6-sulfatoxymelatonin Excretion Research Articles

Disruption of the circadian rhythm of melatonin: A biomarker of critical illness severity

Circadian dysrhythmias occur commonly in critically ill patients reflecting variable effects of underlying illness, ICU environment, and treatments. We retrospectively analyzed the relationship between clinical outcomes and 24-h urinary 6-sulfatoxymelatonin (aMT6s) excretion profiles in 37 critically ill patients with shock and/or respiratory failure. Nonlinear regression was used to fit a 24-h cosine curve to each patient's aMT6s profile, with rhythmicity determined by the zero-amplitude test. From these curves we determined acrophase, amplitude, phase, and night/day ratio. After assessing unadjusted relationships, we identified the optimal multivariate models for hospital survival and for discharge to home (vs. death or transfer to another facility). Normalized aMT6s rhythm amplitude was greater (p = 0.005) in patients discharged home than in those who were not, while both groups exhibited a phase delay. Patients with rhythmic aMT6s excretion were more likely to survive (OR 5.25) and be discharged home (OR 8.89; p < 0.05 for both) than patients with arrhythmic profiles, associations that persisted in multivariate modelling. In critically ill patients with shock and/or respiratory failure, arrhythmic and/or low amplitude 24-h aMT6s rhythms were associated with worse clinical outcomes, suggesting a role for the melatonin-based rhythm as a novel biomarker of critical illness severity.

Rat resistance to rheumatoid arthritis induction as a function of the early-phase adrenal-pineal crosstalk.

Chronic inflammatory diseases are triggered by causal stimuli that might occur long before the appearance of the symptoms. Increasing evidence suggests that these stimuli are necessary but not always sufficient to induce the diseases. The murine model of type II collagen emulsified in Freund's incomplete adjuvant (collagen-induced arthritis) to induce rheumatoid arthritis (RA) follows this pattern as some animals do not develop the chronically inflamed phenotype. Considering that in the immune-pineal axis (IPA) theory adrenal-pineal cross-talk adjusts early phases of inflammatory processes, we investigated whether differences in IPA activation could explain why some animals are resistant (RES) while others develop RA. We observed a similar increase in 6-sulfatoxymelatonin (aMT6s) excretion from day 3 to 13 in both RES and RA animals, followed by a significant decrease in RA animals. This pattern of aMT6s excretion positively correlated with plasma corticosterone (CORT) in RES animals. Additionally, RA animals presented a lower aMT6s/CORT ratio than saline-injected or RES animals. Plasmatic levels of tumour necrosis factor were similar in both groups, but interleukin (IL)-1β and monocyte chemotactic protein 1 (MCP-1) levels were lower in RES compared to RA animals. IL-2 and IL-4 were decreased in RES animals compared to saline-injected animals. The aMT6s/CORT ratio inversely correlated with the paw thickness and the inflammatory score (levels of IL-1β, MCP-1, IL-2 and IL-4 combined). Thus, adrenocortical-pineal positive interaction is an early defence mechanism for avoiding inflammatory chronification. KEY POINTS: Immune-pineal axis imbalance is observed in early-phase rheumatoid arthritis development. Only resistant animals present a positive association between adrenal and pineal hormones. The 6-sulfatoxymelatonin/corticosterone ratio is decreased in animals that develop rheumatoid arthritis. The inflammatory score combining the levels of nocturnal interleukin (IL)-1β, monocyte chemotactic protein 1, IL-2 and IL-4 presents a very strong positive correlation with the size of inflammatory lesion. The 6-sulfatoxymelatonin/corticosterone ratio presents a strong negative correlation with the inflammatory score and paw oedema size.

