Plasma Melatonin Concentrations Research Articles

Comparative Pharmacokinetics of Sustained-Release versus Immediate-Release Melatonin Capsules in Fasting Healthy Adults: A Randomized, Open-Label, Cross-Over Study.

Background: Exogenous melatonin, a nutraceutical for maintaining a healthy sleep-wake cycle and managing sleep disorders, requires large, repeated doses due to its low bioavailability and short half-life. This necessitates the development of a sustained-release formulation with a longer half-life and sustained plasma concentration. Therefore, exogenous novel 5 mg sustained-release melatonin capsules (Melatonin-SR, test product) were formulated. Methods: This open-label cross-over study compared the pharmacokinetics (maximum concentration [Cmax], time to reach Cmax [Tmax], area under the curve [AUC], and elimination half-life [t1/2]) and the safety of Melatonin-SR with 5 mg immediate-release melatonin capsules (Melatonin-IR, reference product) after single-dose oral administration in healthy fasting adults. Results: Sixteen participants (aged 18-45 years) were randomized (1:1) to receive either Melatonin-SR or Melatonin-IR in two periods with a 7-day washout period. Melatonin-SR reported a lower Cmax (11,446.87 pg/mL) compared to Melatonin-IR (22,786.30 pg/mL). The mean Tmax of Melatonin-SR and Melatonin-IR was 1.26 h and 0.87 h, respectively. The mean t1/2 of Melatonin-SR (5.10 h) was prolonged by five-fold compared to Melatonin-IR (1.01 h). One adverse event (vomiting) was reported following the administration of the Melatonin-IR. Conclusions: Melatonin-SR resulted in higher and sustained plasma melatonin concentrations for an extended period and was well-tolerated. Hence, Melatonin-SR may be a promising nutraceutical for maintaining healthy sleep.

Melatonin Bioavailability After Oral Administration of a New Delayed-Release Form in Healthy Male Volunteers.

Two main types of galenic formulation, immediate release and prolonged release, have been developed to optimize melatonin bioavailability. We recently described the kinetic profile of a prolonged-release form generating a peak of plasma melatonin 1 h (Tmax) after intake, followed by a prolonged decay over time. We have developed a new oral form of melatonin with the aim of producing a melatonin peak several hours after intake. The objective is to investigate melatonin bioavailability after administration of this new delayed-release form (DR form). In this single-centre open-label study, 12 healthy male volunteers received one tablet of the DR form containing 1.9 mg melatonin, 10 mg zinc and 200 mg lemon balm extract (Melissa officinalisL aerial parts). Blood samples were collected for 12 h, beginning at 8:00 am. Plasma concentrations of melatonin and 6-sulfatoxymelatonin (6-SMT), the main hepatic melatonin metabolite, were determined by radioimmunoassay. A progressive increase in plasma melatonin concentrations was observed from 20 min and a peak about 3 h after intake (Cmax 740 ± 824 pg/mL; Tmax 179 ± 60min). Concentrations remained high between 140 and 220 min, the concentration remaining physiologically significant (over 100pg/mL) up to 7 h after intake. The DR form was well tolerated. The melatonin release profile was consistent with what was anticipated for the DR form. The DR form generated a 2 h delayed Tmax compared with a prolonged-release form previously evaluated. This suggests that the DR form is suitable for the treatment of certain sleep disorders such as short sleep duration or early awakening. Registration number: NCT05419466.

Determination of Rhythmicity and Gestational Stage-Related Distribution of Blood Plasma Melatonin Concentrations in Donkey Mares.

The aim of this study is to obtain a more complete picture of blood plasma melatonin concentrations in the donkey mares. To this purpose, sampling and statistical processing were carried out in such a way that allowed the researchers to establish the annual and daily rhythms. Based on human observations, according to the hypothesis of the authors, the blood plasma melatonin concentration of pregnant individuals rises during the late gestational period, before parturition. To confirm this, the melatonin concentrations of pregnant and non-pregnant jennies were monitored and compared. In regard to the circannual rhythm, the significantly lowest midnight melatonin value (27.67 pg mL-1) was typical for the summer solstice. Under consideration of circadian changes, a significantly strongest melatonin production (45.16 pg mL-1) was observed on the night of the winter solstice (p < 0.001). Considering gestational age, the blood plasma melatonin concentration (around 38 pg mL-1) does not change as gestation progresses (p = 0.136). The results obtained in this studied population of the domestic ass usefully expand the little knowledge previously gathered about the development of the blood plasma melatonin concentrations of this species.

