Melatonin Metabolism Research Articles

Gıdalarda Bulunan L-Triptofan, Serotonin, Melatonin Profilleri ve Sağlık Üzerine Etkileri

Nowadays, depending on the progress of science and technology, our eating habits have changed. The shape and quality of nutrition is important for human health. Especially, some food components have various effect on central nervous system such as depression, anxiety, sleep, appetite. Food constituents are transported into the central nervous system via the neutral amino acids such as phenylalanine, leucine, isoleucine, tyrosine and valine. Amino acids have an important role in human nutrition. It cannot be synthesized in the body and one of the essential amino acids that must be taken outside, trytophan, is indispensable in human nutrition because of it has the many functions. In recent years, scientific community concentrated on the various functions of L-Trytophan (L-Trp) as pioneer in the secretion of the hormones serotonin and melatoninin in the human body. The hormones serotonin and melatonin is responsible for activities such as psychology, sleep, body temperature, blood pressure balance, antioxidant effect, cancer inhibitor, sexuality, autism and circadian rhythms in human body that they are available in various foods such as milk, kefir, yogurt, orange, strawberry, grape, olive oil, walnut, prune, nut, pomegranate, coffee, kiwi and banana. In this study, L-Trp, serotonin and melatonin biosynthesis and metabolism, food profiles and in terms of their physiological and biological effects on human health has been compiled.

Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism.

Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin’s synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress.

Predominance of 2-hydroxymelatonin over melatonin in plants.

The cloning of the gene encoding melatonin 2-hydroxylase (M2H), which is responsible for the synthesis of 2-hydroxymelatonin, has expanded the study of melatonin metabolism in plants. Kinetic analysis of M2H enzymatic activity demonstrated that the catalytic efficiency of M2H is much higher than those of other melatonin biosynthetic enzymes such as serotonin N-acetyltransferase (SNAT) and N-acetylserotonin O-methyltransferase (ASMT), suggesting that melatonin metabolism is rapid in plants. To test this prediction, we selected 24 plant species belonging to 16 families and quantified the levels of melatonin and 2-hydroxymelatonin using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The melatonin levels in most of the species were <1 ng/g fresh weight (FW), while those in leaves from radish and feverfew were 3.5 and 3.3 ng/g FW, respectively. In contrast, the average levels of 2-hydroxymelatonin were much higher at 6.2 ng/g FW. The average ratio of 2-hydroxymelatonin to melatonin in plants was approximately 368:1, indicating that the accumulation of 2-hydroxymelatonin predominates over that of melatonin. These data were consistent with previous results on the kinetics of the corresponding enzymes, as well as with in vivo melatonin conversion data. Among several melatonin metabolites in plants, the most abundant metabolite was found to be 2-hydroxymelatonin (99%) followed by 4-hydroxymelatonin (0.05%), but 6-hydroxymelatonin was not detected in rice seedlings.

Molecular cloning of melatonin 2-hydroxylase responsible for 2-hydroxymelatonin production in rice (Oryza sativa).

Although melatonin biosynthetic genes from plants have been cloned, the melatonin catabolism mechanisms remain unclear. To clone the genes responsible for melatonin metabolism, we ectopically expressed 35 full-length cDNAs of rice 2-oxoglutarate-dependent dioxygenase (2-ODD) in Escherichia coli and purified the corresponding recombinant proteins. In vitro 2-ODD assays showed four independent 2-ODD proteins that were able to catalyze melatonin into 2-hydroxymelatonin, exhibiting melatonin 2-hydroxylase (M2H). These M2H proteins had peak activities at pH 8.0 and 30°C. The Km ranged from 121 μm to 371 μm with the Vmax ranging from 1.7 to 18.5 pkat/mg protein, respectively. The M2H enzyme activities were dependent on cofactors such as α-ketoglutarate, ascorbate, and Fe(2+), similar to the 2-ODD enzymes. M2H activity was inhibited by prohexadione-Ca, an inhibitor of 2-ODD, in a dose-dependent manner. M2H activity was high in the roots of rice seedlings, concurrent with high transcription levels of 2-ODD 21, suggesting that 2-ODD 21 was a major gene for M2H activity. Analogous to the high M2H activity in the roots, 2-hydroxymelatonin was found in large quantities in roots treated with melatonin. These results suggest that melatonin was metabolized into 2-hydroxymelatonin by the M2H genes in plants, but the physiological significance of 2-hydroxymelatonin remains to be examined in the future.

