6-sulfatoxymelatonin Levels Research Articles

Exposure to four typical heavy metals induced telomere shortening of peripheral blood mononuclear cells in relevant with declined urinary aMT6s in rats

Environmental heavy metals pollution have seriously threatened the health of human beings. An increasing number of researches have demonstrated that environmental heavy metals can influence the telomere length of Peripheral Blood Mononuclear Cells (PBMCs), which implicate biological aging as well as predicts diseases. Our previous study has shown that methylmercury (MeHg)-induced telomere shortening in rat brain tissue was associated with urinary melatonin metabolite 6-sulfatoxymelatonin (aMT6s) levels. Here, we aimed to further elucidate the impact of 4 typical heavy metals (As, Hg, Cd and Pb) on telomere length of PBMCs and their association with urinary aMT6s in rats. In this study, eighty-eight male Sprague-Dawley rats were randomized grouped into eleven groups. Among them, forty 3-month-old (young) and forty 12-month-old (middle-aged) rats were divided into young or middle-aged control groups as well as typical heavy metals exposed groups, respectively. Eight 24-month-old rats (old) was divided into aging control group. The results showed that MeHg exposure in young rats while sodium arsenite (iAs), MeHg, cadmium chloride (CdCl2), lead acetate (PbAc) exposure in middle-aged rats for 3 months significantly reduced the levels of and urinary aMT6s, as well as telomere length of PBMCs. In addition, they also induced abnormalities in serum oxidative stress (SOD, MDA and GPx) and inflammatory (IL-1β, IL-6 and TNF-α) indicators. Notably, there was a significant positive correlation between declined level of urinary aMT6s and the shortening of telomere length in PBMCs in rats exposed to 4 typical heavy metals. These results suggested that 4 typical heavy metals exposure could accelerate the reduction of telomere length of PBMCs partially by inducing oxidative stress and inflammatory in rats, while ageing may be an important synergistic factor. Urinary aMT6s detection may be a alternative method to reflect telomere toxic effects induced by heavy metal exposure.

Adiposity, Weight Change, and Urinary Melatonin Levels among Men in the Multiethnic Cohort.

Low levels of 6-sulfatoxymelatonin, the primary urinary metabolite of melatonin, have been linked to cancer and cardiometabolic outcomes in White and female populations. We examined the association between adulthood adiposity and 6-sulfatoxymelatonin levels in a racially and ethnically diverse population. Our study included 4,078 men in the Multiethnic Cohort with adiposity measurements at enrollment (1993-1996) and biomarkers measured in urines collected in 1995 and 2005. Multivariable linear regression models were used to estimate the percent change in 6-sulfatoxymelatonin levels and 95% confidence intervals (CI). Associations were examined separately by racial/ethnic group. The prevalence of obesity varied by race and ethnicity, from 10% for Japanese American men to 34% for Native Hawaiian men. Compared with men with normal body mass index (BMI), men who were overweight (-7.8%; 95% CI, -11.9 to -3.5%) and obese (-18.1%; 95% CI, -23.2 to -12.6%) had significantly lower 6-sulfatoxymelatonin levels adjusting for potential confounding factors. Increasing weight gain in adulthood was also associated with lower 6-sulfatoxymelatonin (Ptrend < 0.0001). The inverse associations for BMI and weight change were qualitatively similar across racial and ethnic groups. Obesity is inversely associated with melatonin in a racially diverse population. This finding is relevant given higher rates of obesity among Black, Native Hawaiian, and Latino men, as well as potential racial and ethnic differences in circadian function. Melatonin may be a relevant biomarker among obesity-associated malignancies and could shed light on a potential mechanism of cancer disparities.

Melatonin as a Coadjuvant in the Treatment of Patients with Fibromyalgia.

