Home About us Contact
|
Home About us Contact | ||
|
|
||
Exogenous Melatonin (exogenous + melatonin)
Selected AbstractsEffect of Exogenous Melatonin on Mood and Sleep Efficiency in Emergency Medicine Residents Working Night ShiftsACADEMIC EMERGENCY MEDICINE, Issue 8 2000Milan Jockovich MD Abstract. Objective: To determine whether melatonin taken prior to attempted daytime sleep sessions will improve daytime sleep quality, nighttime sleepiness, and mood state in emergency medicine (EM) residents, changing from daytime to nighttime work schedules. Methods: A prospective, randomized, double-blind crossover design was used in an urban emergency department. Emergency medicine residents who worked two strings of nights, of at least three nights' duration each, and separated by at least one week of days were eligible. Subjects were randomized to receive either melatonin 1 mg or placebo, 30 to 60 minutes prior to their daytime sleep session, for three consecutive days after each night shift. Crossover to the other agent occurred during their subsequent night shifts. Objective measures of quality of daytime sleep were obtained using the Actigraph 1000. This device measures sleep motion and correlates with sleep efficiency, total sleep time, time in bed, and sleep latency. The Profile of Mood States (POMS) and the Stanford Sleepiness Scale (SSS) were also used to quantify nighttime mood and sleepiness. Results: Among the 19 volunteers studied, there was no difference in sleep efficiency (91.16% vs 90.98%, NS), sleep duration (379.6 min vs 342.7 min, NS), or sleep latency (7.59 min vs 6.80 min, NS), between melatonin and placebo, respectively. In addition, neither the POMS total mood disturbance (5.769 baseline vs 12.212 melatonin vs 5.585 placebo, NS) nor the SSS (1.8846 baseline vs 2.2571 melatonin vs 2.1282 placebo, NS) demonstrated a statistical difference in nighttime mood and sleepiness between melatonin and placebo. Conclusions: There are no beneficial effects of a 1-mg melatonin dose on sleep quality, alertness, or mood state during night shift work among EM residents. [source] Exogenous melatonin enhances bile flow and ATP levels after cold storage and reperfusion in rat liver: implications for liver transplantationJOURNAL OF PINEAL RESEARCH, Issue 4 2005Mariapia Vairetti Abstract:, ,Although the use of melatonin in the transplantation field has been suggested, it has not been previously tested in a liver cold-storage model. We used a rat liver model to study (a) the dose-dependent effect of melatonin on bile production, and (b) the potential of melatonin to improve liver function after cold-storage. Male Wistar rats were perfused with Krebs,Henseleit bicarbonate buffer (KHB) at 37°C without or with 25, 50, 100 and 200 ,m melatonin. Each dose of melatonin stimulated bile production. For cold-storage studies, livers were flushed with either University of Wisconsin (UW) or Celsior solution and stored for 20 hr at 4°C. Reperfusion (120 min) was performed with KHB at 37°C. In subsequent studies, 100 ,m melatonin were added to the perfusate during the reperfusion period. ATP and melatonin levels in the tissue were measured. Bile analysis was performed by measuring melatonin, bilirubin and gamma-glutamyl transpeptidase (, -GT) levels in the fluid. A dose-dependent increase in bile secretion, associated with an enhanced melatonin and bilirubin levels in the bile were observed. Also, tissue levels of melatonin increased in a dose-dependent manner. When melatonin was added during the reperfusion period, bile production and bile bilirubin levels increased both with UW and Celsior solutions. The analysis of , -GT in the bile showed an increase in the Celsior-preserved liver and the addition of melatonin to the perfusate reduced this effect. Tissue ATP levels were higher when melatonin was added to the perfusion medium. Higher levels of melatonin in bile than in tissue were found. In conclusion, we demonstrate that melatonin improves significantly the restoration of liver function after cold-storage and reperfusion. [source] The relationship between melatonin and cortisol rhythms: clinical implications of melatonin therapyDRUG DEVELOPMENT