Melatonin Profiles Research Articles

Gut microbiota-melatonin signaling axis in acute pancreatitis: Revealing the impact of gut health on pancreatic inflammation and disease severity in a case-control study.

Acute pancreatitis (AP), a severe inflammatory condition affecting the pancreas requires investigation into its predictors. Melatonin, a compound with anti-inflammatory and antioxidant properties, has shown promise in managing AP. Additionally, the gut microbiota, a community of microorganisms residing in the intestines has been linked to AP development. This study aims to explore the correlation between melatonin and gut microbiota in predicting AP severity. This study involved 199 participants, with 99 diagnosed with AP and 100 serving as healthy controls. The AP patients were categorized into 2 groups based on the severity of their condition: mild AP (MAP) and severe AP (SAP). Serum melatonin levels were measured on Days 1, 3, and 5 of hospitalization, and gut microbiota composition was examined via 16S rRNA gene sequencing. Other parameters were evaluated, such as the Acute Physiology and Chronic Health Evaluation (APACHE) score, Ranson, and Acute Gastrointestinal Injury (AGI) scores. Melatonin levels were significantly lower in subjects with severe AP compared those with mild AP (18.2 ng/mL vs 32.2 ng/mL, P = .001), and melatonin levels decreased significantly in patients with AP on Days 3 and 5. The study also revealed that individuals with AP exhibited a significantly altered gut microbiota composition compared to control individuals, with a lower Shannon index and higher Simpson index. The AUCs for Simpson index and F/B ratio were significantly higher than those for other biomarkers, indicating that these gut microbiota markers may also be useful for AP prediction. The study proposes that there is a relationship between melatonin levels and the dynamics of gut microbiota profiles in relation to the severity of AP. As a result, the severity of the disease can be assessed by assessing the levels of serum melatonin and gut microbiota profiles.

The dark side of apnea: altered 24-hour melatonin secretion in obstructive sleep apnea (OSAS) is disease severity dependent

PurposeMelatonin aids in the synchronization of the circadian rhythm to the external environment. Few studies have tried to elucidate the relationship between melatonin and obstructive sleep apnea syndrome (OSAS). These often include few patients, do not differentiate between OSAS severity and/or do not analyse a 24-h melatonin profile. This study set out to investigate disease severity dependent differences in 24-h salivary melatonin secretion of OSAS patients compared to a reference population in a retrospective design.Methods24-h salivary melatonin profiles of 169 OSAS patients were analysed (55 light, 66 moderate, 48 severe) as well as 91 reference patients. Several aspects of the melatonin curve were analysed and stratified according to OSAS severity. Parameters included: dim light melatonin onset (DLMO), time of returning below DLMO (DLMOoff), peak melatonin concentration and time, and total melatonin exposure.ResultsSignificant effects were corrected for confounding by age and sex using linear regression. Our analysis shows that, compared to reference and in a disease dependent manner, OSAS patients have a significantly lower 24-h melatonin curve, lower melatonin peak concentration, lower total melatonin exposure and a smaller proportion of patients reach DLMO. The differences in peak melatonin production and total melatonin exposure were resistant to confounding by age and/or sex.ConclusionThis study describes clear OSAS severity dependent abnormalities in melatonin production in OSAS patients, independent of sex and/or age. Future research should indicate whether oral melatonin supplementation has beneficial effects in OSAS patients with attenuated endogenous melatonin production.

A Comprehensive Review on the Role of Melatonin's Anesthetic Applications in Pediatric Care.

Anesthesia is critical to pediatric care, ensuring the safety and comfort of children undergoing medical procedures. With a growing interest in alternative anesthetic agents, melatonin has emerged as a promising candidate due to its sedative, analgesic, anti-inflammatory, and neuroprotective properties. This comprehensive review explores the potential applications of melatonin in pediatric anesthesia. We delve into the pharmacological characteristics of melatonin, its anesthetic properties, and its clinical applications in pediatric care, including preoperative sedation, adjunct to general anesthesia, postoperative pain management, and prevention of emergence delirium. Additionally, we discuss the safety profile of melatonin, potential adverse effects, and comparative analysis with traditional anesthetics. Finally, we highlight future research directions to provide insights into melatonin's role in pediatric anesthesia and its implications for clinical practice.

Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase.

Melatonin, a pineal hormone that modulates circadian rhythms, sleep, and neurotransmitters, is widely used to treat sleep disorders. However, there are limited studies on the safety of melatonin. Therefore, we aimed to present the overall patterns of adverse events (AEs) following melatonin administration and identify potential safety signals associated with melatonin. Using VigiBase, a global individual case safety report (ICSRs) database managed by the World Health Organization (WHO), we conducted a retrospective, observational, pharmacovigilance study of melatonin between January 1996 and September 2022. Disproportionality analysis was conducted using two comparator settings: all other drugs and other sleep medications. We used multivariable logistic regression to estimate reporting odds ratios (RORs) with 95% confidence intervals (CIs) to compare the frequencies of AEs reporting between melatonin and each comparator setting. Furthermore, we assessed adverse events of special interests (AESIs) that could potentially be associated with melatonin. Signals were identified when the following criteria were met: cases ≥3, x2 ≥ 4, IC025 ≥ 0, and the lower end of the 95% CI of ROR > 2. These signals were then compared with the AE information on the drug labels provided by regulatory bodies. A total of 35 479 AE reports associated with melatonin were identified, with a higher proportion of reports from females (57.1%) and individuals aged 45-64 years (20.8%). We identified 21 AEs that were commonly detected as safety signals in the disproportionality analyses, including tic, educational problems, disturbance in social behavior, body temperature fluctuation, and growth retardation. In AESI analyses, accidents and injuries (adjusted ROR 2.97; 95% CI, 2.80-3.16), fall (2.24; 2.12-2.37), nightmare (4.90; 4.37-5.49), and abnormal dreams (3.68; 3.19-4.25) were detected as a signal of melatonin when compared to all other drugs, whereas those signals were not detected when compared to other sleep medications. In this pharmacovigilance study, exogenous melatonin showed safety profiles comparable to other sleep medications. However, several unexpected potential safety signals were identified, underscoring the need for further investigation at the population level.

Repetitive Transcranial Magnetic Stimulation Alleviates MPTP-Induced Parkinson's Disease Symptoms by Regulating CaMKII-CREB-BMAL1 Pathway in Mice Model.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that shows promise for the treatment of Parkinson's disease (PD). However, there is still limited understanding of the optimal stimulation frequencies and whether rTMS can alleviate PD symptoms by regulating the CaMKII-CREB-BMAL1 pathway. A PD mouse model was induced intraperitoneally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and treated with 1 Hz, 5 Hz, and 10 Hz rTMS. The neurological function, survival of dopaminergic neurons, and protein levels of Tyrosine hydroxylase (TH), α-synuclein(α-syn), and brain-derived neurotrophic factor (BDNF) in the striatum were measured to determine the optimal stimulation frequencies of rTMS treatment in PD mice. The levels of melatonin, cortisol, and the circadian rhythm of Brain and muscle ARNT-like 1 (BMAL1) in PD model mice were detected after optimal frequency rTMS treatment. Additionally, KN-93 and Bmal1siRNA interventions were used to verify that rTMS could alleviate PD symptoms by regulating the CaMKII-CREB-BMAL1 pathway. Administration of 10 Hz rTMS significantly improved neurological function, increased the protein levels of TH and BDNF, and inhibited abnormal aggregation of a-syn. Furthermore, administration of 10 Hz rTMS regulated the secretion profile of cortisol and melatonin and reversed the circadian arrhythmia of BMAL1 expression. After the KN-93 intervention, the MPTP+rTMS+KN-93 group exhibited decreased levels of P- Ca2+/calmodulin-dependent protein kinase II (CaMKII)/CaMKII, P-cAMP-response-element-binding protein (CREB)/CREB, BMALI, and TH. After Bmal1siRNA intervention, the protein levels of BMAL1 and TH were significantly reduced in the MPTP+10 Hz+ Bmal1siRNA group. At the same time, there were no significant changes in the proportions of P-CaMKIIα/CaMKIIα and P-CREB/CREB expression levels. Finally, immunohistochemical analysis showed that the number of TH-positive neurons was high in the MPTP+10 Hz group, but decreased significantly after KN-93 and Bmal1siRNA interventions. Treatment with 10 Hz rTMS alleviated MPTP-induced PD symptoms by regulating the CaMKII-CREB-BMAL1 pathway. This study provides a comprehensive perspective of the therapeutic mechanisms of rTMS in PD.

