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Sample records for nocturnal melatonin elevation

  1. Effects of illumination on human nocturnal serum melatonin levels and performance

    Dollins, A. B.; Lynch, H. J.; Wurtman, R. J.; Deng, M. H.; Lieberman, H. R.

    1993-01-01

    In humans, exposure to bright light at night suppresses the normal nocturnal elevation in circulating melatonin. Oral administration of pharmacological doses of melatonin during the day, when melatonin levels are normally minimal, induces fatigue. To examine the relationship between illumination, human pineal function, and behavior, we monitored the overnight serum melatonin profiles and behavioral performance of 24 healthy male subjects. On each of three separate occasions subjects participated in 13.5 h (1630-0800 h) testing sessions. Each subject was assigned to an individually illuminated workstation that was maintained throughout the night at an illumination level of approximately 300, 1500, or 3000 lux. Melatonin levels were significantly diminished by light treatment, F(2, 36) = 12.77, p light intensity and circulating melatonin levels.

  2. Nocturnal melatonin secretion in suicidal patients with multiple sclerosis.

    Sandyk, R; Awerbuch, G I

    1993-01-01

    Multiple sclerosis (MS) is characterised by the occurrence of patchy CNS demyelinating lesions, leading to various degrees of motor, sensory, affective, and cognitive deficits. MS is associated also with an increased risk of suicide accounting for a substantial rate of death among these patients. Post-mortem studies in suicide victims with various psychiatric disorders demonstrate a decreased concentration of serotonin (5-HT) and its metabolites in the brain. Since 5-HT is a precursor in the synthesis of melatonin and as pineal melatonin content was found to be low in suicide victims, we predicted lower melatonin secretion in suicidal versus non-suicidal MS patients during an acute exacerbation of symptoms. To test this hypothesis, we investigated nocturnal plasma melatonin levels in a cohort of 28 relapsing patients who were admitted consecutively to an inpatient Neurology service, 6 of whom had a history of suicide attempts and were having suicidal ideation at the time of admission. While both cohorts of patients were not distinguishable on any of the demographic data including use of psychotrophic drugs on the day of admission to hospital, the mean melatonin level in the suicidal group was significantly lower than in the control group (19.0 pg/ml +/- 11.9 versus 45.5 pg/ml +/- 27.1; p suicidality in MS and reinforce the concept that a biological rather than a reactive etiology underlies the development of psychiatric symptoms in MS. PMID:8407143

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

    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.

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

    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. Melatonin

    ... blood levels of melatonin.Vitex agnus-castusTaking vitex agnus-castus increases melatonin levels in the body. In theory, taking vitex agnus-castus with melatonin might increase both the effects and ...

  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

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

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

    1995-12-31

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

  8. Melatonin

    ... no scientific studies have shown that melatonin can slow down the aging process or prolong your life. Does melatonin require a doctor's prescription? No. Melatonin is sold without a prescription in health food stores and drug stores in the United States. ...

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

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

    2000-01-01

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

  10. The characteristics of the melatonin secretory rhythm are not modified by the stage of pregnancy in ewes

    Zarazaga Garcés, Luis Ángel; Malpaux, B; Chemineau, Phileppe

    1996-01-01

    An experiment was designed to study if, in the same animals, characteristics of the plasma melatonin rhythm vary during pregnancy in ewes. Thirteen Ile-de-France ewes were maintained in natural photoperiod and measurements of the characteristics of the rhythm of melatonin secretion were determined during one estrous cycle and then during pregnancy. Duration and mean plasma concentrations of the nocturnal melatonin elevation were measured at four stages of pregnancy. Melatonin c...

  11. Melatonin

    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

    2015-01-01

    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...

  12. Melatonin rhythms in women with anorexia nervosa and bulimia nervosa.

    Mortola, J F; Laughlin, G A; Yen, S S

    1993-12-01

    To discern whether the multiple neuroendocrine-metabolic dysfunctions observed in women with anorexia nervosa (AN) and bulimia nervosa (BN) are associated with altered diurnal variations in serum melatonin profiles, we compared cycling and amenorrheic women with normal weight BN (n = 8) and AN (n = 7) to 21 normal cycling controls. Endogenous depression, which has confounded prior studies of melatonin profiles in women with eating disorders, was excluded in all subjects. Serum samples for melatonin measurements were obtained at frequent intervals (every 20 min) in a controlled light-dark environment, and cycling women were studied in the early follicular phase of the menstrual cycle. Mean (+/- SE) peak melatonin levels were similar in AN, BN, and controls (325 +/- 43, 310 +/- 33, and 334 +/- 30 pmol/L, respectively). The time of melatonin peak, the time of onset and offset of the nocturnal serum melatonin excursion, and the duration of the nocturnal elevation were also similar in the three groups. Analysis of covariance revealed no independent effects of age or time of year on the data. Moreover, when subjects were separated into those with and without menstrual cyclicity, no significant differences in any parameter of melatonin diurnal variation were observed. Taken together, these data suggest that pineal melatonin secretion is unaltered in women with eating disorders, in whom depression is excluded, and that the frequent occurrence of amenorrhea in this population is not mediated by melatonin. PMID:8263138

  13. Urinary melatonin in depression.

    Rao, A V; Devi, S P; Srinivasan, V

    1983-07-01

    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 levels. An association between melatonin levels with suicide behaviour, insomnia, psychomotor retardation and diurnal variation is discussed. PMID:21847281

  14. 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

    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

  15. Melatonin: an inhibitor of breast cancer.

    Hill, Steven M; Belancio, Victoria P; Dauchy, Robert T; Xiang, Shulin; Brimer, Samantha; Mao, Lulu; Hauch, Adam; Lundberg, Peter W; Summers, Whitney; Yuan, Lin; Frasch, Tripp; Blask, David E

    2015-06-01

    The present review discusses recent work on melatonin-mediated circadian regulation, the metabolic and molecular signaling mechanisms that are involved in human breast cancer growth, and the associated consequences of circadian disruption by exposure to light at night (LEN). The anti-cancer actions of the circadian melatonin signal in human breast cancer cell lines and xenografts heavily involve MT1 receptor-mediated mechanisms. In estrogen receptor alpha (ERα)-positive human breast cancer, melatonin suppresses ERα mRNA expression and ERα transcriptional activity via the MT1 receptor. Melatonin also regulates the transactivation of other members of the nuclear receptor superfamily, estrogen-metabolizing enzymes, and the expression of core clock and clock-related genes. Furthermore, melatonin also suppresses tumor aerobic metabolism (the Warburg effect) and, subsequently, cell-signaling pathways critical to cell proliferation, cell survival, metastasis, and drug resistance. Melatonin demonstrates both cytostatic and cytotoxic activity in breast cancer cells that appears to be cell type-specific. Melatonin also possesses anti-invasive/anti-metastatic actions that involve multiple pathways, including inhibition of p38 MAPK and repression of epithelial-mesenchymal transition (EMT). Studies have demonstrated that melatonin promotes genomic stability by inhibiting the expression of LINE-1 retrotransposons. Finally, research in animal and human models has indicated that LEN-induced disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer and drives breast tumors to endocrine and chemotherapeutic resistance. These data provide the strongest understanding and support of the mechanisms that underpin the epidemiologic demonstration of elevated breast cancer risk in night-shift workers and other individuals who are increasingly exposed to LEN. PMID:25876649

  16. CIRCADIAN REGULATION METABOLIC SIGNALING MECHANISMS OF HUMAN BREAST CANCER GROWTH BY THE NOCTURNAL MELATONIN SIGNAL AND THE CONSEQUENCES OF ITS DISRUPTION BY LIGHT AT NIGHT

    Blask, David E.; Hill, Steven M.; Dauchy, Robert T; Xiang, Shulin; Yuan, Lin; Duplessis, Tamika; Mao, Lulu; Dauchy, Erin; Sauer, Leonard A.

    2011-01-01

    This review article discusses recent work on the melatonin-mediated circadian regulation and integration of molecular, dietary and metabolic signaling mechanisms involved in human breast cancer growth and the consequences of circadian disruption by exposure to light-at-night (LAN). The antiproliferative effects of the circadian melatonin signal are mediated through a major mechanism involving the activation of MT1 melatonin receptors expressed in human breast cancer cell lines and xenografts....

  17. Spring snow lowers human melatonin

    Leppäluoto, Juhani; Sikkilä, Kirsti; Meyer-Rochow, Victor Benno; Hassi, Juhani

    2004-01-01

    Objectives. We set out to find out in which way seasonal changes of environmental luminosity could affect melatonin secretion in humans. Study design. For an entire year we collected every two months nocturnal urine samples from 20 male outdoor workers who lived and worked in an area of the circumpolar region from which exact data of solar irradiance and temperature were available. Methods. Melatonin secretion rates were assessed with our melatonin-specific radioimmunoassay. Results. Melatoni...

  18. Nocturnal Asthma

    ... Medical Director, Health Initiatives View full profile Nocturnal Asthma Worsening of asthma at night, or nocturnal asthma, ... give extra protection during the night. More Nocturnal Asthma Information Back to Asthma: Types Print Page Email ...

  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

    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. Doxorubicin resistance in breast cancer is driven by light at night-induced disruption of the circadian melatonin signal.

    Xiang, Shulin; Dauchy, Robert T; Hauch, Adam; Mao, Lulu; Yuan, Lin; Wren, Melissa A; Belancio, Victoria P; Mondal, Debasis; Frasch, Tripp; Blask, David E; Hill, Steven M

    2015-08-01

    Chemotherapeutic resistance, particularly to doxorubicin (Dox), represents a major impediment to successfully treating breast cancer and is linked to elevated tumor metabolism and tumor over-expression and/or activation of various families of receptor- and non-receptor-associated tyrosine kinases. Disruption of circadian time structure and suppression of nocturnal melatonin production by dim light exposure at night (dLEN), as occurs with shift work, and/or disturbed sleep-wake cycles, is associated with a significantly increased risk of an array of diseases, including breast cancer. Melatonin inhibits human breast cancer growth via mechanisms that include the suppression of tumor metabolism and inhibition of expression or phospho-activation of the receptor kinases AKT and ERK1/2 and various other kinases and transcription factors. We demonstrate in tissue-isolated estrogen receptor alpha-positive (ERα+) MCF-7 human breast cancer xenografts, grown in nude rats maintained on a light/dark cycle of LD 12:12 in which dLEN is present during the dark phase (suppressed endogenous nocturnal melatonin), a significant shortening of tumor latency-to-onset, increased tumor metabolism and growth, and complete intrinsic resistance to Dox therapy. Conversely, a LD 12:12 dLEN environment incorporating nocturnal melatonin replacement resulted in significantly lengthened tumor latency-to-onset, tumor regression, suppression of nighttime tumor metabolism, and kinase and transcription factor phosphorylation, while Dox sensitivity was completely restored. Melatonin acts as both a tumor metabolic inhibitor and circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to Dox and drive tumor regression, indicating that dLEN-induced circadian disruption of nocturnal melatonin production contributes to a complete loss of tumor sensitivity to Dox chemotherapy. PMID:25857269

  1. Phytoremediative Capacity of Plants Enriched with Melatonin

    Tan, Dun-Xian; Manchester, Lucien C.; Helton, Pat; Reiter, Russel J.

    2007-01-01

    Melatonin is an environmentally friendly-molecule with broad spectrum antioxidant capacity. Melatonin is widely present in the plant kingdom. High levels of melatonin exist in an aquatic plant, the water hyacinth, which is highly tolerant of environmental pollutants. Elevated levels of melatonin probably help plants to protect against environmental stress caused by water and soil pollutants. To investigate the potential relationships between melatonin supplementation and environmental toleran...

  2. Melatonin: Physiological effects in humans.

    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

  3. Endogenous melatonin and oxidatively damaged guanine in DNA

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

    2009-01-01

    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...

  4. Clinical uses of melatonin in pediatrics.

    Sánchez-Barceló, Emilio J; 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 properties of melatonin have been used in diagnostic situations requiring sedation or as a premedicant in children undergoing anesthetic procedures. Epilepsy and febrile seizures are also susceptible to treatment with melatonin, alone or associated with conventional antiepileptic drugs. Melatonin has been also used to prevent the progression in some cases of adolescent idiopathic scoliosis. In newborns, and particularly those delivered preterm, melatonin has been used to reduce oxidative stress associated with sepsis, asphyxia, respiratory distress, or surgical stress. Finally, the administration of melatonin, melatonin analogues, or melatonin precursors to the infants through the breast-feeding, or by milk formula adapted for day and night, improves their nocturnal sleep. Side effects of melatonin treatments in children have not been reported. Although the above-described results are promising, specific studies to resolve the problem of dosage, formulations, and length of treatment are necessary. PMID:21760817

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

    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.

  6. Melatonin and LH secretion patterns in pubertal boys

    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

  7. Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal.

    Blask, David E; Dauchy, Robert T; Sauer, Leonard A

    2005-07-01

    Physiological and pharmacological blood concentrations of melatonin inhibit tumorigenesis in a variety of in vivo and in vitro experimental models of neoplasia. Evidence indicates that melatonin's anticancer effects are exerted via inhibition of cell proliferation and a stimulation of differentiation and apoptosis. A new mechanism by which physiological and pharmacological blood levels of melatonin inhibit cancer growth in vivois via a melatonin-induced suppression of tumor linoleic acid (LA) uptake and its metabolism to the important mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin suppresses cAMP formation and inhibits tumor uptake of LA and its metabolism to 13-HODE via a melatonin receptor-mediated mechanism in both tissue-isolated rat hepatoma 7288 CTC and human breast cancer xenografts. It has been postulated that in industrialized societies, light at night, by suppressing melatonin production, poses a new risk for the development of breast cancer and, perhaps, other cancers as well. In support of this hypothesis, light during darkness suppresses nocturnal melatonin production and stimulates the LA metabolism and growth of rat hepatoma and human breast cancer xenografts. Nocturnal dietary supplementation with melatonin, at levels contained in a melatonin-rich diet, inhibits rat hepatoma growth via the mechanisms described above. The nocturnal melatonin signal organizes tumor metabolism and growth within circadian time structure that can be further reinforced by appropriately timed melatonin supplementation. Dietary melatonin supplementation working in concert with the endogenous melatonin signal has the potential to be a new preventive/therapeutic strategy to optimize the host/cancer balance in favor of host survival and quality of life. PMID:16217131

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

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

    2014-01-01

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

  9. Improving melatonin circadian phase estimates.

    Van Someren, Eus J W; Nagtegaal, Elsbeth

    2007-09-01

    The quality and quantity of sleep is to a large extent determined by whether the sleep period is in alignment with the most favorable circadian time window for sleep. Misalignment results in compromised sleep. In order to determine this circadian time window, the 24-h profile of melatonin secretion is generally considered to provide the most optimal estimate. Melatonin secretion occurs only during the night, and several methods to determine its onset and offset markers have been proposed. In spite of the usefulness of determining circadian phase estimates from melatonin, its feasibility is somewhat restricted because the required number of repeated measurements comes at a high cost for compliance and laboratory assays. In addition, the complexity of some of the previously proposed methods to analyze data and obtain phase estimates may require a statistician. We here propose a set of novel functions to better describe the typical melatonin profile, which usually has a rather fixed baseline level during the day, has differences in the steepness of its rising and falling limbs, and may have a nocturnal plateau or even two peaks instead of one during the night. The functions can easily be fitted, even to incomplete or noisy melatonin data, with the most common statistical software packages, and the resulting parameters give direct information on the mentioned characteristics, which provide important additions to complete the usual restricted information on phase and amplitude. We show that the proposed curves fit better than single- to three-harmonic cosine curves to the typical melatonin profiles of both healthy subjects (n=13) and subjects diagnosed with Delayed Sleep Phase Syndrome (DSPS, n=27), Disorders of Initiating and Maintaining Sleep (DIMS, n=9), or sleep complaints not otherwise specified (n=7). Of note, because the functions provide a parsimonious description of the melatonin profile, phase estimates derived from them are more reliable (i.e., robust for noise and data loss). We illustrate that phase estimates deviate on average only by about 10 min in case of the loss of some of the data points and in case of the addition of noise. Finally, we introduce a sparse-sampling schedule tailored to capture the most important aspects of the melatonin curve. It is shown that such schedule - reducing the number of samples by more than 50% - in combination with the proposed functions results in reliable melatonin onset phase estimates, deviating only about 10 min from estimates based on 24 samples. The proposed methods strongly contribute to the feasibility, in terms of both cost and analysis availability, for researchers and clinicians to include the most reliable marker of the circadian timing system in their diagnosis and treatment evaluations. PMID:17493871

  10. MELATONIN: POTENTIAL UTILITY FOR IMPROVING PUBLIC HEALTH

    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

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

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

    2013-01-01

    Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests. PMID:24129182

  12. Analgesic effects of melatonin

    Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J; Rosenberg, Jacob; Gögenur, Ismail

    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...

  13. Homeobox genes and melatonin synthesis

    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 indu......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 c......AMP-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 c...

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

    Vigo; MF Vidal; 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...

  15. Nasal versus temporal illumination of the human retina: Effects on core body temperature, melatonin, and circadian phase

    Ruger, M; Gordijn, MCM; BEERSMA, DGM; de Vries, B.; DAAN, S

    2005-01-01

    The mammalian retina contains both visual and circadian photoreceptors. In humans, nocturnal stimulation of the latter receptors leads to melatonin suppression, which might cause reduced nighttime sleepiness. Melatonin suppression is maximal when the nasal part of the retina is illuminated. Whether circadian phase shifting in humans is due to the same photoreceptors is not known. The authors explore whether phase shifts and melatonin suppression depend on the same retinal area. Twelve healthy...

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

    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.

  17. The role of melatonin in diabetes: therapeutic implications.

    Sharma, Shweta; Singh, Hemant; Ahmad, Nabeel; Mishra, Priyanka; Tiwari, Archana

    2015-10-01

    Melatonin referred as the hormone of darkness is mainly secreted by pineal gland, its levels being elevated during night and low during the day. The effects of melatonin on insulin secretion are mediated through the melatonin receptors (MT1 and MT2). It decreases insulin secretion by inhibiting cAMP and cGMP pathways but activates the phospholipaseC/IP3 pathway, which mobilizes Ca2+from organelles and, consequently increases insulin secretion. Both in vivo and in vitro, insulin secretion by the pancreatic islets in a circadian manner, is due to the melatonin action on the melatonin receptors inducing a phase shift in the cells. Melatonin may be involved in the genesis of diabetes as a reduction in melatonin levels and a functional interrelationship between melatonin and insulin was observed in diabetic patients. Evidences from experimental studies proved that melatonin induces production of insulin growth factor and promotes insulin receptor tyrosine phosphorylation. The disturbance of internal circadian system induces glucose intolerance and insulin resistance, which could be restored by melatonin supplementation. Therefore, the presence of melatonin receptors on human pancreatic islets may have an impact on pharmacotherapy of type 2 diabetes. PMID:26331226

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

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

    2014-01-01

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

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

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

    2009-01-01

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

  20. Nocturnal leg cramps.

    Allen, Richard E; Kirby, Karl A

    2012-08-15

    Up to 60 percent of adults report that they have had nocturnal leg cramps. The recurrent, painful tightening usually occurs in the calf muscles and can cause severe insomnia. The exact mechanism is unknown, but the cramps are probably caused by muscle fatigue and nerve dysfunction rather than electrolyte or other abnormalities. Nocturnal leg cramps are associated with vascular disease, lumbar canal stenosis, cirrhosis, hemodialysis, pregnancy, and other medical conditions. Medications that are strongly associated with leg cramps include intravenous iron sucrose, conjugated estrogens, raloxifene, naproxen, and teriparatide. A history and physical examination are usually sufficient to differentiate nocturnal leg cramps from other conditions, such as restless legs syndrome, claudication, myositis, and peripheral neuropathy. Laboratory evaluation and specialized testing usually are unnecessary to confirm the diagnosis. Limited evidence supports treating nocturnal leg cramps with exercise and stretching, or with medications such as magnesium, calcium channel blockers, carisoprodol, or vitamin B(12). Quinine is no longer recommended to treat leg cramps. PMID:22963024

  1. Paroxysmal Nocturnal Hemoglobinuria

    ... Children Special Issues Myelodysplastic Syndromes (MDS) What is MDS? iPad App Causes Symptoms Diagnosis Types Treatment Wait and Watch Blood ... and Bone Marrow Basics Aplastic Anemia Myelodysplastic Syndromes (MDS) Paroxysmal Nocturnal Hemoglobinuria (PNH) ... Trials Special Issues Living ...

  2. Altered melatonin secretion in hypogonadal men: clinical evidence.

    Kumanov, Philip; Tomova, Analia; Isidori, Aldo; Nordio, Maurizio

    2005-08-01

    The pineal gland, through the rhythmic production of melatonin, seems to play an important role in the control of the reproductive function of many vertebrate species. In contrast, the effects of the pineal gland in humans and the relationship between gonadotropins and melatonin secretion are not yet clarified. On the basis of these considerations, the aim of the present study was to clarify whether melatonin serum concentrations were altered in males with different hypothalamo-pituitary-gonadal disturbances, in comparison to normal individuals. We have studied 36 individuals divided into three groups according to their gonadotropin status: normals, hypogonadotropic hypogonadism and hypergonadotropic hypogonadism. They were submitted to blood sample withdrawal at 03.00, 11.00 and 19.00 h for melatonin determination according to a radioimmunological method, without extraction of the sample. The results obtained in the present study suggest the existence of an interaction between the pituitary and the pineal gland. In fact, in the case of hypersecretion of gonadotropins, nocturnal melatonin release is reduced, while night melatonin secretion is increased in the opposite situation (hypogonadotropic hypogonadism). Both these endocrine pathologies are characterized by a reduced sexual steroid secretion; for that reason, this reduction cannot be regarded as responsible for the two opposite dysfunctions of melatonin release. In conclusion, our study shows that darkness-dependent release of melatonin in males with hypogonadotropic hypogonadism is significantly higher in comparison with the healthy men, while it is significantly reduced in patients with hypergonadotropic hypogonadism. A strong significant negative correlation is also found between gonadotropins and melatonin release. PMID:16048636

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

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

    2015-01-01

    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

  4. Analgesic effects of melatonin

    Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J; Rosenberg, Jacob; Gögenur, Ismail

    2011-01-01

    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...

  5. Ocular input for human melatonin regulation: relevance to breast cancer

    Glickman, Gena; Levin, Robert; Brainard, George C.

    2002-01-01

    The impact of breast cancer on women across the world has been extensive and severe. As prevalence of breast cancer is greatest in industrialized regions, exposure to light at night has been proposed as a potential risk factor. This theory is supported by the epidemiological observations of decreased breast cancer in blind women and increased breast cancer in women who do shift-work. In addition, human, animal and in vitro studies which have investigated the melatonin-cancer dynamic indicate an apparent relationship between light, melatonin and cancer, albeit complex. Recent developments in understanding melatonin regulation by light in humans are examined, with particular attention to factors that contribute to the sensitivity of the light-induced melatonin suppression response. Specifically, the role of spectral characteristics of light is addressed, and recent relevant action spectrum studies in humans and other mammalian species are discussed. Across five action spectra for circadian and other non-visual responses, a peak sensitivity between 446-484 nm was identified. Under highly controlled exposure circumstances, less than 1 lux of monochromatic light elicited a significant suppression of nocturnal melatonin. In view of the possible link between light exposure, melatonin suppression and cancer risk, it is important to continue to identify the basic related ocular physiology. Visual performance, rather than circadian function, has been the primary focus of architectural lighting systems. It is now necessary to reevaluate lighting strategies, with consideration of circadian influences, in an effort to maximize physiological homeostasis and health.

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

    Amnon Brzezinski

    2014-01-01

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

  7. Pathophysiology of nocturnal enuresis

    Rittig, Søren; Kamperis, Konstantinos

    vasopressin levels and renal factors such as increased GFR and solute excretion (e.g. sodium) as well as increased prostaglandin PGE2 excretion. Furthermore, nocturnal polyuria has been associated with poor sleep (e.g. sleep fragmentation) and increased nocturnal arterial blood pressure levels. Another...... that dysfunction of the intrinsic circadian regulation located in the suprachiasmatic nucleus results in dysfunction of one or more of the brainstem centers involved in AVP secretion, arousal function, bladder control, and blood pressure regulation. Furthermore, nocturnal enuresis has a strong genetic...... influence that in some families present as autosomal dominant inheritance with high degree of penetrance. Linkage to several chromosomal areas have been confirmed in such families although a specific causative enuresis gene has not yet been identified. In conclusion, our understanding of enuresis...

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

    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

  9. Nocturnal continuous glucose monitoring

    Bay, Christiane; Kristensen, Peter Lommer; Pedersen-Bjergaard, Ulrik; Tarnow, Lise; Thorsteinsson, Birger

    2013-01-01

    Abstract Background: A reliable method to detect biochemical nocturnal hypoglycemia is highly needed, especially in patients with recurrent severe hypoglycemia. We evaluated reliability of nocturnal continuous glucose monitoring (CGM) in patients with type 1 diabetes at high risk of severe...... from 23:00 to 07:00 h for plasma glucose (PG) measurements (gold standard). Results: Valid data were obtained in 217 nights. The sensitivity of CGM was 65% (95% confidence interval, 53-77%) below 4 mmol/L, 40% (24-56%) below 3 mmol/L, and 17% (0-47%) below 2.2 mmol/L. PG and CGM readings correlated in...

  10. Nocturnality and species survival.

    Daily, G C; Ehrlich, P R

    1996-10-15

    Surveys of butterfly and moth diversity in tropical forest fragments suggest that nocturnality confers a dispersal, and possibly a survival, advantage. The butterfly faunas of smaller fragments were depauperate; in contrast, the species richness of nocturnal moths was similar in all fragments and even in pasture. The lack of correlation between butterfly and moth species richness among fragments (r2 = 0.005) is best explained by movements of moths at night when ambient conditions in forest and pasture are most similar; butterflies face substantial daytime temperature, humidity, and solar radiation barriers. This interpretation is supported by information on birds, beetles, and bats. PMID:8876201

  11. Nocturnal panic attacks

    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.

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

    Lammertyn, Leandi; Schutte, Aletta Elisabeth; Schutte, Rudolph, et al.

    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. Nocturn and Aubade

    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...

  14. Nocturnal intermittent hemodialysis.

    Thumfart, Julia; Müller, Dominik

    2015-05-01

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

  15. Effects of day-time exposure to different light intensities on light-induced melatonin suppression at night

    Kozaki, Tomoaki; Kubokawa, Ayaka; Taketomi, Ryunosuke; Hatae, Keisuke

    2015-01-01

    Background Bright nocturnal light has been known to suppress melatonin secretion. However, bright light exposure during the day-time might reduce light-induced melatonin suppression (LIMS) at night. The effective proportion of day-time light to night-time light is unclear; however, only a few studies on accurately controlling both day- and night-time conditions have been conducted. This study aims to evaluate the effect of different day-time light intensities on LIMS. Methods Twelve male subj...

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

    E. Redondo; S Regodón; A. J. MASOT; Gázquez, A.; Franco, A.

    2003-01-01

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

  17. Absence of an increase in the duration of the circadian melatonin secretory episode in totally blind human subjects

    Klerman, E. B.; Zeitzer, J. M.; Duffy, J. F.; Khalsa, S. B.; Czeisler, C. A.

    2001-01-01

    The daily rhythm of melatonin influences multiple physiological measures, including sleep tendency, circadian rhythms, and reproductive function in seasonally breeding mammals. The biological signal for photoperiodic changes in seasonally breeding mammals is a change in the duration of melatonin secretion, which in a natural environment reflects the different durations of daylight across the year, with longer nights leading to a longer duration of melatonin secretion. These seasonal changes in the duration of melatonin secretion do not simply reflect the known acute suppression of melatonin secretion by ocular light exposure, but also represent long-term changes in the endogenous nocturnal melatonin episode that persist in constant conditions. As the eyes of totally blind individuals do not transmit ocular light information, we hypothesized that the duration of the melatonin secretory episode in blind subjects would be longer than those in sighted individuals, who are exposed to light for all their waking hours in an urban environment. We assessed the melatonin secretory profile during constant posture, dim light conditions in 17 blind and 157 sighted adults, all of whom were healthy and using no prescription or nonprescription medications. The duration of melatonin secretion was not significantly different between blind and sighted individuals. Healthy blind individuals after years without ocular light exposure do not have a longer duration of melatonin secretion than healthy sighted individuals.

  18. Anti-glucocorticoid effects of melatonin on adult rats.

    Aoyama, H; Mori, N; Mori, W

    1987-07-01

    To extend our previous experiment on anti-glucocorticoid effects of melatonin which was performed under a very special condition using young rats, we have carried out another experiment of long term administration of pineal hormone melatonin to adult female rats which were conditioned by overdose glucocorticoid. The results clearly demonstrated significant protection, by melatonin, from the injurious effects of a glucocorticoid, dexamethasone: decrease of body weight gain, atrophy of the thymus and adrenals, and elevation of the level of total cholesterol in blood. Thus, it has been clarified that anti-glucocorticoid effects of melatonin could be shown experimentally not only in young rats but also in adults, and also, could be really seen not only in short term experiment but also in longer ones. Anti-glucocorticoid effects of melatonin seem to be of considerably wide range, not being limited to occur under a special condition, including the age of animals, in experiments. PMID:3661196

  19. Arylalkylamine N-acetyltransferase (AANAT) genotype as a personal trait in melatonin synthesis.

    Blomeke, Brunhilde; Golka, Klaus; Griefahn, Barbara; Roemer, Hermann C

    2008-01-01

    The melatonin rhythm is arguably the best marker for the phase of the endogenous "biological clock." Arylalkylamine N-acetyltransferase (AANAT) is known to catalyze the acetylation of serotonin, a rate-limiting process in melatonin synthesis. Different single-nucleotide polymorphisms (SNPs) in the AANAT gene were identified recently in the Japanese population, and one of the genes was significantly associated with the delayed sleep phase syndrome. Thus, 54 healthy Caucasian males were genotyped to investigate whether these SNPs in the AANAT gene affected melatonin levels. The endogenous melatonin levels were analyzed in saliva under standardized experimental conditions ("constant routines") by radioimmunoassay. Despite the broad temporal variation of the human nocturnal melatonin profiles, none of the investigated SNPs were found in the AANAT gene in this study. These findings point to ethnic differences with respect to these SNPs, rather than time of day termed "morningness." In summary, SNPs in the AANAT gene identified thus far cannot explain the observed interindividual differences for nocturnal melatonin profiles in the subjects investigated. PMID:18569588

  20. Melatonin and cortisol profiles in late midlife and their association with age-related changes in cognition

    Waller, Katja Linda; Mortensen, Erik Lykke; Avlund, Kirsten; Fagerlund, Birgitte; Lauritzen, Martin; Gammeltoft, Steen; Jennum, Poul

    2016-01-01

    Previous studies have reported an association between circadian disturbances and age-related cognitive impairment. The aim was to study the 24-hour profiles of melatonin and cortisol in relation to cognitive function in middle-aged male subjects. Fifty healthy middle-aged males born in 1953 were recruited from a population-based cohort based on previous cognitive assessments in young adulthood and late midlife. The sample included 24 cognitively high-functioning and 26 cognitively impaired participants. Saliva samples were collected every 4 hours over a 24-hour period and analyzed for cortisol and melatonin levels by immunoassay. All participants exhibited clear circadian rhythms of salivary melatonin and cortisol. Salivary melatonin concentrations had a nocturnal peak at approximately 4 am. The median nocturnal melatonin response at 4 am was significantly lower in the cognitively impaired group than in the high-functioning group (−4.6 pg/mL, 95% CI: −7.84, −1.36, P=0.006). The 24-hour mean melatonin concentration (high-functioning group: 4.80±0.70 pg/mL, vs cognitively impaired group: 4.81±0.76 pg/mL; P>0.05) (or the area under the curve, AUC) was not significantly different between the two groups. Cortisol levels were low during the night, and peaked at approximately 8 am. Median cortisol concentrations were similar at all times, as were the 24-hour mean cortisol concentrations and AUC. To the best of our knowledge, ours is the first study to assess circadian measures (ie, melatonin and cortisol) in healthy middle-aged men with different cognitive trajectories in midlife. We found evidence of altered circadian rhythms with a reduced nocturnal melatonin response at 4 am in men with cognitive impairment. The 24-hour concentration and AUC of melatonin and cortisol were similar in the cognitively high-functioning group and in the cognitively impaired. PMID:26858531

  1. Melatonin Promotes Superovulation in Sika Deer (Cervus nippon

    Liang Wang

    2014-07-01

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

  2. Melatonin: the dark force.

    Bergstrom, W H; Hakanson, D O

    1998-01-01

    Although the pineal gland was described 2,300 years ago, its functions remained obscure and productive research was limited until 1958, when Lerner and associates defined melatonin. In 1965 Wurtman and Axelrod advanced the "melatonin hypothesis," according to which the pineal gland acts as a transducer responding to changes in circumambient light by changing its rates of melatonin output. Sites and mechanisms of melatonin action are still poorly understood. Two consistent effects are the induction of sleep and an antigonadotropic influence on reproductive structure and behavior. The former is demonstrable and clinically useful in human subjects; the latter has been shown in birds, rodents, and sheep. Alteration of skin color by the contraction of melanophores was effected by pineal extracts before the discovery of melatonin. This phenomenon, seen in reptiles, amphibians, and fish, has received little recent attention. Areas of greater interest and potential importance include the antimitotic effects of melatonin on some types of tumor cells in culture and the apparent in vivo protection of immunocompetent lymphocytes during chronic stress, which reduces the functional capacity of lymphocytes in control rodents. Clinical application of the antimitotic and immunosupportive properties of melatonin seems likely in the near future. Unfortunately, this innocent molecule has been touted in two recent books and many advertisements as an aphrodisiac, rejuvenator, protector against disease, and general wonder-worker. Because interest in melatonin is high, all physicians can expect questions and may have use for the information provided in this review. PMID:9742299

  3. Paroxysmal nocturnal hemoglobinuria

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

  4. Melatonin in Alzheimer's disease.

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

    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 patients with AD. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning and slows down the progression of cognitive impairment in AD patients. Melatonin efficiently protects neuronal cells from A?-mediated toxicity via antioxidant and anti-amyloid properties. It not only inhibits A? generation, but also arrests the formation of amyloid fibrils by a structure-dependent interaction with A?. Our studies have demonstrated that melatonin efficiently attenuates Alzheimer-like tau hyperphosphorylation. Although the exact mechanism is still not fully understood, a direct regulatory influence of melatonin on the activities of protein kinases and protein phosphatases is proposed. Additionally, melatonin also plays a role in protecting the cholinergic system and in anti-inflammation. The aim of this review is to stimulate interest in melatonin as a potentially useful agent in the prevention and treatment of AD. PMID:23857055

  5. Melatonin for primary insomnia?

    2009-07-01

    Melatonin, a hormone produced by the pineal gland, has a key role in regulating circadian rhythms, most importantly, the sleep-wake cycle. Melatonin's action has led to its being tried as a treatment for a wide range of sleep disorders, such as jet lag, primary insomnia, sleep-wake cycle disruption and sleep problems in children with neuro-developmental disorders. Until recently, it had not been licensed in the UK for any indication. Prolonged-release melatonin (Circadin - Lundbeck) has now been licensed as a treatment for primary insomnia. Here we consider whether this product has a place in the management of people with this condition. PMID:19567841

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

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

    2014-01-01

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

  7. Melatonin in Plants - Diversity of Levels and Multiplicity of Functions.

    Hardeland, Rüdiger

    2016-01-01

    Melatonin has been detected in numerous plant species. A particularly surprising finding concerns the highly divergent levels of melatonin that vary between species, organs and environmental conditions, from a few pg/g to over 20 μg/g, reportedly up to 200 μg/g. Highest values have been determined in oily seeds and in plant organs exposed to high UV radiation. The divergency of melatonin concentrations is discussed under various functional aspects and focused on several open questions. This comprises differences in precursor availability, catabolism, the relative contribution of isoenzymes of the melatonin biosynthetic pathway, and differences in rate limitation by either serotonin N-acetyltransferase or N-acetylserotonin O-methyltransferase. Other differences are related to the remarkable pleiotropy of melatonin, which exhibits properties as a growth regulator and morphogenetic factor, actually debated in terms of auxin-like effects, and as a signaling molecule that modulates pathways of ethylene, abscisic, jasmonic and salicylic acids and is involved in stress tolerance, pathogen defense and delay of senescence. In the context of high light/UV intensities, elevated melatonin levels exceed those required for signaling via stress-related phytohormones and may comprise direct antioxidant and photoprotectant properties, perhaps with a contribution of its oxidatively formed metabolites, such as N (1)-acetyl-N (2)-formyl-5-methoxykynuramine and its secondary products. High melatonin levels in seeds may also serve antioxidative protection and have been shown to promote seed viability and germination capacity. PMID:26925091

  8. Melatonin for the newborn

    Lucia Marseglia; Sara Manti; Gabriella D'Angelo; Eloisa Gitto; Ignazio Barberi

    2014-01-01

    Reactive oxygen species play an important role in the pathogenesis of several diseases during the perinatal and neonatal period. Melatonin, an effective direct free-radical scavenger and indirect antioxidant agent, diffuses through biological membranes easily and exerts pleiotropic actions on every cell. Several studies have tested the efficacy of melatonin to counteract oxidative damage in diseases of newborn such as chronic lung disease, perinatal brain injury, necrotizing enterocolitis and...

  9. [Paroxysmal nocturnal hemoglobinuria (PNH)].

    Nishimura, Jun-ichi; Kanakura, Yuzuru

    2008-03-01

    Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic stem cell disorder. The most common clinical manifestations of PNH include intravascular hemolysis, venous thrombosis, and bone marrow failure. Hematopoietic stems cells with mutant PIG-A are present in normal marrow, but they are not noticed because they have no advantage under normal circumstances. In the setting of immune-mediated bone marrow injury, such as that seen in aplastic anemia, PIG-A mutant cells are selected because they have a survival advantage based on deficiency of one or more GPI-anchored proteins. Expansion of the PIG-A-mutant clones occurs when other events that enhance the growth properties of the cells work together with the effects of the PIG-A mutation to enhance further the growth properties of the mutant cells. PMID:18330025

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

    Kamperis, Konstantinos; Rittig, Søren; Jørgensen, Kaj Anker; Djurhuus, Jens Christian

    2006-01-01

    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 <50% reduction in wet nights on dDAVP. We characterized the patients on the basis of...... their nocturnal urine production. The children with nocturnal polyuria excreted larger amounts of sodium and urea at night than nonpolyurics and controls. Solute-free water reabsorption as well as urinary arginine vasopressin and aquaporin-2 excretion were normal in polyurics, and no differences were...... found in atrial natriuretic peptide, angiotensin II, aldosterone, and renin levels. Urinary prostaglandin E2 (PGE2) excretion was significantly higher in polyurics. The nocturnal polyuria in children with dDAVP-resistant nocturnal enuresis seems to be the result of augmented sodium and urea excretion...

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

    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.

  12. Myocardial infarction and nocturnal hypoxaemia

    Penčić 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. .

  13. Melatonin und das kardiovaskuläre System

    Sakotnik A

    1999-01-01

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

  14. Role of Melatonin in Schizophrenia

    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.