RESEARCH, Issue 3 2005N. Zisapel Abstract Disturbances in circadian rhythm have been linked to chronic diseases such as insomnia, hypertension, diabetes, and depression. Here we review recent studies on the age-related changes in cortisol and melatonin rhythms and then present descriptive statistics on our preliminary findings on the rectification of the cortisol rhythms by melatonin therapy in elderly patients with insomnia. In adults, the melatonin onset typically occurs during low cortisol secretion. Administration of exogenous melatonin around dusk will shift the phase of the human circadian clock to earlier hours (advance phase shift) leading to phase advances in circadian rhythms (e.g., sleep, endogenous melatonin, cortisol). With aging, the production of melatonin declines and is shifted to later hours while the production of cortisol increases and its peak occurs earlier in the night. In a randomized placebo-controlled crossover study with 8 patients with insomnia aged 55 years and older, a group characterized by low and delayed melatonin production, administration of prolonged-release melatonin in the evening was able to rectify the early onset cortisol production. This delay in nocturnal cortisol onset may explain in part the improvement in sleep quality in elderly patients with insomnia, in schizophrenics, and in depressed patients. Support of circadian pacemaker function by melatonin may provide a new strategy in the treatment of disorders related to impairments in the internal temporal order. The clinical benefit from a decrease in cortisol during the early part of the night may lie beyond the improvement of sleep into a better control of blood pressure, metabolism, and mood. Drug Dev. Res. 65:119,125, 2005. © 2005 Wiley-Liss, Inc. [source] Rhythmic expression of clock genes in the ependymal cell layer of the third ventricle of rodents is independent of melatonin signalingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2008Shinobu Yasuo Abstract Reproductive physiology is regulated by the photoperiod in many mammals. Decoding of the photoperiod involves circadian clock mechanisms, although the molecular basis remains unclear. Recent studies have shown that the ependymal cell layer lining the infundibular recess of the third ventricle (EC) is a key structure for the photoperiodic gonadal response. The EC exhibits daylength-dependent changes in the expression of photoperiodic output genes, including the type 2 deiodinase gene (Dio2,). Here we investigated whether clock genes (Per1 and Bmal1) and the albumin D-binding protein gene (Dbp) are expressed in the EC of Syrian hamsters, and whether their expression differs under long-day and short-day conditions. Expression of all three genes followed a diurnal rhythm; expression of Per1 and Dbp in the EC peaked around lights-off, and expression of Bmal1 peaked in the early light phase. The amplitude of Per1 and Dbp expression was higher in hamsters kept under long-day conditions than in those kept under short-day conditions. Notably, the expression of these genes was not modified by exogenous melatonin within 25 h after injection, whereas Dio2 expression was inhibited 19 h after injection. Targeted melatonin receptor (MT1, MT2, and both MT1 and MT2) disruption in melatonin-proficient C3H mice did not affect the rhythmic expression of Per1 in the EC. These data show the existence of a molecular clock in the rodent EC. In the hamster, this clock responds to long-term changes in the photoperiod, but is independent of acute melatonin signals. In mice, the EC clock is not affected by deletion of melatonin receptors. [source] Role of melatonin in mucosal gastroprotection against aspirin-induced gastric lesions in humansJOURNAL OF PINEAL RESEARCH, Issue 4 2010P. C. Konturek Abstract:, Melatonin and its precursor, l -tryptophan, have been shown to exert gastroprotective effects in animals, but their influence on the gastric damage by aspirin (ASA) in humans has been sparingly investigated. In this study, we designed to determine the effects of melatonin and l -tryptophan on ASA-induced gastric mucosal damage, gastric microbleeding, mucosal generation of prostaglandin E2, and plasma melatonin, and