, Jin-Song; Chen, Shou-Yi

    2015-02-01

    Melatonin is a well-known agent that plays multiple roles in animals. Its possible function in plants is less clear. In the present study, we tested the effect of melatonin (N-acetyl-5-methoxytryptamine) on soybean growth and development. Coating seeds with melatonin significantly promoted soybean growth as judged from leaf size and plant height. This enhancement was also observed in soybean production and their fatty acid content. Melatonin increased pod number and seed number, but not 100-seed weight. Melatonin also improved soybean tolerance to salt and drought stresses. Transcriptome analysis revealed that salt stress inhibited expressions of genes related to binding, oxidoreductase activity/process, and secondary metabolic processes. Melatonin up-regulated expressions of the genes inhibited by salt stress, and hence alleviated the inhibitory effects of salt stress on gene expressions. Further detailed analysis of the affected pathways documents that melatonin probably achieved its promotional roles in soybean through enhancement of genes involved in cell division, photosynthesis, carbohydrate metabolism, fatty acid biosynthesis, and ascorbate metabolism. Our results demonstrate that melatonin has significant potential for improvement of soybean growth and seed production. Further study should uncover more about the molecular mechanisms of melatonin's function in soybeans and other crops. PMID:25297548

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

    Data.gov (United States)

    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,...

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

    Science.gov (United States)

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

    2012-01-01

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

  2. Melatonin protects mast cells against cytotoxicity mediated by chemical stimuli PMACI: possible clinical use.

    Science.gov (United States)

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

    2013-09-15

    Melatonin has documented cytoprotective effects on a wide variety of immune cells. The mechanism of action on mast cells (RBL-2H3) still remains in the dark. We found that melatonin significantly attenuated phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-induced cytotoxicity in a concentration and time-dependent manner. It appears that the effect of melatonin on mast cells is two-fold: dependent (MT1 and MT2) and independent membrane receptors. In conclusion, melatonin treatment reduced the cytotoxicity, mediated by PMACI, and could provide a useful therapeutic option in processes where an excessive activation of mast cells occurs. PMID:23870536

  3. 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.

  4. Melatonin alleviates jet lag symptoms caused by an 11-hour eastward flight.

    Science.gov (United States)

    Takahashi, Toshiharu; Sasaki, Mitsuo; Itoh, Hiroshi; Yamadera, Wataru; Ozone, Motohiro; Obuchi, Keita; Hayashida, Ken-Ichi; Matsunaga, Naoki; Sano, Hidetaka

    2002-06-01

    The effect of 3 mg of melatonin on the rate of re-entrainment of plasma melatonin rhythm after an 11-h eastward flight was assessed. Eight subjects participated in the study, and underwent 24-h blood samplings once before the flight and twice after the flight. Subjects were exposed to natural zeitgeber outdoors and took 3 mg of malatonin at 20:00 h local time on the days when no blood sampling was done. Antidromic re-entrainment was dominant whereby melatonin administration in the evening promoted re-entrainment. Melatonin accelerated the rate of re-entrainment by 15 min per day and alleviated the jet lag symptoms. PMID:12047605

  5. 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.

  6. 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...

  7. 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...

  8. 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

  9. Can Fasting Glucose Levels or Post-Breakfast Glucose Fluctuations Predict the Occurrence of Nocturnal Asymptomatic Hypoglycemia in Type 1 Diabetic Patients Receiving Basal-Bolus Insulin Therapy with Long-Acting Insulin?

    Science.gov (United States)

    Mitsuishi, Sumie; Nishimura, Rimei; Ando, Kiyotaka; Tsujino, Daisuke; Utsunomiya, Kazunori

    2015-01-01

    Objective To investigate whether the occurrence of nocturnal asymptomatic hypoglycemia may be predicted based on fasting glucose levels and post-breakfast glucose fluctuations. Patients and Methods The study subjects comprised type 1 diabetic patients who underwent CGM assessments and received basal-bolus insulin therapy with long-acting insulin. The subjects were evaluated for I) fasting glucose levels and II) the range of post-breakfast glucose elevation (from fasting glucose levels to postprandial 1- and 2-hour glucose levels). The patients were divided into those with asymptomatic hypoglycemia during nighttime and those without for comparison. Optimal cut-off values were also determined for relevant parameters that could predict nighttime hypoglycemia by using ROC analysis. Results 64 patients (mean HbA1c 8.7 ± 1.8%) were available for analysis. Nocturnal asymptomatic hypoglycemia occurred in 23 patients (35.9%). Fasting glucose levels (I) were significantly lower in those with hypoglycemia than those without (118 ± 35 mg/dL vs. 179 ± 65 mg/dL; P 54 mg/dL (0.65/0.61/0.71, P = 0.006), 2-h postprandial elevation > 78 mg/dL (0.65/0.73/0.71, P = 0.005). Conclusions Nocturnal asymptomatic hypoglycemia was associated with increases in post-breakfast glucose levels in type 1 diabetes. Study findings also suggest that fasting glucose levels and the range of post-breakfast glucose elevation could help predict the occurrence of nocturnal asymptomatic hypoglycemia. PMID:26625003

  10. 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

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

    Directory of Open Access Journals (Sweden)

    Bagher Minaii

    2014-07-01

    Full Text Available 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.

  12. 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

  13. Nocturnal activity positively correlated with auditory sensitivity in noctuoid moths.

    Science.gov (United States)

    ter Hofstede, Hannah M; Ratcliffe, John M; Fullard, James H

    2008-06-23

    We investigated the relationship between predator detection threshold and antipredator behaviour in noctuoid moths. Moths with ears sensitive to the echolocation calls of insectivorous bats use avoidance manoeuvres in flight to evade these predators. Earless moths generally fly less than eared species as a primary defence against predation by bats. For eared moths, however, there is interspecific variation in auditory sensitivity. At the species level, and when controlling for shared evolutionary history, nocturnal flight time and auditory sensitivity were positively correlated in moths, a relationship that most likely reflects selection pressure from aerial-hawking bats. We suggest that species-specific differences in the detection of predator cues are important but often overlooked factors in the evolution and maintenance of antipredator behaviour. PMID:18319206

  14. Pathophysiology, diagnosis, and treatment of paroxysmal nocturnal hemoglobinuria: a review.

    Science.gov (United States)

    Devalet, Bérangère; Mullier, François; Chatelain, Bernard; Dogné, Jean-Michel; Chatelain, Christian

    2015-09-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder of the hematopoietic stem cell that makes blood cells more sensitive to the action of complement. Patients experience intravascular hemolysis, smooth muscle dystonia, renal failure, arterial and pulmonary hypertension, recurrent infectious diseases and an increased risk of notably dreadful thrombotic complications. The diagnosis is made by flow cytometry. Efforts have been recently performed to improve the sensitivity and the standardization of this technique. PNH is frequently associated with aplastic anemia or low-risk myelodysplasia and may be asymptomatic. Management of the classical form of PNH has been dramatically revolutionized by the development of eculizumab, which brings benefits in terms of hemolysis, quality of life, renal function, thrombotic risk, and life expectancy. Prophylaxis and treatment of arterial and venous thrombosis currently remain a challenge in PNH. PMID:25753400

  15. Differential approach to treatment of primary nocturnal enuresis in children

    Directory of Open Access Journals (Sweden)

    Nesterenko O.V.