Modification in ICU Design May Affect Delirium and Circadian Melatonin: A Proof of Concept Pilot Study.

Nonpharmacologic delirium management is recommended by current guidelines, but studies on the impact of ICU design are still limited. The study's primary purpose was to determine if a multicomponent change in room design prevents ICU delirium. Second, the influence of lighting conditions on serum melatonin was assessed. Prospective observational cohort pilot study. The new design concept was established in two two-bed ICU rooms of a university hospital. Besides modifications aimed at stress relief, it includes a new dynamic lighting system. Seventy-four adult critically ill patients on mechanical ventilation with an expected ICU length of stay of at least 48 hours, treated in modified or standard rooms. None. The clinical examination included a prospective assessment for depth of sedation, delirium, and pain every 8 hours using validated scores. Blood samples for serum melatonin profiles were collected every 4 hours for a maximum of three 24-hour periods. Seventy-four patients were included in the analysis. Seventy-six percent ( n = 28) of patients in the standard rooms developed delirium compared with 46% of patients ( n = 17) in the modified rooms ( p = 0.017). Patients in standard rooms (vs. modified rooms) had a 2.3-fold higher delirium severity (odds ratio = 2.292; 95% CI, 1.582-3.321; p < 0.0001). Light intensity, calculated using the measure of circadian effective irradiance, significantly influenced the course of serum melatonin ( p < 0.0001). Significant interactions ( p < 0.001) revealed that differences in serum melatonin between patients in standard and modified rooms were not the same over time but varied in specific periods of time. Modifications in ICU room design may influence the incidence and severity of delirium. Dedicated light therapy could potentially influence delirium outcomes by modulating circadian melatonin levels.

An independent comparison of the Novolytix salivary melatonin radioimmunoassay with the new Novolytix salivary melatonin enzyme-linked immunosorbent assay.

The dim light melatonin onset (DLMO) is the current gold standard biomarker of the timing of the central circadian clock in humans and is often assessed from saliva samples. To date, only one commercially available salivary melatonin assay is considered accurate at the low daytime levels required to accurately detect the DLMO (Novolytix RIA RK-DSM2). The aim of this study was to conduct the first independent evaluation of a newly improved enzyme-linked immunosorbent assay (ELISA; Novolytix MLTN-96) and compare it with the recommended radioimmunoassay (RIA)-both in terms of melatonin concentrations and derived DLMOs. Twenty participants (15 females, 18-59 years old) provided saliva samples every 30 min in dim light starting 6 h before their habitual bedtime, yielding a total of 260 saliva samples. Both the RIA and ELISA yielded daytime melatonin concentrations <2 pg/mL, indicating adequate accuracy to detect the DLMO. The melatonin concentrations from the two assays were highly correlated (r = .94, p < .001), although the RIA yielded lower levels of melatonin concentration than the ELISA, on average by 0.70 pg/mL (p = .006). Seventeen DLMOs were calculated from the melatonin profiles and the DLMOs from both assays were not statistically different (p = .36) and were highly correlated (r = .97, p < .001). Two DLMOs derived from the RIA occurred more than 30 min earlier than the DLMO derived from the ELISA. These results indicate that the new Novolytix ELISA is an appropriate assay to use if the Novolytix RIA is not feasible or available.

