aMT6s In Urine Research Articles

Melatonin exchange in infertile women with repeated implantation failures

Background. Repeated implantation failure occurs in approximately 10–15% of women undergoing in vitro fertilization and embryo transfer (IVF-ET) cycles. One of the important factors is the changed morpho-functional state of the endometrium and chronodestruction in the woman’s body. Objective of the study: to determine the characteristics of melatonin (MT) metabolism in infertile women with repeated implantation failures in IVF-ET cycles. Material and methods. 103 women of reproductive age with infertility and repeated implantation failures who were treated in IVF-ET cycles were observed. Depending on the onset of pregnancy in the current IVF-ET cycle, women were divided into 2 groups: group A – 35 women with the onset of pregnancy, group B – 68 patients without the onset of pregnancy. The control group (group C) included 32 healthy fertile women. The MT level in blood serum and 6-sulfatoxymelatonin (aMT6s) in urine was determined. Results. The initial levels of MT in patients of group A (11.38 ± 0.38 pg/ml) and in group B (9.55 ± 0.27 pg/ml) were lower than in group C (13.67 ± 0.65 pg/ml) in 1.20 (p < 0.01) and 1.43 (p < 0.01) times, respectively. At the same time, the level of MT in women of group A was 1.19 times higher than in the group B (p < 0.03). Excretion of aMT6s in urine in group A (5.09 ± 0.19 ng/ml Cr) and in group B (3.03 ± 0.09 ng/ml Cr) were lower than in group C (6.12 ± 0.21 ng/ml Cr) respectively in 1.20 (p < 0.01) and 2.02 (p < 0.01) times. The aMT6s concentration in urine in patients of group A was 1.68 times higher than in group B (p < 0.01). A direct relationship was established between the levels of serum MT and urinary aMT6s, which was most adequately approximated by a polynomial dependence: y = 0.0139x2 – 0.1127x + 3.2978, R² = 0.2994, r = 0.51, p < 0.01. Conclusions. Women with repeated implantation failures are characterized by a decrease in the level of MT in blood serum and its main metabolite aMT6s in urine, which may be one of the key factors of implantation failure.

Association between nocturnal light exposure and melatonin in humans: a meta-analysis.

Night shift workers are more susceptible to circadian rhythm disturbances due to their prolonged exposure to nighttime light. This exposure during abnormal periods causes inappropriate suppression of melatonin synthesis and secretion in the pineal gland, thereby disrupting circadian rhythms. While it is believed that nocturnal light exposure is involved in suppressing melatonin secretion, research findings in this area have been inconsistent. Thirteen publications retrieved from PubMed and Web of Science databases were included to compare the differences between night shift workers and controls using aggregated mean differences (MD) and 95% confidence intervals (CI). After a comprehensive review, 13 publications were included and data on urinary melatonin metabolite 6-sulfameoxymelatonin(aMT6s) were collected for meta-analysis. The results showed that the morning urinary aMT6s levels were significantly lower in the exposed group than in the non-exposed group (MD = -3.69, 95%CI = (-5.41, -1.98), P < 0.0001), with no significant heterogeneity among the original studies (I2 = 42%, P = 0.13). In addition, night shift workers had significantly lower mean levels of 24-h urinary aMT6s than day shift workers (MD = -3.38, 95%CI = (-4.27, -2.49), P < 0.00001, I2 = 0). Nocturnal light was correlated with nocturnal urine aMT6s secretion and inhibited nocturnal aMT6s secretion (MD = -11.68, 95%CI = (-15.70, -7.67), P < 0.00001, I2 = 0). Additionally, nocturnal light inhibited the secretion of melatonin in the blood, with no significant heterogeneity between studies (MD = -11.37, 95%CI = (-15.41, -7.33), P < 0.00001, I2 = 0). The findings of this study indicate that exposure to nocturnal light among night shift workers leads to inhibition of melatonin secretion.

Subchronic Low-Dose Methylmercury Exposure Accelerated Cerebral Telomere Shortening in Relevant with Declined Urinary aMT6s Level in Rats