    2011-09-01

    Full Text Available The aim of the work is to develop an algorithm of differentiated therapy in children with PNE. 234 children aged 5-15 years were studied. Results of treatment of children with primary nocturnal enuresis using the traditional therapeutic scheme and the algorithm of differential therapy based on identification of individual pathology were analyzed. The best clinical effect (recovery— in 73,1%, improvement— in 19,4% of cases was obtained in children undergone the complex of recommended measures: psychological consultation, rational and family psychotherapy, medication correction, physical and physiotherapy, alarm-monitoring; the complex was used differentially, i.e. depending on the identified pathology. In conclusion the article stated that individual treatment program with the obligatory inclusion of alarm-control for child with PNE should be selected after performing the recommended set of diagnostic measures

  16. Decomposition of Spatial Structure of Nocturnal Flow over Gentle Terrain

    Science.gov (United States)

    Geiss, Andrew; Mahrt, Larry

    2015-09-01

    A network of sonic anemometers was deployed over gentle terrain in north-eastern Colorado, USA to observe and characterize local nocturnal circulations. Our study focuses on a small valley about 270 m wide and 12 m deep with a down-valley slope of 2-3 %. The measurements include 19 stations with sonic anemometers at 1 m and a 20-m tower that includes six sonic anemometers in the lowest 5 m. Shallow cold pools and drainage down the valley develop for weak ambient flow and relatively clear skies. However, transient modes constantly modulate or intermittently eliminate the cold pool, which makes extraction and analysis of the horizontal structure of the cold pool difficult with traditional analysis methods. Singular value decomposition successfully isolates the effects of large-scale flow from local down-valley cold-air drainage within the cold pool in spite of the intermittent nature of this local flow. Shortcomings of the method are noted.

  17. 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

  18. 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 recep...

  19. Identification of Pathway-Biased and Deleterious Melatonin Receptor Mutants in Autism Spectrum Disorders and in the General Population

    OpenAIRE

    Chaste, Pauline; Clement, Nathalie; Mercati, Oriane; Guillaume, Jean-Luc; Delorme, Richard; Botros, Hany Goubran; Pagan, Cécile; Périvier, Samuel; Scheid, Isabelle; Nygren, Gudrun; Anckarsäter, Henrik; Rastam, Maria; Ståhlberg, Ola; Gillberg, Carina; Serrano, Emilie

    2010-01-01

    Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of the melatonin pathway has been reported in circadian disorders, diabetes and autism spectrum disorders (ASD). However, very little is known about the genetic variability of melatonin receptors in humans. Here, we sequenced the melatonin receptor MTNR1A and MTNR1B, genes coding for MT1 and MT2 receptors, respectively, in a large panel of 941 individuals including 295 patients with ASD, 362 con...

  20. Nocturnal thyrotropin surge in growth hormone-deficient children.

    Science.gov (United States)

    Municchi, G; Malozowski, S; Nisula, B C; Cristiano, A; Rose, S R

    1992-08-01

    Because some patients with growth hormone (GH) deficiency are found to be hypothyroid after initiation of treatment with GH, we assessed the predictive value of the nocturnal thyrotropin surge (a sensitive test for central hypothyroidism) in 56 untreated GH-deficient children and adolescents. Eighteen patients had a subnormal thyrotropin surge (mean 18% (range -30% to 46%)), significantly less than that of 96 normal control subjects (mean 124%; 95% confidence limits, 47% to 300%; p less than 0.01); 13 of the 18 had a subnormal total thyroxine (T4) level or a subnormal free T4 level, or both. These 18 patients were given thyroid hormone replacement therapy; GH deficiency was confirmed during treatment with thyroxine. Of the remaining 38 patients, who had no initial evidence of dysfunction of the hypothalamic-pituitary-thyroid axis, 23 were re-examined while they were receiving GH treatment. Hypothyroidism developed in none of those 23 children during GH therapy. The nocturnal thyrotropin surge test and determination of iodothyronine levels were repeated in 14 of these euthyroid patients. There was no significant change in mean thyrotropin surge (129% (range +49% to +300) vs 125% (range +51% to +222%)), mean serum level of total T4 (111 +/- 4 vs 103 +/- 3 nmol/L), mean serum level of free T4 (19 +/- 0.7 vs 18 +/- 0.8 pmol/L), mean serum level of triiodothyronine (2.5 +/- 0.1 vs 2.5 +/- 0.1 nmol/L), or mean serum level of thyrotropin (2.9 +/- 0.3 vs 2.9 +/- 0.5 mU/L (mean +/- SEM)). We conclude that GH treatment does not appreciably alter thyroid function in GH-deficient patients who have no evidence of thyroid axis dysfunction before GH treatment. PMID:1640286

  1. Niche convergence suggests functionality of the nocturnal fovea

    Directory of Open Access Journals (Sweden)

    Gillian L. Moritz

    2014-07-01

    Full Text Available 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 prevailing view that the fovea is a functional adaptation to diurnal color vision. The foveae of nocturnal taxa, such as tarsiers, are widely interpreted as vestigial traits and therefore evidence of a diurnal ancestry. This enduring premise has been central to adaptive hypotheses on the origins of anthropoid primates; however, the question of whether the fovea of tarsiers is a functionless anachronism or a nocturnal adaptation remains open. To address this question, we focused on the diets of tarsiers (Tarsius and scops owls (Otus, two taxa united by numerous anatomical homoplasies, including foveate vision. A functional interpretation of these homoplasies predicts dietary convergence and competition. This prediction can be tested with an analysis of carbon and nitrogen stable isotopes in tissues, which integrate dietary information. As predicted, the isotopic niches of Tarsius and Otus overlapped. In both Borneo and the Philippines, the ?13C values were indistinguishable, whereas the ?15N values of Otus were marginally higher than those of Tarsius. Our results indicate that both diets consisted mainly of ground-dwelling prey and raise the possibility of some resource partitioning. Taken together, our isotopic analysis supports 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.

  2. Simvastatin-induced nocturnal leg pain disappears with pravastatin substitution

    Directory of Open Access Journals (Sweden)

    Stojakovi? Nataša

    2013-01-01

    Full Text Available Introduction. Statins have similar side effects that do not always occur at the same rate among the various statins. We present a case of simvastatin-induced muscle toxicity that disappeared when pravastatin was substituted for the original drug. Case Outline. A 74-year-old male, a nonsmoker, complained of severe nocturnal leg cramps. The patient also complained that similar painful cramping occurred when he walked rapidly or jogged. Because some components of his lipid panel exceeded the ‘desirable’ range, and as he had a history of myocardial infarction, his family physician prescribed simvastatin (40 mg/day. The patient had taken this medication for the past eight years. The painful nocturnal episodes started two years ago and affected either one or the other leg. Four months ago we discontinued his simvastatin and prescribed pravastatin (80 mg/day. At a follow-up visit six weeks later, the patient reported that his leg pains at night and the pain experienced after brisk walking had disappeared. Four months after the substitution of pravastatin for simvastatin, the patient reported that his complete lack of symptoms had continued. Conclusion. These painful muscle cramps were probably caused by an inadequate vascular supply to the calf and foot muscles. Perhaps a combination of advanced age and atherosclerotic changes created a predisposition for the simvastatin-induced leg cramps. Pravastatin differs from simvastatin in several ways. It is not metabolized by cytochrome P450 (CYP 3A4 oxidases, and thus is not influenced by CYP 3A4 inhibitors like simvastatin. Also, simvastatin is associated with single-nucleotide polymorphisms located within the SLCO1B1 gene on the chromosome 12 and established myopathy, while pravastatin lacks this association. These differences may contribute to increased tolerance to pravastatin in this particular case.

  3. 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.