  15. Melatonin labeled with hydrogen isotopes

    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)

  16. Light-induced melatonin suppression at night after exposure to different wavelength composition of morning light.

    Kozaki, Tomoaki; Kubokawa, Ayaka; Taketomi, Ryunosuke; Hatae, Keisuke

    2016-03-11

    Bright nocturnal light has been shown to suppress melatonin secretion. However, bright light exposure during the day might reduce light-induced melatonin suppression at night. The human circadian system is sensitive to short wavelength light. This study evaluated the preventive effect of different wavelengths of daytime light on light-induced melatonin suppression at night. Twelve male subjects were exposed to various light conditions (dim, white, and bluish white light) between the hours of 09:00 and 10:30 (daytime light conditions). They were then exposed to light (300lx) again between 01:00 and 02:30 (night-time light exposure). Subjects provided saliva samples before (00:55) and after night-time light exposure (02:30). A two-tailed paired t-test yielded significant decrements in melatonin concentrations after night-time light exposure under daytime dim and white light conditions. No significant differences were found in melatonin concentrations between pre- and post-night-time light exposure with bluish-white light. Present findings suggest that daytime blue light exposure has an acute preventive impact on light-induced melatonin suppression in individuals with a general life rhythm (sleep/wake schedule). These findings may be useful for implementing artificial light environments for humans in, for example, hospitals and underground shopping malls to reduce health risks. PMID:26777427

  17. Experience with sustained-release melatonin for the treatment of sleep disorders in depression

    Svetlana Vladimirovna Prokhorova

    2015-10-01

    Full Text Available The data available in the literature on the role of melatonin in the regulation of circadian rhythms and sleep disorders in the population and in patients with mental diseases are analyzed. The cause of insomnia may be circadian rhythm disorders due to the age-related decline in the elaboration of the endogenous hormones that are responsible for the quality and duration of sleep, one of which is melatonin.Sustained-release melatonin is a synthetic analogue of the endogenous human pineal hormone melatonin. According to clinical findings, the main proven clinical effects of sustained-release melatonin 2 mg are a reduction in the latency of sleep, improvement of its quality, and lack of daytime sleepiness. The drug causes no dependence on its long use and rebound symptoms (increased insomnia symptoms, positively affects cognitive functions, and lowers nocturnal blood pressure in hypertensive patients.The paper describes a clinical case of a female patient with recurrent depressive disorder, in whom sustained-release melatonin 2 mg has demonstrated high efficacy and good tolerability in the combination therapy of sleep disorders in the pattern of depression.

  18. Role of melatonin on diabetes-related metabolic disorders

    Javier Espino

    2011-01-01

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

  19. MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective.

    Liu, Jiabei; Clough, Shannon J; Hutchinson, Anthony J; Adamah-Biassi, Ekue B; Popovska-Gorevski, Marina; Dubocovich, Margarita L

    2016-01-01

    Melatonin, or 5-methoxy-N-acetyltryptamine, is synthesized and released by the pineal gland and locally in the retina following a circadian rhythm, with low levels during the day and elevated levels at night. Melatonin activates two high-affinity G protein-coupled receptors, termed MT1 and MT2, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer. Progress in understanding the role of melatonin receptors in the modulation of sleep and circadian rhythms has led to the discovery of a novel class of melatonin agonists for treating insomnia, circadian rhythms, mood disorders, and cancer. This review describes the pharmacological properties of a slow-release melatonin preparation (i.e., Circadin®) and synthetic ligands (i.e., agomelatine, ramelteon, tasimelteon), with emphasis on identifying specific therapeutic effects mediated through MT1 and MT2 receptor activation. Discovery of selective ligands targeting the MT1 or the MT2 melatonin receptors may promote the development of novel and more efficacious therapeutic agents. PMID:26514204

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

    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 (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

  1. Seasonality, suicidality and melatonin.

    Havaki-Kontaxaki, B J; Papalias, E; Kontaxaki, M-E V; Papadimitriou, G N

    2010-01-01

    Seasonality of suicidal behavior has been investigated regarding both neurobiological and climatic factors, as well as psychopathological and social aspects. Most of the studies detectedpeaks in late spring and troughs in the winter. Several lines of evidence evaluated the role of extended periods of light associated with probability of suicides whereas others summarize the alterations of melatonin excretion and its seasonal variation along with seasonaldistribution of psychiatric disorders. The purpose of this paper is to provide an overview of studies attempted to reach an explanatory model of underlying pathophysiology of melatonin in thepathogenesis of seasonal variation in suicidality. There is argument on the interconnection between suicide rates and weather factors. However, an inverse pattern of melatonin levels and the seasonalpeak in suicides was observed. These findings suggest that sunlight exposure along with a wide spectrum of other factors may explain the aetiopathogenesis of suicidal behavior. PMID:21914615

  2. Activation of Melatonin Receptors Reduces Relapse-Like Alcohol Consumption.

    Vengeliene, Valentina; Noori, Hamid R; Spanagel, Rainer

    2015-12-01

    Melatonin is an endogenous synchronizer of biological rhythms and a modulator of physiological functions and behaviors of all mammals. Reduced levels of melatonin and a delay of its nocturnal peak concentration have been found in alcohol-dependent patients and rats. Here we investigated whether the melatonergic system is a novel target to treat alcohol addiction. Male Wistar rats were subjected to long-term voluntary alcohol consumption with repeated abstinence phases. Circadian drinking rhythmicity and patterns were registered with high temporal resolution by a drinkometer system and analyzed by Fourier analysis. We examined potential antirelapse effect of the novel antidepressant drug agomelatine. Given that agomelatine is a potent MT1 and MT2 receptor agonist and a 5-HT2C antagonist we also tested the effects of melatonin itself and the 5-HT2C antagonist SB242084. All drugs reduced relapse-like drinking. Agomelatine and melatonin administered at the end of the light phase led to very similar changes on all measures of the post-abstinence drinking behavior, suggesting that effects of agomelatine on relapse-like behavior are mostly driven by its melatonergic activity. Both drugs caused a clear phase advance in the diurnal drinking pattern when compared with the control vehicle-treated group and a reduced frequency of approaches to alcohol bottles. Melatonin given at the onset of the light phase had no effect on the circadian phase and very small effects on alcohol consumption. We conclude that targeting the melatonergic system in alcohol-dependent individuals can induce a circadian phase advance, which may restore normal sleep architecture and reduce relapse behavior. PMID:25994077

  3. [Monosymptomatic nocturnal enuresis

    Meneses, R de P

    2001-01-01

    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 patient? families. PMID:14647579

  4. Therapeutic applications of melatonin

    Kostoglou-Athanassiou, Ifigenia

    2013-01-01

    Melatonin is a methoxyindole synthesized within the pineal gland. The hormone is secreted during the night and appears to play multiple roles within the human organism. The hormone contributes to the regulation of biological rhythms, may induce sleep, has strong antioxidant action and appears to contribute to the protection of the organism from carcinogenesis and neurodegenerative disorders.

  5. Clinical pharmacokinetics of melatonin

    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...

  6. New insights into nocturnal nucleation

    I. K. Ortega

    2012-05-01

    Full Text Available Formation of new aerosol particles by nucleation and growth is a significant source of aerosols in the atmosphere. New particle formation events usually take place during daytime, but in some locations they have been observed also at night. In the present study we have combined chamber experiments, quantum chemical calculations and aerosol dynamics models to study nocturnal new particle formation. All our approaches demonstrate, in a consistent manner, that the oxidation products of monoterpenes play an important role in nocturnal nucleation events. By varying the conditions in our chamber experiments, we were able to reproduce the very different types of nocturnal events observed earlier in the atmosphere. The exact strength, duration and shape of the events appears to be sensitive to the type and concentration of reacting monoterpenes, as well as the extent to which the monoterpenes are exposed to ozone and potentially other atmospheric oxidants.

  7. Endogenous melatonin and oxidatively damaged guanine in DNA

    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.

  8. Genetics Home Reference: paroxysmal nocturnal hemoglobinuria

    ... mutations in paroxysmal nocturnal hemoglobinuria and in normal hematopoiesis. Leuk Lymphoma. 2006 Jul;47(7):1215-21. ... Kinoshita T. Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH). ...

  9. Melatonin: Buffering the Immune System

    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.

  10. Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

    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.

  11. Role of Melatonin in Schizophrenia

    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...

  12. Melatonin Poisoning: A Case Report

    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.

  13. Pineal and circulating melatonin rhythms in the box turtle, Terrapene carolina triunguis: effect of photoperiod, light pulse, and environmental temperature.

    Vivien-Roels, B; Pévet, P; Claustrat, B

    1988-02-01

    Pineal and circulating melatonin concentrations have been measured throughout the 24-hr cycle in the box turtle, Terrapene carolina triunguis, under different conditions of photoperiod and temperature. An obvious effect of photoperiod on the duration of the night rise of pineal and circulating melatonin is observed; the period of elevated melatonin is 4.30 hr in long photoperiod (18L:6D) and 11.00 hr in short photoperiod (8L:16D). A single pulse of 1 hr illumination beginning 1.30 hr after the onset of darkness, in a 16L:8D cycle, has no effect on pineal or circulating melatonin levels. A clear effect of environmental temperature on the amplitude of the day-night rhythm of melatonin production is observed. A possible role of the pineal of poikilotherms in the transduction of several environmental factors, via the daily pattern of melatonin secretion, is hypothesized. PMID:3366352

  14. Melatonin protects hepatocytes against bile acid-induced mitochondrial oxidative stress via the AMPK-SIRT3-SOD2 pathway.

    Chen, Y; Qing, W; Sun, M; Lv, L; Guo, D; Jiang, Y

    2015-10-01

    Mitochondrial oxidative damage is hypothesized to contribute to the pathogenesis of chronic cholestatic liver diseases. Melatonin, an indolamine synthesized in the pineal gland, shows a wide range of physiological functions, and is under clinical investigation for expanded applications. Melatonin has demonstrated efficient protective effects against various types of oxidative damage in the liver system. This study investigates the protective effects of melatonin pretreatment on glycochenodeoxycholic acid (GCDCA)-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. Melatonin markedly decreased mitochondrial ROS (mROS) production in L02 cells treated with 100 μM GCDCA, and inhibited GCDCA-stimulated cytotoxicity. Notably, melatonin exerted its hepatoprotective effects by upregulating sirtuin 3 (SIRT3) activity and its expression level, thus regulating superoxide dismutase 2 (SOD2) acetylation and inhibiting the production of mROS induced by GCDCA. Moreover, siRNA targeting SIRT3 blocked the melatonin-mediated elevation in mitochondrial function by inhibiting SIRT3/SOD2 signaling. Importantly, melatonin-activated SIRT3 activity was completely abolished by AMP-activated, alpha 1 catalytic subunit (AMPK) siRNA transfection. Similar results were obtained in rat with bile duct ligation or BDL. In summary, our findings indicate that melatonin is a novel hepatoprotective small molecule that functions by elevating SIRT3, stimulating SOD2 activity, and suppressing mitochondrial oxidative stress at least through AMPK, and that SIRT3 may be of therapeutic value in liver cell protection for GCDCA-induced hepatotoxicity. PMID:26118716

  15. Nocturnal Lagrangian Transport of Industrial Plumes from a US Megacity

    Zhang, R.; Fortner, E.; Zheng, J.; Zaveri, R.; Berkowitz, C.; Voss, P.; Valente, R.; Culis, A.; Olaguer, J.

    2007-05-01

    A Twin Otter research aircraft equipped with a suite of instruments measuring O3, NOx, and volatile organic compounds (VOCs) in conjunction with an altitude controlled balloon (tetroon) was used to investigate nocturnal transport of industrial plumes from the Houston metropolitan area during the 2005 Southeast Texas Tetroon Study (SETTS). Polluted air masses with elevated O3, CO, and NOx along with elevated mass peaks characteristic of industrial VOCs detected by a proton transfer reaction-mass spectrometer (PTR-MS) were tracked from the Houston metropolitan area to remote locations over distances as far as 200 miles. In addition, high levels of biogenic isoprene and its oxidation products such methyl vinyl ketone and methacrolein were detected outside of the polluted plumes. The measurements revealed efficient nocturnal transport of highly reactive VOCs, particularly light alkenes and their oxidation products from the industrial sources, which needs to be considered when assessing the regional effects of a major metropolitan/industrial urban center.

  16. Melatonin Receptor Genes in Vertebrates

    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.

  17. Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome.

    Beck-Friis, J; Kjellman, B F; Aperia, B; Undén, F; von Rosen, D; Ljunggren, J G; Wetterberg, L

    1985-04-01

    Maximum nocturnal serum melatonin level (MTmax) in relation to some clinical variables was studied in 32 patients with a major depressive episode and in 33 healthy subjects with reference to the outcome of the dexamethasone suppression test (DST). Significant regressions were found between MTmax levels and clinical rating scores in CPRS, interpreted as retardation symptoms. Four healthy subjects with disposition for dysthymic reactions had subnormal MTmax levels, which differed from MTmax levels in subjects without such disposition. Patients but not the healthy subjects, who reported parental loss before 17 years of age, had subnormal MTmax levels and differed from patients with no reported parental loss. Patients with no reported suicidal behaviour in clinical history had significantly lower MTmax levels than patients with reported suicide attempts. No relations were found between low MTmax levels and diagnoses, duration of illness, reported inheritance for depressive illness or sleep disturbances. A hypothetical low melatonin syndrome in depression is proposed: low nocturnal melatonin, abnormal dexamethasone suppression test, disturbed 24-h rhythm of cortisol, less pronounced daily and annual cyclic variation in depressive symptomatology. PMID:4039876

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

    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-γ (PPAR-γ), 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-γ coactivator 1 α, 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

  19. Inverted rhythm of melatonin secretion in Smith-Magenis syndrome: from symptoms to treatment.

    De Leersnyder, Hélène

    2006-09-01

    Smith-Magenis syndrome (SMS) is a mental retardation syndrome with distinctive behavioral characteristics, dysmorphic features and congenital anomalies ascribed to an interstitial deletion of chromosome 17p11.2. Severe sleep disturbances and maladaptative daytime behavior have been linked to an abnormal circadian secretion pattern of melatonin, with a diurnal instead of nocturnal secretion of this hormone. SMS provides a demonstration of a biological basis for sleep disorder in a genetic disease. Considering that clock genes mediate the generation of the circadian rhythm, haploinsufficiency for a circadian system gene, mapping to chromosome 17p11.2 might cause the inversion of the melatonin circadian rhythm in SMS. The disorder of circadian timing in SMS might also affect the entrainment pathway (retinohypothalamic tract), pacemaker functions (suprachiasmatic nucleus) or synthesis and release of melatonin by the pineal gland. Elucidating pathophysiological mechanisms of behavioral phenotypes in genetic disease can provide an original therapeutic approach in SMS: blockade of endogenous melatonin production during the day combined with exogenous melatonin administration in the evening. PMID:16890450

  20. Short-term sleep deprivation with nocturnal light exposure alters time-dependent glucagon-like peptide-1 and insulin secretion in male volunteers.

    Gil-Lozano, Manuel; Hunter, Paola M; Behan, Lucy-Ann; Gladanac, Bojana; Casper, Robert F; Brubaker, Patricia L

    2016-01-01

    The intestinal L cell is the principal source of glucagon-like peptide-1 (GLP-1), a major determinant of insulin release. Because GLP-1 secretion is regulated in a circadian manner in rodents, we investigated whether the activity of the human L cell is also time sensitive. Rhythmic fluctuations in the mRNA levels of canonical clock genes were found in the human NCI-H716 L cell model, which also showed a time-dependent pattern in their response to well-established secretagogues. A diurnal variation in GLP-1 responses to identical meals (850 kcal), served 12 h apart in the normal dark (2300) and light (1100) periods, was also observed in male volunteers maintained under standard sleep and light conditions. These findings suggest the existence of a daily pattern of activity in the human L cell. Moreover, we separately tested the short-term effects of sleep deprivation and nocturnal light exposure on basal and postprandial GLP-1, insulin, and glucose levels in the same volunteers. Sleep deprivation with nocturnal light exposure disrupted the melatonin and cortisol profiles and increased insulin resistance. Moreover, it also induced profound derangements in GLP-1 and insulin responses such that postprandial GLP-1 and insulin levels were markedly elevated and the normal variation in GLP-1 responses was abrogated. These alterations were not observed in sleep-deprived participants maintained under dark conditions, indicating a direct effect of light on the mechanisms that regulate glucose homeostasis. Accordingly, the metabolic abnormalities known to occur in shift workers may be related to the effects of irregular light-dark cycles on these glucoregulatory pathways. PMID:26530153

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

    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.

  2. Melatonin and Melatonin Agonists as Adjunctive Treatments in Bipolar Disorders.

    Geoffroy, Pierre Alexis; Etain, Bruno; Franchi, Jean-Arthur Micoulaud; Bellivier, Frank; Ritter, Philipp

    2015-01-01

    Bipolar disorders (BD) present with abnormalities of circadian rhythmicity and sleep homeostasis, even during phases of remission. These abnormalities are linked to the underlying neurobiology of genetic susceptibility to BD. Melatonin is a pineal gland secreted neurohormone that induces circadian-related and sleep-related responses. Exogenous melatonin has demonstrated efficacy in treating primary insomnia, delayed sleep phase disorder, improving sleep parameters and overall sleep quality, and some psychiatric disorders like autistic spectrum disorders. In order to evaluate the efficacy of melatonin among patients with BD, this comprehensive review emphasizes the abnormal melatonin function in BD, the rationale of melatonin action in BD, the available data about the exogenous administration of melatonin, and melatonin agonists (ramelteon and tasimelteon), and recommendations of use in patients with BD. There is a scientific rationale to propose melatonin-agonists as an adjunctive treatment of mood stabilizers in treating sleep disorders in BD and thus to possibly prevent relapses when administered during remission phases. We emphasized the need to treat insomnia, sleep delayed latencies and sleep abnormalities in BD that are prodromal markers of an emerging mood episode and possible targets to prevent future relapses. An additional interesting adjunctive therapeutic effect might be on preventing metabolic syndrome, particularly in patients treated with antipsychotics. Finally, melatonin is well tolerated and has little dependence potential in contrast to most available sleep medications. Further studies are expected to be able to produce stronger evidence-based therapeutic guidelines to confirm and delineate the routine use of melatonin-agonists in the treatment of BD. PMID:26088111

  3. Daytime Blue Light Enhances the Nighttime Circadian Melatonin Inhibition of Human Prostate Cancer Growth.

    Dauchy, Robert T; Hoffman, Aaron E; Wren-Dail, Melissa A; Hanifin, John P; Warfield, Benjamin; Brainard, George C; Xiang, Shulin; Yuan, Lin; Hill, Steven M; Belancio, Victoria P; Dauchy, Erin M; Smith, Kara; Blask, David E

    2015-12-01

    Light controls pineal melatonin production and temporally coordinates circadian rhythms of metabolism and physiology in normal and neoplastic tissues. We previously showed that peak circulating nocturnal melatonin levels were 7-fold higher after daytime spectral transmittance of white light through blue-tinted (compared with clear) rodent cages. Here, we tested the hypothesis that daytime blue-light amplification of nocturnal melatonin enhances the inhibition of metabolism, signaling activity, and growth of prostate cancer xenografts. Compared with male nude rats housed in clear cages under a 12:12-h light:dark cycle, rats in blue-tinted cages (with increased transmittance of 462-484 nm and decreased red light greater than 640 nm) evinced over 6-fold higher peak plasma melatonin levels at middark phase (time, 2400), whereas midlight-phase levels (1200) were low (less than 3 pg/mL) in both groups. Circadian rhythms of arterial plasma levels of linoleic acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were disrupted in rats in blue cages as compared with the corresponding entrained rhythms in clear-caged rats. After implantation with tissue-isolated PC3 human prostate cancer xenografts, tumor latency-to-onset of growth and growth rates were markedly delayed, and tumor cAMP levels, uptake-metabolism of linoleic acid, aerobic glycolysis (Warburg effect), and growth signaling activities were reduced in rats in blue compared with clear cages. These data show that the amplification of nighttime melatonin levels by exposing nude rats to blue light during the daytime significantly reduces human prostate cancer metabolic, signaling, and proliferative activities. PMID:26678364

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

    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.

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

    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...

  6. Circadian Gating of Epithelial-to-Mesenchymal Transition in Breast Cancer Cells Via Melatonin-Regulation of GSK3β

    Mao, Lulu; Dauchy, Robert T; Blask, David E.; Slakey, Lauren M; Xiang, Shulin; Yuan, Lin; Dauchy, Erin M; Shan, Bin; Brainard, George C.; Hanifin, John P.; Frasch, Tripp; Duplessis, Tamika T.; Hill, Steven M.

    2012-01-01

    Disturbed sleep-wake cycle and circadian rhythmicity are associated with cancer, but the underlying mechanisms are unknown. Employing a tissue-isolated human breast xenograft tumor nude rat model, we observed that glycogen synthase kinase 3β (GSK3β), an enzyme critical in metabolism and cell proliferation/survival, exhibits a circadian rhythm of phosphorylation in human breast tumors. Exposure to light-at-night suppresses the nocturnal pineal melatonin synthesis, disrupting the circadian rhyt...

  7. In the Heat of the Night: Thermo-TRPV Channels in the Salmonid Pineal Photoreceptors and Modulation of Melatonin Secretion.

    Nisembaum, Laura Gabriela; Besseau, Laurence; Paulin, Charles-Hubert; Charpantier, Alice; Martin, Patrick; Magnanou, Elodie; Fuentès, Michael; Delgado, Maria-Jesus; Falcón, Jack

    2015-12-01

    Photoperiod plays an essential role in the synchronization of metabolism, physiology, and behavior to the cyclic variations of the environment. In vertebrates, information is relayed by the pineal cells and translated into the nocturnal production of melatonin. The duration of this signal corresponds to the duration of the night. In fish, the pinealocytes are true photoreceptors in which the amplitude of the nocturnal surge is modulated by temperature in a species-dependent manner. Thus, the daily and annual variations in the amplitude and duration of the nocturnal melatonin signal provide information on daily and calendar time. Both light and temperature act on the activity of the penultimate enzyme in the melatonin biosynthesis pathway, the arylalkylamine N-acetyltransferase (serotonin ? N-acetylserotonin). Although the mechanisms of the light/dark regulation of melatonin secretion are quite well understood, those of temperature remain unelucidated. More generally, the mechanisms of thermoreception are unknown in ectotherms. Here we provide the first evidence that two thermotransient receptor potential (TRP) channels, TRPV1 and TRPV4, are expressed in the pineal photoreceptor cells of a teleost fish, in which they modulate melatonin secretion in vitro. The effects are temperature dependent, at least for TRPV1. Our data support the idea that the pineal of fish is involved in thermoregulation and that the pineal photoreceptors are also thermoreceptors. In other nervous and nonnervous tissues, TRPV1 and TRPV4 display a ubiquitous but quantitatively variable distribution. These results are a fundamental step in the elucidation of the mechanisms of temperature transduction in fish. PMID:26389691

  8. Visual Navigation in Nocturnal Insects.

    Warrant, Eric; Dacke, Marie

    2016-05-01

    Despite their tiny eyes and brains, nocturnal insects have evolved a remarkable capacity to visually navigate at night. Whereas some use moonlight or the stars as celestial compass cues to maintain a straight-line course, others use visual landmarks to navigate to and from their nest. These impressive abilities rely on highly sensitive compound eyes and specialized visual processing strategies in the brain. PMID:27053732

  9. Acute melatonin and para-chloroamphetamine interactions on pineal, brain and serum serotonin levels as well as stress hormone levels.

    Manzana, E J; Chen, W J; Champney, T H

    2001-08-01

    para-Chloroamphetamine, an amphetamine analog, alters serotonergic neurochemistry. In previous reports, melatonin (MEL), when administered with other amphetamine analogs, altered the decline in serotonin content produced by these analogs. The present studies assessed the effects of various doses of melatonin and p-chloroamphetamine on serotonin levels in numerous brain regions in male rats. Melatonin (10, 25 or 50 mg/kg, s.c.) and p-chloroamphetamine (3 or 5 mg/kg, s.c.) were administered and, 3 h later, brain samples and serum were collected. Serotonin levels in the serum and various regions of the brain were assayed using high-performance liquid chromatography. Melatonin in combination with a high dose of p-chloroamphetamine (5 mg/kg) produced cumulative deficits in serotonin levels in the serum. However, serotonin levels in the pineal, cortex or brain stem in all combined melatonin and p-chloroamphetamine groups were not significantly different from groups that received p-chloroamphetamine alone. Serum adrenocorticotropin (ACTH) and corticosterone levels were significantly elevated in the melatonin and p-chloroamphetamine combined groups, suggesting that animals receiving both treatments were more stressed than control animals or animals receiving melatonin or p-chloroamphetamine alone. These results indicate that melatonin does not alter p-chloroamphetamine-induced deficits in central serotonin levels. The increased serum adrenocorticotropic hormone, corticosterone and serotonin levels observed following melatonin and p-chloroamphetamine treatment suggest that this combination may have adverse peripheral effects. PMID:11478929

  10. The cause of ischaemic nocturnal rest pain

    Jelnes, Rolf; Bülow, J; Tønnesen, K H; Lassen, N A; Holstein, P

    1988-01-01

    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....

  11. Review of disrupted sleep patterns in Smith-Magenis syndrome and normal melatonin secretion in a patient with an atypical interstitial 17p11.2 deletion.

    Boudreau, Eilis A; Johnson, Kyle P; Jackman, Angela R; Blancato, Jan; Huizing, Marjan; Bendavid, Claude; Jones, Marypat; Chandrasekharappa, Settara C; Lewy, Alfred J; Smith, Ann C M; Magenis, R Ellen

    2009-07-01

    Smith-Magenis syndrome (SMS) is a disorder characterized by multiple congenital anomalies and behavior problems, including abnormal sleep patterns. It is most commonly due to a 3.5 Mb interstitial deletion of chromosome 17 band p11.2. Secretion of melatonin, a hormone produced by the pineal gland, is the body's signal for nighttime darkness. Published reports of 24-hr melatonin secretion patterns in two independent SMS cohorts (US and France) document an inverted endogenous melatonin pattern in virtually all cases (96%), suggesting that this finding is pathognomic for the syndrome. We report on a woman with SMS due to an atypical large proximal deletion ( approximately 6Mb; cenTNFRSFproteinB) of chromosome band (17)(p11.2p11.2) who presents with typical sleep disturbances but a normal pattern of melatonin secretion. We further describe a melatonin light suppression test in this patient. This is the second reported patient with a normal endogenous melatonin rhythm in SMS associated with an atypical large deletion. These two patients are significant because they suggest that the sleep disturbances in SMS cannot be solely attributed to the abnormal diurnal melatonin secretion versus the normal nocturnal pattern. PMID:19530184

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

    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.

  13. Melatonin in Plants – Diversity of Levels and Multiplicity of Functions

    Hardeland, Rüdiger

    2016-01-01

    Melatonin has been detected in numerous plant species. A particularly surprising finding concerns the highly divergent levels of melatonin that vary between species, organs and environmental conditions, from a few pg/g to over 20 μg/g, reportedly up to 200 μg/g. Highest values have been determined in oily seeds and in plant organs exposed to high UV radiation. The divergency of melatonin concentrations is discussed under various functional aspects and focused on several open questions. This comprises differences in precursor availability, catabolism, the relative contribution of isoenzymes of the melatonin biosynthetic pathway, and differences in rate limitation by either serotonin N-acetyltransferase or N-acetylserotonin O-methyltransferase. Other differences are related to the remarkable pleiotropy of melatonin, which exhibits properties as a growth regulator and morphogenetic factor, actually debated in terms of auxin-like effects, and as a signaling molecule that modulates pathways of ethylene, abscisic, jasmonic and salicylic acids and is involved in stress tolerance, pathogen defense and delay of senescence. In the context of high light/UV intensities, elevated melatonin levels exceed those required for signaling via stress-related phytohormones and may comprise direct antioxidant and photoprotectant properties, perhaps with a contribution of its oxidatively formed metabolites, such as N1-acetyl-N2-formyl-5-methoxykynuramine and its secondary products. High melatonin levels in seeds may also serve antioxidative protection and have been shown to promote seed viability and germination capacity. PMID:26925091

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

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

    1995-12-31

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

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

    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.

  16. The organization of melatonin in lipid membranes.

    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

  17. Melatonin and human skin aging

    Kleszczynski, Konrad; Fischer, Tobias W.

    2012-01-01

    Like the whole organism, skin follows the process of aging during life-time. Additional to internal factors, several environmental factors, such as solar radiation, considerably contribute to this process. While fundamental mechanisms regarding skin aging are known, new aspects of anti-aging agents such as melatonin are introduced. Melatonin is a hormone produced in the glandula pinealis that follows a circadian light-dependent rhythm of secretion. It has been experimentally implicated in ski...

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

    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

  19. HEME OXYGENASE-1 UPREGULATED BY MELATONIN: POTENTIAL PROTECTION AGAINST BURN-INDUCED OXIDATIVE GASTRIC MUCOSAL INJURY.

    Minka Hristova

    2015-05-01

    Full Text Available Melatonin is indoleamine hormone derived from L-tryptophan. Due to its lipophilic nature, it is accessible to every cell. Melatonin has immunomodulatory and antioxidant activities thus protecting tissue injury. Heat shock proteins such as HSP32 known as heme oxygenase-1 (HO-1 possesses antioxidant, anti-inflammatory, and vasodilatory properties and plays an important role in the protecting of tissues from several stresses. The aim of study is to investigate the expression of HO-1 in gastric mucosa and its connection with oxidative stress and melatonin mediated protection after thermal injury. On rats back, under anesthesia, third degree burn was applied involving 30% of total body surface area (TBSA. Melatonin (10 mg per kg body mass was injected i.p. immediately and 12 hours after thermal skin injury. We used tissue malondialdehyde (MDA, lipid peroxidation product, as a marker of oxidative stress. Gastric mucosa histopathology were observed on light microscopy and light immunohistochemistry investigating the HO-1 too. Results: The levels of MDA in gastric mucosa were elevated (p< 0.05. The HO-1 expression was significantly increased in rats with trauma. Melatonin inhibited elevation in lipid peroxidation product and augmented the increase in expression of HO-1 in the gastric mucosa. In conclusion, our data suggest that HO-1 induction following burn injury is an adaptive response protecting gastric mucosal against further oxidative damage. Melatonin increased the antioxidant capacity and restricted burn-induced oxidative damage in gastric mucosa and thus could be used therapeutically in organ protection.

  20. Melatonin and Sleep-Wake Rhythms before and after Ocular Lens Replacement in Elderly Humans.

    Giménez, Marina; Beersma, Domien; Daan, Serge; Pol, Bert van der; Kanis, Martijn; van Norren, Dick; Gordijn, Marijke

    2016-01-01

    Light of short wavelengths has been shown to play a key role in non-image forming responses. Due to aging, the ocular lens becomes more yellow reducing the transmission of short wavelengths in the elderly. In the present study, we make use of cataract surgery to investigate the effects of a relative increase of short wavelength transmission on melatonin- and sleep-wake rhythms (N = 14). We observed, on average, a delay of the sleep-wake and the nocturnal melatonin rhythms after cataract surgery. This delay is tentatively attributed to a relatively large increase of light transmittance in the evening hours more than an increase of the already relatively high light intensities found in the daytime. The later phase that we observed after cataract surgery (clear lens) as compared to the earlier phase observed before cataract (yellowish lens) is in agreement with the general later phase reported in the young (clear lens) population. PMID:26891336

  1. Melatonin and Sleep-Wake Rhythms before and after Ocular Lens Replacement in Elderly Humans

    Marina Giménez

    2016-02-01

    Full Text Available Light of short wavelengths has been shown to play a key role in non-image forming responses. Due to aging, the ocular lens becomes more yellow reducing the transmission of short wavelengths in the elderly. In the present study, we make use of cataract surgery to investigate the effects of a relative increase of short wavelength transmission on melatonin- and sleep-wake rhythms (N = 14. We observed, on average, a delay of the sleep-wake and the nocturnal melatonin rhythms after cataract surgery. This delay is tentatively attributed to a relatively large increase of light transmittance in the evening hours more than an increase of the already relatively high light intensities found in the daytime. The later phase that we observed after cataract surgery (clear lens as compared to the earlier phase observed before cataract (yellowish lens is in agreement with the general later phase reported in the young (clear lens population.

  2. Melatonin Suppression by Light in Humans Is More Sensitive Than Previously Reported.

    Vartanian, Garen V; Li, Benjamin Y; Chervenak, Andrew P; Walch, Olivia J; Pack, Weston; Ala-Laurila, Petri; Wong, Kwoon Y

    2015-08-01

    The retina drives various non-image-forming photoresponses, including circadian photoentrainment and pupil constriction. Previous investigators showed that in humans, photic suppression of the clock-controlled hormone melatonin is most sensitive to 460-nm blue light, with a threshold of ~12 log photons cm(-2) s(-1). This threshold is surprising because non-image-forming vision is mediated by intrinsically photosensitive retinal ganglion cells, which receive rod-driven synaptic input and can respond to light levels as low as ~7 log photons cm(-2) s(-1). Using a protocol that enhances data precision, we have found the threshold for human melatonin suppression to be ~10 log photons cm(-2) s(-1) at 460 nm. This finding has far-reaching implications since there is mounting evidence that nocturnal activation of the circadian system can be harmful. PMID:26017927

  3. Sleep and psychological disturbance in nocturnal asthma

    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 ...

  4. The Safety of Melatonin in Humans.

    Andersen, Lars Peter Holst; Gögenur, Ismail; Rosenberg, Jacob; Reiter, Russel J

    2016-03-01

    Exogenous melatonin has been investigated as treatment for a number of medical and surgical diseases, demonstrating encouraging results. The aim of this review was to present and evaluate the literature concerning the possible adverse effects and safety of exogenous melatonin in humans. Furthermore, we provide recommendations concerning the possible risks of melatonin use in specific patient groups. In general, animal and human studies documented that short-term use of melatonin is safe, even in extreme doses. Only mild adverse effects, such as dizziness, headache, nausea and sleepiness have been reported. No studies have indicated that exogenous melatonin should induce any serious adverse effects. Similarly, randomized clinical studies indicate that long-term melatonin treatment causes only mild adverse effects comparable to placebo. Long-term safety of melatonin in children and adolescents, however, requires further investigation. Due to a lack of human studies, pregnant and breast-feeding women should not take exogenous melatonin at this moment. PMID:26692007

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

    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

  6. Sertraline and venlafaxine-induced nocturnal enuresis

    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.

  7. Melatonin, melatonin receptors and melanophores: a moving story.

    Sugden, David; Davidson, Kathryn; Hough, Kate A; Teh, Muy-Teck

    2004-10-01

    Melatonin (5-methoxy N-acetyltryptamine) is a hormone synthesized and released from the pineal gland at night, which acts on specific high affinity G-protein coupled receptors to regulate various aspects of physiology and behaviour, including circadian and seasonal responses, and some retinal, cardiovascular and immunological functions. In amphibians, such as Xenopus laevis, another role of melatonin is in the control of skin coloration through an action on melanin-containing pigment granules (melanosomes) in melanophores. In these cells, very low concentrations of melatonin activate the Mel(1c) receptor subtype triggering movement of granules toward the cell centre thus lightening skin colour. Mel(1c) receptor activation reduces intracellular cAMP via a pertussis toxin-sensitive inhibitory G-protein (Gi), but how this and other intracellular signals regulate pigment movement is not yet fully understood. However, melanophores have proven an excellent model for the study of the molecular mechanisms which coordinate intracellular transport. Melanosome transport is reversible and involves both actin- (myosin V) and microtubule-dependent (kinesin II and dynein) motors. Melanosomes retain both kinesin and dynein during anterograde and retrograde transport, but the myosin V motor seems to be recruited to melanosomes during dispersion, where it assists kinesin II in dominating dynein thus driving net dispersion. Recent work suggests an important role for dynactin in coordinating the activity of the opposing microtubule motors. The melanophore pigment aggregation response has also played a vital role in the ongoing effort to devise specific melatonin receptor antagonists. Much of what has been learnt about the parts of the melatonin molecule required for receptor binding and activation has come from detailed structure-activity data using novel melatonin ligands. Work aiming to devise ligands specific for the distinct melatonin receptor subtypes stands poised to deliver selective agonists and antagonists which will be valuable tools in understanding the role of this enigmatic hormone in health and disease. PMID:15357831

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

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

    2015-04-01

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

  9. Investigation of Solar about 5-Month Cycle in Human Circulating Melatonin: Signature of Weather in Extraterrestrial Space?

    Cornélissen, G.; Tarquini, R.; Perfetto, F.; Otsuka, K.; Gigolashvili, M.; Halberg, F.

    2009-12-01

    Melatonin, produced mainly in the pineal and the gut, is often thought of as the "dark hormone" as its concentration in the circulation is high during darkness and low during light in diurnally- and nocturnally-active mammals in health. About-daily and about-yearly periodicities can thus be anticipated to characterize melatonin, matching the two major photic environmental cycles. Non-photic solar influences have also been observed, melatonin being depressed in association with magnetic storms. While less stable than the daily and yearly changes, non-photic solar dynamics also undergo various periodicities. Among them is an about 0.42-year (about 5-month or 154-day) cycle, reported by several physicists in relation to Zürich relative sunspot numbers and to solar flares. This putative signature of solar activity was found in the incidence pattern of sudden cardiac death in Minnesota, USA, among other geographic locations. A cycle with a period of about 0.42 year is here reported in data on circulating melatonin of 172 patients studied between Oct 1992 and Dec 1995 in Florence, Italy. Melatonin may mediate some of the Sun's effects upon the biosphere in certain frequency-windows such as a cis-half-year of about 5 months.

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

    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 (0 lx, 1 lx, 10 lx, 100 lx) 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 (1 lx). 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

  11. Melatonin, immune function and aging

    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.

  12. Iatrogenic nocturnal eneuresis- an overlooked side effect of anti histamines?

    D Italiano; F Italiano; Genovese, C.; R S Calabro

    2015-01-01

    Nocturnal enuresis is a common disorder in childhood, but its pathophysiological mechanisms have not been fully elucidated. Iatrogenic nocturnal enuresis has been described following treatment with several psychotropic medications. Herein, we describe a 6-year-old child who experienced nocturnal enuresis during treatment with the antihistamine cetirizine. Drug rechallenge was positive. Several neurotransmitters are implicated in the pathogenesis of nocturnal enuresis, including noradrenaline,...

  13. Radioimmunoassay for melatonin in human serum

    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.)

  14. Protective effects of thymoquinone and melatonin on intestinal ischemia–reperfusion injury

    Ufuk Tas

    2015-01-01

    Full Text Available Background/Aim: In the present study, we aimed to compare the potential protective effects of thymoquinone and melatonin by using equivalent dose, on oxidative stress-induced ischemia–reperfusion (IR injury in the intestinal tissue of rats. Materials and Methods: The study was performed using 32 male Wistar–Albino rats (weighing 180–200 g randomly divided into four groups: Group I, sham group; Group II, IR group; Group III, IR with melatonin group; and Group IV, IR with thymoquinone group. After laparotomy, ischemia and reperfusion were performed for 60 and 120 min, respectively, on all the groups. Intestinal tissue sections were stained using routine histological methods and examined under the light microscope. In addition, the sections were immunohistochemically stained using the TUNEL method for determination of apoptosis. Superoxide dismutase (SOD activity, glutathione peroxidase (GSH-Px activity, and malondialdehyde (MDA levels in the intestinal tissue were also measured. Results: The IR group had significantly elevated tissue SOD activity, GSH-Px activity, and MDA levels compared with the sham group. Administration of thymoquinone and melatonin efficiently reduced these increases. Statistically significant number of apoptotic cells was observed in the intestinal tissue of IR group rats compared with the sham group. Treatment with thymoquinone and melatonin markedly reduced the number of apoptotic cells. Conclusion: The effects of melatonin and thymoquinone on IR-induced oxidative stress in rat intestines were similar. Our findings suggest that melatonin and thymoquinone protect against IR-induced injury to intestinal tissues.