Correlation of melatonin and TNF-α levels with characteristics of sleep in patients with rheumatoid arthritis

Specific immune and neuroendocrine factors are considered in the pathogenic mechanisms of sleep disorders in RA. The aim was to investigate the nature of the correlation between sleep disorders and levels of serum melatonin and TNF-α in RA patients. Methods and results. 105 patients and 30 healthy control subjects were examined in the study. Investigation of sleep disorders was conducted by semi-structured clinical interview using the Insomnia severity index (ISI) and with the visual analogue scale (VAS) of sleep disorders. It was found significant differences in the metabolism of melatonin and TNF-α in healthy and RA patients with different variants of insomnia (p <0.01). Differences between the levels of TNF-α and all variants of insomnia (p <0.05) were identified. Conclusion. The lack of a direct relations between melatonin and insomnia in patients with RA indicates complex multifactorial nature of sleep disorders in this pathology.

Aluminum and Glyphosate Can Synergistically Induce Pineal Gland Pathology: Connection to Gut Dysbiosis and Neurological Disease

Many neurological diseases, including autism, depression, dementia, anxiety disorder and Parkinson’s disease, are associated with abnormal sleep patterns, which are directly linked to pineal gland dysfunction. The pineal gland is highly susceptible to environmental toxicants. Two pervasive substances in modern industrialized nations are aluminum and glyphosate, the active ingredient in the herbicide, Roundup?. In this paper, we show how these two toxicants work synergistically to induce neurological damage. Glyphosate disrupts gut bacteria, leading to an overgrowth of Clostridium difficile. Its toxic product, p-cresol, is linked to autism in both human and mouse models. p-Cresol enhances uptake of aluminum via transferrin. Anemia, a result of both aluminum disruption of heme and impaired heme synthesis by glyphosate, leads to hypoxia, which induces increased pineal gland transferrin synthesis. Premature birth is associated with hypoxic stress and with substantial increased risk to the subsequent development of autism, linking hypoxia to autism. Glyphosate chelates aluminum, allowing ingested aluminum to bypass the gut barrier. This leads to anemia-induced hypoxia, promoting neurotoxicity and damaging the pineal gland. Both glyphosate and aluminum disrupt cytochrome P450 enzymes, which are involved in melatonin metabolism. Furthermore, melatonin is derived from tryptophan, whose synthesis in plants and microbes is blocked by glyphosate. We also demonstrate a plausible role for vitamin D3 dysbiosis in impaired gut function and impaired serotonin synthesis. This paper proposes that impaired sulfate supply to the brain mediates the damage induced by the synergistic action of aluminum and glyphosate on the pineal gland and related midbrain nuclei.

Phase advance of circadian rhythms in Smith–Magenis syndrome: A case study in an adult man

Melatonin secretion is usually increased during the daytime and decreased at night in Smith–Magenis syndrome (SMS) and consequently is not a pertinent marker of the circadian phase of the clock in these cases. No data on temperature rhythm is available in SMS, another reliable marker of circadian clock activity. For this reason, we assessed the 24h profiles of core temperature, sleep–wake cycle, hormones (plasma cortisol and melatonin) and plasma and urine 6sulfatoxy-melatonin, the main hepatic melatonin metabolism in a 31-year-old man diagnosed with a SMS. All circadian rhythms, especially temperature rhythm showed a phase-advance, associated with reverse melatonin secretion. Plasma and urine 6sulfatoxy-melatonin profiles showed normal melatonin catabolism and confirmed the reversed melatonin secretion. Taking in consideration the reverse melatonin secretion and the phase-advanced temperature rhythm, which is driven by the suprachiasmatic nucleus, we hypothesize that the central clock is more sensitive to afternoon than to morning melatonin. This different responsiveness to melatonin according to the time of the day (i.e. chronaesthesia) corroborates the phase response curve of melatonin secretion to exogenous melatonin.