Methylmercury (MeHg) is a global pollutant with established toxic effects on the central nervous system (CNS). However, early events and early-warning biomarkers of CNS damage following exposure to low-dose MeHg are still lacking. This study aimed to investigate whether subchronic low-dose MeHg exposure had adverse effects on the cerebral telomere length, as well as serum melatonin and its urinary metabolite 6-sulfatoxymelatonin (aMT6s) in rats. Sixteen male Sprague Dawley rats were divided into two groups. Group I was the control group. In group II, rats were exposed to MeHg by gavage at a dose of 0.1 mg/kg/day for 3 months. This study revealed that MeHg exposure resulted in impairment of learning and memory ability, a slightly reduced number of neurons and an irregular arrangement of neurons in the hippocampus. It also significantly accelerated telomere shortening in the cerebral cortex, hippocampus and hypothalamus. Moreover, MeHg exposure decreased the levels of melatonin in serum and aMT6s in urine, partly by suppressing the synthesis of 5-hydroxytryptamine (5-HT) in the brain but promoted the expression of melatonin-catalyzing AANAT and ASMT. Importantly, cerebral telomere length was positively correlated with MT and aMT6s after MeHg exposure. These results suggested that the shortened telomere length in the brain may be an early event in MeHg-induced CNS toxicity, and the level of aMT6s in urine may serve as an early-warning biomarker for MeHg-induced CNS damage.

Meta-analysis of melatonin levels in cluster headache-Review of clinical implications.

Cluster headache (CH) has been associated with circadian disturbances. The present systematic review examined available evidence for the utilization of melatonin (MT) in CH prophylaxis. First, case-control studies assessing nocturnal MT or its urine-expelled metabolite 6-sulfatoxymelatonin (aMT6s) in CH individuals and healthy controls (HC) were reviewed and meta-analyzed. Secondly, the results from randomized controlled trials (RCTs) and non-randomized studies evaluating MT's use in the prevention of CH were discussed. Literature search included MEDLINE, EMBASE, CENTRAL, PsycINFO, trial registries, Google Scholar, and OpenGrey. Bouts and remissions were assessed separately. Ten case-control studies (adult participants) were retrieved. Seven evaluated serum MT; meta-analysis involved only three of them (due to deficient reporting, n: bout=31, remission=38, HC=31). Results were compatible with lower nocturnal serum MT levels during bouts [bout-HC; FE-MD=-29.89pg/mL, 95% CI=(-46.00, -13.78), remission-HC; FE-MD=-2.40pg/mL, 95% CI=(-16.57, 21.38), bout-remission; RE-MD=-32.10pg/mL, 95% CI=(-56.78, -7.42)]. Nocturnal urinary melatonin was appraised in two studies, but reporting issues impeded the capitalization of the results. Nocturnal urine aMT6s was evaluated by two studies (n: bout=29, remission=22, HC=20), and pooled results were indicative of lower aMT6s concentration in CH individuals during both active and inactive periods [bout-HC; FE-MD=-9.63μg/nocturnal urine collection, 95% CI=(-14.40, -4.85), remission-HC; FE-MD=-9.12μg/nocturnal urine collection, 95% CI=(-14.63,-3.62), bout-remission; FE-MD=-0.58μg/nocturnal urine collection, 95% CI=(-4.58, 3.42)]. Regarding CH prophylaxis, one RCT and two non-randomized trials were retrieved, involving a total of 41 adult CH individuals (11-episodic, 31-chronic) and rendering the deduction of any conclusions precarious. Overall, available data for the role use of MT in CH are insufficient and inconclusive. Complementary studies evaluating endogenous MT concentrations and MT administration to patients with CH are warranted.

Melatonin Levels in Preterm and Term Infants and Their Mothers.

The prevention of perinatal brain damage following preterm birth remains a public health priority. Melatonin has been shown to be a promising neuroprotectant in neonatal preclinical models of brain damage, but few studies have investigated melatonin secretion in newborns. We hypothesized that melatonin circulating levels would be lower in preterm compared to term infants. We conducted a prospective, longitudinal, multicenter study to assess melatonin, and 6-sulfatoxy-melatonin (aMT6s) concentrations, measured by radioimmunoassay. Among 209 neonates recruited, 110 were born before 34 gestational weeks (GW) and 99 born after 34 GW. Plasma melatonin concentrations, measured at birth and on Day 3 were below detectable levels (≤7 pg/mL) in 78% and 81%, respectively, of infants born before 34 GW compared to 57% and 34%, respectively, of infants born after 34 GW. The distribution of plasma melatonin concentrations was found to be correlated with gestational age at both time-points (p < 0.001). Median urine aMT6s concentrations were significantly lower in infants born before 34 GW, both on Day 1 (230 ng/L vs. 533 ng/L, p < 0.0001) and on Day 3 (197 ng/L vs. 359 ng/L, p < 0.0001). In conclusion, melatonin secretion appears very low in preterm infants, providing the rationale for testing supplemental melatonin as a neuroprotectant in clinical trials.

Seasonal fluctuation in the secretion of the antioxidant melatonin is not associated with alterations in sperm DNA damage.