Concentrations of plasma estradiol, progesterone, melatonin, serotonin and nitric oxide in Tuj ewes after estrus syncronization in and out of breeding season

Concentrations of plasma estradiol, progesterone, melatonin, serotonin and nitric oxide in Tuj ewes after estrus syncronization in and out of breeding season

Dysregulation of circadian clock gene expression patterns in a treatment-resistant animal model of depression.

Circadian rhythm (CR) disturbances are among the most commonly observed symptoms during major depressive disorder, mostly in the form of disrupted sleeping patterns. However, several other measurable parameters, such as plasma hormone rhythms and differential expression of circadian clock genes (ccgs), are also present, often referred to as circadian phase markers. In the recent years, CR disturbances have been recognized as an essential aspect of depression; however, most of the known animal models of depression have yet to be evaluated for their eligibility to model CR disturbances. In this study, we investigate the potential of adrenocorticotropic hormone (ACTH)-treated animals as a disease model for research in CR disturbances in treatment-resistant depression. For this purpose, we evaluate the changes in several circadian phase markers, including plasma concentrations of corticosterone, ACTH, and melatonin, as well as gene expression patterns of 13 selected ccgs at 3 different time points, in both peripheral and central tissues. We observed no impact on plasma corticosterone and melatonin concentrations in the ACTH rats compared to vehicle. However, the expression pattern of several ccgs was affected in the ACTH rats compared to vehicle. In the hippocampus, 10 ccgs were affected by ACTH treatment, whereas in the adrenal glands, 5 ccgs were affected and in the prefrontal cortex, hypothalamus and liver 4 ccgs were regulated. In the blood, only 1 gene was affected. Individual tissues showed changes in different ccgs, but the expression of Bmal1, Per1, and Per2 were most generally affected. Collectively, the results presented here indicate that the ACTH animal model displays dysregulation of a number of phase markers suggesting the model may be appropriate for future studies into CR disturbances.

The Role of Melatonin and Matrix Metalloproteinases in Breast Cancer Pathogenesis: A Comprehensive Review

Background: Breast cancer is a heterogeneous disease with molecular subtypes including Triple Negative Breast Cancer (TNBC), HER2/neu-positive, Luminal Type A, and Luminal Type B, each with unique clinical behaviors and therapeutic responses. This study investigates the role of melatonin, matrix metalloproteinases (MMPs), pro-inflammatory cytokines (IL6 and TNF-alpha), and lactate dehydrogenase (LDH) isoenzymes in breast cancer pathogenesis. Methods: Over three years, 171 breast cancer patients were studied. Blood and urine samples were collected to measure melatonin, MMPs, IL-6, TNF-alpha, LDH-1, and LDH-5 levels. Circulating tumor cells (CTCs) were isolated using density gradient centrifugation and immunomagnetic separation. Melatonin receptor expression on CTCs was analyzed by flow cytometry and immunocytochemistry. Plasma concentrations of melatonin were measured using high-performance liquid chromatography (HPLC), and MMPs, IL-6, TNF-alpha, LDH isoenzymes were quantified using enzyme-linked immunosorbent assays (ELISAs) and electrophoretic methods. Results: The expression of melatonin receptors was lowest in TNBC patients, higher in HER2/neu-positive and ER/PRnegative patients, and highest in Luminal Type A and B patients. TNBC patients exhibited elevated LDH-1 and inflammatory cytokines (IL-6, TNF-alpha), with significantly decreased melatonin levels. HER2/neu-positive patients showed elevated LDH5 and moderate decreases in melatonin. Luminal Type B and A patients had varying degrees of biomarker elevation and melatonin receptor expression. Discussion: The findings suggest a correlation between reduced melatonin signaling and aggressive breast cancer phenotypes, particularly TNBC. Elevated MMPs and pro-inflammatory cytokines underscore the role of inflammation and ECM degradation in cancer progression. Melatonin’s potential inhibitory effects on these pathways highlight its therapeutic promise. The combined assessment of melatonin, MMPs, cytokines, and LDH could guide personalized treatment strategies. Conclusion: This study underscores melatonin’s multifaceted role in breast cancer pathogenesis. Melatonin receptor expression, along with MMP, IL-6, TNF-alpha, and LDH levels, provides a detailed molecular landscape of breast cancer subtypes. Integrating melatonin supplementation into therapeutic regimens holds promise for improving outcomes, particularly inaggressive subtypes like TNBC. Further research and clinical trials are essential to validate these findings and develop effective melatonin-based therapies.