SEX-RELATED DIFFERENCES IN THE LEVELS OF URINE 6-SULFATOXYMELATONIN IN VERY LOW BIRTH WEIGHT INFANTS

Background. The sex-related differences of the urinary 6-sulfatoxymelatonin have not been studied in premature infants yet. The purpose of the work was to measure the daily urinary 6-sulfatoxymelatonin in premature infants with a very low birth weight. Materials and Methods. Fifty premature infants (28 males and 22 females) with gestational age less than 33 weeks and body weight from 999 g to 1499 g were involved in the study. Urine 6-sulfatoxymelatonin was assessed using urine collection on the 1st day and on the 10th‒14th days of life. Results. The level of urine 6-sulfatoxymelatonin on the 1st day of life showed a significant increase in its excretion in females compared to males. The median values in males were 202.0 (95% CI 77.1–390.9) pg/ml and in females 437.0 (279.6–501.0) pg/ml, p=0.0103. Its level on the 10th–14th days of life significantly decreased both in males 57.0 (95 % СІ 45,0–99.7) pg/ml, p=0.0028 and in females 90.0 (51.9–160.7) pg/ml, p=0.0021 without differences in sex-related distribution, p=0.3940. Conclusions. The melatonin metabolite as urinary 6-sulfatoxymelatonin in premature infants with a very low birth weight demonstrates sex-related differences with significant increase in females compared to males on the 1st day of life and no sex-related difference on the 10th–14th days of life. The trend of reduced pineal function is a key point in understanding the neuroendocrine reactivity in male preterms. Future investigation of sex-related aspects of urinary 6-sulfatoxymelatonin excretion in children, especially premature infants, is required.

Short-wavelength light exposure at night and sleep disturbances accompanied by decreased melatonin secretion in real-life settings: a cross-sectional study of the HEIJO-KYO cohort

ObjectivesTo determine the association between short-wavelength light exposure at night (LAN) power and sleep quality or melatonin levels in real-life settings. MethodsIn this cross-sectional study of 580 older adults (mean age, 71.0 years), we measured short-wavelength LAN power at cornea level using an originally developed light loggers over two nights. Sleep quality and physiological melatonin levels were measured using the Pittsburgh sleep quality index (PSQI) questionnaire and overnight urinary 6-sulfatoxymelatonin excretion (UME), respectively. ResultsThe first and second tertile short-wavelength LAN power values obtained were 0.77 × 10−2 μW/cm2 and 7.0 × 10−2 μW/cm2, respectively, and the overall prevalence of sleep disturbances was 34.7%. The mean UME was 1.88 ± 0.70 log μg. The mean global PSQI score and the prevalence of sleep disturbances significantly increased (P = 0.004 and 0.006, respectively) with increasing tertile groups of short-wavelength LAN power. In multivariable analysis adjusted for potential confounders, the odds ratio (OR) for sleep disturbances was significantly higher in the highest tertile group of short-wavelength LAN power compared with that in the lowest tertile group (adjusted OR, 1.90; 95% confidence interval [CI]: 1.20, 3.00; P = 0.006). In addition, UME was significantly lower in the highest tertile group of short-wavelength LAN power than that in the lowest tertile group (adjusted mean difference, −0.14 log μg; 95% CI: −0.28, −0.007; P = 0.039). ConclusionsAlthough short-wavelength LAN power measured at cornea level in real-life settings seemed to be significantly low, our findings suggest that short-wavelength LAN power is significantly associated with both melatonin levels and sleep disturbance.

Effects of an earplug placement intervention on sleep quality in patients in a medical intensive care unit: A randomized controlled trial.

This study aimed to evaluate the effects of an intervention involving earplug placement during nocturnal sleep in non-ventilated intensive care unit patients. A randomized controlled trial was conducted in 107 adult patients between January 2017 and December 2018. Participants in the intervention group (n = 55) slept with earplugs between 10 pm and 7 am on the second night of their intensive care unit stay. In the control group, participants slept with no earplugs. Outcome parameters included sleep, urinary 6-sulfatoxymelatonin levels, relaxation responses measured using the Richards-Campbell Sleep Questionnaire, liquid chromatography-mass spectrometry results and vital signs. Urine was collected between 10 pm and 7 am. Overall, 28.03% of participants showed virtually no 6-sulfatoxymelatonin excretion in the collected urine. Outcome parameters were not significantly different between the groups, indicating that wearing earplugs alone did not affect sleep quality, urinary 6-sulfatoxymelatonin and vital signs. The effects of using earplugs alone on sleep quality, urinary 6-sulfatoxymelatonin and relaxation responses in patients admitted to the intensive care unit were inconclusive. Additional research is required before earplugs alone can be widely used to improve sleep quality.

