WorldWideScience

Sample records for nocturnal melatonin elevation

  1. Association of Nocturnal Melatonin Secretion With Insulin Resistance in Nondiabetic Young Women

    OpenAIRE

    Mcmullan, Ciaran J.; Curhan, Gary C.; Schernhammer, Eva S.; Forman, John P.

    2013-01-01

    Exogenous melatonin ameliorates insulin resistance in animals, while among humans, polymorphisms in the melatonin receptor gene are associated with insulin resistance. We aimed to investigate the association of endogenous nocturnal melatonin secretion with insulin resistance in humans. We analyzed the association between endogenous nocturnal melatonin secretion, estimated by measuring the main melatonin metabolite, 6-sulfatoxymelatonin, from the first morning urinary void, and the prevalence ...

  2. Nocturnal cortisol and melatonin secretion in primary insomnia.

    Science.gov (United States)

    Riemann, Dieter; Klein, Torsten; Rodenbeck, Andrea; Feige, Bernd; Horny, Andrea; Hummel, Ruth; Weske, Gesa; Al-Shajlawi, Anam; Voderholzer, Ulrich

    2002-12-15

    The present study investigated evening and nocturnal serum cortisol and melatonin concentrations in patients with primary insomnia to test if this clinical condition is accompanied by an increase of cortisol secretion and a simultaneous decrease of nocturnal melatonin production. Ten drug-free patients (4 males, 6 females) with primary insomnia (mean age+/-S.D.: 39.2+/-9.1 years) and 10 age- and gender-matched healthy controls participated in the study. All subjects spent three consecutive nights in the sleep laboratory with polysomnography. Measurement of cortisol and melatonin (from 19:00 h to 09:00 h) was performed prior to and during the last laboratory night. Contrary to expectation, cortisol secretion did not differ between healthy controls and insomniac patients. On the other hand, nocturnal melatonin production was significantly diminished in insomniac patients. Polysomnographically determined sleep patterns, in contrast to subjective ratings of sleep, demonstrated only minor alterations of sleep in the insomniac group. The lack of increased cortisol secretion in the patients with primary insomnia indicates that results from studies on the biological consequences of experimental sleep loss in healthy subjects cannot be applied to primary insomnia in general, especially if there are only minor objective sleep alterations. In spite of the negligible objective sleep disturbances in the present sample, nocturnal melatonin production was reduced, which tentatively suggests a role for this hormone in primary insomniacs. The pathophysiological significance of this finding is, however, still a matter of debate. PMID:12467942

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

    OpenAIRE

    Fusani, Leonida; Gwinner, Eberhard

    2004-01-01

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

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

    Science.gov (United States)

    McMullan, Ciaran J; Curhan, Gary C; Schernhammer, Eva S; Forman, John P

    2013-07-15

    Exogenous melatonin ameliorates insulin resistance in animals, while among humans, polymorphisms in the melatonin receptor gene are associated with insulin resistance. We aimed to investigate the association of endogenous nocturnal melatonin secretion with insulin resistance in humans. We analyzed the association between endogenous nocturnal melatonin secretion, estimated by measuring the main melatonin metabolite, 6-sulfatoxymelatonin, from the first morning urinary void, and the prevalence of insulin resistance based on fasting blood samples collected in a cross-sectional study of 1,075 US women (1997-1999) without diabetes, hypertension, or malignancy. Urinary 6-sulfatoxymelatonin level was standardized to urinary creatinine level; insulin resistance was defined as an insulin sensitivity index value (using the McAuley formula) less than 7.85. Logistic regression models included adjustment for age, body mass index, smoking, physical activity, alcohol intake, dietary glycemic index, family history of diabetes mellitus, blood pressure, plasma total cholesterol, uric acid, and estimated glomerular filtration rate. Higher nocturnal melatonin secretion was inversely associated with insulin levels and insulin resistance. In fully adjusted models, the odds ratio for insulin resistance was 0.45 (95% confidence interval: 0.28, 0.74) among women in the highest quartile of urinary 6-sulfatoxymelatonin:creatinine ratio compared with women in the lowest quartile. Nocturnal melatonin secretion is independently and inversely associated with insulin resistance. PMID:23813704

  5. Circadian regulation of molecular, dietary, and metabolic signaling mechanisms of human breast cancer growth by the nocturnal melatonin signal and the consequences of its disruption by light at night.

    Science.gov (United States)

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

    2011-10-01

    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 MT(1) melatonin receptors expressed in human breast cancer cell lines and xenografts. In estrogen receptor (ER?+) human breast cancer cells, melatonin suppresses both ER? mRNA expression and estrogen-induced transcriptional activity of the ER? via MT(1) -induced activation of G(?i2) signaling and reduction of 3',5'-cyclic adenosine monophosphate (cAMP) levels. Melatonin also regulates the transactivation of additional members of the steroid hormone/nuclear receptor super-family, enzymes involved in estrogen metabolism, expression/activation of telomerase, and the expression of core clock and clock-related genes. The anti-invasive/anti-metastatic actions of melatonin involve the blockade of p38 phosphorylation and the expression of matrix metalloproteinases. Melatonin also inhibits the growth of human breast cancer xenografts via another critical pathway involving MT(1) -mediated suppression of cAMP leading to blockade of linoleic acid uptake and its metabolism to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Down-regulation of 13-HODE reduces the activation of growth factor pathways supporting cell proliferation and survival. Experimental evidence in rats and humans indicating that LAN-induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism, and signaling provides the strongest mechanistic support, thus far, for population and ecological studies demonstrating elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LAN. PMID:21605163

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

    Scientific Electronic Library Online (English)

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

    2009-05-01

    Full Text Available SciELO Spain | Language: Spanish Abstract in spanish Objetivo: Evaluar la supresión de la secreción nocturna de melatonina inducida por exposición a la luz en pacientes con neuropatías ópticas bilaterales. Métodos: Estudio clínico de casos controles, observacional y prospectivo. Tamaño muestral de 20 pacientes distribuidos en 3 grupos: Grupo A (n=5, 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).

  7. Melatonin

    Science.gov (United States)

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

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

    2000-01-01

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

  11. Melatonin

    Science.gov (United States)

    ... melatonin. It is not yet clear why this interaction occurs. Taking flumazenil (Romazicon) along with melatonin might ... Zenapax), muromonab-CD3 (OKT3, Orthoclone OKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus (Rapamune), prednisone (Deltasone, Orasone), corticosteroids ( ...

  12. URINARY MELATONIN IN DEPRESSION

    Science.gov (United States)

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

    1983-01-01

    SUMMARY 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

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

    Directory of Open Access Journals (Sweden)

    Kline Lawrence E

    2006-05-01

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

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

    OpenAIRE

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

    2012-01-01

    Melatonin and serotonin rhythms, which exhibit a close association with the endogenous circadian component of sleep, are attenuated with increasing age. This decrease seems to be linked to sleep alterations in the elderly. Chrononutrition is a field of chronobiology that establishes the principle of consuming foodstuffs at times of the day when they are more useful for health, improving, therefore, biorhythms and physical performance. Our aim was to analyze whether the consumption of cereals ...

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

    Scientific Electronic Library Online (English)

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

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

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

    DEFF Research Database (Denmark)

    EkelØf, Sarah V; Halladin, Natalie L

    2014-01-01

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

  17. 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

    OpenAIRE

    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....

  18. Impaired growth and elevated Fas receptor expression in PIGA+ stem cells in primary paroxysmal nocturnal hemoglobinuria

    OpenAIRE

    Chen, Rui; Nagarajan, Shanmugam; Prince, Gregory M.; Maheshwari, Uma; Terstappen, Leon W. M. M.; Kaplan, David R.; Gerson, Stanton L.; Albert, Jeffrey M.; Dunn, Daniel E.; Lazarus, Hillard M.; Medof, M. Edward

    2000-01-01

    The genetic defect underlying paroxysmal nocturnal hemoglobinuria (PNH) has been shown to reside in PIGA, a gene that encodes an element required for the first step in glycophosphatidylinositol anchor assembly. Why PIGA-mutated cells are able to expand in PNH marrow, however, is as yet unclear. To address this question, we compared the growth of affected CD59–CD34+ and unaffected CD59+CD34+ cells from patients with that of normal CD59+CD34+ cells in liquid culture. One hundred FACS-sorted c...

  19. Melatonin in animal models

    Science.gov (United States)

    Pévet, Paul

    2003-01-01

    Melatonin is a hormone synthesized and secreted during the night by the pineal gland. Its production is mainly driven by the Orcadian clock, which, in mammals, is situated in the suprachiasmatic nucleus of the hypothalamus. The melatonin production and release displays characteristic daily (nocturnal) and seasonal patterns (changes in duration proportional to the length of the night) of secretion. These rhythms in circulating melatonin are strong synchronizers for the expression of numerous physiological processes. In mammals, the role of melatonin in the control of seasonality is well documented, and the sites and mechanisms of action involved are beginning to be identified. The exact role of the hormone in the diurnal (Orcadian) timing system remains to be determined. However, exogenous melatonin has been shown to affect the circadian clock. The molecular and cellular mechanisms involved in this well-characterized “chronobiotic” effect have also begun to be characterized. The circadian clock itself appears to be an important site for the entrapment effect of melatonin and the presence of melatonin receptors appears to be a prerequisite. A better understanding of such “chronobiotic” effects of melatonin will allow clarification of the role of endogenous melatonin in circadian organization. PMID:22033558

  20. Breast cancer therapy based on melatonin.

    Science.gov (United States)

    Sanchez-Barcelo, Emilio J; Mediavilla, Maria D; Alonso-Gonzalez, Carolina; Rueda, Noemi

    2012-05-01

    The usefulness of melatonin and melatoninergic drugs in breast cancer therapy is based on its Selective Estrogen Receptor Modulator (SERM) and Selective Estrogen Enzyme Modulator (SEEM) properties. Because of the oncostatic properties of melatonin, its nocturnal suppression by light-at-night (LAN) has been considered a risk-factor for breast cancer. Melatonin's SERM actions include modulation of estrogen-regulated cell proliferation, invasiveness and expression of proteins, growth factors and proto-oncogenes (hTERT, p53, p21, TGF?, E-cadherin, etc.). These actions are observable with physiologic doses of melatonin only in cells expressing ER?, and mediated by MT1 melatonin receptors. Melatonin acts like a SEEM, inhibiting expression and activity of P450 aromatase, estrogen sulfatase and type 1, 17?- hydroxysteroid dehydrogenase, but stimulating that of estrogen sulfotransferase. This double action mechanism (SERM and SEEM), and the specificity for ER? bestows melatonin with potential advantages for breast cancer treatments, associated with other antiestrogenic drugs, and idea already patented. LAN enhances the growth of rat mammary tumors by decreasing or suppressing melatonin production. Epidemiologic studies have also described increased breast cancer risk in women exposed to LAN. Since the strongest suppression of nocturnal melatonin occurs with wavelength light of the blue spectral region, optical and lightening devices filtering the blue light spectrum have been proposed to avoid the risks of light-induced suppression of nocturnal melatonin. PMID:22369716

  1. Delivery of pineal melatonin to the brain and SCN: role of canaliculi, cerebrospinal fluid, tanycytes and Virchow-Robin perivascular spaces.

    Science.gov (United States)

    Reiter, Russel J; Tan, Dun Xian; Kim, Seok Joong; Cruz, Maria Helena C

    2014-11-01

    Historically, the direct release of pineal melatonin into the capillary bed within the gland has been accepted as the primary route of secretion. Herein, we propose that the major route of melatonin delivery to the brain is after its direct release into the cerebrospinal fluid (CSF) of the third ventricle (3V). Melatonin concentrations in the CSF are not only much higher than in the blood, also, there is a rapid nocturnal rise at darkness onset and precipitous decline of melatonin levels at the time of lights on. Because melatonin is a potent free radical scavenger and antioxidant, we surmise that the elevated CSF levels are necessary to combat the massive free radical damage that the brain would normally endure because of its high utilization of oxygen, the parent molecule of many toxic oxygen metabolites, i.e., free radicals. Additionally, the precise rhythm of CSF melatonin provides the master circadian clock, the suprachiasmatic nucleus, with highly accurate chronobiotic information regarding the duration of the dark period. We predict that the discharge of melatonin directly into the 3V is aided by a number of epithalamic structures that have heretofore been overlooked; these include interpinealocyte canaliculi and evaginations of the posterodorsal 3V that directly abut the pineal. Moreover, the presence of tanycytes in the pineal recess and/or a discontinuous ependymal lining in the pineal recess allows melatonin ready access to the CSF. From the ventricles melatonin enters the brain by diffusion and by transport through tanycytes. Melatonin-rich CSF also circulates through the aqueduct and eventually into the subarachnoid space. From the subarachnoid space surrounding the brain, melatonin penetrates into the deepest portions of the neural tissue via the Virchow-Robin perivascular spaces from where it diffuses into the neural parenchyma. Because of the high level of pineal-derived melatonin in the CSF, all portions of the brain are better shielded from oxidative stress resulting from toxic oxygen derivatives. PMID:24553808

  2. Nocturnal Asthma

    Science.gov (United States)

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

  3. Melatonin and associated signaling pathways that control normal breast epithelium and breast cancer.

    Science.gov (United States)

    Hill, Steven M; Blask, David E; Xiang, Shulin; Yuan, Lin; Mao, Lulu; Dauchy, Robert T; Dauchy, Erin M; Frasch, Tripp; Duplesis, Tamika

    2011-09-01

    This review article discusses recent work on the melatonin-mediated circadian regulation and integration of molecular and metabolic signaling mechanisms involved in human breast cancer growth and the associated consequences of circadian disruption by exposure to light-at-night (LAN). The anti-proliferative effects of the circadian melatonin signal are, in general, mediated through mechanisms involving the activation of MT(1) melatonin receptors expressed in human breast cancer cell lines and xenografts. In estrogen receptor-positive (ER?+) human breast cancer cells, melatonin suppresses both ER? mRNA expression and estrogen-induced transcriptional activity of the ER? via MT(1)-induced activation of G(?i2) signaling and reduction of cAMP levels. Melatonin also regulates the transcriptional activity of additional members of the nuclear receptor super-family, enzymes involved in estrogen metabolism, and the expression of core clock and clock-related genes. The anti-invasive/anti-metastatic actions of melatonin involve the blockade of p38 phosphorylation and matrix metalloproteinase expression. Melatonin also inhibits the growth of human breast cancer xenografts via MT(1)-mediated suppression of cAMP leading to a blockade of linoleic acid (LA) uptake and its metabolism to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Down-regulation of 13-HODE reduces the activation of growth factor pathways supporting cell proliferation and survival. Finally, studies in both rats and humans indicate that light-at-night (LAN) induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism, and signaling, providing the strongest mechanistic support, thus far, for epidemiological studies demonstrating the elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LAN. PMID:21773809

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

    OpenAIRE

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2005-01-01

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

  6. Melatonin and LH secretion patterns in pubertal boys

    International Nuclear Information System (INIS)

    Plasma melatonin and LH were measured at 20 minute intervals for 24 hours in four normal pubertal boys. All four subjects showed a significant augmentation of LH and melatonin during nocturnal sleep. There was also a significant correlation between the LH and melatonin levels (p<0.001). There were periods of episodic secretion of melanin during the diurnal waking period which seemed related to 'stress'. These data indicate that the peripheral concentrations of melatonin which occur during sleep are insufficient to prevent spontaneous LH secretion during puberty

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

    Science.gov (United States)

    Hardeland, Rüdiger

    2015-02-01

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

  8. Effects of daytime melatonin infusion in young adults.

    Science.gov (United States)

    Van Den Heuvel, C J; Kennaway, D J; Dawson, D

    1998-07-01

    Daytime oral melatonin typically exerts soporific and thermoregulatory effects; however, it is not clear whether these effects reflect the normal physiological response to endogenous nocturnal melatonin production. We infused melatonin at doses that produced physiological and supraphysiological steady-state levels in 24 young adults during two daytime bed rest protocols. From 1000 to 1630, subjects were infused intravenously with saline or melatonin in counterbalanced order. Each group of eight subjects received melatonin (and saline) infusions at one dose rate: 0.04 microg . h-1 . kg body wt-1 (low), 0.08 microg . h-1 . kg-1 (medium), or 8.0 microg . h-1 . kg-1 (high). Low and medium melatonin infusions produced plasma and saliva levels within the normal nocturnal range observed in young adults. These levels were not associated with any changes in rectal, hand, forehead, or tympanic temperatures or with subjective sleepiness. High melatonin produced supraphysiological plasma and saliva levels and was associated with a significant attenuation in the daytime increase in rectal temperature, significantly increased hand temperature, and greater sleepiness. It is not yet clear whether the thermoregulatory and soporific effects of daytime supraphysiological melatonin administration are equivalent to the physiological responses to endogenous melatonin. PMID:9688869

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

    OpenAIRE

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

    2013-01-01

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

  10. Melatonin signaling controls circadian swimming behavior in marine zooplankton.

    Science.gov (United States)

    Tosches, Maria Antonietta; Bucher, Daniel; Vopalensky, Pavel; Arendt, Detlev

    2014-09-25

    Melatonin, the "hormone of darkness," is a key regulator of vertebrate circadian physiology and behavior. Despite its ubiquitous presence in Metazoa, the function of melatonin signaling outside vertebrates is poorly understood. Here, we investigate the effect of melatonin signaling on circadian swimming behavior in a zooplankton model, the marine annelid Platynereis dumerilii. We find that melatonin is produced in brain photoreceptors with a vertebrate-type opsin-based phototransduction cascade and a light-entrained clock. Melatonin released at night induces rhythmic burst firing of cholinergic neurons that innervate locomotor-ciliated cells. This establishes a nocturnal behavioral state by modulating the length and the frequency of ciliary arrests. Based on our findings, we propose that melatonin signaling plays a role in the circadian control of ciliary swimming to adjust the vertical position of zooplankton in response to ambient light. PMID:25259919

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

    OpenAIRE

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

    2014-01-01

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

  12. Photic and circadian regulation of retinal melatonin in mammals

    Science.gov (United States)

    Tosini, G.; Fukuhara, C.

    2003-01-01

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

  13. Melatonin responses to clonidine and yohimbine challenges.

    OpenAIRE

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

    1995-01-01

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

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

    OpenAIRE

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

    1996-01-01

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

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

    Science.gov (United States)

    Lee, Jack Monroe, Jr.

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

  16. Adrenaline and nocturnal asthma

    OpenAIRE

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

    1990-01-01

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

  17. Calcium modulates circadian variation in cAMP-stimulated melatonin in chick pineal cells.

    Science.gov (United States)

    Nikaido, S S; Takahashi, J S

    1996-04-15

    In chick pineal cells, melatonin synthesis is regulated by both calcium and cAMP. Calcium-dependent regulation of melatonin is suggested by the monotonic decrease in melatonin observed with decreasing extracellular calcium ion concentrations ([Ca2+]0), the stimulation of melatonin with Bay K8644, and the inhibition of nocturnal melatonin by several calmodulin antagonists. At submicromolar [Ca2+]0, a stimulation of melatonin was observed in the presence of 8-Br cAMP, but not with Bay K8644, suggesting that this amount of stimulation of melatonin by 8-Br cAMP is independent of Ca2+ influx through dihydropyridine-sensitive Ca2+ channels. At micromolar [Ca2+]0, there was a further increase in the stimulation of melatonin by 8-Br cAMP that was not blocked by nifedipine, a dihydropyridine-sensitive Ca2+ channel antagonist. Micromolar [Ca2+]0 is required for the greater stimulation of melatonin by 8-Br cAMP during the night than during the day. Melatonin was stimulated by 8-Br cAMP to higher levels during the night than during the subjective day under normal [Ca2+]0 (1.3 mM). This difference in the amount of melatonin stimulated by 8-Br cAMP during the subjective night versus the subjective day was blocked by lowering [Ca2+]0 to a submicromolar concentration (0.2 microM). Both nifedipine and calmidazolium partially blocked nocturnal increases in melatonin, but were ineffective during the day. These results suggest that Ca2+ plays an important role in the differential ability of cAMP to stimulate melatonin during the night versus the day. PMID:8738214

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

    Science.gov (United States)

    Pévet, P

    2014-11-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

    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

  2. Melatonin and the skeleton

    DEFF Research Database (Denmark)

    Amstrup, A K; Sikjaer, T

    2013-01-01

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

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

    Science.gov (United States)

    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.

  4. Nocturnal panic attacks

    OpenAIRE

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

    2002-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

  7. Melatonin agonists and insomnia.

    Science.gov (United States)

    Ferguson, Sally A; Rajaratnam, Shantha M W; Dawson, Drew

    2010-02-01

    The ability of melatonin to shift biological rhythms is well known. As a result, melatonin has been used in the treatment of various circadian rhythm sleep disorders, such as advanced and delayed sleep phase disorders, jet lag and shiftwork disorder. The current evidence for melatonin being efficacious in the treatment of primary insomnia is less compelling. The development of agents that are selective for melatonin receptors provides opportunity to further elucidate the actions of melatonin and its receptors and to develop novel treatments for specific types of sleep disorders. The agonists reviewed here - ramelteon, tasimelteon and agomelatine - all appear to be efficacious in the treatment of circadian rhythm sleep disorders and some types of insomnia. However, further studies are required to understand the mechanisms of action, particularly for insomnia. Clinical application of the agonists requires a good understanding of their phase-dependent properties. Long-term effects of melatonin should be evaluated in large-scale, independent randomized controlled trials. PMID:20136385

  8. Melatonin: functions and ligands.

    Science.gov (United States)

    Singh, Mahaveer; Jadhav, Hemant R

    2014-09-01

    Melatonin is a chronobiotic substance that acts as synchronizer by stabilizing bodily rhythms. Its synthesis occurs in various locations throughout the body, including the pineal gland, skin, lymphocytes and gastrointestinal tract (GIT). Its synthesis and secretion is controlled by light and dark conditions, whereby light decreases and darkness increases its production. Thus, melatonin is also known as the 'hormone of darkness'. Melatonin and analogs that bind to the melatonin receptors are important because of their role in the management of depression, insomnia, epilepsy, Alzheimer's disease (AD), diabetes, obesity, alopecia, migraine, cancer, and immune and cardiac disorders. In this review, we discuss the mechanism of action of melatonin in these disorders, which could aid in the design of novel melatonin receptor ligands. PMID:24792719

  9. Melatonin Promotes Superovulation in Sika Deer (Cervus nippon

    Directory of Open Access Journals (Sweden)

    Liang Wang

    2014-07-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  11. Natural and melatonin-stimulated changes in the circadian rhythm of prolactin secretion in the ewe during seasonal anestrus.

    Science.gov (United States)

    Misztal, T; Romanowicz, K; Barcikowski, B

    1997-11-01

    The relations between the circadian rhythms of melatonin and prolactin, and the effect of melatonin infused into the third ventricle or the mediobasal hypothalamus (MBH) on prolactin secretion and dopamine (DA) release were studied in anestrous ewes under increasing daylength conditions. The decreased amplitude and duration of nocturnal melatonin secretion were accompanied with changes in the daily pattern of prolactin secretion. Marked peaks of prolactin occurred after sunrise and melatonin decreases in February, as well as significant evening or nocturnal peaks under long day conditions between April and July. Melatonin infused into the third ventricle evoked an abrupt increase in the concentration of prolactin after 30 min, and the enhanced prolactin level was significantly higher than during the control infusion (range from 204 +/- 75 to 248 +/- 48 ng/ml vs. 128 +/- 68 to 149 +/- 93 ng/ml, mean +/- SD). The concentrations of DA in MBH perfusates decreased during perfusion of melatonin but to a degree similar to that noted in untreated ewes. These data suggest that short-term infusions of melatonin stimulate the secretion of prolactin in the ewe under increasing daylength conditions, and that this effect is not mediated by changes in DA release. PMID:9387855

  12. Nocturnal panic attacks

    Directory of Open Access Journals (Sweden)

    Lopes Fabiana L.

    2002-01-01

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

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

    Science.gov (United States)

    Vriend, Jerry; Reiter, Russel J

    2015-01-01

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

  14. Molecular Structure of Melatonin

    Science.gov (United States)

    2002-08-12

    Melatonin is a hormone essential for functioning normally on a daily basis. This compound is heavily released into circulation when light sources are diminished, allowing for the process of sleep to ensue. Without production of proper melatonin levels, it is difficult to sleep and may be the cause for insomnia in many people. Melatonin is not only important in promoting sleep, it also helps regulate proper immune responses, brain maturation, and may help alleviate anxiety and depression. In the body, melatonin is biosynthesized in the pineal gland, which is located in the brain between the two cerebral hemispheres, or the seat of the soul as coined by Descartes. The major precursor to melatonin synthesis is the neurotransmitter serotonin.

  15. Serum Melatonin in Juvenile Rheumatoid Arthritis: Correlation with Disease Activity

    Directory of Open Access Journals (Sweden)

    Hanaa Mahmoud El-Awady

    2007-01-01

    Full Text Available The study was conducted to investigate the abnormalities in early morning serum melatonin among patients with Juvenile Rheumatoid Arthritis (JRA and to outline its relation to disease activity and severity. Twenty one patients with JRA and twenty healthy age and sex matched controls were enrolled in the study. Fifteen patients had polyarticular JRA, 3 had oligoarticular and 3 had systemic onset JRA. Evaluation was carried out clinically, functionally and radiologically by using disease activity score, Juvenile Arthritis Functional Assessment Report for Children (JAFAR-C score and modified Larsen score, respectively. Laboratory investigations included Complete Blood Picture (CBC, The Erythrocyte Sedimentation Rate ( ESR, C-Reactive Protein (CRP, classic IgM Rheumatoid Factor (RF, Anti-nuclear Antibodies (ANA and melatonin estimation in serum. The serum levels of melatonin were significantly increased in JRA patients (mean±SD = 13.9±8 pg mL-1 as compared to healthy controls (mean±SD = 8.1±2.7 pg mL-1, p<0.01. A significant positive correlation could link serum melatonin levels to disease activity scores and ESR (r = 0.91, p<0.001 and r = 0.55, p<0.01, respectively. No significant correlation was found between melatonin and either Larsen or JAFAR scores (r = 0.19, r = 0.15, respectively. According to melatonin levels, there were 2 groups of patients: Group I with elevated melatonin level (more than 11 pg mL-1 (n = 15 and group II with normal melatonin level (less than 11 pg mL-1 (n = 6. Patients with elevated melatonin levels had higher ESR (p<0.05, higher disease activity scores (p<0.01 and Larsen scores (p<0.05, than the group of patients with normal serum melatonin. The results of GAFAR scores were comparable between the two groups (p>0.05. Hence the study conclude that the elevated melatonin levels among JRA patients with active synovitis and its close relation to disease activity rather than disease severity suggests that melatonin might play a promoting role in rheumatoid arthritis. Hence, inhibition of its synthesis and/or action by specific antagonists may be of therapeutic value.

  16. Paroxysmal Nocturnal Hemoglobinuria

    Science.gov (United States)

    About Bone Marrow Failure Paroxysmal Nocturnal Hemoglobinuria (PNH) PNH is a rare and serious blood disease that causes red blood cells to break apart. Doctors call this breaking apart " hemolysis ". It happens because your blood cells are missing a protein that protects ...

  17. Nocturnal intermittent hemodialysis.

    Science.gov (United States)

    Thumfart, Julia; Müller, Dominik

    2015-05-01

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

  18. Nocturn and Aubade

    OpenAIRE

    Morteza Dehghani

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

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

    Science.gov (United States)

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

    2014-06-26

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

  1. Circadian and melatonin disruption by exposure to light at night drives intrinsic resistance to tamoxifen therapy in breast cancer.

    Science.gov (United States)

    Dauchy, Robert T; Xiang, Shulin; Mao, Lulu; Brimer, Samantha; Wren, Melissa A; Yuan, Lin; Anbalagan, Muralidharan; Hauch, Adam; Frasch, Tripp; Rowan, Brian G; Blask, David E; Hill, Steven M

    2014-08-01

    Resistance to endocrine therapy is a major impediment to successful treatment of breast cancer. Preclinical and clinical evidence links resistance to antiestrogen drugs in breast cancer cells with the overexpression and/or activation of various pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift work or disturbed sleep-wake cycles may lead to an increased risk of breast cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the nocturnal production of melatonin that inhibits breast cancer growth. In this study, we used a rat model of estrogen receptor (ER?(+)) MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN) speed the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. These characteristics were not observed in animals in which the circadian melatonin rhythm was not disrupted, or in animals subjected to dLEN if they received nocturnal melatonin replacement. Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to tamoxifen and tumor regression. Together, our findings show how dLEN-mediated disturbances in nocturnal melatonin production can render tumors insensitive to tamoxifen. PMID:25062775

  2. Nocturnal paroxysmal dystonia.

    Science.gov (United States)

    Lugaresi, E; Cirignotta, F; Montagna, P

    1986-04-01

    Sleep-related seizures characterised by choreoathetoid, dystonic and ballic movements occurred in 12 patients, repeatedly each night and over a period of years. The nocturnal attacks were short-lasting, responded well to carbamazepine and were sometimes associated with clearly or possibly epileptic seizures during night- or daytime. They resembled the paroxysmal kinesigenic dystonias of wakefulness. Similar dystonic-dyskinetic attacks, but of long duration and unresponsive to medication, were also observed in two other patients, in one 20 years before the onset of clinically apparent Huntington's chorea. Nocturnal paroxysmal dystonia represents a syndrome of sleep-related motor attacks which comprises two variants, respectively characterised by short and long-lasting seizures. Its precise nosological definition still awaits elucidation. PMID:2939199

  3. Nocturnal paroxysmal dystonia.

    OpenAIRE

    Berger, H. J.; Berendsen-versteeg, T. M.; Joosten, E. M.

    1986-01-01

    Sleep-related seizures characterised by choreoathetoid, dystonic and ballic movements occurred in 12 patients, repeatedly each night and over a period of years. The nocturnal attacks were short-lasting, responded well to carbamazepine and were sometimes associated with clearly or possibly epileptic seizures during night- or daytime. They resembled the paroxysmal kinesigenic dystonias of wakefulness. Similar dystonic-dyskinetic attacks, but of long duration and unresponsive to medication, were...

  4. Nocturnal cough in asthma.

    OpenAIRE

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

    1987-01-01

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

  5. Effects of different colors of light on melatonin suppression and expression analysis of Aanat1 and melanopsin in the eye of a tropical damselfish.

    Science.gov (United States)

    Takeuchi, Yuki; Imamura, Satoshi; Sawada, Yuji; Hur, Sung-Pyo; Takemura, Akihiro

    2014-08-01

    Ocular melatonin production exhibits a daily rhythm with a decrease during photophase and an increase during scotophase (nocturnal pattern) in teleost fish due to day-night changes in the activity of the rate-limiting melatonin synthesizing enzyme arylalkylamine N-acetyltransferase (AANAT). Acute light exposure during scotophase suppresses AANAT activity and melatonin production in the eyes, suggesting that external light signals are a principal regulator of ocular melatonin synthesis. To better understand the photic regulation of ocular melatonin synthesis in teleost fish, this study sought to characterize the effect of light on ocular melatonin synthesis in the sapphire devil Chrysiptera cyanea, which shows a nocturnal pattern and light-induced inhibition of ocular melatonin production during scotophase. Exposure to three different wavelengths of light (half-peak bandwidth=435-475 nm with a peak of 455 nm, 495-565 nm with a peak of 530 nm, and 607-647 nm with a peak of 627 nm for the blue, green, and red LEDs) for 2h during scotophase resulted in the blue wavelength significantly decreasing ocular melatonin content within 30 min after light exposure. This result clearly indicates that the effective range of visible light on ocular melatonin suppression is distributed within the wavelengths of blue light and that a blue light-sensitive opsin is involved in ocular melatonin suppression in the fish. A PCR-based cloning method revealed the expression of melanopsin, a putative blue light-sensitive nonvisual opsin, in the eyes. Furthermore, in situ hybridization using the sapphire devil Aanat1 and melanopsin RNA probes showed mRNA expressions of both genes in the inner nuclear and ganglion cell layer of the fish retina. These results suggest that melanopsin is a possible candidate photoreceptor involved in ocular melatonin suppression by an external light signal in the sapphire devil. PMID:24859252

  6. Paroxysmal nocturnal hemoglobinuria

    International Nuclear Information System (INIS)

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

  7. Role of melatonin on diabetes-related metabolic disorders

    Directory of Open Access Journals (Sweden)

    Javier Espino

    2011-01-01

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

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

    DEFF Research Database (Denmark)

    Ucar, Ebru; Lehtinen, Emilia K

    2012-01-01

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

  9. Melatonin labelled by hydrogen isotopes

    International Nuclear Information System (INIS)

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

  10. Melatonin labeled with hydrogen isotopes

    International Nuclear Information System (INIS)

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

  11. Npas4 is activated by melatonin, and drives the clock gene Cry1 in the ovine pars tuberalis.

    Science.gov (United States)

    West, A; Dupré, S M; Yu, L; Paton, I R; Miedzinska, K; McNeilly, A S; Davis, J R E; Burt, D W; Loudon, A S I

    2013-06-01

    Seasonal mammals integrate changes in the duration of nocturnal melatonin secretion to drive annual physiologic cycles. Melatonin receptors within the proximal pituitary region, the pars tuberalis (PT), are essential in regulating seasonal neuroendocrine responses. In the ovine PT, melatonin is known to influence acute changes in transcriptional dynamics coupled to the onset (dusk) and offset (dawn) of melatonin secretion, leading to a potential interval-timing mechanism capable of decoding changes in day length (photoperiod). Melatonin offset at dawn is linked to cAMP accumulation, which directly induces transcription of the clock gene Per1. The rise of melatonin at dusk induces a separate and distinct cohort, including the clock-regulated genes Cry1 and Nampt, but little is known of the up-stream mechanisms involved. Here, we used next-generation sequencing of the ovine PT transcriptome at melatonin onset and identified Npas4 as a rapidly induced basic helix-loop-helix Per-Arnt-Sim domain transcription factor. In vivo we show nuclear localization of NPAS4 protein in presumptive melatonin target cells of the PT (?-glycoprotein hormone-expressing cells), whereas in situ hybridization studies identified acute and transient expression in the PT of Npas4 in response to melatonin. In vitro, NPAS4 forms functional dimers with basic helix loop helix-PAS domain cofactors aryl hydrocarbon receptor nuclear translocator (ARNT), ARNT2, and ARNTL, transactivating both Cry1 and Nampt ovine promoter reporters. Using a combination of 5'-deletions and site-directed mutagenesis, we show NPAS4-ARNT transactivation to be codependent upon two conserved central midline elements within the Cry1 promoter. Our data thus reveal NPAS4 as a candidate immediate early-response gene in the ovine PT, driving molecular responses to melatonin. PMID:23598442

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

    Scientific Electronic Library Online (English)

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

    2008-10-01

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

  13. Melatonin stimulates the release of gonadotropin-inhibitory hormone by the avian hypothalamus.

    Science.gov (United States)

    Chowdhury, Vishwajit S; Yamamoto, Kazutoshi; Ubuka, Takayoshi; Bentley, George E; Hattori, Atsuhiko; Tsutsui, Kazuyoshi

    2010-01-01

    Gonadotropin-inhibitory hormone (GnIH), a neuropeptide that inhibits gonadotropin synthesis and release, was first identified in quail hypothalamus. GnIH acts on the pituitary and GnRH neurons in the hypothalamus via GnIH receptor to inhibit gonadal development and maintenance. In addition, GnIH neurons express melatonin receptor and melatonin induces GnIH expression in the quail brain. Thus, it seems that melatonin is a key factor controlling GnIH neural function. In the present study, we investigated the role of melatonin in the regulation of GnIH release and the correlation of GnIH release with LH release in quail. Melatonin administration dose-dependently increased GnIH release from hypothalamic explants in vitro. GnIH release was photoperiodically controlled. A clear diurnal change in GnIH release was observed in quail, and this change was negatively correlated with changes in plasma LH concentrations. GnIH release during the dark period was greater than that during the light period in explants from quail exposed to long-day photoperiods. Conversely, plasma LH concentrations decreased during the dark period. In contrast to LD, GnIH release increased under short-day photoperiods, when the duration of nocturnal secretion of melatonin increases. These results indicate that melatonin may play a role in stimulating not only GnIH expression but also GnIH release, thus inhibiting plasma LH concentrations in quail. This is the first report describing the effect of melatonin on neuropeptide release. PMID:19952272

  14. The Timing of the Shrew: Continuous Melatonin Treatment Maintains Youthful Rhythmic Activity in Aging Crocidura russula

    Science.gov (United States)

    Magnanou, Elodie; Attia, Joël; Fons, Roger; Boeuf, Gilles; Falcon, Jack

    2009-01-01

    Background Laboratory conditions nullify the extrinsic factors that determine the wild expected lifespan and release the intrinsic or potential lifespan. Thus, wild animals reared in a laboratory often show an increased lifespan, and consequently an increased senescence phase. Senescence is associated with a broad suite of physiological changes, including a decreased responsiveness of the circadian system. The time-keeping hormone melatonin, an important chemical player in this system, is suspected to have an anti-aging role. The Greater White-toothed shrew Crocidura russula is an ideal study model to address questions related to aging and associated changes in biological functions: its lifespan is short and is substantially increased in captivity; daily and seasonal rhythms, while very marked the first year of life, are dramatically altered during the senescence process which starts during the second year. Here we report on an investigation of the effects of melatonin administration on locomotor activity of aging shrews. Methodology/Principal Findings 1) The diel fluctuations of melatonin levels in young, adult and aging shrews were quantified in the pineal gland and plasma. In both, a marked diel rhythm (low diurnal concentration; high nocturnal concentration) was present in young animals but then decreased in adults, and, as a result of a loss in the nocturnal production, was absent in old animals. 2) Daily locomotor activity rhythm was monitored in pre-senescent animals that had received either a subcutaneous melatonin implant, an empty implant or no implant at all. In non-implanted and sham-implanted shrews, the rhythm was well marked in adults. A marked degradation in both period and amplitude, however, started after the age of 14–16 months. This pattern was considerably delayed in melatonin-implanted shrews who maintained the daily rhythm for significantly longer. Conclusions This is the first long term study (>500 days observation of the same individuals) that investigates the effects of continuous melatonin delivery. As such, it sheds new light on the putative anti-aging role of melatonin by demonstrating that continuous melatonin administration delays the onset of senescence. In addition, the shrew appears to be a promising mammalian model for elucidating the precise relationships between melatonin and aging. PMID:19526053

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

    Science.gov (United States)

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

    2014-01-01

    Currently, in developed countries, nights are excessively illuminated (light at night), whereas daytime is mainly spent indoors, and thus people are exposed to much lower light intensities than under natural conditions. In spite of the positive impact of artificial light, we pay a price for the easy access to light during the night: disorganization of our circadian system or chronodisruption (CD), including perturbations in melatonin rhythm. Epidemiological studies show that CD is associated with an increased incidence of diabetes, obesity, heart disease, cognitive and affective impairment, premature aging and some types of cancer. Knowledge of retinal photoreceptors and the discovery of melanopsin in some ganglion cells demonstrate that light intensity, timing and spectrum must be considered to keep the biological clock properly entrained. Importantly, not all wavelengths of light are equally chronodisrupting. Blue light, which is particularly beneficial during the daytime, seems to be more disruptive at night, and induces the strongest melatonin inhibition. Nocturnal blue light exposure is currently increasing, due to the proliferation of energy-efficient lighting (LEDs) and electronic devices. Thus, the development of lighting systems that preserve the melatonin rhythm could reduce the health risks induced by chronodisruption. This review addresses the state of the art regarding the crosstalk between light and the circadian system. PMID:25526564

  16. Myocardial infarction and nocturnal hypoxaemia

    Directory of Open Access Journals (Sweden)

    Pen?i? Biljana

    2007-01-01

    Full Text Available Introduction: There is an increased risk of cardiovascular morbidity and mortality in patients with nocturnal intermittent hypoxaemia. Objecive. The aim of this study was to evalute the influence of nocturnal hypoxaemia on ventricular arrhythmias and myocardial ischaemia in patients with myocardial infarction (MI. Method. We studied 77 patients (55.8±7.9 years with MI free of complications, chronic pulmonary diseases, abnormal awake blood gases tension. All patients underwent overnight pulse oximetry and 24-hour electrocardiography. Patients were divided into two groups according to nocturnal hypoxaemia. Total number of ventricular premature complex (VPC; maximal VPC/h; incidence of VPC Lown class>2 and occurrence of ST-segment depression were analyzed for nocturnal (10 PM to 6 AM, daytime (6 AM to 22 PM periods and for the entire 24 hours. Results. Both groups were similar in age, gender, standard risk factors, myocardial infarction size and did not differ in VPC during the analyzed periods. The number of nocturnal maximal VPC/h was insignificantly greater in group 1 (with hypoxaemia compared to group 2 (without hypoxaemia, (p=0.084. Maximal VPC/h did not differ significantly either for daytime or for 24 hours among the groups. Nocturnal VPC Lown>2 were significantly more frequent in group 1 (25% vs 0%, p=0.002. The incidence of VPC Lown>2 was similar during the daytime, and during 24 hrs in both groups. Occurrence of ST-segment depression did not differ between groups 1 and 2. Conclusion. Nocturnal hypoxaemia was associated with complex nocturnal ventricular arrhythmias in patients with MI. .