A high sperm DNA fragmentation index (DFI) is associated with reduced fertility. DFI is influenced by the balance between reactive oxygen species and antioxidants. A circannual variation in melatonin, an antioxidant and free radical scavenger, could thus impact semen quality and fertility. The association between the major melatonin metabolite, urine 6-sulfatoxymelatonin (aMT6s), and DFI was analyzed in 110 Oslo men (south of the Arctic Circle) and 86 Tromsoe men (north of the Arctic Circle). Two semen analyses, summer and winter, and four urine samples (early/late summer; early/late winter), were analyzed. The associations between aMT6s in urine and DFI were characterized in a cross-sectional and longitudinal manner using correlation analysis and linear regression. Regardless of season and location, no significant correlations between aMT6s and DFI were observed. The correlation coefficients for associations between changes over time (early winter–early summer) in aMT6s and DFI were for the total cohort: rho = −0.08 (P = 0.322), for the Oslo cohort: rho = −0.07 (P = 0.485), and for the Tromsoe cohort: rho = −0.14 (P = 0.273), respectively. Similar results were seen when comparing late winter and late summer. There was no any statistically significant correlation between changes over time in aMT6s and DFI for men with DFI below and above the median value (10%), respectively. The seasonal variation in melatonin excretion seems not to have any impact on DFI.

Disturbed sleep in individuals with idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF): Melatonin assessment as a biological marker.

Individuals who suffer from idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF) complain of a variety of adverse health effects. Troubled sleep remains a recurrent and common symptom in IEI-EMF individuals. Melatonin, a circadian hormone, plays a major role in the sleep process. In this study, we compared levels of melatonin between a sensitive group (IEI-EMF, n = 30) and a non-sensitive control group (non IEI-EMF, n = 25) without exposure to electromagnetic sources. Three questionnaires were used to evaluate the subjective quality and sleep quantity: the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index and the Spiegel Sleep Inventory. Melatonin was quantified in saliva and its major metabolite 6-sulfatoxymelatonin (aMT6s) in urine. Melatonin levels were compared by a two-way analysis of variance at various times between the control and IEI-EMF group. Despite significantly different sleep scores between the two groups, with a lower score in the IEI-EMF group (P < 0.001), no statistical difference was found between the two groups for saliva melatonin (P > 0.05) and urine aMT6s (P > 0.05). Bioelectromagnetics. 37:175-182, 2016. © 2016 Wiley Periodicals, Inc.

Study of prevention and control of delirium in ventilated patients by simulating blockage of circadian rhythm with sedative in intensive care unit

To explore the effect of giving sedatives according to the circadian rhythm in prevention of occurrence of delirium and the prognosis of patients undergoing mechanical ventilation in intensive care unit (ICU). A prospective double-blinded randomized controlled trial (RCT) was conducted. The patients admitted to Department of Critical Care Medicine of the Second Hospital of Lanzhou University from July 2014 to February 2015, undergoing invasive mechanical ventilation over 12 hours were enrolled. All the patients were given fentanyl for analgesia, and they were randomly divided into simulated circadian clock group (study group, n = 35) and non-simulated circadian clock group (control group, n = 35). The patients in each group were subdivided into three subgroups according to the kinds of sedative drugs, namely dexmedetomidine group (n = 8), propofol group (n = 14), and dexmedetomidine combined with propofol group (combination group, n = 13). Visual analogue scale (VAS) standard and Richmond agitation-sedation scale (RASS) were used to control the analgesic and to quantify the depth of sedation by titrating the dose of sedative drugs, the simulated circadian clock was set to control the RASS score at 0-1 during the day, and -1 to -2 at night in study group. The RASS score in the control group was set at -1 to -2 day and night. The urine 6-hydroxy acid melatonin (aMT6s) levels at different time points in the first diurnal rhythm (06:00, 12:00, 18:00, 24:00) were determined by enzyme linked immunosorbent assay (ELISA). The incidence of delirium, severe hypotension, severe bradycardia and other adverse reactions, duration of mechanical ventilation and the time of extubation, length of ICU stay, amount of sedative and analgesic drugs used were recorded. The correlation between delirium and other indexes was analyzed by using Spearman correlation analysis. (1) There were no significant differences in gender, age, acute physiology and chronic health evaluation II (APACHEII) score among groups. (2) Urine aMT6s levels did not show circadian rhythm in both groups, aMT6s level at 06:00 in study group showed an increasing tendency as compared with the control group, but the difference was not statistically significant. (3) Compared with the control group, the incidence of delirium was significantly lowered in the study group (14.3% vs. 37.1%, P = 0.029), but no significant differences were found in the incidence of severe hypotension or severe bradycardia (20.0% vs. 25.7%, 11.4% vs. 20.0%, both P > 0.05). In simulated circadian clock group, the incidence of delirium in dexmedetomidine group was significantly lower than that of the propofol group (6.3% vs. 32.1%, P < 0.05). (4) Compared with control group with the same sedative, the duration of mechanical ventilation, extubation time, length of ICU stay were significantly shortened, and the dosage of sedative drugs used was reduced in study group (all P < 0.05). In simulated circadian clock group, the duration of mechanical ventilation in dexmedetomidine group was significantly shorter than that of propofol group and combination group (hours: 75.75±26.78 vs. 102.00±26.31 and 100.31±25.38, both P < 0.05), and the length of ICU stay was significantly shorter than that of propofol group (days: 5.75±1.04 vs. 7.00±1.52, P < 0.05). (5) The occurrence of delirium was positively correlated with duration of mechanical ventilation (r = 0.705), extubation time (r = 0.704), length of ICU stay (r = 0.666, all P = 0.000), and no correlation was found between the occurrence of delirium and aMT6s level at 06:00, 12:00, 18:00, and 24:00 (r = -0.135, r = 0.163, r = 0.269, r = -0.077, all P > 0.05). Administration of sedatives according to simulating circadian time could decrease the duration of mechanical ventilation, extubation time, and the length of ICU stay, decrease the dosage of sedative drugs, and reduce the incidence of delirium. Dexmedetomidine could reduce the incidence of delirium, and improve the prognosis of patients.