The influence of multi-way sources of illumination of monitor screens and changes in the color temperature on the excretion of melatonin metabolite

Intensive use of computers leads to an increase in the light load on the human body. The purpose of this research was to study the impact of the differential illumination of matrices of computer monitors (CM) on a melatonine-forming function, in which healthy male volunteers (average age 22.8 ± 2.09 years) took part. The light exposure was carried out by series for seven days with the help of CM, from which volunteers in the evening (from 9 pm to 11 pm) read standard text. CM had various backlit devices: Cold Cathode Fluorescent Lamp (CCFL) and White Light Emitting Diode (WLED), different color temperatures (CT). After each series, the excretion of 6-sulfatoxymelatonin (6-SOM) with urine was investigated. The peak intensity (PI) and the dominant wavelength (DW) in the WLED series, the parameters turned out to be within High Energy Visible Light (HEVL). The study revealed reliable differences in 6-SOM concentrations in different series of studies with indicators in the series with wised and CT 5512-5903 K. The research also detected correlations between the indicators 6-SOM, the values of PI (R = 0.692, p = 0.05) and the DW (R = 0.587, p = 0.01), which are in the HEVL range.

Daily periodicity of labor in pregnant women in physiological and complicated pregnancy depending on the sex of the fetus

Objective: the study aimed to reveal the daily periodicity of labor, the nature of melatonin metabolism, and the outcome of childbirth in women with a physiological and complicated pregnancy, depending on the sex of the fetus.Materials and methods: to study the chronophysiological characteristics of birth outcomes depending on fetal sex, 1 980 birth histories and stories of newborns were analyzed. The neonates were born between January 1 and December 31, 2016, in a maternity ward of the Federal State Budgetary Educational Institution of Higher Education “RostGMU” of the Ministry of Health of Russia. Melatonin production was identified by the level of urinary excretion of 6-sulfatoxymelatonin (6-SM) (its main metabolite) examining the morning portion of the urine of women by the ELISA method (at 8 am 3 ml of urine were collected in Eppendorf tube).Results: it was revealed that fetal sex modulated the activity of the central regulatory mechanisms responsible for the daily period functional processes in the female body and the initiation of labor. The largest number of spontaneous births by male fetuses occurred in the early evening before midnight when daily illumination was decreased, while the birth of girls was observed more often in the period from midnight to early morning. At the same time, mothers of boys had lower production of melatonin compared to that of girls’ mothers.Conclusions. The peculiarities of labor and birth complications associated with the sex of the fetus were identified.

Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances.

Sleep disturbances, abnormal melatonin secretion, and increased inflammation are aspects of autism spectrum disorder (ASD) pathophysiology. The present study evaluated the daily urinary 6-sulfatoxymelatonin (aMT6s) excretion profile and the salivary levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in 20 controls and 20 ASD participants, as well as correlating these measures with sleep disturbances. Although 60% of ASD participants showed a significant night-time rise in aMT6s excretion, this rise was significantly attenuated, compared to controls (P<.05). The remaining 40% of ASD individuals showed no significant increase in nocturnal aMT6s. ASD individuals showed higher nocturnal levels of saliva TNF, but not IL-6. Dysfunction in the initiation and maintenance of sleep, as indicated by the Sleep Disturbance Scale for Children, correlated with night-time aMT6s excretion (r=-.28, P<.05). Dysfunction in sleep breathing was inversely correlated with aMT6s (r=-.31, P<.05) and positively associated with TNF level (r=.42, P<.01). Overall such data indicate immune-pineal axis activation, with elevated TNF but not IL-6 levels associated with disrupted pineal melatonin release and sleep dysfunction in ASD. It is proposed that circadian dysregulation in ASD is intimately linked to heightened immune-inflammatory activity. Such two-way interactions of the immune-pineal axis may underpin many aspects of ASD pathophysiology, including sleep disturbances, as well as cognitive and behavioral alterations.