  17. Melatonin: Buffering the Immune System

    Directory of Open Access Journals (Sweden)

    Juan M. Guerrero

    2013-04-01

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

  18. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

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

  19. Evidence for RGS4 modulation of melatonin and thyrotrophin signalling pathways in the pars tuberalis.

    Science.gov (United States)

    Dupré, S M; Dardente, H; Birnie, M J; Loudon, A S I; Lincoln, G A; Hazlerigg, D G

    2011-08-01

    In mammals, the pineal hormone melatonin is secreted nocturnally and acts in the pars tuberalis (PT) of the anterior pituitary to control seasonal neuroendocrine function. Melatonin signals through the type 1 Gi-protein coupled melatonin receptor (MT1), inhibiting adenylate cyclase (AC) activity and thereby reducing intracellular concentrations of the second messenger, cAMP. Because melatonin action ceases by the end of the night, this allows a daily rise in cAMP levels, which plays a key part in the photoperiodic response mechanism in the PT. In addition, melatonin receptor desensitisation and sensitisation of AC by melatonin itself appear to fine-tune this process. Opposing the actions of melatonin, thyroid-stimulating hormone (TSH), produced by PT cells, signals through its cognate Gs-protein coupled receptor (TSH-R), leading to increased cAMP production. This effect may contribute to increased TSH production by the PT during spring and summer, and is of considerable interest because TSH plays a pivotal role in seasonal neuroendocrine function. Because cAMP stands at the crossroads between melatonin and TSH signalling pathways, any protein modulating cAMP production has the potential to impact on photoperiodic readout. In the present study, we show that the regulator of G-protein signalling RGS4 is a melatonin-responsive gene, whose expression in the PT increases some 2.5-fold after melatonin treatment. Correspondingly, RGS4 expression is acutely sensitive to changing day length. In sheep acclimated to short days (SP, 8 h light/day), RGS4 expression increases sharply following dark onset, peaking in the middle of the night before declining to basal levels by dawn. Extending the day length to 16 h (LP) by an acute 8-h delay in lights off causes a corresponding delay in the evening rise of RGS4 expression, and the return to basal levels is delayed some 4 h into the next morning. To test the hypothesis that RGS4 expression modulates interactions between melatonin- and TSH-dependent cAMP signalling pathways, we used transient transfections of MT1, TSH-R and RGS4 in COS7 cells along with a cAMP-response element luciferase reporter (CRE-luc). RGS4 attenuated MT1-mediated inhibition of TSH-stimulated CRE-luc activation. We propose that RGS4 contributes to photoperiodic sensitivity in the morning induction of cAMP-dependent gene expression in the PT. PMID:21623959

  20. Melatonin--a modulator of the GnRH/LH axis in sheep.

    Science.gov (United States)

    Misztal, Tomasz; Romanowicz, Katarzyna; Barcikowski, Bernard

    2002-11-01

    The nocturnal secretion of pineal melatonin provides information to vertebrates on changes in day length under the circumstances in which they live. In sheep, which are seasonal breeders, the secretion of melatonin is also a signal to the neural structures controlling the secretion of gonadotropins from the pituitary gland to drive their activity in accordance with the season of the year. The sites and mechanisms of melatonin action on GnRH/LH secretion has been the subject of intensive studies in the last decade. This article briefly reviews the most important discoveries and methods used in this research, which has led to a better understanding of the role of melatonin in the modulation of hypothalamo-pituitary-gonadotropic axis activity in sheep. The identification of melatonin receptors within the central nervous system and in the pars tuberalis of the pituitary gland, as well as the use of specific techniques of micro-implantation and micro-infusion were crucial in this aspect. PMID:14666149

  1. Do magnetic fields cause increased risk of childhood leukemia via melatonin disruption?

    Science.gov (United States)

    Henshaw, Denis L; Reiter, Russel J

    2005-01-01

    Epidemiological studies have reported associations between exposure to power frequency magnetic fields and increased risk of certain cancer and noncancer illnesses. For childhood leukemia, a doubling of risk has been associated with exposures above 0.3/0.4 microT. Here, we propose that the melatonin hypothesis, in which power frequency magnetic fields suppress the nocturnal production of melatonin in the pineal gland, accounts for the observed increased risk of childhood leukemia. Such melatonin disruption has been shown in animals, especially with exposure to electric and/or rapid on/off magnetic fields. Equivocal evidence has been obtained from controlled laboratory magnetic field exposures of volunteers, although the exposure conditions are generally atypical of neighborhood exposures. In contrast, support for the hypothesis is found in the body of studies showing magnetic field disruption of melatonin in human populations chronically exposed to both electric and magnetic fields associated with electricity distribution. Further support comes from the observation that melatonin is highly protective of oxidative damage to the human haemopoietic system. Aspects of the hypothesis are amenable to further investigation. PMID:16059923

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

    Directory of Open Access Journals (Sweden)

    Alexander M Mathes

    2010-12-01

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

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

    DEFF Research Database (Denmark)

    Kamperis, K; Rittig, S

    2006-01-01

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

  4. Duration of Nocturnal Hypoglycemia Before Seizures

    OpenAIRE

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

    2008-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  6. First-morning urinary melatonin and breast cancer risk in the Guernsey Study.

    Science.gov (United States)

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

    2014-03-01

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

  7. Effect of melatonin implants on reproduction in the male silver fox (Vulpes vulpes).

    Science.gov (United States)

    Forsberg, M; Fougner, J A; Hofmo, P O; Einarsson, E J

    1990-01-01

    In June 1987, when the testes were fully regressed, 5 males were given s.c. implants of 40 mg melatonin. The same treatment was repeated in August and October 1987. Five males served as controls. Plasma concentrations of melatonin increased significantly in treated males and were still elevated at the end of the study in April 1988. The changes in testicular volume and blood plasma concentrations of testosterone in response to GnRH indicated that melatonin administration promoted testicular development. However, testicular regression was observed earlier in treated than control animals, perhaps because of refractoriness to melatonin or to a down-regulation of melatonin receptors. Semen was collected and frozen in November 1987, 2 months ahead of the natural breeding season, from the melatonin-treated males, and 10 blue fox vixens were inseminated the following breeding season: 9 vixens conceived, and the average litter size was 7.6 +/- 0.5. The results demonstrate that melatonin treatment initiated during exposure to naturally long days (a) promotes testicular development in a way similar to an artificial short photoperiod and (b) may induce a refractory condition after an extended period of treatment. PMID:2179546

  8. Studies on pineal melatonin levels in a diurnal species, the eastern chipmunk (Tamias striatus): effects of light at night, propranolol administration or superior cervical ganglionectomy.

    Science.gov (United States)

    Reiter, R J; King, T S; Richardson, B A; Hurlbut, E C

    1982-01-01

    Five experiments were carried out on the control of melatonin levels in the pineal gland of a diurnal species, the Eastern chipmunk (Tamias striatus). We confirmed that the exposure of chipmunks of fluorescent white light of 3,981-4,304 lux during the normal dark period does not prevent the rise in pineal melatonin levels normally associated with darkness. Also, the administration of propranolol (20 mg/kg) at 8 p.m. did not block the rise in pineal melatonin in animals exposed to either dark or light at night. Similarly, if chipmunks received propranolol 4 hours into the dark phase, pineal melatonin levels were not depressed 2 hours later. When animals were superior cervical ganglionectomized, however, the pineal content of melatonin remained low regardless of whether animals were exposed to darkness or light at night. The exposure of chipmunks acutely to light at midnight (4 hours after darkness onset) had only a slight depressive effect on pineal melatonin 30 min later; by comparison, when chipmunks were acutely exposed to light at 3 a.m. (7 hours after darkness onset) daytime pineal melatonin levels were reached within 15 min after light onset. These findings in a diurnal species, The Eastern chipmunk, differ markedly when compared to previously reported observations on nocturnal laboratory rodents. PMID:6890095

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

    Directory of Open Access Journals (Sweden)

    Isabel Cubero-Millán

    2014-09-01

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

  10. [Melatonin: a popular hormone].

    Science.gov (United States)

    Tarquini, B; Perfetto, F; Tarquini, R

    1998-05-01

    This contribution makes an attempt to critically reassess the impressive career of melatonin (MEL) from a stepchild of hormone research to a best-seller of drug marketing. Melatonin, the hormone of the pineal gland, provides temporal information on diurnal and seasonal variation to the body and brain and it is involved in the synchronization of many different aspects of circadian systems to the light-dark cycle. In addition to these receptor-mediated functions, MEL may act as a modulator of intracellular signal transduction to enhance or suppress the responses of many different cells to other incoming signals. Melatonin is also a potent scavenger of reactive oxygen species and may thus protect cells and tissues against radical-mediated damages. The production of MEL declines with increasing age, and circulating MEL levels are affected by certain pharmacological or physiological manipulations. Animal and cell culture experiments suggest that MEL may have beneficial effects on certain aspects of aging and age-associated diseases. Of particular interest in this respect are reports on the influence of MEL on the brain and the immune system. The sole sufficiently investigated indication in humans is the treatment of certain sleep disorders from the group of sleep-wake-rhythm disturbances. These manifest themselves by sleep time of the day, i.e. in shift workers, after flights across time zones and in some aged persons. Clinical studies need to be performed in order to identify possible side effects of long-term MEL treatment. Serious concerns are raised about the use of uncontrolled, impure, or partially degraded MEL preparations. PMID:9676179

  11. Melatonin and human cancer.

    OpenAIRE

    Terzolo, Massimo; Angeli, Alberto; Tampellini, Marco; Berruti, Alfredo; Dogliotti, Luigi

    1990-01-01

    A number of studies performed in vitro and on experimental animals supported the view that pineal gland inhibits neoplastic growth. Data in humans are scanty and controversial. In the present study we measured serum melatonin (MT), prolactin (PRL) and growth hormone (GH) concentrations, at 08.00 and 24.00, in 132 cancer patients and in 58 healthy control subjects. The patients were stratified according to histology and stage of disease as follows: 30 stage I-II and 45 stage III-IV breast canc...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Melatonin in pathogenesis and therapy of cancer

    Directory of Open Access Journals (Sweden)

    Ravindra T

    2006-12-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  15. 21 CFR 522.1350 - Melatonin implant.

    Science.gov (United States)

    2010-04-01

    ...INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1350 Melatonin implant. (a) Specifications . The drug is a silicone rubber elastomer implant containing 2.7 milligrams of melatonin. (b) Sponsor . See No. 053923 in §...

  16. The effects of prior light history on the suppression of melatonin by light in humans

    OpenAIRE

    He?bert, Marc; Martin, Stacia K.; Lee, Clara; Eastman, Charmane I.

    2002-01-01

    We investigated the impact of light exposure history on light sensitivity in humans, as assessed by the magnitude of the suppression of melatonin secretion by nocturnal light. The hypothesis was that following a week of increased daytime bright-light exposure, subjects would become less sensitive to light, and that after a week of restriction to dimmer light they would become more sensitive. During the bright week, subjects (n = 12) obtained 4.3 ± 0.4 hr of bright light per day (by going out...

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-05-01

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

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

    DEFF Research Database (Denmark)

    Kamperis, Konstantinos; Rittig, SØren

    2012-01-01

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

  20. [NPT: nocturnal penile tumescence test].

    Science.gov (United States)

    Colombo, F; Fenice, O; Austoni, E

    1994-09-01

    The recording of the variations of penile tumescence and rigidity during nocturnal unconscious erections that usually occur with the REM phases of sleep, has been considered the diagnostic tool of choice in the workup of erectile disturbances for a number of years. Such a success is partly due to its absence of invasiveness. Moreover this test was believed to allow to differentiate between the psychogenic and organic origin of impotence. As some authors have recently reported, anxiety state (common among patients who undergo invasive andrological procedure in the office) can at times influence the content of the dream state, thus negatively affecting the spontaneous nocturnal erections. Besides, sleep disturbances such as apnea and motor agitation can also induce erroneous interpretations of NPT graphs. Further, dysfunctions at the level of the cortex and the spine still allow the occurrence of nocturnal tumescence but determine an erectile deficit in the awake state. Clinically, all this poses new questions about the effectiveness of the NPT test in the study of the origin of impotence. The diagnostic methods, despite its world-wide diffusion, remains, under certain aspects, obscure: the operative details and, above all, its interpretative criteria. All this impedes the achievement of uniformity in the evaluation of the results obtained thanks to this test (e.g. the number and duration of erectile episodes, the interpretation of tumescence on its own, of the basal-apical dissociation, of the erectile episodes occurring immediately before waking, and of those of short duration). PMID:7951352

  1. Electric power, melatonin, and breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, R.G.

    1987-08-01

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

  2. Electric power, melatonin, and breast cancer

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

    Halladin, Natalie L; Busch, Sarah EkelØf

    2014-01-01

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

  4. Mitochondrial and metabolic dysfunction in renal convoluted tubules of obese mice: protective role of melatonin.

    Science.gov (United States)

    Stacchiotti, Alessandra; Favero, Gaia; Giugno, Lorena; Lavazza, Antonio; Reiter, Russel J; Rodella, Luigi Fabrizio; Rezzani, Rita

    2014-01-01

    Obesity is a common and complex health problem, which impacts crucial organs; it is also considered an independent risk factor for chronic kidney disease. Few studies have analyzed the consequence of obesity in the renal proximal convoluted tubules, which are the major tubules involved in reabsorptive processes. For optimal performance of the kidney, energy is primarily provided by mitochondria. Melatonin, an indoleamine and antioxidant, has been identified in mitochondria, and there is considerable evidence regarding its essential role in the prevention of oxidative mitochondrial damage. In this study we evaluated the mechanism(s) of mitochondrial alterations in an animal model of obesity (ob/ob mice) and describe the beneficial effects of melatonin treatment on mitochondrial morphology and dynamics as influenced by mitofusin-2 and the intrinsic apoptotic cascade. Melatonin dissolved in 1% ethanol was added to the drinking water from postnatal week 5-13; the calculated dose of melatonin intake was 100 mg/kg body weight/day. Compared to control mice, obesity-related morphological alterations were apparent in the proximal tubules which contained round mitochondria with irregular, short cristae and cells with elevated apoptotic index. Melatonin supplementation in obese mice changed mitochondria shape and cristae organization of proximal tubules, enhanced mitofusin-2 expression, which in turn modulated the progression of the mitochondria-driven intrinsic apoptotic pathway. These changes possibly aid in reducing renal failure. The melatonin-mediated changes indicate its potential protective use against renal morphological damage and dysfunction associated with obesity and metabolic disease. PMID:25347680

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

    Directory of Open Access Journals (Sweden)

    José Antonio Muñoz-Cueto

    2013-04-01

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

  6. Melatonin, immune function and aging

    Directory of Open Access Journals (Sweden)

    Perumal SR Pandi

    2005-11-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

  8. Nocturnal drainage wind characteristics in two converging air sheds

    International Nuclear Information System (INIS)

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

  9. Light at night, chronodisruption, melatonin suppression, and cancer risk: a review.

    Science.gov (United States)

    Reiter, Russel J; Tan, Dun-Xian; Korkmaz, Ahmet; Erren, Thomas C; Piekarski, Claus; Tamura, Hiroshi; Manchester, Lucien C

    2007-12-01

    Light exposure during the night is becoming progressively more common throughout the world, particularly in areas where electricity is commonly used. Also, the availability of artificial light has allowed humans to work or recreate throughout the 24-hour day. Based on photographs taken of the Earth from outer space, it is also apparent that true darkness is disappearing. For years it was assumed that polluting the daily dark period with light was inconsequential in terms of animal/human physiology. That assumption, however, has proven incorrect. Light at night has two major physiological actions, i.e., it disrupts circadian rhythms and suppresses the production of melatonin by the pineal gland. Moreover, both these changes are light intensity and wavelength dependent. Both human epidemiological and experimental studies on animals have documented that a potential negative consequence of chronodisruption and nocturnal melatonin inhibition is cancer initiation and growth. In epidemiological studies, the frequency of each of the following cancers has been reportedly increased in individuals who routinely work at night or whose circadian rhythms are disrupted for other reasons (e.g., due to jet lag): breast, prostate, endometrial, and colorectal. Likewise, in experimental animals, cancer growth is exaggerated when the animals are repeatedly phase advanced (as occurs during easterly flights) or exposed to light at night. A variety of mechanisms have been examined to explain how the suppression of melatonin exaggerates cancer risk. Mechanistically, how chronodisruption (without a consideration of melatonin suppression) would enhance cancer frequency is less clear. In addition to cancer, there may be other diseases that result from the chronic suppression of melatonin by light at night. PMID:18540832

  10. Melatonin Anticancer Effects: Review

    Directory of Open Access Journals (Sweden)

    Luigi Di Bella

    2013-01-01

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

  11. Pharmacology and function of melatonin receptors

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Pharmacology and function of melatonin receptors

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Melatonin enhances adult rat hippocampal progenitor cell proliferation via ERK signaling pathway through melatonin receptor.

    Science.gov (United States)

    Tocharus, C; Puriboriboon, Y; Junmanee, T; Tocharus, J; Ekthuwapranee, K; Govitrapong, P

    2014-09-01

    Melatonin, a neurohormone secreted mainly by the pineal gland, has a variety of physiological functions and neuroprotective effects. Previous studies have shown that melatonin could stimulate the proliferation of neural stem/progenitor cells (NS/PCs). Recent studies reported that the activities of mitogen-activated protein kinase (MAPK) of neural stem cells (NSCs) changed in response to the proliferative effect of melatonin. Therefore, the aim of the present study was to explore the proliferative mechanism mediated by melatonin on the adult rat hippocampal NS/PCs. Treatment with melatonin significantly increased the number of neurospheres in a concentration-dependent manner and up-regulated nestin protein. Pretreatment with luzindole, a melatonin receptor antagonist, and PD98059, a mitogen-activated protein kinase kinase (MEK) inhibitor, prevented the increase in the number of neurospheres formed by the activation of melatonin. The levels of phospho-c-Raf and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) increased when treated with melatonin. Pretreatment with luzindole or PD98059 prevented the melatonin-induced increase in these signaling molecules. The present results showed that melatonin could induce NS/PCs to proliferate by increasing phosphorylation of ERK1/2 and c-Raf through melatonin receptor. These results provide further evidence for a role of melatonin in promoting neurogenesis, adding to the remarkably pleiotropic nature of this neurohormone. This intrinsic modulator deserves further investigation to better understand its physiological and therapeutic implication. PMID:24956284

  16. Colour vision in diurnal and nocturnal hawkmoths.

    Science.gov (United States)

    Kelber, Almut; Balkenius, Anna; Warrant, Eric J

    2003-08-01

    Diurnal and nocturnal hawkmoths (Sphingidae, Lepidoptera) have three spectral types of receptor sensitive to ultraviolet, blue and green light. As avid flower visitors and pollinators, they use olfactory and visual cues to find and recognise flowers. Moths of the diurnal species Macroglossum stellatarum and the nocturnal species Deilephila elpenor, Hyles lineata and Hyles gallii use and learn the colour of flowers. Nocturnal species can discriminate flowers at starlight intensities when humans and honeybees are colour-blind. M. stellatarum can use achromatic, intensity-related cues if colour cues are absent, and this is probably also true for D. elpenor. Both species can recognise colours even under a changed illumination colour. PMID:21680465

  17. Circadian gating of epithelial-to-mesenchymal transition in breast cancer cells via melatonin-regulation of GSK3?.

    Science.gov (United States)

    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

    2012-11-01

    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 3? (GSK3?), 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 rhythm of GSK3? phosphorylation. Melatonin activates GSK3? by inhibiting the serine-threonine kinase Akt phosphorylation, inducing ?-catenin degradation and inhibiting epithelial-to-mesenchymal transition, a fundamental process underlying cancer metastasis. Thus, chronic circadian disruption by light-at-night via occupational exposure or age-related sleep disturbances may contribute to cancer incidence and the metastatic spread of breast cancer by inhibiting GSK3? activity and driving epithelial-to-mesenchymal transition in breast cancer patients. PMID:23002080

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

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2014-10-01

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

  19. Does melatonin have therapeutic use in tinnitus?

    Science.gov (United States)

    Merrick, Leah; Youssef, Dima; Tanner, Michelle; Peiris, Alan N

    2014-06-01

    Melatonin, a hormone produced by the pineal gland, may be a promising treatment option for tinnitus. The primary functions of this hormone are believed to be the initiation and maintenance of sleep because its secretions coincide with circadian rhythms. Some investigators have noted that melatonin may alleviate subjective symptoms of tinnitus. Moreover, melatonin may have properties protective against ototoxic drugs such as amikacin, gentamicin, or cancer therapeutic agents that are dose dependent. In vitro, melatonin has demonstrated antioxidative properties and it has been postulated that these antioxidative properties contribute to the alleviation of tinnitus. Melatonin levels used to obtain these findings in vitro, however, are at supraphysiologic levels; therefore, it is more likely that the benefits from taking supplemental melatonin occur from minimal antioxidative properties, sleep enhancement, or other potential methods of action that are not yet understood. Melatonin offers minimal risk of toxicity with modest daily doses such as 1 to 3 mg, as well as a low cost and favorable adverse effect profile for older adults. In addition to potential benefits in the treatment of tinnitus, melatonin also may have beneficial neurogenerative properties. We recommend that melatonin be considered for use in patients with significant tinnitus. PMID:24945170

  20. Plasma melatonin is reduced in Huntington's disease.

    Science.gov (United States)

    Kalliolia, Eirini; Silajdži?, Edina; Nambron, Rajasree; Hill, Nathan R; Doshi, Anisha; Frost, Chris; Watt, Hilary; Hindmarsh, Peter; Björkqvist, Maria; Warner, Thomas T

    2014-10-01

    This study was undertaken to determine whether the production of melatonin, a hormone regulating sleep in relation to the light/dark cycle, is altered in Huntington's disease. We analyzed the circadian rhythm of melatonin in a 24-hour study of cohorts of control, premanifest, and stage II/III Huntington's disease subjects. The mean and acrophase melatonin concentrations were significantly reduced in stage II/III Huntington's disease subjects compared with controls. We also observed a nonsignificant trend toward reduced mean and acrophase melatonin in premanifest Huntington's disease subjects. Onset of melatonin rise was significantly more temporally spread in both premanifest and stage II/III Huntington's disease subjects compared with controls. A nonsignificant trend also was seen for reduced pulsatile secretion of melatonin. Melatonin concentrations are reduced in Huntington's disease. Altered melatonin patterns may provide an explanation for disrupted sleep and circadian behavior in Huntington's disease, and represent a biomarker for disease state. Melatonin therapy may help the sleep disorders seen in Huntington's disease. PMID:25164424

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

    International Nuclear Information System (INIS)

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

  2. Melatonin implants do not alter estrogen feedback or advance puberty in gilts.

    Science.gov (United States)

    Kennaway, D J; Hughes, P E; van Wettere, W H E J

    2015-05-01

    Puberty in pigs is often delayed during late summer and autumn, with long daylength the most likely cause. We hypothesised (1) that gilts born around the shortest day would have a later release from the negative feedback actions of estradiol than gilts born around the spring equinox and (2) melatonin treatment would result in an earlier release from estradiol negative feedback and advance the onset of puberty in gilts born around the spring equinox. We first determined the optimal number of estradiol implants required to monitor the release from estradiol negative feedback in ovariectomised gilts. Secondly we determined whether melatonin implants altered negative feedback in 4 cohorts of ovariectomised gilts born between the winter solstice and spring equinox, and in the following year whether melatonin altered the time of the first ovulation in 5 cohorts of intact gilts born between the winter solstice and spring equinox. Plasma LH and FSH increased between 126 and 210d of age (P0.05). Age at first detection of elevated plasma progesterone in untreated, intact gilts decreased across the 4 cohorts (P0.05). In conclusion, while we confirmed that estradiol sensitivity is decreased as gilts age, we failed to demonstrate any effects of season or melatonin on estradiol feedback or melatonin on puberty. PMID:25618532

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

    Directory of Open Access Journals (Sweden)

    P.S.R. Mattos

    2000-10-01

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

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

    Scientific Electronic Library Online (English)

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

    2000-10-01

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

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

    International Nuclear Information System (INIS)

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

  6. Melatonin improves experimental colitis with sleep deprivation.

    Science.gov (United States)

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

    2015-04-01

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

  7. Melatonin in sperm biology: breaking paradigms.

    Science.gov (United States)

    Cebrián-Pérez, J A; Casao, A; González-Arto, M; dos Santos Hamilton, T R; Pérez-Pé, R; Muiño-Blanco, T

    2014-10-01

    Melatonin is a ubiquitous molecule, present in a wide range of organisms, and involved in multiple functions. Melatonin relays the information about the photoperiod to the tissues that express melatonin-binding sites in both central and peripheral nervous systems. This hormone has a complex mechanism of action. It can cross the cell plasma membrane and exert its actions in all cells of the body. Certain melatonin actions are mediated by receptors that belong to the superfamily of G-protein-coupled receptors (GPCRs), the MT1 and MT2 membrane. Melatonin can also bind to calmodulin as well as to nuclear receptors of the retinoic acid receptor family, ROR?1, ROR?2 and RZR?. The purpose of this review is to report on recent developments in the physiological role of melatonin and its receptors. Specific issues concerning the biological function of melatonin in mammalian seasonal reproduction and spermatozoa are considered. The significance of the continuous presence of melatonin in seminal plasma with a fairly constant concentration is also discussed. PMID:25277428

  8. Role of melatonin in embryo fetal development.

    Science.gov (United States)

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

    2014-01-01

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

  9. Decreased melatonin levels and increased levels of advanced oxidation protein products in the seminal plasma are related to male infertility.

    Science.gov (United States)

    Kratz, Ewa Maria; Piwowar, Agnieszka; Zeman, Michal; Stebelová, Katarína; Thalhammer, Theresia

    2014-09-12

    Melatonin, an indolamine secreted by the pineal gland, is known as a powerful free-radical scavenger and wide-spectrum antioxidant. Therefore, the aim of this study was to correlate markers of oxidative protein damage (advanced oxidation protein products, AOPPs) and the total antioxidant capacity (TAC) with melatonin levels in the seminal plasma of men with azoospermia (n=37), theratozoospermia (n=29) and fertile controls (normozoospermia, n=37). Melatonin concentration was measured by radioimmunoassay. The levels of AOPP as well as TAC efficiency (determined by the ferric reducing antioxidant power, FRAP) were estimated by spectrophotometric methods. The concentration of melatonin and AOPP significantly differed in azoospermic (PPr=-0.33, P=0.0016). The TAC levels were significantly higher in azoospermia than in theratozoospermia (P=0.0022) and the control group (P=0.00016). In azoospermia, the AOPP concentration was also significantly higher than that observed in theratozoospermia (P=0.00029). Decreased levels of melatonin together with elevated AOPP altered the oxidative-antioxidative balance in the ejaculate, thereby reducing fertility. Therefore, melatonin and AOPP levels may serve as additional diagnostic markers of semen quality and male reproductive potential. PMID:25218686

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

    International Nuclear Information System (INIS)

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

  11. Melatonin and aging: prospects for human treatment.

    Science.gov (United States)

    Bubenik, G A; Konturek, S J

    2011-02-01

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

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

    OpenAIRE

    Hardeland, Ru?diger

    2012-01-01

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

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

    Science.gov (United States)

    Tiryaki, Iskender; Keles, Huseyin

    2012-04-01

    Possible role of melatonin in the germination of negatively photoblastic and thermosensitive seeds of Phacelia tanacetifolia Benth was studied. Final germination percentage (FGP) was determined in the presence or absence of light at various temperatures, ranging from 0 to 40°C. The highest FGP was determined as 48.7% and 92% at temperature of 15°C in the presence and absence of light, respectively. Seeds were primed with 1% KNO(3) containing various concentrations (0.3, 1, 6, 12, 30, 60, or 90 ?M) of melatonin for 2 days at 15°C in darkness. Primed seeds were germinated at an inhibitory temperature of 30°C, and results were compared to those occurring at the optimum temperature of 15°C under both light and no light conditions. Melatonin incorporated into priming medium significantly reversed the inhibitory effects of light and high temperature. Germination was elevated from 2.5% to 52% of FGP for seeds primed in the presence of 6 ?M melatonin in darkness at 30°C, while 1 ?M melatonin had the highest FGP (21.0%) in the presence of light at 30°C. The highest FGP (47.5%) was obtained from seeds primed in the presence of 0.3 ?M melatonin under the light condition at 15°C, while untreated seeds had 1.5% of FGP. The fastest seed germination was determined from seeds primed in the presence of 0.3 ?M melatonin (G(50) = 0.56 days) at 15°C in darkness. The possible roles of melatonin in promoting germination parameters of photo- and thermosensitive seed germination are discussed. PMID:22225610

  14. Melatonin effects on Fundulus heteroclitus reproduction.

    Science.gov (United States)

    Lombardo, Francesco; Giorgini, Elisabetta; Gioacchini, Giorgia; Maradonna, Francesca; Ferraris, Paolo; Carnevali, Oliana

    2012-01-01

    This study aimed to investigate the effects of two different doses (100nM (M1) and 1µM (M2)) of exogenous melatonin on the reproductive capacity of Fundulus heteroclitus. Eight days of melatonin exposure significantly increased the fecundity and embryo survival of F. heteroclitus only in the M2 group compared with the control; the hatching rate was unaffected. Moreover, increases in the local expression of the melatonin receptor (mtnr) gene during follicle maturation were found; however, there were no differences between the experimental groups. Furthermore, in vitro melatonin-treated follicles showed a significantly higher germinal vesicle break down percentage compared with the control, while SDS-PAGE showed no difference in the electrophoretic pattern of the major yolk proteins. Nevertheless, densitometry revealed a greater intensity of the 118-, 95- and 40-kDa components in groups treated with melatonin. Finally, Fourier transform infrared microspectroscopy was applied to classify the different stages of oocyte development (Stages I-II, III and IV) on the basis of their macromolecular composition. The effects induced by melatonin on oogenesis were investigated by comparing vibrational spectra of females exposed to melatonin with those of controls. Changes to the Amide I band, corresponding to an increase in ?-structure, were found in oocytes of females exposed to the highest melatonin dose. These results highlight the positive role of melatonin, which is able to enhance the reproductive capacity of F. heteroclitus. Further studies are in progress to better explain the molecular mechanisms by which melatonin treatment affects reproduction in this marine species. PMID:22781930

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

    Science.gov (United States)

    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. Eosinophilic fasciitis with paroxysmal nocturnal hemoglobinuria.

    Science.gov (United States)

    de Boysson, Hubert; Chèze, Stéphane; Chapon, Françoise; Le Mauff, Brigitte; Auzary, Christophe; Geffray, Loïk

    2013-03-01

    Eosinophilic fasciitis is a rare connective tissue disorder, which can be associated with hematological complications in 10% of cases, such as aplastic anemia or acquired amegakaryocytic thrombocytopenia. Paroxysmal nocturnal hemoglobinuria had never been described in a patient suffering from eosinophilic fasciitis. We report an original case of a 59-year-old patient who developed a moderate aplastic pancytopenia while he was treated for a biopsy-proven eosinophilic fasciitis. A complete set of investigations was carried out and was found to be negative, including a first research of paroxysmal nocturnal hemoglobinuria. Two years after disease onset, while pancytopenia remained stable, occurrence of morning dark urine led to found a paroxysmal nocturnal hemoglobinuria clone. We discuss a potential link between the two conditions and hypothesize that paroxysmal nocturnal hemoglobinuria blood cells may pre-exist for a long time and take a survival advantage in the setting of marrow injury, as observed in eosinophilic fasciitis with hematological complications. We finally suggest that paroxysmal nocturnal hemoglobinuria should be included as a hematological complication of eosinophilic fasciitis. PMID:22999899

  17. Antepartum depression severity is increased during seasonally longer nights: Relationship to melatonin and cortisol timing and quantity

    Science.gov (United States)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-12-01

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

  20. The effect of sleep on nocturnal urine output

    DEFF Research Database (Denmark)

    Kamperis, Konstantinos; HagstrØm, SØren

    2005-01-01

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

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

    Science.gov (United States)

    Rocco, Michael V; Lockridge, Robert S; Beck, Gerald J; Eggers, Paul W; Gassman, Jennifer J; Greene, Tom; Larive, Brett; Chan, Christopher T; Chertow, Glenn M; Copland, Michael; Hoy, Christopher D; Lindsay, Robert M; Levin, Nathan W; Ornt, Daniel B; Pierratos, Andreas; Pipkin, Mary F; Rajagopalan, Sanjay; Stokes, John B; Unruh, Mark L; Star, Robert A; Kliger, Alan S; Kliger, A; Eggers, P; Briggs, J; Hostetter, T; Narva, A; Star, R; Augustine, B; Mohr, P; Beck, G; Fu, Z; Gassman, J; Greene, T; Daugirdas, J; Hunsicker, L; Larive, B; Li, M; Mackrell, J; Wiggins, K; Sherer, S; Weiss, B; Rajagopalan, S; Sanz, J; Dellagrottaglie, S; Kariisa, M; Tran, T; West, J; Unruh, M; Keene, R; Schlarb, J; Chan, C; McGrath-Chong, M; Frome, R; Higgins, H; Ke, S; Mandaci, O; Owens, C; Snell, C; Eknoyan, G; Appel, L; Cheung, A; Derse, A; Kramer, C; Geller, N; Grimm, R; Henderson, L; Prichard, S; Roecker, E; Rocco, M; Miller, B; Riley, J; Schuessler, R; Lockridge, R; Pipkin, M; Peterson, C; Hoy, C; Fensterer, A; Steigerwald, D; Stokes, J; Somers, D; Hilkin, A; Lilli, K; Wallace, W; Franzwa, B; Waterman, E; Chan, C; McGrath-Chong, M; Copland, M; Levin, A; Sioson, L; Cabezon, E; Kwan, S; Roger, D; Lindsay, R; Suri, R; Champagne, J; Bullas, R; Garg, A; Mazzorato, A; Spanner, E; Rocco, M; Burkart, J; Moossavi, S; Mauck, V; Kaufman, T; Pierratos, A; Chan, W; Regozo, K; Kwok, S

    2011-11-01

    Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome. PMID:21775973

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

    Science.gov (United States)

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

    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

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

    Science.gov (United States)

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

    2015-01-01

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

  4. Influence of light-dark and lunar cycles on the ocular melatonin rhythms in the seagrass rabbitfish, a lunar-synchronized spawner.

    Science.gov (United States)

    Rahman, Md Saydur; Kim, Byung-Ho; Takemura, Akihiro; Park, Chang-Bum; Lee, Young-Don

    2004-09-01

    The aim of this study was to investigate the effects of light-dark (LD) cycles and lunar phases on ocular melatonin rhythms in the seagrass rabbitfish, Siganus canaliculatus, a lunar-synchronized spawner. Under a natural 24-hr LD (12.00:12.00) cycle, ocular melatonin levels were low during daylight hours. The levels significantly elevated to peak during the mid-dark phase at 24.00 hr and then declined sharply in the early morning around 06.00 hr. These rhythms disappeared under either constant light (LL) or constant dark (DD) conditions. Melatonin levels remained low in LL compared with those in DD condition. These results suggest that ocular melatonin rhythms in the seagrass rabbitfish are suppressed in the presence of light. When fish were exposed to natural moon phases, ocular melatonin concentrations were higher around the new moon than both the first quarter and full moon phases. Exposure to experimental new moon conditions caused a significant increase in melatonin levels while those of the fish exposed to experimental full moon conditions were decreased. These results suggest that the seagrass rabbitfish perceives moonlight through the eye and that moonlight directly causes melatonin suppression. PMID:15298671

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

    OpenAIRE

    Rüdiger Hardeland

    2013-01-01

    The mammalian circadian system is composed of numerous oscillators, which gradually differ with regard to their dependence on the pacemaker, the suprachiasmatic nucleus (SCN). Actions of melatonin on extra-SCN oscillators represent an emerging field. Melatonin receptors are widely expressed in numerous peripheral and central nervous tissues. Therefore, the circadian rhythm of circulating, pineal-derived melatonin can have profound consequences for the temporal organization of almost all organ...