gastrin levels. Three groups of healthy male volunteers (n = 30) with intact gastric mucosa received daily for 11 days either ASA alone or that combined with melatonin or tryptophan. Gastric blood loss and mucosal damage were evaluated at 3rd, 7th, and 11th days of ASA administration by endoscopy using Lanza score. ASA alone caused a marked rise of gastric damage and gastric blood loss, mainly at day 3rd and 7th, but they were significantly reduced at 11th day. Pretreatment with melatonin or tryptophan remarkably reduced ASA-induced gastric lesions and microbleeding. Gastric mucosal generation of PGE2 was suppressed by about 90% in all subjects treated with ASA alone without or with addition of melatonin or tryptophan. Plasma melatonin was markedly increased after treatment with melatonin or tryptophan plus ASA, but it was also raised significantly after application of ASA alone. Plasma gastrin levels were raised in subjects given melatonin or tryptophan plus ASA, but not in those with ASA alone. We conclude that melatonin and its precursor tryptophan given orally significantly reduce gastric lesions induced by ASA possibly due to (a) direct gastroprotective action of exogenous melatonin or that generated from tryptophan and (b) gastrin released from the gastric mucosa by melatonin or tryptophan. [source] Melatonin treatment in peri- and postmenopausal women elevates serum high-density lipoprotein cholesterol levels without influencing total cholesterol levelsJOURNAL OF PINEAL RESEARCH, Issue 1 2008Hiroshi Tamura Abstract:, The purpose of this study was to investigate the effects of melatonin on lipid metabolism in peri- and postmenopausal women. Forty-six women were enrolled in these studies. The relationship between night-time serum melatonin levels and serum total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol was investigated in 36 women. Night-time serum melatonin levels had a negative correlation with serum total cholesterol and LDL-cholesterol, and a loose positive correlation with HDL-cholesterol. To examine the effects of exogenous melatonin on lipid metabolism, serum levels of total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were determined in 10 women before the onset of therapy and after 1 month of oral melatonin administration (1 mg melatonin daily). Melatonin administration significantly increased the serum levels of HDL-cholesterol. These results show that melatonin may influence cholesterol metabolism and suggest that the melatonin administration may become a new medical application for improvement of lipid metabolism and prevention of cardiovascular disease in peri- and postmenopausal women. [source] Melatonin reduces uranium-induced nephrotoxicity in ratsJOURNAL OF PINEAL RESEARCH, Issue 1 2007Montserrat Bellés Abstract:, The protective role of exogenous melatonin on U-induced nephrotoxicity was investigated in rats. Animals were given single doses of uranyl acetate dihydrate (UAD) at 5 mg/kg (subcutaneous), melatonin at 10 or 20 mg/kg (intraperitoneal), and UAD (5 mg/kg) plus melatonin (10 or 20 mg/kg), or vehicle (control group). In comparison with the UAD-treated group only, significant beneficial changes were noted in some urinary and serum parameters of rats concurrently exposed to UAD and melatonin. The increase of U excretion after UAD administration was accompanied by a significant reduction in the renal content of U when melatonin was given at a dose of 20 mg/kg. Melatonin also reduced the severity of the U-induced histological alterations in kidney. In renal tissue, the activity of the superoxide dismutase (SOD) and the thiobarbituric acid reactive substances (TBARS) levels increased significantly as a result of UAD exposure. Following UAD administration, oxidative stress markers in erythrocytes showed a reduction in SOD activity and an increase in TBARS levels, which were significantly restored by melatonin administration. In plasma, reduced glutathione (GSH) and its oxidized form (GSSG) were also altered in UAD-exposed rats. However, only the GSSG/GSH ratio was restored to control levels after melatonin treatment. Oxidative damage was observed in kidneys. Melatonin administration