Urine 6-sulfatoxymelatonin levels are inversely associated with arterial stiffness in post-menopausal women

ObjectThe secretion of melatonin, a pleiotropic hormone mainly synthesized by the pineal gland, typically decreases with age and may be associated with the development of aging-related pathologic conditions such as cardiovascular disease. Atherosclerosis is an aging-related disease, the pathogenesis of which involves chronic inflammation and increased oxidative stress. Since melatonin has both anti-oxidant and anti-inflammatory properties, it may be associated with atherosclerosis. Therefore, we investigated the relationship between urine concentrations of 6-sulfatoxymelatonin (aMT6s) and arterial stiffness in post-menopausal women. MethodsA total of 66 post-menopausal women participated in the study. Melatonin secretion was estimated by measuring aMT6s levels in first morning urine samples. The cardio-ankle vascular index (CAVI) was used as an indicator of arterial stiffness. ResultsEstimated mean CAVI decreased gradually with increasing aMT6s quartiles. The multivariate logistic regression analysis showed that the fourth aMT6s quartile was associated with a high CAVI with an adjusted odds ratio of 0.03 (95% confidence interval, 0.01–0.47). ConclusionOur study revealed an inverse relationship between urine aMT6s and arterial stiffness as determined by CAVI. Although it is impossible to determine causality, our results suggest that melatonin may have a beneficial role in the pathogenesis of atherosclerosis. Further prospective studies are required to establish the clinical significance of our study.

Urine melatonin levels are inversely associated with sarcopenia in postmenopausal women

Mainly secreted in the pineal gland, melatonin is a neurohormone that has versatile functions, including cellular protection. Decreased melatonin levels are associated with the aging process and age-related conditions. Melatonin may be associated with sarcopenia because it is one of the most common age-related diseases and because disrupted cellular vitality in skeletal muscle is known to be involved in its pathogenesis. Therefore, we investigated the relationship between first-morning-urine 6-sulfatoxymelatonin (aMT6s) levels and sarcopenia in Korean postmenopausal women. Seventy-eight Korean postmenopausal women participated. Biomarkers of metabolic risk factors, along with the presence of sarcopenia, were assessed using dual-energy x-ray absorptiometry. Urine aMT6s levels were measured using enzyme-linked immunosorbent assay. The prevalence of sarcopenia increased significantly with increasing aMT6s quartiles. Furthermore, multivariate logistic regression analysis showed that the fourth aMT6s quartile was associated with sarcopenia, with an adjusted odds ratio of 0.13 (95% CI, 0.03-0.70; P = 0.02). Our study shows an inverse association between urine melatonin and sarcopenia, suggesting that melatonin may have a protective role in the pathophysiology of sarcopenia. Further studies are required to better understand the clinical significance of our findings.