  15. Protective Effects of Thymoquinone and Melatonin on Intestinal Ischemia–reperfusion Injury

    Tas, Ufuk; Ayan, Murat; Sogut, Erkan; Kuloglu, Tuncay; Uysal, Murat; Tanriverdi, Halil I.; Senel, Ufuk; Ozyurt, Birsen; Sarsilmaz, Mustafa

    2015-01-01

    Background/Aim: In the present study, we aimed to compare the potential protective effects of thymoquinone and melatonin by using equivalent dose, on oxidative stress-induced ischemia–reperfusion (IR) injury in the intestinal tissue of rats. Materials and Methods: The study was performed using 32 male Wistar–Albino rats (weighing 180–200 g) randomly divided into four groups: Group I, sham group; Group II, IR group; Group III, IR with melatonin group; and Group IV, IR with thymoquinone group. After laparotomy, ischemia and reperfusion were performed for 60 and 120 min, respectively, on all the groups. Intestinal tissue sections were stained using routine histological methods and examined under the light microscope. In addition, the sections were immunohistochemically stained using the TUNEL method for determination of apoptosis. Superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, and malondialdehyde (MDA) levels in the intestinal tissue were also measured. Results: The IR group had significantly elevated tissue SOD activity, GSH-Px activity, and MDA levels compared with the sham group. Administration of thymoquinone and melatonin efficiently reduced these increases. Statistically significant number of apoptotic cells was observed in the intestinal tissue of IR group rats compared with the sham group. Treatment with thymoquinone and melatonin markedly reduced the number of apoptotic cells. Conclusion The effects of melatonin and thymoquinone on IR-induced oxidative stress in rat intestines were similar. Our findings suggest that melatonin and thymoquinone protect against IR-induced injury to intestinal tissues. PMID:26458854

  16. Importance of light and of the serotonin-melatonin-system on neurophysiology of milk synthesis and ejection in dairy cows

    Kollmann, Maria Theresia

    2008-01-01

    The aim of the study was to influence the serotonin-melatonin-system and thus to investigate its effect to milk synthesis and ejection in dairy cows. Melatonin concentration of heifers but not of lactating cows could be influenced after elevating plasma tryptophan concentration by oral administration of rumen protected tryptophan. A variation of the daily photoperiod affected prolactin , but not oxytocin concentration. Via directed use of artificial sunlight during milking oxytocin, but not p...

  17. Examination of the melatonin hypothesis in women exposed at night to EMF or bright light.

    Graham, C; Cook, M R; Gerkovich, M M; Sastre, A

    2001-05-01

    It has been hypothesized that the increased incidence of breast cancer in industrial societies is related to greater exposure to power-frequency electric and magnetic fields (EMF) and/or the presence of high levels of light at night (LAN). EMF and LAN are said to reduce circulating levels of the hormone melatonin which, in turn, allows estrogen levels to rise and stimulate the turnover of breast epithelial stem cells and increase the risk for malignant transformation. Three laboratory-based studies, in which a total of 53 healthy young women were exposed at night to EMF or to LAN under controlled exposure conditions, were performed to determine whether such exposures reduce melatonin and are associated with further alterations in estrogen. All-night exposure to industrial-strength magnetic fields (60 Hz, 28.3 microT) had no effect on the blood levels of melatonin or estradiol. In contrast, nocturnal melatonin levels were profoundly suppressed, and the time of peak concentration was significantly delayed in women exposed to LAN, regardless of whether they were in the follicular or luteal phase of the menstrual cycle. These changes, however, were not associated with alterations in point-for-point matching measures of estradiol. Women who chronically secrete high or low amounts of melatonin each night (area-under-curve range: 86-1,296 pg/mL) also did not differ in their blood levels of estradiol. Taken together, these results are consistent with a growing body of evidence which generally suggests that environmental EMF exposure has little or no effect on the parameters measured in this report. PMID:11401762

  18. Melatonin Anticancer Effects: Review

    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.

  19. Nocturnal coastal fronts in the Mediterranean basin

    Mazón, Jordi

    2015-01-01

    The main goal of this thesis is to investigate the formation of nocturnal coastal fronts (hereafter CF) in the Mediterranean basin producing nocturnal offshore precipitation near the coastline. After sunset the cooled inland air moves to the coastline driven by drainage winds as a density current. When this air encounters the warm and wet sea-air a CF is formed. Therefore the warm air mass is lifted and when ascending clouds may form producing in some cases precipitation. The influence of ...

  20. 'Melatonin isomer' in wine is not an isomer of the melatonin but tryptophan-ethylester.

    Gardana, Claudio; Iriti, Marcello; Stuknytė, Milda; De Noni, Ivano; Simonetti, Paolo

    2014-11-01

    Melatonin is a neurohormone, chronobiotic, and antioxidant compound found in wine and deriving directly from grapes and/or synthesized by yeast during alcoholic fermentation. In addition, a melatonin isomer has been detected in different foods, wine among them. The special interest for melatonin isomer related to the fact that it was found in greater quantities than melatonin and probably shares some of its biological properties. Despite this, its chemical structure has not yet been defined; although some researchers hypothesize, it could be melatonin with the ethylacetamide group shifted into position N1. Thus, the aim of our study was to identify the structures of the melatonin isomer. For this purpose, melatonin and melatonin isomer in Syrah wine were separated chromatographically by a sub-2 μm particle column and detected by tandem mass spectrometry. The sample was then purified and concentrated by solid-phase extraction, hydrolyzed with alkali or esterase, and substrates and products quantified by UPLC-MS/MS. Moreover, melatonin, melatonin isomer, and their product ions were evaluated by high-resolution mass spectrometry. The amount of melatonin isomer and melatonin in the wine was 84 ± 4 and 3 ± 0 ng/mL, respectively. In the solutions, containing diluted alkali or esterase, melatonin isomer was hydrolyzed in about 8 min. Correspondingly, tryptophan was detected, and its amount increased and reached the maximum concentration in about 8 min. Melatonin concentration was not affected by diluted alkali or esterase. The fragmentation pattern of melatonin isomer was different from that of melatonin but comparable to that of tryptophan-ethylester. Finally, the so-called melatonin isomer identity was verified by cochromatography with authentic standard of tryptophan-ethylester. PMID:25251161

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

    Eckhard Mühlbauer

    2013-03-01

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

  2. Pharmacology and function of melatonin receptors

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

  3. Pharmacology and function of melatonin receptors

    Dubocovich, M.L.

    1988-09-01

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

  4. Melatonin use in sleep disorders

    Chung, KF

    1997-01-01

    Melatonin is a widely publicized 'magical drug'. Claims of its use include regulation of sleep, circadian rhythm, mood, immune system and reproduction, anti-aging, protection against cancer, and treatment of AIDS. This article reviews the evidence of its use in sleep disorders. Its possible indications and adverse effects are discussed.

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

    Rüdiger Hardeland

    2013-03-01

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

  6. Problems in assessment of acute melatonin overdose.

    Holliman, B J; Chyka, P A

    1997-04-01

    Melatonin is sold in the United States as a dietary supplement and is promoted primarily as an aid for insomnia, stress, jet lag, and aging. Cases of acute poisoning have not been reported, partially because of problems in assessment of toxicity. We report the case of a 66-year-old man who became lethargic and disoriented after taking 24 mg melatonin to aid relaxation and sleep the evening before prostate surgery. He recovered uneventfully, and after the scheduled surgery he resumed his regular practice of taking 6 mg melatonin with prescription sedative drugs. Although melatonin is not regulated as a drug, it may interact with benzodiazepines, be antagonized by naloxone and flumazenil, and interact with melatonin receptors in the central nervous system and elsewhere in the body. Melatonin appears to be pharmacologically active and should not be considered a benign agent on overdose. PMID:9114843

  7. Melatonin: an Inhibitor of Breast Cancer

    Hill, Steven M.; Belancio, Victoria P; Dauchy, Robert T; Xiang, Shulin; Brimer, Samantha; Mao, Lulu; Hauch, Adam; Lundberg, Peter W.; Summers, Whitney; Yuan, Lin; Frasch, Tripp; Blask, David E.

    2015-01-01

    This review discusses recent work on melatonin-mediated circadian regulation and metabolic and molecular signaling mechanisms involved in human breast cancer growth and associated consequences of circadian disruption by exposure to light at night (LEN). The anti-cancer actions of the circadian melatonin signal in human breast cancer cell lines and xenografts heavily involve MT1 receptor-mediated mechanisms. In estrogen receptor alpha (ERα)-positive human breast cancer, melatonin, via the MT1 ...

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

    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.

  9. Can nocturnal hypertension predict cardiovascular risk?

    Oded Friedman

    2009-09-01

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

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

    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

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

    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

  12. Genetics Home Reference: autosomal dominant nocturnal frontal lobe epilepsy

    ... Health Conditions ADNFLE autosomal dominant nocturnal frontal lobe epilepsy Enable Javascript to view the expand/collapse boxes. ... Close All Description Autosomal dominant nocturnal frontal lobe epilepsy ( ADNFLE ) is an uncommon form of epilepsy that ...

  13. Genetics Home Reference: Autosomal dominant nocturnal frontal lobe epilepsy

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

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

    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.

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

    Leu-Semenescu, Smaranda; Arnulf, Isabelle

    2010-06-01

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

  16. Melatonin and cortisol profiles in late midlife and their association with age-related changes in cognition

    Waller KL

    2016-01-01

    Full Text Available Katja Linda Waller,1,2 Erik Lykke Mortensen,2,3 Kirsten Avlund,2,3,†, Merete Osler,3,4 Birgitte Fagerlund,5 Martin Lauritzen,2,6 Steen Gammeltoft,7 Poul Jennum1,2 1Danish Center for Sleep Medicine, Clinic of Clinical Neurophysiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 2Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; 3Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 4Research Center for Prevention and Health, Rigshospitalet, Glostrup, Denmark; 5Center for Neuropsychiatric Schizophrenia Research (CNSR, Lundbeck Foundation Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS, Mental Health Center Glostrup, Glostrup, Denmark; 6Department of Clinical Neurophysiology, Rigshospitalet, Glostrup, Denmark; 7Department of Clinical Biochemistry, Rigshospitalet, Glostrup, Denmark †Kirsten Avlund passed away on June 15, 2012 Abstract: Previous studies have reported an association between circadian disturbances and age-related cognitive impairment. The aim was to study the 24-hour profiles of melatonin and cortisol in relation to cognitive function in middle-aged male subjects. Fifty healthy middle-aged males born in 1953 were recruited from a population-based cohort based on previous cognitive assessments in young adulthood and late midlife. The sample included 24 cognitively high-functioning and 26 cognitively impaired participants. Saliva samples were collected every 4 hours over a 24-hour period and analyzed for cortisol and melatonin levels by immunoassay. All participants exhibited clear circadian rhythms of salivary melatonin and cortisol. Salivary melatonin concentrations had a nocturnal peak at approximately 4 am. The median nocturnal melatonin response at 4 am was significantly lower in the cognitively impaired group than in the high-functioning group (−4.6 pg/mL, 95% CI: −7.84, −1.36, P=0.006. The 24-hour mean melatonin concentration (high-functioning group: 4.80±0.70 pg/mL, vs cognitively impaired group: 4.81±0.76 pg/mL; P>0.05 (or the area under the curve, AUC was not significantly different between the two groups. Cortisol levels were low during the night, and peaked at approximately 8 am. Median cortisol concentrations were similar at all times, as were the 24-hour mean cortisol concentrations and AUC. To the best of our knowledge, ours is the first study to assess circadian measures (ie, melatonin and cortisol in healthy middle-aged men with different cognitive trajectories in midlife. We found evidence of altered circadian rhythms with a reduced nocturnal melatonin response at 4 am in men with cognitive impairment. The 24-hour concentration and AUC of melatonin and cortisol were similar in the cognitively high-functioning group and in the cognitively impaired. Keywords: diurnal variation, middle-aged males, minimal cognitive impairment

  17. Iatrogenic nocturnal eneuresis- an overlooked side effect of anti histamines?

    D Italiano

    2015-01-01

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

  18. High membrane permeability for melatonin.

    Yu, Haijie; Dickson, Eamonn J; Jung, Seung-Ryoung; Koh, Duk-Su; Hille, Bertil

    2016-01-01

    The pineal gland, an endocrine organ in the brain, synthesizes and secretes the circulating night hormone melatonin throughout the night. The literature states that this hormone is secreted by simple diffusion across the pinealocyte plasma membrane, but a direct quantitative measurement of membrane permeability has not been made. Experiments were designed to compare the cell membrane permeability to three indoleamines: melatonin and its precursors N-acetylserotonin (NAS) and serotonin (5-HT). The three experimental approaches were (1) to measure the concentration of effluxing indoleamines amperometrically in the bath while cells were being dialyzed internally by a patch pipette, (2) to measure the rise of intracellular indoleamine fluorescence as the compound was perfused in the bath, and (3) to measure the rate of quenching of intracellular fura-2 dye fluorescence as indoleamines were perfused in the bath. These measures showed that permeabilities of melatonin and NAS are high (both are uncharged molecules), whereas that for 5-HT (mostly charged) is much lower. Comparisons were made with predictions of solubility-diffusion theory and compounds of known permeability, and a diffusion model was made to simulate all of the measurements. In short, extracellular melatonin equilibrates with the cytoplasm in 3.5 s, has a membrane permeability of ∼1.7 µm/s, and could not be retained in secretory vesicles. Thus, it and NAS will be "secreted" from pineal cells by membrane diffusion. Circumstances are suggested when 5-HT and possibly catecholamines may also appear in the extracellular space passively by membrane diffusion. PMID:26712850

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

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

    2013-09-01

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

  20. The effects of melatonin on a molecular level

    M. Haag

    1992-07-01

    Full Text Available The indole hormone melatonin is secreted in a biphasic circadian rhythm by the pineal gland. This review presents a summary of recent results concerning — (i factors that influence melatonin synthesis; (ii the existence of melatonin receptors in brain tissue; (iii the effects of melatonin as a modulator of dopaminergic, noradrenergic, GABAergic and opioidergic neurotransmitter processes; (iv the influence of melatonin on the electric activity and metabolic rate of certain brain nuclei; and (v melatonin effects on hormone secretion in the hypothalamic-pituitary axis. A basic mechanism of melatonin action via cyclic nucleotides and thus protein phosphorylation is presented.

  1. 21 CFR 522.1350 - Melatonin implant.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Melatonin implant. 522.1350 Section 522.1350 Food... Melatonin implant. (a) Specifications. The drug is a silicone rubber elastomer implant containing 2.7...—(1) Amount. One implant per mink. (2) Indications for use. For use in healthy male and female kit...

  2. Body position and late postoperative nocturnal hypoxaemia

    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 ...

  3. Nocturnal petal movements in the Asteraceae

    C. H. Stirton

    1983-01-01

    Nocturnal petal movements were recorded from 48 genera and 106 species growing in cultivation at the Royal Botanic Gardens, Kew and in the wild in Canada, Great Britain, France, Italy, Greece, Canary Islands and South Africa. Seven different night positions of petals, as distinct from day positions, are recognized and discussed.

  4. Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling.

    Dong, Yushu; Fan, Chongxi; Hu, Wei; Jiang, Shuai; Ma, Zhiqiang; Yan, Xiaolong; Deng, Chao; Di, Shouyin; Xin, Zhenlong; Wu, Guiling; Yang, Yang; Reiter, Russel J; Liang, Guobiao

    2016-04-01

    Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults. Melatonin is reported to possess substantial anti-inflammatory properties, which is beneficial for early brain injury (EBI) after SAH. However, the molecular mechanisms have not been clearly identified. This study was designed to investigate the protective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 hr after SAH. Melatonin was neuroprotective, as shown by increased survival rate, as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels, and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood-brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved caspase-1, interleukin-1β (IL-1β), and interleukin-6 (IL-6); these changes were also associated with an increase in the anti-apoptotic factor (Bcl2) and reduction in the pro-apoptotic factor (Bim). In summary, our results demonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome-associated apoptosis. PMID:26639408

  5. Melatonin attenuates hypoxic pulmonary hypertension by inhibiting the inflammation and the proliferation of pulmonary arterial smooth muscle cells.

    Jin, Haifeng; Wang, Yueyue; Zhou, Lei; Liu, Lu; Zhang, Peng; Deng, Wuguo; Yuan, Yuhui

    2014-11-01

    Hypoxia-induced inflammation and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) play important roles in the pathological process of hypoxic pulmonary hypertension (HPH). Melatonin possesses anti-inflammatory and antiproliferative properties. However, the effect of melatonin on HPH remains unclear. In this study, adult Sprague-Dawley rats were exposed to intermittent chronic hypoxia for 4 wk to mimic a severe HPH condition. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of the right ventricle/left ventricle plus septum (RV/LV+S) ratio, and median width of pulmonary arterioles. Melatonin attenuated the elevation of RVSP, RV/LV+S, and mitigated the pulmonary vascular structure remodeling. Melatonin also suppressed the hypoxia-induced high expression of proliferating cell nuclear antigen (PCNA), hypoxia-inducible factor-1? (HIF-1?), and nuclear factor-?B (NF-?B). In vitro, melatonin concentration-dependently inhibited the proliferation of PASMCs and the levels of phosphorylation of Akt and extracellular signal-regulated kinases1/2 (ERK1/2) caused by hypoxia. These results suggested that melatonin might potentially prevent HPH via anti-inflammatory and antiproliferative mechanisms. PMID:25251287

  6. Melatonin treatment during the incubation of sensitization attenuates methamphetamine-induced locomotor sensitization and MeCP2 expression.

    Wu, Jintao; Zhu, Dexiao; Zhang, Jing; Li, Guibao; Liu, Zengxun; Sun, Jinhao

    2016-02-01

    Behavior sensitization is a long-lasting enhancement of locomotor activity after exposure to psychostimulants. Incubation of sensitization is a phenomenon of remarkable augmentation of locomotor response after withdrawal and reflects certain aspects of compulsive drug craving. However, the mechanisms underlying these phenomena remain elusive. Here we pay special attention to the incubation of sensitization and suppose that the intervention of this procedure will finally decrease the expression of sensitization. Melatonin is an endogenous hormone secreted mainly by the pineal gland. It is effective in treating sleep disorder, which turns out to be one of the major withdrawal symptoms of methamphetamine (MA) addiction. Furthermore, melatonin can also protect neuronal cells against MA-induced neurotoxicity. In the present experiment, we treated mice with low dose (10mg/kg) of melatonin for 14 consecutive days during the incubation of sensitization. We found that melatonin significantly attenuated the expression of sensitization. In contrast, the vehicle treated mice showed prominent enhancement of locomotor activity after incubation. MeCP2 expression was also elevated in the vehicle treated mice and melatonin attenuated its expression. Surprisingly, correlation analysis suggested significant correlation between MeCP2 expression in the nucleus accumbens (NAc) and locomotion in both saline control and vehicle treated mice, but not in melatonin treated ones. MA also induced MeCP2 over-expression in PC12 cells. However, melatonin failed to reduce MeCP2 expression in vitro. Our results suggest that melatonin treatment during the incubation of sensitization attenuates MA-induced expression of sensitization and decreases MeCP2 expression in vivo. PMID:26416230

  7. Protein interactome mining defines melatonin MT1 receptors as integral component of presynaptic protein complexes of neurons.

    Benleulmi-Chaachoua, Abla; Chen, Lina; Sokolina, Kate; Wong, Victoria; Jurisica, Igor; Emerit, Michel Boris; Darmon, Michèle; Espin, Almudena; Stagljar, Igor; Tafelmeyer, Petra; Zamponi, Gerald W; Delagrange, Philippe; Maurice, Pascal; Jockers, Ralf

    2016-01-01

    In mammals, the hormone melatonin is mainly produced by the pineal gland with nocturnal peak levels. Its peripheral and central actions rely either on its intrinsic antioxidant properties or on binding to melatonin MT1 and MT2 receptors, belonging to the G protein-coupled receptor (GPCR) super-family. Melatonin has been reported to be involved in many functions of the central nervous system such as circadian rhythm regulation, neurotransmission, synaptic plasticity, memory, sleep, and also in Alzheimer's disease and depression. However, little is known about the subcellular localization of melatonin receptors and the molecular aspects involved in neuronal functions of melatonin. Identification of protein complexes associated with GPCRs has been shown to be a valid approach to improve our understanding of their function. By combining proteomic and genomic approaches we built an interactome of MT1 and MT2 receptors, which comprises 378 individual proteins. Among the proteins interacting with MT1 , but not with MT2 , we identified several presynaptic proteins, suggesting a potential role of MT1 in neurotransmission. Presynaptic localization of MT1 receptors in the hypothalamus, striatum, and cortex was confirmed by subcellular fractionation experiments and immunofluorescence microscopy. MT1 physically interacts with the voltage-gated calcium channel Cav 2.2 and inhibits Cav 2.2-promoted Ca(2+) entry in an agonist-independent manner. In conclusion, we show that MT1 is part of the presynaptic protein network and negatively regulates Cav 2.2 activity, providing a first hint for potential synaptic functions of MT1 . PMID:26514267

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

    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

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

    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

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

    Terry PD

    2013-03-01

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

  11. Functions of melatonin in plants: a review.

    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

  12. Chapter 16: Melatonin and nerve regeneration.

    Odaci, Ersan; Kaplan, Suleyman

    2009-01-01

    Melatonin is a widely distributed and important signal molecule that occurs in unicellular organisms, plants, and fungi in addition to animals and humans. It is the main hormone of the pineal gland and its synthesis occurs mainly in this gland. It has free radical scavenging and antioxidative properties and shows clinical antibacterial and analgesic effects. By means of these properties, it is able to protect cells, tissues, and organs against oxidative damage from free radicals. Recently, widespread interest has grown among researchers regarding the apparent protective effects of melatonin following traumatic events to peripheral nerves, especially the sciatic nerve and its pathological conditions, as melatonin administration could be beneficial following surgery. Although there are great numbers of studies that have mentioned protective effects of melatonin on peripheral nerve pathologies, there are also some studies that report toxic effects of melatonin on peripheral nerves. This paper reviews the available literature in terms of both the beneficial and the toxic effects of melatonin on peripheral nerves. Short descriptions of the structure of pineal gland and synthesis and secretion of melatonin are also given. PMID:19682645

  13. Melatonin in Alzheimer’s Disease

    Jian-Zhi Wang

    2013-07-01

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

  14. Melatonin as a radioprotective agent: a review

    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

  15. Immunoregulatory actions of melatonin and zinc during chronic Trypanosoma cruzi infection.

    Brazão, Vânia; Santello, Fabricia Helena; Filipin, Marina Del Vecchio; Azevedo, Angela Palamin; Toldo, Míriam Paula Alonso; de Morais, Fabiana Rossetto; do Prado, José Clóvis

    2015-03-01

    After one century of the discovery of Chagas' disease and the development of an efficient drug with amplitude of actions both in the acute and chronic phase is still a challenge. Alternative immune modulators have been exhaustively used. For that purpose, melatonin and zinc were administered during chronic Trypanosoma cruzi-infected Wistar rats and several endpoints were assessed. Melatonin has a remarkable functional versatility, being associated with important antioxidant, anti-inflammatory, and anti-apoptotic effects. The cross-talk between zinc and the immune system includes its ability to influence the production and signaling of numerous inflammatory cytokines in a variety of cell types. Our study showed that zinc triggered a decrease in the generation of IFN-? for TCD4(+) cells. Reduced percentage of CD4(+) T cells producing TNF-? was observed in control melatonin or zinc-and-melatonin-treated animals as compared with untreated rats. On the other hand, a significant increase in the percentage of IL-4 from CD4(+) and CD8(+) T lymphocytes producers was observed 60 days after infection, for all zinc-treated animals, whether infected or not. Melatonin and zinc therapies increased the percentages of CD4(+) and CD8(+) T lymphocytes IL-10 producers. CD4(+) CD25(high) Foxp3(+) T cells were also elevated in zinc- and melatonin-treated animals. The modulation of the immune system influenced by these molecules affected cytokine production and the inflammatory process during chronic T. cruzi infection. Elucidation of the interplay between cytokine balance and the pathogenesis of Chagas' disease is extremely relevant not only for the comprehension of the immune mechanisms and clinical forms but, most importantly, also for the implementation of efficient and adequate therapies. PMID:25611919

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

    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 α 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.

  17. Melatonin in perioperative medicine: Current perspective

    Souvik Maitra

    2013-01-01

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

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

    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.

  19. Nocturnal enuresis in sickle cell haemoglobinopathies.

    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...

  20. Bat predation on nocturnally migrating birds

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

    2001-01-01

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

  1. Melatonin Attenuates Methamphetamine-Induced Neurotoxicity.

    Wongprayoon, Pawaris; Govitrapong, Piyarat

    2016-01-01

    Methamphetamine (METH), an illegal psycho-stimulant, is widely known as a recreational drug. In addition to its addictive effect, METH induces neurotoxicity via multiple mechanisms. The major contributors to METH-induced neurotoxicity are reactive oxygen species, which lead to cell death through apoptotic pathway and disturbances in mitochondria, the generation of neuroinflammation, and autophagy. Melatonin, a neurohormone secreted by the pineal gland, is a potent antioxidant compound that plays a beneficial role by protecting against the oxidative stress caused by METH. Melatonin also plays a role in maintaining mitochondrial homeostasis. Nanomolar concentrations of melatonin have been shown to protect against the inflammation caused by METH and to prevent the decrease in neurogenesis caused by METH in progenitor cells obtained from adult rat hippocampal tissue. The intent of this review is to describe the underlying mechanisms involving melatonin that protect against the neurodegeneration caused by METH. PMID:25248807

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

    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

  3. Antioxidant activity of melatonin in mice.

    Pierrefiche, G; Topall, G; Courboin, G; Henriet, I; Laborit, H

    1993-05-01

    Melatonin (in gum tragacanth as solvent) was administered to mice in the dose range of 100 to 450 mg/kg intraperitoneally. It prevented the increase in plasma glucose resulting from pancreatic toxicity caused by the intravenous administration of alloxan at 40 mg/kg. This action of melatonin was significant and dose-dependent. In parallel work using mouse brain homogenates, melatonin and more so its principal hepatic metabolite, 6-hydroxymelatonin, inhibited the formation of colored products reacting with thiobarbituric acid. Again, this inhibition was significant and dose-dependent. Alloxan-induced diabetes and lipoperoxidation induced by thiobarbituric acid are imputed to the production of oxygen free radicals. The consistent results obtained using these two experimental models show the antioxidant activity of melatonin, both in vivo and in vitro. This effect may be reasonably attributed to the indole structure of the molecule. PMID:8321921

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

    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)

  5. Color indirect effects on melatonin regulation

    Mian, Tian; Liu, Timon C.; Li, Yan

    2002-04-01

    Color indirect effect (CIE) is referred to as the physiological and psychological effects of color resulting from color vision. In previous papers, we have studied CIE from the viewpoints of the integrated western and Chinese traditional medicine, put forward the color-autonomic- nervous-subsystem model (CAM), and provided its time-theory foundation. In this paper, we applied it to study light effects on melatonin regulation in humans, and suggested that it is CIE that mediates light effects on melatonin suppression.

  6. Topical Melatonin for Treatment of Androgenetic Alopecia

    Tobias W. Fischer; Trüeb, Ralph M.; Hänggi, Gabriella; Innocenti, Marcello; Elsner, Peter

    2012-01-01

    Background: In the search for alternative agents to oral finasteride and topical minoxidil for the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth modulator, was identified as a promising candidate based on in vitro and in vivo studies. Materials and Methods: One pharmacodynamic study on topical application of melatonin and four clinical pre-post studies were performed in patients with androgenetic alopecia or general hair loss and evaluated by standardise...

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

    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...

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

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

    2013-03-01

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

  9. Update in glaucoma medicinal chemistry: emerging evidence for the importance of melatonin analogues.

    Crooke, A; Colligris, B; Pintor, J

    2012-01-01

    Glaucoma is a chronic progressive optic neuropathy, which can result in visual impairment and blindness. Elevated intraocular pressure (IOP) is currently the only modifiable risk factor. Several recent studies have shown the benefits of IOP reduction in open-angle glaucoma. Therefore, current glaucoma drugs are IOP-lowering substances such as α(2)-adrenergic agonists, β(2)-adrenergic antagonists, carbonic anhydrase inhibitors and hypotensive lipids, which are used separately or in combination. In spite of the wide variety of antiglaucoma medicines, all therapies have several undesirable side effects. As a consequence, there are constant research attempts on the discovery of novel ocular hypotensive drugs. In the current paper, we review the latest available patents and literature for the pharmacological treatment of glaucoma, focusing on their molecular targets and/or their chemical characteristics and especially directed to melatoninergic drugs. Melatonin is a hormone secreted into the blood mainly from the pineal gland allowing the entrainment of the circadian rhythms of several biological functions. Melatonin and its analogues potently reduce IOP in rabbits, monkeys and humans. In addition, there are indications of long-term hypotensive effects and a proven neuroprotective role of melatoninergic substances. Furthermore, antidepressant and normalizing circadian rhythm actions of melatonin analogues might be beneficial for glaucoma patients. All the above mentioned facts suggest these agents as proper candidates for the glaucoma treatment. Consequently, the scientific research has given new and significant progress on the development of new, potent and selective melatonin ligands. PMID:22709004

  10. Putative melatonin receptors in a human biological clock

    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

  11. Putative melatonin receptors in a human biological clock

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

    1988-10-07

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

  12. The role of melatonin in the light of current knowledge

    Barbara Algiert

    2016-02-01

    Full Text Available Recent studies have shed new light on the role of melatonin. Local tissue synthesis has been investigated. A special system responsible for the synthesis and metabolism of melatonin has developed in the human skin. The primary role of melatonin is the regulation of circadian rhythms, but studies have demonstrated the diversity of its activities. Potent antioxidant action of melatonin in the skin is emphasized. The skin has developed a specific antioxidant melatoninergic system which protects against oxidative stress. Presence of melatonin metabolites in the skin confirms its strong antioxidant properties. Melatonin has the ability to restore the physiological balance between synthesis and degradation of extracellular matrix proteins by induction of heme oxygenase in murine fibroblasts irradiated with UVR. There is a hypothesis concerning the participation of melatonin in etiology of vitiligo. Disturbances of melatonin skin synthesis and dysregulation of its receptors may explain the pathogenesis of disease.

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

    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)

  14. Melatonin Signaling Modulates Clock Genes Expression in the Mouse Retina

    Hiragaki, Susumu; Baba, Kenkichi; Coulson, Elise; Kunst, Stefanie; Spessert, Rainer; Tosini, Gianluca

    2014-01-01

    Previous studies have shown that retinal melatonin plays an important role in the regulation of retinal daily and circadian rhythms. Melatonin exerts its influence by binding to G-protein coupled receptors named melatonin receptor type 1 and type 2 and both receptors are present in the mouse retina. Earlier studies have shown that clock genes are rhythmically expressed in the mouse retina and melatonin signaling may be implicated in the modulation of clock gene expression in this tissue. In t...

  15. Pharmacokinetics of oral and intravenous melatonin in healthy volunteers

    Andersen, Lars P. H.; Werner, Mads U.; Rosenkilde, Mette M; Harpsøe, Nathja G.; Fuglsang, Hanne; Rosenberg, Jacob; Gögenur, Ismail

    2016-01-01

    Background The aim was to investigate the pharmacokinetics of oral and iv melatonin in healthy volunteers. Methods The study was performed as a cohort crossover study. The volunteers received either 10 mg oral melatonin or 10 mg intravenous melatonin on two separate study days. Blood samples were collected at different time points following oral administration and short iv infusion, respectively. Plasma melatonin concentrations were determined by RIA technique. Pharmacokinetic analyses were p...

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

    Fourtillan, Jean B.

    2002-01-01

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

  17. Melatonin enhances vertical bone augmentation in rat calvaria secluded spaces

    Shino, Hiromichi; Hasuike, Akira; Arai, Yoshinori; Honda, Masaki; Isokawa, Keitaro; Sato, Shuichi

    2015-01-01

    Background Melatonin has many roles, including bone remodeling and osseointegration of dental implants. The topical application of melatonin facilitated bone regeneration in bone defects. We evaluated the effects of topical application of melatonin on vertical bone augmentation in rat calvaria secluded spaces. Material and Methods In total, 12 male Fischer rats were used and two plastic caps were fixed in the calvarium. One plastic cap was filled with melatonin powder and the other was left e...

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

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

    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 s...

  19. Green Light for Nocturnally Migrating Birds

    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.

  20. Extended Driving Impairs Nocturnal Driving Performances

    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...

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

    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-γ, programmed cell death-receptor (Fas and Tumor necrosis factor-alpha (TNF-α 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-α and Fas mRNA expression was significantly restored by the three treatments. Melatonin, folic acid or their combination also restored the baseline levels of IFN-γ 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.

  2. The in vitro and in ovo effects of environmental illumination and temperature on the melatonin secretion from the embryonic chicken pineal gland.

    Faluhelyi, Nándor; Matkovits, Attila; Párniczky, Andrea; Csernus, Valér

    2009-04-01

    Pineal glands of chicken embryos were placed into a perifusion system for 4 days. The pineal glands were illuminated or exposed to elevated temperature for 8 or 12 h during the in vitro experiment and/or in ovo. Both daily illumination and repeated elevations of environmental temperature transitionally inhibited melatonin release before, and controlled the phase of melatonin rhythm after, the 17th day of embryonic life (E17). In addition, the in ovo rhythmic illumination applied before E13 advances the development of the circadian hormone synthesis. PMID:19456366

  3. Melatonin phase-shifts human circadian rhythms with no evidence of changes in the duration of endogenous melatonin secretion or the 24-hour production of reproductive hormones

    Rajaratnam, SMW; Dijk, D-J; Middleton, B; Stone, BM; Arendt, J

    2003-01-01

    The pineal hormone melatonin is a popular treatment for sleep and circadian rhythm disruption. Melatonin administered at optimal times of the day for treatment often results in a prolonged melatonin profile. In photoperiodic (day length-dependent) species, changes in melatonin profile duration influence the timing of seasonal rhythms. We investigated the effects of an artificially prolonged melatonin profile on endogenous melatonin and cortisol rhythms, wrist actigraphy, and reproductive horm...

  4. Melatonin in Mitochondrial Dysfunction and Related Disorders

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

    2011-01-01

    Mitochondrial dysfunction is considered one of the major causative factors in the aging process, ischemia/reperfusion (I/R), septic shock, and neurodegenerative disorders like Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). Increased free radical generation, enhanced mitochondrial inducible nitric oxide (NO) synthase activity, enhanced NO production, decreased respiratory complex activity, impaired electron transport system, and opening of mitochondrial permeability transition pore all have been suggested as factors responsible for impaired mitochondrial function. Melatonin, the major hormone of the pineal gland, also acts as an antioxidant and as a regulator of mitochondrial bioenergetic function. Both in vitro and in vivo, melatonin was effective for preventing oxidative stress/nitrosative stress-induced mitochondrial dysfunction seen in experimental models of PD, AD, and HD. In addition, melatonin is known to retard aging and to inhibit the lethal effects of septic shock or I/R lesions by maintaining respiratory complex activities, electron transport chain, and ATP production in mitochondria. Melatonin is selectively taken up by mitochondrial membranes, a function not shared by other antioxidants. Melatonin has thus emerged as a major potential therapeutic tool for treating neurodegenerative disorders such as PD or AD, and for preventing the lethal effects of septic shock or I/R. PMID:21629741

  5. Melatonin Preserves Blood-Brain Barrier Integrity and Permeability via Matrix Metalloproteinase-9 Inhibition

    Alluri, Himakarnika; Wilson, Rickesha L.; Anasooya Shaji, Chinchusha; Wiggins-Dohlvik, Katie; Patel, Savan; Liu, Yang; Peng, Xu; Beeram, Madhava R.; Davis, Matthew L.; Huang, Jason H.; Tharakan, Binu

    2016-01-01

    Microvascular hyperpermeability that occurs at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema and elevated intracranial pressure following traumatic brain injury (TBI). At a cellular level, tight junction proteins (TJPs) between neighboring endothelial cells maintain the integrity of the BBB via TJ associated proteins particularly, zonula occludens-1 (ZO-1) that binds to the transmembrane TJPs and actin cytoskeleton intracellularly. The pro-inflammatory cytokine, interleukin-1β (IL-1β) as well as the proteolytic enzymes, matrix metalloproteinase-9 (MMP-9) are key mediators of trauma-associated brain edema. Recent studies indicate that melatonin a pineal hormone directly binds to MMP-9 and also might act as its endogenous inhibitor. We hypothesized that melatonin treatment will provide protection against TBI-induced BBB hyperpermeability via MMP-9 inhibition. Rat brain microvascular endothelial cells grown as monolayers were used as an in vitro model of the BBB and a mouse model of TBI using a controlled cortical impactor was used for all in vivo studies. IL-1β (10 ng/mL; 2 hours)-induced endothelial monolayer hyperpermeability was significantly attenuated by melatonin (10 μg/mL; 1 hour), GM6001 (broad spectrum MMP inhibitor; 10 μM; 1 hour), MMP-9 inhibitor-1 (MMP-9 specific inhibitor; 5 nM; 1 hour) or MMP-9 siRNA transfection (48 hours) in vitro. Melatonin and MMP-9 inhibitor-1 pretreatment attenuated IL-1β-induced MMP-9 activity, loss of ZO-1 junctional integrity and f-actin stress fiber formation. IL-1β treatment neither affected ZO-1 protein or mRNA expression or cell viability. Acute melatonin treatment attenuated BBB hyperpermeability in a mouse controlled cortical impact model of TBI in vivo. In conclusion, one of the protective effects of melatonin against BBB hyperpermeability occurs due to enhanced BBB integrity via MMP-9 inhibition. In addition, acute melatonin treatment provides protection against BBB hyperpermeability in a mouse model of TBI indicating its potential as a therapeutic agent for brain edema when established in humans. PMID:27152411

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

    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

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

    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.

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

    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-α 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

  9. Melatonin and its precursors scavenge nitric oxide

    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.

  10. Vibrational and electronic spectroscopic studies of melatonin

    Singh, Gurpreet; Abbas, J. M.; Dogra, Sukh Dev; Sachdeva, Ritika; Rai, Bimal; Tripathi, S. K.; Prakash, Satya; Sathe, Vasant; Saini, G. S. S.

    2014-01-01

    We report the infrared absorption and Raman spectra of melatonin recorded with 488 and 632.8 nm excitations in 3600-2700 and 1700-70 cm-1 regions. Further, we optimized molecular structure of the three conformers of melatonin within density functional theory calculations. Vibrational frequencies of all three conformers have also been calculated. Observed vibrational bands have been assigned to different vibrational motions of the molecules on the basis of potential energy distribution calculations and calculated vibrational frequencies. Observed band positions match well with the calculated values after scaling except Nsbnd H stretching mode frequencies. It is found that the observed and calculated frequencies mismatch of Nsbnd H stretching is due to intermolecular interactions between melatonin molecules.

  11. Prolactin response in Border-Leicester x merino ewes to administration of melatonin, melatonin analogues, a melatonin metabolite and 6-methoxybenzoxazolinone.

    Kennaway, D J; Royles, P; Dunstan, E A; Hugel, H M

    1986-01-01

    The effect of structural modifications of the melatonin molecule on plasma half-life of the analogues and basal prolactin secretion was studied in Border-Leicester x Merino ewes. Halogenation at position 6 and/or unsaturation of the 2,3-double bond of the melatonin molecule slightly lengthened the half-life of the analogues. Melatonin, 6-chloromelatonin, 2,3-dihydromelatonin and 6-chloro-2,3-dihydromelatonin decreased plasma prolactin to 31, 45, 54 and 48% of control levels respectively when administered daily (100 micrograms at 1600 h) for 21 days. The brain metabolite of melatonin, N-acetyl-N'-formyl-5-methoxykynurenamine, and the putative natural melatonin analogue, 6-methoxybenzoxazolinone, failed to affect prolactin levels when administered in a similar manner. These results indicate that certain structural modifications to the melatonin molecule can be tolerated biologically; however, the modifications reported here still did not prevent rapid clearance from the circulation. PMID:3593120

  12. Melatonin administration reduces inflammatory pain in rats

    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

  13. Raconter Accident nocturne de Patrick Modiano Raconter Accident nocturne de Patrick Modiano

    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 ?