Differential Effects of DHA- and EPA-Rich Oils on Sleep in Healthy Young Adults: A Randomized Controlled Trial.

Emerging evidence suggests that adequate intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs), which include docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), might be associated with better sleep quality. N-3 PUFAs, which must be acquired from dietary sources, are typically consumed at suboptimal levels in Western diets. Therefore, the current placebo-controlled, double-blind, randomized trial, investigated the effects of an oil rich in either DHA or EPA on sleep quality in healthy adults who habitually consumed low amounts of oily fish. Eighty-four participants aged 25–49 years completed the 26-week intervention trial. Compared to placebo, improvements in actigraphy sleep efficiency (p = 0.030) and latency (p = 0.026) were observed following the DHA-rich oil. However, these participants also reported feeling less energetic compared to the placebo (p = 0.041), and less rested (p = 0.017), and there was a trend towards feeling less ready to perform (p = 0.075) than those given EPA-rich oil. A trend towards improved sleep efficiency was identified in the EPA-rich group compared to placebo (p = 0.087), along with a significant decrease in both total time in bed (p = 0.032) and total sleep time (p = 0.019) compared to the DHA-rich oil. No significant effects of either treatment were identified for urinary excretion of the major melatonin metabolite 6-sulfatoxymelatonin. This study was the first to demonstrate some positive effects of dietary supplementation with n-3 PUFAs in healthy adult normal sleepers, and provides novel evidence showing the differential effects of n-3 PUFA supplements rich in either DHA or EPA. Further investigation into the mechanisms underpinning these observations including the effects of n-3 PUFAs on sleep architecture are required.

Effects of daytime exposure to different monochromatic lights on the excretion of 6-sulfatoxymelatonin (aMT6s) in a hospital environment

ABSTRACT Hospitalized patients are frequently deprived of contact with natural light and constantly exposed to artificial lighting, losing biological synchronism. However, few studies have been conducted to assess the consequences of inadequate exposure to light in hospital environments, whether related to insufficient light in the period daytime, or to light peaks at night. This study assesses the effect of daytime exposure to different monochromatic lights on the excretion of 6-sulfatoxymelatonin (aMT6s), a hormone that reflects variations in the light/dark cycle. The light intensity was adjusted to 300 lx. Forty voluntary patients under transfusion were randomly assigned into five groups of light exposure for five hours, during the day. The concentration of aMT6s was determined in the urine samples collected at four intervals in a period of 24 hours during two days (before and at intervention). Exposure to green light resulted in significant acute melatonin reduction; blue light, in delay of night secretion; red, yellow and white light, kept it unaltered. These findings indicate that exposure to light during the day can lead to changes in the pattern of melatonin secretion. This research can be useful in artificial lighting environments, such as hospitals, to maintain adequate lighting and preserve the sleep/wake cycle.

The effect of long-term beta-blockers on melatonin secretion, sleep quality, and vascular brain damage