Fibromyalgia syndrome (FMS) is a chronic widespread pain syndrome that is accompanied by fatigue, sleep disturbances, anxiety, depression, lack of concentration, and neurocognitive impairment. As the currently available drugs are not completely successful against these symptoms and frequently have several side effects, many scientists have taken on the task of looking for nonpharmacological remedies. Many of the FMS-related symptoms have been suggested to be associated with an altered pattern of endogenous melatonin. Melatonin is involved in the regulation of several physiological processes, including circadian rhythms, pain, mood, and oxidative as well as immunomodulatory balance. Preliminary clinical studies have propounded that the administration of different doses of melatonin to patients with FMS can reduce pain levels and ameliorate mood and sleep disturbances. Moreover, the total antioxidant capacity, 6-sulfatoxymelatonin and urinary cortisol levels, and other biological parameters improve after the ingestion of melatonin. Recent investigations have proposed a pathophysiological relationship between mitochondrial dysfunction, oxidative stress, and FMS by looking at certain proteins involved in mitochondrial homeostasis according to the etiopathogenesis of this syndrome. These improvements exert positive effects on the quality of life of FMS patients, suggesting that the use of melatonin as a coadjuvant may be a successful strategy for the management of this syndrome.

PS-C30-1: URINARY ANGIOTENSINOGEN-MELATONIN RATIO IN GESTATIONAL DIABETES AND PREECLAMPSIA

Objective: A large research portfolio indicates that an activated renal renin-angiotensin system or a deficit on melatonin is associated with several cardiovascular pathologies. In this observational clinical study, we hypothesized that alterations in urinary melatonin or angiotensinogen levels may be altered in two common conditions, preeclampsia and gestational diabetes. Our primary objective was to assess melatonin and angiotensinogen as novel disease biomarkers detectable and quantifiable in the urine of pregnant women with or without pregnancy complications. Design and Methods: This was a concurrent cohort study of pregnant women with selected obstetric pathologies (gestational diabetes, preeclampsia, hypertension and obesity with hypertension). A group of healthy controls was also included. Urinary 6-sulfatoxymelatonin and angiotensinogen were measured by sensitive and specific ELISAs in first morning void urine samples. The patients were included in the cohort consecutively, and the diagnosis was blinded at the level of urine collection. Urinary 6-sulfatoxymelatonin and angiotensinogen levels were investigated in the patients included in the cohort. Results: Urinary levels of angiotensinogen were significantly higher in the gestational diabetes [angiotensinogen/creatinine ratio median (25th, 75th): 0.11 (0.07, 0.18)] and preeclampsia [0.08 (0.06, 0.18)] groups than in those with healthy pregnancy [0.05(0.04, 0.06]; 6-sulfatoxymelatonin levels were significantly lower in the gestational diabetes [ug/h: median (25th, 75th): 0.12(0.08, 0.17)] and preeclampsia [0.12 (0.09, 0.15)] groups than in those with healthy pregnancy [0.20 (0.15, 0.27]. Neither morning void protein/creatinine ratio nor 24-h urine protein estimate were significantly different between the study groups. Conclusion: These results suggest that urinary angiotensinogen levels may indicate an intrarenal RAS activation while melatonin production appears to be defective in gestational diabetes or hypertension. An angiotensinogen/melatonin ratio is suggested as an early biomarker for identification of gestational diabetes or hypertension. This report provides a basis for the potential use of melatonin for the treatment of preeclampsia. A prospective study in a larger number of patients to determine the operative characteristics of these markers as potential diagnostic tests is justified.

Chronobiological parameters as predictors of early treatment response in major depression

BackgroundAlterations in circadian system organization have been related to major depressive disorder manifestations. This study aimed to evaluate chronobiological parameters, such as sleep, levels of 6-sulfatoxymelatonin, and others derived from actimetry as potential predictors of adequate treatment response in MDD. Methods98 adult women with confirmed diagnosis of MDD were included. Participants completed standard questionnaires (Hamilton Depression Rating Scale – HAM-D; Munich Chronotype Questionnaire - MCTQ) at baseline and after 4 weeks of treatment. Urinary samples for assessing 6-sulfatoxymelatonin were collected on the day before and immediately after pharmacological treatment administration, and 28 continuous days of actigraphy data were collected during the protocol. Participants were classified into Responder (R) or Non-responder (NR) to antidepressant treatment in 4 weeks (early responder), which was characterized by a ≥50 % decrease in the HAM-D score. ResultsThe following biological rhythms variables significantly predicted a better treatment response in a model controlling for age, sex, and previous treatments: higher levels of activity (M10 - average activity in the 10 most active hours within the 24 h-day) and an earlier center of the 10 most active hours (M10c), as well as lower intradaily variability (IV) of light exposure. Sleep parameters and 6-sulfatoxymelatonin levels did not associate with treatment response prediction. LimitationActimetry data were not assessed before changing in the treatment plan. ConclusionDifferent patterns in activity and light exposure might be linked to early antidepressant response.