Protective effect of melatonin against metabolic disorders and neuropsychiatric injuries in type 2 diabetes mellitus mice

BackgroundType 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia and progressive cognitive dysfunction, and our clinical investigation revealed that the plasma concentration of melatonin (Mlt) decreased and was closely related to cognition in T2DM patients. However, although many studies have suggested that Mlt has a certain protective effect on glucose and lipid metabolism disorders and neuropsychiatric injury, the underlying mechanism of Mlt against T2DM-related metabolic and cognitive impairments remains unclear. PurposeThe aim of the present study was to investigate the therapeutic effect of Mlt on metabolic disorders and Alzheimer's disease (AD)-like neuropsychiatric injuries in T2DM mice and to explore the possible underlying molecular mechanism involved. MethodsA T2DM mouse model was established by a combination of a high-fat diet (HFD) and streptozotocin (STZ, 100 mg/kg, i.p.), and Mlt (5, 10 or 20 mg/kg) was intragastrically administered for six consecutive weeks. The serum levels of glycolipid metabolism indicators were measured, behavioral performance was tested, and the protein expression of key molecules involved in the regulation of synaptic plasticity, circadian rhythms, and neuroinflammation in the hippocampus was detected. Moreover, the fluorescence intensities of glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1 (IBA-1), amyloid β-protein (Aβ) and phosphorylated Tau (p-Tau) in the hippocampus were also observed. ResultsTreatment with Mlt not only improved T2DM-related metabolic disorders, as indicated by increased serum concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbAlc), insulin (INS), total cholesterol (TC) and triglyceride (TG), improved glucose tolerance and liver and pancreas function but also alleviated AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, as indicated by decreased immobility time in the tail suspension test (TST) and forced swimming test (FST), increased preference indices of novel objects or novel arms in the novel object recognition test (NOR) and Y-maze test (Y-maze), and improved platform positioning capability in the Morris water maze (MWM) test. Moreover, treatment with Mlt also improved the hyperactivation of astrocytes and microglia in the hippocampus of mice, accompanied by reduced expression of interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), Aβ, and p-Tau and increased expression of brain-derived neurotrophic factor (BDNF), Synapsin I, Synaptotagmin I, melatonin receptor 1B (MT1B), brain muscle arnt-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), period 2 (Per2), and cryptochrome 2 (Cry2). ConclusionMlt alleviated T2DM-related metabolic disorders and AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, possibly through a mechanism involving the regulation of glial activation and associated neuroinflammation and the balancing of synaptic plasticity and circadian rhythms in the hippocampus.

Sperm melatonin receptors, seminal plasma melatonin and semen freezability in goats