The influence of long-term administration of beta-blockers to melatonin synthesis, sleep quality and vascular brain damage. The main study group included 114 patients, aged 47-83, with cardiovascular diseases, who were under a complex therapy with long-term administration of beta-blockers. The comparison group included 110 patients with cardiovascular diseases, similar in age and sex, who did not receive beta-blockers in their complex therapy. The circadian dynamics of melatonin synthesis was observed by excretion of 6-sulfatoxymelatonin (6-SM), the major metabolite of melatonin, in three urinary samples (day, evening, night). All the patients underwent night polysomnography to assess the severity of sleep disorders. The severity of vascular brain damage was assessed using magnetic resonance imaging. The analyses showed large variability in individual values of 6-SM circadian excretion of patients with cardiovascular diseases (from 0.9 to 133 μg/24h with a mid-point 16.8 μg/24h). A considerable decrease of 6-SM circadian excretion is detected in the group of patients taking beta-blockers comparing to those not Me [q 25; q 75]: 12.8 [6.2; 21.1] and 24.0 [12.5; 41.5] μg/24h, respectively (p<0.001), with no differences in sleep values and severity of vascular brain damage. Comparing subgroups of patients with 6-SM circadian excretion lower and higher than 16.8 μg/24h showed a significant increase of sleep latency, decrease of rapid eye movement sleep (REM sleep), increasing number of gliosis foci in white matter of the brain with higher values of leptin, leptin/adiponectin ratio and glycohemoglobin in the group of patients with 6-SM circadian excretion ≤16.8 μg/24h. A low level of endogenous melatonin is a risk factor for development of sleep structure and quality disorders, vascular white matter brain damages with a higher risk for metabolic disorders. Long-term beta-blockers administration decrease endogenous melatonin synthesis to 50% increasing the risk for insomnia and vascular brain damage, mostly in patients with lower initial level of 6-SM circadian excretion.: melatonin, 6-sulfatoxymelatonin, beta-blockers, insomnia, vascular white matter brain damage, leptin, adiponectin.

AEDG Peptide Regulation of the Expression of Human Circadian Rhythm Genes upon Accelerated Aging of the Pineal Gland

Night work desynchronizes biorhythms, disturbs melatonin production, and accelerates pineal-gland aging. A promising geroprotector for the restoration of pineal melatonin synthesis is AEDG (Ala-Glu-Asp-Gly) peptide. AEDG peptide increases 6-sulfatoxymelatonin (6-SOMT) excretion in the urine of middle-aged people by 1.7 times. Moreover, AEDG peptide normalizes the hyperexpression of the Clock and Csnk1e circadian genes in leukocytes and increases Cry2 gene hypoexpression in peripheral blood lymphocytes by two times in people with reduced epiphyseal melatonin-production. The geroprotective effect of AEDG peptide is based on its ability to restore epiphyseal melatonin production via regulation of the expression of human circadian genes.

Melatonin secretion in patients with Parkinson's disease receiving different-dose levodopa therapy

ObjectiveMelatonin is involved in the regulation of sleep and circadian biological rhythmicity; decreased melatonin secretion has been associated with circadian disruptions. Previous studies evaluating melatonin levels between patients with Parkinson's disease (PD) and controls without PD have found conflicting results; however, large-scale studies have not been performed. Our aim is to compare endogenous melatonin levels between patients with Parkinson's disease (PD) and non-PD older adults. MethodsIn this cross-sectional study on 201 outpatients with PD and 380 community-dwelling older Japanese adults (controls), urinary 6-sulfatoxymelatonin excretion was measured to estimate endogenous melatonin levels. ResultsUrinary 6-sulfatoxymelatonin excretion (UME) did not significantly differ overall between PD patients and non-PD controls, even after adjusting for age, gender, medications, sleep habits, and seasons. Among PD patients, a clear and robust dose–response association was found between levodopa equivalent dose and UME, independent of potential confounding factors, including Parkinson's disease severity. Compared with the lowest levodopa equivalent dose quartile group (mean levodopa equivalent dose, 132 mg/day), the highest group (mean levodopa equivalent dose, 973 mg/day) exhibited a 68% increase in UME (17.8 vs. 30.0 ng/mg cre, respectively). In addition, compared with the non-PD controls, PD patients receiving a lower levodopa equivalent dose displayed decreased UME and those receiving higher levodopa equivalent dose displayed increased UME. ConclusionOur study suggests that melatonin levels in PD patients receiving average levodopa doses are comparable with those in older adults, even after considering confounding factors. This association was modulated by daily levodopa dose in PD patients.

Total Daily Production and Periodicity of Melatonin Metabolite in Critically Ill Children.

