Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melatonin is synthesized and secreted during the dark period of the light-dark cycle. The rhythmic nocturnal melatonin secretion is directly generated by the circadian clock, located in mammals within the suprachiasmatic nucleus (SCN), and is entrained to a 24-hour period by the light-dark cycle. The periodic secretion of melatonin may be used as a circadian mediator to any system that can 'read' the message. In addition, direct effects of the hormone on the SCN could explain some of the melatonin effects on the circadian system. Duration of the melatonin nocturnal secretion is directly proportional to the length of the night and it has experimentally been demonstrated to be the critical parameter for photoperiod integration. The sites and mechanisms of action of melatonin for circadian and photoperiodic responses are far from being elucidated, but action through specific membrane receptor sites starts to emerge. A possible bicompartmental model of distribution for melatonin, the first compartment in plasma acting on peripheral organs and the second in the cerebrospinal fluid affecting neurally mediated functions at a much higher concentration, has recently been proposed. From earlier studies it was concluded that melatonin administration to humans reduces sleep latency and induces sleepiness and fatigue. More recently, the effect of lower pharmacologic or physiologic doses of melatonin was examined in different laboratories. These studies included young normal volunteers and patients with chronic insomnia, as well as dementia patients exhibiting sundowning syndrome. Irrespective of the method of assessment, melatonin showed effects in insomniac patients in most studies. With some exceptions, melatonin administration reduced sleep latency and/or increased total sleep time and sleep efficiency. Furthermore, melatonin was more effective when given to elderly insomniacs, or Alzheimer disease patients, although sleep improvement was not strictly correlated with prior levels of the hormone.
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PMID:A critical assessment of the melatonin effect on sleep in humans. 1102 39

Subjective, physiological and physical performance variables are affected following travel across multiple time-zones (jet-lag). The objective of the study was to examine the effects of oral melatonin in alleviating jet-lag by investigating its effects on subjects who had flown from London to Eastern Australia, 10 time-zones to the east. Melatonin (5 mg day(-1)) or placebo capsules were administered to 14 experimental (13 males and 1 female) and 17 control subjects (15 males and 2 females), respectively, in a double-blind study; the time of administration was in accord with the current consensus for maximizing its hypnotic effect. Grip strength and intra-aural temperature were measured on alternate days after arrival at the destination, at four different times of day (between the times 07:00 - 08:00 h, 12:00 - 13:00 h, 16:00 - 17:00 h and 19:00 - 20:00 h local time). In addition, for the first 6 - 7 days after arrival in Australia, subjective ratings of jet-lag on a 0 - 10 visual analogue scale and responses to a Jet-lag Questionnaire (incorporating items for tiredness. sleep, meal satisfaction and ability to concentrate) were recorded at the above times and also on retiring (at about midnight). Subjects continued normally with their work schedules between the data collection times. Subjects with complete data (13 melatonin and 13 placebo subjects), in comparison with published data, showed partial adjustment of the diurnal rhythm in intra-aural temperature after 6 days. A time-of-day effect was evident in both right and left grip strength during adjustment to Australian time; there was no difference between the group taking melatonin and that using the placebo. Right and left grip strength profiles on day 6 were adjusted either by advancing or delaying the profiles, independent of whether subjects were taking melatonin or placebo tablets. Subjects reported disturbances with most measures in the Jet-lag Questionnaire but, whereas poorer concentration and some negative effects upon sleep had disappeared after 3 - 5 days, ratings of jet-lag and tiredness had not returned to 'zero' (or normal values), respectively, by the sixth day of the study. Subjects taking melatonin showed no significant differences from the placebo group in perceived irritability, concentration, meal satisfaction, ease in getting to sleep and staying asleep, frequency of bowel motion and consistency of the faeces. These results suggest that, in subjects who, after arrival, followed a busy schedule which resulted in frequent and erratic exposure to daylight, melatonin had no benefit in alleviating jet-lag or the components of jet-lag, and it did not influence the process of phase adjustment.
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PMID:Use of melatonin in recovery from jet-lag following an eastward flight across 10 time-zones. 1108 31