  6. Melatonin as a radioprotective agent: a review

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Karolina Danielczyk

    2009-09-01

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

  8. Neuromodulatory role of melatonin in retinal information processing.

    Science.gov (United States)

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

    2013-01-01

    The neurohormone melatonin is implicated in a variety of physiological processes. In the retina, a major source for melatonin production, melatonin is involved in modulation of neuronal activities. In this article we review recent advances in this research field, which is preceded by a concise account of general information about melatonin, melatonin receptors and intracellular signaling pathways for melatonin actions. Melatonin is mainly synthesized in and released from photoreceptors in the retina. Different subtypes of melatonin receptors are present on major types of retinal neurons, and the expression of these receptors is highly species- and neuron subtype-dependent. By activating different melatonin receptor subtypes, melatonin modulates activities of retinal neurons. In the outer retina, melatonin regulates the activity of photoreceptors. In addition, melatonin reduces the light responsiveness of cone-driven horizontal cells, but potentiates rod signal to rod-dominant ON type bipolar cells in teleost fish or inhibits the TEA-sensitive potassium channel of rod-driven ON type bipolar cells in rats. In the inner retina, melatonin potentiates inputs from glycinergic amacrine cells to ganglion cells in rats. These actions of melatonin on retinal neurons are mediated by distinct intracellular signaling pathways via different subtypes of melatonin receptors and all serve to improve visual performance in a world of changing ambient illumination. The topics, concerning allosteric action of melatonin, interplay between melatonin and dopamine systems, and potential interaction between melatonin and melanopsin systems, are also discussed. An in-depth discussion of future directions in this research field is presented. PMID:22986412

  9. Nocturnal faecal soiling and anal masturbation.

    OpenAIRE

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

    1990-01-01

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

  10. Nocturnal activity and the enuresis alarm device.

    OpenAIRE

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

    1984-01-01

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

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

    Science.gov (United States)

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

    2015-02-01

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

  12. Melatonin inhibits hippocampal long-term potentiation

    OpenAIRE

    Wang, Louisa M.; Suthana, Nanthia A.; Chaudhury, Dipesh; Weaver, David R.; Colwell, Christopher S.

    2005-01-01

    The goal of this study is to investigate the effect of the hormone melatonin on long-term potentiation and excitability measured by stimulating the Schaffer collaterals and recording the field excitatory postsynaptic potential from the CA1 dendritic layer in hippocampal brain slices from mice. Application of melatonin produced a concentration-dependent inhibition of the induction of long-term potentiation, with a concentration of 100 nM producing an ?50% inhibition of long-term potentiation...

  13. Melatonin in Plants: More Studies are Necessary

    OpenAIRE

    Arnao, Marino B.; Herna?ndez-ruiz, Josefa

    2007-01-01

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

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

    Science.gov (United States)

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

    2014-10-01

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

  15. Putative melatonin receptors in a human biological clock

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Ebaid Hossam

    2013-02-01

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

  17. Non-suppressibility by room light of pineal N-acetyltransferase activity and melatonin levels in two diurnally active rodents, the Mexican ground squirrel (Spermophilus mexicanus) and the eastern chipmunk (Tamias striatus).

    Science.gov (United States)

    Reiter, R J; Peters, J F

    1984-01-01

    The rhythms in pineal N-acetyltransferase (NAT) activity and melatonin levels were studied in the diurnally active Mexican ground squirrel and Eastern chipmunk. In the ground squirrel, both NAT activity and melatonin levels exhibited a marked nocturnal rise; these increases were not prevented by the exposure of these animals to a light irradiance of 200 microW/cm2 throughout the night. In the Eastern chipmunk, darkness at night was also associated with a marked rise in both the activity of the acetylating enzyme as well as the levels of melatonin. Again, these rhythms were not suppressed by the exposure of these animals to a light irradiance of 200 microW/cm2 for either 1 night or for 7 nights; exposure of chipmunks to light for 7 consecutive days did, however, reduce the rise in melatonin normally associated with darkness. The non-suppressibility of pineal NAT and melatonin by a 200 microW/cm2 light irradiance may relate either to the activity pattern of these animals, i.e., diurnal, or to their previous lighting history. PMID:6541997

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

    OpenAIRE

    Fourtillan, Jean B.

    2002-01-01

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

  19. Melatonin protects liver from intestine ischemia reperfusion injury in rats

    OpenAIRE

    Jian-yi Li, Hong-zhuan Yin

    2008-01-01

    AIM: To investigate the protective effect of melatonin on liver after intestinal ischemia-reperfusion injury in rats.METHODS: One hundred and fifty male Wistar rats, weighing 190-210 g, aged 7 wk, were randomly divided into melatonin exposure group, alcohol solvent control group and normal saline control group. Rats in the melatonin exposure group received intraperitoneal (IP) melatonin (20 mg/kg) 30 min before intestinal ischemia-reperfusion (IR), rats in the alcohol solvent control group re...

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

    Science.gov (United States)

    Iizuka, Hideaki; Yajima, Takehiko

    2003-01-01

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

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

    OpenAIRE

    Kong, Pil-jae; Byun, Jong-seon; Lim, So-young; Lee, Jae-jun; Hong, Sung-jun; Kwon, Kwang-jun; Kim, Sung-soo

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

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

    2010-01-01

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

  3. Nocturnal radiation from a solar collector

    Science.gov (United States)

    Wang, H. F.; Chiang, C. W.

    1980-11-01

    As the sky temperature during the night is relatively low compared to the ambient temperature, the temperature of the absorber plate in a solar collector can be lower than the ambient temperature due to nocturnal radiation. Measurements have been made for Lennox Solar Collectors installed in a solar heating and cooling project, a same collector in Rapid City and a simple home-made collector in the laboratory. The home-made collector consists of a brass-copper plate sprayed with flat-black paint, covered with glass sheets and boxed with two inch thick styrofoam insulation. A cooling as much as 10 C in winter has been observed. It is expected to be appreciably more in summer. This suggests a potential utilization of nocturnal radiation for air conditioning. Theoretical analysis is presented.

  4. Neutral evolution in paroxysmal nocturnal hemoglobinuria

    OpenAIRE

    Dingli, David; Luzzatto, Lucio; Pacheco, Jorge M.

    2008-01-01

    Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic stem cell (HSC) disorder characterized by the partial or complete deficiency of glycosyl-phosphatidylinositol (GPI)-linked membrane proteins, which leads to intravascular hemolysis. A loss of function mutation in the PIG-A gene, required for GPI biosynthesis, explains how the deficiency of many membrane proteins can result from a single genetic event. However, to date the mechanism of expansion of the GPI? clone has not been f...

  5. How I treat paroxysmal nocturnal hemoglobinuria

    OpenAIRE

    Brodsky, Robert A.

    2009-01-01

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

  6. Paroxysmal Nocturnal Hemoglobinuria from Bench to Bedside

    OpenAIRE

    Pu, Jeffrey J.; Brodsky, Robert A.

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Piero Bagnaresi

    2009-04-01

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

  8. Reduced nocturnal asthma by improved nasal breathing.

    Science.gov (United States)

    Petruson, B; Theman, K

    1996-05-01

    The nose and not the mouth should be used for breathing as the nose has better air conditioning capacity. When air is inhaled through the mouth it may dry and cool the respiratory mucosa, which can lead to bronchoconstriction in sensitive patients with asthma. By dilating the nostrils you can increase nasal breathing in most subjects. The aim of this study was to investigate whether sleeping with dilated nostrils reduces nocturnal asthma. At the Asthma and Allergy Research Centre, Gothenburg, 15 out-patients with nocturnal asthma were selected. Every other night for 10 nights the test subjects slept with the nasal dilator Nozovent which has been shown to increase the nasal air-flow and decrease the need for mouthbreathing. Every morning the patients self-reported on a form whether they had woken with asthma during the night or if they had had to take asthma medication. When sleeping with the nasal dilator the patients woke up with asthma on 17 of 75 nights as compared with 32 of 75 when sleeping without the device (p Nozovent, which mechanically dilates the nostrils and improves nasal breathing, can reduce nocturnal asthma. PMID:8790753

  9. Melatonin and its relevance to jet lag.

    Science.gov (United States)

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

    2009-03-01

    Jet lag is a disorder in which body rhythms are out of phase with the environment because of rapid travel across time zones. Although it often produces minor symptoms it can cause serious problems in those who need to make rapid critical decisions including airline pilots and business travelers. In this article the authors review basic knowledge underlying the body clock, the suprachiasmatic nucleus (SCN) of the hypothalamus, and the manner in which it regulates the sleep/wake cycle. The regulation of melatonin by the SCN is described together with the role of the melatonin receptors which are integral to its function as the major hormonal output of the body clock. Several factors are known that help prevent and treat jet lag, including ensuring adequate sleep, appropriate timing of exposure to bright light and treatment with melatonin. Because travel can cross a variable number of time zones and in two different directions, recommendations for treatment are given that correspond with these different types of travel. In addition to use of bright light and melatonin, other factors including timed exercise, timed and selective diets and social stimuli deserve study as potential treatments. Moreover, new melatonin agonists are currently under investigation for treatment of jet lag. PMID:19237140

  10. Melatonin as an antiaging drug: between facts and fantasy.

    Science.gov (United States)

    Huether, G

    1996-01-01

    This contribution makes an attempt to critically reassess the impressive career of melatonin from a stepchild of hormone research to a best-seller of drug marketing. Melatonin is an extremely interesting hormone. It is involved in the regulation of seasonal and circadian fluctuations of other hormones and in the synchronization of many different aspects of circadian rhythmicity to the light-dark cycle. In addition to these receptor-mediated functions, melatonin may act as a modulator of intracellular signal transduction to enhance or suppress the responses of many different cells to other incoming signals. Melatonin is also a potent scavenger of reactive oxygen species and may thus protect cells and tissues against radical-mediated damage. The production of melatonin declines with increasing age, and circulating melatonin levels are affected by certain pharmacological or physiological manipulations, notably food restriction which increases melatonin levels and prevents its age-related decline. Animal and cell culture experiments suggest that melatonin may have beneficial effects on certain aspects of aging and age-associated diseases. Of particular interest in this respect are reports on the influence of melatonin on the brain and the immune system. More research data are urgently needed in order to more clearly define the possible sites and mechanisms of these actions. Clinical studies need to be performed in order to identify possible side effects of long-term melatonin treatment, especially in elderly and diseased subjects. Serious concerns are raised about the use of uncontrolled, impure, or partially degraded melatonin preparations. PMID:9138978

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

    Science.gov (United States)

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

    2014-01-01

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

  12. Vibrational and electronic spectroscopic studies of melatonin.

    Science.gov (United States)

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

    2014-01-24

    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 NH stretching mode frequencies. It is found that the observed and calculated frequencies mismatch of NH stretching is due to intermolecular interactions between melatonin molecules. PMID:24041531

  13. Urinary Melatonin Levels and Skin Malignancy

    OpenAIRE

    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...

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

    Science.gov (United States)

    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

  15. Green Light for Nocturnally Migrating Birds

    Directory of Open Access Journals (Sweden)

    Marcel R. Wernand

    2008-12-01

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

  16. [Paroxysmal nocturnal hemoglobinuria and aplastic anemia].

    Science.gov (United States)

    Thollot, F; Bordigoni, P; Olive, D

    1984-03-01

    The case of a 14 year-old adolescent girl presenting with paroxysmal nocturnal hemoglobinuria (PNH) associated with aplastic anemia is reported. This disease, rare in children, is characterized by an acquired hemolytic anemia, with abnormal sensitivity to complement: PNH actually affects the bone marrow stem cell. This explains its possible association with any type of malignant blood disease and with aplastic anemia. When aplastic anemia is the first sign of the disease, diagnosis is delayed, due to the possible negative response of the specific Ham's test. Therefore, the proper complications of PNH, especially thromboses, may be misappreciated and poorly managed. PMID:6742973

  17. Early dinner reduces nocturnal gastric acidity.

    OpenAIRE

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

    1989-01-01

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

  18. The research of melatonin in hypoxic-ischemic encephalopathy

    International Nuclear Information System (INIS)

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

  19. Small doses of melatonin increase intestinal motility in rats.

    Science.gov (United States)

    Drago, Filippo; Macauda, Silvia; Salehi, Soudabeh

    2002-09-01

    Since melatonin receptors are present in the intestines, the possibility that this hormone may affect intestinal motility has been studied in the rat. Sprague-Dawley male rats were given a carmine cochineal powder meal and were injected intraperitoneally with 1, 10, 100, or 1000 microg/kg melatonin. Sixty minutes after treatment, intestinal transit was found to be faster in animals treated with small doses of melatonin (1 or 10 microg/kg) than in saline-injected controls. This effect, however, appear to be clearly reversed with 100 or 1000 microg/kg melatonin. In fact, these doses of the hormone reduced intestinal transit in rats. The nonselective melatonin receptor antagonist, luzindole (administered intraperitoneally in a dose of 0.25 mg/kg, 15 min prior to melatonin injection) totally prevented the accelerating effect of melatonin (10 microg/kg) on intestinal transit. Luzindole per se failed to affect gut motility. Injection of the reversible acetylcholinesterase inhibitor and cholinergic agent, neostigmine, accelerated intestinal transit but failed to influence melatonin effect on this parameter. In contrast, intraperitoneal injection of the muscarinic receptor antagonist atropine delayed intestinal transit per se but did not reduce the stimulating effect of melatonin on this parameter. Intestinal myoelectrical recording revealed that intestinal myoelectrical activity was increased by intraperitoneal injection of melatonin (10 microg/kg). Administration of luzindole totally prevented melatonin-induced increase of intestinal myoelectrical activity. These results indicate that melatonin may affect intestinal motility in rats when administered in small doses. This effect might be mediated by melatonin receptors in the intestines, although the involvement of central receptors for the hormone is also possible. PMID:12353839

  20. Therapeutic implications of melatonin in cerebral edema.

    Science.gov (United States)

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

    2014-12-01

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

  1. Isolation of melatonin by immunoaffinity chromatography.

    Czech Academy of Sciences Publication Activity Database

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

    2002-01-01

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

  2. Visual orientation and navigation in nocturnal arthropods.

    Science.gov (United States)

    Warrant, Eric; Dacke, Marie

    2010-01-01

    With their highly sensitive visual systems, the arthropods have evolved a remarkable capacity to orient and navigate at night. Whereas some navigate under the open sky, and take full advantage of the celestial cues available there, others navigate in more difficult conditions, such as through the dense understory of a tropical rainforest. Four major classes of orientation are performed by arthropods at night, some of which involve true navigation (i.e. travel to a distant goal that lies beyond the range of direct sensory contact): (1) simple straight-line orientation, typically for escape purposes; (2) nightly short-distance movements relative to a shoreline, typically in the context of feeding; (3) long-distance nocturnal migration at high altitude in the quest to locate favorable feeding or breeding sites, and (4) nocturnal excursions to and from a fixed nest or food site (i.e. homing), a task that in most species involves path integration and/or the learning and recollection of visual landmarks. These four classes of orientation--and their visual basis--are reviewed here, with special emphasis given to the best-understood animal systems that are representative of each. PMID:20733292

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

    OpenAIRE

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

    2013-01-01

    Abstract This study investigated the protective effects of melatonin and folic acid against carbon tetrachloride (CCl4)-induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. The levels of protein kinase B (Akt1), interferon gamma (IFN-?), programmed cell death-receptor (Fas) and Tumor necrosis factor-alpha (TNF-?) mRNA expression were analyzed. CCl4 significantly elevated the levels of lipid peroxidation (MDA), choleste...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-12-31

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

  5. Nocturnal hypertension and impaired sympathovagal tone in Turner syndrome

    DEFF Research Database (Denmark)

    Gravholt, Claus HØjbjerg; Hansen, Klavs Würgler

    2006-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2013-01-01

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

  8. Melatonin and its use in atherosclerosis and dyslipidemia

    Directory of Open Access Journals (Sweden)

    Danilenko KV

    2013-03-01

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

  9. Immunohistochemical assessment of melatonin binding in the pineal gland.

    Science.gov (United States)

    Holloway, W R; Grota, L J; Brown, G M

    1985-01-01

    Melatonin binding in the pineal gland of albino rats is estimated using an immunohistochemical procedure. Binding is saturable, has relatively high affinity (Apparent KD = 2.7 nM), and competition studies indicate binding of indoleamines possessing an N-acetyl group on the terminus of the side chain (N-acetylserotonin and melatonin). These data are consistent with the interpretation that immunohistochemically determined melatonin in unfixed pineal tissue is assessing binding of N-acetylated indolealkylamines to pineal cell components. In albino rats maintained on 12-hour light: 12-hour dark cycles, melatonin binding exhibits a diurnal rhythm with low levels of saturation (30%) early in the light and saturation by endogenous melatonin near the onset of darkness. An annual rhythm of melatonin binding was observed in albino rats with low levels during the summer and high levels during the winter. Other rats were maintained on 12-hour light:dark cycles and fed for 2 hours either early in the light period or early in the dark period. For both morning- and evening-fed animals, melatonin binding was high prior to feeding and dropped immediately after feeding. Changes in melatonin binding that occur in response to alterations of feeding and time of year suggest the possibility that this binding reflects a functional site for melatonin. PMID:3913762

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

    Science.gov (United States)

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

    2014-06-01

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

  11. Molecular mechanisms of melatonin's inhibitory actions on breast cancers.

    Science.gov (United States)

    Proietti, Sara; Cucina, Alessandra; Reiter, Russel J; Bizzarri, Mariano

    2013-06-01

    Melatonin is involved in many physiological functions and it plays an important role in many pathological processes as well. Melatonin has been shown to reduce the incidence of experimentally induced cancers and can significantly inhibit the growth of some human tumors, namely hormone-dependent cancers. The anticancer effects of melatonin have been observed in breast cancer, both in in vivo with models of chemically induced rat mammary tumors, and in vitro studies on human breast cancer cell lines. Melatonin acts at different physiological levels and its antitumoral properties are supported by a set of complex, different mechanisms of action, involving apoptosis activation, inhibition of proliferation, and cell differentiation. PMID:23007844

  12. Raconter Accident nocturne de Patrick Modiano Raconter Accident nocturne de Patrick Modiano

    Directory of Open Access Journals (Sweden)

    Jurate Kaminskas

    2012-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Sezgin Erdiman

    2011-01-01

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

  14. Nocturnal choking episodes: under-recognized and misdiagnosed.

    Science.gov (United States)

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

    2010-11-01

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

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

    International Nuclear Information System (INIS)

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

  16. Nocturnal flow on a western Colorado slope

    International Nuclear Information System (INIS)

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

  17. Expression of melatonin receptors in arteries involved in thermoregulation

    International Nuclear Information System (INIS)

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

  18. Urinary melatonin levels and skin malignancy.

    Science.gov (United States)

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

    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 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 (Pcancer. This association, however, requires further investigation. PMID:24453396

  19. Microorganisms for the production of melatonin

    DEFF Research Database (Denmark)

    Knight, Eric Michael Technical University of Denmark,

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

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

    Science.gov (United States)

    George, Kelly A; Archer, Melanie S; Toop, Tes

    2013-01-01

    Worldwide research into nocturnal colonization by blowflies has produced many contradictory findings, prompting investigation specific to southeastern Australia. Initial experiments showed that blowfly colonization begins shortly after sunrise and continues until sunset; nocturnal colonization never occurred. Colonization peaks occurred at mid-morning, midday, and in the hours preceding sunset. In an additional experiment, wild blowflies were captured and placed in cages with colonization medium supplied nocturnally. Colonization occurred on four of five nights, and Calliphora augur (Fabricius) (Diptera: Calliphoridae) was the main species colonizing baits nocturnally. Results suggest that colonization is most likely to occur during warm weather and when flies are able to walk or crawl to bait. In particular, blowflies trapped within a confined space (such as a room or car) with warmer-than-ambient temperature may be stimulated to colonize nearby remains. Entomologists should consider these findings when estimating minimum postmortem interval under these environmental conditions. PMID:22994948

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

    Directory of Open Access Journals (Sweden)

    Dun-Xian Tan

    2014-09-01

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

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

    Science.gov (United States)

    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

  3. The impact of nocturnal hemodialysis on sexual function

    OpenAIRE

    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...

  4. Working for Food Shifts Nocturnal Mouse Activity into the Day

    OpenAIRE

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

    2011-01-01

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

  5. Nocturnal sleep pattern in native Brazilian Terena adults

    OpenAIRE

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

    2000-01-01

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

  6. Hearing is not necessarily believing in nocturnal anurans

    OpenAIRE

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2002-01-01

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

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

    Science.gov (United States)

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

    2015-05-01

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

  9. Melatonin improves spatial navigation memory in male diabetic rats

    Directory of Open Access Journals (Sweden)

    Farrin Babaei-Balderlou

    2012-09-01

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

  10. Potentiation of Isoniazid Activity against Mycobacterium tuberculosis by Melatonin

    OpenAIRE

    Wiid, Ian; Hoal-van Helden, Eileen; Hon, Dinie; Lombard, Carl; Helden, Paul

    1999-01-01

    The limited number of effective antituberculosis drugs available necessitates optimizing current treatments. We show that melatonin, which is synthesized in the pineal gland, can cause at least a threefold increase in the efficacy of isoniazid. This suggests that tuberculosis chemotherapy can be improved by innate molecules such as melatonin.

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

    Science.gov (United States)

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

    2014-08-27

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

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

    Science.gov (United States)

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

    1999-01-01

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

  13. Oxcarbazepine in children with nocturnal frontal-lobe epilepsy.

    Science.gov (United States)

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

    2007-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Ahmet Korkmaz

    2011-02-01

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

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

    OpenAIRE

    Michielsen, Dirk P. J.; Jean-Jacques Amy

    2005-01-01

    Objectives: The NEVA® device (Urometrics, Inc) measures changes in penile blood flow during nocturnal erections and enables one to make the diagnosis of either arterial insufficiency or venous leakage. The RigiScan® (Osbon Medical Systems) determines the quality of nocturnal erections to establish the organic or psychogenic nature of erectile dysfunction (ED) without indicating the nature of the impotence. This study compares both devices and tries to answer two questions. Does NEVA® give ...

  16. Melatonin promotes differentiation of 3T3-L1 fibroblasts.

    Science.gov (United States)

    González, Alicia; Alvarez-García, Virginia; Martínez-Campa, Carlos; Alonso-González, C; Cos, Samuel

    2012-01-01

    Melatonin inhibits the genesis and growth of breast cancer by interfering at different levels in the estrogen-signaling pathways. Melatonin inhibits aromatase activity and expression in human breast cancer cells, thus behaving as a selective estrogen enzyme modulator. As the adipose tissue adjacent to the tumor seems to account for most aromatase expression and enzyme activity in breast tumors and also mediates the desmoplastic reaction or accumulation of undifferentiated fibroblasts around malignant epithelial cells, in this work, we studied the effects of melatonin on the conversion of preadipocytes (3T3-L1) into adipocytes and on the capability of these cells to synthesize estrogens by regulating the expression and enzyme activity of aromatase, one of the main enzymes that participates in the synthesis of estrogens in the peritumoral adipose tissue. Thus, in both differentiating and differentiated 3T3-L1 adipocytes, high concentrations of melatonin increased intracytoplasmic triglyceride accumulation, an indicator of adipogenic differentiation. Melatonin (1 mm) significantly increased the expression of both CCAAT/enhancer-binding protein ? and peroxisome proliferator-activated receptor ?, two main regulators of terminal adipogenesis, in 3T3-L1 cells. The presence of melatonin during differentiation also induced a parallel reduction in aromatase expression and activity and expression of the cells. The effects of melatonin were reversed by luzindole, a melatonin receptor antagonist, indicating that melatonin acts through known receptor-mediated mechanisms. These findings suggest that, in human breast tumors, melatonin could stimulate the differentiation of fibroblasts and reduce the aromatase activity and expression in both fibroblasts and adipocytes, thereby reducing the number of estrogen-producing cells proximal to malignant cells. PMID:21718362

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

    Directory of Open Access Journals (Sweden)

    Da_-Evcimen N.

    2009-01-01

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

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Dirk P.J. Michielsen

    2005-09-01

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

  20. Spectral modulation of light wavelengths using optical filters: effect on melatonin secretion.

    Science.gov (United States)

    Casper, Robert F; Rahman, Shadab

    2014-08-01

    Shiftwork has been identified as a risk factor for various medical problems, such as cancer, heart disease, metabolic disturbances, depression, and anxiety disorders, and as reviewed this month, adverse reproductive function. Shiftwork misaligns physiological rhythms with respect to each other and to external environmental rhythms such as the 24-hour light/dark cycle. Light is the strongest time cue for entraining circadian rhythms in mammals, and aberrant light exposure patterns during shiftwork is one of the key factors that induce circadian misalignment. We have recently demonstrated, in both animal and clinical models, that filtering short wavelengths (below 480 nm) from nocturnal lighting can attenuate alterations in hormone secretion (melatonin and glucocorticoids) and in central and peripheral clock gene expression induced by nighttime light exposure. We also demonstrated that the use of optical filters led to an improvement in mood and in cognitive performance under controlled laboratory conditions and during field-based shiftwork studies. Moreover, there was an increase in sleep duration and quality on nights immediately following night shifts. We believe it is likely that optical filters incorporated into glasses or as coverings for light bulbs could be used as a method to improve or prevent many of the medical problems associated with circadian misalignment and rotating shiftwork. PMID:25015557

  1. Paroxysmal nocturnal hemoglobinuria from bench to bedside.

    Science.gov (United States)

    Pu, Jeffrey J; Brodsky, Robert A

    2011-06-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease that presents with protean manifestations. Clinical and laboratory investigation over the past 25 years has uncovered most of the basic science underpinnings of PNH and has led to the development of a highly effective targeted therapy. PNH originates from a multipotent hematopoietic stem cell (HSC) that acquires a somatic mutation in a gene called phosphatidylinositol glycan anchor biosynthesis, class A (PIG-A). The PIG-A gene is required for the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Failure to synthesize GPI anchors leads to an absence of all proteins that utilize GPI to attach to the plasma membrane. Two GPI-anchor proteins, CD55 and CD59, are complement regulatory proteins; their absence on the surface of PNH cells leads to complement-mediated hemolysis. The release of free hemoglobin leads to scavenging of nitric oxide and contributes to many clinical manifestations, including esophageal spasm, fatigue, and possibly thrombosis. Aerolysin is a pore-forming toxin that binds GPI-anchored proteins and kills normal cells, but not PNH cells. A fluorescinated aerolysin variant (FLAER) binds GPI-anchor and serves as a novel reagent diagnosing PNH. Eculizumab, a humanized monoclonal antibody against C5, is the first effective drug therapy for PNH. PMID:21707954

  2. Paroxysmal nocturnal hemoglobinuria: a red clot syndrome.

    Science.gov (United States)

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

    2014-01-01

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

  3. Laboratory tests for paroxysmal nocturnal hemoglobinuria.

    Science.gov (United States)

    Preis, Meir; Lowrey, Christopher H

    2014-03-01

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

  4. Protective effect of melatonin on thrombocytopoiesis in irratiated mice

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Lemoine P

    2011-07-01

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

  6. Is Nocturnal Systolic Blood Pressure Rise Associated with Central Hemodynamics and Arterial Stiffness?

    Directory of Open Access Journals (Sweden)

    Gülperi ÇEL?K

    2012-05-01

    Full Text Available OBJECTIVE: The aim of this study was to assess central hemodynamics and parameters of arterial stiffness of cases with nocturnal blood pressure rise. MATERIAL and METHODS: In this retrospective study, ambulatory blood pressure monitoring of 252 hypertensive patients was performed with the Mobil-O-Graph Arteriograph. RESULTS: 174 (%69.0 out of 252 patients were female and 78 (%31 were male and the mean age was 54.5±14.4. When Pearson's correlation test was performed, the nocturnal systolic blood pressure (SBP decline was associated with age (r=-0.169, p=0.008, diurnal pulse wave velocity (PWV (r=-0.179, p=0.005, nocturnal diastolic blood pressure (DBP decline (r=0.790, p<0.001, nocturnal central SBP (r=-0.410, p<0.001, and nocturnal augmentation index (Aix@75 (r=-0.215, p=0.001. When patients were divided into three groups as 10 % or more nocturnal SBP decline, less than 10 % nocturnal SBP decline and nocturnal SBP increase, there were statistically signifi cant differences regarding nocturnal pulse pressure (p<0.001, nocturnal DBP decline (p<0.001, nocturnal Aix@75 (p<0.001, and nocturnal peripheral resistance (p<0.001. CONCLUSION: We believe that strict follow up of conventional risk factors causing arterial stiffness in patients with less than 10 % nocturnal BP decline or increase and also the use of chronotherapy may be useful.

  7. Extrapineal melatonin: location and role within diffuse neuroendocrine system.

    Science.gov (United States)

    Kvetnoy, I M

    1999-01-01

    During the last decade, much attention has centred on melatonin, one of the hormones of the diffuse neuroendocrine system. For many years it was considered to be only a hormone of the pineal gland. As soon as highly sensitive antibodies to indolealkylamines became available, melatonin was identified not only in pineal gland, but also in extrapineal tissues. These included the retina, Harderian gland, gut mucosa, cerebellum, airway epithelium, liver, kidney, adrenals, thymus, thyroid, pancreas, ovary, carotid body, placenta and endometrium. It has also been localized in non-neuroendocrine cells such as mast cells, natural killer cells, eosinophilic leukocytes, platelets and endothelial cells. This list of cells indicates that melatonin has a unique position among the hormones of the diffuse neuroendocrine system. It is found in practically all organ systems. Functionally, melatonin-producing cells are part and parcel of the diffuse neuroendocrine system as a universal system of response, control and organism protection. Taking into account the large number of such melatonin-producing cells in many organs, the wide spectrum of biological activities of melatonin and especially its main property as a universal regulator of biological rhythms, it is now possible to consider extrapineal melatonin as a key paracrine signal molecule for the local co-ordination of intercellular relationships. PMID:10405817

  8. Ebola virus: melatonin as a readily available treatment option.

    Science.gov (United States)

    Anderson, George; Maes, Michael; Markus, Regina P; Rodriguez, Moses

    2015-04-01

    There is currently an urgent need for a viable, cheap, and readily available treatment for the Ebola virus outbreak in West Africa. Here, it is proposed that melatonin may have significant utility in helping the management of this outbreak. Optimizing natural killer (NK) cell responses seems crucial to surviving Ebola virus infection. Melatonin increases NK cell cytotoxicity significantly, suggesting efficacy in managing the Ebola virus. Under conditions of challenge, melatonin increases heme oxygenase-1 (HO-1), which inhibits Ebola virus replication. Melatonin also has protective effects in cases of septic shock, which, although bacterial, has similar end-point presentations involving blood vessel leakage. Melatonin's effects on haemorrhage are mediated primarily by a decrease in pro-inflammatory cytokines. By optimizing the appropriate immune response, melatonin is likely to afford protection to those at high risk of Ebola viral infection, as well as having direct impacts on the course of infection per se. Although no direct data pertain to the utility of melatonin in the management of the Ebola virus, convergent bodies of data suggest its utility, which is reviewed in this article. PMID:25611054

  9. A radiobiological review on melatonin. A novel radioprotector

    International Nuclear Information System (INIS)

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

  10. Solubilization and purification of melatonin receptors from lizard brain

    International Nuclear Information System (INIS)

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

  11. Melatonin modulates aromatase activity and expression in endothelial cells.

    Science.gov (United States)

    Alvarez-García, Virginia; González, Alicia; Martínez-Campa, Carlos; Alonso-González, Carolina; Cos, Samuel

    2013-05-01

    Melatonin is known to suppress the development of endocrine-responsive breast cancers by interacting with the estrogen signaling pathways. Paracrine interactions between malignant epithelial cells and proximal stromal cells are responsible for local estrogen biosynthesis. In human breast cancer cells and peritumoral adipose tissue, melatonin downregulates aromatase, which transforms androgens into estrogens. The presence of aromatase on endothelial cells indicates that endothelial cells may contribute to tumor growth by producing estrogens. Since human umbilical vein endothelial cells (HUVECs) express both aromatase and melatonin receptors, the aim of the present study was to evaluate the ability of melatonin to regulate the activity and expression of aromatase on endothelial cells, thus, modulating local estrogen biosynthesis. In the present study, we demonstrated that melatonin inhibits the growth of HUVECs and reduces the local biosynthesis of estrogens through the downregulation of aromatase. These results are supported by three lines of evidence. Firstly, 1 mM of melatonin counteracted the testosterone-induced cell proliferation of HUVECs, which is dependent on the local biosynthesis of estrogens from testosterone by the aromatase activity of the cells. Secondly, we found that 1 mM of melatonin reduced the aromatase activity of HUVECs. Finally, by real?time RT-PCR, we demonstrated that melatonin significantly downregulated the expression of aromatase as well as its endothelial-specific aromatase promoter region I.7. We conclude that melatonin inhibits aromatase activity and expression in HUVECs by regulating gene expression of specific aromatase promoter regions, thereby reducing the local production of estrogens. PMID:23450505

  12. Antiangiogenic effects of melatonin in endothelial cell cultures.

    Science.gov (United States)

    Alvarez-García, Virginia; González, Alicia; Alonso-González, Carolina; Martínez-Campa, Carlos; Cos, Samuel

    2013-05-01

    Endothelial cells represent one of the critical cellular elements in tumor microenvironment playing a crucial role in the growth and progression of cancer through controlling angiogenesis. Vascular endothelial growth factor (VEGF) produced from tumor cells is essential for the expansion of breast cancer and may function in both paracrine and autocrine manners to promote proliferation, growth, survival and migration of endothelial cells. Since melatonin regulates tumor microenvironment by decreasing the secretion of VEGF by malignant epithelial cells and also regulates VEGF expression in human breast cancer cells, the aim of the present study was to investigate the anti-angiogenic activity of melatonin against the pro-angiogenic effects of breast cancer cells. In this work, we demonstrate that melatonin strongly inhibited the proliferation as well as invasion/migration of human umbilical vein endothelial cells (HUVECs). Melatonin disrupted tube formation and counteracted the VEGF-stimulated tubular network formation by HUVEC. In addition, conditioned media collected from human breast cancer cells were angiogenically active and stimulated tubule length formation and this effect was significantly counteracted by the addition of anti-VEGF or melatonin. Melatonin also disintegrated preformed capillary network. All these findings demonstrate that melatonin may play a role in the paracrine interactions that take place between malignant epithelial cells and proximal endothelial cells. Melatonin could be important in reducing endothelial cell proliferation, invasion, migration and tube formation, through a downregulatory action on VEGF. Taken together, our findings suggest that melatonin could potentially be beneficial as an antiangiogenic agent in breast cancer with possible future clinical applications. PMID:23473980

  13. Renal involvement in paroxysmal nocturnal hemoglobinuria.

    Science.gov (United States)

    Hussain, S; Qureshi, A; Kazi, J

    2013-01-01

    Renal involvement in paroxysmal nocturnal hemoglobinuria (PNH) is not usually apparent but in cases with clinical involvement varies from reversible acute dysfunction to chronic irreversible damage. Early diagnosis and treatment is crucial to prevent disease progression and irreversible chronic kidney disease (CKD). The ultimate outcome of CKD in many patients is the need for renal replacement therapy, which necessitates ever-growing dialysis and transplantation programs, thereby imposing a significant economic burden on the healthcare system. In a third-world country like Pakistan, increased burden due to CKD can be very hard on families. Doctor visits, hospitalization, and dialysis are all out-of-pocket expenses, therefore prevention, early detection, and timely intervention are the only cost-effective strategies. We report a case of acute kidney injury (AKI) due to PNH. This case shows AKI as one of the complications of PNH which may have a clinical course like acute tubular necrosis (ATN). This could be due to ATN or AKI superimposed on CKD due to hemosiderin deposits in the renal tubular epithelial cells. Our patient was dialyzed initially and discharged with a permanent catheter in place with advice to continue dialysis three times a week. He required dialysis for 1 week then started producing urine. His subsequent outpatient visits showed improved renal function. The permanent catheter was removed and maintenance dialysis was stopped. Here, we briefly review the literature on renal involvement in PNH, treatment options for PNH and pigment-induced nephropathy followed by a question-and-answer session at the clinicopathological conference held on March 4, 2011, at Sindh Institute of Urology and Transplantation in Karachi, Pakistan. PMID:23752125

  14. Caregiver burden among nocturnal home hemodialysis patients.

    Science.gov (United States)

    Rioux, Jean-Philippe; Narayanan, Ranjit; Chan, Christopher T

    2012-04-01

    Recent studies have suggested improvements in quality of life (QOL) in patients on quotidian dialysis compared with conventional hemodialysis. Few studies have focused on the burden and QOL in caregivers of patients with end-stage renal disease (ESRD) on nocturnal home hemodialysis (NHD). We aim to assess the caregivers' burden, QOL, and depressive symptoms and to compare these parameters with their patients' counterparts. Cross-sectional surveys were sent to 61 prevalent NHD patients and their caregivers. Surveys assessed demographics, general self-perceived health using the 12-Item Short Form Health Survey (SF-12) and the presence of depression using the Beck Depression Inventory. Subjective burden on caregivers was assessed by the Caregiver Burden scale and was compared with perceived burden by the patients. Thirty-six patients and 31 caregivers completed the survey. The majority of caregivers were female (66%), spouse (81%) with no comorbid illness (72%). Their mean age was 51 ± 11 years. Patients were mostly male (64%) with a median ESRD vintage of 60 months (interquartile range [IQR], 18-136 months) and a mean age of 52 ± 10 years. Compared to caregivers, patients had lower perceived physical health score but had similar mental health score. Depression criteria were present in 47% of patients and 25% of caregivers. Total global burden perceived by either caregivers or patients is relatively low. Although there is a relatively low global burden perceived by caregivers and patients undergoing NHD, a significant proportion of both groups fulfilled criteria for depression. Further innovative approaches are needed to support caregivers and patients performing NHD to reduce the intrusion of caring for a chronic illness and the risk of developing depression. PMID:22304491

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

    OpenAIRE

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

    1987-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-01

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

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

    International Nuclear Information System (INIS)

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

  18. Localization of melatonin in the digestive tract of the rat. Effect of maturation, diurnal variation, melatonin treatment and pinealectomy.