Goat bucks are seasonal breeders that show variation in sperm quality, endogenous melatonin (MLT), and presumably in the expression of MLT receptors on the sperm throughout the year, which may modify sperm freezability. The aim of this study was to determine whether sperm freezability is associated with (i) endogenous melatonin levels in seminal plasma and (ii) the expression of sperm plasma membrane melatonin receptors (MT1, MT2). To evaluate this, spermatozoa from seven Saanen goat bucks were cryopreserved throughout the year in Mexico using a standard freezing protocol. Seminal plasma MLT concentrations were determined by ELISA and the expression and localization of MT1 and MT2 were detected by immunocytochemistry and confirmed by western blotting. The recovery rate of progressive motility after thawing was higher in spring than autumn and winter; in contrast, the F pattern (CTC assay) was higher in winter than in the other seasons. A proportional increase in the AR pattern (CTC assay) was smaller in winter than in the other seasons and the proportion of sperm showing high plasma membrane fluidity was higher in spring than in summer and autumn. The seminal plasma MLT concentrations showed no significant interseasonal differences. The MT1 receptor was immunolocalised at the apical region of the sperm head, while MT2 was mainly localised in the neck. The relative expression of MLT receptors showed significant differences between summer and winter for all bands, except at 75 kDa of MT2. In conclusion, there was an association between the relative expression of MT1 and MT2 receptors throughout the year and sperm freezability in goat bucks in México. Post-thaw sperm quality is enhanced in semen samples collected during breeding season.

Changes in Behavior and Diel Melatonin Secretion Toward Estivation in Western Sand Lance, Ammodytes japonicus (Uranoscopiformes, Ammodytidae).

Western sand lance, Ammodytes japonicus, is known to have an estivation period, in which they cease feeding and stay in the sand from early summer to late autumn, followed by gonadal maturation. During the feeding period prior to estivation, they swim in daytime and spend the night in the sand. Before they start swimming, they show a typical behavior of head-exposing from the sand, which is likely to be related to foraging and predation avoidance. Our previous study revealed that melatonin regulates such diel behavior of this species. To elucidate the mechanisms of behavioral regulation throughout the life cycle of this sand lance, the present study examined the changes in behavior and melatonin secretion toward the estivation period. Both head-exposing and swimming behaviors were frequently observed at the transition period toward estivation. On the other hand, occurrence of these behaviors was suppressed just before entering estivation. Subsequently, it was found that plasma melatonin concentration was about three times higher at night than in daytime in the non-estivation period, while it was retained at high levels throughout the day in the estivation period. These results indicate that diurnal swimming behavior of sand lance from the feeding to estivation periods is associated with the daily cycle of melatonin secretion.

Effect of exogenous melatonin implant on post-thaw semen quality of buffalo bulls.

Melatonin is an intracellular antioxidant of sperm membrane that protects the cells from lipid peroxidation. Yet, its role as an antioxidant on semen quality of buffalo bulls is still obscure. The present study was undertaken to assess the effect of exogenous melatonin implant (18 mg/50 kg bodyweight) on post-thaw sperm characteristics, oxidative stress, endocrinological profiles and fertility of buffalo bulls. Six apparently healthy breeding Murrah buffalo bulls were randomly selected at bull farm, Guru Angad Dev Veterinary and Animal Sciences University for the present study and divided into two groups viz. control (n = 3) and melatonin implanted group (n = 3). A total of 120 ejaculates were collected from bulls of both groups (n = 60 each) throughout the study period. Most beneficial effects of melatonin implants were observed during post-implantation period. The percentages of post-thaw sperm total and progressive motility, viability and mitochondrial membrane potential were higher (p < .05) in melatonin implanted buffalo bulls compared to controls during post-implantation period. Following melatonin implantation, MDA production in post-thaw semen was lower (p < .05) in melatonin implanted group than in control group. Plasma melatonin and testosterone concentrations were higher (p < .05) in buffalo bulls implanted with melatonin as compared to their control counterparts. No differences (p > .05) in plasma LH concentrations were observed in both groups. First service pregnancy rate was 43.3% using semen of melatonin implanted bulls and 30.0% with semen of controls (p > .05). Thus, melatonin was able to protect sperm membrane against oxidative damage and improve post-thaw semen quality, thereby resulting in higher fertilizing potential of spermatozoa.

Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM.