Sleep disturbances are common in patients with Asperger disorder. Although these sleep problems are often persistent and may significantly impair the child's daytime well-being, no treatment studies have been reported. In this open clinical trial, the effectiveness of melatonin was studied in a sample of 15 children with Asperger disorder (13 boys, 2 girls) aged 6-17 years using several questionnaires and actigraph measurements. They included assessments of sleep quality, tiredness, and behavior. Melatonin (3 mg/day) was used for 14 days. All the measurements were made three times: before the treatment period, during the treatment (days 12-14), and 3 weeks after the discontinuation of the treatment. The sleep patterns of all the children improved, and half of them displayed excellent responses to melatonin. In particular, actigraphically measured sleep latency decreased from 40.02 +/- 24.09 minutes to 21.82 +/- 9.64 minutes (p = 0.002), whereas sleep duration remained steady at 477.40 +/- 55.56 minutes and 480.48 +/- 50.71 minutes. Despite the short duration of the treatment, behavioral measures also displayed a significant improvement, and most of the effect disappeared after the discontinuation of the melatonin (p = 0.001). In conclusion, melatonin may provide an interesting new and well-tolerated treatment option for children with Asperger disorder suffering from chronic insomnia. However, these results must be confirmed in a controlled study.
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PMID:Effectiveness of melatonin in the treatment of sleep disturbances in children with Asperger disorder. 1280 29

The use of strategies to manage fatigue associated with work was investigated in a sample of 253 pilots operating Air New Zealand regional and international routes. Overall, 13% of pilots responded that they experienced fatigue from their job as a pilot three times a week or more but no differences in overall fatigue levels were found by age, rank or fleet. The use of napping by pilots prior to an overnight duty was variable and 25% of pilots responded that they napped only a little of the time or not at all before such a duty. Pilots who routinely used daytime napping prior to overnight duties reported significantly lower levels of general fatigue. The use of the cockpit napping procedure was evenly split, with 52.5% of pilots reporting the use of cockpit napping over the previous 12 months. The use of the cockpit napping procedure was associated with lower levels of reported fatigue. Hypnotic medication use in the previous 2 months was reported by 19% of pilots mostly on an occasional basis. Melatonin and alternative medicine were used less frequently than hypnotics. This study highlights fatigue as a major problem for many pilots operating regional and international routes. The strategies used by international aircrew to manage fatigue are variable and provide support for the association between napping and lower reported fatigue.
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PMID:Fatigue self-management strategies and reported fatigue in international pilots. 1520 98

The effect of melatonin, a chronobiotic drug, was explored in 29 patients with chronic fatigue syndrome (CFS) and Dim Light Melatonin onset (DLMO) later than 21.30 hours, reflective of delayed circadian rhythmicity. The patients took 5 mg of melatonin orally, 5 h before DLMO during 3 months. Their responses to the checklist individual strength (CIS), a reliable questionnaire measuring the severity of personally experienced fatigue, were assessed twice with a 6-week interval immediately before the treatment and once after 3 months treatment. In the pre-treatment period the fatigue sub-score improved significantly. After treatment, the total CIS score and the sub-scores for fatigue, concentration, motivation and activity improved significantly. The sub-score fatigue normalized in two of the 29 patients in the pre-treatment period and in eight of 27 patients during treatment. This change was significant. In the patients with DLMO later than 22.00 hours (n=21) the total CIS score and the sub-scores for fatigue, concentration and activity improved significantly more than in the patients (n=8) with DLMO earlier than 22.00 hours. Melatonin may be an effective treatment for patients with CFS and late DLMO, especially in those with DLMO later than 22.00 hours.
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PMID:Influence of melatonin on fatigue severity in patients with chronic fatigue syndrome and late melatonin secretion. 1642 Mar 93

Melatonin, the hormone produced nocturnally by the pineal gland, is an endogenous regulator of the sleep-wake cycle. The effects of melatonin on brain activities and their relation to induction of sleepiness were studied in a randomized, double-blind, placebo controlled functional magnetic resonance imaging (fMRI) study. Melatonin, but not placebo, reduced task-related activity in the rostro-medial aspect of the occipital cortex during a visual-search task and in the auditory cortex during a music task. These effects correlated with subjective measurements of fatigue. In addition, melatonin enhanced the activation in the left parahippocampus in an autobiographic memory task. Results demonstrate that melatonin modulates brain activity in a manner resembling actual sleep although subjects are fully awake. Furthermore, the fatigue inducing effect of melatonin on brain activity is essentially different from that of sleep deprivation thus revealing differences between fatigues related to the circadian sleep regulation as opposed to increased homeostatic sleep need. Our findings highlight the role of melatonin in priming sleep-associated brain activation patterns in anticipation of sleep.
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PMID:Sleep-anticipating effects of melatonin in the human brain. 1642 87