    Science.gov (United States)

    Bubenik, G A

    1980-01-01

    Using highly specific antibodies, melatonin was identified in the gastrointestinal tract of the rat as early as several hours of postnatal life. Its amount progressively increased and reached the adult levels around day 21. Exogenously administered melatonin concentrates in all parts of the gastrointestinal tract with most pronounced accumulation in the colon and the rectum. Diurnal variations were not clearly demonstrated in any part of the alimentary canal. Pinealectomy had no visible effect on the levels of melatonin in the tissues investigated. A hypothesis of ontogenic as well as phylogenic development of production of N-acetylated indolealkylamines in the pineal and the extrapineal tissues and their physiological role is presented. PMID:6998853

  19. Urinary Melatonin Levels and Skin Malignancy

    Science.gov (United States)

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

    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 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. PMID:24453396

  20. Urinary Melatonin Levels and Skin Malignancy

    Directory of Open Access Journals (Sweden)

    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.

  1. Diurnality, nocturnality, and the evolution of primate visual systems.

    Science.gov (United States)

    Ankel-Simons, F; Rasmussen, D T

    2008-01-01

    Much of the recent research on the evolution of primate visual systems has assumed that a minimum number of shifts have occurred in circadian activity patterns over the course of primate evolution. The evolutionary origins of key higher taxonomic groups have been interpreted by some researchers as a consequence of a rare shift from nocturnality to diurnality (e.g., Anthropoidea) or from diurnality to nocturnality (e.g., Tarsiidae). Interpreting the evolution of primate visual systems with an ecological approach without parsimony constraints suggests that the evolutionary transitions in activity pattern are more common than what would be allowed by parsimony models, and that such transitions are probably less important in the origin of higher level taxa. The analysis of 17 communities of primates distributed widely around the world and through geological time shows that primate communities consistently contain both nocturnal and diurnal forms, regardless of the taxonomic sources of the communities. This suggests that primates in a community will adapt their circadian pattern to fill empty diurnal or nocturnal niches. Several evolutionary transitions from one pattern to the other within narrow taxonomic groups are solidly documented, and these cases probably represent a small fraction of such transitions throughout the Cenozoic. One or more switches have been documented among platyrrhine monkeys, Malagasy prosimians, Eocene omomyids, Eocene adapoids, and early African anthropoids, with inconclusive but suggestive data within tarsiids. The interpretation of living and extinct primates as fitting into one of two diarhythmic categories is itself problematic, because many extant primates show significant behavioral activity both nocturnally and diurnally. Parsimony models routinely interpret ancestral primates to have been nocturnal, but analyses of morphological and genetic data indicate that they may have been diurnal, or that early primate radiations were likely to have generated both nocturnal and diurnal forms, especially given the unusual annual light regimes faced by Early Tertiary primates living outside today's latitudinal tropics. We review the essential morphology and physiology of the primate visual system to look for features that might constrain evolutionary switches, and we find that the pattern of variation within and among primate groups in eye size, corneal size, retinal morphology, and opsin distribution are all consistent with the idea that there is considerable evolutionary flexibility in the visual system. These results suggest that primate lineages may evolve from diurnal to nocturnal, and vice versa, more readily and more rapidly than has been suggested by the use of strict parsimony models. This has implications for interpreting the fossil record and reconstructing key evolutionary events in primate evolution. PMID:19003895

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Mohammadreza Gholami

    2014-02-01

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

  4. New actions of melatonin and their relevance to biometeorology

    Science.gov (United States)

    Hardeland, Rüdiger

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

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

    Science.gov (United States)

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

    2015-03-18

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

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

    Scientific Electronic Library Online (English)

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

    2013-08-01

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

  7. Variations in sea bass melatonin concentration and receptors

    OpenAIRE

    Bayarri, Mari?a J.; Falcon, Jack; Zanuy, Silvia; Carrillo, Manuel

    2010-01-01

    The present study reports on the daily and seasonal variations in plasma melatonin concentration, and also in optic tectum and hypothalamus melatonin binding sites, in male European sea bass maintained under natural photoperiod (NP) or continuous light (LL) from early stages of development. Samples were collected on a 24-h cycle, at four physiological phases of their first annual reproductive cycle, i.e., pre-spermatogenesis, spermatogenesis, spermiation and post-spermiation. Under NP, ...

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

    OpenAIRE

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

  10. Melatonin prevents methotrexate-induced hepatorenal oxidative injury in rats.

    Science.gov (United States)

    Jahovic, Nermina; Cevik, Hülya; Sehirli, A Ozer; Ye?en, Berrak C; Sener, Göksel

    2003-05-01

    Regarding the mechanisms of methotrexate (MTX) hepatotoxicity and nephrotoxicity, several hypotheses have been put forward, among which oxidative stress (including depletion of glutathione) is likely. This investigation elucidates the role of free radicals in MTX-induced toxicity and the protection by melatonin. Wistar albino rats were injected with MTX intraperitoneally. Following a single dose of MTX (20 mg/kg), either saline (MTX group) or melatonin (10 mg/kg, MTX + Mel group) was administered for 5 days. In other rats, physiologic saline (control group) or melatonin (10 mg/kg, Mel group) was injected for 5 days, following a single injection of saline. On the sixth day, rats were killed to obtain blood, liver, and kidney tissue samples. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH), a key antioxidant, levels were evaluated in blood and tissue homogenates. Reactive oxygen metabolite-induced inflammatory changes in kidney and liver tissues were evaluated by measuring myeloperoxidase (MPO) activity, an index of neutrophil infiltration. MTX administration resulted in increased MDA levels and MPO activity and decreased GSH levels in the blood, liver, and kidney whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin may be of therapeutic benefit when used with MTX. PMID:12662351

  11. Serum levels of melatonin and cytokines in multiple sclerosis.

    Science.gov (United States)

    Farhadi, Naser; Oryan, Shahrbanoo; Nabiuni, Mohammad

    2014-01-01

    Cytokines are important factors of the immune system in autoimmune diseases such as multiple sclerosis (MS) in which damage caused by oxidants plays a major role in the pathology. Melatonin secreted by the pineal gland has recently been considered as an antioxidant. The purpose of this study was to determine the relationship between melatonin and cytokines in patients with MS. Thirty patients with MS and 30 healthy controls were selected. Serum levels of melatonin and cytokines, including interleukin-4, interferon-?, and tumor necrosis factor alpha (TNF-?), were detected in all participants by the enzyme-linked immunosorbent assay (ELISA) method. There was a significant difference between patient and control groups in the levels of melatonin and TNF-?. Also, no significant correlation between the serum levels of melatonin and cytokines in both patient and control groups was seen. We concluded that decrease of melatonin and subsequent increase of pro-inflammatory cytokine, TNF-?, could be a factor in the inflammatory reactions in the pathologic process of MS. PMID:24732664

  12. Melatonin and female hormone secretion in postmenopausal overweight women.

    Science.gov (United States)

    Walecka-Kapica, Ewa; Chojnacki, Jan; St?pie?, Agnieszka; Wachowska-Kelly, Patrycja; Klupi?ska, Gra?yna; Chojnacki, Cezary

    2015-01-01

    Estrogen deficiency is considered to be the main cause of increased appetite and increased weight in postmenopausal women. In this period, reduced secretion of melatonin (MEL) was also observed. The aim of the study was to evaluate the secretion of melatonin, 17-? estradiol and follicle-stimulating hormone (FSH) in relation to body mass index (BMI) in pre- and postmenopausal women. The study included 90 women divided into three equal groups: group I (control)-women without menstrual disorders, group II-postmenopausal women without change in appetite and body weight, group III-postmenopausal women experiencing increased appetite and weight gain. In each patient, serum melatonin, 17-?-estradiol, FSH and urine a 6-sulfatoxymelatonin (aMT6s) were determined. Compared to the control group, the level of melatonin and estradiol was statistically lower. The FSH level was higher than in the groups of postmenopausal women. No significant correlation was found in all groups between the level of melatonin and the levels of estradiol and FSH. A negative correlation was found between aMT6s excretion and BMI, and a positive correlation between the level of FSH and BMI, mainly in overweight women. The obtained results indicate a significant effect of melatonin deficiency on the process of weight gain in postmenopausal women and justify its use in treatment of these disorders. PMID:25569084

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

    Directory of Open Access Journals (Sweden)

    Jacek Drobnik

    2012-02-01

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

  14. Multiple sclerosis: The role of melatonin and N-acetylserotonin.

    Science.gov (United States)

    Anderson, George; Rodriguez, Moses

    2015-03-01

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

  15. Pineal melatonin synthesis in Syrian hamsters: A summary

    Science.gov (United States)

    Rollag, M. D.

    1982-12-01

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

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

    International Nuclear Information System (INIS)

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

  17. Health effects of extremely low-frequency magnetic fields: reconsidering the melatonin hypothesis in the light of current data on magnetoreception.

    Science.gov (United States)

    Vanderstraeten, Jacques; Verschaeve, Luc; Burda, Hynek; Bouland, Catherine; de Brouwer, Christophe

    2012-12-01

    The so-called 'Melatonin Hypothesis' proposed that decreased nocturnal production of melatonin (MLT) might explain the increased risk of breast cancer that has been formerly attributed to extremely low-frequency (ELF) magnetic fields (MF) of weak intensity. Although the risk of ELF MF upon breast cancer was later dismissed, repeated reports were published of partial inhibition of MLT secretion in rats under long-term (? 4 weeks) exposure to weak ELF MF. Since 2004, however, this topic has not been experimentally studied any more. In the present study, we propose to go back to the MLT hypothesis and apply it to childhood leukemia, for which an increased risk has been robustly associated with residential exposure to ELF MF. Contrary to the original hypothesis, however, we do not consider decreased MLT levels, but disruption of circadian rhythmicity per se as the effector mechanism. Indeed, the role of the circadian timing system in the development of childhood leukemia has been well established. Motivation for going back to the MLT hypothesis comes from recent data that suggest magnetosensory disruption by ELF MF in mammals, and magnetosensitivity in humans, together with current evidence for an influence on circadian rhythmicity from disruption of non-photic sensory stimuli of various natures. We thus suggest further study on circadian rhythmicity in humans (children if possible) under long-term exposure to weak ELF MF. PMID:22696437

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

    DEFF Research Database (Denmark)

    Alamili, Mahdi; Bendtzen, Klaus

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

  20. Ameliorative effect of melatonin against contrast media induced renal tubular cell injury

    OpenAIRE

    Nasri, Hamid; Tavakoli, Maryam; Ahmadi, Ali; Baradaran, Azar; Nematbakhsh, Mehdi; Rafieian-kopaei, Mahmoud

    2014-01-01

    Background and Objective: Reactive oxygen species (ROS) is a mediator of renal damage. Melatonin is a potent-free radical scavenger. Our objective was to test whether melatonin would protect against the nephrotoxicity of contrast media.

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

    Science.gov (United States)

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

    2015-01-01

    Supplemental melatonin has been used to treat sleep onset insomnia in children with autism spectrum disorders (ASD), although the mechanism of action is uncertain. We assessed endogenous and supplemental melatonin profiles in relation to sleep in nine children with ASD. In endogenous samples, maximal melatonin concentration (Cmax) and time to peak concentration (Tmax) were comparable to those previously published in the literature for typically developing children, and dim light melatonin onsets were captured in the majority of children. In treatment samples (supplemental melatonin), melatonin parameters were also comparable to those previously published for typically developing children. Our findings support that children with ASD and insomnia responsive to low dose melatonin treatment have relatively normal profiles of endogenous and supplemental melatonin. PMID:24752680

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-01-01

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

  3. Nocturnal Fog and Stratus Over the Northern Plains

    Science.gov (United States)

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

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

    OpenAIRE

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

    1987-01-01

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

  5. The impact of nocturnal hemodialysis on sexual function

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

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

  7. Paroxysmal nocturnal haemoglobinuria and Budd-Chiari syndrome.

    OpenAIRE

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

    1995-01-01

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

  8. Antibodies to indolealkylamines II: site of conjugation of melatonin to protein using formaldehyde.

    Science.gov (United States)

    Grota, L J; Snieckus, V; de Silva, S O; Brown, G M

    1983-10-01

    The site of coupling on the hapten was investigated for melatonin, formaldehyde, and protein conjugates. Model reactions of glycine ethyl ester and piperidine with formaldehyde and melatonin suggested that coupling first occurred through the indole nitrogen and then a stable bond was formed at C-2. Cross-reaction studies of antisera stimulated by melatonin, formaldehyde, and protein conjugates support the hypothesis that C-2 is the site of conjugation of melatonin to protein. PMID:6652560

  9. Hemoglobinuria paroxística nocturna: Actualización Paroxysmal nocturnal haemoglobinuria

    Directory of Open Access Journals (Sweden)

    María Teresa Milanés Roldán

    2003-04-01

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

  10. Hemoglobinuria paroxística nocturna: Actualización / Paroxysmal nocturnal haemoglobinuria

    Scientific Electronic Library Online (English)

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

    2003-04-01

    Full Text Available SciELO Cuba | Language: Spanish Abstract in spanish 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

  11. Nocturnal Systemic Hypotension Increases the Risk of Glaucoma Progression

    Science.gov (United States)

    Charlson, Mary E.; de Moraes, Carlos Gustavo; Link, Alissa; Wells, Martin T.; Harmon, Gregory; Peterson, Janey C.; Ritch, Robert; Liebmann, Jeffrey M.

    2015-01-01

    Objective The objective of this prospective, longitudinal study of patients with normal-tension glaucoma (NTG) was to determine whether patients with nocturnal hypotension are at greater risk for visual field (VF) loss over 12 months than those without nocturnal hypotension. Design Prospective, longitudinal study. Participants Consecutive patients with NTG with at least 5 prior VF tests were screened for eligibility. Methods The baseline evaluation assessed demographic and clinical characteristics, covering systemic comorbid conditions, including systemic hypertension. All oral and ophthalmologic medications were recorded. A complete ophthalmological examination was performed at baseline and follow-up. Patients had their blood pressure (BP) monitored every 30 minutes for 48 hours with an ambulatory recording device at baseline and 6 and 12 months. Main Outcome Measures The primary outcome was based on the global rates of VF progression by linear regression of the mean VF threshold sensitivity over time (decibels/year). Results Eighty-five patients with NTG (166 eyes; mean age, 65 years; 67% were women) were included. Of the 85 patients, 29% had progressed in the 5 VFs collected before study enrollment. The nocturnal mean arterial pressure (MAP) was compared with the daytime MAP. Multivariate analysis showed that the total time that sleep MAP was 10 mmHg below the daytime MAP was a significant predictor of subsequent VF progression (Pduration and magnitude of decrease in nocturnal blood pressure below the daytime MAP, especially pressures that are 10 mmHg lower than daytime MAP, predict progression of NTG. Low nocturnal blood pressure, whether occurring spontaneously or as a result of medications, may lead to worsening of VF defects. PMID:24869467

  12. Under cover of darkness: nocturnal life of diurnal birds.

    Science.gov (United States)

    Mukhin, Andrey; Grinkevich, Vitaly; Helm, Barbara

    2009-06-01

    Songbirds are generally considered diurnal, although many species show periodic nocturnal activity during migration seasons. From a breeding-range perspective, such migratory species appear to be diurnal because they are observed to nest and feed their young during the day. But are they really exclusively diurnal? The authors tested how a passerine long-distance migrant, the Eurasian reed warbler, schedules movements during the breeding period by tracking birds in 2 experimental situations: 1) Birds experienced simulated nest loss and were monitored during their search for alternative locations, and 2) birds were translocated to reed beds at distances from 2 to 21 km and tracked during homing. The simulated unpredictable events disrupted normal breeding, forced birds to move over relatively long distances, and triggered rapid change in diel activity. In all but 1 case, birds resorted to nocturnality to find their way home and to search for new places to breed. Nocturnality during the breeding season indicates that songbird schedules are far more flexible than previously assumed. The reasons for nocturnal movements are poorly understood. Among the presumed advantages, the reduced predation pressure at night stands out because it is advantageous for movements on local as well as global scales. Predation may be particularly relevant for inhabitants of fragmented habitats, which encounter unfavorable conditions when crossing gaps in their preferred habitat. Therefore, similar selection pressures around the year may have favored the evolution of a general circadian mechanism for switches to nocturnality. Furthermore, the novel finding of homing and dispersal at night may give leads toward understanding the still enigmatic navigational abilities of songbirds. PMID:19465699

  13. Melatonin protects against myocardial hypertrophy induced by lipopolysaccharide.

    Science.gov (United States)

    Lu, Qi; Yi, Xin; Cheng, Xiang; Sun, Xiaohui; Yang, Xiangjun

    2015-04-01

    Melatonin is thought to have the ability of antiatherogenic, antioxidant, and vasodilatory. It is not only a promising protective in acute myocardial infarction but is also a useful tool in the treatment of pathological remodeling. However, its role in myocardial hypertrophy remains unclear. In this study, we investigated the protective effects of melatonin on myocardial hypertrophy induced by lipopolysaccharide (LPS) and to identify their precise mechanisms. The cultured myocardial cell was divided into six groups: control group, LPS group, LPS + ethanol (4%), LPS + melatonin (1.5 mg/ml) group, LPS + melatonin (3 mg/ml) group, and LPS + melatonin (6 mg/ml) group. The morphologic change of myocardial cell was observed by inverted phase contrast microscope. The protein level of myocardial cell was measured by Coomassie brilliant blue protein kit. The secretion level of tumor necrosis factor-? (TNF-?) was evaluated by enzyme-linked immunosorbent assay (ELISA). Ca(2+) transient in Fura-2/AM-loaded cells was measured by Till image system. The expression of Ca(2+)/calmodulin-dependent kinase II (CaMKII) and calcineurin (CaN) was measured by Western blot analysis. Our data demonstrated that LPS induced myocardial hypertrophy, promoted the secretion levels of TNF-?, and increased Ca(2+) transient level and the expression of CaMKII and CaN. Administration of melatonin 30 min prior to LPS stimulation dose-dependently attenuated myocardial hypertrophy. In conclusion, the results revealed that melatonin had the potential to protect against myocardial hypertrophy induced by LPS in vitro through downregulation of the TNF-? expression and retains the intracellular Ca(2+) homeostasis. PMID:25475041

  14. A radiobiological review on melatonin. A novel radioprotector

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Figueiro MG

    2013-10-01

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

  16. Study Of The Effect Of Melatonin On Water Immersion Stress-Induced Gastric Lesions

    Directory of Open Access Journals (Sweden)

    M. Samini

    2003-08-01

    Full Text Available One of the useful function of melatonin is its protective effect against endogenous oxidants. The object of this investigation was to study the protective effect of melatonin on stress-induced gastric lesions."nResults: Our results show that pretreatment of animals with melatonin decrease the stress-induced gastric lesions dose dependently."nL-NAME, a nitric oxide synthesis inhibitor, potentiat the stress-induce gastric lesions and melatonin produced gastro-protective effect against concurrent stress and L-NAME-induced gastric lesions."nConclusion: Our results indicate that melatonin may produce its gastro-protective effect Via increasing level of nitric oxide.

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Oner J.

    2005-01-01

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

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

    Science.gov (United States)

    Ren, Da-Long; Li, Ya-Juan; Hu, Bing-Bing; Wang, Han; Hu, Bing

    2015-05-01

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

  20. Melatonin prevents hyperglycemia in a model of sleep apnea

    Scientific Electronic Library Online (English)

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

    2015-02-01

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

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

    Science.gov (United States)

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

    2012-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Seyed Saadat Seyedeh Nazanin

    2014-03-01

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

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

    Science.gov (United States)

    She, Meihua; Laudon, Moshe; Yin, Weidong

    2014-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-15

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

  5. Melatonin and its potential biological functions in the fruits of sweet cherry.

    Science.gov (United States)

    Zhao, Yu; Tan, Dun-Xian; Lei, Qiong; Chen, Hao; Wang, Lin; Li, Qing-tian; Gao, Yinan; Kong, Jin

    2013-08-01

    Melatonin is a well-known molecule which possesses many beneficial effects on human health. Many agriculture products provide natural melatonin in the diet. Cherry is one such fruit as they are rich in melatonin. In order to understand the biological roles of melatonin in cherry fruit, melatonin synthesis and its changes over 24 hr period were systematically monitored both during their development and in the ripe cherries in two cultivars, 'Hongdeng' (Prunus avium L. cv. Hongdeng) and 'Rainier' (Prunus avium L. cv. Rainier). It was found that both darkness and oxidative stress induced melatonin synthesis, which led to dual melatonin synthetic peaks during a 24 hr period. The high levels of malondialdehyde induced by high temperature and high intensity light exposure were directly related to up-regulated melatonin production. A primary function of melatonin in cherry fruits is speculated to be as an antioxidant to protect the cherry from the oxidative stress. Importantly, plant tryptophan decaboxylase gene (PaTDC) was identified in cherry fruits. Our data shows that PaTDC expression is positively related to the melatonin production in the cherry. This provides additional information to suggest that tryptophan decaboxylase is a rate-limiting enzyme of melatonin synthesis in plants. PMID:23480341

  6. Melatonin content of pepper and tomato fruits: effects of cultivar and solar radiation.

    Science.gov (United States)

    Riga, Patrick; Medina, Sonia; García-Flores, Libia Alejandra; Gil-Izquierdo, Ángel

    2014-08-01

    We evaluated the effect of cultivar and solar radiation on the melatonin content of Capsicum annuum (pepper) and Solanum lycopersicum (tomato) fruits. The melatonin content of red pepper fruits ranged from 31 to 93ngg(-1) (dry weight). The melatonin content of tomato ranged from 7.5 to 250ngg(-1) (dry weight). We also studied the effect of ripeness on melatonin content and identified one group of pepper cultivars in which the melatonin content increased as the fruit ripened and another in which it decreased as the fruit ripened. Under shade conditions, the melatonin content in most of tomato cultivars tended to increase (up to 135%), whereas that of most pepper cultivars decreased (to 64%). Overall, the results also demonstrated that the melatonin content of the fruits was not related to carbon fluxes from leaves. PMID:24629979

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

    Science.gov (United States)

    Y?lmaz, Cemile; Kocada?l?, 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

  8. [Nocturnal cardiac arrhythmias in the sleep apnea syndrome].

    Science.gov (United States)

    Bolm-Audorff, U; Köhler, U; Becker, E; Fuchs, E; Mainzer, K; Peter, J H; von Wichert, P

    1984-06-01

    A day vs. night comparison of type and frequency of cardiac arrhythmias documented by long-term ECG was done in 30 patients with nocturnal respiratory disorders in the form of the sleep apnoea syndrome. The commonest nocturnal arrhythmia was pronounced sinus arrhythmia during the apnoeic phases with variations of cardiac frequency between 40 and 120/min. Supraventricular and ventricular extrasystoles occurred significantly more frequently during the night than during the day. In three patients bradycardiac arrhythmias presenting as sinoauricular and atrioventricular blockades of the 3rd degree with node or ventricular substitute rhythm were seen during the sleep apnoea which could not be demonstrated during the day. Predominantly nightly occurrence of cardiac arrhythmias should lead to differential diagnostic consideration of the sleep apnoea syndrome. PMID:6202478

  9. Nocturnal water storage in plants having Crassulacean acid metabolism.

    Science.gov (United States)

    Lüttge, U

    1986-06-01

    Measurements of water uptake and transpiration, during the dark period of plants having Crassulacean acid metabolism (CAM) allow calculation of leaf-volume changes (?V). Nocturnal leaf-volume changes of CAM plants have also been reported in the literature on the basis of waterdisplacement measurements. A third way of estimation is from measurements of turgor changes and cellular water-storage capacity using the pressure probe, cytomorphometry and the Scholander pressure chamber. An extension of the interpretation of results reported in the literature shows that for leaf succulent CAM plants the three different approaches give similar values of ?V ranging between 2.3 and 10.7% (v/v). It is evident that nocturnal malic-acid accumulation osmotically drives significant water storage in CAM leaf tissue. PMID:24232034

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

    International Nuclear Information System (INIS)

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

  11. Two Components of Nocturnal Locomotor Suppression by Light

    OpenAIRE

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

    2010-01-01

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

  12. Deep sequencing reveals stepwise mutation acquisition in paroxysmal nocturnal hemoglobinuria

    OpenAIRE

    Shen, Wenyi; Clemente, Michael J.; Hosono, Naoko; Yoshida, Kenichi; Przychodzen, Bartlomiej; Yoshizato, Tetsuichi; Shiraishi, Yuichi; Miyano, Satoru; Ogawa, Seishi; Maciejewski, Jaroslaw P.; Makishima, Hideki

    2014-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disease of hematopoietic stem cells that is associated with hemolysis, marrow failure, and thrombophilia. PNH has been considered a monogenic disease that results from somatic mutations in the gene encoding PIGA, which is required for biosynthesis of glycosylphosphatidylinisotol-anchored (GPI-anchored) proteins. The loss of certain GPI-anchored proteins is hypothesized to provide the mutant clone with an extrinsic growth advan...

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

    OpenAIRE

    Vilma Takayasu; Márcia Yoshie Kanegae; Jairo Rays

    2012-01-01

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

  14. Impaired phagocyte responses to lipopolysaccharide in paroxysmal nocturnal hemoglobinuria.

    OpenAIRE

    Duchow, J.; Marchant, A.; Crusiaux, A.; Husson, C.; Alonso-vega, C.; Groote, D.; Neve, P.; Goldman, M.

    1993-01-01

    Bone marrow-derived cells from patients suffering from paroxysmal nocturnal hemoglobinuria (PNH) show a defect in the expression of phosphatidylinositol-anchored membrane proteins, including the CD14 molecule. Blocking experiments with anti-CD14 monoclonal antibodies have shown that lipopolysaccharide (LPS)-induced tumor necrosis factor alpha production by monocytes depends on the interaction between CD14 and a complex formed by LPS and LPS-binding protein. We used a whole-blood model to exam...

  15. Abnormality of glycophorin-alpha on paroxysmal nocturnal hemoglobinuria erythrocytes.

    OpenAIRE

    Parker, C. J.; Soldato, C. M.; Rosse, W. F.

    1984-01-01

    To investigate the greater enzymatic activity of the alternative pathway convertase (and the subsequent greater fixation of C3b) on paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes, we have examined the topography of binding of C3b to PNH and normal erythrocytes. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography, the alpha-chain of C3b was found to bind via predominantly ester bonds to free hydroxyl groups on glycophorin-alpha, the major erythrocyte sia...

  16. Characterization of the complement sensitivity of paroxysmal nocturnal hemoglobinuria erythrocytes.

    OpenAIRE

    Parker, C. J.; Wiedmer, T.; Sims, P. J.; Rosse, W. F.

    1985-01-01

    The affected erythrocytes of paroxysmal nocturnal hemoglobinuria (PNH II and PNH III cells) are abnormally sensitive to complement-mediated lysis. Normal human erythrocytes chemically modified by treatment with 2-amino-ethylisothiouronium bromide (AET) have been used as models for PNH cells inasmuch as they also exhibit an enhanced susceptibility to complement. To investigate the bases for the greater sensitivity of these abnormal cells to complement-mediated lysis, we compared binding of C3 ...

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

    OpenAIRE

    1987-01-01

    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 ...

  18. Targeting nocturnal hypertension in type 2 diabetes mellitus.

    Science.gov (United States)

    Rossen, Niklas Blach; Knudsen, Søren Tang; Fleischer, Jesper; Hvas, Anne-Mette; Ebbehøj, Eva; Poulsen, Per Løgstrup; Hansen, Klavs Würgler

    2014-11-01

    Several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular events than daytime BP. Consequently, treatment strategies to target nighttime BP have come into focus. The aim of the present study was to investigate the effect of change of administration time of antihypertensive drugs. We included 41 patients with type 2 diabetes mellitus and nocturnal hypertension (nighttime systolic BP >120 mm Hg) in an open-label, crossover study. Patients were randomized to 8 weeks of either morning or bedtime administration of all of the individual's once-daily antihypertensive drugs, followed by 8 weeks of switched dosing regimen. Bedtime administration of antihypertensive drugs resulted in a significant reduction in nighttime (7.5 mm Hg; P<0.001) and 24-hour (3.1 mm Hg; P=0.014) systolic BP, with a nonsignificant reduction in daytime (1.3 mm Hg; P=0.336) systolic BP. We did not find morning BP surge to be different between dosing regimens. Levels of C-reactive protein were significantly lower with bedtime administration, which may indicate an effect on low-grade inflammation. We found no difference in urinary albumin excretion, regardless of albuminuria status. Urinary sodium/creatinine was significantly increased and urinary osmolality significantly reduced with bedtime administration, which can be interpreted as increased nocturnal natriuresis. In patients with type 2 diabetes mellitus and nocturnal hypertension, administration of once-daily antihypertensive drugs at bedtime may be favorable. The increased nocturnal natriuresis may reflect increased effect of bedtime-administered thiazides and renin-angiotensin system inhibitors, suggesting a potential mechanism of the observed effects on BP with chronotherapeutic intervention. PMID:25259747

  19. Targeting nocturnal hypertension in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Rossen, Niklas Blach; Knudsen, SØren Tang

    2014-01-01

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

  20. Cold and hunger induce diurnality in a nocturnal mammal

    OpenAIRE

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

    2014-01-01

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

  1. Niche convergence suggests functionality of the nocturnal fovea

    OpenAIRE

    Moritz, Gillian L.; Melin, Amanda D.; Fred Tuh Yit Yu; Henry Bernard; Ong, Perry S.; Dominy, Nathaniel J.

    2014-01-01

    The fovea is a declivity of the retinal surface associated with maximum visual acuity. Foveae are widespread across vertebrates, but among mammals they are restricted to haplorhine primates (tarsiers, monkeys, apes, and humans), which are primarily diurnal. Thus primates have long contributed to the 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...

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

    OpenAIRE

    Boonen, Eva; Meersseman, Philippe; Vervenne, Hilke; Meyfroidt, Geert; Gui?za, Fabian; Wouters, Pieter J.; Veldhuis, Johannes D.; Den Berghe, Greet

    2014-01-01

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

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

    OpenAIRE

    Miller, Maxine F.

    2012-01-01

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

  4. Hormone melatonin influence on cell to cell information transfer

    International Nuclear Information System (INIS)

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

  5. Melatonin and the metabolic syndrome: physiopathologic and therapeutical implications.

    Science.gov (United States)

    Cardinali, Daniel P; Cano, Pilar; Jiménez-Ortega, Vanesa; Esquifino, Ana I

    2011-01-01

    Metabolic syndrome (MS) patients exhibit sleep/wake disturbances and other circadian abnormalities, and these may be associated with more rapid weight increase and development of diabetes and atherosclerotic disease. On this basis, the successful management of MS may require an ideal drug that besides antagonizing the trigger factors of MS could also correct the disturbed sleep-wake rhythm. Melatonin is an effective chronobiotic agent able to change the phase and amplitude of circadian rhythms. Melatonin has also significant cytoprotective properties preventing a number of MS sequelae in animal models of diabetes and obesity. A small number of controlled trials indicate that melatonin is useful to treat the metabolic and cardiovascular comorbidities of MS. Whether the recently introduced melatonergic agents (ramelteon, agomelatine, tasimelteon) have the potential for treating sleep disorders in MS patients and, more generally, for arresting the progression of disease, merits further investigation. PMID:21358175

  6. Melatonin treatment improves primary progressive multiple sclerosis: a case report.

    Science.gov (United States)

    López-González, Antonio; Álvarez-Sánchez, Nuria; Lardone, Patricia J; Cruz-Chamorro, Ivan; Martínez-López, Alicia; Guerrero, Juan M; Reiter, Russel J; Carrillo-Vico, Antonio

    2015-03-01

    We describe the case of a female patient who, at the age of 28, was diagnosed with symptoms of primary progressive multiple sclerosis (PPMS). Glucocorticoid treatment was immediately initiated. The disease and the demyelinating lesions progressed during the following 9 years reaching Expanded Disability Status Scale (EDSS) 8.0 (patient essentially restricted to bed, a chair or perambulated in a wheelchair). At this point, the patient began taking melatonin at doses ranging from 50 to 300 mg per day. Melatonin was her only treatment for the next 4 years; during this interval, her EDSS progressively recovered to 6.0 (the person needs intermittent or unilateral constant assistance such as cane, crutch, or brace to walk 100 meters with or without resting). This long-lasting improvement is likely due to melatonin usage since it is related in time and because of its exceptionally long duration. PMID:25546814

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

    Science.gov (United States)

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

    2013-08-01

    Exposure to light at night increases alertness, but light at night (especially short-wavelength light) also disrupts nocturnal physiology. Such disruption is thought to underlie medical problems for which shiftworkers have increased risk. In 33 male subjects we investigated whether short-wavelength attenuated polychromatic white light (DPG) and its pattern over time remained similar under short-wavelength attenuated polychromatic white light compared with dim light. Subjects performed equally well on an addition task under short-wavelength attenuated polychromatic white light compared with full-spectrum light. Although subjective ratings of activation were lower under short-wavelength attenuated polychromatic white light compared with full-spectrum light, subjective sleepiness was not increased. Short-wavelength attenuated polychromatic white light at night has some advantages over bright light. It hardly suppresses melatonin concentrations, whereas performance is similar to the bright light condition. Yet, alertness is slightly reduced as compared with bright light, and DPG shows similarity to the dim light condition, which is a physiological sign of reduced alertness. Short-wavelength attenuated polychromatic white light might therefore not be advisable in work settings that require high levels of alertness. PMID:23705821

  8. Nocturnal sleep pattern in native Brazilian Terena adults

    Directory of Open Access Journals (Sweden)

    REIMÃO RUBENS

    2000-01-01

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

  9. Hearing is not necessarily believing in nocturnal anurans

    Science.gov (United States)

    Richardson, Christina; Gomez, Doris; Durieux, Romain; Théry, Marc; Joly, Pierre; Léna, Jean-Paul; Plénet, Sandrine; Lengagne, Thierry

    2010-01-01

    The recent discovery of the use of visual cues for mate choice by nocturnal acoustic species raises the important, and to date unaddressed, question of how these signals affect the outcome of mate choice predicted by female preference for male calls. In order to address this question, we presented female Hyla arborea tree frogs with a series of choices between combinations of acoustic and visual cues of varying quality in nocturnal conditions. While females exhibited the expected preference for a combination of attractive values for visual and acoustic signals over combinations of unattractive values for both signals, when presented with conflicting acoustic and visual cues, they equally adopted one of two strategies, preferring either attractive calls or intense vocal sac coloration. This constitutes novel evidence that the outcome of mate choice, as predicted on the basis of male calling quality, can be drastically different when additional communication modalities—in this case vision—are taken into account. These results also highlight the possible existence of individual variation in female rules for cue prioritization. The implications of these results for the study of mate choice in nocturnal acoustic species are discussed. PMID:20335196

  10. High endogenous melatonin concentrations enhance sperm quality and short-term in vitro exposure to melatonin improves aspects of sperm motility.

    Science.gov (United States)

    Ortiz, A; Espino, J; Bejarano, I; Lozano, G M; Monllor, F; García, J F; Pariente, J A; Rodríguez, A B

    2011-03-01

    Although human seminal fluid contains melatonin and spermatozoa reportedly possess membrane melatonin receptors, there are no experimental studies that have ascertained the relationship between melatonin and male infertility. This study evaluated whether urinary 6-sulfatoxymelatonin and urinary total antioxidant capacity correlate with different seminal parameters including sperm concentration, motility and morphology. Also, the in vitro effects of melatonin on human sperm motility were investigated. Semen samples from 52 men who were counselled for infertility were obtained. Sperm concentration was determined using the haemocytometer method, motility kinematic parameters were assessed using a computer-aided semen analysis system, while morphology and vitality were evaluated after Diff-Quick and Eosin-Nigrosin vital staining, respectively. For the quantification of urinary 6-sulfatoxymelatonin, a commercial ELISA kit was used, and urinary total antioxidant capacity was evaluated by means of a colorimetric assay kit. For the in vitro effects of melatonin, samples were incubated for 30min in the presence or absence of 1mm melatonin. Both urinary 6-sulfatoxymelatonin and total antioxidant capacity levels positively correlated with sperm concentration, motility and morphology, as well as negatively correlated with the number of round cells. Additionally, 30-min exposure of sperm to 1mm melatonin improved the percentage of motile and progressively motile cells and decreased the number of static cells, thereby promoting the proportion of rapid cells. Therefore, melatonin improves semen quality, which is important because melatonin supplementation may be potentially used to obtain a successful assisted reproductive technique outcome. PMID:20964711

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Science.gov (United States)

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

    2014-08-01

    The relationship between the prevalence of multiple sclerosis (MS) and sunlight's ultraviolet radiation was proved. Oxidative stress plays a role in the pathogenic traits of MS. Melatonin possesses antioxidative properties and regulates circadian rhythms. Sleep disturbances in MS patients are common and contribute to daytime fatigue. The aim of study was to evaluate 5 mg daily melatonin supplementation over 90 days on serum total oxidant status (TOS), total antioxidant capacity (TAC) and its influence on sleep quality and depression level of MS patients. A case-control prospective study was performed on 102 MS patients and 20 controls matched for age and sex. The Kurtzke's Expanded Disability Status Scale, magnetic resonance imaging examinations, Athens Insomnia Scale (AIS), Beck Depression Inventory questionnaires were completed. Serum TOS and TAC levels were measured. We observed higher serum levels of TOS in all MS groups, while after melatonin treatment the TOS levels significantly decreased. The TAC level was significantly lower only in mitoxantrone-treated group and it increased after melatonin supplementation. A strong positive correlation between T1Gd(+) number lesions and TAC level in interferon-beta-1A group was observed. AIS group mean score above 6 defining insomnia were observed in interferon-beta-1B-group, glatiramer acetate-group and mitoxantrone-group: 6.62 ± 2.88, 8.45 ± 2.07, 11.1 ± 3.25, respectively. After melatonin treatment the AIS mean scores decrease in glatiramer acetate-group and mitoxantrone-group achieving 5.25 ± 1.14 and 7.08 ± 2.39, respectively (p < 0.05). Finding from our study suggest that melatonin can act as an antioxidant and improves reduced sleep quality in MS patients. PMID:24974099

  13. Melatonin combats molecular terrorism at the mitochondrial level.

    Science.gov (United States)

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

    2008-09-01

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

  14. Multiple binding sites for melatonin on Kv1.3.

    OpenAIRE

    Varga, Z.; Panyi, G.; Pe?ter, M.; Pieri, C.; Cse?csei, G.; Damjanovich, S.; Ga?spa?r, R.