To determine whether total daily 6-sulfatoxymelatonin excretion and diurnal variation of melatonin secretion was maintained during the early phase of PICU admission through examination of the melatonin urinary metabolite, 6-sulfatoxymelatonin. Exploratory prospective, observational study. Twelve-bed medical-surgical PICU of a Children's Hospital. Fifty children 3 months to 18 years old enrolled within 24 hours of PICU admission with access for urinary sampling. None. Urine samples were collected at 4-hour intervals for 24 hours and stored at -80C. 6-sulfatoxymelatonin was determined in duplicate by direct enzyme-linked immunosorbent assay. Patients were heterogeneous for diagnosis, had a mean age of 8.1 years (SD = 6.1 yr), and median (interquartile range) Pediatric Risk of Mortality III of 10 (4-13). Mean (SD) total daily 6-sulfatoxymelatonin production was 30.0 µg (25.6 µg) for the first 24 hours, which did not differ significantly from the means on days 2 (p = 0.56) or 3 (p = 0.29), and was similar to literature controls. Mean 6-sulfatoxymelatonin production for the population fit a periodic function well, with a reliable amplitude of 326 ng/hr and peak excretion from 04:00 to 08:00 (F = 4.4, p = 0.01), even when 6-sulfatoxymelatonin was corrected for body weight (F = 3.4, p = 0.03) and when sedation was included in the model (F = 3.95, p = 0.004). There was no significant correlation between lighting and 6-sulfatoxymelatonin excretion at any time period (R values: 0.11-0.25, p = 0.10-0.94). Mean 6-sulfatoxymelatonin excretion did not fit the model for a periodic function well for the subpopulations studied (sepsis [n = 18, F = 1.1, p = 0.32], respiratory failure requiring deep sedation [n = 10, F = 0.4, p = 0.66], and neurologic injury [n = 7, F = 0.6, p = 0.55]). Total daily and diurnal variation of 6-sulfatoxymelatonin excretion is heterogeneously maintained early in pediatric critical illness. However, this may not hold true for specific diagnostic categories.

Mass spectrometric quantification of urinary 6-sulfatoxymelatonin: age-dependent excretion and biological variation.

Regulators of circadian rhythm, including melatonin, influence fundamental biological processes. Measuring the melatonin metabolite 6-sulfatoxymelatonin in urine can estimate melatonin production. 6-sulfatoxymelatonin is mainly analyzed by immunoassays, but these methods are hampered by cross-reactivity and poor reproducibility when used to analyze small molecules. Therefore, we validated a high-throughput liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to quantify 6-sulfatoxymelatonin in urine. We evaluated age-dependent 24-h excretion of 6-sulfatoxymelatonin into urine and the biological variation of urinary excretion in healthy individuals. The online solid phase extraction method combined with LC-MS/MS was validated according to international guidelines, and used to measure the excretion of 6-sulfatoxymelatonin into urine of 240 healthy individuals. Biological variation of 6-sulfatoxymelatonin excretion was examined in 10 healthy individuals. Urinary 6-sulfatoxymelatonin results were well within the validation criteria (interassay coefficient of variation:<5.4%, quantification limit: 0.2nmol/L). There was an age-related decrease in 6-sulfatoxymelatonin excretion into 24-h urine [F(5, 234)=13.9; p<0.001]. Within-subject variation of 6-sulfatoxymelatonin was 39.2% in day urine, 15.1% in night urine, and 12.2% in 24-h urine. Between-subject variation was 39.1% in day urine, 37.9% in night urine, and 36.8% in 24-h urine. This MS-based method enables straightforward, reproducible, and sensitive quantification of 6-sulfatoxymelatonin in urine. Urinary 6-sulfatoxymelatonin levels decreased with age. Biological variation of 6-sulfatoxymelatonin excretion into urine was high between subjects and lower within subjects, indicating that repeated measurements of 6-sulfatoxymelatonin in 24-h urine are needed in future studies.

Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients.

