1,721,079 research outputs found
Vida moderna y déficit de sueño : la fisiología no se globaliza
Full text linkFil: Cardinali, Daniel P. Universidad de Buenos Aires. Facultad de Medicina; Argentina.Para tener una buena vida resulta indispensable disfrutar de un buen sueño. Sin embargo, las
exigencias propias de la vida moderna, impuestas por un modelo productivo que da lugar a una
sociedad que está en marcha las 24 horas de manera permanente, está alterando nuestros ciclos
naturales de sueño y vigilia. Los seres humanos estamos durmiendo menos horas que las que
necesitamos y cada vez sufrimos más trastornos del sueño. Esta situación está provocando graves
consecuencias, tanto en el orden individual como en el social
Trastornos del sueño y seguridad vial : un tema no resuelto
Full text linkFil: Cardinali, Daniel P. Universidad de Buenos Aires. Facultad de Medicina; Argentina.Fil: Pérez Chada, Daniel. Hospital Universitario Austral. Departamento de Medicina Interna; ArgentinaLos mayores accidentes industriales y vehiculares de nuestros días pueden vincularse a la utilización de
"las máquinas humanas" más allá de sus especificaciones naturales. En nuestro país, y a pesar de la
creciente preocupación pública por la seguridad vial, se presta poco interés al hecho de que la influencia
del sueño insuficiente es causa en una importante proporción de accidentes vehiculares
Inflammaging, Metabolic Syndrome and Melatonin: A Call for Treatment Studies
Full text linkThe metabolic syndrome (MS) is a collection of risk factors for cardiovascular disease, including obesity, hypertension, hyperinsulinemia, glucose intolerance and dyslipidemia. MS is associated with low-grade inflammation of the white adipose tissue, which can subsequently lead to insulin resistance, impaired glucose tolerance and diabetes. Adipocytes secrete proinflammatory cytokines as well as leptin and trigger a vicious circle which leads to additional weight gain largely as fat. The imbalance between inflammatory and anti-inflammatory signals is crucial to aging. Healthy aging can benefit from melatonin, a compound known to possess direct and indirect antioxidant properties, to have a significant protective effect on mitochondrial function, to enhance circadian rhythm amplitudes, to modulate the immune system and to exhibit neuroprotective actions. Melatonin levels decrease in the course of senescence and are more strongly reduced in diseases related to insulin resistance. This short review article analyzes the multiple protective actions of melatonin that are relevant to the attenuation of inflammatory responses and progression of inflammaging and how melatonin is effective to curtail MS in animal models of hyperadiposity. The clinical data supporting the possible therapeutic use of melatonin in human MS are also reviewed. Since attention has been focused on the development of potent melatonin analogs with prolonged effects (ramelteon, agomelatine, tasimelteon, piromelatine) and in clinical trials these analogs were administered in doses considerably higher than those usually employed for melatonin, clinical trials on melatonin in the range of 50-100 mg/day are needed to further assess its therapeutic value in MS.Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina ; ArgentinaFil: Hardeland, Rüdiger. Universität Göttingen; Alemani
Melatonin
No full textMelatonin, originally discovered as a hormone of the pineal gland, is produced by bacteria, protozoa, plants, fungi, invertebrates, and various extrapineal sites of vertebrates, including out, skin, Harderian gland, and leukocytes. Biosynthetic pathways seem to be identical. Actions are pleiotropic, mediated by membrane and nuclear receptors, other binding sites or chemical interactions. Melatonin regulates the sleep/wake cycle, other circadian and seasonal rhythms, and acts as an immunostimulator and cytoprotective agent. Circulating melatonin is mostly 6-hydroxylated by hepatic P-450 monooxygenases and excreted as 6-sulfatoxymelatonin. Pyrrole-ring cleavage is of higher importance in other tissues, especially the brain. The product, N-1-acetyl-N-2-formyl-5-methoxykynuramine, is formed by enzymatic, pseudoenzymatic, photocatalytic, and numerous free-radical reactions. Additional metabolites result from hydroxylation and nitrosation. The secondary metabolite, N-1-acetyl-5-methoxykynuramine, supports mitochondrial function and downregulates cyclooxygenase 2. Antioxidative protection, safeguarding of mitochondrial electron flux, and in particular, neuroprotection, have been demonstrated in many experimental systems. Findings are encouraging to use melatonin as a sleep promoter and in preventing progression of neurodegenerative diseases. (C) 2005 Elsevier Ltd. All rights reserved
Melatonergic drugs in clinical practice