  14. Correlations between behavior, memory, sleep-wake and melatonin in Williams-Beuren syndrome.

    Santoro, Stella Donadon; Giacheti, Celia Maria; Rossi, Natalia Freitas; Campos, Leila Maria Guissoni; Pinato, Luciana

    2016-05-15

    Williams-Beuren syndrome (WBS), a neurodevelopmental disorder caused by a microdeletion on chromosomic region 7q11.23, presents with peculiar behavioral and neurocognitive phenotypes that are marked by apparently preserved social and communicative abilities, which contrasts with low overall cognitive and particularly visuospatial performance. In addition, parents often report complaints of sleep disorders and behavioral problems of unknown cause. Sleep is a biological phenomenon that is modulated by the plasma concentration of melatonin and with influence on behavioral aspects and memory. Thus, this study sought to investigate the behavior, memory and the presence of sleep disorders in WBS and to correlate these factors with each other and with the plasma melatonin content. We used the Child Behavior Checklist for ages 6-18 (CBCL), the digit subtest of the Wechsler scale for auditory memory, the visual sequential memory subtest of the Illinois Test of Psycholinguistic Abilities (ITPA) and the Sleep Disturbance Scale for Children (SDSC). Determination of urinary aMT6s, an indirect measure of plasma melatonin content, was held for 72h by ELISA, and the analysis of the circadian rhythm of this content was performed by the Cosinor method. The results of the CBCL showed that 87% of the WBS group presented with a clinical score on the overall competence and total behavioral problems. Furthermore, the behavioral problems that were most frequently reported by parents were anxiety and problems of thought. All individuals with WBS presented with impairments in auditory memory and 47% with impairments in visual sequential memory; 65% of the WBS group presented with an indicative of at least one sleep disorder, where respiratory, initiation and maintenance of sleep (DIMS) and hyperhidrosis were the most frequent disorders. The night time aMT6s levels were lower in individuals with WBS when compared with controls; 53% of the WBS group did not present with circadian rhythm variations in aMT6s levels. In addition, there was a negative correlation between the scores of auditory memory and the total score of sleep disorders and between the DIMS and nocturnal aMT6s content. In conclusion, in the present study, individuals with WBS showed a high frequency of behavioral and memory problems, sleep disturbances and no rhythm variation in aMT6s levels. The low melatonin content may be related with sleep disorders in this population, which, in turn, can have an adverse effect on specific cognitive skills such as memory. PMID:26976740

  15. Urinary Melatonin Levels and Skin Malignancy

    Reza Ghaderi; Samineh Sehatbakhsh; Mehdi Bakhshaee; Gholam Reza Sharifzadeh

    2014-01-01

    Melatonin inhibits tumor genesis in a variety of in vivo and in vitro experimental models of neoplasia. In industrialized societies, light at night, by suppressing melatonin production, poses a new risk for the development of a variety of cancers such as breast cancer. This effect on skin has been previously studied only in animals and not in humans. Our goal was to examine the relationship between 24-hour 6-sulphatoxymelatonin levels and skin cancer in a case-control study of 70 patients wit...

  16. Structural requirements at the melatonin receptor.

    Sugden, D; Chong, N W; D. F. Lewis

    1995-01-01

    1. High affinity, specific binding sites for the pineal hormone, melatonin (5-methoxy N-acetyltryptamine) can be detected in chick brain membranes by use of the radiolabelled agonist, 2-[125I]-iodomelatonin (2-[125I]-aMT). 2. The affinity of a number of analogues of melatonin at the 2-[125I]-aMT binding site was determined and compared with an analysis of their electronic structure and significant quantitative relationships obtained. 3. The best correlations indicated that binding affinity wa...

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

    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 Bakırköy 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.

  18. Jet lag: therapeutic use of melatonin and possible application of melatonin analogs.

    Srinivasan, Venkataramanujan; Spence, D Warren; Pandi-Perumal, Seithikurippu R; Trakht, Ilya; Cardinali, Daniel P

    2008-01-01

    Each year millions of travelers undertake long distance flights over one or more continents. These multiple time zone flights produce a constellation of symptoms known as jet lag. Familiar to almost every intercontinental traveler is the experience of fatigue upon arrival in a new time zone, but almost as problematic are a number of other jet lag symptoms. These include reduced alertness, nighttime insomnia, loss of appetite, depressed mood, poor psychomotor coordination and reduced cognitive skills, all symptoms which are closely affected by both the length and direction of travel. The most important jet lag symptoms are due to disruptions to the body's sleep/wake cycle. Clinical and pathophysiological studies also indicate that jet lag can exacerbate existing affective disorders. It has been suggested that dysregulation of melatonin secretion and occurrence of circadian rhythm disturbances may be the common links which underlie jet lag and affective disorders. Largely because of its regulatory effects on the circadian system, melatonin has proven to be highly effective for treating the range of symptoms that accompany transmeridian air travel. Additionally, it has been found to be of value in treating mood disorders like seasonal affective disorder. Melatonin acts on MT(1) and MT(2) melatonin receptors located in the hypothalamic suprachiasmatic nuclei, the site of the body's master circadian clock. Melatonin resets disturbed circadian rhythms and promotes sleep in jet lag and other circadian rhythm sleep disorders, including delayed sleep phase syndrome and shift-work disorder. Although post-flight melatonin administration works efficiently in transmeridian flights across less than 7-8 times zones, in the case longer distances, melatonin should be given by 2-3 days in advance to the flight. To deal with the unwanted side effects which usually accompany this pre-departure treatment (acute soporific and sedative effects in times that may not be wanted), the suppression of circadian rhythmicity by covering symmetrically the phase delay and the phase advance portions of the phase response curve for light, together with the administration of melatonin at local bedtime to resynchronize the circadian oscillator, have been proposed. The current view that sleep loss is a major cause of jet lag has focused interest on two recently developed pharmacological agents. Ramelteon and agomelatine are melatonin receptor agonists which, compared to melatonin itself, have a longer half-life and greater affinity for melatonin receptors and consequently are thought to hold promise for treating a variety of circadian disruptions. PMID:18342269

  19. Nocturnal flow on a western Colorado slope

    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

  20. Melatonin as a possible antidote to UV radiation induced cutaneous damages and immune-suppression: An overview.

    Goswami, Soumik; Haldar, Chandana

    2015-12-01

    The sun rays brings along the ultraviolet radiations (UVRs) which prove deleterious for living organisms. The UVR is a known mutagen and is the prime cause of skin carcinomas. UVR causes acute oxidative stress and this in turn deteriorates other physiological functions. Inflammatory conditions and elevation of pro-inflammatory molecules are also associated with UVR mediated cellular damages. The inflammatory conditions can secondarily trigger the generation of free radicals and this act cumulatively in further deterioration of tissue homeostasis. Photoimmunologists have also related UVR to the suppression of not only cutaneous but also systemic immunity by different mechanisms. Some researchers have proposed the use of various plant products as antioxidants against UVR induced oxidative imbalances but Melatonin is gaining rapid interest as a product that can be utilized to delineate the pathological effects of UVR since it is an established antioxidant. Besides the antioxidative nature, the capacity of melatonin to attenuate apoptosis and more importantly the efficacy of its metabolites to further aid in the detoxification of free radicals have made it a key player to be utilized against UVR mediated aggravated conditions. However, there is need for further extensive investigation to speculate melatonin as an antidote to UVR. Although too early to prescribe melatonin as a clinical remedy, the hormone can be integrated into dermal formulations or oral supplements to prevent the ever increasing incidences of skin cancers due to the prevalence of the UVR on the surface of the earth. The present review focuses and substantiates the work by different photo-biologists demonstrating the protective effects of melatonin and its metabolites against solar UVR - Melatonin as a possible antidote to UV radiation induced cutaneous damages and immune-suppression: an overview. J Photochem Photobiol B. PMID:26496791

  1. Dietary melatonin alters uterine artery hemodynamics in pregnant Holstein heifers.

    Brockus, K E; Hart, C G; Gilfeather, C L; Fleming, B O; Lemley, C O

    2016-04-01

    The objective was to examine uterine artery hemodynamics and maternal serum profiles in pregnant heifers supplemented with dietary melatonin (MEL) or no supplementation (CON). In addition, melatonin receptor-mediated responses in steroid metabolism were examined using a bovine endometrial epithelial culture system. Twenty singleton pregnant Holstein heifers were supplemented with 20 mg of melatonin (n = 10) or no melatonin supplementation (control; n = 10) from days 190 to 262 of gestation. Maternal measurements were recorded on days 180 (baseline), 210, 240, and 262 of gestation. Total uterine blood flow was increased by 25% in the MEL-treated heifers compared with the CON. Concentrations of progesterone were decreased in MEL vs CON heifers. Total serum antioxidant capacity was increased by 43% in MEL-treated heifers when compared with CON. Activity of cytochrome P450 1A, 2C, and superoxide dismutase was increased in bovine endometrial epithelial cells treated with melatonin, whereas the melatonin receptor antagonist, luzindole, negated the increase in cytochrome P450 2C activity. Moreover, estradiol or progesterone treatment altered bovine uterine melatonin receptor expression, which could potentiate the melatonin-mediated responses during late gestation. The observed increase in total uterine blood flow during melatonin supplementation could be related to its antioxidant properties. Compromised pregnancies are typically accompanied by increased oxidative stress; therefore, melatonin could serve as a therapeutic supplementation strategy. This could lead to further fetal programming implications in conjunction with offspring growth and development postnatally. PMID:26641925

  2. The research of melatonin in hypoxic-ischemic encephalopathy

    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)

  3. Melatonin attenuates postharvest physiological deterioration of cassava storage roots.

    Ma, Qiuxiang; Zhang, Ting; Zhang, Peng; Wang, Zhen-Yu

    2016-05-01

    Melatonin reportedly increases abiotic and biotic stress tolerance in plants, but information on its in vivo effects during postharvest physiological deterioration (PPD) in cassava is limited. In this study, we investigated the effect of melatonin in regulating cassava PPD. Treatment with 500 mg/L melatonin significantly delayed cassava PPD and reduced the accumulation of hydrogen peroxide (H2 O2 ) while increasing the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR), but not ascorbate peroxidase (APX). Transcript analysis further showed that expression of copper/zinc SOD (MeCu/ZnSOD), MeCAT1, glutathione peroxidase (MeGPX), peroxidase 3 (MePX3), and glutathione S-transferases (MeGST) was higher in cassava roots sliced treated with 500 mg/L melatonin than in those not exposed to exogenous melatonin. These data demonstrate that melatonin delays cassava PPD by directly or indirectly maintaining homoeostasis of cellular reactive oxygen species (ROS). We also found that accumulation of endogenous melatonin and the transcript levels of melatonin biosynthesis genes changed dynamically during the PPD process. This finding suggested that endogenous melatonin acts as a signal modulator for maintaining cassava PPD progression and that manipulation of melatonin biosynthesis genes through genetic engineering might prevent cassava root deterioration. PMID:26989849

  4. The Impact of Melatonin in Research

    Elena Maria Varoni

    2016-02-01

    Full Text Available Citation indexes represent helpful tools for evaluating the impact of articles on research. The aim of this study was to obtain the top-100 ranking of the most cited papers on melatonin, a relevant neurohormone mainly involved in phase-adjusting the biological clock and with certain sleep-promoting capability. An article search was carried out on the Institute for Scientific Information (ISI Web of Science platform. Numbers of citations, names of authors, journals and their 2014-impact factor, year of publication, and experimental designs of studies were recorded. The ranking of the 100-most cited articles on melatonin research (up to February 2016 revealed a citation range from 1623 to 310. Narrative reviews/expert opinions were the most frequently cited articles, while the main research topics were oxidative stress, sleep physiology, reproduction, circadian rhythms and melatonin receptors. This study represents the first detailed analysis of the 100 top-cited articles published in the field of melatonin research, showing its impact and relevance in the biomedical field.

  5. The Australian Bogong Moth Agrotis infusa: A Long-Distance Nocturnal Navigator

    Warrant, Eric; Frost, Barrie; Green, Ken; Mouritsen, Henrik; Dreyer, David; Adden, Andrea; Brauburger, Kristina; Heinze, Stanley

    2016-01-01

    The nocturnal Bogong moth (Agrotis infusa) is an iconic and well-known Australian insect that is also a remarkable nocturnal navigator. Like the Monarch butterflies of North America, Bogong moths make a yearly migration over enormous distances, from southern Queensland, western and northwestern New South Wales (NSW) and western Victoria, to the alpine regions of NSW and Victoria. After emerging from their pupae in early spring, adult Bogong moths embark on a long nocturnal journey towards the Australian Alps, a journey that can take many days or even weeks and cover over 1000 km. Once in the Alps (from the end of September), Bogong moths seek out the shelter of selected and isolated high ridge-top caves and rock crevices (typically at elevations above 1800 m). In hundreds of thousands, moths line the interior walls of these cool alpine caves where they “hibernate” over the summer months (referred to as “estivation”). Towards the end of the summer (February and March), the same individuals that arrived months earlier leave the caves and begin their long return trip to their breeding grounds. Once there, moths mate, lay eggs and die. The moths that hatch in the following spring then repeat the migratory cycle afresh. Despite having had no previous experience of the migratory route, these moths find their way to the Alps and locate their estivation caves that are dotted along the high alpine ridges of southeastern Australia. How naïve moths manage this remarkable migratory feat still remains a mystery, although there are many potential sensory cues along the migratory route that moths might rely on during their journey, including visual, olfactory, mechanical and magnetic cues. Here we review our current knowledge of the Bogong moth, including its natural history, its ecology, its cultural importance to the Australian Aborigines and what we understand about the sensory basis of its long-distance nocturnal migration. From this analysis it becomes clear that the Bogong moth represents a new and very promising model organism for understanding the sensory basis of nocturnal migration in insects. PMID:27147998

  6. The Australian Bogong Moth Agrotis infusa: A Long-Distance Nocturnal Navigator.

    Warrant, Eric; Frost, Barrie; Green, Ken; Mouritsen, Henrik; Dreyer, David; Adden, Andrea; Brauburger, Kristina; Heinze, Stanley

    2016-01-01

    The nocturnal Bogong moth (Agrotis infusa) is an iconic and well-known Australian insect that is also a remarkable nocturnal navigator. Like the Monarch butterflies of North America, Bogong moths make a yearly migration over enormous distances, from southern Queensland, western and northwestern New South Wales (NSW) and western Victoria, to the alpine regions of NSW and Victoria. After emerging from their pupae in early spring, adult Bogong moths embark on a long nocturnal journey towards the Australian Alps, a journey that can take many days or even weeks and cover over 1000 km. Once in the Alps (from the end of September), Bogong moths seek out the shelter of selected and isolated high ridge-top caves and rock crevices (typically at elevations above 1800 m). In hundreds of thousands, moths line the interior walls of these cool alpine caves where they "hibernate" over the summer months (referred to as "estivation"). Towards the end of the summer (February and March), the same individuals that arrived months earlier leave the caves and begin their long return trip to their breeding grounds. Once there, moths mate, lay eggs and die. The moths that hatch in the following spring then repeat the migratory cycle afresh. Despite having had no previous experience of the migratory route, these moths find their way to the Alps and locate their estivation caves that are dotted along the high alpine ridges of southeastern Australia. How naïve moths manage this remarkable migratory feat still remains a mystery, although there are many potential sensory cues along the migratory route that moths might rely on during their journey, including visual, olfactory, mechanical and magnetic cues. Here we review our current knowledge of the Bogong moth, including its natural history, its ecology, its cultural importance to the Australian Aborigines and what we understand about the sensory basis of its long-distance nocturnal migration. From this analysis it becomes clear that the Bogong moth represents a new and very promising model organism for understanding the sensory basis of nocturnal migration in insects. PMID:27147998

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

    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...

  8. The impact of nocturnal hemodialysis on sexual function

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

    2012-01-01

    Abstract Background Sexual dysfunction is common in patients with end stage renal disease (ESRD) and treatment options are limited. Observational studies suggest that nocturnal hemodialysis may improve sexual function. We compared sexual activity and responses to sexual related questions in the Kidney Disease Quality of Life Short Form questionnaire among patients randomized to frequent nocturnal or thrice weekly conventional hemodialysis. Methods We performed a secondary analysis of data fro...

  9. Kiwi genome provides insights into evolution of a nocturnal lifestyle

    Le Duc, Diana; Renaud, Gabriel; Krishnan, Arunkumar; Almén, Markus Sällman; Huynen, Leon; Prohaska, Sonja J.; Ongyerth, Matthias; Bitarello, Barbara D.; Schiöth, Helgi B; Hofreiter, Michael; Stadler, Peter F; Pruefer, Kay; LAMBERT, David; Kelso, Janet; Schoeneberg, Torsten

    2015-01-01

    Background Kiwi, comprising five species from the genus Apteryx, are endangered, ground-dwelling bird species endemic to New Zealand. They are the smallest and only nocturnal representatives of the ratites. The timing of kiwi adaptation to a nocturnal niche and the genomic innovations, which shaped sensory systems and morphology to allow this adaptation, are not yet fully understood. Results We sequenced and assembled the brown kiwi genome to 150-fold coverage and annotated the genome using k...

  10. Coexistence of Epileptic Nocturnal Wanderings and an Arachnoid Cyst

    Jiménez-Genchi, Alejandro; Díaz-Galviz, John L.; García-Reyna, Juan Carlos; Ávila-Ordoñez, Mario U.

    2007-01-01

    Episodic nocturnal wanderings (ENWs) have rarely been associated with gross abnormalities of brain structures. We describe the case of a patient with ENWs in coexistence with an arachnoid cyst (AC). The patient was a 15-year-old boy who presented with nocturnal attacks characterized by complex motor behaviors. An MRI revealed a left temporal cyst and a SPECT Tc99 scan showed left temporal hypoperfusion and bilateral frontal hyperperfusion, more evident on the right side.

  11. Melatonin decreases the expression of inflammation and apoptosis markers in the lung of a senescence-accelerated mice model.

    Puig, Ángela; Rancan, Lisa; Paredes, Sergio D; Carrasco, Adrián; Escames, Germaine; Vara, Elena; Tresguerres, Jesús A F

    2016-03-01

    Aging is associated with an increase in oxidative stress and inflammation. The aging lung is particularly affected since it is continuously exposed to environmental oxidants while antioxidant machinery weakens with age. Melatonin, a free radical scavenger, counteracts inflammation and apoptosis in healthy cells from several tissues. Its effects on the aging lung are, however, not yet fully understood. This study aimed to investigate the effect of chronic administration of melatonin on the expression of inflammation markers (TNF-?, IL-1?, NF?B2, HO-1) and apoptosis parameters (BAD, BAX, AIF) in the lung tissue of male senescence-accelerated prone mice (SAMP8). In addition, RNA oxidative damage, as the formation of 8-hydroxyguanosine (8-OHG), was also evaluated. Young and old animals, aged 2 and 10months respectively, were divided into 4 groups: untreated young, untreated old, old mice treated with 1mg/kg/day melatonin, and old animals treated with 10mg/kg/day melatonin. Untreated young and old male senescence accelerated resistant mice (SAMR1) were used as controls. After 30days of treatment, animals were sacrificed. Lungs were collected and immediately frozen in liquid nitrogen. mRNA and protein expressions were measured by RT-PCR and Western blotting, respectively. Levels of 8-OHG were quantified by ELISA. Mean values were analyzed using ANOVA. Old nontreated SAMP8 animals showed increased (p<0.05) mRNA and protein levels of TNF-?, IL-1?, NF?B2, and HO-1 compared to young mice and SAMR1 mice. Melatonin treatment with either dose reversed the aging-derived inflammation (p<0.05). BAD, BAX and AIF expressions also rose with aging, the effect being counteracted with melatonin (p<0.05). Aging also caused a significant elevation (p<0.05) in SAMP8 8-OHG values. This increase was not observed in animals treated with melatonin (p<0.05). In conclusion, melatonin treatment was able to modulate the inflammatory and apoptosis status of the aging lungs, exerting a protective effect on age-induced damage. PMID:26656745

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

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

    2010-01-01

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

  13. Impact of oral melatonin on the electroretinogram cone response.

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

    2009-01-01

    BACKGROUND: In the eye, melatonin plays a role in promoting light sensitivity at night and modulating many aspects of circadian retinal physiology. It is also an inhibitor of retinal dopamine, which is a promoter of day vision through the cone system. Consequently, it is possible that oral melatonin (an inhibitor of retinal dopamine) taken to alleviate circadian disorders may affect cone functioning. Our aim was to assess the impact of melatonin on the cone response of the human retina using ...

  14. Melatonin in sleepless children : everything has a rhythm?

    van Geijlswijk, I.M.

    2011-01-01

    Every living organism has an biological clock regulating endogenous melatonin production, synchronized by exogenous impulses like daylight, temperature and feeding. Inappropriately applied bright light disturbs this melatonin rhythm. Some large swine producers apply artificial light three times a day for three hours; we compared the 24 hour melatonin rhythm of pigs in a large swine production unit with pigs in a farm with natural light schemes (chapter two). No significant differences were fo...

  15. Melatonin Supplementation in Patients with Complete Tetraplegia and Poor Sleep

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

    2013-01-01

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

  16. RESPONSE OF COMMIPHORA MUKUL (GUGGULU) ON MELATONIN INDUCED HYPOTHYROIDISM

    A.K.Singh; Tripathi, S. N.; Prasad, G. C.

    1983-01-01

    The results of this study indicate that melatonin induces hypothyroidism in mice within eight days. Simultaneous administration of melatonin and petroleum ether extract of Commiphora mukul brings about a significant improvement in thyroid structure and function. Further, melatonin induced hypothyroidism is although a little reversible yet it is normalized quickly after C. mukul treatment. These data suggest that C. mukul directly stimulates thyroid function probably through some enzymatic mec...

  17. The agonistic adrenal: melatonin elicits female aggression via regulation of adrenal androgens.

    Rendon, Nikki M; Rudolph, Lauren M; Sengelaub, Dale R; Demas, Gregory E

    2015-11-22

    Classic findings have demonstrated an important role for sex steroids as regulators of aggression, but this relationship is lacking within some environmental contexts. In mammals and birds, the adrenal androgen dehydroepiandrosterone (DHEA), a non-gonadal precursor of biologically active steroids, has been linked to aggression. Although females, like males, use aggression when competing for limited resources, the mechanisms underlying female aggression remain understudied. Here, we propose a previously undescribed endocrine mechanism regulating female aggression via direct action of the pineal hormone melatonin on adrenal androgens. We examined this in a solitary hamster species, Phodopus sungorus, in which both sexes are highly territorial across the seasons, and display increased aggression concomitant with decreased serum levels of sex steroids in short 'winter-like' days. Short- but not long-day females had increased adrenal DHEA responsiveness co-occurring with morphological changes in the adrenal gland. Further, serum DHEA and total adrenal DHEA content were elevated in short days. Lastly, melatonin increased DHEA and aggression and stimulated DHEA release from cultured adrenals. Collectively, these findings demonstrate that DHEA is a key peripheral regulator of aggression and that melatonin coordinates a 'seasonal switch' from gonadal to adrenal regulation of aggression by direct action on the adrenal glands. PMID:26582025

  18. Necrotizing Fasciitis in Paroxysmal Nocturnal Hemoglobinuria.

    Patir, Pusem; Isik, Yakup; Turk, Yigit; Ugur, Mehmet Can; Ceylan, Cengiz; Gorgun, Gulnur; Mete Gokmen, Nihal; Saydam, Guray; Sahin, Fahri

    2015-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, progressive, and life-threatening hematopoietic stem cell disorder characterized by complement-mediated intravascular hemolysis and a prothrombotic state. Patients with PNH might have slightly increased risk of infections due to complement-associated defects subsequent to CD59 deficiency. Here, we report a rare case of a 65-year-old male patient with necrotic ulcers on both legs, where the recognition of pancytopenia and microthrombi led to the diagnosis of PNH based on FLAER (FLuorescent AERolysin) flow cytometric analysis. He was subsequently started on eculizumab therapy, with starting and maintenance doses set as per drug labelling. Progression of the patient's leg ulcers during follow-up, with fulminant tissue destruction, purulent discharge, and necrotic patches, led to a later diagnosis of necrotizing fasciitis due to Pseudomonas aeruginosa and Klebsiella pneumonia infection. Courses of broad-spectrum antibiotics, surgical debridement, and superficial skin grafting were applied with successful effect during ongoing eculizumab therapy. This case highlights the point that it is important to maintain treatment of underlying disorders such as PNH in the presence of life-threatening infections like NF. PMID:26347833

  19. Nocturnal enuresis among primary school children

    Hasan Mohamed Aljefri

    2013-01-01

    Full Text Available To determine the prevalence and personal and family risk factors for nocturnal enuresis (NE among primary school children in Al-Mukalla City, Yemen, we conducted a cross-sectional survey using a self-administered, three-part structured questionnaire involving 832 school children aged 6 - 15 years between 2007 and 2008. We assessed participants′ socio-demographic factors, family characteristics and factors related to the presence of NE. The mean age of the children was 11.5 (±2.7 years. The overall prevalence of NE was 28.6%, with a predominance of girls, and the prevalence decreased with increasing age (P 0.002 and a higher number of siblings (P = 0.01. Our findings reveal a high prevalence of NE among children in Al-Mukalla City, Yemen, with a higher prevalence in girls than in boys compared with the other studies. Sleep pattern, stressful life events, family history of NE, large family size and more children in the household may act as a risk factor for NE.

  20. Melatonin improves spatial navigation memory in male diabetic rats

    Farrin Babaei-Balderlou; Samad Zare

    2012-01-01

    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 ...

  1. Melatonin Effects on Hard Tissues: Bone and Tooth

    Hong-Wen He

    2013-05-01

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

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

    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.

  3. Peripheral reproductive organ health and melatonin: ready for prime time.

    Reiter, Russel J; Rosales-Corral, Sergio A; Manchester, Lucien C; Tan, Dun-Xian

    2013-01-01

    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. PMID:23549263

  4. Melatonin regulates proteomic changes during leaf senescence in Malus hupehensis.

    Wang, Ping; Sun, Xun; Xie, Yinpeng; Li, Mingjun; Chen, Wei; Zhang, Sheng; Liang, Dong; Ma, Fengwang

    2014-10-01

    Despite the relationship between melatonin and aging, the overall changes and regulation of proteome profiling by long-term melatonin exposure during leaf senescence is not well understood. In this study, leaf senescence in Malus hupehensis plants was delayed when exogenous melatonin was regularly applied to the roots for 2 months compared with natural leaf senescence. Proteins of samples 0 and 50 day for both treatments were extracted and labeled with TMT regents before being examined via NanoLC-MS/MS. The proteomics data showed that 622 and 309 proteins were altered by senescence and melatonin, respectively. Our GO analysis by Blast2GO revealed that most of the altered proteins that are involved in major metabolic processes exhibited hydrolase activity and were mainly located in the plastids. These proteins were classified into several senescence-related functional categories, including degradation of macromolecules, redox and stress responses, transport, photosynthesis, development, and other regulatory proteins. We found that melatonin treatment led to the downregulation of proteins that are normally upregulated during senescence. The melatonin-related delay in senescence might have occurred due to the altering of proteins involved in processes associated with senescence. And as well, there are many unknown regulatory proteins possibly being involved in the melatonin's function. This study is the first to demonstrate changes at the proteome level in response to exogenous melatonin in plants. Our findings provide a set of informative and fundamental data about the role of melatonin in apple leaf senescence. PMID:25146528

  5. Melatonin is rhythmic in newborn seals exposed to continuous light.

    Aarseth, J J; Van't Hof, T J; Stokkan, K-A

    2003-02-01

    We have investigated the effect of continuous light and darkness on plasma levels of melatonin in relation to the extremely large and active pineal gland typically found in newborn seals. Plasma levels of melatonin in captive newborn harp (Phoca groenlandica) and hooded seals (Cystophora cristata) were generally extremely high, with peak concentrations ranging from 0.8 ng/ml to 62.3 ng/ml. Moreover, plasma melatonin showed a similar, pronounced rhythmicity, both outdoors under natural light conditions (hooded seal only) and indoors under either 30 h of continuous light (490 lux) or 30 h of darkness (0 lux). In all animals, the melatonin rhythm was closely associated with the outdoor light-dark cycle. We suggest that the melatonin rhythmicity in newborn seals is mainly under circadian control and that it originates by maternal influence in the foetus. Daytime plasma concentrations of melatonin were also measured in foetal hooded seals and their mothers. The foetal melatonin level was similar to daytime levels in newborns and was about five times higher than in their mothers, which indicates a significant flow of foetal melatonin to the mother. We speculate that the large pineal gland and high melatonin levels in the newborn seals are temporary consequences of a foetal strategy to affect the maternal blood supply during diving. PMID:12592441

  6. Detection of melatonin receptor mRNA in human muscle

    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)

  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

    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 μg/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 μg/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 off adequate replacement therapy. One of the major aspects of this study has been the evaluation of baseline 6-SM concentrations, with no physiological or pharmacological stimulation. Even if under the conditions of this study we found no differences in nocturnal excretion of 6-SM between untreated and treated GHD individuals in both groups, this does not rule out the potential existence of differences that might be detected by studying diurnal melatonin secretion and its difference with nocturnal secretion. Such studies may contribute to an understanding of potential chronobiological disorders involved in GH deficiency.

  8. Melatonin in Alzheimer's disease and other neurodegenerative disorders

    Poeggeler B

    2006-05-01

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

  9. Evidence of a role for melatonin in fetal sheep physiology: direct actions of melatonin on fetal cerebral artery, brown adipose tissue and adrenal gland

    Torres-Farfan, Claudia; Valenzuela, Francisco J; Mondaca, Mauricio; Valenzuela, Guillermo J; Krause, Bernardo; Herrera, Emilio A; Riquelme, Raquel; Llanos, Anibal J; Seron-Ferre, Maria

    2008-01-01

    Although the fetal pineal gland does not secrete melatonin, the fetus is exposed to melatonin of maternal origin. In the non-human primate fetus, melatonin acts as a trophic hormone for the adrenal gland, stimulating growth while restraining cortisol production. This latter physiological activity led us to hypothesize that melatonin may influence some fetal functions critical for neonatal adaptation to extrauterine life. To test this hypothesis we explored (i) the presence of G-protein-coupled melatonin binding sites and (ii) the direct modulatory effects of melatonin on noradrenaline (norepinephrine)-induced middle cerebral artery (MCA) contraction, brown adipose tissue (BAT) lypolysis and ACTH-induced adrenal cortisol production in fetal sheep. We found that melatonin directly inhibits the response to noradrenaline in the MCA and BAT, and also inhibits the response to ACTH in the adrenal gland. Melatonin inhibition was reversed by the melatonin antagonist luzindole only in the fetal adrenal. MCA, BAT and adrenal tissue displayed specific high-affinity melatonin binding sites coupled to G-protein (Kd values: MCA 64 ± 1 pm, BAT 98.44 ± 2.12 pm and adrenal 4.123 ± 3.22 pm). Melatonin binding was displaced by luzindole only in the adrenal gland, supporting the idea that action in the MCA and BAT is mediated by different melatonin receptors. These direct inhibitory responses to melatonin support a role for melatonin in fetal physiology, which we propose prevents major contraction of cerebral vessels, restrains cortisol release and restricts BAT lypolysis during fetal life. PMID:18599539

  10. Melatonin in Alzheimer’s Disease

    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...

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

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

    2015-06-01

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

  12. Nocturnal asthma in school children of south punjab, pakistan

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

  13. Fundamental issues related to the origin of melatonin and melatonin isomers during evolution: relation to their biological functions.

    Tan, Dun-Xian; Zheng, Xiaodong; Kong, Jin; Manchester, Lucien C; Hardeland, Ruediger; Kim, Seok Joong; Xu, Xiaoying; 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 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. PMID:25207599

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

    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.

  15. Melatonin improves spatial navigation memory in male diabetic rats

    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.

  16. Melatonin Therapy in Patients with Alzheimer’s Disease

    Cardinali, Daniel P.; Vigo, Daniel E.; Olivar, Natividad; Vidal, María F.; Brusco, Luis I.

    2014-01-01

    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. PMID:26784870

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

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

    2015-08-01

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

  18. A systematic review of peri-operative melatonin

    Andersen, L P H; Werner, M U; Rosenberg, J; Gögenur, I

    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......%, respectively. Qualitative reviews suggested the melatonin improved sleep quality and emergence behaviour, and might be capable of reducing oxidative stress and anaesthetic requirements....

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

    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

  20. Melatonin-mediated effects on killifish reproductive axis.

    Lombardo, Francesco; Gioacchini, Giorgia; Fabbrocini, Adele; Candelma, Michela; D'Adamo, Raffaele; Giorgini, Elisabetta; Carnevali, Oliana

    2014-06-01

    The aim of this study was to investigate the melatonin-mediated effects upon the neuroendocrine axis of the brackish killifish (Fundulus heteroclitus), a suitable experimental model to study reproductive events. The ability of melatonin to enhance reproductive capacity (fecundity, embryo survival and hatching rate) inducing the transcriptional activity of gonadotropin releasing hormone (gnrh), luteinizing hormone receptor (lhr) and melatonin receptor (mtnr) was investigated in adult females. Moreover, the melatonin-mediated enhancement of killifish sperm motility and velocity was found consistent with higher fecundity of melatonin-exposed fishes. As a further extent, Fourier Transform Infrared (FT-IR) microspectroscopy evidenced a reduction of lipid unsaturation level on isolated spermatozoa from treated males. Moreover, the reduction of mtnr gene expression during embryo development and lower biometric parameters documented in the larvae from melatonin-exposed parents suggest that melatonin acts as a hormonal mediator able to transfer the environmental signal to oocytes and then to embryos as inheritance of adaptive environmental changes. These results support the positive role of melatonin on killifish reproduction and its role as a maternal factor on embryo and larval development. PMID:24548909

  1. 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

    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.

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

    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

  3. Melatonin in the skin: synthesis, metabolism and functions.

    Slominski, Andrzej; Tobin, Desmond J; Zmijewski, Michal A; Wortsman, Jacobo; Paus, Ralf

    2008-01-01

    Melatonin, a ubiquitous methoxyindole, is produced by and metabolized in the skin. Melatonin affects skin functions and structures through actions mediated by cell-surface and putative-nuclear receptors expressed in skin cells. Melatonin has both receptor-dependent and receptor-independent effects that protect against oxidative stress and can attenuate ultraviolet radiation-induced damage. The widespread expression and pleiotropic activity of the cutaneous melatoninergic system provides for a high level of cell-specific selectivity. Moreover, intra-, auto- and para-crine mechanisms equip this system with exquisite functional selectivity. The properties of endogenous melatonin suggest that this molecule is an important effector of stress responses in the skin. In this way, melatonin actions may counteract or buffer both environmental and endogenous stressors to maintain skin integrity. PMID:18155917

  4. The role of melatonin in mood disorders

    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 

  5. Myocardial infarction:aspects relating to endogenous and exogenous melatonin and cardiac contractility

    Sallinen, P.

    2008-01-01

    Abstract Melatonin is an important modulator of several physiological and behavioural processes, and it influences the function of many different tissues. Melatonin has effective antioxidative properties, but some of its actions in mammals are also mediated through the MT1 and MT2 melatonin receptors. Antioxidative properties are seen especially when the melatonin concentration is high (? nM), and melatonin's affinity for its receptors appears at lower concentrations (pM). Recently, ...

  6. [Treatment of paroxysmal nocturnal hemoglobinuria (PNH)].

    Chrobák, L; Dulícek, P; Zák, P

    2001-12-01

    Paroxysmal nocturnal hemoglobinuria is an acquired clonal disorder of the hematopoietic stem cell in which intravascular hemolysis is due to an intrinsic defect in the membrane of red cells that makes them increasingly susceptible to lysis by complement. The phenotypic hallmark of PNH cells is an absence or marked deficiency of GPI-anchored proteins such as CD 59+, CD 55+ and others which normally protect cells from the action of complement. PHN is closely associated with aplastic anemia. Some degree of bone marrow failure is always present. Management of PNH is complicated by a highly variable clinical picture and course. Some patients have severe anemia aggravated by hemolytic crises and associated thromboses. Bone marrow failure is accompanied with frequent infections and hemorrhagic manifestations due to thrombocytopenia. With the exception of marrow transplantation, no definite therapy is available. In the exceptional circumstance in which the patient has a syngeneic twin, bone marrow transplantation is the most appropriate therapy for severe PNH because of absence of graft-versus-host disease. In general syngeneic transplantation without preconditioning has been unsuccessful because abnormal hematopoiesis returns. Allogeneic bone marrow transplantation has been used, but the transplant-associated morbidity and mortality are high due mainly to the fatal graft-versus-host disease and severe posttransplant marrow failure. Use of an unrelated donor transplant has to be considered as contraindicated. PNH is associated with striking predisposition to intravascular thrombosis which often involves the portal system or the brain. Fatal thromboses account for about 40-50% of all deaths in patients with PNH. The etiology of the thrombophilia in PNH is not fully clarified. Anticoagulation or thrombolytic therapy is required for treatment of venous thrombosis, the latter vena cava. Prophylactic anticoagulation in patients without contraindications such as severe thrombocytopenia seems to be justified. However, whether such therapy may be efficacious in reducing the incidence of thromboses or affect survival is conjectural. PNH patients have varying degree of platelet activation and some authors suggest that antiplatelet therapy might be efficacious in reducing the incidence and severity of venous thrombosis in PNH. Pregnancy is hazardous. Female patients should avoid the use of oral contraceptives. Pregnant patients require combined care of an experienced hematologist and obstetrician specialized in the management of high-risk pregnancies. PMID:11826554

  7. Melatonin prevents neonatal dexamethasone induced programmed hypertension: histone deacetylase inhibition.

    Wu, Ting-Hsin; Kuo, Hsuan-Chang; Lin, I-Chun; Chien, Shao-Ju; Huang, Li-Tung; Tain, You-Lin

    2014-10-01

    Adulthood hypertension can be programmed by corticosteroid exposure in early life. Oxidative stress, epigenetic regulation by histone deacetylases (HDACs), and alterations of renin-angiotensin system (RAS) are involved in the developmental programming of hypertension. We examined whether melatonin prevented neonatal dexamethasone (DEX)-induced programmed hypertension and how melatonin prevented these processes. We also examined whether HDAC inhibition by trichostatin A (TSA, a HDAC inhibitor) had similar effects. Male offspring were assigned to 5 groups (n=6/group): control, DEX, melatonin, DEX+melatonin, and DEX+TSA. Male rat pups were injected i.p. with DEX on day 1 (0.5mg/kg BW), day 2 (0.3mg/kg BW), and day 3 (0.1mg/kg BW) after birth. Melatonin was administered in drinking water at the dose of 0.01% during the lactation period. The DEX+TSA group received DEX and 0.5mg/kg TSA subcutaneous injection once daily for 1 week. All rats were killed at 16 weeks of age. Neonatal DEX exposure induced hypertension in male offspring at 16 weeks of age, which melatonin prevented. Neonatal DEX exposure decreased gene expression related to apoptosis, nephrogenesis, RAS, and sodium transporters. Yet DEX treatment increased protein levels of HDAC-1, -2, and -3 in the kidney. Melatonin therapy preserved the decreases of gene expression and decreased HDACs. Similarly, HDAC inhibition prevented DEX-induced programmed hypertension. In conclusion, melatonin therapy exerts a long-term protection against neonatal DEX-induced programmed hypertension. Its beneficial effects include alterations of RAS components and inhibition of class I HDACs. Given that the similar protective effects of melatonin and TSA, melatonin might inhibit HDACs to epigenetic regulation of hypertension-related genes to prevent programmed hypertension. PMID:25090636

  8. Radioprotective effects of melatonin on radiation-induced cataract

    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)

  9. Nocturnal sleep pattern in native Brazilian Terena adults

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

    2000-01-01

    Social-economic factors influence sleep habits. This research analyzes characteristics of nocturnal sleep in Brazilian Native Terena adults. Sixty-four adults (31 M; 33 F) from 18 to 75 years, with a mean age of 37.0, from the Indian Reservation village of Córrego do Meio, in the central region of Mato Grosso do Sul, an agriculturally oriented group were evaluated. Nocturnal sleep characteristics were evaluated by means of a standard questionnaire applied to each individual. It was observed t...