Urinary Melatonin Metabolite in Premature Infants with Extremely and Very Low Birth Weight

The aim. Determination of daily urinary 6-sulfatoxymelatonin in premature infants with extremely and very low birth weight. Materials and methods. A non-invasive, descriptive, single-centered study involving data of 96 premature infants with weight less than 1500 g : 46 infants with extremely and 50 infants with very low birth weight. The study included a detailed scrutiny of history and objective examinations, data from medical records, anthropometric measurements, and daily urine collection. Determination of 6 - SM in the 24-hours urine collection from premature infants was performed by enzyme immunoassay on the analyzer “Labline-90” (Austria) using a commercial test system manufactured by “LDR” (LABOR DIAGNOSTIKA NORD GmbH &amp; Co.KG, Germany) according to the provided instruction. 166 portions of urine were collected during the examination in time intervals: 96 portions of urine in premature infants at 1st day of life and 70 portions at 10th – 14th day of life. Results. Ante- and intranatal periods for the infants enrolled in the study were characterized by conditions: premature rupture of membranes 37 (38.5%), multiple pregnancy 16 (16.6%), preeclampsia 15 (15.6%), isthmic-cervical insufficiency 11 (11.5%), placental abruption 8 (8.3%), extra corporal fertilization 5 (5.2%), chorioamnionitis 4 (4.2%); caesarean section urgent 33 (34.4%) and planned 24 (25.0%). There was no any significant difference in frequency of ante – and intranatal pathology between ELBW and VLBW. Antenatal administration of corticosteroids for reduce the severity of neonatal respiratory distress syndrome occurred in all mothers of infants enrolled in the study. There was significant low urinary 6-sulfatoxymelatonin level in extremely low birth weight infants (median 120.0 pg /mL) on the 1st day of life compared with very low birth weight (median 348.5 pg / mL). There was no difference at 10 – 14th days. The predictive level of lethal outcome in infants with extremely low birth weight is ≤ 84 pg / mL with sensitivity 84.62% and specificity 70.0%. Conclusion. In infants with extremely and very low birth weight the determining the urinary 6-sulfatoxymelatonin is a non-invasive method. The significant decrease level of urinary 6-sulfatoxymelatonin in infants with extremely low birth weight on the first day of life was found. The measurement of urinary 6-sulfatoxymelatonin will allow to establish the prediction of perinatal outcomes. Its levels &lt;87 pg / mL is associated with lethal outcomes. Authors speculate than it will the way for future supplement of melatonin to premature infants and study of its effect on perinatal outcomes

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.

Urinary Angiotensinogen-Melatonin Ratio in Gestational Diabetes and Preeclampsia.

Background: A large research portfolio indicates that an activated renal renin-angiotensin system or a deficit on melatonin is associated with several cardiovascular pathologies. In this observational clinical study, we hypothesized that alterations in urinary melatonin or angiotensinogen levels may be altered in two common conditions, preeclampsia and gestational diabetes. Our study’s primary objective was to assess melatonin and angiotensinogen as novel disease biomarkers detectable and quantifiable in the urine of pregnant women with or without pregnancy complications. Methods: This was a concurrent cohort study of pregnant women with selected obstetric pathologies (gestational diabetes, preeclampsia, hypertension and obesity with hypertension). A group of healthy controls was also included. Urinary 6-sulfatoxymelatonin and angiotensinogen were measured by sensitive and specific ELISAs in first morning void urine samples. The patients were included in the cohort consecutively, and the diagnosis was blinded at the level of urine collection. Urinary 6-sulfatoxymelatonin and angiotensinogen levels were investigated in the patients included in the cohort. Results: Urinary levels of angiotensinogen were significantly higher in the gestational diabetes [angiotensinogen/creatinine ratio median (25th, 75th): 0.11 (0.07, 0.18)] and preeclampsia [0.08 (0.06, 0.18)] groups than in those with healthy pregnancy [0.05(0.04, 0.06]; 6-sulfatoxymelatonin levels were significantly lower in the gestational diabetes [ug/h: median (25th, 75th): 0.12(0.08, 0.17)] and preeclampsia [0.12 (0.09, 0.15)] groups than in those with healthy pregnancy [0.20 (0.15, 0.27]. Neither morning void protein/creatinine ratio nor 24-h urine protein estimate were significantly different between the study groups. Conclusion: These results suggest that urinary angiotensinogen levels may indicate an intrarenal RAS activation while melatonin production appears to be defective in gestational diabetes or hypertension. An angiotensinogen/melatonin ratio is suggested as an early biomarker for identification of gestational diabetes or hypertension. This report provides a basis for the potential use of melatonin for the treatment of preeclampsia. A prospective study in a larger number of patients to determine the operative characteristics of these markers as potential diagnostic tests is justified.