Colorectal Cancer Risk, Genetic Susceptibility and Night Shift Work in a Population-Based Case-Control Study in Spain

Background and aims: Epidemiological studies on shift work have focused on breast cancer while evidence on other tumors is limited. We evaluated colorectal cancer risk in relation to shift work and genetic susceptibility in a population based case-control study in Spain (MCC-Spain study). Methods: 1066 male and 592 female incident colorectal cancer cases and 3388 randomly selected population controls in 11 regions of Spain were included. Information was collected on socio-demographic, lifestyle, medical history and other variables by face-to- face interviews. Lifetime occupational history on daily time schedules, day/night/rotating shifts shift-work intensity and duration of each job was examined. We used unconditional logistic regression analysis adjusting for potential confounders. We examined gene- environment interactions with genes in circadian rhythm pathways and melatonin metabolism testing simultaneously the main effect and the GxE interaction (2 d.f test). Results: Among controls 10% of males and 4% of females had ever worked full time in permanent night shifts (working between midnight and 6am) and 24% of males and 14% of females in rotating shifts for =1 year. Having ever performed rotating shift work was associated with an increased risk for colorectal cancer (adjusted Odds Ratio 1.33, 95%CI 1.15-1.55) compared to permanent day workers. ORs increased with cumulative years of rotating shift work and the OR for more than 30 years work was 1.54 (1.22-1.94). Having ever worked in permanent night shift was not associated with colorectal cancer risk. We observed nominal interactions between ever night shift work and several SNPs in circadian genes including PER2, TPH2, ARNTL2 although individual SNP associations did not remain statistically significant after Bonferroni correction. Conclusions: In this large population based study we found an increase in colorectal cancer risk in shift workers and an indication of interaction with genes in circadian pathways.

Melatonin in sperm biology: breaking paradigms.

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, RORα1, RORα2 and RZRβ. 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.

Local melatoninergic system as the protector of skin integrity.

The human skin is not only a target for the protective actions of melatonin, but also a site of melatonin synthesis and metabolism, suggesting an important role for a local melatoninergic system in protection against ultraviolet radiation (UVR) induced damages. While melatonin exerts many effects on cell physiology and tissue homeostasis via membrane bound melatonin receptors, the strong protective effects of melatonin against the UVR-induced skin damage including DNA repair/protection seen at its high (pharmocological) concentrations indicate that these are mainly mediated through receptor-independent mechanisms or perhaps through activation of putative melatonin nuclear receptors. The destructive effects of the UVR are significantly counteracted or modulated by melatonin in the context of a complex intracutaneous melatoninergic anti-oxidative system with UVR-enhanced or UVR-independent melatonin metabolites. Therefore, endogenous intracutaneous melatonin production, together with topically-applied exogenous melatonin or metabolites would be expected to represent one of the most potent anti-oxidative defense systems against the UV-induced damage to the skin. In summary, we propose that melatonin can be exploited therapeutically as a protective agent or as a survival factor with anti-genotoxic properties or as a “guardian” of the genome and cellular integrity with clinical applications in UVR-induced pathology that includes carcinogenesis and skin aging.

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

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.