  10. Role of melatonin in mitigating chemotherapy-induced testicular dysfunction in Wistar rats.

    Madhu, P; Reddy, K Pratap; Reddy, P Sreenivasula

    2016-04-01

    Testicular cancer is the most common cancer affecting men of reproductive age, and its incidence is increasing steadily. A regimen of cisplatin (P), vinblastin (V) and bleomycin (B) (PVB) is the standard chemotherapy for testicular cancer. Though PVB-based chemotherapy has been widely used against germ cell tumors, it is associated with induction of oxidative toxicity and a transient or permanent loss of fertility. However, the mechanism of action of PVB on the testis is not thoroughly elucidated. Using a rat model, we investigated the persistence of the effects of PVB on steroidogenesis, spermatogenesis and testicular oxidative status and architecture. Further, we have also studied whether administration of melatonin has any protective effect on testicular physiology in the PVB-treated rats, since melatonin exerts influence on the antioxidant defense system. The body weight of the PVB-treated rats did not show significant change as compared with the control group. Significant decrease in the weight of the testis was observed with a reduction in volume in the PVB-treated rats. Administration of PVB caused a reduction in the testicular steroidogenesis and spermatogenesis. The circulatory levels of testosterone were also significantly reduced with an elevation of FSH and LH in the PVB-treated rats. Testicular architecture was severely affected with a reduction in seminiferous tubule diameter and epithelial height. The activities of superoxide dismutase and catalase were decreased while the levels of lipid peroxidation increased significantly in the testis of the PVB-treated rats indicating depletion of antioxidant defence system and elevation of oxidative stress. Co-administration of melatonin mitigated these changes in the PVB-treated rats. PMID:26072956

  11. Melatonin deacetylation: retinal vertebrate class distribution and Xenopus laevis tissue distribution.

    Grace, M S; Cahill, G M; Besharse, J C

    1991-09-13

    Deacetylation is a rapid clearance mechanism for ocular melatonin. We have studied the distribution of retinal melatonin deacetylase activity among vertebrate classes. Exogenous radiolabeled melatonin is metabolized by ocular tissue prepared from the amphibian Xenopus laevis, the reptile Anolis carolinensis, the teleost fish Carassius auratus, and the bird Gallus domesticus. In contrast, we were unable to detect ocular melatonin breakdown in rat or pig. In each species exhibiting ocular melatonin breakdown, melatonin is first deacetylated to 5-methoxytryptamine, which is deaminated, producing 5-methoxyindoleacetic acid and 5-methoxytryptophol. Deacetylation of melatonin is inhibited by eserine (physostigmine), causing a reduction in the levels of all 3 metabolites. Deamination of 5-methoxytryptamine is inhibited by the monoamine oxidase inhibitor pargyline, such that 5-methoxyindoleacetic acid and 5-methoxytryptophol levels are decreased while levels of 5-methoxytryptamine are increased. Incubation with the deacetylase inhibitor eserine increases endogenous melatonin levels in Xenopus and Carassius eyecups, indicating that endogenous melatonin is metabolized via the deacetylase. We also studied the tissue distribution of the deacetylase in Xenopus laevis. Melatonin deacetylation occurs in retina, retinal pigment epithelium, and skin, all of which are sites of melatonin action. These results indicate that among non-mammalian vertebrates, deacetylation is a common clearance mechanism for ocular melatonin, and may degrade melatonin at other sites of action as well. Melatonin deacetylation may help regulate local melatonin concentration, and generates other biologically active methoxyindoles. PMID:1782560

  12. Characteristics and mechanisms of the sudden warming events in the nocturnal atmospheric boundary layer: A case study using WRF

    Ma, Yuanyuan; Yang, Yi; Hu, Xiao-Ming; Gan, Ruhui

    2015-10-01

    Although sudden nocturnal warming events near the earth's surface in Australia and the United States have been examined in previous studies, similar events observed occasionally over the Loess Plateau of Northwest China have not yet been investigated. The factors that lead to these warming events in such areas with their unique topography and climate remain not clear. To understand the formation mechanisms and associated thermal and dynamical features, a nocturnal warming event recorded in Gansu Province (northwest of the Loess Plateau) in June 2007 was investigated by using observations and model simulations with the Weather Research and Forecasting (WRF) model. Observations showed that this near-surface warming event lasted for 4 h and the temperature increased by 2.5°C. During this event, a decrease in humidity occurred simultaneously with the increase of temperature. The model simulation showed that the nocturnal warming was caused mainly by the transport of warmer and drier air aloft downward to the surface through enhanced vertical mixing. Wind shear played an important role in inducing the elevated vertical mixing, and it was enhanced by the continuous development of the atmospheric baroclinicity, which converted more potential energy to kinetic energy.

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

    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.

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

    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

  15. Hemoglobinuria paroxística nocturna: Actualización / Paroxysmal nocturnal haemoglobinuria

    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. The effect of the melatonin on cryopreserved mouse testicular cells

    Ghasem Saki

    2016-01-01

    Full Text Available Background: After improvements in various cancer treatments, life expectancy has been raised, but success in treatment causes loss of fertility in many of the survived young men. Cryopreservation of immature testicular tissues or cells introduced as the only way to preserve fertility. However, freezing has some harmful effects. Melatonin, a pineal gland hormone, has receptors in reproductive systems of different species. It is assumed that melatonin has free radical scavenger properties. Objective: The aim of this study was to evaluate the effects of melatonin on the cryopreserved testicular cells in mouse. Materials and Methods: Cells from 7- 10 days old NMRI mice testes were isolated using two step enzymatic digestion. The testicular cells were divided into two groups randomly and cryopreserved in two different freezing media with and without the addition of 100 μm melatonin. Finally, apoptosis of the cells was assayed by flow cytometry. Also, lactate dehydrogenase activity test was performed to assess the cytotoxicity. Results: The results of lactate dehydrogenase showed the nearly cytotoxic effect of melatonin. The results of flow cytometry showed increase in apoptosis in the cryopreserved cells in the media containing melatonin compared to the control group. Conclusion: The present study shows that melatonin has an apoptotic effect on cryopreserved mouse testicular cells.

  17. Effect of Melatonin on Human Dental Papilla Cells

    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.

  18. The central role of melatonin in Danio rerio appetite regulation

    Oliana Carnevali

    2010-08-01

    Full Text Available Melatonin is the hormonal mediator of photoperiodic information to the central nervous system in vertebrates and allows the regulation of energy homeostasis through the establishment of a proper balance between energy intake and energy expenditure. The aim of this study was to evaluate the role of melatonin in the regulation of feeding behavior in the zebrafish Danio rerio. For this purpose, the effect of two different melatonin doses (100 nM and 1µM administered for ten days via water to zebrafish adults was evaluated at both physiological and molecular level and the effect of melatonin was considered in relation to the most prominent systems involved in appetite regulation. The melatonin control of food intake by the modulation of leptin, MC4R, ghrelin, NPY and CB1 gene expression was evaluated. The results obtained indicate that melatonin significantly reduces food intake and the reduction is in agreement with the changes observed at the molecular level. A significant increase in genes codifying for molecules involved in feeding inhibition, such as leptin and MC4R, and a significant reduction in the major orexigenic signals including ghrelin, NPY and CB1 was demonstrated. These results support the idea that melatonin falls fully into the complex network of signals that regulate food intake and therefore this hormone plays a key role in central appetite regulation.

  19. The effect of the melatonin on cryopreserved mouse testicular cells

    Saki, Ghasem; Mirhoseini, Mehri; Hemadi, Masoud; Khodadadi, Ali; Beygom Talebpour Amiri, Fereshteh

    2016-01-01

    Background: After improvements in various cancer treatments, life expectancy has been raised, but success in treatment causes loss of fertility in many of the survived young men. Cryopreservation of immature testicular tissues or cells introduced as the only way to preserve fertility. However, freezing has some harmful effects. Melatonin, a pineal gland hormone, has receptors in reproductive systems of different species. It is assumed that melatonin has free radical scavenger properties. Objective: The aim of this study was to evaluate the effects of melatonin on the cryopreserved testicular cells in mouse. Materials and Methods: Cells from 7- 10 days old NMRI mice testes were isolated using two step enzymatic digestion. The testicular cells were divided into two groups randomly and cryopreserved in two different freezing media with and without the addition of 100 µm melatonin. Finally, apoptosis of the cells was assayed by flow cytometry. Also, lactate dehydrogenase activity test was performed to assess the cytotoxicity. Results: The results of lactate dehydrogenase showed the nearly cytotoxic effect of melatonin. The results of flow cytometry showed increase in apoptosis in the cryopreserved cells in the media containing melatonin compared to the control group. Conclusion: The present study shows that melatonin has an apoptotic effect on cryopreserved mouse testicular cells.

  20. Nocturnal hypoxemia in children and adolescents with cystic fibrosis

    Regina Terse Trindade Ramos

    2013-12-01

    Full Text Available OBJECTIVE: To determine the prevalence of nocturnal hypoxemia and its association with pulmonary function, nutritional status, sleep macrostructure, and obstructive respiratory events during sleep in a population of clinically stable children and adolescents with cystic fibrosis (CF.METHODS: This was a cross-sectional study involving 67 children and adolescents with CF between 2 and 14 years of age. All of the participants underwent polysomnography, and SpO2 was measured by pulse oximetry. We also evaluated the Shwachman-Kulczycki (S-K scores, spirometry findings, and nutritional status of the patients.RESULTS: The study involved 67 patients. The mean age of the patients was 8 years. The S-K scores differed significantly between the patients with and without nocturnal hypoxemia, which was defined as an SpO2 < 90% for more than 5% of the total sleep time (73.75 ± 6.29 vs. 86.38 ± 8.70; p < 0.01. Nocturnal hypoxemia correlated with the severity of lung disease, FEV1 (rs= −0.42; p = 0.01, FVC (rs= −0.46; p = 0.01, microarousal index (rs= 0.32; p = 0.01, and apnea-hypopnea index (rs = 0.56; p = 0.01.CONCLUSIONS: In this sample of patients with CF and mild-to-moderate lung disease, nocturnal oxygenation correlated with the S-K score, spirometry variables, sleep macrostructure variables, and the apnea-hypopnea index.

  1. Sleep board review question: nocturnal hypoxemia in COPD

    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…

  2. Wild chimpanzees on the edge: nocturnal activities in croplands.

    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

  3. The impact of nocturnal hemodialysis on sexual function

    Bass Adam

    2012-07-01

    Full Text Available Abstract Background Sexual dysfunction is common in patients with end stage renal disease (ESRD and treatment options are limited. Observational studies suggest that nocturnal hemodialysis may improve sexual function. We compared sexual activity and responses to sexual related questions in the Kidney Disease Quality of Life Short Form questionnaire among patients randomized to frequent nocturnal or thrice weekly conventional hemodialysis. Methods We performed a secondary analysis of data from an RCT which enrolled 51 patients comparing frequent nocturnal and conventional thrice weekly hemodialysis. Sexual activity and responses to sexual related questions were assessed at baseline and six months using relevant questions from the Kidney Disease Quality of Life Short Form questionnaire. Results Overall, there was no difference in sexual activity, or the extent to which people were bothered by the impact of kidney disease on their sex life between the two groups between randomization and 6 months. However, women and patients age  Conclusions Our results suggest that frequent nocturnal hemodialysis is not associated with an improvement in sexual activity in all patients but might have an effect on the burden of kidney disease on sex life in women and patients less than 60 years of age. The validity of these subgroup findings require confirmation in future RCTs.

  4. Renal and hepatic scintigraphy in paroxysmal nocturnal hemoglobinuria (PNH)

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

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

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

    2011-07-01

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

  6. Clinical uses of melatonin: evaluation of human trials.

    Sánchez-Barceló, E J; Mediavilla, M D; Tan, D X; Reiter, R J

    2010-01-01

    During the last 20 years, numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine. The objective of this article is to review, in depth, the science regarding clinical trials performed to date. The efficacy of melatonin has been assessed as a treatment of ocular diseases, blood diseases, gastrointestinal tract diseases, cardiovascular diseases, diabetes, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome, infectious diseases, neurological diseases, sleep disturbances, aging and depression. Melatonin has been also used as a complementary treatment in anaesthesia, hemodialysis, in vitro fertilization and neonatal care. The conclusion of the current review is that the use of melatonin as an adjuvant therapy seems to be well funded for macular degeneration, glaucoma, protection of the gastric mucosa, irritable bowel syndrome, arterial hypertension, diabetes, side effects of chemotherapy and radiation in cancer patients or hemodialysis in patients with renal insufficiency and, especially, for sleep disorders of circadian etiology (jet lag, delayed sleep phase syndrome, sleep deterioration associated with aging, etc.) as well as in those related with neurological degenerative diseases (Alzheimer, etc.,) or Smith-Magenis syndrome. The utility of melatonin in anesthetic procedures has been also confirmed. More clinical studies are required to clarify whether, as the preliminary data suggest, melatonin is useful for treatment of fibromyalgia, chronic fatigue syndrome, infectious diseases, neoplasias or neonatal care. Preliminary data regarding the utility of melatonin in the treatment of ulcerative colitis, Crohn's disease, rheumatoid arthritis are either ambiguous or negative. Although in a few cases melatonin seems to aggravate some conditions, the vast majority of studies document the very low toxicity of melatonin over a wide range of doses. PMID:20423309

  7. Adenosine triphosphate inhibits melatonin synthesis in the rat pineal gland.

    Souza-Teodoro, Luis Henrique; Dargenio-Garcia, Letícia; Petrilli-Lapa, Camila Lopes; Souza, Ewerton da Silva; Fernandes, Pedro A C M; Markus, Regina P; Ferreira, Zulma S

    2016-03-01

    Adenosine triphosphate (ATP) is released onto the pinealocyte, along with noradrenaline, from sympathetic neurons and triggers P2Y1 receptors that enhance β-adrenergic-induced N-acetylserotonin (NAS) synthesis. Nevertheless, the biotransformation of NAS into melatonin, which occurs due to the subsequent methylation by acetylserotonin O-methyltransferase (ASMT; EC 2.1.1.4), has not yet been evaluated in the presence of purinergic stimulation. We therefore evaluated the effects of purinergic signaling on melatonin synthesis induced by β-adrenergic stimulation. ATP increased NAS levels, but, surprisingly, inhibited melatonin synthesis in an inverse, concentration-dependent manner. Our results demonstrate that enhanced NAS levels, which depend on phospholipase C (PLC) activity (but not the induction of gene transcription), are a post-translational effect. By contrast, melatonin reduction is related to an ASMT inhibition of expression at both the gene transcription and protein levels. These results were independent of nuclear factor-kappa B (NF-kB) translocation. Neither the P2Y1 receptor activation nor the PLC-mediated pathway was involved in the decrease in melatonin, indicating that ATP regulates pineal metabolism through different mechanisms. Taken together, our data demonstrate that purinergic signaling differentially modulates NAS and melatonin synthesis and point to a regulatory role for ATP as a cotransmitter in the control of ASMT, the rate-limiting enzyme in melatonin synthesis. The endogenous production of melatonin regulates defense responses; therefore, understanding the mechanisms involving ASMT regulation might provide novel insights into the development and progression of neurological disorders since melatonin presents anti-inflammatory, neuroprotective, and neurogenic effects. PMID:26732366

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

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

    2013-04-01

    The pineal product melatonin has remarkable antioxidant properties. It is secreted during darkness and plays a key role in various physiological responses including regulation of circadian rhythms, sleep homeostasis, retinal neuromodulation, and vasomotor responses. It scavenges hydroxyl, carbonate, and various organic radicals as well as a number of reactive nitrogen species. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, and glutathione reductase, and by augmenting glutathione levels. Melatonin preserves mitochondrial homeostasis, reduces free radical generation and protects mitochondrial ATP synthesis by stimulating Complexes I and IV activities. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases. The efficacy of melatonin in preventing oxidative damage in either cultured neuronal cells or in the brains of animals treated with various neurotoxic agents, suggests that melatonin has a potential therapeutic value as a neuroprotective drug in treatment of Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and brain trauma. Therapeutic trials with melatonin indicate that it has a potential therapeutic value as a neuroprotective drug in treatment of AD, ALS, and HD. In the case of other neurological conditions, like PD, the evidence is less compelling. Melatonin's efficacy in combating free radical damage in the brain suggests that it can be a valuable therapeutic agent in the treatment of cerebral edema following traumatic brain injury or stroke. Clinical trials employing melatonin doses in the range of 50-100 mg/day are warranted before its relative merits as a neuroprotective agent is definitively established. PMID:22739839

  9. Melatonin-insulin interactions in patients with metabolic syndrome.

    Robeva, R; Kirilov, G; Tomova, A; Kumanov, Ph

    2008-01-01

    Metabolic syndrome (MS) as a group of risk factors is strongly associated with diabetes type 2 and cardiovascular disease. Insulin resistance plays a key role in the pathogenesis of MS. Recent studies have shown that melatonin may influence insulin secretion and glucose homeostasis. Therefore, the present study analyzed the relationships between the melatonin and the insulin in patients with MS and controls. The melatonin rhythm, insulin and lipid levels were studied in 40 subjects (21 patients and 19 controls) in reproductive age. The night melatonin-insulin ratio was correlated negatively with low-density lipoprotein cholesterol (r = -0.370, p = 0.024) and total cholesterol (r = -0.348, p = 0.030), and positively with high-density lipoprotein cholesterol levels (r = +0.414, p = 0.010). Night-time melatonin levels were related to night-time insulin concentrations (r = +0.313, p = 0.049). The correlation was pronounced in patients with MS (r = +0.640, p = 0.002), but did not reach statistical significance in controls (P > 0.05). In the patients with MS unlike the controls the night-day melatonin difference (%) correlated negatively with the fasting glucose (r = -0.494, p = 0.023) and positively to daily insulin (r = +0.536, p = 0.012). Our results show that melatonin-insulin interactions may exist in patients with MS, as well as relationships between melatonin-insulin ratio and the lipid profile. Pineal disturbances could influence the pathogenesis and the phenotype variations of the MS. Larger studies are needed to confirm or reject this hypothesis and to clarify the role of the melatonin in the metabolic disturbances. PMID:18078448

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

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

    2014-11-01

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

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

    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.

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

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

  13. Melatonin Attenuates Colistin-Induced Nephrotoxicity in Rats▿

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

  14. Urinary Melatonin Levels and Skin Malignancy

    Reza Ghaderi

    2014-01-01

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

  15. New actions of melatonin and their relevance to biometeorology

    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.

  16. Melatonin in higher plants: occurrence and possible functions

    Kolář, Jan; Macháčková, Ivana

    2005-01-01

    Roč. 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

  17. Melatonin for Sleep Disorders in Patients with Neurodegenerative Diseases.

    Trotti, Lynn Marie; Karroum, Elias G

    2016-07-01

    In patients with neurodegenerative diseases, sleep disorders are common; they impair the quality of life for patients and caregivers and are associated with poorer clinical outcomes. Melatonin has circadian, hypnotic, and free radical-scavenging effects, and preclinical data suggest benefits of melatonin on neurodegeneration. However, randomized, controlled trials of melatonin in patients with neurodegenerative diseases have not shown strong effects. Trials in Alzheimer's patients demonstrate a lack of benefit on sleep quantity. Subjective measures of sleep quality are mixed, with possible symptomatic improvements seen only on some measures or at some time points. Benefits on cognition have not been observed across several studies. In Parkinson's patients, there may be minimal benefit on objective sleep measures, but a suggestion of subjective benefit in few, small studies. Effective treatments for the sleep disorders associated with neurodegenerative diseases are urgently needed, but current data are insufficient to establish melatonin as such a treatment. PMID:27180068

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

    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.

  19. 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

    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.

  20. Melatonin for the treatment of irritable bowel syndrome

    Siah, Kewin Tien Ho; Wong, Reuben Kong Min; Ho, Khek Yu

    2014-01-01

    Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain or discomfort, in combination with disturbed bowel habits in the absence of identifiable organic cause. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced by the pineal gland and also large number by enterochromaffin cells of the digestive mucosa. Melatonin plays an important part in gastrointestinal physiology which includes regulation of gastrointestinal motility, local anti-inflammator...

  1. Melatonin agonists for treatment of sleep and depressive disorders

    Pandi-Perumal, Seithikurippu R.; Brown, Gregory M.; Daniel P Cardinali; 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...

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

    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...

  3. Serum levels of melatonin and cytokines in multiple sclerosis

    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-γ, and tumor necrosis factor alpha (TNF-α, 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-α. 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-α, could be a factor in the inflammatory reactions in the pathologic process of MS.

  4. Gut melatonin response to microbial infection in carp Catla catla.

    Pal, Palash Kumar; Hasan, Kazi Nurul; Maitra, Saumen Kumar

    2016-04-01

    The purpose of present study was to demonstrate the response of gut melatoninergic system to Aeromonas hydrophila infection for 3 or 6 days and search for its correlation with the activity of different antioxidative and digestive enzymes to focus their interplay under pathophysiological conditions in carp (Catla catla). Microscopic study of gut in infected fish revealed degenerative changes in the tunica mucosa and lamina propria layers with sloughed off epithelial cells in the lumen. The activity of each digestive enzyme was reduced, but the levels of melatonin, arylalkylamine-N-acetyl transferase protein, the key regulator of melatonin biosynthesis, and different enzymatic antioxidants in gut were gradually and significantly increased with the progress of infection. Gut melatonin concentrations in A. hydrophila challenged carp by showing a positive correlation with the activity of each antioxidative enzyme, and a negative correlation with different digestive enzymes argued in favor of their functional relation, at least, during pathological stress. Moreover, parallel changes in the gut and serum melatonin titers indicated possible contribution of gut to circulating melatonin. Collectively, present carp study provided the first data to suggest that endogenous gut melatonin may be implicated to the mechanism of response to microbial infections in any fish species. PMID:26563281

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

    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.

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

    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 β-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. Melatonin, cardiolipin and mitochondrial bioenergetics in health and disease.

    Paradies, Giuseppe; Petrosillo, Giuseppe; Paradies, Valeria; Reiter, Russel J; Ruggiero, Francesca M

    2010-05-01

    Melatonin is a natural occurring compound with well-known antioxidant properties. Melatonin is ubiquitously distributed and because of its small size and amphiphilic nature, it is able to reach easily all cellular and subcellular compartments. The highest intracellular melatonin concentrations are found in mitochondria, raising the possibility of functional significance for this targeting with involvement in situ in mitochondrial activities. Mitochondria, the powerhouse of the cell, are considered to be the most important cellular organelles to contribute to degenerative processes mainly through respiratory chain dysfunction and formation of reactive oxygen species, leading to damage to mitochondrial proteins, lipids and DNA. Therefore, protecting mitochondria from oxidative damage could be an effective therapeutic strategy against cellular degenerative processes. Many of the beneficial effects of melatonin administration may depend on its effect on mitochondrial physiology. Cardiolipin, a phospholipid located at the level of inner mitochondrial membrane is known to be intimately involved in several mitochondrial bioenergetic processes as well as in mitochondrial-dependent steps of apoptosis. Alterations to cardiolipin structure, content and acyl chain composition have been associated with mitochondrial dysfunction in multiple tissues in several physiopathological situations and aging. Recently, melatonin was reported to protect the mitochondria from oxidative damage by preventing cardiolipin oxidation and this may explain, at least in part, the beneficial effect of this molecule in mitochondrial physiopathology. In this review, we discuss the role of melatonin in preventing mitochondrial dysfunction and disease. PMID:20433638

  8. [MORPHOFUNCTIONAL STATE OF THE THYROID GLAND AFTER EXPOSURE TO MELATONIN].

    Yanko, R V

    2015-01-01

    Morphofunctional state of the thyroid gland (TG) of young rats after exposure of exogenous melatonin in the spring and autumn periods was investigated. Exogenous melatonin (Unipharm Inc., USA) was administered to experimental group of animals daily at a dose 5 mg/kg. The duration of the experiment was 28 days. It was shown an increase of the cross-section area of follicles by 31% and colloid by 30% (in spring), reduction of the area of follicle epithelium by 12% (in autumn), an increase in the follicle internal diameter and a decline in the thyroid epithelium height by 12% (in autumn) in TG of experimental groups rats. Also it was shown a decline of follicle-colloid index and growth of colloid accumulation index, reduction amount of interfollicular islets. The introduction of melatonin in the spring period brought down the amount of connecting tissue elements. Melatonin introduction in the autumn period reduced the thickness of connective tissue trabecules in TG. The introduction of melatonin in the spring period resulted in more substantial changes in the structure of TG, as compared to an autumn experiment. Thus, melatonin administered both in the spring and in the autumn periods reduces the functional activity and physiological regeneration of TG. PMID:26845843

  9. The effect of sleep on nocturnal urine output

    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 methods....../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...... 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...

  10. Late postoperative nocturnal episodic hypoxaemia and associated sleep pattern

    Rosenberg, J; Wildschiødtz, G; Pedersen, M H; von Jessen, F; Kehlet, H

    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 sig...... 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....

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

    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...

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

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

    2014-01-01

    Background: The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. The authors hypothesized that nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea. Objective: To analyze the relationship between obstructive sleep apnea and abnormal heart rhythm during sleep in a population sample. Methods: Cross-sectional study with 1,101 volunteers...

  13. Kiwi Forego Vision in the Guidance of Their Nocturnal Activities

    Martin, Graham R.; Wilson, Kerry-Jayne; Martin Wild, J.; Parsons, Stuart; Fabiana Kubke, M.; Corfield, Jeremy

    2007-01-01

    Background In vision, there is a trade-off between sensitivity and resolution, and any eye which maximises information gain at low light levels needs to be large. This imposes exacting constraints upon vision in nocturnal flying birds. Eyes are essentially heavy, fluid-filled chambers, and in flying birds their increased size is countered by selection for both reduced body mass and the distribution of mass towards the body core. Freed from these mass constraints, it would be predicted that in...

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

    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

  15. Melatonin's effect on inflammatory cytokines in oxidative stress induced PC12 cells

    Yap??lar, Hande; Özda?, ?ule; Ak?n, Demet; Ersöz, Melike

    2013-01-01

    Introduction: Melatonin is primarily synthesized and secreted by the pineal gland. Melatonin participate in many physiological and biochemical functions. The etiology of neurodegenerative diseases has not been well understood.

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

    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.

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

    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.

  18. Sound imaging of nocturnal animal calls in their natural habitat.

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

    2011-09-01

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

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

    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.

  20. [Melatonin and oxidative stress in elderly patients with type 2 diabetes].

    Kupczyk, Daria; Rybka, Joanna; Kedziora-Kornatowska, Kornelia; Kedziora, Józef

    2010-05-01

    Type 2 diabetes is a metabolic disease, which frequency increases substantially with age. Oxidative stress as a result of production and deactivation of free radicals unbalance, may play an important role in a complex pathogenesis of disease. Free radicals are by-products of metabolism, which in regard to their chemical structure, readily react with DNA, lipids, proteins and carbohydrates and cause changes in their structure and function. Antioxidant enzyme system and small molecule antioxidants protect organism against harmful effect of free radicals. In accordance to free radical theory of aging, antioxidant enzymes and molecules activity decrease with age. At the same time, quantity of disadvantageous changes caused by reactive oxygen species (RFT) increase. Disturbance in the prooxidant-antioxidant balance causes organism senescence and development of age-related diseases including diabetes mellitus. Hyperglycemia is an additional factor which can escalate systemic oxidative stress in diabetes mellitus. Elevated concentration of glucose increases generation of reactive oxygen species and accumulation of oxidative modified macromolecules as a result of accelerated activation of a few independent molecular pathways such as autooxidation of monosacharides, non-enzymatic glycosylation, activation of protein kinase C, phospholipase A2 and polyol pathway. Moreover aging is associated with decrease of melatonin concentration, which leads to physiological dysfunctions including depressed antioxidant defense mechanisms. Antioxidant properties of melatonin, which protects macromolecules, especially DNA, from harmful effects of RFT, are particularly important in aspect of free radical theory of aging. PMID:20568408

  1. ARM Support for the Plains Elevated Convection at Night (AS-PECAN) Field Campaign Report

    Turner, D. D. [National Oceanic and Atmospheric Administration (NOAA), Silver Spring, MD (United States); Geerts, B. [Univ. of Wyoming, Laramie, WY (United States)

    2016-04-01

    The Plains Elevated Convection at Night (PECAN) field campaign was a large multi-agency/multi-institutional experiment that targeted nighttime convection events in the central plains of the United States in order to better understand a range of processes that lead to the initiation and upscale growth of deep convection. Both weather and climate models struggle to properly represent the timing and intensity of precipitation in the central United States in their simulations. These models must be able to represent the interactions between the nocturnal stable boundary layer (SBL), the nocturnal low-level jet (LLJ), and a reservoir of convectively available potential energy (CAPE) that frequently exists above the SBL. Furthermore, a large fraction of the nocturnal precipitation is due to the organization of mesoscale convective systems (MCSs). In particular, there were four research foci for the PECAN campaign: •The initiation of elevated nocturnal convection focus seeks to elucidate the mesoscaleenvironmental characteristics and processes that lead to convection initiation (CI) and provide baseline data on the early evolution of mesoscale convective clusters. •The dynamics and internal structure and microphysics of nocturnal MCSs focus will investigatethe transition from surface-based to elevated storm structure, the interaction of cold pools generated by MCSs with the nocturnal stable boundary layer, and how the organization and evolution of elevated convection is influenced by the SBL and the vertical profile of wind and stability above the LLJ. •The bores and wave-like disturbances focus seeks to advance knowledge of the initiation of boredisturbances by convection, how the vertical profile of stability and winds modulate bore structure, the role of these disturbances in the initiation, maintenance, and organization of deep convection, and their impact on the LLJ and SBL. •The LLJ focus seeks to understand the processes that influence the spatial and temporal evolutionof the LLJ, how it affects the SBL, and the interaction between the LLJ and atmospheric boundaries in the development of CI.

  2. Role of melatonin on the regulation of ovarian function: new findings in Danio rerio

    Oliana Carnevali

    2010-01-01

    Melatonin is involved in a number of activities including reproduction acting on hypothalamus , pituitary and gonads . The mechanism by which melatonin acts on the reproductive axis is still unknown although this hormone does not appear to have a direct influence on GnRH neurons. The nature of relationship between pineal melatonin and reproductive physiology remains controversial, in mammals the administration of melatonin may induce or inhibit reproduction depending on the species reproducti...

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

    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...

  4. Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells

    Martínez-Campa, C; González, A.; Mediavilla, M. D.; Alonso-González, C.; Alvarez-García, V; Sánchez-Barceló, E. J.; Cos, S.

    2009-01-01

    Background: Melatonin reduces the development of breast cancer interfering with oestrogen-signalling pathways, and also inhibits aromatase activity and expression. Our objective was to study the promoters through which melatonin modifies aromatase expression, evaluate the ability of melatonin to regulate cyclooxygenases and assess whether the effects of melatonin are related to its effects on intracellular cAMP, in MCF-7 cells. Methods: Total aromatase mRNA, aromatase mRNA promoter regions an...

  5. Scientific Basis for the Potential Use of Melatonin in Bone Diseases: Osteoporosis and Adolescent Idiopathic Scoliosis

    R. J. Reiter; D. X. Tan; Mediavilla, M. D.; E. J. Sánchez-Barceló

    2010-01-01

    The objective of this paper was to analyze the data supporting the possible role of melatonin on bone metabolism and its repercussion in the etiology and treatment of bone pathologies such as the osteoporosis and the adolescent idiopathic scoliosis (AIS). Melatonin may prevent bone degradation and promote bone formation through mechanisms involving both melatonin receptor-mediated and receptor-independent actions. The three principal mechanisms of melatonin effects on bone function could be: ...

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

    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

    2014-01-01

    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-s...

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

    Singh, Prabhat; Gupta, Surbhi; Sharma, Bhupesh

    2015-04-01

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

  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

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

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

    2008-01-01

    melatonin intravenously up to 60 mg in the intraoperative phase was safe and without complications. Melatonin may decrease oxidative damage resulting from surgery, but randomized clinical trials are required before definitive conclusions can be drawn regarding the clinical benefit of melatonin in surgical...

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

    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 diabetes. MATERIALS AND METHODS: In a randomised, double-blind, two-way cross-over study, 24 normoalbuminuric...... patients with type 1 diabetes with CAN will be treated for 12 weeks with either morning or bedtime dosing of 20 mg enalapril, followed by 12 weeks of switched treatment regimen. During each treatment period, two 24 h ambulatory blood pressure measurements will be performed and after each treatment period...

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

    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

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

    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.

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

    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.

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

    Lewczuk, Bogdan; Ziółkowska, 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

  15. Alternative Radioligands for Investigating the Molecular Pharmacology of Melatonin Receptors.

    Legros, Céline; Brasseur, Chantal; Delagrange, Philippe; Ducrot, Pierre; Nosjean, Olivier; Boutin, Jean A

    2016-03-01

    Melatonin exerts a variety of physiologic activities that are mainly relayed through the melatonin receptors MT1 and MT2 Low expressions of these receptors in tissues have led to widespread experimental use of the agonist 2-[(125)I]-iodomelatonin as a substitute for melatonin. We describe three iodinated ligands: 2-(2-[(2-iodo-4,5-dimethoxyphenyl)methyl]-4,5-dimethoxy phenyl) (DIV880) and (2-iodo-N-2-[5-methoxy-2-(naphthalen-1-yl)-1H-pyrrolo[3,2-b]pyridine-3-yl])acetamide (S70254), which are specific ligands at MT2 receptors, and N-[2-(5-methoxy-1H-indol-3-yl)ethyl]iodoacetamide (SD6), an analog of 2-[(125)I]-iodomelatonin with slightly different characteristics. Here, we further characterized these new ligands with regards to their molecular pharmacology. We performed binding experiments, saturation assays, association/dissociation rate measurements, and autoradiography using sheep and rat tissues and recombinant cell lines. Our results showed that [(125)I]-S70254 is receptor, and can be used with both cells and tissue. This radioligand can be used in autoradiography. Similarly, DIV880, a partial agonist [43% of melatonin on guanosine 5'-3-O-(thio)triphosphate binding assay], selective for MT2, can be used as a tool to selectively describe the pharmacology of this receptor in tissue samples. The molecular pharmacology of both human melatonin receptors MT1 and MT2, using a series of 24 ligands at these receptors and the new radioligands, did not lead to noticeable variations in the profiles. For the first time, we described radiolabeled tools that are specific for one of the melatonin receptors (MT2). These tools are amenable to binding experiments and to autoradiography using sheep or rat tissues. These specific tools will permit better understanding of the role and implication in physiopathologic processes of the melatonin receptors. PMID:26759496

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

    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 ...

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

    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 (λmax ≈ 480 nm light once every minute for 1 hour, (2 131 W/m2 of green (λmax ≈ 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

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

    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...

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

    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...

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

    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...

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

    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 of NO emissions. Our project shows that the urban canopy should be included in future air quality models to better represent nocturnal chemistry. This project has considerably advanced our understanding of the chemistry of the urban nocturnal boundary layer. The results of this project have implications for air quality studies in the urban nocturnal boundary layer. The study has also identified new questions on nocturnal processes, which we will continue to address through other projects.

  2. Prolonged-release melatonin for children with neurodevelopmental disorders.

    De Leersnyder, Hélène; Zisapel, Nava; Laudon, Moshe

    2011-07-01

    Previous studies demonstrated the efficacy and safety of prolonged-release melatonin in children and adolescents with neurodevelopmental and behavioral disorders. The long-term effectiveness and safety of prolonged-release melatonin treatment were assessed in 88 children (42 girls and 46 boys) with neurodevelopmental disorders. These patients participated in a compassionate-use program with the drug Circadin (2 mg; Neurim Pharmaceuticals, Tel Aviv, Israel) in France, and received treatment in the context of regular care by a specialized physician. The study involved a structured questionnaire for the parents, comprising a combination of multiple-choice and numeric questions addressing sleep onset/offset, sleep quality problems, and mood. The dose of melatonin ranged from 4-6 mg, and treatment duration ranged from 6-72 months. Within 3 months, sleep latency with prolonged-release melatonin decreased by 44.0% (P < 0.001), sleep duration increased by 10.1% (P < 0.001), the number of awakenings decreased by 75% (P < 0.001), and sleep quality improved by 75%, compared with baseline (P < 0.001). No serious adverse events or treatment-related comorbidities were reported. Prolonged-release melatonin remains a safe, effective therapy for the long-term treatment of sleep disorders in children with neurodevelopmental disorders. PMID:21723455

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

    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.

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

    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 μg/kg, Group C: injected with melatonin 10 μg, Group D: injected with nicotine 40 μg/kg and melatonin 10 μg. 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

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

    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.

  6. Melatonin prevents hyperglycemia in a model of sleep apnea

    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

  7. Is Melatonin Protective in Contrast Material Related Renal Failure?

    Ozum Tuncyurek

    2014-03-01

    Full Text Available Aim: The aim of the study was to investigate the effect of melatonin on the renal injury resulting from radiocontrast media and myoglobinuria in male Wistar albino rats. Material and Method: 50% glycerol at equal amounts was intramuscularly administered to both hind legs of all animals under ether anesthesia at the dose of 10 mg/kg. Three hours later, the groups were administered the following: Group I (number:7: Iopromide(Ultravist -300® at the dose of 2 ml/kg (intracardiac; Group II (number:7: Iopromide(Ultravist -300® and intraperitoneally administered Melatonin at the dose of 10 mg/kg (Melatonin was dissolved in 7.5% absolute ethanol and further dilutions were made in saline.; and Group III (number:7: 2 ml/kg of sterile physiologic saline (Control group. The levels of Uurea, Ccreatinine and Ccystatin C were studied on the blood samples collected. The renal samples were evaluated by 2two distinct pathologists who did not know the protocol. Results: There was no difference in the values of Creatinine and cystatin c between Groups 2 and 3 (p=0.9; 0.2. Discussion: In conclusion, we evaluated the possible prevention of contrast-induced oxidative stress in the kidney with using melatonin. However, additional clinical studies are needed to evaluate the role of preventive melatonin treatment in humans.

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

    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.

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

    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.

  10. Melatonin: Current Status and Future Perspectives in Plant Science

    Nawaz, Muhammad A.; Huang, Yuan; Bie, Zhilong; Ahmed, Waqar; Reiter, Russel J.; Niu, Mengliang; Hameed, Saba

    2016-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is a ubiquitous molecule with pleiotropic actions in different organisms. It performs many important functions in human, animals, and plants; these range from regulating circadian rhythms in animals to controlling senescence in plants. In this review, we summarize the available information regarding the presence of melatonin in different plant species, along with highlighting its biosynthesis and mechanisms of action. We also collected the available information on the effects of melatonin application on commercially important crops to improve their growth and development. Additionally, we have identified many new aspects where melatonin may have possible roles in plants, for example, its function in improving the storage life and quality of fruits and vegetables, its role in vascular reconnection during the grafting process and nutrient uptake from roots by modifying root architecture. Another potentially important aspect is the production of melatonin-rich food crops (cereals, fruits, and vegetables) through combination of conventional and modern breeding approaches, to increase plant resistance against biotic and abiotic stress, leading to improved crop yields, and the nutraceutical value of produce to solve food security issues. PMID:26793210

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

    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)

  12. [Effective melatonin therapy in a case of Machado-Joseph disease with insomnia].