  4. Alleviation of cold damage to photosystem II and metabolisms by melatonin in Bermudagrass

    Science.gov (United States)

    Fan, Jibiao; Hu, Zhengrong; Xie, Yan; Chan, Zhulong; Chen, Ke; Amombo, Erick; Chen, Liang; Fu, Jinmin

    2015-01-01

    As a typical warm-season grass, Bermudagrass [Cynodon dactylon (L).Pers.] is widely applied in turf systems and animal husbandry. However, cold temperature is a key factor limiting resource utilization for Bermudagrass. Therefore, it is relevant to study the mechanisms by which Burmudagrass responds to cold. Melatonin is a crucial animal and plant hormone that is responsible for plant abiotic stress responses. The objective of this study was to investigate the role of melatonin in cold stress response of Bermudagrass. Wild Bermudagrass pre-treated with 100 ?M melatonin was subjected to different cold stress treatments (?5°C for 8 h with or without cold acclimation). The results showed lower malondialdehyde (MDA) and electrolyte leakage (EL) values, higher levels of chlorophyll, and greater superoxide dismutase and peroxidase activities after melatonin treatment than those in non-melatonin treatment under cold stress. Analysis of chlorophyll a revealed that the chlorophyll fluorescence transient (OJIP) curves were higher after treatment with melatonin than that of non-melatonin treated plants under cold stress. The values of photosynthetic fluorescence parameters increased after treatment with melatonin under cold stress. The analysis of metabolism showed alterations in 46 metabolites in cold-stressed plants after melatonin treatment. Among the measured metabolites, five sugars (arabinose, mannose, glucopyranose, maltose, and turanose) and one organic acid (propanoic acid) were significantly increased. However, valine and threonic acid contents were reduced in melatonin-treated plants. In summary, melatonin maintained cell membrane stability, increased antioxidant enzymes activities, improved the process of photosystem II, and induced alterations in Bermudagrass metabolism under cold stress. PMID:26579171

  5. Homology Models of Melatonin Receptors: Challenges and Recent Advances

    Directory of Open Access Journals (Sweden)

    Silvia Rivara

    2013-04-01

    Full Text Available Melatonin exerts many of its actions through the activation of two G protein-coupled receptors (GPCRs, named MT1 and MT2. So far, a number of different MT1 and MT2 receptor homology models, built either from the prototypic structure of rhodopsin or from recently solved X-ray structures of druggable GPCRs, have been proposed. These receptor models differ in the binding modes hypothesized for melatonin and melatonergic ligands, with distinct patterns of ligand-receptor interactions and putative bioactive conformations of ligands. The receptor models will be described, and they will be discussed in light of the available information from mutagenesis experiments and ligand-based pharmacophore models. The ability of these ligand-receptor complexes to rationalize structure-activity relationships of known series of melatonergic compounds will be commented upon.

  6. Homology models of melatonin receptors: challenges and recent advances.

    Science.gov (United States)

    Pala, Daniele; Lodola, Alessio; Bedini, Annalida; Spadoni, Gilberto; Rivara, Silvia

    2013-01-01

    Melatonin exerts many of its actions through the activation of two G protein-coupled receptors (GPCRs), named MT1 and MT2. So far, a number of different MT1 and MT2 receptor homology models, built either from the prototypic structure of rhodopsin or from recently solved X-ray structures of druggable GPCRs, have been proposed. These receptor models differ in the binding modes hypothesized for melatonin and melatonergic ligands, with distinct patterns of ligand-receptor interactions and putative bioactive conformations of ligands. The receptor models will be described, and they will be discussed in light of the available information from mutagenesis experiments and ligand-based pharmacophore models. The ability of these ligand-receptor complexes to rationalize structure-activity relationships of known series of melatonergic compounds will be commented upon. PMID:23584026

  7. 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.

  8. The reno-pineal axis: A novel role for melatonin

    Science.gov (United States)

    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. PMID:22470854

  9. Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

    OpenAIRE

    Bonmati-Carrion, Maria Angeles; Arguelles-Prieto, Raquel; Martinez-Madrid, Maria Jose; Reiter, Russel; Hardeland, Ruediger; Rol, Maria Angeles; Madrid, Juan Antonio

    2014-01-01

    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 ...

  10. The reno-pineal axis: A novel role for melatonin

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2012-01-01

    Full Text Available 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.

  11. Antinociceptive properties of selective MT2 melatonin receptor partial agonists.

    Science.gov (United States)

    López-Canul, Martha; Comai, Stefano; Domínguez-López, Sergio; Granados-Soto, Vinicio; Gobbi, Gabriella

    2015-10-01

    Melatonin is a neurohormone involved in the regulation of both acute and chronic pain whose mechanism is still not completely understood. We have recently demonstrated that selective MT2 melatonin receptor partial agonists have antiallodynic properties in animal models of chronic neuropathic pain by modulating ON/OFF cells of the descending antinociceptive system. Here, we examined the antinociceptive properties of the selective MT2 melatonin receptor partial agonists N-{2-[(3-methoxyphenyl)phenylamino]ethyl}acetamide (UCM765) and N-{2-[(3-bromophenyl)-(4-fluorophenyl)amino]ethyl}acetamide (UCM924) in two animal models of acute and inflammatory pain: the hot-plate and formalin tests. UCM765 and UCM924 (5-40mg/kg, s.c.) dose-dependently increased the temperature of the first hind paw lick in the hot-plate test, and decreased the total time spent licking the injected hind paw in the formalin test. Antinociceptive effects of UCM765 and UCM924 were maximal at the dose of 20mg/kg. At this dose, the effects of UCM765 and UCM924 were similar to those produced by 200mg/kg acetaminophen in the hot-plate test, and by 3mg/kg ketorolac or 150mg/kg MLT in the formalin test. Notably, antinociceptive effects of the two MT2 partial agonists were blocked by the pre-treatment with the MT2 antagonist 4-phenyl-2-propionamidotetralin (4P-PDOT, 10mg/kg) in both paradigms. These results demonstrate the antinociceptive properties of UCM765 and UCM924 in acute and inflammatory pain models and corroborate the concept that MT2 melatonin receptor may be a novel target for analgesic drug development. PMID:26162699

  12. Subjective pseudocyesis (false pregnancy) and elevated temporal lobe signs: an implication.

    Science.gov (United States)

    Persinger, M A

    1991-04-01

    Twenty-two percent of 106 undergraduate university women reported symptoms of pseudocyesis: cessation of menstruation, abdominal enlargement, morning sickness, and breast changes. These women also displayed significant elevations in temporal lobe signs with particular involvement of putative right hemispheric processes. Women prone to pseudocyesis displayed more memory blanks, nocturnal akinesia, awareness of abdominal sensations, and exotic beliefs such as alien intelligence; the phenomenon was 10 times more frequent in Roman Catholic women than in Protestant women. PMID:1852557

  13. Melatonin agonists for treatment of sleep and depressive disorders

    Directory of Open Access Journals (Sweden)

    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

  14. Effects of acute ethanol administration on nocturnal pineal serotonin N-acetyltransferase activity

    International Nuclear Information System (INIS)

    The effect of acute ethanol administration on pineal serotonin N-acetyltransferase (NAT) activity, norepinephrine and indoleamine content was examined in male rats. When ethanol was administered in two equal doses (2 g/kg body weight) over a 4 hour period during the light phase, the nocturnal rise in NAT activity was delayed by seven hours. The nocturnal pineal norepinephrine content was not altered by ethanol except for a delay in the reduction of NE with the onset of the following light phase. Although ethanol treatment led to a significant reduction in nocturnal levels of pineal serotonin content, there was no significant effect upon pineal content of 5-hydroxyindoleacetic acid (5-HIAA). The data indicate that ethanol delays the onset of the rise of nocturnal pineal NAT activity

  15. Effects of acute ethanol administration on nocturnal pineal serotonin N-acetyltransferase activity

    Energy Technology Data Exchange (ETDEWEB)

    Creighton, J.A.; Rudeen, P.K.