partially restored these adverse effects. It is concluded that melatonin offers some benefit as a potential agent to treat acute U-induced nephrotoxicity. [source] Intravenous administration of melatonin reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in ratsJOURNAL OF PINEAL RESEARCH, Issue 3 2007Ming-Yang Lee Abstract:, We have previously shown that exogenous melatonin improves the preservation of the blood,brain barrier (BBB) and neurovascular unit following cerebral ischemia,reperfusion. Recent evidence indicates that postischemic microglial activation exaggerates the damage to the BBB. Herein, we explored whether melatonin mitigates the cellular inflammatory response after transient focal cerebral ischemia for 90 min in rats. Melatonin (5 mg/kg) or vehicle was given intravenously at reperfusion onset. Immunohistochemistry and flow cytometric analysis were used to evaluate the cellular inflammatory response at 48 hr after reperfusion. Relative to controls, melatonin-treated animals did not have significantly changed systemic cellular inflammatory responses in the bloodstream (P > 0.05). Melatonin, however, significantly decreased the cellular inflammatory response by 41% (P < 0.001) in the ischemic hemisphere. Specifically, melatonin effectively decreased the extent of neutrophil emigration (Ly6G-positive/CD45-positive) and macrophage/activated microglial infiltration (CD11b-positive/CD45-positive) by 51% (P < 0.01) and 66% (P < 0.01), respectively, but did not significantly alter the population composition of T lymphocyte (CD3-positive/CD45-positive; P > 0.05). This melatonin-mediated decrease in the cellular inflammatory response was accompanied by both reduced brain infarction and improved neurobehavioral outcome by 43% (P < 0.001) and 50% (P < 0.001), respectively. Thus, intravenous administration of melatonin upon reperfusion effectively decreased the emigration of circulatory neutrophils and macrophages/monocytes into the injured brain and inhibited focal microglial activation following cerebral ischemia,reperfusion. The finding demonstrates melatonin's inhibitory ability against the cellular inflammatory response after cerebral ischemia,reperfusion, and further supports its pleuripotent neuroprotective actions suited either as a monotherapy or an add-on to the thrombolytic therapy for ischemic stroke patients. [source] Melatonin and its precursor, L -tryptophan: influence on pancreatic amylase secretion in vivo and in vitroJOURNAL OF PINEAL RESEARCH, Issue 3 2004Jolanta Jaworek Abstract:, Melatonin, considered as a main pineal product, may be also synthetized in the gastrointestinal tract from l -tryptophan. Melatonin has been recently shown to affect insulin release and its receptors have been characterized in the pancreas however, the effects of melatonin on the pancreatic enzyme secretion have not been examined. The aim of this study was to investigate the effects of melatonin or l -tryptophan on amylase secretion in vivo in anaesthetized rats with pancreato-biliary fistulas, and in vitro using isolated pancreatic acini. Melatonin (1, 5 or 25 mg/kg) or l -tryptophan (10, 50 or 250 mg/kg) given to the rats as a intraperitoneal (i.p.) bolus injection produced significant and dose-dependent increases in pancreatic amylase secretion under basal conditions or following stimulation of enzyme secretion by diversion of bile-pancreatic juice. This was accompanied by a dose-dependent rise in melatonin plasma level. Stimulation of pancreatic enzyme secretion caused by melatonin or l -tryptophan was completely abolished by vagotomy, deactivation of sensory nerves with capsaicin or pretreatment with CCK1 receptor antagonists (tarazepide or l -364,718). Pretreatment with luzindole, an antagonist of melatonin MT2 receptor failed to affect melatonin- or l -tryptophan-induced amylase secretion. Administration of melatonin (1, 5 or 25 mg/kg i.p.) or l -tryptophan (10, 50 or 250 mg/kg i.p.) to the rats resulted in the dose-dependent increase of cholecystokinin (CCK) plasma immunoreactivity. Enzyme secretion from isolated pancreatic acini was not significantly affected by melatonin or l -tryptophan used at doses of10,8,10,5 m. We conclude