Purpose: Type 2 diabetes mellitus (T2DM) is associated with multiple neuropsychiatric impairments, including cognitive dysfunction, and melatonin (MLT) plays a crucial role in maintaining normal neuropsychiatric functions. This study is aimed at investigating the change in plasma MLT levels and its association with neuropsychiatric impairments in T2DM patients. Methods: One hundred twenty-six T2DM patients were recruited, and their demographics and clinical data were collected. Apart from the plasma glycated hemoglobin (HbA1c) levels and other routine metabolic indicators, the plasma concentrations of MLT, C-reactive protein (CRP), Interleukin 6 (IL-6), soluble myeloid triggered receptor 1 (sTREM 1), and receptor 2 (sTREM 2) were measured. Moreover, the executive function and depressive tendency were evaluated via the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and the Epidemiological Research Center Depression Scale (CES-D), respectively. Result: Compared with the low HbA1c group, the T2DM patients in the high HbA1c group presented lower plasma MLT levels but higher plasma concentrations of inflammatory biomarker levels, together with higher scores in the BRIEF-A and CES-D scales. Moreover, results of the Pearson correlation test showed that the plasma MLT levels were negatively correlated with the BRIEF-A and CES-D scores, as well as plasma concentrations of HbA1c and inflammatory indications, indicating that MLT may mediate their neuroinflammation and neuropsychiatric impairments. Furthermore, the ROC curve results indicated that plasma MLT levels have a predictive effect on executive impairment and depressive status in T2DM patients. Conclusion: MLT levels decreased in patients with T2DM and were associated with neuropsychiatric impairments and inflammatory status, and MLT might be developed as a therapeutic agent and predictive indicator for T2DM-associated executive impairment and depression status.

Behavioural Parameters of Circadian Rhythm Are Not Correlated with Dim Light Melatonin Onset: An Observational Study on Healthy Volunteers.

Dim light melatonin onset (DLMO) is considered the most reliable marker of the circadian rhythm phase in humans. DLMO may moderately correlate with sleep onset and sleep offset time. There are no sufficient data about the correlations between DLMO and clinical scales assessing sleep quality and daytime symptoms of poor night sleep. The aim of the study was to determine the association between DLMO and basic sleep parameters from actigraphy and sleep diaries, as well as the association between DLMO and the following insomnia clinical scales: the Athens Insomnia Scale (AIS), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and chronotype questionnaires: Morningness-Eveningness Questionnaire (MEQ) and Composite Scale of Morningness (CSM). Participants of the study were healthy volunteers. Sleep parameters were measured by sleep diaries and actigraphy, and the following clinical scales: the AIS, ISI, and ESS, and chronotype questionnaires: MEQ and CSM. DLMO was calculated based on plasma melatonin concentration. The blood samples were collected hourly at five time points between 20:00 and 00:00 during the session in dim red light (<50 lux). Melatonin concertation was determined by LC-MS/MS. Twenty-one volunteers participated in the study. DLMO was calculated in 12 participants. There was a significant correlation between DLMO and ISI (r = 0.60, p = 0.038) and ESS (r = 0.61, p = 0.034). The correlation coefficient between the DLMO and the AIS was also high, however insignificant (r = 0.57, p = 0.054). There were no significant correlations between DLMO and chronotype scales MEQ and CSM. DLMO did not correlate with sleep onset and sleep offset; however, DLMO correlated with the Sleep Fragmentation Index (SFI) (r = 0.67, p = 0.017). DLMO is associated with poorer sleep maintenance, a stronger feeling of insomnia, and sleepiness during the day. Simultaneously, chronotype pattern and circadian rhythm parameters do not correlate with DLMO. Biological circadian rhythm does not reflect the real-life sleep-wake rhythm, indicating that the lifestyle is more often disconnected from the biological clock.

Plasma melatonin night‐time peak levels and 24‐hour area under the curve profile seem higher in AD patients with epileptiform activity than in those without