No full textMelatonin (CAS 73-31-4) has both hypnotic and sleep/wake rhythm regulating properties. These sleep promoting actions, which are already demonstrable in healthy humans, have been found useful in subjects suffering from circadian rhythm sleep disorders (CRSD) like delayed sleep phase syndrome (DSPS), jet lag and shift-work sleep disorder. Low nocturnal melatonin production and secretion have been documented in elderly insomniacs, and exogenous melatonin has been shown to be beneficial in treating sleep disturbances of these patients. In comparison to a number of sleep-promoting compounds that are usually prescribed, such as bertzodiazepines and z-drugs (zolpidem and zopiclon belonging to the latter ones), melatonin has several advantages of clinical value: it does not cause hangover nor withdrawal effects and is devoid of any addictive potential. However, recent meta-analyses revealed that melatonin is not sufficiently effective in treating most primary sleep disorders. Some of the reasons for a limited efficacy of this natural hormone are related to its extremely short half-life in the circulation, and to the fact that sleep maintenance is also regulated by mechanisms downstream of primary melatonergic actions. Hence, there is an urgent need for the development of melatonin receptor agonists with a longer half-life, which could be suitable for a successful treatment of insomnia. Such requirements are fulfilled by rarnelteon (CAS 196597-26-9), which possesses a high affinity for the melatonin receptors MT1 and MT2 present in the circadian pacemaker, the suprachiasmatic nucleus (SCN). Ramelteon also has a substantially longer half-life than melatonin. This new drug has been successfully used in treating elderly insomniacs without any adverse effects reported, and is promising for treating patients with primary insomnia and also those suffering from CRSD. Since sleep disturbances constitute the most prevalent symptoms of various forms of depression, the need for the development of an ideal antidepressant was felt, which would both improve sleep and mitigate depressive symptoms. Since most of the currently used antidepressants, including the selective serotonin re-uptake inhibitors worsen the sleep disturbances of depressive patients, another novel melatonergic drug, agomelatine (CAS 13811276-2), holds some promise because of its particular combination of actions: it has a high affinity for MT, and MT2 receptors in the SCN, but it acts additionally as a 5-HT2C antagonist 15-hydroxytryptamine (serotonin) receptor 2C antagonist]. The latter property, which is decisive for the antidepressive action, would not favor but potentially antagonize sleep, but this is overcome during night by the melatonergic, sleep-promoting effect. This drug has been found beneficial in treating patients with major depressive and seasonal affective disorders. Unlike the other antidepressants, agomelatine improves both sleep and clinical symptoms of depressive illness and does not have any of the side effects on sleep seen with other compounds in use. This property seems to be of particular value because of the aggravating effects of disturbed sleep in the development of depressive symptoms. Based on these facts, agomelatine seems to be a drug of superior efficacy with a promising future in the treatment of depressive disorders. However, long-term safety studies are required for both ramelteon and agomelatine, with a consideration of the pharmacology of their metabolites, their effects on redox metabolism, and of eventual undesired mlatonergic effects, e. g., on reproductive functions. According to current data, both compounds seem to be safe during short-term treatment
Melatonergic drugs in clinical practice
No full textMelatonin (CAS 73-31-4) has both hypnotic and sleep/wake rhythm regulating properties. These sleep promoting actions, which are already demonstrable in healthy humans, have been found useful in subjects suffering from circadian rhythm sleep disorders (CRSD) like delayed sleep phase syndrome (DSPS), jet lag and shift-work sleep disorder. Low nocturnal melatonin production and secretion have been documented in elderly insomniacs, and exogenous melatonin has been shown to be beneficial in treating sleep disturbances of these patients. In comparison to a number of sleep-promoting compounds that are usually prescribed, such as bertzodiazepines and z-drugs (zolpidem and zopiclon belonging to the latter ones), melatonin has several advantages of clinical value: it does not cause hangover nor withdrawal effects and is devoid of any addictive potential. However, recent meta-analyses revealed that melatonin is not sufficiently effective in treating most primary sleep disorders. Some of the reasons for a limited efficacy of this natural hormone are related to its extremely short half-life in the circulation, and to the fact that sleep maintenance is also regulated by mechanisms downstream of primary melatonergic actions. Hence, there is an urgent need for the development of melatonin receptor agonists with a longer half-life, which could be suitable for a successful treatment of insomnia. Such requirements are fulfilled by rarnelteon (CAS 196597-26-9), which possesses a high affinity for the melatonin receptors MT1 and MT2 present in the circadian pacemaker, the suprachiasmatic nucleus (SCN). Ramelteon also has a substantially longer half-life than melatonin. This new drug has been successfully used in treating elderly insomniacs without any adverse effects reported, and is promising for treating patients with primary insomnia and also those suffering from CRSD. Since sleep disturbances constitute the most prevalent symptoms of various forms of depression, the need for the development of an ideal antidepressant was felt, which would both improve sleep and mitigate depressive symptoms. Since most of the currently used antidepressants, including the selective serotonin re-uptake inhibitors worsen the sleep disturbances of depressive patients, another novel melatonergic drug, agomelatine (CAS 13811276-2), holds some promise because of its particular combination of actions: it has a high affinity for MT, and MT2 receptors in the SCN, but it acts additionally as a 5-HT2C antagonist 15-hydroxytryptamine (serotonin) receptor 2C antagonist]. The latter property, which is decisive for the antidepressive action, would not favor but potentially antagonize