    2001-01-01

    Melatonin is a small amino acid derivative hormone of the pineal gland. Melatonin quickly and reversibly blocked Kv1.3 channels, the predominant voltage-gated potassium channel in human T-lymphocytes, acting from the extracellular side. The block did not show state or voltage dependence and was associated with an increased inactivation rate of the current. A half-blocking concentration of 1.5 mM was obtained from the reduction of the peak current. We explored several models to describe the st...

  15. Extraocular light exposure does not suppress plasma melatonin in humans

    OpenAIRE

    Lockley, Sw; Skene, Dj; Thapan, K.; English, J.; Ribeiro, D.; Haimov, I.; Hampton, S.; Middleton, B.; Von Schantz, M.; Arendt, J.

    1998-01-01

    Light affects the circadian axis in at least two ways. It can cause the acute suppression of pineal melatonin synthesis, and/or a phase-shift of the circadian oscillator. As recent evidence has suggested that extraocular light exposure may cause phase-shifts of the circadian clock, we have investigated whether suppression of melatonin can be induced by the same type of light exposure. In the first study subjects’ eyes were exposed to white light (2250 lux for 30 min) via a fibre optic cable...

  16. [Autoimmune hemolytic anemia with a paroxysmal nocturnal hemoglobinuria-like defect: report of one case].

    Science.gov (United States)

    Tong, Juxian; Kou, Wei; Chen, Qi; Xiao, Duan

    2013-12-01

    Both autoimmune hemolytic anemia and paroxysmal nocturnal hemoglobinuria are common hemolytic diseases. The former causes hemolysis because of immune disorder, and the latter is an acquired clonal hematologic disorder of stem cells. The two entities are often separate diseases, but can also occur concomitantly or secondary to each other. paroxysmal nocturnal haemoglobinuria-like defect-like defect is a special type of autoimmune haemolytic anaemia and should be distinguished from typical paroxysmal nocturnal haemoglobinuria-like defect. PMID:24369265

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

    OpenAIRE

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

    2011-01-01

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

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

    OpenAIRE

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

    1994-01-01

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

  19. Moonstruck Primates: Owl Monkeys (Aotus) Need Moonlight for Nocturnal Activity in Their Natural Environment

    OpenAIRE

    Ferna?ndez-duque, Eduardo; La Iglesia, Horacio; Erkert, Hans G.

    2010-01-01

    Primates show activity patterns ranging from nocturnality to diurnality, with a few species showing activity both during day and night. Among anthropoids (monkeys, apes and humans), nocturnality is only present in the Central and South American owl monkey genus Aotus. Unlike other tropical Aotus species, the Azara's owl monkeys (A. azarai) of the subtropics have switched their activity pattern from strict nocturnality to one that also includes regular diurnal activity. Harsher climate, food a...

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

    OpenAIRE

    Sheng-liang Chen, Jie-ru Ji

    2010-01-01

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

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

    OpenAIRE

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

    1987-01-01

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

  2. Nocturnal hypoxaemia after myocardial infarction: association with nocturnal myocardial ischaemia and arrhythmias.

    DEFF Research Database (Denmark)

    Galatius-Jensen, S; Hansen, J

    1994-01-01

    OBJECTIVE--To document the trend in arterial hypoxaemia and electrocardiographic abnormalities on the second to sixth nights after acute myocardial infarction. PATIENTS--Nineteen consecutive patients with acute myocardial infarction who were monitored continuously during the night (minimum 2300-0700) with a Holter tape recorder and a pulse oximeter. Fifteen patients were monitored for five nights, one patient for four nights, one patient for three nights, and two patients for two nights. RESULTS--Five patients had > 30 episodic oxygen desaturations of > or = 5% during the nights of monitoring and many patients had episodes with oxygen desaturations to < 80% ranging from 46% to 61% (from 7/15 to 11/18 patients) during the nights of monitoring. Constant hypoxaemia was found in 11-13% (2/15) of the patients. Simultaneous episodic hypoxaemia and episodic tachycardia was seen in 9/17 (52%) patients on the second night, 11/18 (61%) on the third, 7/15 (46%) on the fourth, 8/15 (53%) on the fifth, and 5/15 (33%) on the sixth night. Simultaneous episodic hypoxaemia and ST deviation was seen in 5/17 (29%) patients on the second night, 3/18 (16%) on the third, 4/15 (26%) on the fourth, in no patients on the fifth, and in 3/5 (20%) on the sixth night. Simultaneous occurrence of episodic hypoxaemia and arrhythmias (supraventricular, ventricular ectopy, and atrioventricular blockade) was seen in 5/17 (29%) on the second night, 4/18 (22%) on the third, 4/15 (26%) on the fourth, 2/15 (14%) on the fifth, and in no patients on the sixth night. Overall, simultaneous occurrence of episodic hypoxaemia and electrocardiographic abnormalities (episodic tachycardia, ST deviations, and arrhythmias) was seen in 11/17 patients (64%) on the second night, 13/18 (72%) on the third, 10/15 (66%) on the fourth, 8/15 (53%) on the fifth, and 7/15 (46%) on the sixth night. One patient who died of cardiogenic shock had simultaneously occurring episodic hypoxaemia and nonsustained ventricular fibrillation on the night before she died. CONCLUSION--Episodic and constant hypoxaemia are common during the first week after acute myocardial infarction. Episodic hypoxaemia was associated with electrocardiographic abnormalities in most patients. Thus, episodic nocturnal hypoxaemia may be particularly detrimental to the infarcted myocardium in the early phase after infarction; special attention should therefore be directed towards oxygenation in this group of patients.

  3. Melatonin treatment affects the attractiveness of the anogenital area scent in meadow voles (Microtus pennsylvanicus).

    Science.gov (United States)

    Ferkin, M H; Kile, J R

    1996-09-01

    Seasonal differences exist in the attractiveness of scents in meadow voles, Microtus pennsylvanicus. To determine whether photoperiodically induced changes in the attractiveness of a sex-specific scent is governed by melatonin, we implanted long-photoperiod male and female scent donors with a Silastic implant containing a 10-mm active length of melatonin, a 20-mm active length of melatonin, or no melatonin. The first experiment shows that 8 weeks of melatonin treatment is sufficient to induce long-photoperiod voles to produce scents that are no longer attractive to the opposite sex. The second experiment shows that a similar time course of melatonin treatment was sufficient to induce long-photoperiod females treated with melatonin to produce scents that are attractive to short-photoperiod females. Melatonin implants lowered the gonadal hormone titers and reduced the weight of the gonads of treated long-photoperiod voles to titers and weights that are characteristic of short-photoperiod voles. In both experiments, the behavioral and physiological effects were independent of whether scent donors received 10- or 20-mm implants of melatonin. Together, the results of the two experiments reveal that melatonin mediates the photoperiodically induced changes in gonadal hormone titers that control the seasonal differences in the sexual attractiveness of the anogenital area scent produced by meadow voles. PMID:8918678

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

    Directory of Open Access Journals (Sweden)

    Chun-Qiu Chen

    2011-01-01

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

  5. Age-related decline in melatonin and its MT1 receptor are associated with decreased sensitivity to melatonin and enhanced mammary tumor growth.

    Science.gov (United States)

    Hill, Steven M; Cheng, Chi; Yuan, Lin; Mao, Lulu; Jockers, Rolf; Dauchy, Bob; Blask, David E

    2013-02-01

    The pineal hormone melatonin (MLT) has potent anti-breast cancer activity, its actions are heavily mediated via the MT1 receptor and subsequent modulation of downstream signaling pathways including cAMP/PKA, Erk/MAPK, p38, and Ca2+/calmodulin. Also, via the MT1 pathway, MLT can repress the transcriptional activity of some mitogenic nuclear receptors including ER?, GR, and ROR?, while potentiating the activity of other receptors (RAR? and RXR?) involved in differentiation, anti-proliferation, and apoptosis. A review of the literature supports the view that MLT, via its MT1 receptor, can suppress all phases of breast cancer including initiation, promotion, and progression. During the fifth and sixth decades of life, the production of MLT diminishes, concurrently with an increase in the incidence of breast cancer. Inasmuch as MLT has been demonstrated to have anti-cancer activity, we hypothesized that there may be a causal link between the reduction in MLT production in the pineal gland and the incidence of breast cancer which increases with age. We designed this study to establish whether a truly inverse relationship exists between tissue-isolated mammary tumor growth in young (2 months), adult (12 months), and old (20 months) female Buffalo rats and the decrease in both MLT and the MT1 receptor with age, such that a causal link could be found. Serum MLT levels were measured in both the light and dark phases. A significant 29% decrease in serum MLT levels, measured at the nocturnal peak, was found in the adult and senescent rats (75% decrease) in comparison to that in young rats. In young rats, the nocturnal pineal gland MLT content exceeded daytime levels by 19-fold compared to a sevenfold increase in old mice. Also, the MT1 receptor was found to be significantly lower in the nighttime and early morning in the senescent rat uterus as compared to uteri from young and adult rats. Analysis of the rate of growth in transplanted, tissue-isolated, mammary tumors induced by N-nitroso-n-methyl-urea (NMU) showed a significant increase in the senescent rats, but not in the young or adult rats Additionally, diminished response to the inhibitory action on tumor growth of exogenous MLT was noted in senescent rats such that tumor growth was suppressed by only 33% compared to 48% and 66% in adult and young rats, respectively. The diminution of the response of tumors to exogenous MLT was found to correlate with reduced MT1 receptor expression in senescent compared to young and adult rats. These data suggest that the observed age-associated enhanced growth of tumors is related to the much reduced levels of MLT and its receptor in aged animals which reduce the sensitivity of tumors to inhibition by exogenous MLT. PMID:23895529

  6. Production and purification of polyclonal antibody against melatonin hormone

    Directory of Open Access Journals (Sweden)

    Fooladsaz K

    1999-09-01

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

  7. Circadian rhythm in salivary melatonin in narcoleptic patiens.

    Czech Academy of Sciences Publication Activity Database

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

    2008-01-01

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

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

    OpenAIRE

    Wurtman, R. J.

    1985-01-01

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

  9. Melatonin ameliorates radiation induced mutilation of learning in mice

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    Youngjeon Lee

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    C.D. Cisternas

    2010-09-01

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

  12. Light deprivation improves melatonin related suppression of hippocampal plasticity.

    Science.gov (United States)

    Talaei, Sayyed Alireza; Sheibani, Vahid; Salami, Mahmoud

    2010-03-01

    In early postnatal life, sensory inputs deeply influence development as well as function of the brain. Plasticity of synaptic transmission including its experimentally induced form, long-term potentiation (LTP), is affected by sensory deprivation in neocortex. This study is devoted to assess if dark rearing and a dark phase synthesized hormone melatonin influence LTP in the hippocampus, an area of brain involved in learning and memory. In vivo experiments were carried out on two groups of 45-days-old male Wistar rats kept in standard 12-h light/dark condition [light reared (LR) tested during the light phase] or in complete darkness [dark reared (DR)] since birth to testing. Each group, in turn, was divided to two, vehicle- and melatonin-treated, groups. Stimulating the Schaffer collaterals of CA3 area of hippocampus extracellular postsynaptic potentials (EPSPs) were recorded in the CA1 area. Having the stable baseline responses to the test pulses, the hippocampus was perfused by either vehicle or 2 microg melatonin and EPSPs were recorded for 30 min. Then, for induction of LTP, the tetanus was applied to the Schaffer collaterals and the field potentials were pooled for 120-min post-tetanus. The light deprivation resulted in a significant augmentation in the amplitude of baseline responses. Also, we observed a melatonin-induced increase in amplitude of the baseline recordings in either LR or DR animals. Tetanic stimulation elicited LTP of EPSPs in both LR and DR groups, robustly in the former where it lasted for about 90 min. Generally, melatonin inhibited the production of LTP in the two groups especially in the LR animals leading to a noticeable depression. We concluded that higher level of neuronal activity in the DR rats gives rise to a lower level of LTP. Weaker effect of melatonin on blocking the potentiation of post-tetanus EPSPs in the DR rats may be the result of a desensitization of melatonin receptors due to chronically increased levels of this hormone in the visually deprived rats. PMID:19475653

  13. Genome-wide profiling in melatonin-exposed human breast cancer cell lines identifies differentially methylated genes involved in the anticancer effect of melatonin.

    Science.gov (United States)

    Lee, Seung Eun; Kim, Seung Jun; Yoon, Hyo-Jeong; Yu, So Yeon; Yang, Hana; Jeong, Seong Il; Hwang, Seung Yong; Park, Cheung-Seog; Park, Yong Seek

    2013-01-01

    Epigenetic alterations have emerged as an important mechanism involved in tumorigenesis. The epigenetic impact of DNA methylation in various types of human cancer is not completely understood. Previously, we observed melatonin-induced differential expression of miRNA and miRNA-related genes in human breast cancer cell lines that indicated an anticancer effect of melatonin. In this report, we further characterized epigenetic changes in melatonin-exposed MCF-7 cells through the analysis of DNA methylation profiles in breast cancer cells to provide new insights into the potential mechanisms of the anticancer effect of melatonin. Microarray-based DNA methylation and gene expression profiling were carried out using human breast cancer cell lines. We further identified a number of mRNAs whose expression levels show an inverse correlation with DNA methylation levels. The mRNA expression levels and methylation status of candidate genes in melatonin-exposed cells were confirmed by real-time quantitative PCR and bisulfite PCR. This approach led to the detection of cancer-related genes, which were oncogenic genes, including EGR3 and POU4F2/Brn-3b were down-regulated, while the tumor suppressor gene, GPC3, was up-regulated by 1 nm melatonin-treated MCF-7 cells. Our results provide detailed insights into the DNA methylation patterns induced by melatonin and suggest a potential mechanism of the anticancer effect of aberrant DNA methylation in melatonin-treated breast cancer cells. PMID:22856590

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

    DEFF Research Database (Denmark)

    BrØns, Charlotte; LilleØre, S K

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    Dogs kept under controlled photoperiodic conditions of 12h light and 12h dark expressed a clear diurnal melatonin rhythm in the peripheral blood, with a swift peak restricted to the late part of the scotophase. The highest density of high-affinity, G-protein-linked 2-[125I]iodomelatonin binding sites was found in the pars tuberalis of the pituitary gland. Binding sites were found also in the pars distalis, and light microscopy/high-resolution autoradiography showed that binding was located exclusively over the chromophobe and basophilic cells forming the adenopituitary zona tuberalis, well developed in the species, and extending into the gland as a continuation of pars tuberalis. Cords of basophilic cells located in the pars distalis proper also expressed high receptor density. Quantitative autoradiography inhibition experiments revealed that the apparent melatonin inhibitory constant in all those areas was around 0.1 nmol/l, which is a physiologically appropriate value considering the peripheral blood melatonin levels. Co-incubation with guanosine 3-thiotriphosphate led to a consequential decrease in the binding density. Collectively, these data show that the dog possesses all the prerequisites for an efficient network adapted to photoperiodic time measurements. A circadian melatonin signal in the peripheral blood and an apparently functional readout receptor system located in key positions within the brain are both present in this species. 43 refs. 6 figsh present in this species. 43 refs. 6 figs., 1 tabs

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

    Directory of Open Access Journals (Sweden)

    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

  20. Pregnancy in a patient with paroxysmal nocturnal hemoglobinuria

    Directory of Open Access Journals (Sweden)

    Anju Singh

    2014-02-01

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

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

    OpenAIRE

    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...

  2. Melatonin counteracts BMP-6 regulation of steroidogenesis by rat granulosa cells.

    Science.gov (United States)

    Nakamura, Eri; Otsuka, Fumio; Terasaka, Tomohiro; Inagaki, Kenichi; Hosoya, Takeshi; Tsukamoto-Yamauchi, Naoko; Toma, Kishio; Makino, Hirofumi

    2014-09-01

    The ovarian bone morphogenetic protein (BMP) system is a physiological inhibitor of luteinization in growing ovarian follicles. BMP-6, which is expressed in oocytes and granulosa cells of healthy follicles, specifically inhibits FSH actions by suppressing adenylate cyclase activity. In the present study, we studied the role of melatonin in ovarian steroidogenesis using rat primary granulosa cells of immature female rat ovaries by focusing on the interaction with BMP-6 activity. Treatment with melatonin had no direct effect on FSH-induced progesterone or estradiol production by granulosa cells, and the results were not affected by the presence of co-cultured oocytes. In addition, synthesis of cAMP by granulosa cells was not significantly altered by melatonin treatment. To elucidate the interaction between activities of melatonin and BMPs, the effect of melatonin treatment on suppression of progesterone synthesis by BMP-6 was investigated. Interestingly, the inhibitory effect of BMP-6 on FSH-induced progesterone production was impaired by co-treatment with melatonin. Granulosa cells express higher levels of MT1 than MT2, and BMP-6 had no significant effect on MT1 expression in granulosa cells. However, BMP-6-induced Smad1/5/8 phosphorylation and Id-1 transcription were suppressed by melatonin, suggesting that melatonin has an inhibitory effect on BMP receptor signaling in granulosa cells. Although the expression levels of ALK-2, -6, ActRII and BMPRII were not affected by melatonin, inhibitory Smad6, but not Smad7, expression was upregulated by melatonin. Thus, melatonin plays a role in the regulation of BMP-6 signal intensity for controlling progesterone production in the ovary. These findings suggest that the effect of melatonin on maintenance of ovarian function is, at least in part, due to the regulation of endogenous BMP activity in granulosa cells. PMID:24751708

  3. Inhibitory effects of pharmacological doses of melatonin on aromatase activity and expression in rat glioma cells

    OpenAIRE

    Gonza?lez, A.; Marti?nez-campa, C.; Mediavilla, M. D.; Alonso-gonza?lez, C.; Sa?nchez-barcelo?, E. J.; Cos, S.

    2007-01-01

    Melatonin exerts oncostatic effects on different kinds of neoplasias, especially on oestrogen-dependent tumours. Recently, it has been described that melatonin, on the basis of its antioxidant properties, inhibits the growth of glioma cells. Glioma cells express oestrogen receptors and have the ability to synthesise oestrogens from androgens. In the present study, we demonstrate that pharmacological concentrations of melatonin decreases the growth of C6 glioma cells and reduces the local bios...

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

    OpenAIRE

    SimonVincenzi; ShanthaMRajaratnam

    2010-01-01

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

  5. Influence of Dietary Melatonin on Photoreceptor Survival in the Rat Retina: An Ocular Toxicity Study

    OpenAIRE

    Wiechmann, Allan F.; Chignell, Colin F.; Roberts, Joan E.

    2007-01-01

    Previous studies have shown that melatonin treatment increases the susceptibility of retinal photoreceptors to light-induced cell death. The purpose of this study was to evaluate under various conditions the potential toxicity of dietary melatonin on retinal photoreceptors. Male and female Fischer 344 (non-pigmented) and Long-Evans (pigmented) rats were treated with daily single doses of melatonin by gavage for a period of 14 days early in the light period or early in the dark period. In anot...

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

    Directory of Open Access Journals (Sweden)

    Sheng-Liang Chen, Jie-Ru Ji, Ping Xu, Zhi-Jun Cao, Jian-Zhong Mo, Jing-Yuan Fang, Shu-Dong Xiao

    2010-02-01

    Full Text Available AIM: To investigate the incidence of nocturnal dyspeptic symptoms in patients with functional dyspepsia (FD and whether prokinetic drugs can alleviate them.METHODS: Eighty-five consecutive Chinese patients with FD were included in this study. One week after single-blinded placebo run-in treatment, baseline nocturnal intragastric pH, bile reflux and nocturnal dyspeptic symptoms of eligible patients, including epigastric pain or discomfort, abdominal distention and belching, were investigated with questionnaires. Patients exhibiting nocturnal dyspeptic symptoms were randomly and double-blindly assigned to domperidone group or placebo group. Nocturnal intragastric pH and percentage of duodenogastric bile reflux time were determined after treatment.RESULTS: Of the 85 FD patients, 2 females without nocturnal symptoms, who responded to placebo run-in treatment, were excluded from the study, 30 (36.1% exhibited nocturnal dyspeptic symptoms with increased duodenogastric bile reflux time (intragastric bilirubin absorbance > 0.14 and mean gastric pH (confirming the existence of bile reflux (P = 0.021, 0.023 at night were included in the study. Of these 30 patients, 21 (70% had overt nocturnal duodenogastric bile reflux, which was significantly higher than that of those without nocturnal symptoms (P = 0.026. The 30 patients were allocated to domperidone group or placebo group (n = 15. The nocturnal duodenogastric bile reflux and gastric pH were significantly decreased after domperidone treatment (P = 0.015, 0.021. The severity score of nocturnal dyspeptic symptoms was also significantly decreased after domperidone treatment (P = 0.010, 0.015, 0.026, which was positively correlated with the reduced nocturnal bile reflux or gastric pH (r = 0.736, 0.784, 0.753 or r = 0.679, 0.715, 0.697, P = 0.039, 0.036, 0.037 or P = 0.043, 0.039, 0.040.CONCLUSION: A subgroup of Chinese FD patients show overt nocturnal dyspeptic symptoms, which may be correlated with the excessive nocturnal duodenogastric bile reflux. Domperidone therapy can alleviate these symptoms.

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

    Directory of Open Access Journals (Sweden)

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

  8. Decreased mitochondrial DNA copy number in the hippocampus and peripheral blood during opiate addiction is mediated by autophagy and can be salvaged by melatonin.

    Science.gov (United States)

    Feng, Yue-Mei; Jia, Yun-Fang; Su, Ling-Yan; Wang, Dong; Lv, Li; Xu, Lin; Yao, Yong-Gang

    2013-09-01

    Drug addiction is a chronic brain disease that is a serious social problem and causes enormous financial burden. Because mitochondrial abnormalities have been associated with opiate addiction, we examined the effect of morphine on mtDNA levels in rat and mouse models of addiction and in cultured cells. We found that mtDNA copy number was significantly reduced in the hippocampus and peripheral blood of morphine-addicted rats and mice compared with control animals. Concordantly, decreased mtDNA copy number and elevated mtDNA damage were observed in the peripheral blood from opiate-addicted patients, indicating detrimental effects of drug abuse and stress. In cultured rat pheochromocytoma (PC12) cells and mouse neurons, morphine treatment caused many mitochondrial defects, including a reduction in mtDNA copy number that was mediated by autophagy. Knockdown of the Atg7 gene was able to counteract the loss of mtDNA copy number induced by morphine. The mitochondria-targeted antioxidant melatonin restored mtDNA content and neuronal outgrowth and prevented the increase in autophagy upon morphine treatment. In mice, coadministration of melatonin with morphine ameliorated morphine-induced behavioral sensitization, analgesic tolerance and mtDNA content reduction. During drug withdrawal in opiate-addicted patients and improvement of protracted abstinence syndrome, we observed an increase of serum melatonin level. Taken together, our study indicates that opioid addiction is associated with mtDNA copy number reduction and neurostructural remodeling. These effects appear to be mediated by autophagy and can be salvaged by melatonin. PMID:23800874

  9. Assessing complement blockade in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab.

    Science.gov (United States)

    Peffault de Latour, Régis; Fremeaux-Bacchi, Véronique; Porcher, Raphaël; Xhaard, Aliénor; Rosain, Jérémie; Castaneda, Diana Cadena; Vieira-Martins, Paula; Roncelin, Stéphane; Rodriguez-Otero, Paula; Plessier, Aurélie; Sicre de Fontbrune, Flore; Abbes, Sarah; Robin, Marie; Socié, Gérard

    2015-01-29

    Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis, which is effectively controlled with eculizumab, a humanized monoclonal antibody that binds complement protein 5 (C5). The residual functional activity of C5 can be screened using a 50% hemolytic complement (CH50) assay, which is sensitive to the reduction, absence, and/or inactivity of any components of the classical and terminal complement pathway. Little data exist on complement blockade during treatment. From 2010 to 2012, clinical data, hemolysis biomarkers, complement assessment, and free eculizumab circulating levels were systematically measured immediately before every injection given to 22 patients with hemolytic PNH while receiving eculizumab therapy. During the study, 6 patients received ?1 red blood cell transfusion. Lack of detectable CH50 activity (defined by CH50 ? 10% of normal values) was found in 184 samples (51%) and was significantly associated with lower lactate dehydrogenase levels (P = .002). Low levels of circulating free eculizumab ( 10%; P = .004), elevated bilirubin levels (P < .0001), and the need for transfusions (P = .034). This study suggests that both CH50 activity and circulating free eculizumab levels may help physicians to manage PNH patients receiving eculizumab. PMID:25477495

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2012-10-01

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

  12. Exogenous melatonin positively influences follicular dynamics, oocyte developmental competence and blastocyst output in a goat model.

    Science.gov (United States)

    Berlinguer, Fiammetta; Leoni, Giovanni G; Succu, Sara; Spezzigu, Antonio; Madeddu, Manuela; Satta, Valentina; Bebbere, Daniela; Contreras-Solis, Ignacio; Gonzalez-Bulnes, Antonio; Naitana, Salvatore

    2009-05-01

    The role of melatonin in modulating mammalian reproduction is of particular interest; however, its effects on ovarian follicles and their oocytes still remain to be characterized. This study determined the influence of melatonin treatment on follicular growth patterns and on in vitro oocyte developmental competence. In a first experiment, the effects of melatonin supplementation on follicular dynamics were evaluated using daily transrectal ultrasonographies for 21 days, in 7 multiparous Sarda goats receiving a subcutaneous implant of 18 mg of melatonin and in 5 control untreated does. Melatonin caused more follicular waves (5.2 +/- 0.2 versus 4 +/- 0.3; P melatonin treated control goats (P melatonin-treated (n = 265) goats given follicle stimulating hormone to induce follicular development. Differences in oocyte developmental competence between the two groups became evident after in vitro fertilization and culture; melatonin increased the rate of cleaved oocytes in comparison with control animals (82.5 versus 63.4%; P melatonin treatment is beneficial for increasing ovarian follicle turnover and improving oocyte developmental competence and kinetics of the blastocyst. PMID:19552761

  13. Effect of melatonin or maternal nutrient restriction on vascularity and cell proliferation in the ovine placenta.

    Science.gov (United States)

    Eifert, Adam W; Wilson, Matthew E; Vonnahme, Kimberly A; Camacho, Leticia E; Borowicz, Pawel P; Redmer, Dale A; Romero, Sinibaldo; Dorsam, Sheri; Haring, Jodie; Lemley, Caleb O

    2015-02-01

    Previously we reported increased umbilical artery blood flow in ewes supplemented with melatonin from mid- to late-pregnancy, while maternal nutrient restriction decreased uterine artery blood flow. To further unravel these responses, this study was designed to assess placental cell proliferation and vascularity following supplementation with melatonin or maternal nutrient restriction. For the first experiment, 31 primiparous ewes were supplemented with 5mg of melatonin per day (MEL) or no melatonin (CON) and allocated to receive 100% (adequate fed; ADQ) or 60% (restricted; RES) of their nutrient requirements from day 50 to 130 of gestation. To examine melatonin receptor dependent effects, a second experiment was designed utilizing 14 primiparous ewes infused with vehicle, melatonin, or luzindole (melatonin receptor 1 and 2 antagonist) from day 62 to 90 of gestation. For experiment 1, caruncle concentrations of RNA were increased in MEL-RES compared to CON-RES. Caruncle capillary area density and average capillary cross-sectional area were decreased in MEL-RES compared to CON-RES. Cotyledon vascularity was not different across dietary treatments. For experiment 2, placental cellular proliferation and vascularity were not affected by infusion treatment. In summary, melatonin interacted with nutrient restriction to alter caruncle vascularity and RNA concentrations during late pregnancy. Although melatonin receptor antagonism alters feto-placental blood flow, these receptor dependent responses were not observed in placental vascularity. Moreover, placental vascularity measures do not fully explain the alterations in uteroplacental blood flow. PMID:25578503

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

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Amirian, Ilda

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-01-01

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

  16. Epigenetic mechanisms of melatonin action in human SH-SY5Y neuroblastoma cells.

    Science.gov (United States)

    Pan, Yi; Niles, Lennard P

    2015-02-15

    We have shown that melatonin induces histone hyperacetylation in vitro and in vivo. To clarify the mechanisms involved, we have now investigated its effects on histone acetylation and signaling pathways in human SH-SY5Y neuroblastoma cells, which express melatonin MT1 receptors. Melatonin caused significant concentration-dependent increases in both histone H3 and H4 acetylation. Blockade of melatonin receptors with luzindole abolished the histone hyperacetylating effect of melatonin, whereas inhibition of MAPK-ERK by PD98059 attenuated but did not block this effect. Melatonin treatment for 24-h decreased the levels of phospho-ERK1/2, but significantly increased Akt phosphorylation and protein expression of the histone acetyltransferase, p300. These findings suggest that the epigenetic effects of melatonin in SH-SY5Y cells are mediated by G protein-coupled MT1 melatonin receptors. Furthermore, upregulation of the histone acetyltransferase/transcriptional co-activator p300, along with phosphorylation of Akt, which is essential for p300 activation, appear to be key mechanisms underlying the epigenetic effects of melatonin. PMID:25578604

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

    Science.gov (United States)

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

    2015-02-01

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

  18. The effect of melatonin treatment regimen on mammary adenocarcinoma development in HER-2/neu transgenic mice.

    Science.gov (United States)

    Anisimov, Vladimir N; Alimova, Irina N; Baturin, Dmitri A; Popovich, Irina G; Zabezhinski, Mark A; Manton, Kenneth G; Semenchenko, Anna V; Yashin, Anatoly I

    2003-01-20

    The effect of various regimens of treatment with melatonin on the development of mammary tumors in HER2/neu transgenic mice was investigated. Female HER-2/neu mice starting from the age of 2 months were kept under standard light/dark regimen and as given melatonin with tap water (20 mg/l) during the night time 5 times monthly (interrupted treatments) or constantly to natural death. Intact mice served as controls. Treatment with melatonin slowed down age-related disturbances in estrous function most in the group exposed to interrupted treatment with the hormone. Constant treatment with melatonin decreased incidence and size of mammary adenocarcinomas, and incidence of lung metastases, compared to controls. The number of mice bearing 4 and more tumors was reduced in the group with constant melatonin treatment. Interrupted treatment with melatonin promote mammary carcinogenesis in HER-2/neu transgenic mice. The data demonstrate the regimen-dependent inhibitory effect of melatonin on the development of spontaneous mammary tumors in HER-2/neu mice but not on overall survival with implication about the likely cause of the effect. Polycystic kidney disease is common in this transgenic line. Adverse effect of melatonin on the life span in our study may be unique to the transgenic model used and may not be relevant to the suppressive effect of melatonin in delay of mammary cancer. PMID:12471612

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

    Science.gov (United States)

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

    2013-06-01

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

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

    International Nuclear Information System (INIS)

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

  1. Melatonin Prevents Myeloperoxidase Heme Destruction and the Generation of Free Iron Mediated by Self-Generated Hypochlorous Acid

    Science.gov (United States)

    Shaeib, Faten; Khan, Sana N.; Ali, Iyad; Najafi, Tohid; Maitra, Dhiman; Abdulhamid, Ibrahim; Saed, Ghassan M.; Pennathur, Subramaniam; Abu-Soud, Husam M.

    2015-01-01

    Myeloperoxidase (MPO) generated hypochlorous acid (HOCl) formed during catalysis is able to destroy the MPO heme moiety through a feedback mechanism, resulting in the accumulation of free iron. Here we show that the presence of melatonin (MLT) can prevent HOCl-mediated MPO heme destruction using a combination of UV-visible photometry, hydrogen peroxide (H2O2)-specific electrode, and ferrozine assay techniques. High performance liquid chromatography (HPLC) analysis showed that MPO heme protection was at the expense of MLT oxidation. The full protection of the MPO heme requires the presence of a 1:2 MLT to H2O2 ratio. Melatonin prevents HOCl–mediated MPO heme destruction through multiple pathways. These include competition with chloride, the natural co-substrate; switching the MPO activity from a two electron oxidation to a one electron pathway causing the buildup of the inactive Compound II, and its subsequent decay to MPO-Fe(III) instead of generating HOCl; binding to MPO above the heme iron, thereby preventing the access of H2O2 to the catalytic site of the enzyme; and direct scavenging of HOCl. Collectively, in addition to acting as an antioxidant and MPO inhibitor, MLT can exert its protective effect by preventing the release of free iron mediated by self-generated HOCl. Our work may establish a direct mechanistic link by which MLT exerts its antioxidant protective effect in chronic inflammatory diseases with MPO elevation. PMID:25835505

  2. The pathophysiology of paroxysmal nocturnal hemoglobinuria and treatment with eculizumab

    Directory of Open Access Journals (Sweden)

    Richard Kelly

    2009-11-01

    Full Text Available Richard Kelly1, Stephen Richards1, Peter Hillmen1, Anita Hill21Institute of Oncology, St. James’s University Hospital, Leeds, UK; 2Department of Haematology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UKAbstract: Paroxysmal nocturnal hemoglobinuria is a rare disorder of hemopoietic stem cells. Affected individuals have a triad of clinical associations – intravascular hemolysis, an increased risk of thromboembolism, and bone marrow failure. Most of the symptoms experienced in this disease occur due to the absence of complement regulatory proteins on the surface of the red blood cells. Complement activation is thus not checked and causes destruction of these cells. Eculizumab is a monoclonal antibody treatment which specifically binds to the complement protein C5, preventing its cleavage, and so halts the complement cascade and prevents the formation of the terminal complement proteins. Eculizumab prevents intravascular hemolysis, stabilizes hemoglobin levels, reduces or stops the need for blood transfusions, and improves fatigue and patient quality of life as well as reducing pulmonary hypertension, decreasing the risk of thrombosis and protecting against worsening renal function. It is not a curative therapy but has a great benefit on those with this rare debilitating condition.Keywords: eculizumab, paroxysmal nocturnal hemoglobinuria, hemolysis

  3. Nocturnal awakening and sleep efficiency estimation using unobtrusively measured ballistocardiogram.

    Science.gov (United States)

    Da Woon Jung; Su Hwan Hwang; Hee Nam Yoon; Lee, Yu-Jin G; Do-Un Jeong; Kwang Suk Park

    2014-01-01

    Fragmented sleep due to frequent awakenings represents a major cause of impaired daytime performance and adverse health outcomes. Currently, the gold standard for studying and assessing sleep fragmentation is polysomnography (PSG). Here, we propose an alternative method for real-time detection of nocturnal awakening via ballistocardiography using an unobtrusive polyvinylidene fluoride (PVDF) film sensor on a bed mattress. From ballistocardiogram, heart rate and body movement information were extracted to develop an algorithm for classifying sleeping and awakening epochs. In total, ten normal subjects (mean age 38.7 ± 14.6 years) and ten patients with obstructive sleep apnea (OSA) (mean age 44.2 ± 16.5 years) of varying symptom severity participated in this study. Our study detected awakening epochs with an average sensitivity of 85.3% and 85.2%, specificity of 98.4% and 97.7%, accuracy of 97.4% and 96.5%, and Cohen's kappa coefficient of 0.83 and 0.81 for normal subjects and OSA patients, respectively. Also, sleep efficiency was estimated using detected awakening epochs and then compared with PSG results. Mean absolute errors in sleep efficiency were 1.08% and 1.44% for normal subjects and OSA patients, respectively. The results presented here indicate that our suggested method could be reliably applied to real-time nocturnal awakening detection and sleep efficiency estimation. Furthermore, our method may ultimately be an effective tool for long-term, home monitoring of sleep-wake behavior. PMID:23955694

  4. Spina Bifida Occulta in Persistent Primary Nocturnal Enuresis

    Directory of Open Access Journals (Sweden)

    "A. Kajbafzadeh

    2004-06-01

    Full Text Available Background/Objectives: Of congenital malformations of the central nervous system 46% are abnormalities of the spinal cord, which includes spina bifida occulta (SBO. The occurrence and significance of spina bifida occulta in patients with persistent primary nocturnal enuresis (PPNE were evaluated. Materials and Methods: Between January 2000 and February 2001, 109 consecutive children who had nocturnal enuresis more than once a week after the age of 7 years for an uninterrupted period of at least 3 months, with less than 50% reduction in wet nights despite different treatments for at least 6 months, were prospectively evaluated for the presence of associated spina bifida occulta. The results were com-pared with data from a group of 40 normal children. Results: The mean age was 9.9 years in PPNE patients and 7.5 years in normal group. SBO was present in 86 (78.9% of PPNE patients and 10 (25% of normal children. This difference was statistically significant using chi-square test. (P-value < 0.001 Conclusion: Spina bifida occulta was thought to have no clinical significance but our results showed its significant higher rate among PPNE patients. There is no direct causal relation between spina bifida occulta and enuresis, apparently, but the findings suggest a common developmental etiology.