    1988-01-01

    The effect of acute ethanol administration on pineal serotonin N-acetyltransferase (NAT) activity, norepinephrine and indoleamine content was examined in male rats. When ethanol was administered in two equal doses (2 g/kg body weight) over a 4 hour period during the light phase, the nocturnal rise in NAT activity was delayed by seven hours. The nocturnal pineal norepinephrine content was not altered by ethanol except for a delay in the reduction of NE with the onset of the following light phase. Although ethanol treatment led to a significant reduction in nocturnal levels of pineal serotonin content, there was no significant effect upon pineal content of 5-hydroxyindoleacetic acid (5-HIAA). The data indicate that ethanol delays the onset of the rise of nocturnal pineal NAT activity.

  16. [Factorial analysis of correspondence of the social representations about nurse nocturnal work].

    Science.gov (United States)

    Veiga, Kátia Conceição Guimarães; Fernandes, Josicelia Dumet; Paiva, Mirian Santos

    2013-01-01

    The study aimed to apprehend the Social Representations of nurses on nocturnal work. It was based on the Theory of Social Representations with qualitative and quantitative approaches. The free evocations of 25 nurses in a public hospital in Salvador-Bahia were collected, that underwent the Factorial Analysis of Correspondence (FAC). The FAC revealed on the opposition game demonstrated, in Factor 1, opposition between shifts service and, in Factor 2, age x length of service. Seized on the semantic universe of nurses the nocturnal work is a Responsibility Work, Hard Work, Initiative Work and Financial Need. The nurses refer to the nocturnal work through representations that give normative character, prescribing attitudes and behaviors socially constructed and accepted as from the category itself, emphasizing the historical development of the profession. Those results indicate the need for strategies that contribute to the development of policies for managing people, considering the specificity, subjectivity and complexity of nocturnal work. PMID:23681374

  17. Antioxidative effects of melatonin administration in elderly primary essential hypertension patients.

    Science.gov (United States)

    Kedziora-Kornatowska, Kornelia; Szewczyk-Golec, Karolina; Czuczejko, Jolanta; Pawluk, Hanna; van Marke de Lumen, Katarzyna; Kozakiewicz, Mariusz; Bartosz, Grzegorz; Kedziora, Józef

    2008-10-01

    The imbalance of the redox state of the aging organism may be involved in the development of primary essential hypertension. Melatonin, a potent antioxidant agent, was found to exert a hypotensive effect and improve the function of the cardiovascular system. The aim of this study was to determine the influence of melatonin supplementation on oxidative stress parameters in elderly primary essential hypertensive (EH) patients, controlled by a diuretic (indapamide) monotherapy. The levels of malondialdehyde (MDA) and reduced glutathione (GSH), activities of Cu-Zn superoxide dismutase (SOD-1), catalase (CAT) and glutathione peroxidase (GSH-Px) in erythrocytes, the plasma level of nitrate/nitrite, the content of carbonyl groups of plasma proteins and morning melatonin levels in the serum of 17 elderly EH patients were determined at the baseline and after the 15th and 30th days of melatonin supplementation (5 mg daily). Melatonin administration resulted in a significant increase in the morning melatonin concentration, SOD-1 and CAT activities, and a reduction in the MDA level. Statistically significant alterations in the levels of GSH, nitrate/nitrite and carbonyl groups and the activity of GSH-Px were not observed. These results indicate an improvement in the antioxidative defense of the organism by melatonin supplementation in the examined group and may suggest melatonin supplementation as an additional treatment supporting hypotensive therapy in elderly EH patients. PMID:18363674

  18. 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

  19. Effects of melatonin and ethanol on the heart rate of Daphnia magna

    Directory of Open Access Journals (Sweden)

    Rebecca Kohn

    2009-01-01

    Full Text Available Melatonin, an endogenous hormone that may regulate circadian rhythms by modulating cholinergic activity, is increasing in popular use as a natural treatment for sleep disorders. However, the effects of melatonin on the human heart are not well characterized, and the consequences of combining alcohol with melatonin are unknown. The myogenic heart of the water flea Daphnia magna (D. magna is regulated by inhibitory cholinergic neurons that modulate cardiac function, including heart rate. D. magna is a useful model organism for cardiovascular function, due to its physical transparency and susceptibility to cardioactive drugs known to affect the human heart. In this study, the effects of immersion in 10 mg/L melatonin and 5% ethanol on the heart rate of D. magna were quantified. Two-hour exposure to melatonin caused a significant decrease in heart rate, from 228 ± 2 bpm to 167 ± 8 bpm. Six-minute immersion in ethanol also significantly depressed the heart rate to 176 ± 10 bpm. Pretreatment with melatonin prior to the addition of ethanol resulted in a greater decrease in heart rate (89 ± 7 bpm than ethanol or melatonin alone. These findings indicate that melatonin and alcohol may combine to cause a greater depressive effect on cardiac function.

  20. Experimental scoliosis in melatonin-deficient C57BL/6J mice without pinealectomy.

    Science.gov (United States)

    Machida, Masafumi; Dubousset, Jean; Yamada, Thoru; Kimura, Jun; Saito, Masashi; Shiraishi, Tateru; Yamagishi, Masaaki

    2006-08-01

    The etiology of idiopathic scoliosis is unknown. Scoliosis with many characteristics closely resembling those seen in idiopathic scoliosis has been produced in young chickens and bipedal rats after pinealectomy. In this study, we induced experimental scoliosis in C57BL/6J mice without pinealectomy and melatonin treatment suppressed the development of scoliosis. A total of 100 mice were divided into four groups: 20 quadrupedal mice served as controls; 30 mice underwent resection of two forelegs and tail at 3 wk of age (bipedal mice); the remaining 20 quadrupedal and 30 bipedal mice received intraperitoneal melatonin (8 mg/kg BW) at 19:00 hr daily. Before killing, blood samples were collected in the middle of dark cycle and melatonin levels were measured by radioimmunoassay. Spine X-ray and helical 3D-CT were examined after killing at 5 months of age. The bipedal mice without a tail were able to walk with standing posture, whereas the quadrupedal mice did not walk with standing posture. In C57BL/6J mice, the serum melatonin was reduced to nearly zero; however, the normal level was restored in both bipedal and quadrupedal mice after the injection of melatonin. Scoliosis with rib humps developed in 29 of 30 bipedal and in five quadrupedal mice. None of mice with melatonin treatment developed scoliosis. The results suggest that melatonin deficiency in bipedal mice appears to play crucial role for development of scoliosis. Also the restoration of melatonin levels prevents the development of scoliosis. PMID:16842534

  1. 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…

  2. Melatonin as a modulator of the gastrointestinal function of the rat.

    Czech Academy of Sciences Publication Activity Database

    Mrnka, Libor; Soták, Matúš; Pácha, Ji?í

    2005-01-01

    Ro?. 61, ?. 4 (2005), s. 602-602. ISSN 1138-7548. [European Intestinal Transport Group Meeting /20./. 24.09.2005-27.09.2005, Oléron] R&D Projects: GA ?R(CZ) GP305/03/D140 Keywords : melatonin * gastrointestinal tract * short-circuit current * melatonin receptor Subject RIV: ED - Physiology

  3. 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...

  4. 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.