Urinary 6-sulfatoxymelatonin Levels and Prostate Cancer Risk among Men in the Multiethnic Cohort.

The circadian hormone melatonin has anticancer properties, and prior studies suggest a positive association between low melatonin and prostate cancer risk. The purpose of this study was to examine urinary melatonin levels and prostate cancer in a racially/ethnically diverse cohort. We conducted a nested case-control study, including 1,263 prostate cancer cases and 2,346 controls, sampled from participants in the Multiethnic Cohort Study with prediagnostic urine samples assayed for 6-sulfatoxymelatonin, the primary melatonin metabolite. Conditional logistic regression was used to examine the association between melatonin levels and the development of prostate cancer outcomes (all incident cases, advanced, lethal, high-grade, and aggressive), overall and by race/ethnicity. Among 1,263 cases, 135 were advanced stage, 101 were lethal cases, and 282 were high-grade disease. Median melatonin levels were similar in controls [17.12 ng/mL; interquartile range (IQR), 19.78] and cases (17.93 ng/mL; IQR, 19.76), and we found no significant association between urinary melatonin levels and prostate cancer risk overall or in any clinical or racial subgroup. In this diverse cohort, there was no significant association between melatonin and any prostate cancer outcome, nor were there any differences by racial/ethnic group. These results do not support a strong association between melatonin levels and risk of prostate cancer.

Evaluation of structural variations in the pituitary gland, hormonal status and laboratory markers of the central nervous system functioning in patients with chronic disorders of consciousness

BACKGROUND: Consciousness is the state of being awake and aware of oneself and the environment. The disorders of consciousness result from pathologies that impair awareness. The development of effective comprehensive personalized interventions contributing to the recovery of consciousness in patients with chronic disorders of consciousness is one of the most pressing and challenging tasks in modern rehabilitation.&#x0D; AIM: The aim of this study was to understand structural problems of the pituitary gland, blood levels of gonadotropins and melatonin as well as brain damage markers in the blood and cerebrospinal fluid in patients with chronic disorders of consciousness and to analyze the levels of the above markers among different groups of patients depending on the level of impaired consciousness.&#x0D; MATERIALS AND METHODS: We examined 61 chronic disorders of consciousness patients and identified three groups depending on the level of consciousness including 24 patients with unresponsive wakefulness syndrome, 24 patients with a minus minimally conscious state, and 13 patients with minimally conscious state plus. We performed magnetic resonance imaging of chiasmatic-sellar region and determined blood serum levels of follicle-stimulating and luteinizing hormones and melatonin, as well as urinary level of 6-sulfatoxymelatonin and the content of brain derived neurotrophic factor (BDNF), apoptosis antigen (APO-1), FasL, glutamate, and S100 protein in the blood serum and cerebrospinal fluid.&#x0D; RESULTS: The patients were examined in the age ranging from 15 to 61 years old. Patient groups were homogeneous by the level of consciousness in terms of age and duration of chronic disorders of consciousness by the time of examination. The patients did not differ in the pituitary volume regardless of the level of consciousness. No significant differences were found between the groups with different levels of consciousness when studying the levels of melatonin in the blood serum and its metabolite in the urine. A peak in melatonin secretion was detected at 3 a.m. in 54.5 % of the patients, which can be considered as a favorable prognostic marker for further recovery of consciousness. Hypogonadotropic ovarian failure was found in 34 % of the patients, with normogonadotropic ovarian failure in the remaining patients. Serum APO-1 and BDNF levels were significantly higher in patients with minimally conscious state relative to those with unresponsive wakefulness syndrome. Significantly lower levels of glutamate in the cerebrospinal fluid were detected in women with unresponsive wakefulness syndrome compared to patients with minimally conscious state.&#x0D; CONCLUSIONS: Further in-depth examination and accumulation of data on patients with chronic disorders of consciousness may provide an opportunity to identify highly informative markers for predicting outcomes and to develop new effective approaches to rehabilitation of consciousness in this category of patients.