AbstractBackgroundPlasma melatonin levels drop in elderly, which might become more pronounced in Alzheimer’s disease (AD) as compared to controls.(1) Melatonin can serve as a potential biomarker for AD, given the inverse correlation between cerebrospinal fluid (CSF) melatonin levels and severity of neuropathology (Braak stages).(2) Due to suggested antiepileptic effects(6), melatonin can potentially slow down disease progression as epileptiform activity may contribute to AD disease progression.(3‐5). We here present a preliminary interim analysis of an ongoing study.Aims1. To evaluate melatonin’s potential as biomarker for AD by comparing blood melatonin levels between patients with mild cognitive impairment (MCI) and dementia due to AD and preclinical AD subjects.2. To study the link between melatonin levels and epileptiform activity in AD.MethodsAll subjects underwent a neuropsychological examination, and lumbar puncture for analysis of core AD CSF biomarkers or amyloid brain PET. Subjects belonging to the AD continuum (dementia [n = 7]; MCI [n = 4]; preclinical AD [n = 1]) were diagnosed according to the NIA‐AA research criteria. A subset of subjects (n = 6) underwent 50‐minute magnetoencephalography to detect epileptiform activity. Blood samples were taken multiple times during a 24‐hour period, in in‐hospital controlled circumstances, and were analysed by use of liquid chromatography‐mass spectrometry.ResultsAD patients with epileptiform activity (n = 2) tended to have a higher melatonin 24‐hour area under the curve (AUC) and peak concentration (AUC 517.9pg/ml.h [+/‐140.1pg/ml.h] versus 204.5pg/ml.h [+/‐115.5pg/ml.h]; peak 65.4pg/ml [+/‐14.6pg/ml] versus 25.8pg/ml [+/‐17.5pg/ml]) than AD patients without (n = 4) (p = 0.064 for both; MWU test). There was no statistical difference regarding the melatonin 24‐hour plasma AUC or peak levels between patients with dementia, MCI, preclinical AD subjects (p = 0.760 for both; Kruskall‐Wallis test). We have to interpret these data with caution since sample sizes are still small and more patients are being recruited.ConclusionOn the basis of very preliminary data, 24‐hour plasma melatonin profile and peak plasma melatonin concentration tended to be higher in AD patients with epileptiform activity than in those without. Whether this could be a potential compensatory mechanism against epileptiform activity in AD or whether melatonin could rather have pro‐epileptic effects, remains to be elucidated in future research.

Plasma melatonin concentration during the early post-partum period in Thoroughbred mares and their foals.

The authors aimed to determine the plasma melatonin concentration in mares and their new-born foals in the early post-partum period. Blood samples were collected from the jugular vein of 53 mare-foal pairs within twelve hours after parturition. Plasma melatonin levels were measured by ELISA. The melatonin concentration, adjusted for the moment of parturition using a generalised linear model, was34.58 pg mL-1 in mares. It was significantly lower (27.63 pg mL-1) in the new-born foals. However, the melatonin concentration declined differently by the end of the twelve hours, it decreased less in theoffspring than in the mothers. An artificial light supplementation at the end of gestation reduced the melatonin concentration both in mares and their foals by about 10 pg mL-1, compared to the controls. An elevated melatonin production may be related to preparation of mares for parturition and ensures the chances of survival of offspring, therefore the melatonin may reach its peak at the moment of foalingregardless of its actual time. The effect of low melatonin concentration in new-born foals might be associated with the foal's health and subsequent performance. The need to monitor the melatonin concentration in the offspring justifies further studies.

Association between the plasma concentration of melatonin and behavioral temperament in horses

Aggression in horses may engender serious accidents during riding and non-riding activities. Hence, predicting the temperament of horses is essential for selecting suitable horses and ensuring safety during activity. In certain animals, such as hamsters, plasma melatonin concentrations have been correlated with aggressive behavior. However, whether this relationship applies to horses remains unclear. To address this research gap, this study aimed to evaluate differences in the plasma melatonin concentrations among horses of different breeds, ages, and sexes and examine the correlation between plasma melatonin concentrations and the temperament of the horses, including docility, affinity, dominance, and trainability. Blood samples from 32 horses were collected from the Horse Industry Complex Center of Jeonju Kijeon College. The docility, affinity, dominance, and trainability of the horses were assessed by three professional trainers who were well-acquainted with the horses. Plasma melatonin concentrations were measured using an enzyme-linked immunosorbent assay. The consequent values were compared between the horses of different breeds, ages, and sexes using three-way analysis of variance and least significant difference post hoc test. Linear regression analysis was employed to identify the relationship between plasma melatonin concentrations and docility, affinity, dominance, and trainability. The results showed that the plasma melatonin concentrations significantly differed with breeds in Thoroughbred and cold-blooded horses. However, there were no differences in the plasma melatonin concentrations between the horse ages and sexes. Furthermore, plasma melatonin concentrations did not exhibit a significant correlation with the ranking of docility, affinity, dominance, and trainability.