    Takei, A; Okawa, M; Sasaki, H; Hamada, T; Tashiro, K

    2000-07-01

    The effects of melatonin (MLT) therapy on insomnia and serum MLT concentration were studied in a 44-year-old man with Machado-Joseph disease. He suffered from insomia since age 41, and could not sleep well, despite that he was given many kinds of hypnotics. He showed neither noctural central apnea, inspirative stridor, restless leg syndrome, REM without atonia, nor noctural polyuria, all of which are known to cause insomnia in spinocerebellar degeneration. The peak serum level of MLT was low, 9.2 pg/ml. He was administered 9 mg of MLT p.o. at 8 p.m., and it's peak noctural level elevated to 7,000 pg/ml, and this alleviated his intractable insomnia. Our experience indicate that the MLT could be effective for insomnia in MJD which relates to low MLT concentration. PMID:11186915

  13. Melatonin mitigates cadmium phytotoxicity through modulation of phytochelatins biosynthesis, vacuolar sequestration, and antioxidant potential in Solanum lycopersicum L

    Hasan, Md Kamrul; Ahammed, Golam Jalal; Yin, Lingling; Shi, Kai; Xia, Xiaojian; ZHOU, YANHONG; Yu, Jingquan; Zhou, Jie

    2015-01-01

    Melatonin is a ubiquitous signal molecule, playing crucial roles in plant growth and stress tolerance. Recently, toxic metal cadmium (Cd) has been reported to regulate melatonin content in rice; however, the function of melatonin under Cd stress, particularly in higher plants, still remains elusive. Here, we show that optimal dose of melatonin could effectively ameliorate Cd-induced phytotoxicity in tomato. The contents of Cd and melatonin were gradually increased over time under Cd stress. H...

  14. DNA protective effects of melatonin on oxidative stress in streptozotocin - induced diabetic rats.

    Selim Sekkin

    2015-05-01

    Full Text Available Diabetes mellitus is a chronic disease characterized by elevated blood sugar levels resulting from either a lack of insulin production or resistance to insulin. As the prevalence of diabetes has risen to epidemic proportions worldwide, complications of diabetes have now become one of the most challenging health problems. Radicals derived from oxygen (ROS and nitrogen (RNS are the largest class of radical species generated in living systems. ROS and RNS are products of normal cell metabolism and have either beneficial or deleterious effects, depending on the concentration reached in the tissues (1. In diabetic patients, oxidative stress induced by the presence of excessive ROS and RNS is closely associated with chronic inflammation leading to potential tissue damage. The role of oxidative stress in the development of diabetic endothelial dysfunction is underlined by a number of studies. The development of inhibitors against the main sources of ROS generation could be an alternative approach to conventional antioxidant therapies. One of the main challenges of research in recent years has been finding ways to attenuate oxidative stress in order to improve diabetes. Therefore, it seems reasonable that antioxidants can play an important role in the improvement of diabetes. There are many reports on effects of antioxidants in the management of diabetes. Melatonin (MEL (N-acetyl-5-methoxytryptamine is a compound synthesized by the pineal gland in the human brain. MEL is also produced in the retina, thymus, bone marrow, respiratory epithelium, skin, lens, intestine and in other sites. MEL has been characterized as an effective synchronizing agent in several physiological and pathological conditions. MEL is a major scavenger of both ROS and RNS reactive molecules. MEL provokes this effect at both physiological and pharmacological concentrations. Several of its metabolites can also detoxify free radicals and derivatives. With regards to the enzymes of the antioxidant system, MEL regulates the expression of several genes such as those of superoxide dismutase (SOD and glutathione peroxidase (2-4. The aim of this study was to research the effects of MEL on oxidative stress and DNA protective effects in streptozotocin-induced diabetic rats. A total of 32 rats were equally divided into 4 experimental groups as Control, Melatonin, Diabetic, and Diabetic + Melatonin. A pancreatic beta-cell cytotoxic agent, single dose streptozotocin (60 mg/kg was given by intraperitoneal route to induce experimental diabetes in rats. Rats with ≥200mg/dL blood glucose level were established as Diabetic and Diabetic + Melatonin groups. MEL (10 mg/kg per day and sodium citrate solution were administrated to rats by intraperitoneal route for 6 weeks. With the termination of the experiment, tissue and blood samples were obtained for further analysis. SOD, catalase (CAT, reduced glutathione (GSH and malondialdehyde (MDA were evaluated in rat liver, renal, brain and pancreas tissues. Body weight, plasma glucose, and %HbA1c levels were studied. DNA damage was analyzed with the comet assay in rat lymphocytes; %Tail DNA and Mean Tail Moment parameters were evaluated (5. Antioxidant and oxidant enzyme levels were similar in the Control and Melatonin groups, although there were significant differences between the Diabetic and Diabetic + Melatonin groups. SOD levels in brain and liver tissues were higher (P<0,001, and CAT activities in renal tissue (P<0,001, GSH levels in pancreas tissue (P<0,01 as well as MDA levels in liver (P<0,001, renal (P<0,001 and brain (P<0,01 tissues were higher in the Diabetic + Melatonin group compared with the Diabetic group. Body weight changes and blood glucose levels of the rats were evaluated during the 6 weeks. The effect of MEL on the body weights of Control and Melatonin as well as Diabetic and Diabetic + Melatonin group rats were similar. MEL had no effect on body weight and the diabetic rats were lighter (P<0,001. Also, MEL did not affect blood glucose level and the diabetic rats glucose levels were higher (P<0,001. Blood %HbA1c level was also higher in the diabetic rats (P<0,001 and MEL had no effect on %HbA1c levels. DNA damage was higher in Diabetic group rats (P<0,001, although %Tail DNA and Mean Tail Moment parameters were better in the MEL administered groups than the Diabetic group rats (P<0,001. These results indicate that administration of 10 mg/kg intraperitoneal MEL for 6 weeks may cause amelioration in oxidative stress parameters associated with diabetes, with beneficial effects seen on %Tail DNA and Mean Tail Moment parameters in rat lymphocytes.

  15. Protective effects of melatonin on lipopolysaccharide-induced mastitis in mice.

    Shao, Guoxi; Tian, Yinggang; Wang, Haiyu; Liu, Fangning; Xie, Guanghong

    2015-12-01

    Melatonin, a secretory product of the pineal gland, has been reported to have antioxidant and anti-inflammatory effects. However, the protective effects of melatonin on lipopolysaccharide (LPS)-induced mastitis have not been reported. The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of melatonin on LPS-induced mastitis both in vivo and in vitro. In vivo, our results showed that melatonin attenuated LPS-induced mammary histopathologic changes and myeloperoxidase (MPO) activity. Melatonin also inhibited LPS-induced inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) production in mammary tissues. In vitro, melatonin was found to inhibit LPS-induced TNF-α and IL-6 production in mouse mammary epithelial cells. Melatonin also suppressed LPS-induced Toll-like receptor 4 (TLR4) expression and nuclear factor-kappaB (NF-κB) activation in a dose-dependent manner. In addition, melatonin was found to up-regulate the expression of PPAR-γ. Inhibition of PPAR-γ by GW9662 reduced the anti-inflammatory effects of melatonin. In conclusion, we found that melatonin, for the first time, had protective effects on LPS-induced mastitis in mice. The anti-inflammatory mechanism of melatonin was through activating PPAR-γ which subsequently inhibited LPS-induced inflammatory responses. PMID:26590117

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

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

    2008-06-23

    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 many questions about the ecological variables that shape the activity patterns in golden hamsters and the differences between laboratory and field results. PMID:18397863

  17. Nocturnal leg cramps. Clinically mysterious and painful--but manageable.

    Kanaan, N; Sawaya, R

    2001-06-01

    Nocturnal leg cramps are common occurrences among older, generally healthy adults. Although there are many known causes--endocrinologic, neurologic, and vascular disorders, treatment with certain drugs, and occupational factors--a significant portion of cases are idiopathic. History, physical exam, and laboratory testing can provide clues for distinguishing between cramps with identifiable causes and idiopathic cases. For nonidiopathic cases, management consists of treating the underlying cause whenever possible. A nonpharmacologic approach (massaging and stretching) is the recommended first-line treatment for idiopathic cases. Quinine sulfate also appears to offer safe and effective symptom management of idiopathic cases, although its efficacy has not been definitively established in clinical trials. PMID:11417373

  18. The Nocturnal Avian Migration Experiment Final Campaign Report

    Stepanian, P. M. [Univ. of Oklahoma, Norman, OK (United States); Horton, K. G. [Univ. of Oklahoma, Norman, OK (United States)

    2016-03-01

    Remote sensing techniques are playing a greater role in ornithology, and radar has proven a valuable tool for high resolution, long-term observations of airborne animals. The major disadvantage in radar remote sensing is the current inability to gain taxonomic information from these measurements. One solution is the incorporation of collocated acoustic monitoring that can provide recordings of species-specific nocturnal flight calls of migrating birds in flight. In addition, by taking multichannel recordings of these calls, the position of the calling bird can be calculated and linked to collocated radar measurements.

  19. Determination of melatonin in Acyrthosiphon pisum aphids by liquid chromatography-tandem mass spectrometry.

    Escrivá, Laura; Manyes, Lara; Barberà, Miquel; Martínez-Torres, David; Meca, Guiseppe

    2016-03-01

    Melatonin is a hormone mainly involved in the regulation of circadian and seasonal rhythms in both invertebrates and vertebrates. Despite the identification of melatonin in many insects, its involvement in the insect seasonal response remains unclear. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed for melatonin analysis in aphids (Acyrthosiphon pisum) for the first time. After comparing two different procedures and five extraction solvents, a sample preparation procedure with a mixture of methanol/water (50:50) was selected for melatonin extraction. The method was validated by analyzing melatonin recovery at three spiked concentrations (5, 50 and 100pg/mg) and showed satisfactory recoveries (75-110%), and good repeatability, expressed as relative standard deviation (aphid samples demonstrating its usefulness for melatonin determination in insects. This is -to our knowledge- the first identification of melatonin in aphids by LC-MS/MS. PMID:26778054

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

    Yılmaz, Cemile; Kocadağlı, Tolgahan; Gökmen, Vural

    2014-04-01

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

  1. A physiologically based mathematical model of melatonin including ocular light suppression and interactions with the circadian pacemaker. : A physiologically-based mathematical model of melatonin

    St Hilaire, Melissa,; Gronfier, Claude; Zeitzer, Jamie,; Klerman, Elizabeth,

    2007-01-01

    The rhythm of plasma melatonin concentration is currently the most accurate marker of the endogenous human circadian pacemaker. A number of methods exist to estimate circadian phase and amplitude from the observed melatonin rhythm. However, almost all these methods are limited because they depend on the shape and amplitude of the melatonin pulse, which vary among individuals and can be affected by environmental influences, especially light. Furthermore, these methods are not based on the unde...

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

    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.

  3. Molecular aspects of melatonin (MLT)-mediated therapeutic effects.

    Tuli, Hardeep Singh; Kashyap, Dharambir; Sharma, Anil K; Sandhu, Sardul Singh

    2015-08-15

    Hormones are a class of molecules, which mediate their effects by regulating a variety of signalling pathways. Melatonin (N-acetyl-5-methoxytryptamine), a pineal gland hormone, is one among the categories of compounds having various therapeutic and pharmacological effects. Melatonin has many intracellular as well as extracellular targets including apoptosis, metastasis, angiogenesis and inflammatory pathways. Gene-profile studies have further established its antagonist effect on the various genes involved in the tumour progression, neurodegeneration and ageing. It has also been known to reduce the toxicity induced by chemotherapeutic agents in advanced stages of tumour. The present review extensively describes the molecular interactions of melatonin with various recognized cellular targets, which may lead the scientific community to propose novel therapeutic strategies. PMID:26135621

  4. Melatonin for pre- and postoperative anxiety in adults

    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...... effect of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of 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...

  5. Hormone melatonin influence on cell to cell information transfer

    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)

  6. The role of melatonin in anaesthesia and critical care

    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.

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

    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.

  8. Conformational complexity of melatonin in water and methanol.

    Shillady, Donald D; Castevens, Charles M; Trindle, Carl; Sulik, Jeffrey; Klonowski, Paula

    2003-09-01

    The magnetic circular dichroism (MCD) spectra of melatonin in water and methanol solutions is compared to the MCD spectra of indole and five melatonin conformations observed in low temperature jet spectroscopy. Based on a survey of indole compounds using Slater type orbitals-6G(d,p) and B3LYP/6-31G(d) energies, and CNDO/S-D calculations of MCD spectral bands, a dominant structure with a water molecule bridging the amide-keto oxygen and indole Nz-H atoms is proposed as the best fit for the MCD of aqueous melatonin. In methanol an additional band appears at 310 nm which is supported only by solvated structures in which the alkyl-amide arm is extended away from the indole moiety. PMID:14499912

  9. A circadian rhythm sleep disorder: melatonin resets the biological clock.

    Abbas, A; Raju, J; Milles, J; Ramachandran, S

    2010-12-01

    Circadian rhythm sleep disorders are poorly understood and often misdiagnosed. They are all related to the timing of sleep within the 24-hour day. This paper describes a patient with a long history of sleep disturbance whom we diagnosed as having delayed sleep phase syndrome by history and measurement of urinary melatonin metabolite excretion. Literature on the characteristics, diagnosis and management of this syndrome are briefly reviewed. In addition, the relation of the neurohormone melatonin to circadian rhythm and its other physiological roles are described. PMID:21132137

  10. Modelling chemistry in the nocturnal boundary layer above tropical rainforest and a generalised effective nocturnal ozone deposition velocity for sub-ppbv NOx conditions

    Pugh, Thomas A. M.; Ryder, James; MacKenzie, A. Robert; Moller, Sarah J.; Lee, James D.; Helfter, Carol; Nemitz, Eiko; Lowe, Douglas; Hewitt, C. Nicholas

    2010-01-01

    Measurements of atmospheric composition have been made over a remote rainforest landscape. A box model has previously been demonstrated to model the observed daytime chemistry well. However the box model is unable to explain the nocturnal measurements of relatively high [NO] and [O3], but relatively low observed [NO2]. It is shown that a one-dimensional (1-D) column model with simple O3 -NOx chemistry and a simple representation of vertical transport is able to explain the observed nocturnal ...

  11. Effects of artificial illumination on the nocturnal foraging of waders

    Santos, Carlos D.; Miranda, Ana C.; Granadeiro, José P.; Lourenço, Pedro M.; Saraiva, Sara; Palmeirim, Jorge M.

    2010-03-01

    Large areas of natural and semi-natural habitats are exposed to artificial illumination from adjacent urban areas and roads. Estuarine and coastal wetlands are particularly exposed to such illumination because shorelines often are heavily utilized by man. However, the impact of artificial illumination on the waders that forage in these highly productive habitats is virtually unknown. We evaluated the effects of artificial illumination on the nocturnal habitat selection and foraging behaviour of six wader species with different feeding strategies: three visual foragers, two species that alternate visual and tactile strategies (mixed foragers), and one tactile forager. We quantified the number of birds and their foraging behaviour at sites affected and not affected by streetlights, and also before and after illuminating experimental sites. Areas illuminated by streetlights were used more during the night by visual foragers, and to a lesser extent by mixed foragers, than non-illuminated areas. Visual foragers increased their foraging effort in illuminated areas, and mixed foragers changed to more efficient visual foraging strategies. These behavioural shifts improved prey intake rate by an average of 83% in visual and mixed foragers. We have showed that artificial illumination has a positive effect on the nocturnal foraging of waders, but on the other hand may draw them to degraded areas close to urban centres, and potentially raises their exposure to predators. Our findings suggest that artificial illumination is worth investigation as a tool in the management of intertidal habitats for waders.

  12. Nocturnal enuresis and nocturia, differences and similarities - lessons to learn?

    Goessaert, A-S; Everaert, K; Hoebeke, P; Kapila, A; Walle, J Vande

    2015-04-01

    This review highlights the current views on and differences and similarities between nocturnal enuresis (NE) in children and nocturia in adults, which might be a guidance to elucidate the missing links in our knowledge. In both conditions, a genetic factor is suspected. Reduced bladder capacity and nocturnal polyuria are the main underlying lower urinary tract-related conditions. There is a link with sleep disorders, although it is not clear whether this is a cause or consequence. Physical and mental health are comprised in both conditions, however, in different ways. In NE, constipation and attention deficit disorder are the most important comorbidities and the effect on mental health and quality of life is mainly through the negative impact on self-esteem. In nocturia, cardiovascular disease and fall injuries are important comorbidities, mainly affecting the older nocturia population; personal distress and depression are consequences of the related poor sleep quality. For both conditions, treatment is often inadequate and a more individualized approach seems to be necessary. The main difference between NE and nocturia seems to be the difference in arousal to bladder stimuli, suggesting that sleep characteristics might be a key factor in these conditions. PMID:25379877

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

    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.

  14. Using Nocturnal Flight Calls to Assess the Fall Migration of Warblers and Sparrows along a Coastal Ecological Barrier

    Smith, Adam D.; Paton, Peter W. C.; McWilliams, Scott R

    2014-01-01

    Atmospheric conditions fundamentally influence the timing, intensity, energetics, and geography of avian migration. While radar is typically used to infer the influence of weather on the magnitude and spatiotemporal patterns of nocturnal bird migration, monitoring the flight calls produced by many bird species during nocturnal migration represents an alternative methodology and provides information regarding the species composition of nocturnal migration. We used nocturnal flight call (NFC) r...

  15. Urinary calcium excretion in healthy children and children with primary monosymptomatic nocturnal enuresis

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

    2006-01-01

    PURPOSE: We investigated the role of urinary Ca excretion in monosymptomatic nocturnal enuresis, and defined normality and intra-individual variability in Ca excretion in healthy children. MATERIALS AND METHODS: We included 46 Danish children with desmopressin resistant nocturnal enuresis and 96...... healthy controls. We performed fractional urine collections at home during 2 days in controls or during hospitalization in children with enuresis. Urine volume, osmolality, and Ca and creatinine measurements were performed and Ca-to-creatinine ratios were calculated and compared between groups. Based on...... nocturnal urine output children with enuresis were characterized as having polyuria (nocturnal urine volume greater than 130% of expected bladder capacity) or not having polyuria. RESULTS: We did not find any differences in controls compared with children with enuresis who did not and did have nocturnal...

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

    Chun-Qiu Chen

    2011-01-01

    Full Text Available Melatonin is a hormone with endocrine, paracrine and autocrine actions. It is involved in the regulation of multiple functions, including the control of the gastrointestinal (GI system under physiological and pathophysiological conditions. Since the gut contains at least 400 times more melatonin than the pineal gland, a review of the functional importance of melatonin in the gut seems useful, especially in the context of recent clinical trials. Melatonin exerts its physiological effects through specific membrane receptors, named melatonin-1 receptor (MT1, MT2 and MT3. These receptors can be found in the gut and their involvement in the regulation of GI motility, inflammation and pain has been reported in numerous basic and clinical studies. Stable levels of melatonin in the lower gut that are unchanged following a pinealectomy suggest local synthesis and, furthermore, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut.

  17. A physiologically based pharmacokinetics model for melatonin--effects of light and routes of administration.

    Peng, Henry T; Bouak, Fethi; Vartanian, Oshin; Cheung, Bob

    2013-12-15

    Physiologically based pharmacokinetic (PBPK) models were developed using MATLAB Simulink(®) to predict diurnal variations of endogenous melatonin with light as well as pharmacokinetics of exogenous melatonin via different routes of administration. The model was structured using whole body, including pineal and saliva compartments, and parameterized based on the literature values for endogenous melatonin. It was then optimized by including various intensities of light and various dosage and formulation of melatonin. The model predictions generally have a good fit with available experimental data as evaluated by mean squared errors and ratios between model-predicted and observed values considering large variations in melatonin secretion and pharmacokinetics as reported in the literature. It also demonstrates the capability and usefulness in simulating plasma and salivary concentrations of melatonin under different light conditions and the interaction of endogenous melatonin with the pharmacokinetics of exogenous melatonin. Given the mechanistic approach and programming flexibility of MATLAB Simulink(®), the PBPK model could provide predictions of endogenous melatonin rhythms and pharmacokinetic changes in response to environmental (light) and experimental (dosage and route of administration) conditions. Furthermore, the model may be used to optimize the combined treatment using light exposure and exogenous melatonin for maximal phase advances or delays. PMID:24120727

  18. Melatonin directly interacts with cholesterol and alleviates cholesterol effects in dipalmitoylphosphatidylcholine monolayers.

    Choi, Youngjik; Attwood, Simon J; Hoopes, Matthew I; Drolle, Elizabeth; Karttunen, Mikko; Leonenko, Zoya

    2014-01-01

    Melatonin is a pineal 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. Cholesterol is a major membrane constituent with both a structural and functional influence. It is also known that melatonin readily partitions into cellular membranes. We investigated the effects of melatonin and cholesterol on the structure and physical properties of a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayer as a simple membrane model using the Langmuir-Blodgett (L-B) monolayer technique and molecular dynamics (MD) simulations. We report that melatonin increases the area per lipid and elastic compressibility of the DPPC monolayer in a concentration dependent manner, while cholesterol has the opposite effect. When both melatonin and cholesterol were present in the monolayer, the compression isotherms showed normalization of the area per molecule towards that of the pure DPPC monolayer, thus indicating that melatonin counteracts and alleviates cholesterol's effects. Atomistic MD simulations of melatonin enriched DPPC systems correlate with our experimental findings and illustrate the structural effects of both cholesterol and melatonin. Our results suggest that melatonin is able to lessen the influence of cholesterol through two different mechanisms. Firstly, we have shown that melatonin has a fluidizing effect on monolayers comprising only lipid molecules. Secondly, we also observe that melatonin interacts directly with cholesterol. Our findings suggest a direct nonspecific interaction of melatonin may be a mechanism involved in reducing cholesterol associated membrane effects, thus suggesting the existence of a new mechanism of melatonin's action. This may have important biological relevance in addition to the well-known anti-oxidative and receptor binding effects. PMID:24651707

  19. Effects of melatonin and its analogues on neural stem cells.

    Chu, Jiaqi; Tu, Yalin; Chen, Jingkao; Tan, Dunxian; Liu, Xingguo; Pi, Rongbiao

    2016-01-15

    Neural stem cells (NSCs) are multipotent cells which are capable of self-replication and differentiation into neurons, astrocytes or oligodendrocytes in the central nervous system (CNS). NSCs are found in two main regions in the adult brain: the subgranular zone (SGZ) in the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ). The recent discovery of NSCs in the adult mammalian brain has fostered a plethora of translational and preclinical studies to investigate novel approaches for the therapy of neurodegenerative diseases. Melatonin is the major secretory product synthesized and secreted by the pineal gland and shows both a wide distribution within phylogenetically distant organisms from bacteria to humans and a great functional versatility. Recently, accumulated experimental evidence showed that melatonin plays an important role in NSCs, including its proliferation, differentiation and survival, which are modulated by many factors including MAPK/ERK signaling pathway, histone acetylation, neurotrophic factors, transcription factors, and apoptotic genes. The purpose of this review is to summarize the beneficial effects of melatonin on NSCs and further to discuss the potential usage of melatonin and its derivatives or analogues in the treatment of CNS neurodegenerative diseases. PMID:26499395

  20. Melatonin in Chagas´ disease: Possible therapeutic value

    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.

  1. Circadian rhythm in salivary melatonin in narcoleptic patiens

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

    2008-01-01

    Roč. 437, č. 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

  2. Melatonin ameliorates radiation induced mutilation of learning in mice

    Brain is highly susceptible to oxidative damage due to its high utilization of oxygen and rather poorly developed anti oxidative defense mechanism. Present study is aimed at investigating the protective effect of melatonin against radiation-induced impairment in the learning ability of mice

  3. Production and purification of polyclonal antibody against melatonin hormone

    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.

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

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

    2010-01-01

    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...

  5. Melatonin protects against ischemic heart failure in rats.

    ?ehirli, Ahmet Özer; Koyun, Derya; Tetik, ?ermin; Özsavc?, Derya; Yi?iner, Ömer; Çetinel, ?ule; Tok, Olgu Enis; Kaya, Zehra; Akkiprik, Mustafa; K?l?ç, Ertugrul; ?ener, Göksel

    2013-09-01

    Ischemic injury, which occurs as a result of sympathetic hyperactivity, plays an important role in heart failure. Melatonin is thought to have antiatherogenic, antioxidant, and vasodilatory effects. In this study, we investigated whether melatonin protects against ischemic heart failure (HF). In Wistar albino rats, HF was induced by left anterior descending (LAD) coronary artery ligation and rats were treated with either vehicle or melatonin (10 mg/kg) for 4 weeks. At the end of this period, echocardiographic measurements were recorded and the rats were decapitated to obtain plasma and cardiac tissue samples. Lactate dehydrogenase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lysosomal enzymes (?-D-glucuronidase, ?-galactosidase, ?-D-N-acetyl-glucosaminidase, acid phosphatase, and cathepsin-D) were studied in plasma samples, while malondialdehyde and glutathione levels and Na+, K+-ATPase, caspase-3 and myeloperoxidase activities were determined in the cardiac samples. Sarco/endoplasmic reticulum calcium ATPase (SERCA) and caveolin-3 levels in cardiac tissues were evaluated using Western blot analyses. Furthermore, caveolin-3 levels were also determined by histological analyses. In the vehicle-treated HF group, cardiotoxicity resulted in decreased cardiac Na+, K+-ATPase and SERCA activities, GSH contents and caveolin-3 levels, while plasma LDH, CK, and lysosomal enzyme activities and cardiac MDA and Myeloperoxidase (MPO) activities were found to be increased. On the other hand, melatonin treatment reversed all the functional and biochemical changes. The present results demonstrate that Mel ameliorates ischemic heart failure in rats. These observations highlight that melatonin is a promising supplement for improving defense mechanisms in the heart against oxidative stress caused by heart failure. PMID:23551402

  6. Anxiolytic effects of the melatonin MT(2) receptor partial agonist UCM765: comparison with melatonin and diazepam.

    Ochoa-Sanchez, Rafael; Rainer, Quentin; Comai, Stefano; Spadoni, Gilberto; Bedini, Annalida; Rivara, Silvia; Fraschini, Franco; Mor, Marco; Tarzia, Giorgio; Gobbi, Gabriella

    2012-12-01

    Melatonin (MLT) is a neurohormone known to be involved in the regulation of anxiety. Most of the physiological actions of MLT in the brain are mediated by two high-affinity G-protein-coupled receptors, denoted MT(1) and MT(2). However, the particular role of these receptors in anxiety remains to be defined. Here we used a novel MT(2)-selective partial agonist, UCM765 to evaluate the involvement of MT(2) receptors in anxiety. Adult male rats were acutely injected with UCM765 (5-10-20mg/kg), MLT (20mg/kg) or diazepam (DZ, 1mg/kg). Anxiety-related behaviors were assessed in the elevated plus maze test (EPMT), novelty suppressed feeding test (NSFT) and open field test (OFT). UCM765 at the dose of 10mg/kg showed anxiolytic-like properties by increasing the time spent in the open arm of the EPMT, and by reducing the latency to eat in a novel environment in the NSFT. In the EPMT, animals treated with UCM765 (10mg/kg) or MLT (20mg/kg) spent more time in the open arms compared to vehicle-treated animals, but to a lesser extent compared to DZ (1mg/kg). In the NSFT, all treatments similarly decreased the latency to eat in a novel environment compared to vehicle. UCM765 and MLT did not affect the total time and the number of entries into the central area of the OFT, but unlike DZ, did not impair locomotion. The anxiolytic effects of UCM765 and MLT in the EPMT and the NSFT were blocked using a pre-treatment with the MT(1)/MT(2) antagonist luzindole (10mg/kg) or the MT(2) antagonist 4P-PDOT (10mg/kg). These results demonstrated, for the first time, the anxiolytic properties of UCM765 and suggest that MT(2)-receptors may be considered a novel target for the development of anxiolytic drugs. PMID:22789661

  7. Paroxysmal nocturnal hemoglobinuria: a case report of MR, CT findings

    Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease involving multiple hematopoietic cell lines. Characteristics of PNH are intrinsic hemolytic anemia, iron deficiency anemia and venous thrombosis. We report a case of PNH with characterostoc MR and CT findings. The signal intensity of renal cortex was lower than that of medulla on both T1-and T2-weighted MR imaging. On T2 weighted MR images, the liver showed very low signal intensity but the signal intensity of the spleen was normal. On precontrast CT the attenuation of renal cortex was higher than that of renal medulla and the attenuation of liver was higher than that of the spleen. These findings of MR imaging and CT were the result from the deposition of hemosiderin in the cells of proximal convoluted tubules and transfusional hemosiderosis of liver

  8. Paroxysmal nocturnal hemoglobinuria: a case report of MR, CT findings

    Yang, Ik; Chung, Soo Young; Park, Hai Jung; Lee Yul; Chun, Rho Won; Noh, Jung Woo [College of Medicine, Hallym University, Seoul (Korea, Republic of)

    1995-10-15

    Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease involving multiple hematopoietic cell lines. Characteristics of PNH are intrinsic hemolytic anemia, iron deficiency anemia and venous thrombosis. We report a case of PNH with characterostoc MR and CT findings. The signal intensity of renal cortex was lower than that of medulla on both T1-and T2-weighted MR imaging. On T2 weighted MR images, the liver showed very low signal intensity but the signal intensity of the spleen was normal. On precontrast CT the attenuation of renal cortex was higher than that of renal medulla and the attenuation of liver was higher than that of the spleen. These findings of MR imaging and CT were the result from the deposition of hemosiderin in the cells of proximal convoluted tubules and transfusional hemosiderosis of liver.

  9. Nocturnal stomatal conductance and ambient air quality standards for ozone

    Musselman, Robert C.; Minnick, Tamera J.

    Vegetation response to ozone depends on ozone conductance into leaves and the defensive action inside the leaf. Ozone parameters currently used for air quality standards do not incorporate conductance or defensive components. Nighttime flux has often been ignored in ozone metrics relating to plant response, since ozone concentration and conductance are considered to be minimal at night. However, ozone concentration can remain relatively high at night, particularly in mountainous areas. Although conductance is lower at night than during the day for most plants, nocturnal conductance can result in considerable ozone flux into plants. Further, plants can be more susceptible to ozone exposure at night than during the daytime, a result of lower plant defenses at night. Any ozone metric used to relate air quality to plant response should use a 24 h ozone exposure period to include the nighttime exposures. It should also incorporate plant defensive mechanisms or their surrogate.

  10. Autism in siblings with autosomal dominant nocturnal frontal lobe epilepsy.

    Miyajima, Tomoko; Kumada, Tomohiro; Saito, Keiko; Fujii, Tatsuya

    2013-02-01

    In 1999, Hirose et al. reported a Japanese family with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) associated with a neuronal nicotinic acetylcholine receptor ?4 subunit mutation (S252L). We followed the siblings of this family, and found that the elder brother had Asperger's disorder without mental retardation (MR) and the younger brother had autistic disorder with profound MR. The clinical epileptic features of the siblings were very similar, and both had deficits in socialization, but their cognitive development differed markedly. It thus seems that epilepsy is the direct phenotype of the S252L mutation, whereas other various factors modulate the cognitive and social development. No patients with ADNFLE have previously been reported to have autism spectrum disorder or profound MR. PMID:22883468

  11. Acute tubular necrosis in a patient with paroxysmal nocturnal hemoglobinuria

    Eranga S Wijewickrama

    2013-01-01

    Full Text Available Acute renal failure (ARF is a well-recognized complication of paroxysmal nocturnal hemoglobinuria (PNH. The predominant mechanism is intravascular hemolysis resulting in massive hemoglobinuria ARF. We report a case of acute tubular necrosis (ATN developed in the absence of overwhelming evidence of intravascular hemolysis in a 21-year-old man with anemia, who was eventually diagnosed to have PNH. The patient presented with rapidly deteriorating renal functions in the background of iron deficiency anemia, which was attributed to reflux esophagitis. There was no clinical or laboratory evidence of intravascular hemolysis. Renal biopsy revealed ATN with deposition of hemosiderin in the proximal tubular epithelial cells. Diagnosis of PNH was confirmed with a positive Ham′s test and flow cytometry. Our case emphasizes the need to consider ATN as a possible cause for ARF in patients suspected to have PNH even in the absence of overwhelming evidence of intravascular hemolysis.

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

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

    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 their anterior median eyes. Measurement of the eyes' visual fields showed that the secondary eyes...... and temporal resolution of the eyes is insufficient for detecting any visual information on structures in the landscape, and bright stars would be the only objects visible to the spiders. However, by summation in space and time, the spiders can rescue enough vision to detect coarse landscape...

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

    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

  14. Definition of nocturnal gastroesophageal reflux for studies on respiratory diseases.

    Emilsson, Össur Ingi; Benediktsdóttir, Bryndís; Ólafsson, Ísleifur; Cook, Elizabeth; Júlíusson, Sigurður; Berg, Sören; Nordang, Leif; Björnsson, Einar Stefán; Guðlaugsdóttir, Sunna; Guðmundsdóttir, Anna Soffía; Janson, Christer; Gislason, Thorarinn

    2016-05-01

    Objective Nocturnal gastroesophageal reflux (nGER) has been associated with respiratory diseases. Our aim was to study a questionnaire method to identify nGER subjects with respiratory involvement in a general population. Material and methods A subgroup of Icelandic participants in the European Community Respiratory Health Survey III (ECRHS III) reporting symptoms of nGER (n  =  48) as well as age and gender paired controls (n  =  42) were studied further by a structured interview, questionnaires, laryngeal fibrescopy, and exhaled breath condensate. A subgroup underwent 24-h oesophageal pH impedance (24-h MII-pH) measurements. Symptoms of nGER were assessed with a modified version of the reflux disease questionnaire (RDQ), where symptoms were divided into daytime and nocturnal. A report of nGER both at baseline and at follow-up was defined as persistent nGER. Results Participants reporting persistent nGER had significantly more signs of laryngopharyngeal reflux according to the reflux finding score than those without nGER (Mean ± SD: 5.1 ± 2.3 vs. 3.9 ± 2.2, p  =  0.02). Of the 16 persistent nGER subjects that underwent 24-h MII-pH, 11 had abnormal gastroesophageal reflux, but none of three control subjects (69% vs. 0%). Pepsin was more commonly found in exhaled breath condensate in the nGER group (67% vs. 45%, p  =  0.04). Conclusions Participants with nGER symptoms at least once a month, reported on two occasions, had a high level of positive 24-h MII-pH measurements, laryngeal inflammation and pepsin in exhaled breath condensate. This nGER definition identified a representable group for studies on nGER and respiratory diseases in a general population. PMID:26825677

  15. Niche convergence suggests functionality of the nocturnal fovea

    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 δ13C values were indistinguishable, whereas the δ15N 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.

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

    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.

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

    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.

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

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

    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.

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

    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.

  1. Melatonin treatment does not prevent decreases in brain glutathione levels induced by sleep deprivation.

    D'Almeida, V; Hipólide, D C; Lobo, L L; de Oliveira, A C; Nobrega, J N; Tufik, S

    2000-03-01

    Recent findings from this laboratory revealed that sleep deprivation reduces total glutathione (GSH) levels in hypothalamus, suggesting an increased vulnerability to oxidative damage. Since melatonin has been shown to prevent oxidative damage in other experimental situations, the present study tested the effects of exogenous melatonin on sleep deprivation-induced GSH decreases. Rats were deprived of sleep for 96 h on small platforms, and melatonin (10 mg/kg body weight; i.p.) or vehicle was given twice a day. Hypothalamic GSH levels were significantly reduced in sleep-deprived groups, irrespective of melatonin treatment. Indeed, unexpectedly, melatonin treatment resulted in lower hypothalamic GSH levels in all groups, including cage controls. These results confirm that sleep deprivation reduces hypothalamic GSH and further indicate that melatonin treatment not only is ineffective in reversing this effect but may actually potentiate it. PMID:10708737

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

    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.

  3. Pharmacological and biochemical studies on the protective effects of melatonin during stress-induced behavioral and immunological changes in relation to oxidative stress in rats.

    Pal, Rishi; Gulati, Kavita; Banerjee, B D; Ray, Arunabha

    2016-03-01

    Stress is known to precipitate neuropsychiatric diseases, and depending upon its nature and intensity it can also influence the functioning of the immune system. Melatonin (N-acetyl-5-methoxy tryptamine) a pineal gland hormone and potent antioxidant is known to protect against many diseases. Effect of melatonin in stress-induced neuro-immunomodulation is not well elucidated. Therefore in the present study, the protective effects of melatonin were evaluated in restraint stress (RS)-induced behavioral and immunological changes in rats. RS for 1 h significantly reduces (i) percentage of open-arm entries and (ii) percentage of time spent on open-arm in elevated plus maze (EPM) test parameters (p < 0.01) and significant increase in MDA levels in brain homogenate when compared to non-RS control groups (p < 0.05). In immunological studies, both humoral and cell-mediated immune responses to antigen were significantly suppressed by RS for 1 h for 5 consecutive days, as evidenced by significant reduction in (i) anti-SRBC antibody titre, (ii) PFC counts, (iii) percentage change in paw volume, and (iv) Th1 (IFN-γ) and Th2 (IL-4) cytokine levels (p < 0.001 in all parameters). These RS-induced immunological changes were associated with significantly increased lipid peroxidation (MDA) levels in serum and significantly decreased activity of (i) SOD, (ii) CAT, and (iii) GSH levels in RS (X5)-exposed group (p < 0.02). Pretreatment with melatonin (10, 50, and 100 mg/kg) significantly reversed these RS-induced changes in EPM test parameters and humoral and cell-mediated immunological parameters, as well as oxidative stress markers in a dose-dependent manner by differential degrees (p < 0.001). Results are strongly suggestive of the involvement of free radicals during stress-induced neurobehavioral and immunological changes. These changes were significantly restored by melatonin pretreatment. We can conclude that melatonin may have a protective role during such stress-induced neuro-immunomodulation. PMID:26754541

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

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

    SimonVincenzi; ShanthaMRajaratnam

    2010-01-01

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

  6. Timing of Sleep and Its Relationship with the Endogenous Melatonin Rhythm

    Sletten, Tracey L.; Vincenzi, Simon; Redman, Jennifer R.; Lockley, Steven W.; Rajaratnam, Shantha M.W.

    2010-01-01

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

  7. Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders

    Ferracioli-Oda, Eduardo; Qawasmi, Ahmad; Bloch, Michael H

    2013-01-01

    Study Objectives To investigate the efficacy of melatonin compared to placebo in improving sleep parameters in patients with primary sleep disorders. Design PubMed was searched for randomized, placebo-controlled trials examining the effects of melatonin for the treatment of primary sleep disorders. Primary outcomes examined were improvement in sleep latency, sleep quality and total sleep time. Meta-regression was performed to examine the influence of dose and duration of melatonin on reported...