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.

Effect of Melatonin Plus Zinc Supplementation on Fatigue Perception in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem, and profoundly debilitating condition, probably of multifactorial etiology. No effective approved drugs are currently available for its treatment. Several studies have proposed symptomatic treatment with melatonin and zinc supplementation in chronic illnesses; however, little is known about the synergistic effect of this treatment on fatigue-related symptoms in ME/CFS. The primary endpoint of the study was to assess the effect of oral melatonin plus zinc supplementation on fatigue in ME/CFS. Secondary measures included participants’ sleep disturbances, anxiety/depression and health-related quality of life. A proof-of-concept, 16-week, randomized, placebo-controlled, double-blind trial was conducted in 50 ME/CFS patients assigned to receive either oral melatonin (1 mg) plus zinc (10 mg) supplementation (n = 24) or matching placebo (n = 26) once daily. Endpoint outcomes were evaluated at baseline, and then reassessed at 8 and 16 weeks of treatment and 4 weeks after treatment cessation, using self-reported outcome measures. The most relevant results were the significant reduction in the perception of physical fatigue in the Mel-Zinc group at the final treatment follow-up versus placebo (p < 0.05), and the significant improvement in the physical component summary at all follow-up visits in the experimental group. Urinary 6-sulfatoxymelatonin levels were significantly elevated though the treatment in experimental group vs. placebo (p < 0.0001); however, no significantly differences were observed for zinc concentration among participants. Our findings suggest that oral melatonin plus zinc supplementation for 16 weeks is safe and potentially effective in reducing fatigue and improving the quality of life in ME/CFS. This clinical study was registered on ClinicalTrials.gov (NCT03000777).

Metabolic responses to polychromatic LED and OLED light at night

Light exposure at night has various implications for human health, but little is known about its effects on energy metabolism during subsequent sleep. We investigated the effects of polychromatic white light using conventional light-emitting diodes (LED) and an alternative light source, organic light-emitting diodes (OLED), producing reduced spectral content in the short wavelength of blue light (455 nm). Ten male participants were exposed to either LED, OLED (1000 lx), or dim (< 10 lx) light for 4 h before sleep in a metabolic chamber. Following OLED exposure, energy expenditure and core body temperature during sleep were significantly decreased (p < 0.001). Fat oxidation during sleep was significantly reduced (p = 0.001) after the exposure to LED compared with OLED. Following exposure to OLED, fat oxidation positively correlated with the 6-sulfatoxymelatonin levels, suggesting that the role of melatonin in lipolysis differs depending on the light. These findings advance our knowledge regarding the role of light in energy metabolism during sleep and provide a potential alternative to mitigate the negative consequences of light exposure at night.

Exploratory assessment of pineal gland volume, composition, and urinary 6-sulfatoxymelatonin levels on prostate cancer risk.