The protective effect of endogenous melatonin on gilthead seabream sperm during cryopreservation

Cryopreservation is widely used for artificial reproduction techniques (ART) but requires good gamete quality to succeed. Considering the endogenously produced melatonin by the fish and its protective role in the organism, the objective of this experiment was to search for the best moment of the day to collect gilthead seabream (Sparus aurata) sperm with better quality and, at the same time, to test the potential protective effect of the exogenous melatonin during sperm freezing and thawing processes. Fish were first sampled every 6 h, corresponding to the beginning of the light period (6 h), mid-light (12h), beginning of the dark period (18 h), and mid-dark (24 h) to determine melatonin concentration in blood plasma by radioimmunoassay (RIA). The analysis showed higher values at 24 h (244 pg/mL) compared with 12 h (99 pg/mL), which allowed the selection of those moments for the next experiment. After, fish were sampled for sperm collection at mid-light (ML, 12 h) and mid-dark (MD, 24 h), and fresh sperm was used to assess gamete quality and for the cryopreservation assay. Sperm samples were cryopreserved to test supplementation of different melatonin concentrations (0.001 mM, 0.01 mM and 0.1 mM) together with a control group without added melatonin. Gamete quality was assessed through spermatozoa concentration and motility (CASA system), cell viability (PI/SYBR-green) and DNA fragmentation (Comet assay). Despite cell viability that was higher at ML, most of the fresh sperm motility parameters did not differ between ML and MD, only linearity (LIN) was enhanced at MD. Nevertheless, in cryopreserved samples, total motility (TM) was significantly higher at MD in all melatonin treatments, control, and fresh samples, revealing an endogenous night-effect. Moreover, spermatozoa concentration was also higher at MD (28.9 × 109/mL) than at ML (20.7 × 109/mL). Supplemented melatonin did not confer extra protection to gilthead seabream sperm during cryopreservation since the tested concentrations did not differ between the control in any sperm quality test. It is here suggested that endogenously produced melatonin may contribute to the improvement of some gamete quality parameters at mid-dark, allowing the aquaculture sector to select better sperm quality in a non-invasive way by choosing it as the best moment of the day for sperm collection.

Correlation of Plasma Melatonin Concentration and Alertness Level Among Female Nurses in Jakarta Indonesia

Correlation of Plasma Melatonin Concentration and Alertness Level Among Female Nurses in Jakarta Indonesia

Improve sleep in critically ill patients: Study protocol for a randomized controlled trial for a multi-component intervention of environment control in the ICU.

In critically ill patients, sleep and circadian rhythms are greatly altered. These disturbances have been associated with adverse consequences, including increased mortality. Factors associated with the ICU environment, such as exposure to inadequate light and noise levels during the day and night or inflexible schedules of daily care activities, have been described as playing an essential role in sleep disturbances. The main objective of this study is to evaluate the impact of the use of a multifaceted environmental control intervention in the ICU on the quantity and quality of sleep, delirium, and post-intensive care neuropsychological impairment in critically ill patients. This is a prospective, parallel-group, randomized trial in 56 critically ill patients once they are starting to recover from their acute illness. Patients will be randomized to receive a multifaceted intervention of environmental control in the ICU (dynamic light therapy, auditory masking, and rationalization of ICU nocturnal patient care activities) or standard care. The protocol will be applied from enrollment until ICU discharge. Baseline parameters, light and noise levels, polysomnography and actigraphy, daily oscillation of plasma concentrations of Melatonin and Cortisol, and questionnaires for the qualitative evaluation of sleep, will be assessed during the study. In addition, all patients will undergo standardized follow-up before hospital discharge and at 6 months to evaluate neuropsychological impairment. This study is the first randomized clinical trial in critically ill patients to evaluate the effect of a multicomponent, non-pharmacological environmental control intervention on sleep improvement in ICU patients. The results will provide data about the potential synergistic effects of a combined multi-component environmental intervention in ICU on outcomes in the ICU and long term, and the mechanism of action. ClinicalTrials.gov, NCT. Registered on January 10, 2023. Last updated on 24 Jan 2023.