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

    OpenAIRE

    Chaste, Pauline; Clement, Nathalie; Mercati, Oriane; Guillaume, Jean-luc; Delorme, Richard; Botros, Hany Goubran; Pagan, Ce?cile; Pe?rivier, Samuel; Scheid, Isabelle; Nygren, Gudrun; Anckarsa?ter, Henrik; Rastam, Maria; Sta?hlberg, 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. Plasma Melatonin Levels in Relation to the Light-Dark Cycle and Parental Background in Domestic Pigs

    Directory of Open Access Journals (Sweden)

    Andersson H

    2001-06-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2013-11-01

    Melatonin limits obesity in rodents without affecting food intake and activity, suggesting a thermogenic effect. Identification of brown fat (beige/brite) in white adipose tissue (WAT) prompted us to investigate whether melatonin is a brown-fat inducer. We used Zücker diabetic fatty (ZDF) rats, a model of obesity-related type 2 diabetes and a strain in which melatonin reduces obesity and improves their metabolic profiles. At 5 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control and those treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk. Melatonin induced browning of inguinal WAT in both ZDF and ZL rats. Hematoxylin-eosin staining showed patches of brown-like adipocytes in inguinal WAT in ZDF rats and also increased the amounts in ZL animals. Inguinal skin temperature was similar in untreated lean and obese rats. Melatonin increased inguinal temperature by 1.36 ± 0.02°C in ZL and by 0.55 ± 0.04°C in ZDF rats and sensitized the thermogenic effect of acute cold exposure in both groups. Melatonin increased the amounts of thermogenic proteins, uncoupling protein 1 (UCP1) (by ~2-fold, P < 0.01) and PGC-1? (by 25%, P < 0.05) in extracts from beige inguinal areas in ZL rats. Melatonin also induced measurable amounts of UCP1 and stimulated by ~2-fold the levels of PGC-1? in ZDF animals. Locomotor activity and circulating irisin levels were not affected by melatonin. These results demonstrate that chronic oral melatonin drives WAT into a brown-fat-like function in ZDF rats. This may contribute to melatonin's control of body weight and its metabolic benefits. PMID:24007241

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

    Directory of Open Access Journals (Sweden)

    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

  10. Molecular pathways involved in seasonal body weight and reproductive responses governed by melatonin.

    Science.gov (United States)

    Barrett, Perry; Bolborea, Matei

    2012-05-01

    Seasonal mammals typically of temperate or boreal habitats use the predictable annual cycle of daylength to initiate a suite of physiological and behavioural changes in anticipation of adverse environmental winter conditions, unfavourable for survival and reproduction. Daylength is encoded as the duration of production of the pineal hormone melatonin, but how the melatonin signal is decoded has been elusive. From the studies carried out in birds and mammals together with the advent of technologies such as microarray analysis of gene expression, progress has been achieved to demystify how seasonal physiology is regulated in response to the duration of melatonin signalling. The critical tissue for the action of melatonin is the pars tuberalis (PT) where melatonin receptors are located. At the molecular level, regulation of cyclic adenosine monophosphate (cAMP) signalling in this tissue is likely to be a key event for melatonin action, either an acute inhibitory action or sensitization of this pathway by prolonged stimulation of melatonin receptors reflecting durational melatonin presence. Melatonin action at the PT has been shown to have both positive and negative effects on gene transcription, incorporating components of the circadian clock as part of the mechanism of decoding the melatonin signal and regulating thyrotrophin-stimulating hormone (TSH) expression, a key output hormone of the PT. Microarray analysis of gene expression of PT tissue exposed to long and short photoperiods has identified important new genes that may be regulated by melatonin and contributing to the seasonal regulation of TSH production by this tissue. In the brain, tanycytes lining the third ventricle of the hypothalamus and regulation of thyroid hormone synthesis by PT-derived TSH in these cells are now established as an important component of the pathway leading to seasonal changes in physiology. Beyond the tanycyte, identified changes in gene expression for neuropeptides, receptors and other signalling molecules pinpoint some of the areas of the brain, the hypothalamus in particular, that are likely to be involved in the regulation of seasonal physiology. PMID:22017374

  11. Light pollution modifies the expression of daily rhythms and behavior patterns in a nocturnal primate.

    Science.gov (United States)

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

    2013-01-01

    Among anthropogenic pressures, light pollution altering light/dark cycles and changing the nocturnal component of the environment constitutes a threat for biodiversity. Light pollution is widely spread across the world and continuously growing. However, despite the efforts realized to describe and understand the effects of artificial lighting on fauna, few studies have documented its consequences on biological rhythms, behavioral and physiological functions in nocturnal mammals. To determine the impacts of light pollution on nocturnal mammals an experimental study was conducted on a nocturnal primate, the grey mouse lemur Microcebus murinus. Male mouse lemurs (N = 8) were exposed 14 nights to moonlight treatment and then exposed 14 nights to light pollution treatment. For both treatments, chronobiological parameters related to locomotor activity and core temperature were recorded using telemetric transmitters. In addition, at the end of each treatment, the 14(th) night, nocturnal and feeding behaviors were explored using an infrared camera. Finally, throughout the study, body mass and daily caloric food intake were recorded. For the first time in a nocturnal primate, light pollution was demonstrated to modify daily rhythms of locomotor activity and core temperature especially through phase delays and increases in core temperature. Moreover, nocturnal activity and feeding behaviors patterns were modified negatively. This study suggests that light pollution induces daily desynchronization of biological rhythms and could lead to seasonal desynchronization with potential deleterious consequences for animals in terms of adaptation and anticipation of environmental changes. PMID:24236115

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

    OpenAIRE

    Kalra, Sanjay; Agrawal, Swati; Sahay, Manisha

    2012-01-01

    The pineal gland is a tiny endocrine gland whose physiologic role has been the focus of much research and much more speculation over the past century. This mini-review discusses recent findings which correlate melatonin and renal physiology, and postulates the presence of a “reno-pineal axis.” Drawing lessons from comparative endocrinology, while quoting human data, it advocates the need to study the “reno-pineal axis” in greater detail.

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

    OpenAIRE

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

    2009-01-01

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

  14. Protective effect of melatonin against Adriamycin-induced cardiotoxicity.

    Science.gov (United States)

    Zhang, Yan; Li, Lixin; Xiang, Cheng; Ma, Zhiqian; Ma, Tian; Zhu, Shuchai

    2013-05-01

    The aim of this in vivo study was to explore the protective properties of melatonin against Adriamycin-induced myocardial toxicity. A rat model of breast cancer was established and the rats were randomly divided into the blank group (Blank), the solvent group [Diss; dehydrated alcohol: physiological saline (1:9)], the Adriamycin group (ADM), the melatonin group (MLT) and the melatonin + Adriamycin group (M+A). The concentrations of lipid peroxide (LPO), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in myocardial tissues were detected, the changes in myocardial tissues were observed using light microscopy and electron microscopy, and the 1-month survival rates of each group of rats were compared. Breast cancer was established in 116 rats. In the ADM group, the concentration of LPO was higher and the concentrations of SOD and GSH-Px were significantly lower than those in the blank group. In the M+A group, compared with the ADM group, the concentration of LPO was lower (PMelatonin may have a protective role in the myocardium by reducing Adriamycin-induced myocardial oxidative damage. PMID:23737906

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

    Directory of Open Access Journals (Sweden)

    Nesterenko O.V.

    2011-09-01

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

  16. Transmission of primary nocturnal enuresis and attention deficit hyperactivity disorder.

    Science.gov (United States)

    Bailey, J N; Ornitz, E M; Gehricke, J G; Gabikian, P; Russell, A T; Smalley, S L

    1999-12-01

    Primary nocturnal enuresis (PNE) is a prevalent disorder among children with a complex mode of inheritance. Family, twin, and linkage studies have provided evidence that genetic factors underlie the familiality of PNE. Linkage investigations support the hypothesis that PNE is heterogeneous, and the genetic heterogeneity may be reflected in co-morbid clinical conditions such as attention deficit hyperactivity disorder (ADHD). This study used a family study method and examined the transmission of PNE in relatives of PNE and control probands with and without ADHD, to determine if these disorders co-occur due to common genetic susceptibilities or other, i.e. non-genetic, reasons. This study concluded that the pattern of inheritance found is consistent with the independent transmission of PNE and ADHD. PMID:10626523

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

    Science.gov (United States)

    Wijewickrama, Eranga S; Gooneratne, Lalindra; De Silva, Chandu; Lanarolle, Rushika L

    2013-01-01

    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. PMID:23354203

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Paroxysmal nocturnal hemoglobinuria and the age of therapeutic complement inhibition.

    Science.gov (United States)

    Varela, Juan Carlos; Brodsky, Robert A

    2013-11-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease of hematopoietic stem cells due to a mutation in the PIG-A gene leading to a deficiency of GPI-anchored proteins. Lack of two specific GPI-anchored proteins, CD55 and CD59, leads to uncontrolled complement activation that result in both intravascular and extravascular hemolysis. Free hemoglobin leads to nitric oxide depletion that mediates the pathophysiology of some of the common clinical signs of PNH. Clinical symptoms of PNH include evidence of hemolytic anemia, bone marrow failure, smooth muscle dystonias and thromboses. Treatment options for patients with PNH include bone marrow transplantation, a therapy associated with high morbidity and mortality, or treatment with the complement inhibitor eculizumab. Eculizumab is a first-in-class anti-complement drug that in PNH has been shown to block complement-mediated hemolysis, reduce transfusion dependency, reduce thromboembolic complications and improve the quality of life (QoL) of patients. PMID:24168416

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

    International Nuclear Information System (INIS)

    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

  1. Paroxysmal nocturnal hemoglobinuria: current issues in pathophysiology and treatment.

    Science.gov (United States)

    Young, Neal S

    2005-03-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder of the bone marrow that produces intravascular hemolysis, proclivity to venous thrombosis, and hematopoietic failure. Mutation in the PIG-A gene in a stem cell aborts synthesis of glycosyl-phosphoinositol (GPI) anchors and therefore expression of all GPI-anchored proteins on the surface of progeny erythrocytes, leukocytes, and platelets. The hemolytic anemia of PNH is well understood, and erythrocyte susceptibility to complement may be treated with anti-C5a monoclonal antibody. The pathophysiology of PNH cell clonal expansion and its association with immune-mediated marrow failure are not understood, but PNH/aplasia responds to immunosuppressive regimens such as antithymocyte globulin and cyclosporine. The mechanism of thrombosis in PNH is also obscure, but frequently fatal clotting episodes may be prevented by Coumadin (Bristol-Myers Squibb Pharma Co., Wilmington, DE) prophylaxis. PMID:15720958

  2. Oscillating Nocturnal Slope Flow in a Coastal Valley

    DEFF Research Database (Denmark)

    Gryning, Sven-Erik; Larsen, SØren Ejling

    1985-01-01

    Observations of slope flows in a coastal valley are analyzed. The diurnal variation of upslope and downslope flows depends on season in a systematic way which appears to be related to the high latitude of the observational site and the presence of a nearby layer of marine air. Summer nocturnal flow over the sloping valley floor was studied during a special observing campaign. A downslope gravity flow interacts with even colder surface air at the valley floor. The latter originates as cold marine air or previous drainage of cold air. Regular oscillations which appear to be trapped, terrain-related internal gravity waves, exert a major influence on the downslope flow and its interaction with pre-existing cold air at the floor of the valley

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

    Science.gov (United States)

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

    2008-06-23

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

  4. Nocturnal sleep and daytime alertness of aircrew after transmeridian flights

    Science.gov (United States)

    Nicholson, Anthony N.; Pascoe, Peta A.; Spencer, Michael B.; Stone, Barbara M.; Green, Roger L.

    1986-01-01

    The nocturnal sleep and daytime alertness of aircrew were studied by electroencephalography and the multiple sleep latency test. After a transmeridian flight from London To San Francisco, sleep onset was faster and, although there was increased wakefulness during the second half of the night, sleep duration and efficiency over the whole night were not changed. The progressive decrease in sleep latencies observed normally in the multiple sleep latency test during the morning continued throughout the day after arrival. Of the 13 subjects, 12 took a nap of around 1-h duration in the afternoon preceding the return flight. These naps would have been encouraged by the drowsiness at this time and facilitated by the departure of the aircraft being scheduled during the early evening. An early evening departure had the further advantage that the circadian increase in vigilance expected during the early part of the day would occur during the latter part of the return flight.

  5. Melatonin Treatment in Individuals with Intellectual Disability and Chronic Insomnia: A Randomized Placebo-Controlled Study

    Science.gov (United States)

    Braam, W.; Didden, R.; Smits, M.; Curfs, L.

    2008-01-01

    Background: While several small-number or open-label studies suggest that melatonin improves sleep in individuals with intellectual disabilities (ID) with chronic sleep disturbance, a larger randomized control trial is necessary to validate these promising results. Methods: The effectiveness of melatonin for the treatment of chronic sleep…

  6. Essential actions of melatonin in protecting the ovary from oxidative damage.

    Science.gov (United States)

    Cruz, M H C; Leal, C L V; Cruz, J F; Tan, D X; Reiter, R J

    2014-10-15

    Free radicals and other reactive species are involved in normal ovarian physiology. However, they are also highly reactive with complex cellular molecules (proteins, lipids, and DNA) and alter their functions leading to oxidative stress. Oxidative damage may play a prominent role in the development of disorders that considerably influence female fertility. Melatonin, because of its amphiphilic nature that allows for crossing morphophysiological barriers, is an effective antioxidant for protecting macromolecules against oxidative stress caused by reactive species. The balance between reactive oxygen species and antioxidants within the follicle seems to be critical to the function of the oocyte and granulosa cells and evidence has accumulated showing that melatonin is involved in the protection of these cells. Melatonin appears to have varied functions at different stages of follicle development, oocyte maturation, and luteal stage. Melatonin concentration in the growing follicle may be an important factor in avoiding atresia, because melatonin in the follicular fluid reduces apoptosis of critical cells. Melatonin also has protective actions during oocyte maturation reducing intrafollicular oxidative damage. An association between melatonin concentrations in follicular fluid and oocyte quality has been reported; this would allow a preovulatory follicle to fully develop and provide a competent oocyte for fertilization. The functional role of reactive species and the cytoprotective properties of melatonin on the ovary from oxidative damage are summarized in this brief review. PMID:25107629

  7. Effects of moonlight exposure on plasma melatonin rhythms in the seagrass rabbitfish, Siganus canaliculatus.

    Science.gov (United States)

    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

  8. Circadian regulation of bird song, call, and locomotor behavior by pineal melatonin in the zebra finch.

    Science.gov (United States)

    Wang, Gang; Harpole, Clifford E; Trivedi, Amit K; Cassone, Vincent M

    2012-04-01

    As both a photoreceptor and pacemaker in the avian circadian clock system, the pineal gland is crucial for maintaining and synchronizing overt circadian rhythms in processes such as locomotor activity and body temperature through its circadian secretion of the pineal hormone melatonin. In addition to receptor presence in circadian and visual system structures, high-affinity melatonin binding and receptor mRNA are present in the song control system of male oscine passeriform birds. The present study explores the role of pineal melatonin in circadian organization of singing and calling behavior in comparison to locomotor activity under different lighting conditions. Similar to locomotor activity, both singing and calling behavior were regulated on a circadian basis by the central clock system through pineal melatonin, since these behaviors free-ran with a circadian period and since pinealectomy abolished them in constant environmental conditions. Further, rhythmic melatonin administration restored their rhythmicity. However, the rates by which these behaviors became arrhythmic and the rates of their entrainment to rhythmic melatonin administration differed among locomotor activity, singing and calling under constant dim light and constant bright light. Overall, the study demonstrates a role for pineal melatonin in regulating circadian oscillations of avian vocalizations in addition to locomotor activity. It is suggested that these behaviors might be controlled by separable circadian clockworks and that pineal melatonin entrains them all through a circadian clock. PMID:22476775

  9. Regulation of vascular endothelial growth factor by melatonin in human breast cancer cells.

    Science.gov (United States)

    Alvarez-García, Virginia; González, Alicia; Alonso-González, Carolina; Martínez-Campa, Carlos; Cos, Samuel

    2013-05-01

    Melatonin exerts oncostatic effects on breast cancer by interfering with the estrogen-signaling pathways. Melatonin reduces estrogen biosynthesis in human breast cancer cells, surrounding fibroblasts and peritumoral endothelial cells by regulating cytokines that influence tumor microenvironment. This hormone also exerts antiangiogenic activity in tumoral tissue. In this work, our objective was to study the role of melatonin on the regulation of the vascular endothelial growth factor (VEGF) in breast cancer cells. To accomplish this, we cocultured human breast cancer cells (MCF-7) with human umbilical vein endothelial cells (HUVECs). VEGF added to the cultures stimulated the proliferation of HUVECs and melatonin (1 mM) counteracted this effect. Melatonin reduced VEGF production and VEGF mRNA expression in MCF-7 cells. MCF-7 cells cocultured with HUVECs stimulated the endothelial cells proliferation and increased VEGF levels in the culture media. Melatonin counteracted both stimulatory effects on HUVECs proliferation and on VEGF protein levels in the coculture media. Conditioned media from MCF-7 cells increased HUVECs proliferation, and this effect was significantly counteracted by anti-VEGF and 1 mM melatonin. All these findings suggest that melatonin may play a role in the paracrine interactions between malignant epithelial cells and proximal endothelial cells through a downregulatory action on VEGF expression in human breast cancer cells, which decrease the levels of VEGF around endothelial cells. Lower levels of VEGF could be important in reducing the number of estrogen-producing cells proximal to malignant cells as well as decreasing tumoral angiogenesis. PMID:23013414

  10. Molecularly imprinted electrochemical sensing of urinary melatonin in a microfluidic system.

    Science.gov (United States)

    Lee, Mei-Hwa; O'Hare, Danny; Chen, Yi-Li; Chang, Yu-Chia; Yang, Chien-Hsin; Liu, Bin-Da; Lin, Hung-Yin

    2014-09-01

    Melatonin levels may be related to the risks of breast cancer and prostate cancer. The measurement of urinary melatonin is also useful in monitoring serum melatonin levels following oral administration. In this work, melatonin is the target molecule, which is imprinted onto poly(ethylene-co-vinyl alcohol) by evaporation of the solvent on the working electrode of an electrochemical sensing chip. This sensing chip is used directly as a tool for optimizing the imprinting polymer composition, flow rate, and injection volume of the samples. Microfluidic sensing of the target and interference molecules revealed that the lowest detection limit is as low as ?pM, and the electrochemical response is weak even at high interference concentrations. Poly(ethylene-co-vinyl alcohol), containing 44?mol.?% ethylene, had an imprinting effectiveness of more than six-fold. In random urine analysis, the microfluidic amperometric measurements of melatonin levels with an additional and recovery of melatonin, the melatonin recovery achieved 94.78?±?1.9% for melatonin at a concentration of 1.75-2.11?pg/mL. PMID:25584113

  11. A randomized controlled trial of oral melatonin supplementation and breast cancer biomarkers.

    Science.gov (United States)

    Schernhammer, E S; Giobbie-Hurder, A; Gantman, K; Savoie, J; Scheib, R; Parker, L M; Chen, W Y

    2012-04-01

    We examined compliance with and the effects of melatonin supplementation on breast cancer biomarkers (estradiol, insulin-like growth factor I (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP-3), and the IGF-1/IGFBP-3 ratio) in postmenopausal breast cancer survivors. In a double-blind, placebo-controlled study, postmenopausal women with a prior history of stages 0-III breast cancer who had completed active cancer treatment (including hormonal therapy) were randomly assigned to either 3 mg oral melatonin (n = 48) or placebo daily for 4 months. Plasma samples were collected at baseline and after the completion of the intervention. The primary endpoints were compliance and change in estradiol and IGF-1/IGFBP-3 levels. Ninety-five women were randomized (48 to melatonin and 47 to placebo). Eighty-six women (91%) completed the study and provided pre- and postintervention bloods. Melatonin was well tolerated without any grade 3/4 toxicity and compliance was high (89.5%). Overall, among postmenopausal women with a prior history of breast cancer, a 4-month course of 3 mg melatonin daily did not influence circulating estradiol, IGF-1, or IGFBP-3 levels. Compliance was comparable between the two groups. Short-term melatonin treatment did not influence the estradiol and IGF-1/IGBBP-3 levels. Effects of longer courses of melatonin among premenopausal women are unknown. Low baseline estradiol levels in our study population may have hindered the ability to detect any further estradiol-lowering effects of melatonin. PMID:22370698

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

    Directory of Open Access Journals (Sweden)

    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

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

    International Nuclear Information System (INIS)

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

  14. Protective effects of melatonin against arsenic-induced apoptosis and oxidative stress in rat testes.

    Science.gov (United States)

    Uygur, Ramazan; Aktas, Cevat; Caglar, Veli; Uygur, Emine; Erdogan, Hasan; Ozen, Oguz Aslan

    2013-12-01

    This study aimed to investigate the protective effects of melatonin against arsenic-induced apoptosis and oxidative stress in rat testes. A total of 27 male rats were divided into 3 groups: control (saline: 5 ml kg(-1) day(-1), intragastrically), arsenic (sodium arsenite (NaAsO2): 5 mg kg(-1) day(-1), intragastrically), and arsenic + melatonin (sodium arsenite (NaAsO2): 5 mg kg(-1) day(-1), intragastrically and melatonin: 25 mg kg(-1) day(-1), intraperitoneally) group. At the end of 30 days, the rats were killed under anesthesia. Histopathological examination showed that testicular injury mediated by arsenic was ameliorated by the administration of melatonin. The number of apoptotic germ cell was increased, and the number of proliferating cell nuclear antigen (PCNA)-positive germ cell was decreased in testis after arsenic administration. Our data indicate a significant reduction in the activity of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and there was a rise in the expression of PCNA in testis of arsenic + melatonin group. The decreased superoxide dismutase, catalase, and glutathione peroxidase activities as well as increased malondialdehyde levels in testis due to arsenic administration were also counteracted by melatonin. These data suggested that melatonin has beneficial effects against arsenic-induced testicular damage by decreasing morphological damage, germ cell apoptosis, lipid peroxidation, and oxidative stress. Our results suggest that melatonin plays a protective role against arsenic-induced testicular apoptosis and oxidative stress. PMID:24318767

  15. Nocturnal oxygen saturation profiles of healthy term infants

    Science.gov (United States)

    Terrill, Philip Ian; Dakin, Carolyn; Hughes, Ian; Yuill, Maggie; Parsley, Chloe

    2015-01-01

    Objective Pulse oximetry is used extensively in hospital and home settings to measure arterial oxygen saturation (SpO2). Interpretation of the trend and range of SpO2 values observed in infants is currently limited by a lack of reference ranges using current devices, and may be augmented by development of cumulative frequency (CF) reference-curves. This study aims to provide reference oxygen saturation values from a prospective longitudinal cohort of healthy infants. Design Prospective longitudinal cohort study. Setting Sleep-laboratory. Patients 34 healthy term infants were enrolled, and studied at 2?weeks, 3, 6, 12 and 24?months of age (N=30, 25, 27, 26, 20, respectively). Interventions Full overnight polysomnography, including 2?s averaging pulse oximetry (Masimo Radical). Main outcome measurements Summary SpO2 statistics (mean, median, 5th and 10th percentiles) and SpO2 CF plots were calculated for each recording. CF reference-curves were then generated for each study age. Analyses were repeated with sleep-state stratifications and inclusion of manual artefact removal. Results Median nocturnal SpO2 values ranged between 98% and 99% over the first 2?years of life and the CF reference-curves shift right by 1% between 2?weeks and 3?months. CF reference-curves did not change with manual artefact removal during sleep and did not vary between rapid eye movement (REM) and non-REM sleep. Manual artefact removal did significantly change summary statistics and CF reference-curves during wake. Conclusions SpO2 CF curves provide an intuitive visual tool for evaluating whether an individual's nocturnal SpO2 distribution falls within the range of healthy age-matched infants, thereby complementing summary statistics in the interpretation of extended oximetry recordings in infants. PMID:25063836

  16. Niche convergence suggests functionality of the nocturnal fovea

    Directory of Open Access Journals (Sweden)

    Gillian L. Moritz

    2014-07-01

    Full Text Available The fovea is a declivity of the retinal surface associated with maximum visual acuity. Foveae are widespread across vertebrates, but among mammals they are restricted to haplorhine primates (tarsiers, monkeys, apes, and humans, which are primarily diurnal. Thus primates have long contributed to the prevailing view that the fovea is a functional adaptation to diurnal color vision. The foveae of nocturnal taxa, such as tarsiers, are widely interpreted as vestigial traits and therefore evidence of a diurnal ancestry. This enduring premise has been central to adaptive hypotheses on the origins of anthropoid primates; however, the question of whether the fovea of tarsiers is a functionless anachronism or a nocturnal adaptation remains open. To address this question, we focused on the diets of tarsiers (Tarsius and scops owls (Otus, two taxa united by numerous anatomical homoplasies, including foveate vision. A functional interpretation of these homoplasies predicts dietary convergence and competition. This prediction can be tested with an analysis of carbon and nitrogen stable isotopes in tissues, which integrate dietary information. As predicted, the isotopic niches of Tarsius and Otus overlapped. In both Borneo and the Philippines, the ?13C values were indistinguishable, whereas the ?15N values of Otus were marginally higher than those of Tarsius. Our results indicate that both diets consisted mainly of ground-dwelling prey and raise the possibility of some resource partitioning. Taken together, our isotopic analysis supports a functional interpretation of the many homoplasies shared by tarsiers and scops owls, including a retinal fovea. We suggest that the fovea might function similarly in tarsiers and scops owls by calibrating the auditory localization pathway. The integration of auditory localization and visual fixation during prey detection and acquisition might be critical at low light levels.

  17. THE ASSOCIATION BETWEEN NOCTURNAL ENURESIS AND TUBERCULOSIS: COINCIDENCE OR COMORBIDITY?

    Directory of Open Access Journals (Sweden)

    Funda Ba?tu?

    2012-03-01

    Full Text Available Objective: We observed that some children with Tuberculosis (TB had nocturnal enuresis and the enuresis complaint in these children healed with anti TB drugs. We aimed to investigate a possible relation between nocturnal enuresis and tuberculosis in a prospective study.Material and Methods: One hundred and forty two enuretic children were enrolled to our study. Enuretic cases were treated and followed according to the choice of the children and their parents. The PPD test was performed in enuretic and non-enuretic children of similar age and sex. Enuretic cases were divided into five groups; desmopressin was given to 45 cases, PPD positive 33 cases were treated with isoniazid, and anti-tuberculosis treatment was given to 10 cases with pulmonary TB. Ten cases with PPD positive and 44 PPD negative patients were viewed without drug treatment.Results: A positive PPD skin test was found at a ratio of 30.2% and 24% in enuretic and non-enuretic children, respectively. There was no significant difference between these ratios. Although the TB-group had a small number of cases (n=10, full recovery was observed in 60% of these patients, and their relapse rate (28.5% was lower than the desmopressin group (70.3%.Conclusion: Because the TB-group had a high remission rate and low relapse rate, and the PPD positivity rate was high in enuretic patients, we concluded that the hypothesis of a possible association between enuresis and tuberculosis should be examined by future studies.

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

    Directory of Open Access Journals (Sweden)

    Stojakovi? Nataša

    2013-01-01

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

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

    OpenAIRE

    Figueiro Mariana G; Rea Mark S

    2012-01-01

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

  20. Melatonin treatment increases the transcription of cell proliferation-related genes prior to inducing cell death in C6 glioma cells in vitro

    OpenAIRE

    Qu, Jiagui; Rizak, Joshua D.; Li, Xiaomiao; Li, Jiejing; Ma, Yuanye

    2013-01-01

    A number of studies have suggested that melatonin possesses anticancer properties. However, conflicting data exists with regard to the role of melatonin in the treatment of cancer. In the present study, the effects of melatonin on the transcriptional regulation of three genes associated with cell proliferation (Nestin, Bmi-1 and Sox2), and on C6 glioma cell survival and viability, were investigated in vitro to evaluate the use of melatonin in cancer therapy. Melatonin was shown to increase th...

  1. [Model of control of diurnal melatonin secretion by the solar radiation].

    Science.gov (United States)

    Leonidov, A V

    2014-01-01

    The mathematical model of the control process of diurnal melatonin secretion under the influence of solar radiation on retina photoreceptors is proposed. Invariant relations for calculating melatonin secretion rate and its concentration in blood plasma are obtained. Spectral, time and energy characteristics of solar radiation synchronizing diurnal melatonin secretion and circadian rhythms in human are defined. A possibility of using the relations obtained is shown for arbitrary combination of calendar dates, local time of any time zone and geographical coordinates of a calculated point on earth surface. The adequacy of model is confirmed by coincidence of the calculation data with the results of independent experimental studies on diurnal secretion of melatonin and circadian rhythm in human. The model proposed can be used during investigation of diurnal secretion of melatonin and circadian rhythm in human. PMID:25707251

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

    Directory of Open Access Journals (Sweden)

    Ioan Padeanu

    2012-10-01

    Full Text Available Investigations were carried out in a commercial farm from Turnu, Arad County, on a number of 110 indigenous adultewes from the Tigaia breed. It is estimated by some authors that administration of subcutaneous melatonin implantsduring a period of 30 days, in lactating or dry ewes, would improve the reproductive performances in some sheepbreeds. Subcutaneous melatonin implants (Melovin were inserted to the ewes in doses of 18 mg. Current research,emphasized treated that from indigenous Tigaia breed, can be obtained superior reproduction indexes if the animalsare treated with melatonin implants with 35 days before the mating season, differences from the untreated groupbeing significantly (p<0.001. However, in sheep treated used melatonin implants, the lambing interval were reducedwith 40 to 50%. It seems that use of melatonin implants Melovin type near the beginning of normal breeding season,increases the reproductive performance of adult ewes from the Tigaia breed.

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

    Science.gov (United States)

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

    2012-02-26

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

  4. Decreased expression of the melatonin receptor 1 in human colorectal adenocarcinomas.

    Science.gov (United States)

    Nemeth, C; Humpeler, S; Kallay, E; Mesteri, I; Svoboda, M; Rögelsperger, O; Klammer, N; Thalhammer, T; Ekmekcioglu, C

    2011-01-01

    Melatonin exerts anti-proliferative and pro-apoptotic effects in various cancer cell lines. Furthermore, there is evidence for impaired melatonin secretion in human breast and colorectal cancer. Additionally, several studies revealed a modulated expression of the melatonin receptor 1 (MT1), in human breast cancer specimens. Since melatonin binding sites were already identified in the human intestine, our aim is to identify the expression and to characterize the localization of the MT1 receptor in the human colon and in particular to compare MT1 expression levels between non-malignant and malignant colonic tissue. We assessed MT1 transcript levels with real time RT-PCR in colon adenocarcinomas and the adjacent normal colonic mucosa of 39 patients and observed a significant decrease of MT1 mRNA expression in colorectal cancer compared with the healthy adjacent mucosa tissue (0.67 mean difference, P cancer could point to a role of melatonin in this disease. PMID:22217986

  5. Expression and putative functions of melatonin receptors in malignant cells and tissues.

    Science.gov (United States)

    Ekmekcioglu, Cem

    2014-11-01

    Melatonin, the popular hormone of the darkness, is primarily synthesized in the pineal gland, and acts classically through the G-protein coupled plasma membrane melatonin receptors MT1 and MT2, respectively. Although some of the receptor mediated functions of melatonin, especially those on the (central) circadian system, have been more or less clarified, the functional meaning of MT-receptors in various peripheral organs are still not sufficiently investigated yet. There is, however, accumulating evidence for oncostatic effects of melatonin with both, antioxidative and MT-receptor mediated mechanisms possibly playing a role. This review briefly summarizes the physiology of melatonin and MT-receptors, and discusses the expression and function of MT-receptors in human cancer cells and tissues. PMID:25023005

  6. The effects of exogenous melatonin on the morphology of thyrocytes in pinealectomized and irradiated rats

    International Nuclear Information System (INIS)

    We investigated the effects of exogenous melatonin on the thyrocytes morphology in gamma-irradiated rats under condition where the pineal gland, as a main physiological source of endogenous melatonin, was removed. Three months after pinealectomy animals were divided into two groups: one group of animals was treated with 0.5 ml of vehicle (ethanol diluted in water) and other group was injected intraperitoneally 2 mg/kg of melatonin dissolved in 0.5 ml of vehicle daily during the period of fourteen days. After this treatment all the animals were irradiated with a single dose of 8 Gy gamma rays. Ionising radiation induced apoptosis, hydropic swelling or/and necrosis in both groups of animals, however these changes were less discerned in the thyrocytes of melatonin-treated animals. Our findings demonstrate that administration of exogenous melatonin prior to irradiation reduces radiation-induced thyrocytes damage. (author)

  7. Circadian variation in the response to experimental endotoxemia and modulatory effects of exogenous melatonin.

    Science.gov (United States)

    Alamili, Mahdi; Klein, Mads; Lykkesfeldt, Jens; Rosenberg, Jacob; Gögenur, Ismail

    2013-11-01

    Disturbances in circadian rhythms are commonly observed in the development of several medical conditions and may also be involved in the pathophysiology of sepsis. Melatonin, with its antioxidative and anti-inflammatory effects, is known to modulate the response to endotoxemia. In this paper, we investigated the circadian variation with or without melatonin administration in an experimental endotoxemia model based on lipopolysaccharide (LPS). Sixty male Sprague-Dawley rats were assigned to six groups receiving an intraperitoneal injection of either LPS (5?mg/kg), LPS?+?melatonin (1?mg/kg), or LPS?+?melatonin (10?mg/kg) at either daytime or nighttime. Superoxide dismutase (SOD) was analyzed in liver samples collected after decapitation. Furthermore, inflammatory plasma markers (cytokines interleukin [IL]-6, IL-10) and oxidative plasma markers (ascorbic acid [AA], dehydroascorbic acid [DHA], and malondialdehyde [MDA]) were analyzed before and 5?h after the onset of endotoxemia. There were significant higher levels of SOD (p?melatonin 1 and 10?mg reduced the levels of MDA and increased SOD, IL-6, IL-10, and DHA (p?melatonin reduced the levels of MDA and increased DHA (p?melatonin resulted in lower levels of AA during daytime (p?melatonin was observed. The results showed that the response induced by experimental endotoxemia was dependent on time of day. Melatonin administration modulated the inflammatory and oxidative stress responses induced by endotoxemia and also resulted in higher levels of antioxidants during daytime. The effect of circadian time on the endotoxemia response and possible modulatory effects of melatonin need further investigations in a human endotoxemia model. PMID:23998285

  8. In vitro development rate of preimplantation rabbit embryos cultured with different levels of melatonin.

    Science.gov (United States)

    Mehaisen, Gamal Mohamed Kamel; Saeed, Ayman Moustafa

    2015-02-01

    This study aimed to investigate the effect of melatonin supplementation at different levels in culture medium on embryo development in rabbits. Embryos of 2-4 cells, 8-16 cells and morula stages were recovered from nulliparous Red Baladi rabbit does by laparotomy technique 24, 48 and 72 h post-insemination, respectively. Normal embryos from each stage were cultured to hatched blastocyst stages in either control culture medium (TCM-199 + 20% fetal bovine serum) or control supplemented with melatonin at 10(-3) M, 10(-6) M or 10(-9) M. No effect of melatonin was found on development of embryos recovered at 24 h post-insemination. The high level of melatonin at 10(-3) M adversely affected the in vitro development rates of embryos recovered at 48 h post-insemination (52 versus 86, 87 and 80% blastocyst rate; 28 versus 66, 78 and 59% hatchability rate for 10(-3) M versus 10(-9) M, 10(-6) M and control, respectively, P< 0.05). At the morula stage, melatonin at 10-3 M significantly increased the in vitro development of embryos (92% for 10(-3) M versus 76% for control, P < 0.05), while the hatchability rate of these embryos was not improved by melatonin (16-30% versus 52% for melatonin groups versus control, P < 0.05). Results show that a moderate level of melatonin (10(-6) M) may improve the development and hatchability rates of preimplantation rabbit embryos. The addition of melatonin at a 10-3 M concentration enhances the development of rabbit morulae but may negatively affect the development of earlier embryos. More studies are needed to optimize the use of melatonin in in vitro embryo culture in rabbits. PMID:23985360

  9. Effect of melatonin on daily LH secretion in intact and ovariectomized ewes during the breeding season.

    Science.gov (United States)

    Misztal, Tomasz; Romanowicz, Katarzyna; Barcikowski, Bernard

    2002-02-15

    This study was conducted to find out whether daily LH secretion in ewes may be modulated by melatonin during the breeding season, when the secretion of both hormones is raised. Patterns of plasma LH were determined in luteal-phase ewes infused intracerebroventricularly (icv.) with Ringer-Locke solution (control) and with melatonin (100 microg/100 microl/h). Response in LH secretion to melatonin was also defined in ovariectomized (OVX) ewes without and after estradiol treatment (OVX+E2). Basal LH concentrations by themselves did not differ significantly before, during and after both control and melatonin infusions in intact, luteal-phase ewes. However, single significant (P<0.05) increases in LH concentration were noted during the early dark phase in the control and 1h after start of infusion in melatonin treated ewes. In both OVX and OVX+E2 ewes, melatonin decreased significantly (P<0.01, P<0.05, respectively) mean plasma LH concentrations as compared to the levels noted before the infusions. In OVX+E2 ewes, a single significant (P<0.05) increase in LH occurred 1h after start of melatonin treatment, similarly as in luteal-phase ewes. No significant differences in the frequencies of LH pulses before, during and after melatonin infusion were found in all treatments groups. In conclusion, melatonin may exert a modulatory effect on daily LH secretion in ewes during the breeding season, stimulating the release of this gonadotropin in the presence of estradiol feedback and inhibiting it during steroid deprivation. Thus, estradiol seems to be positively linked with the action of melatonin on reproductive activity in ewes. PMID:11812629

  10. A comparative study between oral melatonin and oral midazolam on preoperative anxiety, cognitive, and psychomotor functions

    Science.gov (United States)

    Patel, Tushar; Kurdi, Madhuri S.

    2015-01-01

    Background & Aims: Melatonin, a naturally occurring hormone in the human body, has been reported to cause preoperative anxiolysis and sedation without impairing orientation. The aim of the following study was to evaluate and to compare the effects of oral melatonin and oral midazolam on preoperative anxiety, sedation, psychomotor, and cognitive function. Materials and Methods: A study conducted on 120 patients aged 16-55 years, of American Society of Anesthesiologists Grade 1 and 2 posted for elective surgery, with each group of melatonin, midazolam, and placebo comprising 40 patients. Patients were given either 0.4 mg/kg oral melatonin or 0.2 mg/kg oral midazolam or a placebo 60-90 min before induction. Preoperative anxiety was studied before and 60-90 min after giving medications using visual analog scale (VAS) anxiety score, orientation score, and sedation score. Psychomotor and cognitive functions were studied using the digit symbol substitution test (DSST) and trail making test (TMT) tests. Data were analyzed using Chi-square test or Kruskal–Wallis analysis of variance and the value of P anxiety scores were significant when melatonin was compared with placebo (P = 0.0124) and when midazolam was compared with placebo (P = 0.0003). When melatonin was compared with midazolam, no significant difference (P = 0.49) in VAS anxiety scores was observed. Intergroup comparison of sedation scores showed melatonin (P = 0.0258) and midazolam (P = 0.0000) to be statistically significant when compared with placebo. No changes in orientation scores occurred in melatonin and placebo group. Change in DSST scores and TMT scores were seen to be significant only in midazolam group. Conclusion: Oral melatonin 0.4 mg/kg provides adequate anxiolysis comparable to that of oral midazolam. Unlike midazolam, oral melatonin 0.4 mg/kg does not impair the general cognitive and psychomotor function especially cognitive aspects such as working memory, memory retrieval, sustained attention, and flexibility of thinking.