Sleep disruption in tetraplegia: a randomised, double-blind, placebo-controlled crossover trial of 3 mg melatonin

Randomised, double-blind, placebo-controlled crossover trial of melatonin supplementation to people with complete tetraplegia. To investigate the effect that 3 mg melatonin supplementation has on objective and subjective sleep, quality of life and mood of people living with complete tetraplegia. Austin Hospital Sleep Laboratory and participants' homes, Melbourne, Victoria, Australia. Two week run-in followed by 3 week nightly administration of 3 mg melatonin or placebo, 2-week washout and further 3 week administration of the opposite treatment. Four testing sessions were conducted; the last nights of the run-in, treatment and washout periods. Testing sessions involved recording full polysomnography, completing a questionnaire battery and collecting urine and blood samples. The questionnaires assessed mood, sleep symptoms and health-related quality of life, and the urine and plasma samples assayed 6-sulphatoxymelatonin (aMT6s) and melatonin levels, respectively. A sleep diary was completed throughout the study. Eight participants (mean (s.d.): age 49.5 years (16), postinjury 16.9 years (7.1)) were recruited in which seven concluded the protocol. Endogenous-circulating melatonin was significantly higher (P < or = 0.01) following melatonin (urine: 152.94 μg h(-1) (74.51), plasma: 43,554.57 pM (33,527.11)) than placebo (urine: 0.86 μg h(-1) (0.40), plasma: 152.06 pM (190.55)). Subjective sleep improved significantly following melatonin specifically for duration of sleep per night and psychological wellbeing. Objective sleep showed a significant increase in light sleep with melatonin, with all other sleep parameters being unchanged. These results suggest that increasing melatonin in people with complete tetraplegia is beneficial, especially for subjective sleep. Investigation of the pharmacokinetics of melatonin metabolism in this population is warranted. This project is proudly supported by the Transport Accident Commission.

Potential drug interactions with melatonin

Possible interactions of melatonin with concurrently administered drugs were investigated in in vitro studies utilising human hepatic post-mitochondrial preparations; similar studies were conducted with rat preparations to ascertain whether rat is a suitable surrogate for human. Drugs were selected based not only on the knowledge that the 6-hydroxylation of exogenous melatonin, its principal pathway of metabolism, is mainly mediated by hepatic CYP1A2, but also on the likelihood of the drug being concurrently administered with melatonin. Hepatic preparations were incubated with either melatonin or 6-hydroxymelatonin in the presence and absence of a range of concentrations of interacting drug, and the production of 6-sulphatoxymelatonin monitored using a radioimmunoassay procedure. Of the drugs screened, only the potent CYP1A2 inhibitor 5-methoxypsoralen impaired the 6-melatonin hydroxylation at pharmacologically relevant concentrations, and is likely to lead to clinical interactions; diazepam, tamoxifen and acetaminophen (paracetamol) did not impair the metabolic conversion of melatonin to 6-sulphatoxymelatonin at concentrations attained following therapeutic administration. 17-Ethinhyloestradiol appeared not to suppress the 6-hydroxylation of melatonin but inhibited the sulphation of 6-hydroxymelatonin, but this is unlikely to result in an interaction following therapeutic intake of the steroid. Species differences in the inhibition of melatonin metabolism in human and rat hepatic post-mitochondrial preparations were evident implying that the rat may not be an appropriate surrogate of human in such studies.

Melatonin alterations and brain acetylcholine lesions in sleep disorders in Cockayne syndrome

Cockayne syndrome (CS) is a genetic disorder caused by deficient nucleotide excision repair. Patients with CS exhibit progeroid features, developmental delay, and various neurological disorders; they are also known to suffer from sleep problems, which have never been investigated in detail. The aim of this study is to investigate the pathogenesis of sleep disorders in patients with CS. We performed a questionnaire survey of the families of patients with CS, enzyme-linked immunosorbent analyses of the melatonin metabolite, 6-sulphatoxymelatonin (6-SM), in the patients' urine, and immunohistochemistry in the hypothalamus, the basal nucleus of Meynert (NbM), and the pedunculopontine tegmental nucleus (PPN) in four autopsy cases. Sleep-wakefulness rhythms were disturbed in patients with CS, and these disturbances seemed to be related to a reduced urinary excretion of 6-SM. In addition, although the hypothalamic nuclei were comparatively preserved, acetylcholine neurons (AchNs) were severely decreased in the NbM and PPN. AchNs modulate both arousal and rapid eye movement sleep, and selective lesions of AchNs in the PPN and/or NbM in combination with disturbed melatonin metabolism might be involved in the sleep disorders in CS.