Melatonin is a multifaceted hormone which rises upon the onset of darkness. Pineal synthesis of melatonin is known to be disturbed in patients with end-stage renal disease, but it is not known if its production is restored to normal after successful renal transplantation. We hypothesized that urinary excretion of 6-sulfatoxymelatonin, the major metabolite of melatonin, is lower in renal transplant recipients (RTRs) compared to healthy controls and that this is associated with excess mortality. Urinary 6-sulfatoxymelatonin was measured via LC-MS/MS in 701 stable outpatient RTRs and 285 healthy controls. Median urinary 6-sulfatoxymelatonin in RTR was 13.2 nmol/24 h, which was 47% lower than in healthy controls. Urinary 6-sufatoxymelatonin appeared undetectable in the majority of 36 RTRs with diabetic nephropathy as primary renal disease. Therefore, this subgroup was excluded from further analyses. Of the remaining 665 RTRs, during 5.4 years of follow-up, 110 RTRs died, of whom 38 died due to a cardiovascular cause. In Cox-regression analyses, urinary 6-sulfatoxymelatonin was significantly associated with all-cause mortality (0.60 (0.44–0.81), p = 0.001) and cardiovascular mortality (0.49 (0.29–0.84), p = 0.009), independent of conventional risk factors and kidney function parameters. Based on these results, evaluation and management of melatonin metabolism could be considered for improvement of long-term outcomes in RTRs.

Sleep Extension Increases the Effect of Caloric Restriction Over Body Weight and Improves the Chronic Low-Grade Inflammation in Adolescents With Obesity

PurposeDiminution of sleep may be associated with obesity. However, evidence that extending sleep duration might favor weight loss is insufficient. The aim of this study was to compare the effect of dietary restriction with or without prescription of sleep extension on weight loss in adolescents with obesity. MethodsA total of 52 adolescents with obesity (24 males and 28 females) received a diet with 500 calories restriction, randomly allocated to groups without (n = 27) and with sleep extension (n = 25) for 4 weeks. We collected data on anthropometry, caloric intake, and self-reported sleep diaries. Serum interleukin 6, tumor necrosis factor α, leptin, and insulin levels were quantified by enzyme-linked immunosorbent assay. Cortisol and 6-sulfatoxymelatonin excretions were measured in the first urine collection in the morning by liquid chromatography-mass spectrometry. Measurements were carried out at baseline and at the end of the intervention. ResultsAfter diet, weight decreased in both groups. Sleep extension, improved weight loss (p < .00001), and waist girth reduction (p = .00003), with diminution of insulin (p = .002) and interleukin 6 levels (p = .02). Caloric restriction was less effective in adolescent females. No differences in cortisol or 6-sulfatoxymelatonin excretion were found. ConclusionsA sleep extension favors weight loss in adolescents under caloric restriction and improves inflammation and metabolic conditions, thus supporting a possible additional benefit to diet in the treatment of obesity in adolescents.

Genital endometriosis and melatonin: a role in the pathogenesis and its possible use in the treatment of the disease