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.

Effect of oral melatonin treatment on insulin resistance and diurnal blood pressure variability in night shift workers. A double-blind, randomized, placebo-controlled study

BackgroundNight shift work is associated with sleep disturbances, obesity, and cardiometabolic diseases. Disruption of the circadian clock system has been suggested to be an independent cause of type 2 diabetes and cardiovascular disease in shift workers. We aimed to improve alignment of circadian timing with social and environmental factors with administration of melatonin. MethodsIn a randomized, placebo-controlled, prospective study, we analysed the effects of 2 mg of sustained-release melatonin versus placebo on glucose tolerance, insulin resistance indices, sleep quality, circadian profiles of plasma melatonin and cortisol, and diurnal blood pressure profiles in 24 rotating night shift workers during 12 weeks of treatment, followed by 12 weeks of wash-out. In a novel design, the time of melatonin administration (at night or in the morning) depended upon the shift schedule. We also compared the baseline profiles of the night shift (NS) workers with 12 healthy non-night shift (NNS)-working controls. ResultsWe found significantly impaired indices of insulin resistance at baseline in NS versus NNS (p < 0.05), but no differences in oral glucose tolerance tests nor in the diurnal profiles of melatonin, cortisol, or blood pressure. Twelve weeks of melatonin treatment did not significantly improve insulin resistance, nor did it significantly affect diurnal blood pressure or melatonin and cortisol profiles. Melatonin administration, however, caused a significant improvement in sleep quality which was significantly impaired in NS versus NNS at baseline (p < 0.001). ConclusionsRotating night shift work causes mild-to-moderate impairment of sleep quality and insulin resistance. Melatonin treatment at bedtime improves sleep quality, but does not significantly affect insulin resistance in rotating night shift workers after 12 weeks of administration.

PSIII-18 Effect of Industrial Hemp Supplementation on the Salivary Melatonin Concentrations of Angus Cattle at Different Phase of Reproductive Cycle

Abstract Melatonin is an indoleamine, a neurotransmitter and neurohormone mainly produced in pineal gland but also in the ovary. It has an important role in reproduction, antioxidant, immune system and circadian behavior. Industrial hemp is increasingly being included in animal feeds and it is therefore important to evaluate the effect of industrial hemp supplementation on the profiles of melatonin following different phases of reproductive cycle. Twenty apparently healthy Angus heifers, aged 19 months with average body weight of 363 kg and body condition score of 6.5 were randomly divided into two groups of ten heifers each in a completely randomized design. Group 1 (n = 10) were supplemented with grounded industrial hemp at 20/200mg of the concentrate, and group 2 (n = 10) no industrial hemp supplementation. Hay and water were provided ad libitum. The animals were acclimatized for 1 week after which they were synchronized using the 7-day CO-Synch protocols. Salivary samples were collected at preestrus, during estrus and at post estrus. Melatonin in the saliva was assayed with a competitive ELISA kit. The salivary melatonin concentrations were greater (P &amp;gt; 0.05 in the treated groups at estrus (25.29 ± 1.48 pg/mL), pro-estrus (23.98 ± 2.3 pg/mL) and post-estrus (20.31 ± 3.0 pg/mL) compared with the untreated groups at pre-estrus (18.9 ± 1.5 pg/mL), estrus (20.4 ± 2.22 pg/mL) and post estrus (17.22 ± 2.6 pg/mL).The profiles of the salivary melatonin were greater (P &amp;gt; 0.05) at estrus phase in the hemp treated groups compared with the pre-estrus and post estrus phase of the treated groups; however, numerical but non-significant increases were observed in the untreated group at estrus phase compared with the pre-estrus and post estrus phases. It was concluded that industrial hemp supplementation could improve melatonin concentrations and hence improve reproductive, antioxidant and immune function of the cattle.