Sleep-wake abnormalities in patients with cirrhosis

A considerable proportion of patients with cirrhosis exhibit insomnia, delayed sleep habits, and excessive daytime sleepiness. These have been variously attributed to hepatic encephalopathy and impaired hepatic melatonin metabolism, but the understanding of their pathophysiology remains limited and their treatment problematic. Sleep is regulated by the interaction of a homeostatic and a circadian process. The homeostatic process determines sleep propensity in relation to sleep-wake history, thus the need to sleep increases with the duration of the waking period. The circadian process, which is marked by the 24-hour rhythm of the hormone melatonin, is responsible for the alternation of high/low sleep propensity in relation to dark/light cues. Circadian sleep regulation has been studied in some depth in patients with cirrhosis, who show delays in the 24-hour melatonin rhythm, most likely in relation to reduced sensitivity to light cues. However, while melatonin abnormalities are associated with delayed sleep habits, they do not seem to offer a comprehensive explanation to the insomnia exhibited by these patients. Fewer data are available on homeostatic sleep control: it has been recently hypothesized that patients with cirrhosis and hepatic encephalopathy might be unable, due to excessive daytime sleepiness, to accumulate the need/ability to produce restorative sleep. This review will describe in some detail the features of sleep-wake disturbances in patients with cirrhosis, their mutual relationships, and those, if any, with hepatic failure/hepatic encephalopathy. A separate section will cover the available information on their pathophysiology. Finally, etiological treatment will be briefly discussed.

In-silico study of arylalkylamine-nacetyltransferase enzyme to regulate circadian rhythmicity.

Circadian Rhythmicity is present in the sleeping and breeding patterns of animals, including human beings and also related with brain wave activity, hormone production, cell regeneration and other biological activities. Melatonin is thought to play important roles in regulating circadian rhytmicity of the animals. Arylalkylamine-N-acetyltransferase (AANAT) is an enzyme which is responsible for the melatonin metabolism. In this study AANAT enzyme is targeted for the control of sleeping sickness and other irregular circadian rhythmicity by regulating the melatonin formation. AANAT protein 3D-structure was modeled, followed by loop modeling, refinement through energy minimization processes by molecular dynamics simulation and validation. Analysis of the Ramachandran plot shows 90.9% amino acids falls in the allowed region. The modeled protein was docked with N-Acetyl Serotonin. Combinatorial library was generated by using N-Acetyl Serotonin as a reference molecule and molecules having 80% similarity to N-Acetyl Serotonin was selected from Zinc database. These molecules were virtually screened by MOLEGRO virtual docker and top 5 molecules were selected and docked by using AutoDock. The AutoDock result shows that the ZINC01587152 molecule is having best interactions with the receptor protein. On the basis of this study we can suggest that the ZINC01587152 molecule is the best ligand against AANAT enzyme. It may be further synthesized and tested for sleep related disorders.

Metabolism of melatonin and biological activity of intermediates of melatoninergic pathway in human skin cells

Indolic and kynuric pathways of skin melatonin metabolism were monitored by liquid chromatography mass spectrometry in human keratinocytes, melanocytes, dermal fibroblasts, and melanoma cells. Production of 6-hydroxymelatonin [6(OH)M], N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) and 5-methoxytryptamine (5-MT) was detected in a cell type-dependent fashion. The major metabolites, 6(OH)M and AFMK, were produced in all cells. Thus, in immortalized epidermal (HaCaT) keratinocytes, 6(OH)M was the major product with Vmax = 63.7 ng/10(6) cells and Km = 10.2 μM, with lower production of AFMK and 5-MT. Melanocytes, keratinocytes, and fibroblasts transformed melatonin primarily into 6(OH)M and AFMK. In melanoma cells, 6(OH)M and AFMK were produced endogenously, a process accelerated by exogenous melatonin in the case of AFMK. In addition, N-acetylserotonin was endogenously produced by normal and malignant melanocytes. Metabolites showed selective antiproliferative effects on human primary epidermal keratinocytes in vitro. In ex vivo human skin, both melatonin and AFMK-stimulated expression of involucrin and keratins-10 and keratins-14 in the epidermis, indicating their stimulatory role in building and maintaining the epidermal barrier. In summary, the metabolism of melatonin and its endogenous production is cell type-dependent and expressed in all three main cell populations of human skin. Furthermore, melatonin and its metabolite AFMK stimulate differentiation in human epidermis, indicating their key role in building the skin barrier.