sleep, but this is overcome during night by the melatonergic, sleep-promoting effect. This drug has been found beneficial in treating patients with major depressive and seasonal affective disorders. Unlike the other antidepressants, agomelatine improves both sleep and clinical symptoms of depressive illness and does not have any of the side effects on sleep seen with other compounds in use. This property seems to be of particular value because of the aggravating effects of disturbed sleep in the development of depressive symptoms. Based on these facts, agomelatine seems to be a drug of superior efficacy with a promising future in the treatment of depressive disorders. However, long-term safety studies are required for both ramelteon and agomelatine, with a consideration of the pharmacology of their metabolites, their effects on redox metabolism, and of eventual undesired mlatonergic effects, e. g., on reproductive functions. According to current data, both compounds seem to be safe during short-term treatment
Role of melatonin in neurodegenerative diseases
No full textThe pineal product melatonin has remarkable antioxidant properties. It scavenges hydroxyl, carbonate and various organic radicals, peroxynitrite and other reactive nitrogen species. Melatonyl radicals formed by scavenging combine with and, thereby, detoxify superoxide anions in processes terminating the radical reaction chains. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes like superoxide dismutase, glutathione peroxidase and glutathione reductase, and by augmenting glutathione levels. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases, e.g., Alzheimer's disease. Melatonin has been shown to be effective in arresting neurodegenerative phenomena seen in experimental models of Alzheimer's disease, Parkinsonism and ischemic stroke. Melatonin preserves mitochondrial homeostasis, reduces free radical generation e.g., by enhancing mitochondrial glutathione levels, and safeguards proton potential and ATP synthesis by stimulating complex I and IV activities. Therapeutic trials with melatonin have been effective in slowing the progression of Alzheimer's disease but not of Parkinson's disease. Melatonin's efficacy in combating free radical damage in the brain suggests that it may be a valuable therapeutic agent in the treatment of cerebral edema after traumatic brain injury
Role of melatonin in neurodegenerative diseases
No full textThe pineal product melatonin has remarkable antioxidant properties. It scavenges hydroxyl, carbonate and various organic radicals, peroxynitrite and other reactive nitrogen species. Melatonyl radicals formed by scavenging combine with and, thereby, detoxify superoxide anions in processes terminating the radical reaction chains. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes like superoxide dismutase, glutathione peroxidase and glutathione reductase, and by augmenting glutathione levels. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases, e.g., Alzheimer's disease. Melatonin has been shown to be effective in arresting neurodegenerative phenomena seen in experimental models of Alzheimer's disease, Parkinsonism and ischemic stroke. Melatonin preserves mitochondrial homeostasis, reduces free radical generation e.g., by enhancing mitochondrial glutathione levels, and safeguards proton potential and ATP synthesis by stimulating complex I and IV activities. Therapeutic trials with melatonin have been effective in slowing the progression of Alzheimer's disease but not of Parkinson's disease. Melatonin's efficacy in combating free radical damage in the brain suggests that it may be a valuable therapeutic agent in the treatment of cerebral edema after traumatic brain injury
New concepts in the neurophysiology of sleep and wakefulness
No full textAbstract: The neural substrates of sleep and wakefulness form a highly distributed and, to some extent, redundant network, with hypocretin, monoaminergic and cholinergic systems largely promoting wakefulness and GABAergic systems in the preoptic area, hypothalamus and brainstem promoting sleep. The hypocretin/orexin system plays a special role in the promotion of wakefulness and suppression of REM sleep by providing excitatory input to the monoaminergic and cholinergic systems. Sleep is not a unitary state but involves a cyclic alternation between NREM and REM sleep; the pons is critical for generating the multiple components (ie, EEG synchronization, eye movements and muscle atonia) that characterize REM sleep. Recent findings have implicated the participation of hypothalamus, through MCH/GABA that provide a critical input to pontine generator of REM sleep. The timing of sleep and wakefulness is regulated by an interaction between the circadian pacemaker located in the hypothalamic SCN and a sleep homeostatic system whose anatomic location is yet to be definitively identified. Among various neurochemicals, extracellular AD and nNOS/NK1 accumulate in the BF as wakefulness is extended and inhibits cortically projecting cholinergic neurons, thereby influencing cortical activity. In the future, it seems reasonable to expect a spreading of these insights from basic to clinical grounds for a better understanding of the causes and mechanisms of sleep disorders and the generation of novel therapeutics in sleep medicine.Fil: Garay, Arturo. Hospital Universitario. Sección Medicina del Sueño. Unidad de Neurociencia; ArgentinaFil: Cardinali, Daniel P. Universidad Católica Argentina. Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentin
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