Dietary Intake of Melatonin from Tropical Fruit Altered Urinary Excretion of 6-Sulfatoxymelatonin in Healthy Volunteers

This study assessed the melatonin content of six tropical fruits and examined whether human consumption could contribute to dietary melatonin as measured by 6-sulfatoxymelatonin (aMT6-s, a marker of circulating melatonin in the body). Melatonin was extracted using methanol and analyzed by high-performance liquid chromatography. In a clinical crossover study, 30 healthy volunteers consumed selected fruits one at a time, with a 1week wash-out period between fruits, until completing all six fruits. Most fruits had moderate melatonin content. Significant increases in urine aMT6-s concentrations were seen after the consumption of pineapple (266%, p = 0.004), banana (180%, p = 0.001), and orange (47%, p = 0.007). The need to analyze melatonin both in fruit and as in vivo uptake was demonstrated. Further study is warranted regarding the clinical effect of fruit consumption in people with age-related melatonin reduction problems such as sleeplessness and illnesses involving oxidative damage.

6‐Sulfatoxymelatonin as a predictor of clinical outcome in depressive patients

This study established the value of the 6‐sulfatoxymelatonin (aMT6s) urine concentration as a predictor of the therapeutic response to noradrenaline reuptake inhibitors in depressive patients. Twenty-two women aged 18-60 years were selected. Depressive symptoms were assessed by using the Hamilton Depression Scale. Urine samples were collected at 0600-1200 h, 1200-1800 h, 1800-2400 h, and 2400-0600 h intervals, 1 day before and 1 day after starting on the nortriptyline treatment. Urine aMT6s concentration was analyzed by a one-way analysis of variance/Bonferroni test. Spearman's rank correlation coefficient was used to analyze the correlation between depressive symptoms after 2 weeks of antidepressant treatment and the increase in aMT6s urine concentration. Higher and lower size effect groups were compared by independent Student's t-tests. At baseline, the 2400‐ to 0600‐h interval differed from all other intervals presenting a significantly higher aMT6s urine concentration. A significant difference in aMT6s urine concentrations was found 1 day after treatment in all four intervals. Higher size effect group had lower levels of depressive symptoms 2 weeks after the treatment. A positive correlation between depressive symptoms and the delta of aMT6s in the 2400-0600 h interval was observed. Our results reinforce the hypothesis that aMT6s excretion is a predictor of clinical outcome in depression, especially in regard to noradrenaline reuptake inhibitors.

Changes in the Concentration of Urinary 6-sulphatoxymelatonin during a Week of Simulated Night Work

The aim of the study was to examine the adaptation of participants to a common night work schedule using urinary 6-sulphatoxymelatonin (aMT6s) concentration as the circadian phase marker. Fifteen adults (7 male, 8 female, age = 21.9 yr) spent nine consecutive nights in the laboratory, including: (i) adaptation sleep, (ii) baseline sleep, and (iii) seven simulated night shifts (23:00-07:00 h) followed by daytime sleep. During the baseline and daytime sleeps, participants collected urine samples which were subsequently assayed for aMT6s. The concentration of aMT6s in urine for the first three day sleeps was significantly lower than for the baseline sleep, but there was no difference in aMT6s concentrations between any of the last three day sleeps and the baseline sleep. The data indicate that people may adapt to a pattern of work that includes seven consecutive night shifts if they adhere to a fixed sleep schedule, if their exposure to morning sunlight is minimised, and if they are provided with an ideal sleep environment.

A single nocturnal exposure to 2-7 millitesla static magnetic fields does not inhibit the excretion of 6-sulfatoxymelatonin in healthy young men.

The present study sought to evaluate possible acute effects on 6-sulfatoxymelatonin (aMT6s) excretion, a surrogate for melatonin levels in blood, in volunteers exposed to static magnetic fields with flux densities representative for workers in light metal reduction plants and operators of medical MRI in hospitals. Eleven healthy male volunteers (23-43 years) participated. Urine samples were collected for two consecutive 24 h periods from 22:00 hours day 1 (exposure day) through day 2 (day after exposure) and then for 24 h from 07:00 hours on day 7 (control day). On the day of exposure the subjects slept in the MRI room from 22:00 hours until 07:00 hours next morning, thus receiving a 9 h exposure to the magnetic field (2-7 mT). On the day after exposure and on the control day, they slept at home and otherwise performed their ordinary daily activities. Total daily urine production was collected in four parts: 22:00-07:00 hours, 07:00-11:00 hours, 11:00-18:00 hours, 18:00-22:00 hours, and the volume for each interval was measured and recorded. Samples were transferred to coded bottles and frozen for later RIA analysis of aMT6s. Pairs of values of mean hourly aMT6s excretion, both diurnal and for the four daily intervals, were compared using two-sided Wilcoxon signed ranks test. The day of exposure and the day after exposure were not significantly different from the control day, either for the total diurnal secretion or the interval data. In summary, the study shows no association between a single nocturnal exposure to a static magnetic field of strength 2-7 mT and excretion of aMT6s in urine.