  8. Postnatal dexamethasone-induced programmed hypertension is related to the regulation of melatonin and its receptors.

    Chang, Hsin-Yu; Tain, You-Lin

    2016-04-01

    Adulthood hypertension can be programmed by glucocorticoid exposure in early life. We found that maternal melatonin therapy prevents postnatal dexamethasone (DEX)-induced programmed hypertension. Melatonin acts through specific receptors, including MT1 and MT2 membrane receptors, and retinoid related orphan nuclear receptors of the RZR/ROR family. Thus we tested whether postnatal DEX-induced hypertension is related to changes of melatonin receptors in the kidney and heart, which was preserved by maternal melatonin therapy. Male neonates were assigned to four groups (n=6-8/group): control, DEX, control+melatonin (MEL), and DEX+MEL. Male rat pups were injected i.p. with DEX on d 1 (0.5mg/kg BW), d 2 (0.3mg/kg BW), and d 3 (0.1mg/kg BW) after birth. Melatonin was administered in drinking water (0.01%) during the lactation period. We found DEX group developed hypertension at 16weeks of age, which melatonin therapy prevented. Postnatal DEX treatment increased mRNA expression of MT1 and MT2, while decreased RORα and RZRβ in the kidney. These changes were prevented by melatonin therapy. Postnatal DEX decreased protein level of MT2 in the kidney, which was attenuated by melatonin therapy. Renal protein level of RORα was higher in DEX+MEL group compared to control and DEX group. Renal melatonin level was higher in the MEL and DEX+MEL groups compared to control. We concluded that melatonin therapy has long-term protection on postnatal DEX-induced programmed hypertension, which is associated with regulation on melatonin receptors in the kidney. Our findings would offer potential therapeutic approaches to prevent programmed hypertension in premature baby receiving glucocorticoids. PMID:26921678

  9. Tryptophan-ethylester, the false (unveiled) melatonin isomer in red wine

    Marcello Iriti; Ileana Vigentini

    2015-01-01

    Among the food plants, the presence of melatonin in grapes (Vitis vinifera L.) deserves particular attention because of the production of wine, an alcoholic beverage of economic relevance and with putative healthy effects. Furthermore, melatonin isomers have been detected in wine too. Recently, one of these isomers has been identified as tryptophan-ethylester, a compound with the same molecular weight of melatonin. In this Commentary, we briefly comment the source(s) of tryptophan-ethylester ...

  10. Does Melatonin Ameliorate Neurological Changes Associated With Alzheimer’s Disease in Ovariectomized Rat Model?

    Ahmed, Hanaa H; Estefan, Selim F.; Mohamd, Ehab M.; Farrag, Abd El-Razik H.; Salah, Rania S.

    2012-01-01

    This study aimed to elucidate the mechanisms of melatonin to manage neurological damage in Alzheimer’s disease (AD) induced in ovariectomized rats. Forty adult female rats were enrolled in our study and were classified as; gonad intact control, ovariectomized control group, ovariectomized rats received melatonin, ovariectomized rats injected with AlCl3 to induce AD and AD-induced rats treated with melatonin. Hydrogen peroxide (H2O2), malondialdehyde (MDA), total antioxidant capacity (TAC), su...

  11. Preliminary study: Evaluation of melatonin secretion in children and adolescents with type 1 diabetes mellitus

    Yilmaz Kor

    2014-01-01

    Full Text Available Objective: Melatonin is an indolamine hormone, synthesized from tryptophan in the pineal gland primarily. Melatonin exerts both antioxidative and immunoregulatory roles but little is known about melatonin secretion in patients with type 1 diabetes mellitus (T1DM. The aim of this study was to measure serum melatonin levels in patients with T1DM and investigates their relationship with type 1 diabetes mellitus. Materials and Methods: Forty children and adolescents with T1DM (18 boys and 22 girls and 30 healthy control subjects (17 boys and 13 girls participated in the study. All patients followed in Pediatric Endocrinology and Metabolism Unit of Gaziantep University Faculty of Medicine and also control subjects had no hypertension, obesity, hyperlipidemia, anemia, and infection. Blood samples were collected during routine analysis, after overnight fasting. Serum melatonin levels were analyzed with ELISA. Results: There were no statistically significant differences related with age, sex, BMI distribution between diabetic group and control group. Mean diabetic duration was 2.89 ± 2.69 years. The variables were in the equation. Mean melatonin level in diabetic group was 6.75 ± 3.52 pg/ml and mean melatonin level in control group was 11.51 ± 4.74 pg/ml. Melatonin levels were significantly lower in diabetic group compared to controls (P < 0.01. Conclusions: Melatonin was associated with type 1 diabetes mellitus significantly. Because of the varied roles of melatonin in human metabolic rhythms, these results suggest a role of melatonin in maintaining normal rhythmicity. Melatonin may play role in preventing process of inflammation and oxidative stress.

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

    Figueiro Mariana G

    2012-05-01

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

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

    J. Mazon

    2013-12-01

    Full Text Available Three offshore rain bands associated with nocturnal coastal fronts formed near the Israel coastline, the Gulf of Genoa and on the northeastern coast of the Iberian Peninsula are simulated by using version 3.3 of WRF–ARW mesoscale model to study the dynamics of the atmosphere in each case. A relatively large 1 h and 10 h accumulated precipitation are simulated when comparing with some other similar rain bands formed in the Mediterranean basin. According to the simulations, the coastal fronts formed near the Israel coastline and in the Gulf of Genoa are quasi-stationary, while the one formed on the northeastern of the Iberian Peninsula moves offshore. For the three events, the evolution of the triggering parameter H/LFC, where H is the coastal-front depth and LFC is the Level of Free Convection, is compared and used as an indication of the occurrence of convective precipitation.

  14. Antioxidant capacity of the neurohormone melatonin.

    Sofic, E; Rimpapa, Z; Kundurovic, Z; Sapcanin, A; Tahirovic, I; Rustembegovic, A; Cao, G

    2005-03-01

    The aim of this study was to elucidate the antioxidant behaviour of melatonin (M) and determine its activity-structure relationship. M or 5-metoxy-N acetyltriptamine is a neurohormone secreted by the pineal gland, which plays a proven role in maintaining sleep-wake rhythms. The antioxidant capacity of M was analysed using the oxygen radical absorbance capacity (ORAC) assay. Furthermore, spectral measurements for aerobic photolytic reaction of neutral red (NR) and degree of inhibition of photolysis with M, glutathione (GSH), ascorbic acid (AA) and vitamin E analogue Trolox were studied at room temperature 25 degrees C, using visible (VIS) and ultra-violet (UV) radiations. In the ORAC assay 2,2-azobis (2-amidino-propane)dihydrochloride (AAPH) a peroxyl radical generator, ROO degrees ; H2O2-Cu2+, mainly a hydroxyl radical generator, degrees OH; and Cu2+ a transition metal were used. Although some studies indicated that M is a powerful antioxidant, no one has compared its antioxidant capacities with GSH, E-vitamin and AA, using three free radical (FR) generators in an assay which utilizes an area-under curve technique and thus combines both inhibition time and inhibition degree of FR action by an antioxidant into a single quantity. In the current study, we used ORAC assay with three FR generators. The assay is based on propensity of the fluorescence emitted by the protein beta-phycoerythrin (beta-PE) from porphyridium cruentum to be quenched when exposed to FR action. M in our experiments acted as a universal antioxidant against ROO degrees and degrees OH radicals. Also, M served as an antioxidant in the presence of Cu2+. M, which is a lipid-soluble compound, was a twice more powerful antioxidant than vitamin E, and four times than AA or GSH. Furthermore, M inhibited aerobic photolysis of NR photoinduced with VIS and UV rays faster and more effectively, than AA, GSH or vitamin E. AA with NR, under aerobic conditions during irradiation with VIS and UV acted as a pro-oxidant. M may be the premier molecule to protect the cells from oxidative stress. PMID:15666035

  15. Melatonin and its metabolites as anti-nitrosating and anti-nitrating agents

    Rudiger Hardeland

    2011-04-01

    Full Text Available Although basal and moderately elevated levels of nitric oxide are physiologically necessary and beneficial, excessive upregulations of this signaling molecule can be a cause of damage and cellular dysfunctions. In the presence of increased amounts of superoxide anions (•O2– and carbon dioxide, peroxynitrite (ONOO– and the peroxynitrite-CO2 adduct (ONOOCO2– generate hydroxyl (•OH, nitrogen dioxide (•NO2 and carbonate (•CO3– radicals, which damage biomolecules by oxidation/peroxidation, nitration and nitrosation reactions. Nitrosation also occurs with all three NO congeners (NO+, •NO, and HNO = protonated NO–, with •NO especially in combination with electron/hydrogen-abstracting compounds, or with N2O3. 3-Nitrotyrosine, found in low-density lipoprotein particles (LDL, atherosclerotic plaques, ion channels, receptors, transporters, enzymes and respirasomal subunits, is associated with numerous dysfunctions. Damage to the mitochondrial electron transport chain (ETC is of particular significance and involves nitration, nitrosation and oxidation of proteins, cardiolipin peroxidation, and binding of •NO to ETC irons. Resulting bottlenecks of electron flux cause enhanced electron leakage which leads to elevated •O2–. In combination with high •NO, •O2– initiates a vicious cycle by generating more peroxynitrite that leads to further blockades and electron dissipation. Mitochondrial dysfunction, as induced via the •NO/peroxynitrite pathway, is of utmost importance in inflammatory diseases, especially sepsis, but also relevant to neurodegenerative and various other disorders. It may contribute to processes of aging. Melatonin, hormone of the pineal gland and product of other organs, interacts directly with reactive nitrogen species, but, more importantly, has antiinflammatory properties and downregulates inducible and neuronal NO synthases (iNOS, nNOS. It does not block moderately elevated •NO formation, but rather blunts excessive rises as occurring in sepsis and breaks the vicious cycle of mitochondrial electron leakage. The melatonin metabolite N1-acetyl-5-methoxykynuramine (AMK forms stable nitrosation products and efficiently inhibits iNOS and nNOS, in conjunction with other antiinflammatory properties. [J Exp Integr Med 2011; 1(2.000: 67-81

  16. Intake of bean sprouts influences melatonin and antioxidant capacity biomarker levels in rats.

    Aguilera, Yolanda; Rebollo-Hernanz, Miguel; Herrera, Teresa; Cayuelas, L Tábata; Rodríguez-Rodríguez, Pilar; de Pablo, Ángel L López; Arribas, Silvia M; Martin-Cabrejas, María A

    2016-03-16

    Melatonin is an endogenous antioxidant hormone, which reduces with ageing and the low levels are associated with some chronic diseases. Germination of legumes increases the plant levels of melatonin, making sprouts a suitable food source of this hormone. However, information on its bioavailability after consumption is lacking. We aimed to evaluate in rats the effect of kidney bean sprout intake on the plasma levels of melatonin and metabolically related compounds (serotonin, 6-sulfatoxymelatonin), total phenolic compounds and total antioxidant capacity. In addition, we compared the plasma bioavailability derived from kidney bean sprouts versus synthetic melatonin intake. Kidney beans were germinated for 6 days and an extract was prepared in water. Male young Sprague Dawley rats were used; blood and urine samples were obtained before and after 90 min of administration of kidney bean sprout extract via a gavage. The plasmatic melatonin levels increased after sprout ingestion (16%, p phenolic compounds and antioxidant capacity levels did not exhibit any significant variation. The comparison of the bioavailability between the melatonin contained in the kidney bean sprouts and in a synthetic solution evidenced slightly higher levels of plasmatic melatonin (17%) in rats fed with the solution of synthetic melatonin. We conclude that kidney bean sprouts could be a good source of dietary melatonin and other bioactive compounds known to have health benefits. PMID:26841704

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

    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...

  18. Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells

    Martínez-Campa, C; González, A; Mediavilla, M D; Alonso-González, C; Alvarez-García, V; Sánchez-Barceló, E J; Cos, S

    2009-01-01

    Background: Melatonin reduces the development of breast cancer interfering with oestrogen-signalling pathways, and also inhibits aromatase activity and expression. Our objective was to study the promoters through which melatonin modifies aromatase expression, evaluate the ability of melatonin to regulate cyclooxygenases and assess whether the effects of melatonin are related to its effects on intracellular cAMP, in MCF-7 cells. Methods: Total aromatase mRNA, aromatase mRNA promoter regions and cyclooxygenases mRNA expression were determined by real-time RT–PCR. PGE2 and cAMP were measured by kits. Results: Melatonin downregulated the gene expression of the two major specific aromatase promoter regions, pII and pI.3, and also that of the aromatase promoter region pI.4. Melatonin 1 nM was able to counteract the stimulatory effect of tetradecanoyl phorbol acetate on PGE2 production and inhibit COX-2 and COX-1 mRNA expression. Melatonin 1 nM elicited a parallel time-dependent decrease in both cyclic AMP formation and aromatase mRNA expression. Conclusions: This study shows that melatonin inhibits aromatase activity and expression by regulating the gene expression of specific aromatase promoter regions. A possible mechanism for these effects would be the regulation by melatonin of intracellular cAMP levels, mediated by an inhibition of cyclooxygenase activity and expression. PMID:19773750

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

    2014-01-01

    Background Melatonin content was screened in leaves of seven edible herbs used as sleeping aids in Thai traditional medicine. These plants are Piper nigrum L, Sesbania glandiflora (L.) Desv., Sesbania sesban (L.) Merr., Senna tora (L.) Roxb., Moringa oleifera Lam., Momordica charantia L. and Baccaurea ramiflora Lour. Dried leaves were extracted by sonication in methanol for six hours at room temperature, and then melatonin was purified by C18 solid phase extraction (SPE). Melatonin was then quantified by a validated RP-C18 HPLC method with fluorescent detection. Findings Melatonin contents in extracts of B. ramiflora,?S. glandiflora,?M. charantia,?S. tora and S. sesban were 43.2, 26.3, 21.4, 10.5 and 8.7 ng/g of dry sample weight, respectively. The highest melatonin content was from P. nigrum extract (1092.7 ng/g of dry sample weight). Melatonin was not detected in the extract of M. oleifera. Melatonin identification was confirmed by ELISA. Conclusions Melatonin was found in six of the seven herbs in the traditional Thai sleeping recipe. One of these, P. nigrum, exhibited an encouragingly high amount of melatonin. PMID:24393215

  20. Mitogen-activated protein kinase pathways are required for melatonin-mediated defense responses in plants.

    Lee, Hyoung Yool; Back, Kyoungwhan

    2016-04-01

    Melatonin enhances pathogen resistance by inducing the expression of a number of plant defense-related genes. To examine whether the melatonin-mediated pathogen resistance is associated with mitogen-activated protein kinase (MAPK) cascades, Arabidopsis and tobacco leaves were treated with melatonin and investigated for MAPK activation using an antiphospho-p44/42 MAPK (Erk1/2) monoclonal antibody. Two MAPKs, MPK3 and MPK6, were activated rapidly and transiently by 1 μm melatonin treatment in Arabidopsis. Its tobacco ortholog MAPKs were also activated. The activation of MPK3 and MPK6 by 2-hydroxymelatonin and N-acetylserotonin was also observed, albeit to a lesser degree than that by melatonin. Furthermore, MAPK activation by melatonin was uncoupled from G-protein signaling, because melatonin efficiently activated two MAPKs in a G-protein β knockout mutant (agb1). Suppression of both MPK3 and MPK6 in transgenic Arabidopsis exhibited significant decreases in the induction of defense-related gene expression and pathogen resistance relative to wild-type plants. Using an array of MAP kinase kinase (MKK) knockout mutants, we found that four MKKs, namely MKK4, MKK5, MKK7, and MKK9, are responsible for the activation of MPK3 and MPK6 by melatonin, indicating that melatonin-mediated innate immunity is triggered by MAPK signaling through MKK4/5/7/9-MPK3/6 cascades. PMID:26927635

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

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

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

    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.

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

    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

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

    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

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

    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...

  6. Desmopressin versus Oxybutynin for Nocturnal Enuresis in Children in Bandar Abbas: A Randomized Clinical Trial

    Ghasemi, Kambiz; Esteghamati, Maryam; Mohammadzadeh, Malihe; Zare, Shahram

    2016-01-01

    Background Nocturnal enuresis is among the most common disorders in children. Several pharmacological and non-pharmacological treatments are available for nocturnal enuresis. Studies for reaching the best pharmacological treatment for this disorder are continuing. Objective To compare the effectiveness and safety of Desmopressin and oxybutynin for treatment of nocturnal enuresis in children from Bandar Abbas in 2014. Methods This randomized controlled trial was conducted in 2014 and participants included 66 children with nocturnal enuresis who were more than 5 years old. Patients were randomly assigned into two groups. The first group received 120 microgram Desmopressin daily for 2 months, then 60 microgram daily for 2 months, then 60 microgram every 2 days. The second group received 5 mg oxybutynin twice a day for 6 months. The patients were followed after 1, 3, and 6 months to track treatment response. The study outcomes were frequency of nocturnal enuresis, urinary incontinency, urgency, and frequency. Data were analyzed using SPSS software. Results There were no significant differences between the two groups with respects to sex, age, place of residence, and parents’ education (p<0.05). Nocturnal enuresis, incontinency, urgency, and frequency of nocturnal enuresis was significantly lower with Desmopressin treatment in comparison to the oxybutynin treated group after 1 and 3 months (p<0.05). In addition, constipation and xerostomia were more frequent among the oxybutynin group after 1, 3, and 6 months (p<0.01). Blurred vision was also more frequent among oxybutynin group after 3 months (p<0.01). After 6 months the frequency of nocturnal enuresis and its frequency was higher in oxybutynin group in comparison to the Desmopressin group (p<0.05). Conclusion Desmopressin is more effective and has lower rate of side effects in comparison to oxybutynin for treatment of nocturnal enuresis. We recommend using Desmopressin for treatment of nocturnal enuresis in children. More studies are needed to achieve the best pharmacological treatment option for treatment of nocturnal enuresis. Trial registration The trial is registered at ClinicalTrials.gov with a ClinicalTrials.gov Identifier: NCT02538302 Funding The funder of this research is Hormozgan University of Medical Sciences.

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

    Khalida Anwer Yousef

    2011-01-01

    Full Text Available Nocturnal enuresis is a common problem among children and adolescents. Data regarding this problem in schoolchildren in Yemen are scarce. This study was aimed to determine the prevalence of nocturnal incontinence in Aden school going children, describe its severity and identify the relation between nocturnal enuresis with personal and family characteristics. The study was a cross-sectional survey conducted on the public basic schoolchildren in Aden, Yemen, in the period November 2007-April 2009. A random, multistage sample of 890 students was taken from four districts in eight schools and divided into two strata: males and females. Data were obtained by using pre-recoded questionnaire, which was completed by parents. The response rate was 73.7% (656 students; 113 (17.2% cases of nocturnal enuresis were encountered. Nocturnal enuresis de-creased by age from 31.5% at 6-8 years to 8.7% at 15+ years (P < 0.05. Primary nocturnal enuresis affected 76.1%, of which the majority of children were bedwetting every night. Positive family history of nocturnal enuresis, deeper sleep, daytime enuresis, tea drinking, being non working father or with less education showed significant association with the occurrence of enuresis in the students. Stressful events in the previous 6 months of the study were twice more frequently noted. The study concluded that the prevalence of nocturnal enuresis in Aden public school children and its associated factors are almost comparable with that reported in epidemiological studies from various countries. Health education will encourage the parents to be aware, cope with this problem and seek appropriate medical advice.

  8. Changes in nocturnal and peak acid outputs after duodenal ulcer healing with sucralfate or ranitidine.

    Kummer, A F; Johnston, D.A.; Marks, I. N.; Young, G O; Tigler-Wybrandi, N A; Bridger, S A

    1992-01-01

    Changes in basal and stimulated acid secretion after duodenal ulcer healing have been previously shown to be influenced by the nature of the treatment. This study aimed to determine possible changes in nocturnal acid secretion on duodenal ulcer healing in patients treated with sucralfate or ranitidine. Nocturnal acid output and peak acid output in response to pentagastrin stimulation were studied in 20 patients before and after duodenal ulcer healing with sucralfate (n = 9) or ranitidine (n =...

  9. Nocturnal oxygen desaturation and spirometric parameters in adults with cystic fibrosis.

    Pond, M. N.; Conway, S P

    1995-01-01

    BACKGROUND--Correction of nocturnal hypoxaemia in patients with cystic fibrosis may delay the development of pulmonary hypertension. Descriptive statistics used for nocturnal arterial oxygen saturation (SpO2) lack uniformity. The relationship between SpO2 and spirometric parameters has not previously been explored in a large number of exacerbations in adult patients with cystic fibrosis. METHODS--Over a 21 month period overnight SpO2, forced expiratory volume in one second (FEV1), and forced ...

  10. Response of alfalfa (Medicago sativa L.) to diurnal and nocturnal saline sprinkler

    Isla Climente, Ramón; Aragüés Lafarga, Ramón

    2009-01-01

    Little information is available on the quantitative effects on crops of saline sprinkler irrigations and the presumable beneficial effects of nocturnal versus diurnal irrigations. We measured crude protein content, carbon isotope discrimination and total dry matter (TDM) of alfalfa (Medicago sativa L.) subject to diurnal and nocturnal saline sprinkler irrigations. The work was carried out in Zaragoza (Spain) during the 2004–2006 growing seasons with a triple line source sprinkler system using...

  11. Nocturnal Hypoxia in ALS Is Related to Cognitive Dysfunction and Can Occur as Clusters of Desaturations

    Park, Su-yeon; Kim, Sung-min; Sung, Jung-Joon; Lee, Kyung-min; Park, Kyung-Seok; Kim, Sang-Yun; Nam, Hyun-woo; Lee, Kwang-Woo

    2013-01-01

    Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to progressive weakness of the respiratory and limb muscles. Consequently, most patients with ALS exhibit progressive hypoventilation, which worsens during sleep. The aim of this study was to evaluate the relationship between nocturnal hypoxia and cognitive dysfunction and to assess the pattern of nocturnal hypoxia in patients with ALS. Method Twenty-five patients with definite or probable ALS underwent n...

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

    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...

  13. Melatonin Supports CYP2D-Mediated Serotonin Synthesis in the Brain.

    Haduch, Anna; Bromek, Ewa; Wójcikowski, Jacek; Gołembiowska, Krystyna; Daniel, Władysława A

    2016-03-01

    Melatonin is used in the therapy of sleep and mood disorders and as a neuroprotective agent. The aim of our study was to demonstrate that melatonin supported (via its deacetylation to 5-methoxytryptamine) CYP2D-mediated synthesis of serotonin from 5-methoxytryptamine. We measured serotonin tissue content in some brain regions (the cortex, hippocampus, nucleus accumbens, striatum, thalamus, hypothalamus, brain stem, medulla oblongata, and cerebellum) (model A), as well as its extracellular concentration in the striatum using an in vivo microdialysis (model B) after melatonin injection (100 mg/kg i.p.) to male Wistar rats. Melatonin increased the tissue concentration of serotonin in the brain structures studied of naïve, sham-operated, or serotonergic neurotoxin (5,7-dihydroxytryptamine)-lesioned rats (model A). Intracerebroventricular quinine (a CYP2D inhibitor) prevented the melatonin-induced increase in serotonin concentration. In the presence of pargyline (a monoaminoxidase inhibitor), the effect of melatonin was not visible in the majority of the brain structures studied but could be seen in all of them in 5,7-dihydroxytryptamine-lesioned animals when serotonin storage and synthesis via a classic tryptophan pathway was diminished. Melatonin alone did not significantly increase extracellular serotonin concentration in the striatum of naïve rats but raised its content in pargyline-pretreated animals (model B). The CYP2D inhibitor propafenone given intrastructurally prevented the melatonin-induced increase in striatal serotonin in those animals. The obtained results indicate that melatonin supports CYP2D-catalyzed serotonin synthesis from 5-methoxytryptamine in the brain in vivo, which closes the serotonin-melatonin-serotonin biochemical cycle. The metabolism of exogenous melatonin to the neurotransmitter serotonin may be regarded as a newly recognized additional component of its pharmacological action. PMID:26884482

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

    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.

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

    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 μM 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

  16. Placental melatonin system is present throughout pregnancy and regulates villous trophoblast differentiation.

    Soliman, Ahmed; Lacasse, Andrée-Anne; Lanoix, Dave; Sagrillo-Fagundes, Lucas; Boulard, Véronique; Vaillancourt, Cathy

    2015-08-01

    Melatonin is highly produced in the placenta where it protects against molecular damage and cellular dysfunction arising from hypoxia/re-oxygenation-induced oxidative stress as observed in primary cultures of syncytiotrophoblast. However, little is known about melatonin and its receptors in the human placenta throughout pregnancy and their role in villous trophoblast development. The purpose of this study was to determine melatonin-synthesizing enzymes, arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT), and melatonin receptors (MT1 and MT2) expression throughout pregnancy as well as the role of melatonin and its receptors in villous trophoblast syncytialization. Our data show that the melatonin generating system is expressed throughout pregnancy (from week 7 to term) in placental tissues. AANAT and HIOMT show maximal expression at the 3rd trimester of pregnancy. MT1 receptor expression is maximal at the 1st trimester compared to the 2nd and 3rd trimesters, while MT2 receptor expression does not change significantly during pregnancy. Moreover, during primary villous cytotrophoblast syncytialization, MT1 receptor expression increases, while MT2 receptor expression decreases. Treatment of primary villous cytotrophoblast with an increasing concentration of melatonin (10 pM-1 mM) increases the fusion index (syncytium formation; 21% augmentation at 1 mM melatonin vs. vehicle) and ?-hCG secretion (121% augmentation at 1 mM melatonin vs. vehicle). This effect of melatonin appears to be mediated via its MT1 and MT2 receptors. In sum, melatonin machinery (synthetizing enzymes and receptors) is expressed in human placenta throughout pregnancy and promotes syncytium formation, suggesting an essential role of this indolamine in placental function and pregnancy well-being. PMID:25833399

  17. The possible protective effect of melatonin on streptozotocin induced experimental diabetes

    Hakan Yüzüak

    2014-12-01

    Full Text Available Objective: This experimental study aims to investigate the protective effect of melatonin on the enzymes’, which regulate glucose metabolism in liver tissue. Methods: In this experimental study, four-month-old male Wistar albino rats were used. The rats were divided into 4 groups as 7 rats in each group. Rats were grouped as control group, diabetic group, melatonin protecting group, as well as melatonin treatment group. Before the streptozotocin implementation to melatonin protecting group (seven days ago everyday at 18.00 melatonin was implemented for seven days. On the other hand melatonin was implemented to melatonin treatment group after streptozotocin implementation everyday at 18.00 for seven days. Only a single dose of streptozotocin was implemented to diabetic group. Control group had no intervention throughout the study. In the end of the experiment, blood was taken and rats were sacrificed. Before the sacrifice process rats’ fasting blood pressure was measured. Hexokinases, pyruvate kinase, glucose-6-phosphatase, fructose - 1,6-bisphosphatase, glucose -6 phosphate dehydrogenase levels were measured in the liver samples. Results: Between control and experimental groups of rats, there are statistically significant differences between control and experimental groups for all parameters. Melatonin protecting group levels of investigated parameters were more close to that of control groups’ values and results are statistically significant. Moreover, melatonin treatment group showed a protective effect. However it is not effective as melatonin protecting group. Conclusion: It can be suggested that melatonin shows protective effect on enzymes related to glucose metabolism in the liver tissue in a model of streptozotocin-induced experimental diabetes. J Clin Exp Invest 2014; 5 (4: 592-598

  18. Melatonin administration enhances the reproductive capacity of young rams under a southern Mediterranean environment.

    Rekik, Mourad; Taboubi, Rahma; Ben Salem, Imene; Fehri, Younes; Sakly, Cyrine; Lassoued, Narjess; Hilali, Muhi Eddine

    2015-07-01

    This study tested the effect of melatonin treatment, initiated in late February on reproductive traits of young rams. A total of 14 young Barbarine rams were used. Seven animals were treated with three melatonin subcutaneous implants (Melatonin) on 28 February while the remaining rams remained untreated (Control). After 60 days of melatonin administration, scrotal circumference reached average values of 32.1 ± 1.54 and 29.5 ± 1.0 cm for Melatonin and Control animals, respectively (P < 0.05). Semen characteristics did not differ between groups; melatonin treatment tended (P = 0.091) to increase sperm concentration 60 days after implantation when means reached 5.87 ± 0.703 and 4.61 ± 0.654 × 10(9) spermatozoa/mL for Melatonin and Control rams, respectively. Melatonin treatment significantly affected total activity time, number of lateral approaches and mount attempts in comparison to controls. During a 6-h sampling period, mean plasma testosterone concentrations increased as a result of melatonin treatment (P < 0.001) and testosterone pulse frequency averaged 3.45 ± 2.24 and 1.25 ± 1.0 (P = 0.086) for Melatonin and Control rams. Data clearly suggest that abrupt treatment of young rams with melatonin implants in winter is sufficient to improve reproductive traits. PMID:25689168

  19. The Effects of Melatonin on Brain Arginine Vasotocin: Relationship with Sex and Seasonal Differences in Melatonin Receptor Type 1 in Green Treefrogs (Hyla cinerea).

    Howard, C M; Lutterschmidt, D I

    2015-08-01

    The neuroendocrine mechanisms by which animals synchronise their physiological state with environmental cues are vital to timing life-history events appropriately. One important endocrine transducer of environmental cues in vertebrates is the pineal hormone melatonin, the secretion of which is directly sensitive to photoperiod and temperature. Melatonin modulates arginine vasotocin (AVT)-immunoreactive (-IR) cell number in the brain of green treefrogs (Hyla cinerea) during the summer breeding season, and this modulation is sexually dimorphic. In the present study, we investigated whether the influence of melatonin on vasotocin varies seasonally. We show that treatment of nonreproductive male green treefrogs with melatonin-filled silastic implants for 4 weeks during the winter does not alter vasotocin-IR cell number in any brain region (i.e. nucleus accumbens, amygdala, preoptic area, suprachiasmatic nucleus or ventral hypothalamus). Taken together, these results suggest that the influence of melatonin on AVT is associated with sex and seasonal variation in melatonin receptor expression. We tested this hypothesis by using immunohistochemistry to characterise the distribution of melatonin receptor type 1 (MT1, also known as Mel1a) in the brain of reproductive and nonreproductive male and female frogs. We quantified MT1-IR cell number in regions known to contain AVT cell populations. Reproductive males had significantly more MT1-IR cells than nonreproductive males in all brain regions, including the combined nucleus accumbens, diagonal band of Broca and septum, striatum, amygdala, combined preoptic area and suprachiasmatic nucleus, as well as the ventral hypothalamus. In the accumbens region, where the effect of melatonin on AVT is known to be sexually dimorphic, males had significantly more MT1-IR cells than females during the summer breeding season. Based on these findings, we suggest that MT1 plays a role in mediating the interactions between melatonin and vasotocin that regulate seasonal and sexually dimorphic changes in sociosexual behaviour. PMID:25967351

  20. Sleep–wake and melatonin pattern in craniopharyngioma patients

    Pickering, Line; Jennum, Poul; Gammeltoft, Steen; Poulsgaard, Lars; Feldt-Rasmussen, Ulla; Klose, Marianne

    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...

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

    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.

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

    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

  3. Obesity and nocturnal gastro-oesophageal reflux are related to onset of asthma and respiratory symptoms.

    Gunnbjörnsdóttir, M I; Omenaas, E; Gíslason, T; Norrman, E; Olin, A C; Jõgi, R; Jensen, E J; Lindberg, E; Björnsson, E; Franklin, K; Janson, C; Gulsvik, A; Laerum, B; Svanes, C; Torén, K; Tunsäter, A; Lillienberg, L; Gíslason, D; Blöndal, T; Björnsdottir, U S; Jörundsdóttir, K B; Talvik, R; Forsberg, B; Franklin, K; Lundbäck, B; Söderberg, M; Ledin, M C; Boman, G; Norbäck, D; Wieslander, G; Spetz-Nyström, U; Cashelunge, K Stenudd; Rydén, E

    2004-07-01

    Several studies have identified obesity as a risk factor for asthma in both children and adults. An increased prevalence of asthma in subjects with gastro-oesophageal reflux (GOR) and obstructive sleep apnoea syndrome has also been reported. The aim of this investigation was to study obesity, nocturnal GOR and snoring as independent risk factors for onset of asthma and respiratory symptoms in a Nordic population. In a 5-10 yr follow-up study of the European Community Respiratory Health Survey in Iceland, Norway, Denmark, Sweden and Estonia, a postal questionnaire was sent to previous respondents. A total of 16,191 participants responded to the questionnaire. Reported onset of asthma, wheeze and night-time symptoms as well as nocturnal GOR and habitual snoring increased in prevalence along with the increase in body mass index (BMI). After adjusting for nocturnal GOR, habitual snoring and other confounders, obesity (BMI >30) remained significantly related to the onset of asthma, wheeze and night-time symptoms. Nocturnal GOR was independently related to the onset of asthma and in addition, both nocturnal GOR and habitual snoring were independently related to onset of wheeze and night-time symptoms. This study adds evidence to an independent relationship between obesity, nocturnal gastro-oesophageal reflux and habitual snoring and the onset of asthma and respiratory symptoms in adults. PMID:15293613

  4. Chronic fluoxetine treatment increases daytime melatonin synthesis in the rodent

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

    2009-01-01

    Gillian W Reierson, Claudio A Mastronardi, Julio Licinio, Ma-Li WongCenter on Pharmacogenomics, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USAAbstract: Circadian rhythm disturbances can occur as part of the clinical symptoms of major depressive disorder and have been found to resolve with antidepressant therapy. The pineal gland is relevant to circadian rhythms as it secretes the hormone melatonin following activation of the cyc...

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

    Sanjay Kalra; Swati Agrawal; Manisha Sahay

    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.

  6. The role of melatonin in autoimmune and atopic diseases

    J.R. Calvo

    2016-04-01

    Full Text Available Melatonin is the main secretory product synthesized and secreted by the pineal gland during the night. Melatonin is a pleitropic molecule with a wide distribution within phylogenetically distant organisms and has a great functional versatility, including the regulation of circadian and seasonal rhythms and antioxidant and anti-inflammatory properties. It also possesses the capacity to modulate immune responses by regulation of the TH1/TH2 balance and cytokine production. Immune system eradicates infecting organisms without serious injury to host tissues, but sometimes these responses are inadequately controlled, giving rise to called hypersensitivity diseases, or inappropriately targeted to host tissues, causing the autoimmune diseases. In clinical medicine, the hypersensitivity diseases include the allergic or atopic diseases and the hallmarks of these diseases are the activation of TH2 cells and the production of IgE antibody. Regarding autoimmunity, at the present time we know that the key events in the development of autoimmunity are a failure or breakdown of the mechanisms normally responsible for maintaining self-tolerance in B lymphocytes, T lymphocytes, or both, the recognition of self-antigens by autoreactive lymphocytes, the activation of these cells to proliferate and differentiate into effector cells, and the tissue injury caused by the effector cells and their products. Melatonin treatment has been investigated in atopic diseases, in several animal models of autoimmune diseases, and has been also evaluated in clinical autoimmune diseases. This review summarizes the role of melatonin in atopic diseases (atopic dermatitis and asthma and in several autoimmune diseases, such as arthritis rheumatoid, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes mellitus, and inflammatory bowel diseases.

  7. Antinociceptive properties of selective MT(2) melatonin receptor partial agonists.

    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 (5-40 mg/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 200 mg/kg acetaminophen in the hot-plate test, and by 3 mg/kg ketorolac or 150 mg/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, 10 mg/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

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

    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.

  9. Melatonin and Ischemic Stroke: Mechanistic Roles and Action

    Syed Suhail Andrabi; Suhel Parvez; Heena Tabassum

    2015-01-01

    Stroke is one of the most devastating neurological disabilities and brain's vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca2+ level, and so forth. Melatonin ...

  10. Light and melatonin schedule neuronal differentiation in the habenular nuclei

    de Borsetti, Nancy Hernandez; Dean, Benjamin J; Bain, Emily J.; Clanton, Joshua A.; Robert W. Taylor; Gamse, Joshua T

    2011-01-01

    The formation of the embryonic brain requires the production, migration, and differentiation of neurons to be timely and coordinated. Coupling to the photoperiod could synchronize the development of neurons in the embryo. Here, we consider the effect of light and melatonin on the differentiation of embryonic neurons in zebrafish. We examine the formation of neurons in the habenular nuclei, a paired structure found near the dorsal surface of the brain adjacent to the pineal organ. Keeping embr...

  11. Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases

    Huey-Kang Sytwu

    2013-05-01

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

  12. Paroxysmal nocturnal hemoglobinuria: rare cause of acute renal failure

    Vilma Takayasu

    2012-12-01

    Full Text Available Paroxysmal nocturnal hemoglobinuria is a rare acquired disease, characterized by hemolytic anemia, recurrent infections, cytopenias, and vascular thrombosis. It occurs by non-malignant clonal expansion of one or more hematopoietic stem cells that acquired somatic mutations in PIG-A gene linked to chromosome X. This mutation results in lower erythrocyte expression of CD55 and CD59 surface proteins and consequently increased susceptibility to the complement system. The renal involvement is generally benign, resulting in mild impairment in urinary concentration. Acute renal failure requiring hemodialytic support accompanying PNH is rarely observed. The authors report a case of a 37-year-old male who presented with bicytopenia (hemolytic anemia and thrombocytopenia associated with acute renal failure requiring dialysis. Diagnosis was challenging because of the rarity and unfamiliarity with this entity, but was confirmed by flow cytometry. In the course of the disease, acute pyelonephritis with multiple renal abscesses was diagnosed requiring prolonged antibiotic therapy. Patient outcome was favorable after the control of hemolysis and the infection treatment.

  13. Brainstem evaluation in children with primary nocturnal enuresis.

    Unal M

    2004-02-01

    Full Text Available We investigated the brainstem integrity in children with primary nocturnal enuresis (PNE using auditory brainstem responses (ABR, blink reflex and exteroceptive suppression of the masseter muscle. We examined 23 children with PNE (16 male, 7 female; mean age: 10.4 years and 19 control subjects (11 male, 8 female; mean age: 11.8 years. ABR parameters such as wave latencies, amplitudes and interpeak latencies and blink reflex parameters such as R1 and R2 amplitude and latencies were not significantly different between the 2 groups. Although S2 parameters of the exteroceptive suppression of the masseter muscle were easily and completely obtained from the control subjects, in the PNE group S2 onset latency and duration were not recorded in 26% of the study children (n = 6 (P = 0.01. S2 duration time was significantly lowered in the enuretic group (left side: P = 0.001 and right side: P = 0.003. S2 duration time changes in the enuretic group supports a possible brainstem dysfunction in children with PNE.