Sepsis impairs diaphragmatic contractility and endurance capacity and increases diaphragmatic fatigability. Several investigations have shown that administration of a number of free radical scavengers, such as N-acetylcysteine (NAC), protects the diaphragm from the development of endotoxin-mediated diaphragmatic dysfunction. The aim of this study was to evaluate the effects of melatonin (CAS 73-31-4), a naturally occurring potent antioxidant, on diaphragmatic contractility and lipid peroxidation as a marker of oxidative stress in endotoxemic rats. Rats were randomly divided into four groups: control group, endotoxemic group, melatonin group and endotoxemic plus melatonin group. Melatonin was administered by intraperitoneal injection 30 min before endotoxin inoculation to animals. Diaphragmatic function and malondialdehyde (MDA) level analysis as an indicator of lipid peroxidation were assessed 17 h after endotoxin or saline inoculation. Endotoxemia decreased the development of diaphragm fatigue and diaphragmatic MDA levels. The effects of endotoxemia on diaphragmatic contractions and fatigability were reversed and returned to control levels by melatonin administration. However, melatonin did not prevent the increase in muscle MDA content. In conclusion, the present study demonstrated that melatonin attenuated the endotoxin-induced impairment of diaphragm function. This effect of melatonin does not seem to be related to its antioxidant properties.
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PMID:Beneficial effects of melatonin on diaphragmatic contractility and fatigability in Escherichia coli endotoxemic rats. 1657 23

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.
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PMID:Jet lag: therapeutic use of melatonin and possible application of melatonin analogs. 1834 69

Patients with neurologic disorders commonly experience sleep dysfunction and psychiatric disorders. The most common sleep dysfunction is insomnia, which is a primary symptom in 30% to 90% of psychiatric disorders. Insomnia and fatigue are prominent symptoms of anxiety disorders and major depression that may occur in patients who are treated but have residual sleep dysfunction. Anxiety and depressive disorders account for 40% to 50% of all cases of chronic insomnia. It is also recognized that primary insomnia and other primary sleep disorders produce symptoms that are similar to those reported by patients with psychiatric disorders. A clinician must judge whether sleep deprivation causes mood disturbance or whether depressive or anxiety disorder represents the primary reason for sleep dysfunction. When insomnia is comorbid with mild to moderate depression, therapy should begin with bedtime dosing of sedating antidepressants such as mirtazapine, nefazodone, or tricyclic antidepressants, which are preferred because of their sedative effects. Often side effects limit their usefulness. Intervention for chronic insomnia is similar in nonpsychiatric and psychiatric patients. Behavioral therapies, particularly multicomponent cognitive-behavioral therapy, and lifestyle changes show significant long-term efficacy as treatments for chronic insomnia. The most studied pharmacologic agents to treat insomnia are sedative hypnotic agents, particularly those that are active through the benzodiazepine receptor-GABA (gamma-aminobutyric acid) complex, such as benzodiazepines, eszopiclone, zaleplon, and zolpidem. Melatonin and the melatonin-receptor agonist ramelteon have not had adequate study in psychiatric patients to define their use, but small studies suggest benefit. Prescription of adjunctive trazodone (50-150 mg) is a common clinical practice to treat comorbid insomnia during antidepressant therapy, but published data are surprisingly limited, considering its frequent use. Although there has been insufficient research on the use of atypical antipsychotic agents in severe insomnia, psychiatrists use quetiapine, olanzapine, or others to lessen agitation that disrupts sleep. When insomnia or hypersomnia continue even as mood, anxiety, or thought disorders improve with standard therapy, the physician should consider the potential presence of underlying sleep disorders.
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PMID:Treatment of sleep dysfunction and psychiatric disorders. 1974 1

Since very little is understood about the exact aetiology of tinnitus, this has made treatment of the condition difficult. Even though approximately 10-15% of the general population suffer from tinnitus, only 2% consider it serious enough to warrant any treatment. The main problem arising from tinnitus is the disturbance it causes not only in day to day life but also in sleep, leading to fatigue and general discomfort. The present study focused on the effect of Melatonin in conjunction with Sulodexide as a treatment method for tinnitus. Overall, 102 patients suffering from tinnitus were evaluated in a prospective randomised controlled study conducted in a tertiary care ENT department. After randomisation, 34 patients were treated with Melatonin and Sulodexide, another 34 were treated with Melatonin alone, while the remaining 34 (control group) were managed without treatment in order to evaluate spontaneous variations in the quality of tinnitus. Patients were assessed prospectively with the Tinnitus Handicap Inventory and Acufenometry, both pre- and post-treatment. Among the patients studied, better results with both Tinnitus Handicap Inventory and Acufenometry were found in the group who received Melatonin and Sulodexide compared to those receiving Melatonin alone. No improvement was observed in the control group. In conclusion, Melatonin in combination with Sulodexide is, in our opinion, a viable treatment option for patients suffering from central or sensorineural tinnitus.
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PMID:Treatment of central and sensorineural tinnitus with orally administered Melatonin and Sulodexide: personal experience from a randomized controlled study. 2011 18


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