Melatonin secretion and metabolism in patients with hepatic encephalopathy

The rhythm of melatonin secretion and its blood level changes in cirrhotic patients, but the causes of these alterations have not been sufficiently appreciated. The aim of study was to estimate the dependence between melatonin secretion and metabolism and the severity of hepatic encephalopathy. The study included 75 alcoholic cirrhotic patients (A, B, C) with hepatic insufficiency and 25 healthy subjects (group K). Three groups of patients were identified, 25 patients each, with grade 1, 2, and 3 hepatic encephalopathy according to West-Haven Scale. Immunoenzymatic method was used to measure serum melatonin (at 02:00 h and 09:00 h) level and 6-sulfatoxymelatonin (6-HMS) excretion in the urine (during night and day). Nocturnal serum melatonin levels (pg/mL) in groups were: K-57.1 ± 11.4, A-38.5 ± 11.2, B-53.4 ± 17.9, C-79.5 ± 27.9 (P < 0.01); whereas diurnal levels were: K-10.9 ± 3.5, A-33.5 ± 12.0, B-53.8 ± 23.1, C-98.5 ± 34.6 (P < 0.01). Similar differences were found in the evaluation of 6-HMS excretion (μg/9 h) in urine at night: group K-23.4 ± 14.4, A-16.6 ± 5.4, B-14.3 ± 6.2 (P < 0.01), C-3.3 ± 1.5 (P < 0.001). Diurnal 6-HMS excretion (μg/15 h) was lower only in group C and it was respectively: K-6.9 ± 3.4, A-7.1 ± 1.7, B-7.6 ± 1.7, C-4.3 ± 2.2 (P < 0.001). Serum ammonia concentrations (μg/dL) were: group K-30.4 ± 8.9, A-51.8 ± 25.4 (P < 0.05), B-73.0 ± 29.8 (P < 0.001), C-107.5 ± 34.8 (P < 0.001). No correlation between melatonin and ammonia levels in all groups was found. The elevated melatonin blood levels both at night and day may account for some of the clinical manifestations of hepatic encephalopathy (daytime sleepiness, fatigue).

Perioperative plasma melatonin concentration in postoperative critically ill patients: Its association with delirium

PurposeDelirium is a common complication in postoperative critically ill patients. Although abnormal melatonin metabolism is thought to be one of the mechanisms of delirium, there have been few studies in which the association between alteration of perioperative plasma melatonin concentration and postoperative delirium was assessed. MaterialsWe conducted a prospective observational study to assess the association of perioperative alteration of plasma melatonin concentration with delirium in 40 postoperative patients who required intensive care for more than 48 hours. We diagnosed postoperative delirium using Confusion Assessment Method for the intensive care unit and measured melatonin concentration 4 times (before the operation as the preoperative value, 1 hour after the operation, postoperative day 1, and postoperative day 2). ResultsPostoperative delirium occurred in 13 (33%) of the patients. Although there was no significant difference in preoperative melatonin concentration, Δ melatonin concentration at 1 hour after the operation was significantly lower in patients with delirium than in those without delirium (−1.1 vs 0 pg/mL, P = .036). After adjustment of relevant confounders, Δ melatonin concentration was independently associated with risk of delirium (odds ratio, 0.50; P = .047). ConclusionsDelta melatonin concentration at 1 hour after the operation has a significant independent association with risk of postoperative delirium.

Disturbance in melatonin metabolism as a causative factor for recurrent headaches in a girl with a pineal cyst?

Disturbance in melatonin metabolism as a causative factor for recurrent headaches in a girl with a pineal cyst?