  5. Effect of mobile usage on serum melatonin levels among medical students.

    Science.gov (United States)

    Shrivastava, Abha; Saxena, Yogesh

    2014-01-01

    Exposure to extremely low frequency (ELF) electromagnetic radiations from mobile phones may affect the circadian rhythm of melatonin in mobile users. The study was designed with objective to evaluate the influence of mobile phone on circadian rhythm of melatonin and to find the association if any between the hours of mobile usage with serum melatonin levels. All the volunteers medical students using mobiles for > 2 hrs/day were included in high users group and volunteers who used mobile for ? 2 hrs where included in low users group. Both high and low users volunteers were sampled three times in the same day (Morning-3-4 am, Noon 1-2 pm, Evening-5-6 pm) for estimation of serum melatonin levels: Comparsion of sernum melatonin levels in high users and low users were done by Mann Whitney "U" Test. Reduced morning melatonin levels (3-4 am) was observed in high users (> 2 hrs/day) i.e high users had a disturbed melatonin circadian rhythm.There was a negative correlation between melatonin secretion and hours of mobile usages. PMID:26215007

  6. Melatonin membrane receptor (MT1R) expression and nitro-oxidative stress in testis of golden hamster, Mesocricetus auratus: An age-dependent study.

    Science.gov (United States)

    Mukherjee, Arun; Haldar, Chandana

    2015-09-01

    Age-dependent decline in melatonin level induces nitro-oxidative stress that compromises physiological homeostasis including reproduction. However, less information exist regarding the age-dependent variation in local melatonin (lMel) concentration and MT1R expression in testis and its interaction with testicular steroidogenesis and nitro-oxidative stress in golden hamster, Mesocricetus auratus. Therefore, we evaluated lMel level along with MT1R expression and its possible interaction with steroidogenesis and nitro-oxidative stress in testes of young (6weeks), adult (15weeks) and old (2years) aged hamsters. Further, we injected the old hamsters with melatonin to address whether age-related decline in lMel and MT1R is responsible for the reduction in testicular steroidogenesis and antioxidant status. Increased expression of steroidogenic markers suggests increased testicular steroidogenesis in adult hamsters that declined in old hamsters. An age-dependent elevation in the level of NOX, TBARS, corticosterone and the expression of iNOS and GR with a concomitant decrease in enzyme activities for SOD, CAT, GSH-PX indicate increased nitro-oxidative stress in testes. Data suggest that reproductive senescence in male hamsters might be a consequence of declined lMel concentration with MT1R expression inducing nitro-oxidative stress resulting in diminished testicular steroidogenesis. However, administration of Mel in old-aged hamsters significantly increased steroidogenesis and antioxidant status without a significant variation in lMel concentration and MT1R expression in testes. Therefore, decreased lMel and MT1R might not be the causative factor underlying the age-associated decrease in antioxidant defence and steroidogenesis in testes. In conclusion, Mel induced amelioration of testicular oxidative insult and elevation of steroidogenic activity suggests a potential role of increased nitro-oxidative stress underlying the age-dependent decrease in steroidogenesis. PMID:26151342

  7. 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...

  8. The importance of visual cues for nocturnal species: Eagle owls signal by badge brightness

    OpenAIRE

    Penteriani, Vincenzo; Delgado, María del Mar; Alonso-Álvarez, Carlos; Sergio, Fabrizio

    2007-01-01

    Nocturnal species may communicate by visual signals more frequently than previously thought. In fact, such species are habitually active around sunset and sunrise, when light conditions are still suitable for visual communication. We investigated the communication function of a visual cue in the eagle owl Bubo bubo, a nocturnal predator. In this species, territorial and courtship displays peak during the sunset and sunrise periods and involve the display of a white badge located on the throat...

  9. Light Pollution Modifies the Expression of Daily Rhythms and Behavior Patterns in a Nocturnal Primate

    OpenAIRE

    Le Tallec, Thomas; Perret, Martine; Théry, Marc

    2013-01-01

    Among anthropogenic pressures, light pollution altering light/dark cycles and changing the nocturnal component of the environment constitutes a threat for biodiversity. Light pollution is widely spread across the world and continuously growing. However, despite the efforts realized to describe and understand the effects of artificial lighting on fauna, few studies have documented its consequences on biological rhythms, behavioral and physiological functions in nocturnal mammals. To determine ...

  10. Diurnal and Nocturnal Pollination of Marginatocereus marginatus (Pachycereeae: Cactaceae) in Central Mexico

    OpenAIRE

    DAR, SALEEM; ARIZMENDI, Ma. del CORO; Valiente-Banuet, Alfonso

    2006-01-01

    • Background and Aims Chiropterophillous and ornithophillous characteristics can form part of a single reproductive strategy in plants that have flowers with diurnal and nocturnal anthesis. This broader pollination strategy can ensure seed set when pollinators are scarce or unpredictable. This appears to be true of hummingbirds, which presumably pollinate Marginatocereus marginatus, a columnar cactus with red nocturnal and diurnal flowers growing as part of dense bat-pollinated columnar cacti...

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

    Directory of Open Access Journals (Sweden)

    Oliver Rawashdeh

    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.

  12. Effect of Using Melatonin Implants on Postpartum Reproductive Indices in Tigaia Sheep Breed

    Directory of Open Access Journals (Sweden)

    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.

  13. 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

  14. Melatonin reduces bacterial translocation and apoptosis in trinitrobenzene sulphonic acid-induced colitis of rats

    Directory of Open Access Journals (Sweden)

    Alper Akcan, Can Kucuk, Erdogan Sozuer, Duygu Esel, Hizir Akyildiz, Hulya Akgun, Sabahattin Muhtaroglu, Yucel Aritas

    2008-02-01

    Full Text Available AIM: To investigate the effects of exogenous melatonin on bacterial translocation and apoptosis in a rat ulcerative colitis model.METHODS: Rats were randomly assigned to three groups: groupI: control, group II: experimental colitis, group III: colitis plus melatonin treatment. On d 11 after colitis, plasma tumor necrosis factor-?, portal blood endotoxin levels, colon tissue myeloperoxidase and caspase-3 activity were measured. Bacterial translocation was quantified by blood, lymph node, liver and spleen culture.RESULTS: We observed a significantly reduced incidence of bacterial translocation to the liver, spleen, mesenteric lymph nodes, portal and systemic blood in animals treated with melatonin. Treatment with melatonin significantly decreased the caspase-3 activity in colonic tissues compared to that in trinitrobenzene sulphonic acid- treated rats (16.11 ± 2.46 vs 32.97 ± 3.91, P < 0.01.CONCLUSION: Melatonin has a protective effect on bacterial translocation and apoptosis.

  15. 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)

  16. Melatonin affects the order, dynamics and hydration of brain membrane lipids

    Science.gov (United States)

    Akkas, Sara B.; Inci, Servet; Zorlu, Faruk; Severcan, Feride

    2007-05-01

    The brain is especially susceptible to free radical attack since it is rich in polyunsaturated fatty acids and consumes very high amounts of oxygen. Melatonin is a non-enzymatic amphiphilic antioxidant hormone that is widely used in medicine for protective and treatment purposes in cases of oxidative stress. In the present work, the effects of the clinically used dose of melatonin (a single intraperitoneal dose of 100 mg/kg) on rat brain homogenate were investigated as a function of temperature using Fourier transform infrared spectroscopy. The results showed that the lipid to protein ratio decreases in the melatonin treated brain samples. Moreover, it is revealed that melatonin disorders and decreases the dynamics of lipids and induces a strengthening in the hydrogen bonding between the functional groups of both melatonin and the polar parts of lipids and/or water at physiological temperatures.

  17. Melatonin Regulates Oxidative Stress Initiated by Freund’s Complete Adjuvant

    Directory of Open Access Journals (Sweden)

    Miroslav Pohanka

    2015-07-01

    Full Text Available Melatonin is a hormone with strong antioxidant properties. In this experiment, Freund’s complete adjuvant was used as a stressogenic substance given to laboratory outbred mice, whereas melatonin was investigated as a protectant against the stressogenic effect. Levels of low molecular weight antioxidants, thiobarbituric acid reactive substances, and tumor necrosis factor ? and activity of glutathione reductase were determined in blood from the animals. Surprisingly, melatonin was not involved in direct regulation of antioxidants, thiobarbituric acid reactive substances and tumor necrosis factor ?. On the other hand, melatonin regulated glutathione reductase activity. We can conclude on regulation of metabolism caused by melatonin in the model. The effect was more important than the expected regulation of immunity and basal oxidative homeostasis.