  14. Haploidentical hematopoietic stem cell transplant in paroxysmal nocturnal hemoglobinuria.

    Tian, Hong; Liu, Liming; Chen, Jia; Xu, Yang; Jin, Zhengming; Miao, Miao; Fu, Zhengzheng; Qiu, Huiying; Sun, Aining; Wu, Depei

    2016-04-01

    Eighteen patients with paroxysmal nocturnal hemoglobinuria (PNH) receiving allogeneic hematopoietic stem cell transplant (allo-HSCT), either from HLA-haploidentical donors (HRD; n = 10) or HLA-matched donors (n = 5 from siblings and n = 3 from unrelated donors), were retrospectively evaluated. One showed primary graft failure following unrelated-donor HSCT. He was given a second HRD-HSCT, but died from cytomegalovirus pneumonia after achieving hematopoietic recovery. The other 17 patients achieved sustained engraftment and full-donor chimerism. Four in the HRD-HSCT group experienced grade II/III acute graft-versus-host disease (aGVHD), and five in the HLA-matched HSCT group developed grade II aGVHD. Among all 18 patients, 10 developed chronic GVHD (cGVHD), only one patient receiving HRD-HSCT developed extensive cGVHD. Nine in the HRD-HSCT group and all those in the HLA-matched HSCT group were alive and transfusion-independent at last follow-up. Our findings suggest that allo-HSCT is a promising treatment for PNH, and HRD-HSCT is a viable option for patients with PNH who lack HLA-matched donors. PMID:26911378

  15. Deficiency of the homologous restriction factor in paroxysmal nocturnal hemoglobinuria.

    Zalman, L S; Wood, L M; Frank, M M; Müller-Eberhard, H J

    1987-02-01

    The affected E of two patients with paroxysmal nocturnal hemoglobinuria (PNH) were enriched by lysing the unaffected, normal E with anti-human decay-accelerating factor (DAF) and guinea pig serum. The membranes of the unlysed, DAF-deficient cells (PNH-E) were dissolved and examined by SDS-PAGE and immunoblotting using an antiserum to homologous restriction factor (HRF). Whereas the 65 kD complement regulatory protein was readily detectable in the normal controls, it was completely lacking in both samples of PNH-E membranes. Functional studies likewise indicated the absence of HRF activity from PNH-E. When radiolabeled, isolated HRF protein was offered to PNH-E, it became firmly attached to the cell. Approximately 1,000 molecules of HRF per cell reduced the characteristic susceptibility of these cells to reactive lysis by C5b-9 to nearly normal levels. The results suggest that HRF, which is known to control the action of C8 and C9 on normal human E membranes, is deficient in PNH, as well as acetylcholinesterase and DAF. PMID:2434597

  16. A Moessbauer study of hemoglobin in paroxysmal nocturnal hemoglobinuria

    The 57Fe Moessbauer spectra of concentrated hemoglobin (Hb) of normal subjects and six patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) were studied at 300deg K and 77 K. PNH is a very rate autoimmune hematological disease. The possibility of structural alterations of Hb induced by, or as part of the altered PNH-red cell membrane was the objective of this study. The Moessbauer parameters of the Hb of the normal subjects, both at 300 K and at 77 K, are identical to values previously reported. The PNH-Hb spectra show clear differences. They are wider and more asymmetric. At 77 K, an extra doublet grows in with an isomer shift of 0.425 mm/sec. and a quadrupolar splitting of 1.951 mm/sec. The other two doublets have ?'s and ?Q's slightly, but significantly, different from the corresponding values for normal Hb. These results are rationalized in terms of a population of Hb molecules with structures varying very slightly in a narrow range. The spread in structures manifests itself in a wider and more asymmetric Moessbauer spectrum. (orig.)

  17. [Investigation on apoptosis in paroxysmal nocturnal hemoglobinuria (PNH) granulocytes].

    Shichishima, T

    2001-10-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematologic disordr characterized by increased susceptibility of erythrocytes to complement-mediated hemolysis. Recently, PNH is a stem cell disorder with all hematopoietic lineages affected, which have deficiencies of glycosylphosphtidylinositol-anchored membrane proteins due to the phosphatidylinositol glycan-class A (PIG-A) gene abnormalities. However, it is unknown how PNH clones with PIG-A gene abnormalities increase in bone marrow. The possibility has been suggested that resistance of PNH cells to apoptosis causes the increase. We studied two-color or single-color flow cytometric analysis using Annexin V and propidium iodide or 7-amino actinomycin D for evaluation of spontaneous apoptosis in peripheral blood granulocytes from PNH patient (n = 5) and healthy volunteers (n = 5), respectively. Apoptotic granulocytes were evaluated before and after 6-, 12-, 18- and 24-hour cultures without serum. Flow cytometric analyses showed that there were no significant differences of the number of proportion of apoptotic cells between them. This fact reveals that the sensitivity of PNH cells to apoptosis is similar to that of normal cells, suggesting that PNH clones should not be increased according to resistance to apoptosis as an intrinsic characteristic. PMID:11769477

  18. [Paroxysmal nocturnal hemoglobinuria (PNH). Pathogenesis, diagnosis and treatment].

    Röth, A; Dührsen, U; Schrezenmeier, H; Schubert, J

    2009-02-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the classic clinical triad of corpuscular hemolytic anemia, thrombophilia and cytopenia. This is caused by an acquired mutation of the PIG(phosphatidylinositol glycan)-A gene of the pluripotent hematopoetic stem cell. This results in a deficiency of GPI(glycosylphosphatidylinositol)-anchors and GPI-anchored proteins on the surface of affected blood cells. Flow cytometry is the standard for diagnosis and measurement of type and size of the PNH clone. Treatment of PNH is mainly symptomatic. Allogeneic bone marrow transplantation is the only curative option in case of severe complications during the course of the diseases. A new targeted treatment strategy is the inhibition of the terminal complement cascade with a monoclonal antibody (eculizumab). As shown in clinical studies this is efficient to reduce complement mediated intravascular hemolysis, reduce the need for transfusions, improve the quality of life in patients with PNH and reduce the risk for thromboembolic complications, which are the main cause of mortality in PNH. PMID:19224425

  19. Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy

    Jiang, Tingting; Cai, Jiyang; Fan, Jiawen; Zhang, Xiaozhe

    2016-01-01

    Oxidative stress and inflammation are important pathogenic factors contributing to the etiology of diabetic retinopathy (DR). Melatonin is an endogenous hormone that exhibits a variety of biological effects including antioxidant and anti-inflammatory functions. The goals of this study were to determine whether melatonin could ameliorate retinal injury and to explore the potential mechanisms. Diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Melatonin (10 mg kg−1 daily, i.p.) was administered from the induction of diabetes and continued for up to 12 weeks, after which the animals were sacrificed and retinal samples were collected. The retina of diabetic rats showed depletion of glutathione and downregulation of glutamate cysteine ligase (GCL). Melatonin significantly upregulated GCL by retaining Nrf2 in the nucleus and stimulating Akt phosphorylation. The production of proinflammatory cytokines and proteins, including interleukin 1β, TNF-α, and inducible nitric oxide synthase (iNOS), was inhibited by melatonin through the NF-κB pathway. At 12 weeks, melatonin prevented the significant decrease in the ERG a- and b-wave amplitudes under the diabetic condition. Our results suggest potent protective functions of melatonin in diabetic retinopathy. In addition to being a direct antioxidant, melatonin can exert receptor-mediated signaling effects to attenuate inflammation and oxidative stress of the retina.

  20. Ultrastructural evidence of a secretory role for melatonin in the human parotid gland.

    Loy, F; Isola, M; Isola, R; Solinas, P; Lilliu, M A; Puxeddu, R; Ekstrom, J

    2015-12-01

    In vivo animal studies show that pentagastrin, cholecystokinin and melatonin cause the secretion and synthesis of salivary proteins. Melatonin occurs in large amounts in the gut and is released into the blood on food intake. In vitro experiments suggest that pentagastrin exerts secretory activity in human salivary glands, as judged by ultrastructural changes, reflecting secretion, and an actual protein output. Currently, it is hypothesised that melatonin induces secretory exocytotic events in the human parotid gland. Human parotid tissues were exposed to a high single concentration of melatonin in vitro, processed for high resolution scanning electron microscopy and then assessed morphometrically with the emphasis on the membrane of the intercellular canaliculi, a site of protein secretion. Compared with controls and in terms of density, the melatonin-exposed parotid tissues displayed increases in protrusions (signalling anchored granules) and microbuds (signalling membrane recycling and/or vesicle secretion) and decreases in microvilli (signalling cytoskeletal re-arrangement related to exocytosis), phenomena abolished or very largely reduced by the melatonin receptor blocker, luzindole. In conclusion, acinar serous cells of parotid tissue displayed in vitro exocytotic activity to melatonin, signalling protein secretion. Whether, under physiological conditions, melatonin influences the secretion of human parotid glands remains to be explored, however. PMID:26769834

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

    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.

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

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

    2008-01-01

    intravenously up to 60 mg in the intraoperative phase was safe and without complications. Melatonin may decrease oxidative damage resulting from surgery, but randomized clinical trials are required before definitive conclusions can be drawn regarding the clinical benefit of melatonin in surgical situations....

  3. Melatonin Treatment in Individuals with Intellectual Disability and Chronic Insomnia: A Randomized Placebo-Controlled Study

    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…

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

    G. Take

    2009-07-01

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

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

    Wilhelmsen, Michael; Rosenberg, Jacob; Gögenur, Ismail

    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 brie...

  6. Oxidative stress in relation to surgery: is there a role for the antioxidant melatonin?

    Kücükakin, Bülent; Gögenur, Ismail; Reiter, Russel J; Rosenberg, Jacob

    2009-01-01

    antioxidant and in many studies melatonin has been shown to be more effective than some "classical" antioxidants (e.g., vitamins E and C) in protecting against oxidative/nitrosative stress. There are numerous experimental studies in which the antioxidant properties of melatonin have been proven. In...

  7. Micronuclei Assessment of The Radioprotective Effects of Melatonin and Vitamin C in Human Lymphocytes

    Rostami, Aram; Moosavi, Seyed Akbar; Dianat Moghadam, Hassan; Bolookat, Eftekhar Rajab

    2016-01-01

    Objective Critical macromolecules such as DNA maybe damaged by free radicals that are generated from the interaction of ionizing radiation with biological systems. Melatonin and vitamin C have been shown to be direct free radical scavengers. The aim of this study was to investigate the in vivo/in vitro radioprotective effects of melatonin and vitamin C separately and combined against genotoxicity induced by 6 MV x-ray irradiation in human cultured blood lymphocytes. Materials and Methods In this experimental study, fifteen volunteers were divided into three groups of melatonin, vitamin C and melatonin plus vitamin C treatment. Peripheral blood samples were collected from each group before, and 1, 2 and 3 hours after melatonin and vitamin C administration (separately and combined). The blood samples were then irradiated with 200 cGy of 6 MV x-ray. In order to characterize chromosomal aberrations, the lymphocyte samples were cultured with mitogenic stimulus on cytokinesisblocked binucleated cells. Results The samples collected 1hour after melatonin and vitamin C (separately and combined) ingestion exhibited a significant decrease in the incidence of micronuclei compared with their control group (P<0.05). The maximum synergic protection and reduction in frequency of micronuclei (57%) was observed 1 hour after vitamin C and melatonin administration combined. Conclusion We conclude that simultaneous administration of melatonin and vitamin C as radioprotector substances before irradiation may reduce genotoxicity caused by x-ray irradiation. PMID:27054118

  8. No effect of melatonin to modify surgical-stress response after major vascular surgery

    Kücükakin, B.; Wilhelmsen, M.; Lykkesfeldt, Jens; Reiter, R.J.; Rosenberg, J.; Gögenur, I.

    2010-01-01

    A possible mechanism underlying cardiovascular morbidity after major vascular surgery may be the perioperative ischaemia-reperfusion with excessive oxygen-derived free-radical production and increased levels of circulating inflammatory mediators. We examined the effect of melatonin infusion durin...... surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress....

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

    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.

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

    Hsiao-Wen Lin

    2009-03-01

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

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

    Wilhelmsen, Michael; Rosenberg, Jacob; Gögenur, Ismail

    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...

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

    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

    2015-01-01

    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

  13. Melatonin, a potential effective protector in whole body γ-irradiated rats

    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 γ-irradiated rats. Animals received melatonin (10 mg/ kg body wt/ day) for 10 successive days pre-exposure to 3 Gy of γ-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 γ-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.

  14. Effects of moonlight exposure on plasma melatonin rhythms in the seagrass rabbitfish, Siganus canaliculatus.

    Rahman, Md Saydur; Kim, Byung-Ho; Takemura, Akihiro; Park, Chang-Bum; Lee, Young-Don

    2004-08-01

    Influences of light-dark (LD) cycle and moonlight exposure on plasma melatonin rhythms in the seagrass rabbitfish, Siganus canaliculatus, a lunar synchronized spawner, were determined by time-resolved fluoroimmunoassay (TR-FIA). When the fish were exposed to a natural LD (12:12) cycle, plasma melatonin levels exhibited a clear daily rhythm, with higher levels at midnight and lower levels during the day. These rhythms were not evident under either constant light (LL) or constant dark (DD) conditions. Plasma melatonin levels under LL condition were low and high under DD condition. These results indicate that plasma melatonin rhythms are driven by LD cycle in this species. When the fish were exposed to the 4 lunar phases, plasma melatonin levels around the new moon were significantly higher than during the first quarter moon and the full moon. Exposure to experimental new moon and full moon conditions caused significant increases and decreases of plasma melatonin levels, respectively. The synchronous rhythmicity of melatonin levels in the plasma support the hypothesis that the seagrass rabbitfish perceives moonlight intensity and responds with secretion of melatonin into the bloodstream. PMID:15245651

  15. Duration of melatonin regulates seasonal plasticity in subtropical Indian weaver bird, Ploceus philippinus.

    Surbhi; Kumari, Yatinesh; Rani, Sangeeta; Tsutsui, Kazuyoshi; Kumar, Vinod

    2015-09-01

    Day length regulates seasonal plasticity connected with reproduction in birds. Rhythmic pineal melatonin secretion is a reliable indicator of the night length, hence day length. Removal of rhythmic melatonin secretion by exposure to constant bright light (LLbright) or by pinealectomy renders several species of songbirds including Indian weaver bird (Ploceus philippinus) arrhythmic. Present study investigated whether rhythmic melatonin is involved in the regulation of key reproductive neuropeptides (GnRH I and GnIH) and reproduction linked neural changes, viz. song control nuclei, in Indian weaver birds. Two experiments were performed using birds in an arrhythmic condition with low (under LLbright) or no (in the absence of pineal gland) endogenous melatonin. In experiment I, three groups of birds (n=5 each) entrained to 12L:12D were exposed to LLbright (25lux) for two weeks. Beginning on day 15 of LLbright, a control group received vehicle for 16h and two treatment groups were given melatonin in drinking water for 8h or 16h. In experiment II, one group of sham-operated and three groups of pinealectomized birds (n=5 each) entrained to 12L:12D were exposed to constant dim light (LLdim, 0.5lux). Beginning on day 15 of LLdim, three groups received similar treatment as in experiment I. Birds were perfused after thirty cycles of the melatonin treatment, and brain sections were immunohistochemically double-labeled for GnRH I and GnIH or Nissl stained. Activity was recorded throughout the experiments, while body mass and testes were measured at the beginning and end of the experiment. Birds were synchronized with melatonin cycles and measured the duration of melatonin as "night". Pinealectomized birds that received 16h of melatonin had significantly higher GnIH-ir cells than those received 8h melatonin; there was no difference in the GnRH I immunoreactivity between two treatment groups however. Intact birds that received long duration melatonin cycles exhibited small song control nuclei, specifically the high vocal center (HVC) and the robust nucleus of the arcopallium (RA), while birds that received short duration melatonin or no melatonin exhibited large HVC and RA. Thus, melatonin possibly regulates seasonal reproduction via GnIH secretion, and also controls seasonal neuroplasticity in the song control system in songbirds. PMID:24932714

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

    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......, Denmark. Women, 30-75 years, undergoing surgery for breast cancer and without signs of depression on Major Depression Inventory (MDI) were included 1 week before surgery and received 6 mg oral melatonin or placebo for 3 months. The primary outcome was the incidence of depressive symptoms measured by MDI....... The secondary outcomes were area under the curve (AUC) for the subjective parameters. 54 patients were randomized to melatonin (n = 28) or placebo (n = 26) and 11 withdrew from the study (10 placebo group and 1 melatonin group, P = 0.002). The risk of developing depressive symptoms was significantly...

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

    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.

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

    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.

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

    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.

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

    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.

  1. Potential Relevance of Melatonin Against Some Infectious Agents: A Review and Assessment of Recent Research.

    Elmahallawy, Ehab Kotb; Luque, Javier Ortega; Aloweidi, Abdelkarim Saleh; Gutiérrez-Fernández, José; Sampedro-Martínez, Antonio; Rodriguez-Granger, Javier; Kaki, Abdullah; Agil, Ahmad

    2015-01-01

    Melatonin, a tryptophan-derived neurohormone found in animals, plants, and microbes, participates in various biological and physiological functions. Among other properties, numerous in vitro or in vivo studies have reported its therapeutic potential against many parasites, bacteria and viruses. In this concern, melatonin was found to be effective against many parasites such as Plasmodium, Toxoplasma gondii, and Trypansoma cruzi, via various mechanisms such as modulation of calcium level and/or host immune system. Likewise, a recent investigation has reported in vitro activity of melatonin against Leishmania infantum promastigotes which is the causative agent of fascinating visceral Leishmaniasis. This review was initially undertaken to summarize some facts about certain physiological and therapeutic effects of melatonin. It also reviews the effects and action mechanisms of melatonin in bacterial and viral infection besides biology of different parasites which may provide a promising strategy for control of many diseases of public health importance. PMID:26310920

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

    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

  3. Clock-Controlled Regulation of the Acute Effects of Norepinephrine on Chick Pineal Melatonin Rhythms.

    Li, Ye; Cassone, Vincent M

    2015-12-01

    The chicken pineal gland synthesizes and releases melatonin rhythmically in light/dark (LD) cycles, with high melatonin levels during the dark phase, and in constant darkness (DD) for several cycles before it gradually damps to arrhythmicity in DD. Daily administration of norepinephrine (NE) in vivo and in vitro prevents the damping and restores the melatonin rhythm. To investigate the role of the circadian clock on melatonin rhythm damping and of its restoration by NE, the effects of NE administration at different phases of the melatonin cycle revealed a robust rhythm in NE sensitivity in which NE efficacy in increasing melatonin amplitude peaked in late subjective night and early subjective day, suggesting a clock underlying NE sensitivity. However, NE itself had no effect on circadian phase or period of the melatonin rhythms. Transcriptional analyses indicated that even though the rhythm of melatonin output damped to arrhythmicity, messenger RNA (mRNA) encoding clock genes gper2, gper3, gBmal1, gclock, gcry1, and gcry2; enzymes associated with melatonin biosynthesis; and enzymes involved in cyclic nucleotide signaling remained robustly rhythmic. Of these, only gADCY1 (adenylate cyclase 1) and gPDE4D (cAMP-specific 3',5'-cyclic phosphodiesterase 4D) were affected by NE administration at the mRNA levels, and only ADCY1 was affected at the protein level. The data strongly suggest that damping of the melatonin rhythm in the chick pineal gland occurs at the posttranscriptional level and that a major role of the clock is to regulate pinealocytes' sensitivity to neuronal input from the brain. PMID:26446873

  4. Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy

    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

  5. Melatonin attenuates sepsis-induced cardiac dysfunction via a PI3K/Akt-dependent mechanism.

    An, Rui; Zhao, Lei; Xi, Cong; Li, Haixun; Shen, Guohong; Liu, Haixiao; Zhang, Shumiao; Sun, Lijun

    2016-01-01

    Myocardial dysfunction is an important manifestation of sepsis. Previous studies suggest that melatonin is protective against sepsis. In addition, activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway has been reported to be beneficial in sepsis. However, the role of PI3K/Akt signaling in the protective effect of melatonin against sepsis-induced myocardial dysfunction remains unclear. Here, LY294002, a PI3K inhibitor, was used to investigate the role of PI3K/Akt signaling in mediating the effects of melatonin on sepsis-induced myocardial injury. Cecal ligation and puncture (CLP) surgery was used to establish a rat model of sepsis. Melatonin was administrated to rats intraperitoneally (30 mg/kg). The survival rate, measures of myocardial injury and cardiac performance, serum lactate dehydrogenase level, inflammatory cytokine levels, oxidative stress level, and the extent of myocardial apoptosis were assessed. The results suggest that melatonin administration after CLP surgery improved survival rates and cardiac function, attenuated myocardial injury and apoptosis, and decreased the serum lactate dehydrogenase level. Melatonin decreased the production of the inflammatory cytokines TNF-?, IL-1?, and HMGB1, increased anti-oxidant enzyme activity, and decreased the expression of markers of oxidative damage. Levels of phosphorylated Akt (p-Akt), unphosphorylated Akt (Akt), Bcl-2, and Bax were measured by Western blot. Melatonin increased p-Akt levels, which suggests Akt pathway activation. Melatonin induced higher Bcl-2 expression and lower Bax expression, suggesting inhibition of apoptosis. All protective effects of melatonin were abolished by LY294002, the PI3K inhibitor. In conclusion, our results demonstrate that melatonin mitigates myocardial injury in sepsis via PI3K/Akt signaling activation. PMID:26671026

  6. Esophagoprotection mediated by exogenous and endogenous melatonin in an experimental model of reflux esophagitis.

    Konturek, Peter C; Brzozowska, Iwona; Targosz, Aneta; Pawlik, Michal; Kania, Joanna; Hess, Thomas; Kwiecien, Slawomir; Konturek, Stanislaw J; Reiter, Russel J; Brzozowski, Tomasz

    2013-08-01

    Reflux esophagitis is a common clinical entity in western countries with approximately 30% of the population experiencing the symptoms at least once every month. The imbalance between the protective and aggressive factors leads to inflammation and damage of the esophageal mucosa. We compared the effect of exogenous melatonin and melatonin derived endogenously from L-tryptophan with that of pantoprazole or ranitidine in acid reflux esophagitis due to ligation of the rat pylorus and the limiting ridge between the forestomach and the corpus. Four hours after the induction of gastric reflux, an increase in mucosal lesions associated with edema of the submucosa and with the infiltration of numerous neutrophils and the fall in esophageal blood flow (EBF) were observed. Both melatonin and L-tryptophan or pantoprazole significantly reduced the lesion index (LI) and raised the EBF. Pinealectomy that significantly decreased plasma melatonin levels aggravated LI and these effects were reduced by melatonin and L-tryptophan. Luzindole, the MT2 receptor antagonist, abolished the melatonin-induced reduction in LI and the rise in EBF. L-NNA and capsaicin that augmented LI and decreased EBF, also significantly reduced melatonin-induced protection and hyperemia; both were restored with L-arginine and calcitonin gene-related peptide (CGRP) added to melatonin. Upregulation of IL-1β and TNF-α mRNAs and plasma IL-1β and TNF-α levels were significantly attenuated by melatonin and L-tryptophan. We conclude that melatonin protects against acid reflux-induced damage via activation of MT2 receptors mediated by NO and CGRP released from sensory nerves and the suppression of expression and release of TNF-α and IL-1β. PMID:23480366

  7. Protective effects of melatonin against thioacetamide-induced liver fibrosis in rats.

    Czechowska, G; Celinski, K; Korolczuk, A; Wojcicka, G; Dudka, J; Bojarska, A; Reiter, R J

    2015-08-01

    The aim of this study was to determine the effect of melatonin on thioacetamide (TAA) induced liver fibrosis in rats. The antifibrotic effects of melatonin were assessed by determining activity indirect markers of fibrosis: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and proinflammatory cytokines: interleukin 6 (IL-6), interleukin-1beta (IL-1β), tumour necrosis factor alpha (TNF-α), transforming growth factor-beta (TGF-β) and platelet-derived growth factor (PDGF). Parameters of oxidative stress: oxidised glutathione (GSSG), reduced glutathione (GSH) and presaged activity of paraoxonase 1 (PON-1), an antioxidative enzyme were determined. Inflammatory changes and fibrosis extent were evaluated histologically. Experiments were carried out in Wistar rats. Animals were divided into 4 groups: I - controls, water ad libitum for 12 weeks, group II - TAA, 300 mg/L ad libitum for 12 weeks, III - melatonin, 10 mg/kg b.w. intraperitoneally (i.p.) daily for 4 weeks, IV - TAA, 300 mg/L ad libitum for 12 weeks followed by melatonin, 10 mg/kg/b.w. i.p. daily for 4 weeks. Results of serum determinations demonstrated significantly lower activity of AST, ALT and AP in the group receiving TAA followed by melatonin compared to the group receiving only TAA. Immunoenzymatic findings on effect of melatonin on concentration of proinflammatory cytokines confirmed these data. Biochemical examinations in liver homogenates revealed statistically significant improvement (concentration of GSH increases and concentration of GSSG decreases) in animals with TAA-induced liver damage receiving melatonin. Moreover, the activity of PON-1 toward phenyl acetate and paraoxon was increased in liver homogenates and serum in the group receiving TAA followed by melatonin compared to the TAA group without melatonin treatment. Microscopic evaluation disclosed inhibitory effects of melatonin on inflammatory changes and extent of liver fibrosis. PMID:26348081

  8. Melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, attenuates TNBS-induced colitis in mice.

    Zielińska, Marta; Jarmuż, Agata; Sałaga, Maciej; Kordek, Radzisław; Laudon, Moshe; Storr, Martin; Fichna, Jakub

    2016-05-01

    Melatonin is known as a strong antioxidant and possesses anti-inflammatory properties. Recently, melatonin was shown to improve colitis in animal models of inflammatory bowel diseases. The aim of the present study was to characterize the role of melatonin receptors (MT) in the anti-inflammatory effect of melatonin and to assess the anti-inflammatory potential of two novel MT receptor agonists, Neu-P11 and Neu-P67, in the mouse model of trinitrobenzenesulfonic acid (TNBS)-induced colitis. Colitis was induced on day 1 by intracolonic (i.c.) administration of TNBS in 30 % ethanol in saline. Melatonin (4 mg/kg, per os (p.o.)), Neu-P11 (20 mg/kg, p.o.; 50 mg/kg, intraperitoneally (i.p.), 50 mg/kg, i.c.), and Neu-P67 (20 mg/kg, p.o.) were given twice daily for 3 days. Luzindole (5 mg/kg, i.p.) was injected 15 min prior to melatonin administration. On day 4, macroscopic and microscopic damage scores were assessed and myeloperoxidase (MPO) activity quantified using O-dianisidine-based assay. Melatonin significantly attenuated colitis in mice, as indicated by the macroscopic score (1.90 ± 0.34 vs. 3.82 ± 0.62 for melatonin- and TNBS-treated mice, respectively), ulcer score (0.87 ± 0.18 vs. 1.31 ± 0.19, respectively), and MPO activity (4.68 ± 0.70 vs.6.26 ± 0.94, respectively). Luzindole, a MT receptor antagonist, did not inhibit the anti-inflammatory effect of melatonin (macroscopic score 1.12 ± 0.22, ulcer score 0.50 ± 0.16); however, luzindole increased MPO activity (7.57 ± 1.05). MT receptor agonists Neu-P11 and Neu-P67 did not improve inflammation induced by TNBS. Melatonin, but not MT receptor agonists, exerts potent anti-inflammatory action in acute TNBS-induced colitis. Our data suggests that melatonin attenuates colitis by additional, MT receptor-independent pathways. PMID:26899972

  9. Prevalence of nocturnal enuresis and its associated factors in primary school and preschool children of khorramabad in 2013.

    Bakhtiar, Katayoun; Pournia, Yadollah; Ebrahimzadeh, Farzad; Farhadi, Ali; Shafizadeh, Fathollah; Hosseinabadi, Reza

    2014-01-01

    Background. Nocturnal enuresis refers to an inability to control urination during sleep. This study aimed to determine the prevalence of nocturnal enuresis and its associated factors in children in the city of Khorramabad. Materials and Methods. In this descriptive-analytic, cross-sectional study, 710 male and female children were divided into two groups with equal numbers. The samples were selected from the schools of Khorramabad using the multistage cluster and stratified random sampling methods based on the diagnostic criteria of DSM-IV. The data was analyzed using the logistic regression. Results. The results showed that 8% of the children had nocturnal enuresis, including 5.2% of primary nocturnal enuresis and 2.8% of secondary nocturnal enuresis. The prevalence of nocturnal enuresis in the boys (10.7%) was higher compared with that in the girls (5.4%) (P = 0.009). There were statistically significant relationships between nocturnal enuresis and history of nocturnal enuresis in siblings (P = 0.023), respiratory infections (P = 0.036), deep sleep (P = 0.007), corporal punishment at school (P = 0.036), anal itching (P = 0.043), and history of seizures (P = 0.043). Conclusion. This study showed that the prevalence of nocturnal enuresis in the boys was higher compared with that in the girls. PMID:25374608

  10. Melatonin in the thyroid gland: regulation by thyroid-stimulating hormone and role in thyroglobulin gene expression.

    Garcia-Marin, R; Fernandez-Santos, J M; Morillo-Bernal, J; Gordillo-Martinez, F; Vazquez-Roman, V; Utrilla, J C; Carrillo-Vico, A; Guerrero, J M; Martin-Lacave, I

    2015-10-01

    Melatonin is an indoleamine with multiple functions in both plant and animal species. In addition to data in literature describing many other important roles for melatonin, such as antioxidant, circadian rhythm controlling, anti-aging, antiproliferative or immunomodulatory activities, our group recently reported that thyroid C-cells synthesize melatonin and suggested a paracrine role for this molecule in the regulation of thyroid activity. To discern the role played by melatonin at thyroid level and its involvement in the hypothalamic-pituitary-thyroid axis, in the present study we have analyzed the effect of thyrotropin in the regulation of the enzymatic machinery for melatonin biosynthesis in C cells as well as the effect of melatonin in the regulation of thyroid hormone biosynthesis in thyrocytes. Our results show that the key enzymes for melatonin biosynthesis (AANAT and ASMT) are regulated by thyroid-stimulating hormone. Furthermore, exogenous melatonin increases thyroglobulin expression at mRNA and protein levels on cultured thyrocytes and this effect is not strictly mediated by the upregulation of TTF1 or, noteworthy, PAX8 transcription factors. The present data show that thyroid C-cells synthesize melatonin under thyroid-stimulating hormone control and, consistently with previous data, support the hypothesis of a paracrine role for C-cell-synthesised melatonin within the thyroid gland. Additionally, in the present study we show evidence for the involvement of melatonin in thyroid function by directly-regulating thyroglobulin gene expression in follicular cells. PMID:26579570

  11. Melatonin - a key to the evaluation of the effects of electric; Melatonin - Schluessel fuer die Bewertung der Wirkung elektrischer und magnetischer Felder?

    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.)

  12. Effect of oral melatonin on the date of the first ovulation after ovarian inactivity in mares under artificial photoperiod.

    Guillaume, D; Palmer, E

    1991-01-01

    Two experiments tested the hypothesis that exogenous melatonin (12 mg) given 4 h before dusk (evening melatonin), or near dawn (morning melatonin), would mimic a prolongation of the night and suppress stimulation of the ovaries induced by long days. Experiment 1 consisted of a non-stimulated control group, a control group stimulated by 14.5 h of light, a treated group stimulated with 14.5 h of light plus evening melatonin, a control group given 17.5 h of light and a treatment group given 17.5 h of light plus morning melatonin. The mean (+/- s.e.m.) intervals from the start of treatment to the first ovulation were 135 +/- 26, 68 +/- 4, 147 +/- 11, 94 +/- 6 and 107 +/- 13 days, respectively. Experiment 2 consisted of 3 groups exposed to 14.5 h of light, a control group and a morning and an evening melatonin group. The mean (+/- s.e.m.) intervals from treatment to first ovulation were 53 +/- 12, 62 +/- 8 and 101 +/- 5 days, respectively. Thus, evening melatonin suppressed the stimulatory effect of the applied light, but morning melatonin did not (P greater than 0.05). In non-treated mares, peripheral blood melatonin levels were higher at night than during the day. In the treated mares, very high plasma melatonin concentrations occurred 10-20 min after treatment and levels began to fall again immediately after this peak was reached. This decline was steeper after morning than the evening treatments. Conversely, the endogenous night-time plasma melatonin concentrations before the morning treatment were lower than the night-time levels measured in the treated animals. Two hypotheses are proposed: (a) exogenous treatment with melatonin in the morning is perceived as dusk and is followed by only approximately 5 h of high melatonin concentrations in the blood and (b) in the morning the mare is sensitive to light regardless of the presence of high levels of melatonin in her blood. PMID:1795267

  13. Melatonin stimulates the nonamyloidogenic processing of ?APP through the positive transcriptional regulation of ADAM10 and ADAM17.

    Shukla, Mayuri; Htoo, Htut Htut; Wintachai, Phitchayapak; Hernandez, Jean-Francois; Dubois, Claire; Postina, Rolf; Xu, Huaxi; Checler, Frédéric; Smith, Duncan R; Govitrapong, Piyarat; Vincent, Bruno

    2015-03-01

    Melatonin controls many physiological functions including regulation of the circadian rhythm and clearance of free radicals and neuroprotection. Importantly, melatonin levels strongly decrease as we age and patients with Alzheimer's disease (AD) display lower melatonin than age-matched controls. Several studies have reported that melatonin can reduce aggregation and toxicity of amyloid-? peptides that are produced from the ?-amyloid precursor protein (?APP). However, whether melatonin can directly regulate the ?APP-cleaving proteases ('secretases') has not been investigated so far. In this study, we establish that melatonin stimulates the ?-secretase cleavage of ?APP in cultured neuronal and non-neuronal cells. This effect is fully reversed by ADAM10- and ADAM17-specific inhibitors and requires both plasma membrane-located melatonin receptor activation, and ERK1/2 phosphorylation. Moreover, we demonstrate that melatonin upregulates both ADAM10 and ADAM17 catalytic activities and endogenous protein levels. Importantly, genetic depletion of one or the other protease in mouse embryonic fibroblasts prevents melatonin stimulating constitutive and PKC-regulated sAPP? secretion and ADAM10/ADAM17 catalytic activities. Furthermore, we show that melatonin induces ADAM10 and ADAM17 promoter transactivation, and we identify the targeted promoter regions. Finally, we correlate melatonin-dependent sAPP? production with a protection against staurosporine-induced apoptosis. Altogether, our results provide the first demonstration that melatonin upregulates the nonamyloidogenic ADAM10 and ADAM17 proteases through melatonin receptor activation, ERK phosphorylation and the transactivation of some specific regions of their promoters and further underline the preventive rather than curative nature of melatonin regarding AD treatment. PMID:25491598

  14. Microalbuminuria in patients with non-insulin-dependent diabetes mellitus relates to nocturnal systolic blood pressure.

    Mitchell, T H

    2012-02-03

    PURPOSE: Microalbuminuria predicts early mortality in non-insulin-dependent-diabetes mellitus patients (NIDDM). Our objective in the present study was to compare and assess the relationship between 24-hour, day and nocturnal ambulatory blood pressure (BP) and urinary albumin excretion rate (UAE) in microalbuminuric and normoalbuminuric NIDDM and in normal control subjects. PATIENTS AND METHODS: In the present cross-sectional study, 24 hour ambulatory BP (daytime BP and nocturnal BP) and HbA1c were compared in microalbuminuric (n = 10) and nonmicroalbuminuric NIDDM patients (n = 10) and in nondiabetic controls (n = 9). None of the patients were taking antihypertensive agents. RESULTS: In the microlbuminuric group, whereas 24 hour and daytime systolic BP differed significantly from control values (P < 0.025 and P < 0.05 respectively), there was no difference between diabetic groups. However, nocturnal systolic BP in the microalbuminuric group was significantly higher than in the normoalbuminuric diabetic patients (139 vs. 125) (P < 0.05) and a significant difference was also found between the NIDDM patients and the control group (139, 125 vs. 114) (P < 0.025). In multiple regression analysis, only nocturnal systolic BP showed a significant relationship with UAE (P < 0.05). CONCLUSIONS: We suggest that the higher nocturnal systolic blood pressure seen in our microalbuminuric NIDDM patients may contribute to the increased morbidity in this group.

  15. The vomeronasal complex of nocturnal strepsirhines and implications for the ancestral condition in primates.

    Garrett, Eva C; Dennis, John C; Bhatnagar, Kunwar P; Durham, Emily L; Burrows, Anne M; Bonar, Christopher J; Steckler, Natalie K; Morrison, Edward E; Smith, Timothy D

    2013-12-01

    This study investigates the vomeronasal organ in extant nocturnal strepsirhines as a model for ancestral primates. Cadaveric samples from 10 strepsirhine species, ranging from fetal to adult ages, were studied histologically. Dimensions of structures in the vomeronasal complex, such as the vomeronasal neuroepithelium (VNNE) and vomeronasal cartilage (VNC) were measured in serial sections and selected specimens were studied immunohistochemically to determine physiological aspects of the vomeronasal sensory neurons (VSNs). Osteological features corresponding to vomeronasal structures were studied histologically and related to 3-D CT reconstructions. The VNC consistently rests in a depression on the palatal portion of the maxilla, which we refer to as the vomeronasal groove (VNG). Most age comparisons indicate that in adults VNNE is about twice the length compared with perinatal animals. In VNNE volume, adults are 2- to 3-fold larger compared with perinatal specimens. Across ages, a strong linear relationship exists between VNNE dimensions and body length, mass, and midfacial length. Results indicate that the VNNE of nocturnal strepsirhines is neurogenic postnatally based on GAP43 expression. In addition, based on Olfactory Marker Protein expression, terminally differentiated VSNs are present in the VNNE. Therefore, nocturnal strepsirhines have basic similarities to rodents in growth and maturational characteristics of VSNs. These results indicate that a functional vomeronasal system is likely present in all nocturnal strepsirhines. Finally, given that osteological features such as the VNG are visible on midfacial bones, primate fossils can be assessed to determine whether primate ancestors possessed a vomeronasal complex morphologically similar to that of modern nocturnal strepsirhines. PMID:24249398

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

    P. Di Mascio

    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.

  17. Delayed onset of the diurnal melatonin rise in patients with Huntington's disease.

    Aziz, N Ahmad; Pijl, Hanno; Frölich, Marijke; Schröder-van der Elst, Janny P; van der Bent, Chris; Roelfsema, Ferdinand; Roos, Raymund A C

    2009-12-01

    Sleep disturbances are very prevalent in Huntington's disease (HD) patients and can substantially impair their quality of life. Accumulating evidence suggests considerable dysfunction of the hypothalamic suprachiasmatic nucleus (SCN), the biological clock, in both HD patients and transgenic mouse models of the disease. As melatonin has a major role in the regulation of sleep and other cyclical bodily activities and its synthesis is directly regulated by the SCN, we postulated that disturbed SCN function is likely to give rise to abnormal melatonin secretion in HD. Therefore, we compared 24 h melatonin secretion profiles between early stage HD patients and age-, sex- and body mass index-matched controls. Although mean diurnal melatonin levels were not different between the two groups (p = 0.691), the timing of the evening rise in melatonin levels was significantly delayed by more than 01:30 h in HD patients (p = 0.048). Moreover, diurnal melatonin levels strongly correlated with both motor (r = -0.70, p = 0.036) and functional impairment (r = +0.78, p = 0.013). These findings suggest a delayed sleep phase syndrome-like circadian rhythm disorder in early stage HD patients and suggest that melatonin levels may progressively decline with advancing disease. PMID:19562249

  18. Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin

    Hui Ming Chua

    2016-01-01

    Full Text Available Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used “off-label” to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58, whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.

  19. Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin.

    Chua, Hui Ming; Hauet Richer, Nathalie; Swedrowska, Magda; Ingham, Stephen; Tomlin, Stephen; Forbes, Ben

    2016-01-01

    Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used "off-label" to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58), whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance. PMID:26751472

  20. Pineal gland and melatonin influence on chronic alcohol consumption by hamsters.

    Rudeen, P K; Symmes, S K

    1981-02-01

    Male golden hamsters preferentially consume alcohol solution when given a free-choice between water and the alcohol solution. The pineal gland has been implicated as influencing the predilection for the ethanol solution. Melatonin, a pineal hormone, was administered either daily for 11 weeks as a subcutaneous injection (25 micrograms/animal) or weekly as a subcutaneous beeswax implant (1 mg melatonin/24 mg beeswax) for 5 weeks to hamsters allowed a free-choice between water or a 10% ethanol solution. Food, water and alcohol consumptions were measured on a daily basis. Animals treated by daily injection with melatonin consumed slightly less ethanol than animals not given melatonin. In light-deprived animals given chronic implants of melatonin, alcohol consumption was reduced when compared to alcohol consumption by light-deprived hamsters not receiving melatonin. Melatonin treatment also resulted in reducing daily total fluid intake as well as ethanol consumption in light-deprived hamsters. The results indicate that the pineal gland may influence fluid consumption in the hamster, and indirectly alters the propensity of the hamster to consume alcohol. PMID:7193879