Melatonin levels are partially driven by the parenchyma volume of the pineal gland. Low urinary levels of 6-sulfatoxymelatonin have been associated with increased risk of advanced prostate cancer, but the relationship between pineal gland volume and composition and prostate cancer risk has not been examined. We utilized data from 864 men from the AGES-Reykjavik Study with complete pineal gland volumes and urinary 6-sulfatoxymelatonin measurements. Pineal parenchyma, calcification, and cyst volumes were calculated from brain magnetic resonance imaging. Levels of 6-sulfatoxymelatonin were assayed from prediagnostic urine samples. We calculated Pearson correlation coefficients between parenchyma volume and urinary 6-sulfatoxymelatonin levels. We used Cox proportional hazards regression to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) comparing prostate cancer risk across parenchyma volume tertiles and across categories factoring in parenchyma volume, gland composition, and urinary 6-sulfatoxymelatonin level. Parenchyma volume was moderately correlated with urinary 6-sulfatoxymelatonin level (r = .24; p < .01). There was no statistically significant association between parenchyma volume tertile and prostate cancer risk. Men with high parenchyma volume, pineal cysts and calcifications, and low urinary 6-sulfatoxymelatonin levels had almost twice the risk of total prostate cancer as men with low parenchyma volume, no pineal calcifications or cysts, and low urinary 6-sulfatoxymelatonin levels (HR: 1.98; 95% CI: 1.02, 3.84; p: .04). Although parenchyma volume is not associated with prostate cancer risk, pineal gland composition and other circadian dynamics may influence risk for prostate cancer. Additional studies are needed to examine the interplay of pineal gland volume, composition, and melatonin levels on prostate cancer risk.

Активность зон ядрышковых организаторов у женщин с эндометриозом яичников и бесплодием

Objective. To determine the activity of ribosomal synthesis and its connection with the level of melatonin in women with ovarian endometriosis and infertility. Patients and methods. The study included 49 women with ovarian endometriosis, who were divided into 2 groups: group 1 – 22 women with ovarian endometriosis and infertility, group 2 – 27 women with ovarian endometriosis without infertility. Medical history was collected from all women, who underwent therapeutic and diagnostic laparoscopy, the chronobiological type, the level of 6-sulfatoxymelatonin (aMT6s) in a first morning urine sample and the activity of nucleolar organizer regions in the foci of endometrioid heterotopias of the ovaries were determined. Results. It was found that the level of urinary 6-sulfatoxymelatonin was significantly reduced in patients with ovarian endometriosis and infertility compared to patients with endometriosis without infertility. In group 1, its level was 40.29 ± 7.25 ng/mL, in group 2 – 78.46 ± 15.46 ng/mL (p = 0.044). In patients with ovarian endometriosis and infertility, there was a moderate increase in the activity of ribosomal synthesis due to an increase in the number of intranucleolar inclusions against the background of decreased level of melatonin. In patients of group 2, with a decrease in the level of melatonin, ribosomal synthesis was activated by increasing the number of extranucleolar inclusions. This characterizes the high activity of ribosome synthesis in the cell. Conclusion. In women with ovarian endometriosis and infertility, against the background of low melatonin level, there was an increase in the activity of ribosomal synthesis in the cells of ovarian endometriotic formations. Key words: nucleolar organizer regions activity, melatonin, ovarian endometriosis

Quasi-Experimental study of effects of lighting on rest, activity and melatonin in postpartum women

to compare the parameters of the activity/rest cycle of early postpartum breastfeeding women under a controlled and uncontrolled long wavelength ray light regimen. quasi-experimental study with breastfeeding women and their babies during postnatal rooming-in, São Paulo, Brazil. Participants were allocated to either an experimental (intervention) or a comparison group. The intervention involved exposure of the woman in a controlled room with artificial long wavelength ray light at night. Each woman's level of 6-sulfatoxymelatonin at 24 hours and activity/rest times was analyzed. the mean activity/rest times of women in the experimental and comparison groups were similar. The mean percentages of total load of 6-sulfatoxymelatonin during the day and night were similar (p=0.09). At 24 hours, the experimental group presented a significantly lower mean percentage of total load compared to the comparison group (p=0.04). women who stayed in the room with long-wavelength artificial light showed no difference in activity/rest and 6-sulfatoxymelatonin levels in the early postpartum period.

The Association between Melatonin Levels and Sleep Quality in Patients with Pruritus: A Potential Biomarker on a Candidate Future Treatment.