that exogenous melatonin, as well as that produced endogenously from l -tryptophan, stimulates pancreatic enzyme secretion in vivo while increasing CCK release. Stimulatory effect of melatonin or l -tryptophan on the exocrine pancreas involves vagal sensory nerves and the CCK release by these substances. [source] Stimulatory and entraining effect of melatonin on tuberoinfundibular dopaminergic neuron activity and inhibition on prolactin secretionJOURNAL OF PINEAL RESEARCH, Issue 4 2000Yeh-Shiu Chu The aims of the present study were to determine if melatonin exerts an effect on prolactin (PRL) secretion via the tuberoinfundibular dopaminergic (TIDA) neurons and if endogenous or exogenous melatonin has an entraining effect on the rhythmic changes of TIDA neuronal activity and PRL secretion. Melatonin given in the morning (10:00 h), dose- (0.01,1 mg/kg, ip) and time- (at 15 and 60 min, but not at 30 min) dependently stimulated TIDA neuronal activity in ovariectomized (OVX), estrogen-treated rats as determined by 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the median eminence (ME). Serum PRL was concurrently inhibited by the injection. Melatonin administered in the afternoon (15:00 h) was even more effective in stimulating the lowered TIDA neuronal activity and inhibiting the increased PRL level than that given in the morning (10:00 h). S-20098, a melatonin agonist was also effective in stimulating the TIDA neurons. In contrast, S-20928, a putative melatonin antagonist, while it had no effect by itself, blocked the effect of S-20098. Although S-20928 failed to prevent melatonin's effect on ME DOPAC levels, six interspaced injections of S-20928, from 18:00 to 01:30 h, significantly blocked the increase of ME DOPAC levels at 03:00 h, indicating that the endogenous melatonin may play a role. We further used rats that received daily injection of melatonin (1 mg/kg, ip) at 18:00 h for 10 days and found that the injection augmented basal TIDA neuronal activity at 11:00 h and blunted the afternoon PRL surge. In all, melatonin can have an inhibitory effect on PRL secretion by stimulating the TIDA neurons, and it may help to entrain the circadian rhythms of both TIDA neuronal activity and PRL secretion. [source] Robust circadian rhythm in heart rate and its variability: influence of exogenous melatonin and photoperiodJOURNAL OF SLEEP RESEARCH, Issue 2 2007GILLES VANDEWALLE Summary Heart rate (HR) and heart rate variability (HRV) undergo marked fluctuations over the 24-h day. Although controversial, this 24-h rhythm is thought to be driven by the sleep,wake/rest,activity cycle as well as by endogenous circadian rhythmicity. We quantified the endogenous circadian rhythm of HR and HRV and investigated whether this rhythm can be shifted by repeated melatonin administration while exposed to an altered photoperiod. Eight healthy males (age 24.4 ± 4.4 years) participated in a double-blind cross-over design study. In both conditions, volunteers were scheduled to 16 h,8 h rest : wake and dark : light cycles for nine consecutive days preceded and followed by 29-h constant routines (CR) for assessment of endogenous circadian rhythmicity. Melatonin (1.5 mg) or placebo was administered at the beginning of the extended sleep opportunities. For all polysomnographically verified wakefulness periods of the CR, we calculated the high- (HF) and low- (LF) frequency bands of the power spectrum of the R,R interval, the standard deviation of the normal-to-normal (NN) intervals (SDNN) and the square root of the mean-squared difference of successive NN intervals (rMSSD). HR and HRV variables revealed robust endogenous circadian rhythms with fitted maxima, respectively, in the afternoon (16:36 hours) and in the early morning (between 05:00 and 06:59 hours). Melatonin treatment phase-advanced HR, HF, SDNN and rMSSD, and these shifts were significantly greater than after placebo treatment. We conclude that endogenous circadian rhythmicity influences autonomic control of HR and that the timing of these endogenous rhythms can be altered by extended sleep/rest episodes and associated changes in photoperiod as well as by melatonin treatment. [source] | |||||||||||||