Hypothesis/aims of study. Melatonin is found in almost all living organisms, the range of its effects being quite diverse. Effects of this hormone in the human body are realized via two ways, through specific receptors and non-receptor pathways. Melatonin may act through both membrane and nuclear receptors. In the present work, the expression of MTR1 and MTR2 melatonin receptors was studied in the eutopic endometrium and endometrioid heterotopies, and the level of melatonin metabolite, 6-sulfatoxymelatonin, in daily urine in patients with genital endometriosis (GE) was analyzed.&#x0D; Study design, materials and methods. The experimental group included 67 patients of reproductive age with a verified diagnosis of GE, and the control group consisted of 18 individuals with an ovulatory menstrual cycle without gynecological pathology. The 6-sulfatoxymelatonin level in daily urine was determined by enzyme immunoassay. The study of MTR1 and MTR2 melatonin receptor expression in the endometrium and endometrioid heterotopies was performed in 24 patients with GE and in 10 women of reproductive age who were examined for infertility who did not have gynecological pathology based on diagnostic laparoscopy. To study the expression of melatonin receptors, the endometrium and endometrial heterotopy sampling was carried out from day 18 to day 22 of the menstrual cycle. Morphological assessment included histological and immunofluorescence studies using confocal laser scanning microscopy.&#x0D; Results. In patients with GE, there was found a tendency to a decrease in 6-sulfatoxymelatonin excretion in daily urine compared to the control group. It was also found that the total relative expression area of melatonin receptors in the endometrium of women with GE was significantly lower compared to the endometrium of patients from the control group. Significant differences between the average brightness and optical density were not found. In addition, it was revealed that the relative expression areas of MTR1 and MTR2 melatonin receptors in the eutopic endometrium and in endometrioid heterotopies did not differ significantly. A negative correlation was stated between the relative expression area of melatonin receptors and GE prevalence. Particular attention is paid to the role of melatonin in the development of GE and to the possibilities of working out new treatment regimens with its use.&#x0D; Conclusion. The data obtained confirm the undoubted role of melatonin in the pathogenesis of GE, however, the development of new treatment regimens with its use requires further study.

Melatonin Levels in Patients With Primary Open-angle Glaucoma With High or Low Intraocular Pressure.

To evaluate circulatory melatonin levels by assessing nocturnal urinary excretion of 6-sulfatoxymelatonin (aMT6s) in patients with primary open-angle glaucoma (POAG) and to compare the high-tension group and the low-tension group. This study included 80 eyes of 41 POAG patients and 87 eyes of 44 control subjects. POAG group was further classified into high-tension group and low-tension group according to the pretreatment intraocular pressure (IOP). The first urine in the morning was collected and aMT6s were measured using a commercial ELISA kit. Urinary aMT6s levels were expressed as ng aMT6s/mg creatinine. Differences in melatonin levels among the control and POAG subgroups were evaluated by generalized estimating equation adjusting age, sex, sleep duration, and intereye correlation. Urinary aMT6s/creatinine ratio did not differ between POAG and control group (P=0.097). The difference in the aMT6s/creatinine ratio between the 3 groups-high-tension group with baseline IOP≥21 mm Hg (19.74±3.12 ng/mg), low-tension glaucoma group with baseline IOP<21 mm Hg (26.71±3.47 ng/mg), and control group (30.35±3.05 ng/mg)-was statistically significant (P=0.046). Post hoc analysis revealed that the difference between the control and high-tension glaucoma groups was significant (P=0.014), whereas the difference between the control and low-tension glaucoma groups was not (P=0.436). This study found low melatonin levels in high-tension glaucoma compared with the control.

Special peculiarities of clinical course of osteoarthrosis of knee joints depending on 6-hydroxymelatonin-sulfate urinary excretion profile

The study objective was to define the special features of the clinical course of knee joint osteoarthrosis depending on 6-sulfatoxymelatonin urinaryexcretion profile.Materials and methods.We surveyed 141 patients with radiological Stage II-III osteoarthrosis (OA) of the knee joints (18 female subjects). Diagnosis of OA was established on the basis of ACR criteria (1991) and EULAR (2010) recommendations. We determined the AO clinical indexes (Lequesne, WOMAC, KOOS), HAQ functional index, sleep quality and psycho-emotional state indicators. ELISA was used to assess 6-sulfatoxymelatonin urinary excretion profile.Results. It was established that 66% of patients with OA of knee joints had a reduced 6-sulfatoxymelatonin urinary excretion compared to this of practically healthy individuals. AO patients with low 6-SMT urinary excretion profiles had higher incidence of severe insomnia and depressive disorders. Reduction in 6-SMT excretion was associated with a moderate increase in pain syndrome and deterioration of physical functions by Lequesne, WOMAC, KOOS, and HAQ indexes.Conclusion.The reducedmelatonin production in ОА patients is a factor of more severe clinical course of the disease due to deterioration of the psycho-emotional state, the development of pain syndrome, and functional disorders.