Background:Melatonin is a hormone that regulates the sleep–wake cycle and has immunomodulatory and anti-inflammatory roles.Aims:The aim of this study is to assess melatonin levels and investigate the association with pruritus severity, sleep quality, and depressive symptoms in dermatoses with nocturnal pruritus.Methods:The study was a prospective study with 82 participants, including 41 patients and 41 healthy volunteers. The visual analog scale (VAS), Pittsburg Sleep Quality Index (PSQI), and Beck Depression Inventory (BDI) were recorded for each patient. To assess the melatonin levels, urinary 6-sulfatoxymelatonin levels in the first urine in the morning were measured.Results:Melatonin concentrations were significantly lower (P = 0.007), while the BDI (P = 0.001) and PSQI (P = 0.001) scores were significantly higher in the patients with pruritus than in the healthy control subjects. There was an inverse correlation between melatonin levels and PSQI scores (r = −0.355, P = 0.023), and a positive correlation was detected between BDI scores and PSQI scores (r = 0.631, P = 0.001) in the pruritus group.Conclusion:Melatonin levels were found to decrease in relation to sleep quality in nocturnal pruritus patients. Low melatonin levels in these patients may be associated with sleep disorders and pruritus.

Treatment of metabolic syndrome in young patients with vitamin D deficiency

The purpose of the study is to increase the effectiveness of treatment of metabolic syndrome (MS) in young patients with vitamin D deficiency. The study involved 54 patients with MS and vitamin D deficiency (50% of women, 50% of men), aged 2044years. To assess the concentration of melatonin at a young age, a control group of 42 practically healthy volunteers with comparable demographic characteristics with no signs of MS was formed. In patients with MS and vitamin D deficiency, there was a significant decrease in the average daily level of 6-sulfatoxymelatonin in the urine by 3.7 times, compared with the group of individuals without MS. Patients with MS and vitamin D deficiency (n=54) were randomly assigned to two groups with comparable clinical and demographic characteristics. Patients of the 1st group (n=27) observed dietary recommendations and took the drug Metformin at a dose of 1700 mg/day for 12 months. In the 2nd group (n=27), in addition to the one indicated in the 1st treatment group, correction of vitamin D deficiency was performed (a micelled preparation of cholecalciferol at a dose of 4000 IU/day, for 6 months, then 2000 IU/day for another 6 months) and the level of melatonin (melatonin preparation at a dose of 3 mg/day for 6 months). After treatment in young patients with MS, there was a significant change in the median of the studied parameters in all therapeutic groups, but more pronounced dynamics was observed in group 2 in terms of: WC in women, BMI, insulin resistance index, LDL cholesterol, TG, hs-CRP, hs-TNF-, IL-6, leptin. To increase the effectiveness of MS treatment in young patients with vitamin D deficiency, it is necessary to determine the level of melatonin (urinary 6-sulfatoxymelatonin) and, if it decreases, carry out correction of melatonin and 25 (OH) vitamin D in addition to the standard therapy of this syndrome.

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.

"Seat of the soul"? The structure and function of the pineal gland in women with alleged spirit possession-Results of two experimental studies.

BackgroundCultural traditions attribute to pineal gland an important role for spiritual experiences. Mediumship and spirit possession are cultural phenomena found worldwide which have been described as having dissociative and psychotic‐like characteristics, but with nonpathological aspects. A sympathetic activation pattern in response to spirit possession has been reported in some studies, but empirical data on pineal gland is scarce in this context.MethodsWe aimed to investigate pineal gland and pituitary volumes, as well as urinary 6‐sulfatoxymelatonin levels in 16 alleged mediums (Medium Group‐MG) compared with 16 healthy nonmedium controls (Control Group) (Experiment 1). Furthermore, we aimed to evaluate urinary 6‐sulfatoxymelatonin and stress reactivity in GM (n = 10) under different physiological conditions (Experiment 2).ResultsIn Experiment 1, MG presented higher scores of anomalous experiences, but there were no between‐group differences regarding mental health or subjective sleep quality. Similar pineal gland and pituitary volumes were observed between groups. There were no between‐group differences in urinary 6‐sulfatoxymelatonin collected under equivalent baseline conditions. In Experiment 2, the rise of anxiety and heart rate in response to mediumistic experience was intermediate between a nonstressful control task (reading) and a stressful control task (Trier Social Stress Test—TSST). No significant differences were observed in 6‐sulfatoxymelatonin urinary levels between the three conditions. The pattern of stress reactivity during the TSST was normal, but with an attenuated salivary cortisol response.ConclusionThe normal neuroimaging and stress reactivity findings in MG contrast with the abnormal results usually observed in subjects with psychotic and dissociative disorders.