  18. Nocturnal secondary ozone concentration maxima analysed by sodar observations and surface measurements

    Science.gov (United States)

    Reitebuch, Oliver; Strassburger, Anja; Emeis, Stefan; Kuttler, Wilhelm

    The occurrence of nocturnal secondary ozone maxima was investigated by ground-level meteorological and air quality measurements in an urban park in Essen, Germany, during 29 individual summer measurement campaigns between May 1995 and September 1997. In addition, during an intensive measurement campaign in May 1997, SODAR measurements of wind and turbulence were made. The spatial and temporal distribution of nocturnal ozone maxima within the measurement network of the Environmental Protection Office of North Rhine-Westphalia was also analysed. Two case studies of nocturnal secondary ozone maxima are discussed in more detail. They represent two different types of this phenomenon, associated with a nocturnal low-level jet (LLJ) and the passage of a front, respectively. In both cases, the nocturnal increase in ozone concentration was accompanied by a significant increase in the standard deviation of the vertical wind speed ?w across the lower stable boundary layer, indicating enhanced vertical mixing. During the LLJ case, ozone maxima were observed at 33% of the stations of the Environmental Protection Office network at approximately the same time. In the case of the front, the time of the ozone concentration rise could be allocated to the time of the passage of the front, moving from northwest to southeast across the study area. For the first time, the measurements presented here document turbulent mixing induced by shear forces in the whole layer between the core of the LLJ and the ground surface during secondary nocturnal ozone maxima.

  19. Nocturnal eating predicts tooth loss among adults: results from the Danish MONICA study

    DEFF Research Database (Denmark)

    Lundgren, Jennifer D; Williams, Karen B

    2010-01-01

    The relationship between nocturnal eating, such as that associated with night eating syndrome (NES), and oral health is unknown. This study sought to determine if nocturnal eating is related to tooth loss in a large, epidemiologic sample. Danes (N=2217; age range 30-60 years, M BMI [kg/m(2)]=25.9, % Male=50.1) enrolled in the Danish MONICA (MONItoring trends and determinants of CArdiovascular disease) were assessed on oral health, eating behavior, anthropometrics, general health, and demographic characteristics in both 1987/88 and 1993/94. We hypothesized that nocturnal eating at time one (1987/88) predicts number of missing teeth at time two (1993/94), when controlling for age, education, smoking status, body mass, carbohydrate intake, binge eating behavior, and diabetes diagnosis. A negative binomial model predicting number of missing teeth from nocturnal eating while controlling for covariates was conducted. Expected change in log count of missing teeth was significantly less for non-night eaters (p=.009),non-smokers (p=.001), non-diabetics (p=.001) and for each successive younger age group (p=.0001). Additionally, expected increase in log count of missing teeth was significantly greater for individuals with less than "high school diploma" education compared to those with the highest level of education (p=.0001). In sum, nocturnal eating contributes to tooth loss. Treatment providers should encourage good oral health care practices to reduce the risk of tooth loss associated with nocturnal eating.

  20. Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab

    Science.gov (United States)

    Helley, Dominique; de Latour, Régis Peffault; Porcher, Raphaël; Rodrigues, Celso Arrais; Galy-Fauroux, Isabelle; Matheron, Jeanne; Duval, Arnaud; Schved, Jean-François; Fischer, Anne-Marie; Socié, Gérard

    2010-01-01

    Background Paroxysmal nocturnal hemoglobinuria (PNH) is associated with an increased risk of thrombosis through unknown mechanisms. Design and Methods We studied 23 patients with PNH, before and after five and 11 weeks of treatment with eculizumab. We examined markers of thrombin generation and reactional fibrinolysis (prothrombin fragment 1+2 (F1+2), D-dimers, and plasmin antiplasmin complexes (P-AP), and endothelial dysfunction tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), soluble thrombomodulin (sTM), intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule (sVCAM-1), endothelial microparticles (EMPs), and tissue factor pathway inhibitor (TFPI). Results At baseline, vWF, sVCAM-1, the EMP count, and F1+2 and D-dimer levels were significantly elevated in the patients, including those with no history of clinical thrombosis. Treatment with eculizumab was associated with significant decreases in plasma markers of coagulation activation (F1+2, P=0.012, and D-dimers, P=0.01), and reactional fibrinolysis (P-AP, P=0.0002). Eculizumab treatment also significantly reduced plasma markers of endothelial cell activation (t-PA, P=0.0005, sVCAM-1, P<0.0001, and vWF, P=0.0047) and total (P=0.0008) and free (P=0.0013) TFPI plasma levels. Conclusions Our results suggest a new understanding of the contribution of endothelial cell activation to the pathogenesis of thrombosis in PNH. The terminal complement inhibitor, eculizumab, induced a significant and sustained decrease in the activation of both the plasma hemostatic system and the vascular endothelium, likely contributing to the protective effect of eculizumab on thrombosis in this setting. PMID:20081060

  1. 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

  2. Facilitation and inhibition of G-protein regulated protein secretion by melatonin.

    Science.gov (United States)

    Bubis, M; Zisapel, N

    1995-08-01

    Melatonin has been found to inhibit or enhance the constitutive secretion of proteins from the cultured melanoma cells at nanomolar concentrations (0.5-10 nM), in a dose dependent manner. The amplitude and direction of the response were found to depend on cell density: melatonin inhibited the release early after plating or at low cell density, but facilitated the release later on, or at high cell density. To elucidate the involvement of G-proteins in these responses, the effects of guanosine 5'-O-(3-thiotriphosphate) (GTP tau S; which was introduced into the cells during the process of permeabilization and resealing with ATP), aluminum fluoride, pertussis and cholera toxins on protein secretion from the cells were assessed in the absence and presence of melatonin. At low cell density, melatonin inhibited release, but paradoxically enhanced it when GTP hydrolysis was blocked (by GTP tau S or cholera toxin treatment). Aluminum fluoride and melatonin inhibited protein release in the absence or presence of GTP tau S. At high cell density, melatonin facilitated the release and so did GTP tau S, aluminum fluoride, their combination, and cholera toxin treatment. However, in the presence of the combination of GTP tau S, aluminium fluoride and melatonin, protein release was paradoxically inhibited. Similar treatment of the cells with pertussis toxin, did not affect the melatonin-mediated inhibition or facilitation. These results indicate that the effects of melatonin on protein secretion are mediated by at least one heterotrimeric G protein which belongs to the Gs class. In addition, melatonin can facilitate secretion via a cholera and pertussis toxins-insensitive mechanism which can be inhibited by aluminum fluoride. This effect is manifested when Gs is permanently activated (by GTP tau S or cholera toxin). PMID:7580873

  3. 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.)

  4. 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.)

  5. Late postoperative nocturnal episodic hypoxaemia and associated sleep pattern.

    DEFF Research Database (Denmark)

    Rosenberg, J; WildschiØdtz, G

    1994-01-01

    Ten patients undergoing major abdominal surgery under general anaesthesia were monitored with a pulse oximeter, electroencephalogram, electromyogram, electrocardiogram and eye and hand movement sensors two nights before and three nights after surgery. Episodic hypoxaemic events were increased significantly after surgery (P < 0.05). Rapid eye movement (REM) sleep decreased significantly on the first night after operation (P < 0.05). Seven patients had increased amounts of REM sleep (rebound) on the second, third or both nights after operation compared with the preoperative night. Slow wave sleep was depressed significantly on the first two nights after operation (P < 0.05). REM sleep-associated hypoxaemic episodes for individual patients increased about three-fold on the second and third nights after operation compared with the night before operation (P < 0.05). We conclude that postoperative sleep pattern is disturbed severely with early depression of REM and slow wave sleep and with rebound of REM sleep on the second and third nights. Postoperative rebound of REM sleep may contribute to the development of sleep disordered breathing and nocturnal episodic hypoxaemia.