  11. Melatonin enhances the occurrence of autophagy induced by oxidative stress in Arabidopsis seedlings.

    Science.gov (United States)

    Wang, Ping; Sun, Xun; Wang, Na; Tan, Dun-Xian; Ma, Fengwang

    2015-05-01

    The beneficial effect that melatonin has against mitochondrial dysfunctioning seems to be linked to mitophagy. Roles for melatonin have been demonstrated in promoting health and preventing disease, as well as activating the process of autophagy in general. However, no reports have been made about how the application of melatonin regulates that process when plants are exposed to oxidative stress. We investigated the influence of different concentrations of melatonin (0.0, 0.5, 5.0, 10.0, or 50.0 ?m) on autophagy under methyl viologen (MV)-induced oxidative stress. Arabidopsis seedlings that were pretreated with 5 or 10 ?m melatonin underwent relatively strong induction of autophagy, as evidenced by the number of monodansylcadaverine (MDC)-stained autophagosomes in root samples. Pretreatment with 10 ?m melatonin also alleviated MV-induced photo-oxidation damage and significantly reduced the accumulation of oxidized proteins. Those responses might have been due to the strong upregulation of genes that involved in AtATG8-PE conjugation pathway, which enhanced the capacity for autophagy. Histochemical staining revealed that both O2-· and H2 O2 were highly accumulated upon MV exposure, although the response did not differ significantly between control and melatonin-pretreated seedlings. By contrast, exogenous melatonin upregulated the expression of two genes for H2 O2 -scavenging enzymes, that is, AtAPX1 and AtCATs. The activation of autophagy by melatonin without an alteration in ROS production may be part of a survival mechanism that is enhanced by melatonin after cellular damage. Therefore, it represents a second level of defense to remove damaged proteins when antioxidant activities are compromised. PMID:25788022

  12. Melatonin influences somatostatin secretion from human pancreatic ?-cells via MT1 and MT2 receptors.

    Science.gov (United States)

    Zibolka, Juliane; Mühlbauer, Eckhard; Peschke, Elmar

    2015-03-01

    Melatonin is an effector of the diurnal clock on pancreatic islets. The membrane receptor-transmitted inhibitory influence of melatonin on insulin secretion is well established and contrasts with the reported stimulation of glucagon release from ?-cells. Virtually, nothing is known concerning the melatonin-mediated effects on islet ?-cells. Analysis of a human pancreatic ?-cell model, the cell line QGP-1, and the use of a somatostatin-specific radioimmunoassay showed that melatonin primarily has an inhibitory effect on somatostatin secretion in the physiological concentration range. In the pharmacological range, melatonin elicited slightly increased somatostatin release from ?-cells. Cyclic adenosine monophosphate (cAMP) is the major second messenger dose-dependently stimulating somatostatin secretion, in experiments employing the membrane-permeable 8-Br-cAMP. 8-Br-cyclic guanosine monophosphate proved to be of only minor relevance to somatostatin release. As the inhibitory effect of 1 nm melatonin was reversed after incubation of QGP-1 cells with the nonselective melatonin receptor antagonist luzindole, but not with the MT2-selective antagonist 4-P-PDOT (4-phenyl-2-propionamidotetraline), an involvement of the MT1 receptor can be assumed. Somatostatin release from the ?-cells at low glucose concentrations was significantly inhibited during co-incubation with 1 nm melatonin, an effect which was less pronounced at higher glucose levels. Transient expression experiments, overexpressing MT1, MT2, or a deletion variant as a control, indicated that the MT1 and not the MT2 receptor was the major transmitter of the inhibitory melatonin effect. These data point to a significant influence of melatonin on pancreatic ?-cells and on somatostatin release. PMID:25585597

  13. Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Hikichi T

    2011-05-01

    Full Text Available Taiichi Hikichi1, Naohiro Tateda2, Toshiaki Miura31Department of Ophthalmology, Ohtsuka Eye Hospital, Sapporo; 2Asahikawa National College of Technology, Asahikawa; 3Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, JapanBackground: The purpose of this study was to evaluate the dynamics of plasma melatonin secretion in patients with type 2 diabetes mellitus and diabetic retinopathy.Methods: Plasma melatonin levels were measured by high-performance liquid chromatography in 56 patients. Patients were divided into a diabetic group (30 patients and a nondiabetic group (26 patients. The diabetic group was divided further into a proliferative diabetic retinopathy (PDR group (n = 14 and a nonproliferative diabetic retinopathy (NPDR group (n = 16. Plasma melatonin levels obtained at midnight and 3 am were compared between the groups.Results: Nighttime melatonin levels were significantly lower in the diabetic group than in the nondiabetic group (P < 0.03 and lower in the PDR group than in the nondiabetic and NPDR groups (P < 0.01 and P < 0.03, respectively, but no significant difference was found between the nondiabetic and NPDR groups. The daytime melatonin level did not significantly differ between the nondiabetic and diabetic groups or between the nondiabetic, NPDR, and PDR groups.Conclusion: The nighttime melatonin level is altered in patients with diabetes and PDR but not in diabetic patients without PDR. Although patients with PDR may have various dysfunctions that affect melatonin secretion more severely, advanced dysfunction of retinal light perception may cause altered melatonin secretion. Alteration of melatonin secretion may accelerate further occurrence of complications in diabetic patients.Keywords: circadian rhythm, diabetes, proliferative diabetic retinopathy, melatonin

  14. Melatonin promotes ripening and improves quality of tomato fruit during postharvest life.

    Science.gov (United States)

    Sun, Qianqian; Zhang, Na; Wang, Jinfang; Zhang, Haijun; Li, Dianbo; Shi, Jin; Li, Ren; Weeda, Sarah; Zhao, Bing; Ren, Shuxin; Guo, Yang-Dong

    2015-02-01

    In this study, the effect of melatonin on the postharvest ripening and quality improvement of tomato fruit was carried out. The tomatoes were immersed in exogenous melatonin for 2h, and then the related physiological indicators and the expression of genes during post-harvest life were evaluated. Compared with control check (CK), the 50 µM melatonin treatment significantly increased lycopene levels by 5.8-fold. Meanwhile, the key genes involved in fruit colour development, including phytoene synthase1 (PSY1) and carotenoid isomerase (CRTISO), showed a 2-fold increase in expression levels. The rate of water loss from tomato fruit also increased 8.3%, and the expression of aquaporin genes, such as SlPIP12Q, SlPIPQ, SlPIP21Q, and SlPIP22, was up-regulated 2- to 3-fold under 50 µM melatonin treatment. In addition, 50 µM melatonin treatment enhanced fruit softening, increased water-soluble pectin by 22.5%, and decreased protopectin by 19.5%. The expression of the cell wall modifying proteins polygalacturonase (PG), pectin esterase1 (PE1), ?-galactosidase (TBG4), and expansin1 (Exp1) was up-regulated under 50 µM melatonin treatment. Melatonin increased ethylene production by 27.1%, accelerated the climacteric phase, and influenced the ethylene signalling pathway. Alteration of ethylene production correlated with altered 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS4) expression. The expression of ethylene signal transduction-related genes such as NR, SlETR4, SlEIL1, SlEIL3, and SlERF2, was enhanced by 50 µM melatonin. The effect of melatonin on ethylene biosynthesis, ethylene perception, and ethylene signalling may contribute to fruit ripening and quality improvement in tomato. This research may promote the application of melatonin on postharvest ripening and quality improvement of tomato fruit as well as other horticultural productions in the future. PMID:25147270

  15. Melatonin enhances endogenous heme oxygenase-1 and represses immune responses to ameliorate experimental murine membranous nephropathy.

    Science.gov (United States)

    Wu, Chia-Chao; Lu, Kuo-Cheng; Lin, Gu-Jiun; Hsieh, Hsin-Yi; Chu, Pauling; Lin, Shih-Hua; Sytwu, Huey-Kang

    2012-05-01

    Idiopathic membranous nephropathy (MN), an autoimmune-mediated glomerulonephritis, is one of the most common causes of nephrotic syndrome in adults. Therapeutic agents for MN remain ill defined. We assessed the efficacy of melatonin therapy for MN. Experimental murine MN was induced with cationic bovine serum albumin, and the mice were immediately administered 20?mg/kg melatonin or phosphate-buffered saline subcutaneously once a day. Disease severity was verified by examining serum and urine metabolic profiles and renal histopathology. The expression of cytokines and oxidative stress markers, cell apoptosis, and the associated mechanisms were also determined. Mice treated with melatonin displayed a significant reduction in proteinuria and a marked amelioration of glomerular lesions, with attenuated immunocomplex deposition. The subpopulations of T cells were not altered, but the CD19(+) B-cell subpopulation was significantly reduced in the MN mice treated with melatonin. The expression of cytokine mRNAs in splenocytes indicated that melatonin reduced the expression of proinflammatory cytokines and increased the expression of anti-inflammatory cytokines (interleukin 10). The production of reactive oxygen species and TUNEL-positive apoptotic cells in the kidney were also significantly reduced in the melatonin-treated MN mice. Melatonin also upregulated heme oxygenase 1 (HO1) and ameliorated MN. The blockade of HO1 expression with SnPP, a HO1 inhibitor, attenuated HO1 induction by melatonin and thus mitigated its renoprotective effects during MN. Our results suggest that melatonin treatment ameliorates experimental MN via multiple pathways, including by its antioxidative, antiapoptotic, and immunomodulatory effects. Melatonin should be considered a potential therapeutic intervention for MN in the future. PMID:22288898

  16. Melatonin: a well-documented antioxidant with conditional pro-oxidant actions.

    Science.gov (United States)

    Zhang, Hong-Mei; Zhang, Yiqiang

    2014-09-01

    Melatonin (N-acetyl-5-methoxytryptamine), an indoleamine produced in many organs including the pineal gland, was initially characterized as a hormone primarily involved in circadian regulation of physiological and neuroendocrine function. Subsequent studies found that melatonin and its metabolic derivatives possess strong free radical scavenging properties. These metabolites are potent antioxidants against both ROS (reactive oxygen species) and RNS (reactive nitrogen species). The mechanisms by which melatonin and its metabolites protect against free radicals and oxidative stress include direct scavenging of radicals and radical products, induction of the expression of antioxidant enzymes, reduction of the activation of pro-oxidant enzymes, and maintenance of mitochondrial homeostasis. In both in vitro and in vivo studies, melatonin has been shown to reduce oxidative damage to lipids, proteins and DNA under a very wide set of conditions where toxic derivatives of oxygen are known to be produced. Although the vast majority of studies proved the antioxidant capacity of melatonin and its derivatives, a few studies using cultured cells found that melatonin promoted the generation of ROS at pharmacological concentrations (?m to mm range) in several tumor and nontumor cells; thus, melatonin functioned as a conditional pro-oxidant. Mechanistically, melatonin may stimulate ROS production through its interaction with calmodulin. Also, melatonin may interact with mitochondrial complex III or mitochondrial transition pore to promote ROS production. Whether melatonin functions as a pro-oxidant under in vivo conditions is not well documented; thus, whether the reported in vitro pro-oxidant actions come into play in live organisms remains to be established. PMID:25060102

  17. Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT

    Science.gov (United States)

    van der Heijden, Kristiaan B.; Egberts, A. C. G.; Korzilius, Hubert P. L. M.; Smits, Marcel G.

    2010-01-01

    Rationale Pharmacokinetics of melatonin in children might differ from that in adults. Objectives This study aims to establish a dose–response relationship for melatonin in advancing dim light melatonin onset (DLMO), sleep onset (SO), and reducing sleep onset latency (SOL) in children between 6 and 12 years with chronic sleep onset insomnia (CSOI). Methods The method used for this study is the randomized, placebo-controlled double-blind trial. Children with CSOI (n?=?72) received either melatonin 0.05, 0.1, and 0.15 mg/kg or placebo during 1 week. Sleep was assessed with log and actigraphy during this week and the week before. Outcomes were the shifts in DLMO, SO, and SOL. Results Treatment with melatonin significantly advanced SO and DLMO by approximately 1 h and decreased SOL by 35 min. Within the three melatonin groups, effect size was not different, but the circadian time of administration (TOA) correlated significantly with treatment effect on DLMO (rs?=??0.33, p?=?0.022) and SO (rs?=??0.38, p?=?0.004), whereas clock TOA was correlated with SO shift (r?=??0.35, p?=?0.006) and not with DLMO shift. Conclusions No dose–response relationship of melatonin with SO, SOL, and DLMO is found within a dosage range of 0.05–0.15 mg/kg. The effect of exogenous melatonin on SO, SOL, and DLMO increases with an earlier circadian TOA. The soporific effects of melatonin enhance the SO shift. This study demonstrates that melatonin for treatment of CSOI in children is effective in a dosage of 0.05 mg/kg given at least 1 to 2 h before DLMO and before desired bedtime. PMID:20668840

  18. Reduced anti-diuretic response to desmopressin during wet nights in patients with monosymptomatic nocturnal enuresis

    DEFF Research Database (Denmark)

    Tauris, Lene Hjelle; Andersen, Rene Frydensbjerg

    2012-01-01

    OBJECTIVE: To investigate why not all children with monosymptomatic nocturnal enuresis (MNE) treated with desmopressin give an adequate response. MATERIALS AND METHODS: We included 114 children with MNE aged 5-15 years (9.8 ± 0.2 years) who experienced at least 1 wet night and more than 2 dry nights during desmopressin treatment. The patients made home recordings for 2 weeks as baseline and for 2-4 weeks of desmopressin titration. Nocturnal urine production during wet and dry nights, and maximum voided volumes (MVVs) were documented in all patients. RESULTS: Sixty-four patients were desmopressin non-responders, 29 were either partial responders or responders, while 21 patients were full responders. Desmopressin reduced nocturnal urine production dramatically during dry nights compared with pre-treatment wet nights. Nocturnal urine production during desmopressin treatment was significantly greater during wet nights compared to dry nights (243 ± 9.32 vs 176 ± 5.31 ml, P 

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

    International Nuclear Information System (INIS)

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

  20. Visual and acoustic signaling in three species of Brazilian nocturnal tree frogs (Anura, Hylidae)

    OpenAIRE

    Luís Felipe Toledo; Arau?jo, Oli?via G. S.; Guimara?es, Lorena D.; Rodrigo Lingnau; Haddad, Ce?lio F. B.

    2007-01-01

    Visual communication seems to be widespread among nocturnal anurans, however, reports of these behaviors in many Neotropical species are lacking. Therefore, we gathered information collected during several sporadic field expeditions in central and southern Brazil with three nocturnal tree frogs: Aplastodiscus perviridis, Hypsiboas albopunctatus and H. bischoffi. These species displayed various aggressive behaviors, both visual and acoustic, towards other males. For A. perviridis we described ...

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

    Directory of Open Access Journals (Sweden)

    Yousef Khalida

    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.

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

    OpenAIRE

    Dar, Saleem; Arizmendi, Ma Del Coro; Valiente-banuet, Alfonso

    2006-01-01

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

  3. Nocturnal thoracoabdominal asynchrony in house dust mite-sensitive nonhuman primates

    OpenAIRE

    XiaoJia Wang; Shaun Reece; Stephen Olmstead; et al.

    2010-01-01

    XiaoJia Wang, Shaun Reece, Stephen Olmstead, Robert L Wardle, Michael R Van ScottDepartment of Physiology, East Carolina University, Greenville, North Carolina, USAAbstract: Nocturnal bronchoconstriction is a common symptom of asthma in humans, but is poorly documented in animal models. Thoracoabdominal asynchrony (TAA) is a noninvasive clinical indication of airway obstruction. In this study, respiratory inductive plethysmography (RIP) was used to document nocturnal TAA in house dust mite (H...

  4. Survival with Three-Times Weekly In-Center Nocturnal Versus Conventional Hemodialysis

    OpenAIRE

    Lacson, Eduardo; Xu, Jianglin; Suri, Rita S.; Nesrallah, Gihad; Lindsay, Robert; Garg, Amit X.; Lester, Keith; Ofsthun, Norma; Lazarus, Michael; Hakim, Raymond M.

    2012-01-01

    Whether the duration of hemodialysis treatments improves outcomes remains controversial. Here, we evaluated survival and clinical changes associated with converting from conventional hemodialysis (mean=3.75 h/treatment) to in-center nocturnal hemodialysis (mean=7.85 h/treatment). All 959 consecutive patients who initiated nocturnal hemodialysis for the first time in 77 Fresenius Medical Care facilities during 2006 and 2007 were eligible. We used Cox models to compare risk for mortality during...

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

    OpenAIRE

    Penteriani, Vincenzo; Delgado, Mari?a Del Mar; Alonso-a?lvarez, Carlos; Sergio, Fabrizio

    2007-01-01

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

  6. Nocturnal sleep pattern in native Brazilian Terena adults Padrão de sono noturno em adultos indígenas Terena

    OpenAIRE

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

    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 ...

  7. Nocturnal sweating—a common symptom of obstructive sleep apnoea: the Icelandic sleep apnoea cohort

    Science.gov (United States)

    Arnardottir, Erna Sif; Janson, Christer; Bjornsdottir, Erla; Benediktsdottir, Bryndis; Juliusson, Sigurdur; Kuna, Samuel T; Pack, Allan I; Gislason, Thorarinn

    2013-01-01

    Objectives To estimate the prevalence and characteristics of frequent nocturnal sweating in obstructive sleep apnoea (OSA) patients compared with the general population and evaluate the possible changes with positive airway pressure (PAP) treatment. Nocturnal sweating can be very bothersome to the patient and bed partner. Design Case–control and longitudinal cohort study. Setting Landspitali—The National University Hospital, Iceland. Participants The Icelandic Sleep Apnea Cohort consisted of 822 untreated patients with OSA, referred for treatment with PAP. Of these, 700 patients were also assessed at a 2-year follow-up. The control group consisted of 703 randomly selected subjects from the general population. Intervention PAP therapy in the OSA cohort. Main outcome measures Subjective reporting of nocturnal sweating on a frequency scale of 1–5: (1) never or very seldom, (2) less than once a week, (3) once to twice a week, (4) 3–5 times a week and (5) every night or almost every night. Full PAP treatment was defined objectively as the use for ?4?h/day and ?5?days/week. Results Frequent nocturnal sweating (?3× a week) was reported by 30.6% of male and 33.3% of female OSA patients compared with 9.3% of men and 12.4% of women in the general population (p<0.001). This difference remained significant after adjustment for demographic factors. Nocturnal sweating was related to younger age, cardiovascular disease, hypertension, sleepiness and insomnia symptoms. The prevalence of frequent nocturnal sweating decreased with full PAP treatment (from 33.2% to 11.5%, p<0.003 compared with the change in non-users). Conclusions The prevalence of frequent nocturnal sweating was threefold higher in untreated OSA patients than in the general population and decreased to general population levels with successful PAP therapy. Practitioners should consider the possibility of OSA in their patients who complain of nocturnal sweating. PMID:23674447

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

    OpenAIRE

    Le Tallec, Thomas; Perret, Martine; The?ry, Marc

    2013-01-01

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

  9. Patterns of nocturnal rehydration in root tissues of Vaccinium corymbosum L. under severe drought conditions

    OpenAIRE

    Valenzuela-estrada, Luis R.; Richards, James H.; Diaz, Andres; Eissensat, David M.

    2009-01-01

    Although roots in dry soil layers are commonly rehydrated by internal hydraulic redistribution during the nocturnal period, patterns of tissue rehydration are poorly understood. Rates of nocturnal rehydration were examined in roots of different orders in Vaccinium corymbosum L. ‘Bluecrop’ (Northern highbush blueberry) grown in a split-pot system with one set of roots in relatively moist soil and the other set of roots in dry soil. Vaccinium is noted for a highly branched and extremely fin...

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

    Science.gov (United States)

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

    2014-06-01

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

  11. A simplified radioimmunoassay for melatonin and its application to biological fluids. Preliminary observations on the half-life of plasma melatonin in man

    International Nuclear Information System (INIS)

    A simplified and rapid radioimmunoassay (RIA) for melatonin is presented. Melatonin is extracted from serum, plasma or urine and RIA is performed by using [3H]melatonin as the tracers. The standard curve covers the range 0.2-4.3 nmol/l. By increasing the sample volume the range can be extended to 0.06 nmol/l. The intra-assay variability is 7% (relative standard deviation=rsd) and the inter-assay variability is 10% (rsd). The recovery of melatonin added to calf serum is 96%. The long term variability of the assay (43 assays on aliquots of one serum sample during 6 months) is 13.5% (rsd). The serum levels in man after one oral dose of 430 ?mol melatonin have been measured. The peak value, 620 nmol/l, was noted after 0.5 h and the melatonin concentration was still above the normal range at 24 h (2.1 nmol/l). (Auth.)

  12. Validation of a direct radioimmunoassay of melatonin in the blue fox

    International Nuclear Information System (INIS)

    A direct radioimmunoassay procedure for the determination of melatonin in the blood of blue fox has been validated and applied. The assay required 50 ?l of sample and standard, 100 ?l of antiserum and 100 ?l of (3H)melatonin. After overnight incubation at 4 deg. C the antibody bound melatonin was separated from the free hormone with dextran-coated charcoal. Following centrifugation the antibody bound (3H)melatonin was determined in a beta scintillation counter. The antiserum bound 30-35 % of the (3H)melatonin at a final dilution of 1:36000. The non specific binding represented less than 5 % of the total radioactivity in all assays. The lowest detectable amount of melatonin was 2.6 fmol/tube, corresponding to 52.5 pmol/l. The inter-assay coefficient of variation at 178 and 510 pmol/l was 15.6 and 8.8 %, respectively. The precision profile, calculated from a 10-replicate standard curve, showed that the coefficient of variation decreased from 43 % at 84 pmol/l to 15 % at 336 pmol/l, and remainded at or below 10 % for concentrations exceeding 670 pmol/l. Plasma was collected from 2 male blue foxes at about hourly intervals during a 24 h period in September and assayed for melatonin. Maximum (421 pmol/l) and minimum (97 pmol/l) concentrations of the hormone were inversely related to light intensity. (author)

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

    Science.gov (United States)

    Padhy, Biswa M; Kumar, Vijay L

    2005-12-14

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

  14. Decreased urinary level of melatonin as a marker of disease severity in patients with multiple sclerosis.

    Science.gov (United States)

    Gholipour, Taha; Ghazizadeh, Taher; Babapour, Sahand; Mansouri, Behzad; Ghafarpour, Majid; Siroos, Bahaadin; Harirchian, Mohammad Hossein

    2015-02-01

    Melatonin has both pro-inflammatory and anti-inflammatory properties depending on the stage of inflammation. Despite its therapeutic effect in alleviation of some symptoms of multiple sclerosis; the precise role of melatonin in MS pathogenesis remains a topic of debate. The aim of this study was to measure the urine level of one of melatonin products which is an index of serum melatonin level, in MS patients in the acute phase of relapse and control patients. We also analyzed different clinical and cognitive indices in order to find any correlation with melatonin level. Twenty eight patients who were diagnosed as relapsing-remitting MS, according to the revised McDonald criteria, along with 10 age- and sex-matched control subjects were recruited in our study. Here we showed that urine 6-sulphatoxymelatonin levels (aMT6s; the major metabolite of melatonin) were significantly lower in MS patients compared to control group. Interestingly, urine aMT6s levels significantly correlated with MS Functional Composite score, but not Expanded Disability Severity Score. Based on above findings, there might be new hope in developing a quantitative and objective measure to assess the MS severity especially in neurodegenerative diseases. However, our results should be analyzed cautiously. We didn't evaluate simultaneous level of 25-OH Vitamin D. It has been recently reported that there is a negative correlation between melatonin and vitamin D levels. Further studies are needed to confirm this hypothesis. PMID:25530144

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Liu Ran

    2013-01-01

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

  17. Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer.

    Science.gov (United States)

    Jardim-Perassi, Bruna Victorasso; Arbab, Ali S; Ferreira, Lívia Carvalho; Borin, Thaiz Ferraz; Varma, Nadimpalli R S; Iskander, A S M; Shankar, Adarsh; Ali, Meser M; de Campos Zuccari, Debora Aparecida Pires

    2014-01-01

    As neovascularization is essential for tumor growth and metastasis, controlling angiogenesis is a promising tactic in limiting cancer progression. Melatonin has been studied for their inhibitory properties on angiogenesis in cancer. We performed an in vivo study to evaluate the effects of melatonin treatment on angiogenesis in breast cancer. Cell viability was measured by MTT assay after melatonin treatment in triple-negative breast cancer cells (MDA-MB-231). After, cells were implanted in athymic nude mice and treated with melatonin or vehicle daily, administered intraperitoneally 1 hour before turning the room light off. Volume of the tumors was measured weekly with a digital caliper and at the end of treatments animals underwent single photon emission computed tomography (SPECT) with Technetium-99m tagged vascular endothelial growth factor (VEGF) C to detect in vivo angiogenesis. In addition, expression of pro-angiogenic/growth factors in the tumor extracts was evaluated by membrane antibody array and collected tumor tissues were analyzed with histochemical staining. Melatonin in vitro treatment (1 mM) decreased cell viability (pbreast cancer xenografts nude mice treated with melatonin showed reduced tumor size and cell proliferation (Ki-67) compared to control animals after 21 days of treatment (p0.05) images. In addition, there was a decrease of micro-vessel density (Von Willebrand Factor) in melatonin treated mice (pmelatonin treatment showed effectiveness in reducing tumor growth and cell proliferation, as well as in the inhibition of angiogenesis. PMID:24416386

  18. The effects of melatonin on a molecular level Die effekte van melatonien op molekulêre vlak

    Directory of Open Access Journals (Sweden)

    M. Haag

    1992-07-01

    Full Text Available The indole hormone melatonin is secreted in a biphasic circadian rhythm by the pineal gland. This review presents a summary of recent results concerning — (i factors that influence melatonin synthesis; (ii the existence of melatonin receptors in brain tissue; (iii the effects of melatonin as a modulator of dopaminergic, noradrenergic, GABAergic and opioidergic neurotransmitter processes; (iv the influence of melatonin on the electric activity and metabolic rate of certain brain nuclei; and (v melatonin effects on hormone secretion in the hypothalamic-pituitary axis. A basic mechanism of melatonin action via cyclic nucleotides and thus protein phosphorylation is presented.Die indoolhormoon melatonien word volgens 'n bifasiese sirkadiese ritme deur die pineaalklier afgeskei. Hierdie oorsigartikel bied ’n opsomming van onlangse resultate oor: (i faktore wat melatoniensekresie beinvloed; (ii die bestaan van melatonienreseptore in breinweefsel; (Hi effekte van melatonien as ’n moduleerder van dopaminergiese, noradrenergiese, GABA-ergiese en opioiedergiese neuro- oordragsprosesse; (iv die invloed van melatonien op elektriese aktiwiteit en metaboliese snelheid van sekere breinkerne; asook (v melatonieneffekte op hormoonafskeiding in die hipotalamus-hipofise-as. ’n Grondliggende meganisme van melatonienwerking deur middel van sikliese nukleotiede en proteienfosforilering word verder voorgestel.

  19. The Protective Effect of Melatonin on Neural Stem Cell against LPS-Induced Inflammation.

    Science.gov (United States)

    Song, Juhyun; Kang, So Mang; Lee, Kyoung Min; Lee, Jong Eun

    2015-01-01

    Stem cell therapy for tissue regeneration has several limitations in the fact that transplanted cells could not survive for a long time. For solving these limitations, many studies have focused on the antioxidants to increase survival rate of neural stem cells (NSCs). Melatonin, an antioxidant synthesized in the pineal gland, plays multiple roles in various physiological mechanisms. Melatonin exerts neuroprotective effects in the central nervous system. To determine the effect of melatonin on NSCs which is in LPS-induced inflammatory stress state, we first investigated nitric oxide (NO) production and cytotoxicity using Griess reagent assays, LDH assay, and neurosphere counting. Also, we investigated the effect of melatonin on NSCs by measuring the mRNA levels of SOX2, TLX, and FGFR-2. In addition, western blot analyses were performed to examine the activation of PI3K/Akt/Nrf2 signaling in LPS-treated NSCs. In the present study, we suggested that melatonin inhibits NO production and protects NSCs against LPS-induced inflammatory stress. In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Based on our results, we conclude that melatonin may be an important factor for the survival and proliferation of NSCs in neuroinflammatory diseases. PMID:25705693

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

    International Nuclear Information System (INIS)

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

  1. Hormonal protection in acute pancreatitis by ghrelin, leptin and melatonin.

    Science.gov (United States)

    Jaworek, Jolanta; Konturek, Stanis?aw Jan

    2014-12-01

    Acute pancreatitis is a nonbacterial disease of the pancreas. The severe form of this ailment is characterized by high mortality. Whether acute pancreatitis develops as the severe type or resolves depends on the intensity of the inflammatory process which is counteracted by the recruitment of innate defense mechanisms. It has been shown that the hormones ghrelin, leptin and melatonin are able to modulate the immune function of the organism and to protect the pancreas against inflammatory damage. Experimental studies have demonstrated that the application of these substances prior to the induction of acute pancreatitis significantly attenuated the intensity of the inflammation and reduced pancreatic tissue damage. The pancreatic protective mechanisms of the above hormones have been related to the mobilization of non-specific immune defense, to the inhibition of nuclear factor kappa B and modulation of cytokine production, to the stimulation of heat shock proteins and changes of apoptotic processes in the acinar cells, as well as to the activation of antioxidant system of the pancreatic tissue. The protective effect of ghrelin seems to be indirect and perhaps dependent on the release of growth hormone and insulin-like growth factor 1. Leptin and ghrelin, but not melatonin, employ sensory nerves in their beneficial action on acute pancreatitis. It is very likely that ghrelin, leptin and melatonin could be implicated in the natural protection of the pancreatic gland against inflammatory damage because the blood levels of these substances increase in the initial phase of pancreatic inflammation. The above hormones could be a part of the innate resistance system which might remove noxious factors and could suppress or attenuate the inflammatory process in the pancreas. PMID:25493003

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

    Scientific Electronic Library Online (English)

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

    2000-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Di Mascio P.

    2000-01-01

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

  4. Serum cholesterol and lipid peroxidation are decreased by melatonin in diet-induced hypercholesterolemic rats.

    Science.gov (United States)

    Hoyos, M; Guerrero, J M; Perez-Cano, R; Olivan, J; Fabiani, F; Garcia-Pergañeda, A; Osuna, C

    2000-04-01

    The purpose of this study was to investigate the effect of melatonin, at pharmacological doses, on serum lipids of rats fed with a hypercholesterolemic diet. Therefore, different groups of animals were fed with either the regular Sanders Chow diet or a diet enriched in cholesterol. Moreover, animals were treated with or without melatonin in the drinking water for 3 months. We show that melatonin treatment did not affect the levels of cholesterol or triglycerides in rats fed with a regular diet. However, the increase in total cholesterol and low-density lipoprotein (LDL)-cholesterol induced by a cholesterol-enriched diet was reduced significantly by melatonin administration. On the other hand, melatonin administration prevented the decrease in high-density lipoprotein (HDL)-cholesterol induced by the same diet. No differences in the levels of very low-density lipoprotein (VLDL)-cholesterol and triglycerides were found. We also found that melatonin administration slightly decreased serum uric, bilirubin and increased serum glucose levels. Other biochemical parameters, including total proteins, creatinine, urea, phosphorus, calcium, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-glutamyltranspeptidase (gamma-GT), acetyl cholinesterase (AcCho), and alkaline phosphatase (ALP) were not modified by melatonin treatment. Finally, lipid peroxidation (LPO) was studied in membranes of liver, brain, spleen, and heart as an index of membrane oxidative damage. Results show that hypercholesterolemic diet did not modify the LPO status in any of the tissues studied. However, chronic melatonin administration significantly decreased LPO. Results confirm that melatonin participates in the regulation of cholesterol metabolism and in the prevention of oxidative damage to membranes. PMID:10739301

  5. Radioimmunoassay of serum concentrations of melatonin in sheep exposed to different lighting regimens

    International Nuclear Information System (INIS)

    A specific and sensitive double-antibody radioimmunoassay for melatonin (N-acetyl-5-methoxytryptamine) was developed. The least detectable concentration of melatonin standard was 10 pmolar (2.3 pg/tube) with 50 percent inhibition resulting when the concentration was 100 pmolar (23 pg/tube). Inhibition curves obtained with increasing quantities of melatonin or increasing quantities of chloroform extracts of ovine sera were parallel. Concentrations of melatonin could be accurately determined when 31 to 1000 pg were added to 1 ml ovine serum. Serum samples with melatonin concentrations of 1000 pg/ml, 500 pg/ml and 75 pg/ml had intra-assay coefficients of variation of 9.1 percent, 8.6 percent, and 17.4 percent, respectively. The respective inter-assay coefficients of variation were 22.7 percent, 18.1 percent, and 37.1 percent. Ewes exposed to a 12 h light:12 h dark lighting regimen demonstrated a circadian rhythm in serum concentrations of melatonin. Concentrations ranged from 10 to 30 pg/ml during periods of light to 100 to 300 pg/ml during periods of dark. During exposure to continuous light, the circadian rhythm was abolished and concentrations of melatonin were maintained at 10 to 50 pg/ml. When exposed to conditions of continuous dark the circadian rhythm persisted. A precipitous drop in serum concentrations of melatonin resulted when ewes experiencing peak melatonin concentrations were exposed to light. Concentrations returned to peak levels when the lights were tured to peak levels when the lights were turned off 3.5 h later

  6. Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation.

    Science.gov (United States)

    Wei, Jia-Yi; Li, Wan-Ming; Zhou, Lin-Lin; Lu, Qiu-Nan; He, Wei

    2015-05-01

    Melatonin induces apoptosis in many different cancer cell lines, including colorectal cancer. However, the precise mechanisms involved remain largely unresolved. In this study, we provide evidence to reveal a new mechanism by which melatonin induces apoptosis of colorectal cancer LoVo cells. Melatonin at pharmacological concentrations significantly suppressed cell proliferation and induced apoptosis in a dose-dependent manner. The observed apoptosis was accompanied by the melatonin-induced dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4). Pretreatment with a HDAC4-specific siRNA effectively attenuated the melatonin-induced apoptosis, indicating that nuclear localization of HDAC4 is required for melatonin-induced apoptosis. Moreover, constitutively active Ca(2+) /calmodulin-dependent protein kinase II alpha (CaMKII?) abrogated the melatonin-induced HDAC4 nuclear import and apoptosis of LoVo cells. Furthermore, melatonin decreased H3 acetylation on bcl-2 promoter, leading to a reduction of bcl-2 expression, whereas constitutively active CaMKII?(T286D) or HDAC4-specific siRNA abrogated the effect of melatonin. In conclusion, the present study provides evidence that melatonin-induced apoptosis in colorectal cancer LoVo cells largely depends on the nuclear import of HDAC4 and subsequent H3 deacetylation via the inactivation of CaMKII?. PMID:25752481

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

    Directory of Open Access Journals (Sweden)

    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.

  8. A Mössbauer study of hemoglobin in paroxysmal nocturnal hemoglobinuria

    Science.gov (United States)

    Zamorano-Ulloa, Rafael; Yee-Madeira, Hernani; Flores-Llamas, Hector; Pérez-Ramírez, José G.

    1991-11-01

    The57Fe Mössbauer spectra of concentrated hemoglobin (Hb) of normal subjects and six patients with Paraxysmal Nocturnal Hemoglobinuria (PNH) were studied at 300°K and 77 K. PNH is a very rare 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 Mössbauer 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 Mössbauer spectrum.

  9. A Moessbauer study of hemoglobin in paroxysmal nocturnal hemoglobinuria

    International Nuclear Information System (INIS)

    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.)

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

    DEFF Research Database (Denmark)

    Rosenberg, J; WildschiØdtz, G

    1994-01-01

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

  11. 'Nocturnal noises': an isolated stridor in an adolescent.

    Science.gov (United States)

    Zalewska, K I; Benfield, G F A

    2015-01-01

    An 18-year-old man presented to primary care with a 2-year history of exclusively nocturnal 'noisy breathing'. He was otherwise asymptomatic. He had never smoked and was previously healthy. Spirometry showed a severely obstructive picture with forced expiratory volume in 1?s (FEV1) 1.87?L (44% predicted), forced vital capacity (FVC) 4.0?L (80%) and FEV1/FVC ratio of 47%. A diagnosis of asthma was suspected and a trial of inhaled bronchodilators and corticosteroids was initiated. Failure to improve symptoms led to referral to the Respiratory Clinic, where his mother replayed a recording of the 'noisy breathing' on her mobile phone. Subsequent examination revealed a stridor on expiration. Flow volume loop showed a plateau of the expiratory limb, consistent with intrathoracic upper airway obstruction. CT of the thorax revealed a massively dilated oesophagus, filled with food residue, reflecting an achalasia, causing lower tracheal compression. He is now being considered for a myotomy procedure. PMID:25759269

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

    OpenAIRE

    Carla Roberta de Oliveira Carvalho; José Cipolla-Neto; Rodrigo Antonio Peliciari-Garcia; Amp Xe Ssica Andrade-silva, J.

    2013-01-01

    Pineal melatonin synthesis can be modulated by many peptides, including insulin. Because melatonin appears to alter leptin synthesis, in this work we aimed to investigate whether leptin would have a role on norepinephrine- (NE-)mediated melatonin synthesis in cultured rat pineal glands. According to our data, cultured rat pineal glands express leptin receptor isoform b (Ob-Rb). Pineal expression of Ob-Rb mRNA was also observed in vivo. Administration of leptin (1?nM) associated with NE (1?...

  13. Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats

    OpenAIRE

    Ru-tao Hong, Jian-ming Xu

    2009-01-01

    AIM: To investigate the protective effects of melatonin on carbon tetrachloride (CCl4)-induced hepatic fibrosis in experimental rats.METHODS: All rats were randomly divided into normal control group, model control group treated with CCl4 for 12 wk, CCl4 + NAC group treated with CCl4 + NAC (100 mg/kg, i.p.) for 12 wk, CCl4 + MEL-1 group treated with CCl4 + melatonin (2.5 mg/kg) for 12 wk, CCl4 + MEL-2 group treated with CCl4 + melatonin (5.0 mg/kg) for 12 wk, and CCl4 + MEL-3 group treated wit...