Melatonin in Newborn Infants Undergoing Surgery: A Pilot Study on Its Effects on Postoperative Oxidative Stress

Surgery is frequently associated with excessive oxidative stress. Melatonin acts as an antioxidant and transient melatonin deficiency has been described in neonatal surgical patients. This randomized, blinded, prospective pilot study tested the hypothesis that oral melatonin supplementation in newborn infants undergoing surgery is effective in reducing perioperative oxidative stress. A total of twenty-three newborn infants requiring surgery were enrolled: 10 received a single dose of oral melatonin 0.5 mg/kg in the morning, before surgery (MEL group), and 13 newborns served as the control group (untreated group). Plasma concentrations of melatonin, Non-Protein-Bound Iron (NPBI), Advanced Oxidation Protein Products (AOPP), and F2-Isoprostanes (F2-IsoPs) were measured. Both in the pre- and postoperative period, melatonin concentrations were significantly higher in the MEL group than in the untreated group (preoperative: 1265.50 ± 717.03 vs. 23.23 ± 17.71 pg/mL, p < 0.0001; postoperative: 1465.20 ± 538.38 vs. 56.47 ± 37.18 pg/mL, p < 0.0001). Melatonin significantly increased from the pre- to postoperative period in the untreated group (23.23 ± 17.71 vs. 56.47 ± 37.18 pg/mL; pg/mL p = 0.006). In the MEL group, the mean blood concentrations of NPBI, F2-IsoPs, and AOPP significantly decreased from the pre- to the postoperative period (4.69 ± 3.85 vs. 1.65 ± 1.18 micromol/dL, p = 0.049; 128.40 ± 92.30 vs. 50.25 ± 47.47 pg/mL, p = 0.037 and 65.18 ± 15.50 vs. 43.98 ± 17.92 micromol/dL, p = 0.022, respectively). Melatonin concentration increases physiologically from the pre- to the postoperative period, suggesting a defensive physiologic response to counteract oxidative stress. The administration of exogenous melatonin in newborn infants undergoing surgery reduces lipid and protein peroxidation in the postoperative period, showing a potential role in protecting babies from the deleterious consequences of oxidative stress.

Melatonin Treatment of Circadian Rhythm Sleep-Wake Disorder in Obese Children Affects the Brain-Derived Neurotrophic Factor Level.

Previous studies proved that the brain-derived neurotrophic factor (BDNF) is correlated with sleep regulation, yet how BDNF functions and reacts in the melatonin treatment of circadian rhythm sleep-wake disorder (CRSWD) among obese children remain enigmatic. Focusing on CRSWD in obese children, this study monitored their sleep efficiency and serum BDNF level changes during the treatment of melatonin. In total, 35 obese children diagnosed with CRSWD were included in this study and administrated melatonin (3 mg/night) for 3 months. Blood samples were collected 24 hours before and after the treatment (08:00, 12:00, 16:00, 20:00, 24:00, and 04:00). Subsequently, the plasma melatonin level and serum BDNF level were measured by enzyme-linked immunosorbent assay. Sleep parameters, including sleep quality, Pittsburgh Sleep Quality Index as well as melatonin and BDNF levels before and after treatment, were recorded to profile the effectiveness and safety of melatonin treatment. Melatonin treatment increased plasma melatonin concentration and restored circadian rhythm. Besides, the serum BDNF level showed a significant increase, representing a strong positive correlation with melatonin concentration (p = 0.026). Patients experienced much-improved sleep efficiency (P < 0.001), with longer actual sleep time (P < 0.001), shorter sleep onset latency, and fewer awakenings after treatment (P < 0.001). Besides, melatonin was well tolerated by patients without producing severe side effects. Melatonin treatment effectively improved CRSWD among obese children with their serum BDNF levels increased, indicating that BDNF is a key regulator in CRSWD in obese children. This study may offer theoretical support for melatonin treatment of CRSWD in obese children.