  6. Nocturnal homing: learning walks in a wandering spider?

    Science.gov (United States)

    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). These learning flights and walks are stereotyped movement patterns clearly different from other movement behaviours. If the visual homing of L. arenicola is also based on an image matching strategy they are likely to exhibit learning walks similar to diurnal insects. To explore this possibility we recorded departures of spiders from a new burrow in an unfamiliar area with infrared cameras and analysed their paths using computer tracking techniques. We found that L. arenicola performs distinct stereotyped movement patterns during the first part of their departures in an unfamiliar area and that they seem to learn the appearance of their home during these movement patterns. We conclude that the spiders perform learning walks and this strongly suggests that L. arenicola uses a visual memory of the burrow location when homing. PMID:23145137

  7. Nitrogen Oxides in the Nocturnal Boundary Layer: Chemistry of Nitrous Acid (HONO) and the Nitrate Radical (N03)

    Energy Technology Data Exchange (ETDEWEB)

    Jochen Stutz

    2005-05-24

    Summary Chemical processes occurring at night in the lowest part of the urban atmosphere, the so called nocturnal boundary layer (NBL), can influence the composition of the atmosphere during the night as well as the following day. They may impact the budgets of some of the most important pollutants, such as ozone and nitrogen oxides, as well as influence size and composition of particular matter. Few studies have thus far concentrated on the nocturnal chemistry of the urban NBL, most likely due to the strong influence of vertical transport and mixing, which requires the measurement of trace gas profiles instead of simple point observations. Motivated by our lack of observations and understanding of nocturnal chemistry, the focus of this project was the study of the vertical distribution of trace gases and the altitude dependence of nocturnal chemistry under polluted conditions through field observations and modeling studies. The analysis of three field experiments (TEXAQS, Houston, 2000; Phoenix Sunrise Ozone Experiment, 2001; NAPOX, Boston, 2002), two of which were performed in this project, showed that ozone concentrations typically increase with height in the lowest 150m, while NO2 typically decreases. NO3, the dominant nocturnal radical species, showed much higher concentrations in the upper part of the NBL, and was often not present at the ground. With the help of a one-dimensional chemical transport model, developed in this project, we found that the interaction of ground emissions of NOx and hydrocarbons, together with their vertical transport, is responsible for the vertical profiles. The dominant chemical reactions influencing ozone, NO2 and NO3 are the reaction of ozone and NO3 with freshly emitted NO. Sensitivity studies with our model showed that the magnitude of the trace gas gradients depend both on the emission rates and the vertical stability of the NBL. Observations and model analysis clearly show that nocturnal chemistry in urban areas is altitude dependent. Measurements at one altitude, for example at the ground, where most air quality monitoring stations are located, are not representative for the rest of the NBL. Our model also revealed that radical chemistry is, in general, altitude dependent at night. We distinguish three regions: an unreactive, NO rich, ground layer; an upper, O3 and NO3 dominated layer, and a reactive mixing layer, where RO2 radicals are mixed from aloft with NO from the ground. In this reactive layer an active radical chemistry and elevated OH radical levels can be found. The downward transport of N2O5 and HO2NO2, followed by their thermal decay, was also identified as a radical source in this layer. Our observations also gave insight into the formation of HONO in the NBL. Based on our field experiments we were able to show that the NO2 to HONO conversion was relative humidity dependent. While this fact was well known, we found that it is most likely the uptake of HONO onto surfaces which is R.H. dependent, rather than the NO2 to HONO conversion. This finding led to the proposal of a new NO2 to HONO conversion mechanism, which is based on solid physical chemical principles. Noteworthy is also the observation of enhanced NO2 to HONO conversion during a dust storm event in Phoenix. The final activity in our project investigated the influence of the urban canopy, i.e. building walls and surfaces, on nocturnal chemistry. For the first time the surface area of a city was determined based on a Geographical Information System database of the city of Santa Monica. The surface to volume areas found in this study showed that, in the 2 lower part of the NBL, buildings provide a much larger surface area than the aerosol. In addition, buildings take up a considerable amount of the volume near the ground. The expansion of our model and sensitivity studies based on the Santa Monica data revealed that the surface area of buildings considerably influences HONO levels in urban areas. The volume reduction leads to a decrease of O3 and an increase of NO2 near the ground due to the stronger impact o

  8. Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia.

    Science.gov (United States)

    Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

    2015-12-01

    Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. PMID:26315930

  9. Anatomical specializations for nocturnality in a critically endangered parrot, the Kakapo (Strigops habroptilus).

    Science.gov (United States)

    Corfield, Jeremy R; Gsell, Anna C; Brunton, Dianne; Heesy, Christopher P; Hall, Margaret I; Acosta, Monica L; Iwaniuk, Andrew N

    2011-01-01

    The shift from a diurnal to nocturnal lifestyle in vertebrates is generally associated with either enhanced visual sensitivity or a decreased reliance on vision. Within birds, most studies have focused on differences in the visual system across all birds with respect to nocturnality-diurnality. The critically endangered Kakapo (Strigops habroptilus), a parrot endemic to New Zealand, is an example of a species that has evolved a nocturnal lifestyle in an otherwise diurnal lineage, but nothing is known about its' visual system. Here, we provide a detailed morphological analysis of the orbits, brain, eye, and retina of the Kakapo and comparisons with other birds. Morphometric analyses revealed that the Kakapo's orbits are significantly more convergent than other parrots, suggesting an increased binocular overlap in the visual field. The Kakapo exhibits an eye shape that is consistent with other nocturnal birds, including owls and nightjars, but is also within the range of the diurnal parrots. With respect to the brain, the Kakapo has a significantly smaller optic nerve and tectofugal visual pathway. Specifically, the optic tectum, nucleus rotundus and entopallium were significantly reduced in relative size compared to other parrots. There was no apparent reduction to the thalamofugal visual pathway. Finally, the retinal morphology of the Kakapo is similar to that of both diurnal and nocturnal birds, suggesting a retina that is specialised for a crepuscular niche. Overall, this suggests that the Kakapo has enhanced light sensitivity, poor visual acuity and a larger binocular field than other parrots. We conclude that the Kakapo possesses a visual system unlike that of either strictly nocturnal or diurnal birds and therefore does not adhere to the traditional view of the evolution of nocturnality in birds. PMID:21860663

  10. Melatonin replacement restores the circadian behavior in adult rat Leydig cells after pinealectomy.

    Science.gov (United States)

    Baburski, Aleksandar Z; Sokanovic, Srdjan J; Janjic, Marija M; Stojkov-Mimic, Natasa J; Bjelic, Maja M; Andric, Silvana A; Kostic, Tatjana S