  14. Different effects of melatonin pretreatment on cAMP and LH responses of the neonatal rat pituitary cells.

    Science.gov (United States)

    Pelísek, V; Vanecek, J

    2000-05-01

    The rhythm of the pineal hormone melatonin transduces the effect of photoperiod on seasonal functions. Duration of the melatonin pulse provides information about season and the long melatonin pulse induces reproductive involution in the long day breeders such as photoperiodic rodents. The length of melatonin pulse thus carries photoperiodic information, which regulates the function of target cells. Therefore, we have studied the effects of melatonin pretreatment of various lengths on responsiveness of the neonatal rat pituitary cells cultured in vitro to GnRH or forskolin. In these cells, melatonin treatment inhibits the GnRH-induced LH release as well as the forskolin-induced cAMP accumulation. However, long preincubation with melatonin has a paradoxical stimulatory effect on the cellular responsiveness. When the cells are pretreated with melatonin for 16 hr or more, then rinsed thoroughly and treated with forskolin for 30 min, the increase of cAMP is potentiated. Moreover, in the melatonin-pretreated cells. the subsequent melatonin treatment inhibits the forskolin-induced cAMP accumulation relatively more than in the non-pretreated cells. Although melatonin pretreatment does not potentiate the GnRH-induced LH release, it protects the gonadotrophs against the GnRH-induced desensitization: pretreatment with GnRH for 12 hr or more renders the cells insensitive to subsequent GnRH stimulation, while after pretreatment with GnRH and melatonin, the subsequent GnRH treatment induces significant increase of LH release. These observations indicate that long pretreatment with melatonin improves responsiveness of the pituitary cells to the subsequent stimulation, but its effects on cAMP accumulation and LH release are different. PMID:10831159

  15. Prevalence of nocturnal enuresis and its associated factors in primary school and preschool children of khorramabad in 2013.

    Science.gov (United States)

    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

  16. The diurnal and nocturnal effects of travoprost in normal-tension glaucoma

    Directory of Open Access Journals (Sweden)

    Seibold LK

    2014-10-01

    Full Text Available Leonard K Seibold, Malik Y KahookDepartment of Ophthalmology, University of Colorado Eye Center, Aurora, CO, USAPurpose: To determine the diurnal and nocturnal effects of travoprost with sofZia® (Travatan Z® [TZ] on intraocular pressure (IOP and ocular perfusion pressure (OPP in patients with normal-tension glaucoma (NTG.Methods: Twenty-seven subjects with NTG were admitted to an inpatient sleep laboratory for three 24-hour sessions monitoring IOP, blood pressure (BP, and heart rate every 2 hours in the habitual position (diurnal period: upright; nocturnal period: supine. Baseline IOP and OPP levels were compared to those during active treatment with TZ and 3 days after stopping the medication. OPP was calculated as 2/3 [diastolic BP + 1/3 (systolic BP – diastolic BP] – IOP.Results: TZ significantly reduced the mean diurnal and nocturnal IOP levels compared to baseline at all time points. During treatment, mean IOP decreased from 17.1±3.4 to 14.7±3.0 mmHg during the diurnal period (P<0.01 and from 19.9±3.6 to 18.8±3.5 mmHg during the nocturnal period (P<0.01. Once treatment was discontinued, mean IOP remained at levels significantly less than baseline during both the diurnal (15.6±3.2 mmHg and nocturnal (18.7±3.7 mmHg periods. Mean OPP was not significantly changed with treatment during either period. Conclusion: In this population of NTG patients, TZ significantly lowers IOP at all time points throughout the diurnal and nocturnal periods. The treatment effect on IOP endures for up to 3 days after the last dose. Treatment did not significantly improve OPP.Keywords: ocular perfusion pressure, intraocular pressure, 24-hour, diurnal, nocturnal, sofZia®

  17. Pulsing blue light through closed eyelids: effects on acute melatonin suppression and phase shifting of dim light melatonin onset

    Directory of Open Access Journals (Sweden)

    Figueiro MG

    2014-12-01

    Full Text Available Mariana G Figueiro, Barbara Plitnick, Mark S Rea Lighting Research Center, Rensselaer Polytechnic Institute, Troy, NY, USA Abstract: Circadian rhythm disturbances parallel the increased prevalence of sleep disorders in older adults. Light therapies that specifically target regulation of the circadian system in principle could be used to treat sleep disorders in this population. Current recommendations for light treatment require the patients to sit in front of a bright light box for at least 1 hour daily, perhaps limiting their willingness to comply. Light applied through closed eyelids during sleep might not only be efficacious for changing circadian phase but also lead to better compliance because patients would receive light treatment while sleeping. Reported here are the results of two studies investigating the impact of a train of 480 nm (blue light pulses presented to the retina through closed eyelids on melatonin suppression (laboratory study and on delaying circadian phase (field study. Both studies employed a sleep mask that provided narrowband blue light pulses of 2-second duration every 30 seconds from arrays of light-emitting diodes. The results of the laboratory study demonstrated that the blue light pulses significantly suppressed melatonin by an amount similar to that previously shown in the same protocol at half the frequency (ie, one 2-second pulse every minute for 1 hour. The results of the field study demonstrated that blue light pulses given early in the sleep episode significantly delayed circadian phase in older adults; these results are the first to demonstrate the efficacy and practicality of light treatment by a sleep mask aimed at adjusting circadian phase in a home setting. Keywords: circadian phase, dim light melatonin onset, light through closed eyelids, blue light, sleep

  18. Type 2 diabetes mellitus: Role of melatonin and oxidative stress.

    Science.gov (United States)

    Zephy, Doddigarla; Ahmad, Jamal

    2014-10-29

    Type 2 diabetes mellitus caused by transfer of susceptible immortal gene from parent to progeny in individuals prone, and/or in contribution of factors such as obesity and physical inactivity results in chronic extracellular hyperglycemia due to insulin resistance or impaired glucose tolerance. Hyperglycemia leads to increased production of superoxide radical in mitochondrial electron transport chain, consequently, inhibit glyceraldehyde-3-phosphate dehydrogenase activity, increase the flux of substrates that direct the expression of genes responsible for activation of polyol, hexosamine, advanced glycation end products and protein kinase-C pathways enzymes. Simultaneously, these pathways add-up free radicals in the body, hamper cell redox state, alter genes of insulin sensitivity and are responsible for the diabetic complications like retinopathy, atherosclerosis, cardiovascular diseases, nephropathy and neuropathy. Experimental evidence suggests that the indoleamine hormone melatonin is capable of influencing in development of diabetic complications by neutralizing the unnecessary production of ROS, protection of beta cells, as they possess low antioxidant potential and normalize redox state in the cell. However, studies reported the beneficial effects of pharmacological supplementation of melatonin in humans but it has not been extensively studied in a multicountric, multicentric which should include all ethnic population. PMID:25450812

  19. Localization and dynamics of Mel(1a) melatonin receptor in the ovary of carp Catla catla in relation to serum melatonin levels.

    Science.gov (United States)

    Chattoraj, Asamanja; Seth, Mohua; Maitra, Saumen Kumar

    2009-03-01

    We studied the localization, sub-cellular distribution and daily rhythms of a 37 kDa melatonin receptor (Mel(1a)R) in the ovary to assess its temporal relationship with the serum melatonin levels in four different reproductive phases in carp Catla catla. Our immunocytochemical study accompanied by Western blot analysis of Mel(1a)R in the ovary revealed that the expression of this 37-kDa protein was greater in the membrane fraction than in the cytosol. Ovarian Mel(1a)R protein peaked at midnight and fell at midday in each reproductive phase. Conversely, serum melatonin levels in the same fish demonstrated a minimum diurnal value at midday in all seasons, but a peak at midnight (during pre-spawning, spawning, and post-spawning phases) or at late dark phase (during preparatory phase). In an annual cycle, band intensity of Mel(1a)R protein showed a maximum at night in the spawning phase and a minimum in the post-spawning phase, demonstrating an inverse relationship with the levels of serum melatonin. Our data provide first evidence of the presence of Mel(1a) melatonin receptor in carp ovary and offer interesting perspectives especially for the study of the mechanisms of the control of its rhythmicity and its response to external factors. PMID:19068233

  20. Molecular deficiency (ies) in MT? melatonin signaling pathway underlies the melatonin-unresponsive phenotype in MDA-MB-231 human breast cancer cells.

    Science.gov (United States)

    Mao, Lulu; Yuan, Lin; Xiang, Shulin; Zeringue, Samantha B; Dauchy, Robert T; Blask, David E; Hauch, Adam; Hill, Steven M

    2014-04-01

    Melatonin has been shown repeatedly to inhibit the growth of human breast tumor cells in vitro and in vivo. Its antiproliferative effects have been well studied in MCF-7 human breast cancer cells and several other estrogen receptor ? (ER?)-positive human breast cancer cell lines. However, the MDA-MB-231 breast cancer cell line, an ER?-negative cell line widely used in breast cancer research, has been shown to be unresponsive to melatonin's growth-suppressive effect in vitro. Here, we examined the effect of melatonin on the cell proliferation of several ER?-negative breast cancer cell lines including MDA-MB-231, BT-20, and SK-BR-3 cells. Although the MT1 G-protein-coupled receptor is expressed in all three cell lines, melatonin significantly suppressed the proliferation of SK-BR-3 cells without having any significant effect on the growth of MDA-MB-231 and BT-20 cells. We confirmed that the MT1-associated G? proteins are expressed in MDA-MB-231 cells. Further studies demonstrated that the melatonin unresponsiveness in MDA-MB-231 cells may be caused by aberrant signaling downstream of the G?i proteins, resulting in differential regulation of ERK1/2 activity. PMID:24372669

  1. Distribution and abundance of diurnal and nocturnal dipterous flies in the Federal Territory, Putrajaya.

    Science.gov (United States)

    Nazni, W A; Nooraidah, H; Jeffery, J; Azahari, A H; Mohd Noor, I; Sadiyah, I; Lee, H L

    2007-12-01

    A study of diurnal and nocturnal distribution of flies was conducted in Putrajaya. Six different ecological habitats were selected, namely: botanical garden, lake-area, administration building, wetland, jungle fringes and housing areas. Two different type of traps, cylinderical and rectangular in shape were used in the study. Baits used in these traps were yeast, sugar, salted fish, shrimp paste and fresh liver. Traps were placed at the sites throughout the diurnal and nocturnal periods. The time for sunrise and sunset was determined using a Geographical Positioning System gadget (GARMIN) at the sites. Both type of traps were equally effective in trapping flies. There was no significant difference between both types of traps in their ability to trap flies (p > 0.05). A total of 1,534 flies were collected and identified from both types of trap using the multiple baits and habitats. The collection consisted of 23 species of flies classified under 6 families. The highest number of flies were caught from the lake-area followed by botanical garden, administration building, housing areas, wetland and jungle fringes. The most dominant species was Chrysomya megacephala, followed by species of Sarcophagidae and Musca domestica. Diurnal period had more numbers of flies (81.55%) compared to the nocturnal periods (18.45%). Some species of flies were strictly diurnal, some exibited both diurnal and nocturnal activities while only one species was strictly nocturnal. PMID:18209709

  2. Difference in flowering time can initiate speciation of nocturnally flowering species.

    Science.gov (United States)

    Matsumoto, Tomotaka; Yasumoto, Akiko A; Nitta, Kozue; Hirota, Shun K; Yahara, Tetsukazu; Tachida, Hidenori

    2015-04-01

    Isolation mechanisms that prevent gene flow between populations prezygotically play important roles in achieving speciation. In flowering plants, the nighttime flowering system provides a mechanism for isolation from diurnally flowering species. Although this system has long been of interest in evolutionary biology, the evolutionary process leading to this system has yet to be elucidated because of the lack of good model species. However, the genetic mechanisms underlying the differences in flowering times and the traits that attract pollinators between a pair of diurnally and nocturnally flowering species have recently been identified in a few cases. This identification enables us to build a realistic model for theoretically studying the evolution of a nocturnally flowering species. In this study, based on previous experimental data, we assumed a model in which two loci control the flowering time and one locus determines a trait that attracts pollinators. Using this model, we evaluated the possibility of the evolution of a nocturnally flowering species from a diurnally flowering ancestor through simulations. We found that a newly emerging nighttime flowering flower exhibited a sufficiently high fitness, and the evolution of a nocturnally flowering species from a diurnally flowering species could be achieved when hybrid viability was intermediate to low, even in a completely sympatric situation. Our results suggest that the difference in flowering time can act as a magic trait that induces both natural selection and assortative mating and would play an important role in speciation between diurnally and nocturnally flowering species pairs. PMID:25665720

  3. Microalbuminuria in patients with non-insulin-dependent diabetes mellitus relates to nocturnal systolic blood pressure.

    LENUS (Irish Health Repository)

    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.

  4. Melatonin elicits protein kinase C-mediated calcium response in immortalized GT1-7 GnRH neurons.

    Science.gov (United States)

    Kelestimur, Haluk; Ozcan, Mete; Kacar, Emine; Alcin, Ergul; Y?lmaz, Bayram; Ayar, Ahmet

    2012-01-30

    Melatonin is suggested to have effects on hypothalamic-pituitary-gonadal (HPG) axis. The pulsatile pattern of GnRH release, which results in the intermittent release of gonadotropic hormones from the pituitary, has a critical importance for reproductive function but the factors responsible from this release pattern are not known. Calcium is a second messenger involved in hormone release. Therefore, investigation of the effects of melatonin on intracellular free calcium levels ([Ca(2+)](i)) would provide critical information on hormone release in immortalized GnRH neurons. The pattern of melatonin-induced intracellular calcium signaling was investigated by fluorescence calcium imaging using the immortalized GnRH-secreting GT1-7 hypothalamic neurons. Melatonin caused a significant increase in [Ca(2+)](i,) which was greatly blocked by luzindole, a melatonin antagonist, or attenuated by pre-treatment with protein kinase C inhibitor. This study suggests that melatonin seems to have a direct effect on GnRH neurons. PMID:22177776

  5. Melatonin therapy for REM sleep behavior disorder: a critical review of evidence.

    Science.gov (United States)

    McGrane, Ian R; Leung, Jonathan G; St Louis, Erik K; Boeve, Bradley F

    2015-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia associated with dream enactment often involving violent or potentially injurious behaviors during REM sleep that is strongly associated with synucleinopathy neurodegeneration. Clonazepam has long been suggested as the first-line treatment option for RBD. However, evidence supporting melatonin therapy is expanding. Melatonin appears to be beneficial for the management of RBD with reductions in clinical behavioral outcomes and decrease in muscle tonicity during REM sleep. Melatonin also has a favorable safety and tolerability profile over clonazepam with limited potential for drug-drug interactions, an important consideration especially in elderly individuals with RBD receiving polypharmacy. Prospective clinical trials are necessary to establish the evidence basis for melatonin and clonazepam as RBD therapies. PMID:25454845

  6. Oxidative Stress Induced by Epileptic Seizure and Its Attenuation by Melatonin.

    Czech Academy of Sciences Publication Activity Database

    Mareš, J.; Stopka, Pavel; Nohejlová, K.; Rokyta, R.

    2013-01-01

    Ro?. 62, Suppl.1 (2013), S67-S74. ISSN 0862-8408 Institutional support: RVO:61388980 Keywords : free radicals * seizure * melatonin * EPR Subject RIV: CA - Inorganic Chemistry Impact factor: 1.487, year: 2013

  7. The preparation of a carbon-11 labelled neurohormone -[11C]melatonin

    International Nuclear Information System (INIS)

    Melatonin, a hormone of the pineal gland, has been labelled with the positron-emitting radionuclide, carbon-11 (tsub(1/2) = 20.4 min), for study in vivo by positron emission tomography. Thus a novel labelling agent, [11C]acetyl chloride, was prepared by the carbonation of methylmagnesium bromide with cyclotron-produced [11C]carbon dioxide followed by treatment with phthaloyl dichloride. Acylation of 5-methoxytryptamine then affords [11C]melatonin, which is purified by HPLC and formulated for intravenous injection. The preparation required 35 min from the end of radionuclide production. It provides [11C]melatonin in 13% radiochemical yield (decay-corrected from 11CO2) and in high specific activity. Radiochemical and chemical purity were demonstrated by HPLC and TLC. The validity of the radiosynthesis was also confirmed by a parallel synthesis of [13C]melatonin and examination of the product by 13C-NMR spectroscopy and mass spectrometry. (author)

  8. Picomolar-affinity binding and inhibition of adenylate cyclase activity by melatonin in Syrian hamster hypothalamus

    International Nuclear Information System (INIS)

    1. The effect of melatonin on forskolin-stimulated adenylate cyclase activity was measured in homogenates of Syrian hamster hypothalamus. In addition, the saturation binding characteristics of the melatonin receptor ligand, [125I]iodomelatonin, was examined using an incubation temperature (30 degree C) similar to that used in enzyme assays. 2. At concentrations ranging from 10 pM to 1 nM, melatonin caused a significant decrease in stimulated adenylate cyclase activity with a maximum inhibition of approximately 22%. 3. Binding experiments utilizing [125I]iodomelatonin in a range of approximately 5-80 pM indicated a single class of high-affinity sites: Kd = 55 +/- 9 pM, Bmax = 1.1 +/- 0.3 fmol/mg protein. 4. The ability of picomolar concentrations of melatonin to inhibit forskolin-stimulated adenylate cyclase activity suggests that this affect is mediated by picomolar-affinity receptor binding sites for this hormone in the hypothalamus

  9. Does orchiectomy enhance the immune-stimulatory effects of melatonin during experimental Chagas' disease?

    Science.gov (United States)

    Santello, Fabricia Helena; Caetano, Leony Cristina; Filipin, Marina Del Vecchio; Brazão, Vânia; Caetano, Luana Naiara; Toldo, Míriam Paula Alonso; do Prado, José Clóvis

    2012-10-01

    Melatonin has been reported to play a fundamental role in T-cell immunoregulation. Control of Trypanosoma cruzi parasitism during the acute phase of infection is considered to be critically dependent on direct macrophage activation by cytokines. The aim of this work was to evaluate the influence of exogenous melatonin treatment and the influences exerted by sexual hormones during the acute phase of the experimental Chagas' disease in rats. With melatonin treatment, orchiectomized animals (CMOR and IMOR) displayed the highest concentrations of IFN-? and TNF-?. On the 7th day post-infection, untreated and treated orchiectomized animals (IOR and IMOR) showed an enhanced number of peritoneal macrophages. Nitric oxide levels were also increased in untreated and treated orchiectomized (IOR and IMOR) when compared to the other groups, with or without LPS. Our data suggest that melatonin therapy associated with orchiectomy induced a stimulating effect on the immune response to the parasite. PMID:22177576

  10. The effect of melatonin on sleep quality after laparoscopic cholecystectomy: a randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Gögenur, Ismail; Kücükakin, Bülent

    2009-01-01

    BACKGROUND: In this study, we investigated whether melatonin administration could improve postoperative subjective sleep quality and reduce discomfort. METHODS: One hundred twenty-one patients scheduled for elective ambulatory laparoscopic cholecystectomy were randomized to oral 5 mg melatonin (n = 60) or placebo (n = 61) for 3 nights after surgery. Subjective sleep quality, sleep duration, sleep timing, and subjective discomfort (fatigue, general well-being, and pain) were measured. RESULTS: Sleep latency was significantly reduced in the melatonin group (mean [sd] 14 min [18]) compared with placebo (28 min [41]) on the first postoperative night (P = 0.015). The rest of the measured outcome variables did not differ between groups. CONCLUSIONS: Melatonin did not improve subjective sleep quality or discomfort compared with placebo after laparoscopic cholecystectomy.

  11. Melatonin attenuates inflammation of acute pulpitis subjected to dental pulp injury

    Science.gov (United States)

    Li, Ji-Guo; Lin, Jia-Ji; Wang, Zhao-Ling; Cai, Wen-Ke; Wang, Pei-Na; Jia, Qian; Zhang, An-Sheng; Wu, Gao-Yi; Zhu, Guo-Xiong; Ni, Long-Xing

    2015-01-01

    Acute pulpitis (AP), one of the most common diseases in the endodontics, usually causes severe pain to the patients, which makes the search for therapeutic target of AP essential in clinic. Toll-like receptor 4 (TLR4) signaling is widely involved in the mechanism of pulp inflammation, while melatonin has been reported to have an inhibition for a various kinds of inflammation. We hereby studied whether melatonin can regulate the expression of TLR4/NF-?B signaling in the pulp tissue of AP and in human dental pulp cells (HDPCs). Two left dental pulps of the adult rat were drilled open to establish the AP model, and the serum levels of melatonin and pro-inflammatory cytokines, including interleukin 1? (IL-1?), interleukin 18 (IL-18) and tumor necrosis factor ? (TNF-?), were assessed at 1, 3 and 5 d post injury. At the same time points, the expression of TLR4 signaling in the pulp was explored by quantitative real-time PCR and immunohistochemistry. The AP rats were administered an abdominal injection of melatonin to assess whether melatonin rescued AP and TLR4/NF-?B signaling. Dental pulp injury led to an approximately five-day period acute pulp inflammation and necrosis in the pulp and a significant up-regulation of IL-1?, IL-18 and TNF-? in the serum. ELISA results showed that the level of melatonin in the serum decreased due to AP, while an abdominal injection of melatonin suppressed the increase in serum cytokines and the percentage of necrosis at the 5 d of the injured pulp. Consistent with the inflammation in AP rats, TLR4, NF-?B, TNF-? and IL-1? in the pulp were increased post AP compared with the baseline expression. And melatonin showed an inhibition on TLR4/NF-?B signaling as well as IL-1? and TNF-? production in the pulp of AP rats. Furthermore, melatonin could also regulate the expression of TLR4/NF-?B signaling in LPS-stimulated HDPCs. These data suggested that dental pulp injury induced AP and reduced the serum level of melatonin and that supplementation with melatonin may have a protective effect on AP by modulating TLR4/NF-?B signaling in the pulp and in pulp cells. PMID:25755829

  12. Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial.

    Science.gov (United States)

    Smits, M G; Nagtegaal, E E; van der Heijden, J; Coenen, A M; Kerkhof, G A

    2001-02-01

    To establish the efficacy of melatonin treatment in childhood sleep onset insomnia, 40 elementary school children, 6 to 12 years of age, who suffered more than 1 year from chronic sleep onset insomnia, were studied in a double-blind, placebo-controlled study. The children were randomly assigned to receive either 5-mg melatonin or placebo. The study consisted of a 1-week baseline, consecutively followed by a 4-week treatment period. After that period, treatment was continued if the parents wished so. The study's impact was assessed by measurements of lights-off time, sleep onset, and wake-up time, recorded in a diary (n = 33). Sleep onset was also recorded with an actigraph (n = 25). Endogenous dim light melatonin onset was measured in saliva (n = 27). Sustained attention was evaluated with the Bourdon-Vos reaction time test (n = 36). In the melatonin group, mean (95% CI) lights-off time advanced 34 (6-63) minutes, diary sleep onset 63 (32-94) minutes, actigraphic sleep onset 75 (36-114) minutes, and melatonin onset 57 (24 to 89) minutes; total sleep time increased 41 (19-62) minutes. In the placebo group, these parameters did not shift significantly. The change during the 4-week treatment period differed between the treatment groups significantly as to lights-off time, diary and actigraphic sleep onset, sleep duration, and melatonin onset. There were no significant differences between the treatment groups in the change of sleep latency, wake-up time, and sustained attention reaction times. Mild headache occurred in 2 children during the first 2 days of the melatonin treatment. Eighteen months after the start of the trial, in 13 of the 38 children who could be followed up, melatonin treatment was stopped because their sleep problem was solved and in 1 child because sleep was not improved. Twelve children used melatonin 5 mg, the other 1.0 to 2.5 mg. One child developed mild generalized epilepsy 4 months after the start of the trial. The results show that melatonin, 5 mg at 6 PM, was relatively safe to take in the short term and significantly more effective than placebo in advancing sleep onset and dim light melatonin onset and increasing sleep duration in elementary school children with chronic sleep onset insomnia. Sustained attention was not affected. PMID:11292231

  13. Melatonin suppresses cisplatin-induced nephrotoxicity via activation of Nrf-2/HO-1 pathway

    Directory of Open Access Journals (Sweden)

    Kilic Ulkan

    2013-01-01

    Full Text Available Abstract Background Cisplatin, one of the most effective and potent anticancer drugs, is used in the treatment of a wide variety of both pediatric and adult malignancies. However, the chemotherapeutic use of cisplatin is limited by its serious side-effects such as nephrotoxicity and ototoxicity. Cisplatin chemotherapy induces a reduction in the antioxidant status, leading to a failure of the antioxidant defense against free-radical damage generated by antitumor drugs. Cisplatin-induced oxidative stress in the kidney was partially prevented by antioxidant treatments using superoxide dismutase, glutathione, selenium and flavonoids. Melatonin and its metabolites possess free-radical scavenging activity and it has been shown that they protect against cisplatin toxicity. However, the mechanism of the protective effects of melatonin against cisplatin-induced nephrotoxicity is still essentially unknown. We therefore designed this study to investigate the underlying mechanism of the protective effect of melatonin against cisplatin-induced renal damage in a rat nephrotoxicity model in vivo. Methods Twenty eight 8-week-old male Wistar rats were divided into four groups of control, melatonin treatment (4?mg/kg b.w i.p. for 10?days, cisplatin treatment (7?mg/kg b.w., i.p. and melatonin and cisplatin combination treatment. Serum urea nitrogen (urea-N and creatinine levels were measured. Histopathological changes were evaluated. In addition, we analyzed the expression levels of HO-1, Nrf2, NF-?B and AP-1 in Western blot analysis. Results Both serum creatinine and urea nitrogen increased significantly following cisplatin administration alone; these values decreased significantly with melatonin co-treatment of cisplatin-treated rats. Histological analysis showed that cisplatin caused damage in the proximal tubular cells in the kidneys of cisplatin-treated rats; these changes were reversed by melatonin co-treatment. Upon Western blot analysis, melatonin treatment increased Nrf2 accumulation in the nuclear fraction, and increased the expression of HO-1 in the cytosolic fraction as compared to the cisplatin-treated rats. Expressions of NF-?B p65 and AP-1 were increased significantly in the kidneys of rats treated with cisplatin compared with the expression in the kidneys from the control, melatonin-only-treated and melatonin co-treated rats. Conclusion Our present data suggest that melatonin attenuates cisplatin-induced nephrotoxicity possibly by modulating Nrf2/HO-1 signaling.

  14. Pulsing blue light through closed eyelids: effects on acute melatonin suppression and phase shifting of dim light melatonin onset.

    Science.gov (United States)

    Figueiro, Mariana G; Plitnick, Barbara; Rea, Mark S

    2014-01-01

    Circadian rhythm disturbances parallel the increased prevalence of sleep disorders in older adults. Light therapies that specifically target regulation of the circadian system in principle could be used to treat sleep disorders in this population. Current recommendations for light treatment require the patients to sit in front of a bright light box for at least 1 hour daily, perhaps limiting their willingness to comply. Light applied through closed eyelids during sleep might not only be efficacious for changing circadian phase but also lead to better compliance because patients would receive light treatment while sleeping. Reported here are the results of two studies investigating the impact of a train of 480 nm (blue) light pulses presented to the retina through closed eyelids on melatonin suppression (laboratory study) and on delaying circadian phase (field study). Both studies employed a sleep mask that provided narrowband blue light pulses of 2-second duration every 30 seconds from arrays of light-emitting diodes. The results of the laboratory study demonstrated that the blue light pulses significantly suppressed melatonin by an amount similar to that previously shown in the same protocol at half the frequency (ie, one 2-second pulse every minute for 1 hour). The results of the field study demonstrated that blue light pulses given early in the sleep episode significantly delayed circadian phase in older adults; these results are the first to demonstrate the efficacy and practicality of light treatment by a sleep mask aimed at adjusting circadian phase in a home setting. PMID:25506253

  15. Quantitative structure-activity relationships within a series of melatonin analogs and related indolealkylamines.

    Science.gov (United States)

    Lewis, D F; Arendt, J; English, J

    1990-01-01

    The results of molecular orbital calculations by the complete neglect of differential overlap, 2nd version on 10 indolealkylamines and amides related to melatonin are reported. Quantitative structure-activity relationships have been derived by regression analysis of electronic structural parameters and biological data in the form of melatonin receptor affinities. On the basis of these results, together with electrostatic potential energy calculations, a possible receptor binding site model is proposed. PMID:2153808

  16. Transcutaneous Auricular Vagus Nerve Stimulation Triggers Melatonin Secretion and Is Antidepressive in Zucker Diabetic Fatty Rats

    OpenAIRE

    Li, Shaoyuan; Zhai, Xu; Rong, Peijing; Mccabe, Michael F.; Zhao, Jingjun; Ben, Hui; Wang, Xing; Wang, Shuxing

    2014-01-01

    Decreased circulating melatonin is implicated in depression. We recently found that Zucker diabetic fatty rats (ZDF, fa/fa) develop depression-like behaviors and that transcutaneous auricular vagus nerve stimulation (taVNS) is antidepressive in ZDF rats. Here we studied whether the ZDF rats could be used as a depression rodent model and whether the antidepressive effect of taVNS is mediated through modulation of melatonin secretion. Adult male ZDF and Zucker lean (ZL, fa/+) littermates were u...

  17. Sonographic monitoring of early follicle growth induced by melatonin implants in camels and the subsequent fertility

    OpenAIRE

    Dholpuria, S.; Vyas, S.; Purohit, G. N.; Pathak, K. M. L.

    2012-01-01

    The present study examined the effect of melatonin implants on follicle growth in dromedary camels two months ahead of their natural breeding season (December to March). Female camels (n = 6) were treated with melatonin implants at the dose rate of 1 implant per 28 kg body weight sc. Control camels (n = 6) were administered an SC placebo implant of 8 ml vitamin A. Ovarian ultrasonography was performed at weekly interval upto 7 weeks. Camels were mated with virile stud when a follicle (?...

  18. Melatonin modulates the effects of diethylstilbestrol (DES) on the anterior pituitary of the female Wistar rat.

    OpenAIRE

    Yazhuo Zhang; Yilin Sun; Guilin Li; Fang Yuan; Zhongfang Shi; Weijiang Zhao; Zhongcheng Wang

    2010-01-01

    We studied the anti-tumorigenic effect of melatonin in diethylstilbestrol (DES)-treated anterior pituitaries in rats. Twenty-one female Wistar rats were randomly allocated into three groups: vehicle control rats, DES-treated rats, and DES-treated rats co-administrated with melatonin beginning at week 13. At the end of 16 weeks, rats were weighed and decapitated for morphological studies, including an H+E staining-based score evaluation in regard to cell proliferation, angiogenesis, immunostai...

  19. Protein kinase C activation antagonizes melatonin-induced pigment aggregation in Xenopus laevis melanophores

    OpenAIRE

    1992-01-01

    The pineal hormone, melatonin (5-methoxy N-acetyltryptamine) induces a rapid aggregation of melanin-containing pigment granules in isolated melanophores of Xenopus laevis. Treatment of melanophores with activators of protein kinase C (PKC), including phorbol esters, mezerein and a synthetic diacylglycerol, did not affect pigment granule distribution but did prevent and reverse melatonin-induced pigment aggregation. This effect was blocked by an inhibitor of PKC, Ro 31- 8220. The inhibitory ef...

  20. Melatonin decreases muscular oxidative stress and inflammation induced by strenuous exercise and stimulates growth factor synthesis.

    Science.gov (United States)

    Borges, Leandro da Silva; Dermargos, Alexandre; Junior, Edenilson Pinto da Silva; Weimann, Eleine; Lambertucci, Rafael Herling; Hatanaka, Elaine

    2015-03-01

    Strenuous exercise is detrimental to athletes because of the overproduction of reactive oxygen species. Melatonin, a classic antioxidant, has been shown to exhibit beneficial effects regarding intense exercise and tissue repair. In this study, we evaluated the onset and resolution of inflammation in melatonin-treated and nontreated rats subjected to a strenuous exercise session. We also analyzed the formation of thiobarbituric acid reactive substances (TBARS) and the activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Control and treated rats were subjected to exhaustive exercise after a period of 10 days of melatonin treatment (20 mg/dL). Plasma and muscle levels of tumor necrosis factor-alpha (TNF-?), interleukin 1 beta (IL-1?), interleukin 6 (IL-6), cytokine-induced neutrophil chemoattractant-2-alpha/beta (CINC-2?/?), l-selectin, macrophage inflammatory protein-3-alpha (MIP-3?), and vascular endothelial growth factor (VEGF) were measured prior to, immediately after, and 2 hr after exercise. Our data revealed decreases in the muscle concentrations of IL-1? (35%), TNF-? (13%), IL-6 (48%), and TBARS (40%) in the melatonin-treated group compared with the control group. We also observed decreases in the plasma concentrations of IL-1? (17%) in the melatonin-treated group. VEGF-? concentrations and SOD activity increased by 179% and 22%, respectively, in the melatonin-treated group compared with the control group. We concluded that muscle inflammation and oxidative stress resulting from exhaustive exercise were less severe in the muscles of melatonin-treated animals than in the muscles of control animals. Thus, melatonin treatment may reverse exercise-induced skeletal muscle inflammation and stimulate growth factor synthesis. PMID:25546615

  1. Melatonin improves memory acquisition under stress independent of stress hormone release

    OpenAIRE

    Rimmele, U.; Spillmann, M.; Ba?rtschi, C.; Wolf, O. T.; Weber, C. S.; Ehlert, U.; Wirtz, P. H.

    2009-01-01

    RATIONALE: Animal studies suggest that the pineal hormone melatonin influences basal stress hormone levels and dampens hormone reactivity to stress. OBJECTIVES: We investigated whether melatonin also has a suppressive effect on stress-induced catecholamine and cortisol release in humans. As stress hormones affect memory processing, we further examined a possible accompanying modulation of memory function. MATERIALS AND METHODS: Fifty healthy young men received a single oral dose of either 3...

  2. Modulation of Intercellular Calcium Signaling by Melatonin, in Avian and Mammalian Astrocytes, is Brain Region Specific

    OpenAIRE

    Peters, Jennifer L.; Earnest, Barbara J.; Tjalkens, Ronald B.; Cassone, Vincent M.; Zoran, Mark J.

    2005-01-01

    Calcium waves among glial cells impact many central nervous system functions, including neural integration and brain metabolism. Here, we have characterized the modulatory effects of melatonin, a pineal neurohormone that mediates circadian and seasonal processes, on glial calcium waves derived from different brain regions and species. Diencephalic and telencephalic astrocytes, from both chick and mouse brains, expressed melatonin receptor proteins. Further, using the calcium-sensitive dye Flu...

  3. The potential therapeutic effect of melatonin in gastro-esophageal reflux disease

    Directory of Open Access Journals (Sweden)

    El-Gendy Ahmed A

    2010-01-01

    Full Text Available Abstract Background Gastro-Esophageal Reflux Disease (GERD defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Many drugs are used for the treatment of GERD such as omeprazole (a proton pump inhibitor which is a widely used antiulcer drug demonstrated to protect against esophageal mucosal injury. Melatonin has been found to protect the gastrointestinal mucosa from oxidative damage caused by reactive oxygen species in different experimental ulcer models. The aim of this study is to evaluate the role of exogenous melatonin in the treatment of reflux disease in humans either alone or in combination with omeprazole therapy. Methods 36 persons were divided into 4 groups (control subjects, patients with reflux disease treated with melatonin alone, omeprazole alone and a combination of melatonin and omeprazole for 4 and 8 weeks Each group consisted of 9 persons. Persons were subjected to thorough history taking, clinical examination, and investigations including laboratory, endoscopic, record of esophageal motility, pH-metry, basal acid output and serum gastrin. Results Melatonin has a role in the improvement of Gastro-esophageal reflux disease when used alone or in combination with omeprazole. Meanwhile, omeprazole alone is better used in the treatment of GERD than melatonin alone. Conclusion The present study showed that oral melatonin is a promising therapeutic agent for the treatment of GERD. It is an effective line of treatment in relieving epigastric pain and heartburn. However, further studies are required to confirm the efficacy and long-term safety of melatonin before being recommended for routine clinical use. Trial Registration QA13NCT00915616

  4. CANCER CHRONOMICS III: Chronomics for cancer, aging, melatonin and experimental therapeutics researchers

    OpenAIRE

    Halberg, Franz; Corne?lissen, Germaine; Ulmer, Waldemar; Blank, Mikhail; Hrushesky, William; Wood, Patricia; Singh, Rajesh K.; Wang, Zhengrong

    2006-01-01

    This position paper documents the merit of including for basic and clinical investigations the mapping of circadian and other rhythms and yet broader chronomes, time structures in and around us. Chronobiometry used herein relies on inferential statistical methods and on materials documented earlier. The circadian amplitude of melatonin is shown to relate both to cancer risk and to the presence of overt cancer, when no differences are found in the 24-hour average of melatonin. Optimization of ...

  5. Melatonin interferes in the desmoplastic reaction in breast cancer by regulating cytokine production.

    Science.gov (United States)

    Alvarez-García, Virginia; González, Alicia; Alonso-González, Carolina; Martínez-Campa, Carlos; Cos, Samuel

    2012-04-01

    Melatonin exerts oncostatic effects on breast cancer by interfering with the estrogen signaling pathways. Melatonin inhibits aromatase enzyme in breast cancer cells and fibroblasts. In addition, melatonin stimulates the adipogenic differentiation of fibroblasts. Our objective was to study whether melatonin interferes in the desmoplastic reaction by regulating some factors secreted by malignant cells, tumor necrosis factor (TNF)-?, interleukin (IL)-11, and interleukin (IL)-6. To accomplish this, we co-cultured 3T3-L1 cells with MCF-7 cells. The addition of breast cancer cells to the co-cultures inhibited the differentiation of 3T3-L1 preadipocytes to mature adipocytes, by reducing the intracytoplasmic triglyceride accumulation, an indicator of adipogenic differentiation, and also stimulated their aromatase activity. Melatonin counteracted the inhibitory effect on adipocyte differentiation and aromatase activity induced by MCF-7 cells in 3T3-L1 cells. The levels of cytokines in the co-culture media were 10 times those found in culture of 3T3-L1 cells alone. Melatonin decreased the concentrations of cytokines in the media and counteracted the stimulatory effect induced by MCF-7 cells on the cytokine levels. One millimolar melatonin induced a reduction in TNF-?, IL-6, and IL-11 mRNA expression in MCF-7 and 3T3-L1 cells. The findings suggest that melatonin may play a role in the desmoplastic reaction in breast cancer through a downregulatory action on the expression of antiadipogenic cytokines, which decreas