    2015-09-15

    Melatonin actions on oscillators in reproductive organs are poorly understood. Here we analyzed melatonin effects on rhythmic expression of clock and steroidogenesis-related genes in adult rat Leydig cells (LCs). The effect of melatonin was tested both in vivo using pinealectomized and melatonin-substituted rats and in vitro on isolated LCs. Data revealed 24-h-rhythmic expression of clock genes (Bmal1, Per1,2,3, Rev-erba,b, Rorb), steroidogenic genes (Star, Cyp11a1, Cyp17a1), and genes of steroidogenic regulators (positive-Nur77, negative-Arr19). Pinealectomy increased 24-h-oscillations of serum testosterone and LC's cAMP levels, expression of Insl3, Per1, Star/StAR, Hsd3b1/2, Nur77, decreased Arr19 and canceled Per2 oscillatory expression pattern. At hypothalamic-pituitary level, pinealectomy increased mesor of Gnrh, Lhb and rhythm robustness of Mntr1a expression. All parameters disturbed were restored by melatonin-replacement. In vitro studies did not confirm direct melatonin effects on neither clock nor steroidogenic genes. Accordingly, melatonin influence 24-h-rhythmic LC-function likely through hypothalamic-pituitary axis and consequently cAMP-signaling in LCs. PMID:26116827

  11. 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

  12. Leptin Modulates Norepinephrine-Mediated Melatonin Synthesis in Cultured Rat Pineal Gland

    Science.gov (United States)

    Peliciari-Garcia, Rodrigo Antonio; Andrade-Silva, Jéssica; Cipolla-Neto, José; Carvalho, Carla Roberta de Oliveira

    2013-01-01

    Pineal melatonin synthesis can be modulated by many peptides, including insulin. Because melatonin appears to alter leptin synthesis, in this work we aimed to investigate whether leptin would have a role on norepinephrine- (NE-)mediated melatonin synthesis in cultured rat pineal glands. According to our data, cultured rat pineal glands express leptin receptor isoform b (Ob-Rb). Pineal expression of Ob-Rb mRNA was also observed in vivo. Administration of leptin (1?nM) associated with NE (1?µM) reduced melatonin content as well as arylalkylamine-N-acetyl transferase (AANAT) activity and expression in cultured pineal glands. Leptin treatment per se induced the expression of STAT3 in cultured pineal glands, but STAT3 does not participate in the leptin modulation of NE-mediated pineal melatonin synthesis. In addition, the expression of inducible cAMP early repressor (ICER) was further induced by leptin challenge when associated with NE. In conclusion, leptin inhibition of pineal melatonin synthesis appears to be mediated by a reduction in AANAT activity and expression as well as by increased expression of Icer mRNA. Peptidergic signaling within the pineal gland appears to be one of the most important signals which modulates melatonin synthesis; leptin, as a member of this system, is not an exception. PMID:23936817

  13. Melatonin prevents neural tube defects in the offspring of diabetic pregnancy.

    Science.gov (United States)

    Liu, Shangming; Guo, Yuji; Yuan, Qiuhuan; Pan, Yan; Wang, Liyan; Liu, Qian; Wang, Fuwu; Wang, Jingjing; Hao, Aijun

    2015-11-01

    Melatonin, an endogenous neurohormone secreted by the pineal gland, has a variety of physiological functions and neuroprotective effects. However, its protective role on the neural tube defects (NTDs) was not very clear. The aim of this study was to investigate the effects of melatonin on the incidence of NTDs (including anencephaly, encephalocele, and spina bifida) of offspring from diabetic pregnant mice as well as its underlying mechanisms. Pregnant mice were given 10 mg/kg melatonin by daily i.p. injection from embryonic day (E) 0.5 until being killed on E11.5. Here, we showed that melatonin decreased the NTDs (especially exencephaly) rate of embryos exposed to maternal diabetes. Melatonin stimulated proliferation of neural stem cells (NSCs) under hyperglycemic condition through the extracellular regulated protein kinases (ERK) pathway. Furthermore, as a direct free radical scavenger, melatonin decreased apoptosis of NSCs exposed to hyperglycemia. In the light of these findings, it suggests that melatonin supplementation may play an important role in the prevention of neural malformations in diabetic pregnancy. PMID:26475080

  14. 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)

  15. 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.

  16. Ghost protein damage by peroxynitrite and its protection by melatonin

    Directory of Open Access Journals (Sweden)

    Di Mascio P.

    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 Troloxregistered (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.

  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 controls experimental autoimmune encephalomyelitis by altering the T effector/regulatory balance.

    Science.gov (United States)

    Álvarez-Sánchez, Nuria; Cruz-Chamorro, Ivan; López-González, Antonio; Utrilla, José C; Fernández-Santos, José M; Martínez-López, Alicia; Lardone, Patricia J; Guerrero, Juan M; Carrillo-Vico, Antonio

    2015-11-01

    Experimental autoimmune encephalomyelitis (EAE), the experimental model for multiple sclerosis (MS), is triggered by myelin-specific Th1 and Th17 cells. The immunomodulatory activities of melatonin have been shown to be beneficial under several conditions in which the immune system is exacerbated. Here, we sought to elucidate the basis of the melatonin protective effect on EAE by characterizing the T effector/regulatory responses, particularly those of the memory cell subsets. Melatonin was tested for its effect on Th1, Th17 and T regulatory (Treg) cells in the lymph nodes and CNS of immunodominant peptide of myelin oligodendrocyte glycoprotein (pMOG)-immunized and EAE mice, respectively. The capacity of melatonin to ameliorate EAE as well as modifying both T cell response and effector/regulatory balance was surveyed. T cell memory subsets and CD44, a key activation marker involved in the EAE pathogenesis, were also examined. Melatonin protected from EAE by decreasing peripheral and central Th1/Th17 responses and enhancing both the Treg frequency and IL-10 synthesis in the CNS. Melatonin reduced the T effector memory population and its pro-inflammatory response and regulated CD44 expression, which was decreased in T effector cells and increased in Tregs. The alterations in the T cell subpopulations were associated with a reduced mononuclear infiltration (CD4 and CD11b cells) of the melatonin-treated mice CNS. For the first time, we report that melatonin protects against EAE by controlling peripheral and central T effector/regulatory responses, effects that might be partially mediated by CD44. This immunomodulatory effect on EAE suggests that melatonin may represent an effective treatment option for MS. PMID:26130320

  19. Age-related changes in melatonin synthesis in rat extrapineal tissues.

    Science.gov (United States)

    Sanchez-Hidalgo, M; de la Lastra, C Alarcon; Carrascosa-Salmoral, M P; Naranjo, M C; Gomez-Corvera, A; Caballero, B; Guerrero, J M

    2009-05-01

    In the search of new therapeutic targets improving the quality of life of elderly, melatonin, "the chemical expression of darkness", seems to play a remarkable role in aging process possibly due to its antioxidant, immunoenhancer and anti-aging properties. The present study was designed to elucidate effects of aging in melatonin extrapineal synthesis and investigate evident age-related alterations in the action mechanisms involved. The presence of the two key enzymes involved in melatonin synthesis, arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) was analyzed in thymus, spleen, liver, kidney and heart of 3- and 12month-old rats using real time PCR as well as its functionality by enzymatic activity assays. In addition, extrapineal melatonin content was measured by a competitive enzyme immunoassay (ELISA). The results of this study reveal that all rat tissues studied including thymus, and for the first time, spleen, liver, kidney and heart have the necessary machinery to synthesize melatonin. Moreover, we report an age-related decline in rat extrapineal melatonin synthesis with a consequent HIOMT functionality decrease in spleen, liver and heart during physiological aging. On the contrary, NAT enzymatic activity maintains unchanged without evident alterations with advancing age. Moreover, diminished melatonin concentrations were measured in these tissues cited above during aging except in the thymus, where, surprisingly, melatonin content, NAT/HIOMT expression, and enzymatic functionality assays revealed no significant alterations with age. As a conclusion, we report evident age-related changes in melatonin synthesis in some rat peripheral organs. We suggest that thymus may develop compensatory mechanisms to counteract the loss of immune activity and consequently, the loss of this potent antioxidant, during physiological aging. PMID:19233254

  20. 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.