Changes in Melatonin Concentration in a Clinical Observation Study under the Influence of Low-Frequency Magnetic Fields (Magnetic Stimulation in Men with Low Back Pain)-Results of Changes in an Eight-Point Circadian Profile.

The aim of this study was to assess the changes in melatonin concentration under the influence of magnetic stimulation in men with low back pain. A total of 15 men were used in this study, divided into two groups. In Group 1, consisting of seven men, the M1P1 Viofor JPS program was used twice a day for 8 min, at 08:00 and 13:00. In Group 2, consisting of eight men, the M2P2 Viofor JPS program was used once a day for 12 min at 10:00. The application was subjected to the whole body of patients. The treatments in both groups lasted 3 weeks, for 5 days each week, with breaks on weekends. The diurnal melatonin profile was determined the day before exposure and the day after the last treatment, as well as at one-month follow-up. Blood samples were collected eight times a day. In both programs, magnetic stimulation did not reduce the nocturnal peak of melatonin concentration. After exposure, prolonged secretion of melatonin was observed until the morning hours. The impact of the magnetic field was maintained 1 month after the end of the application. The effect of the magnetic field was maintained for 1 month from the end of the application, which confirms the thesis about the occurrence of the phenomenon of biological hysteresis. The parameters of the magnetic fields, the application system, and the time and length of the application may affect the secretion of melatonin.

THU611 Circadian Misalignment Of Melatonin Secretion In Adrenal Insufficiency (AI)

Abstract Disclosure: M. Darji: None. S. Pannain: None. S. Sam: None. E. Van Cauter: None. E.C. Hanlon: None. Background: Despite glucocorticoid replacement, the mortality risk of AI remains markedly elevated. Under normal conditions, the circadian rhythm of endogenous cortisol levels is a major internal synchronizing signal between central and peripheral circadian clocks. There is increasing evidence indicating that circadian misalignment has a host of adverse effects, including increased cardio-metabolic risk. The present study aimed to assess circadian function in AI patients, as compared to individually-matched healthy subjects, under controlled laboratory conditions. The 24-h profile of melatonin, normally secreted exclusively at night, was used as the marker of central circadian timing. The 24-h profile of leptin was used as a marker of peripheral circadian function. Methods: Plasma cortisol, melatonin, and leptin were measured over a 24-h period every 30-60 minutes under controlled light-dark, sleep-wake and dietary conditions. A best-fit curve was calculated for each individual hormonal profile using a locally weighted nonlinear regression procedure with a window of 4 hours. The peak and the nadir were defined as the maximum and minimum of the best-fit curve, respectively. The amplitude was defined as half of the difference between the peak and the nadir. Sleep was polygraphically recorded. During daytime hours, the participants completed validated questionnaires assessing Vigor, Mood and Sleepiness. Results: Complete data sets were obtained in 15 AI patients (12 women; age: 47.9 ±12.5 years, BMI: 26.6 ± 12.5 kg/m2; mean ± SD). Twelve AI patients were on hydrocortisone treatment (total dose range: 20 to 40mg/day, number of doses: 1-5 /day) and 3 were on prednisone treatment. Controls (n=15, 12 women) were aged 48.5 ±14.5 years with BMI of 26.5 ± 5.4 kg/m2. The amplitude of the cortisol profile was wider in AI patients, relative to controls, with a higher morning peak and an extended and lower nocturnal nadir. Unexpectedly, we observed a marked difference in the melatonin profile in AI patients as compared to controls. A daytime phase of elevated melatonin levels, culminating prior to lights off while the patients were awake, was detected in 9 of the 15 AI patients. The nocturnal elevation persisted with a similar amplitude to that observed in controls but was advanced by 1-2 hours. The 24-h leptin profile was similar in the two groups. The presence of a daytime melatonin peak in AI patients was associated with lower ratings of vigor and mood, and higher ratings of sleepiness. Conclusion: Glucocorticoid treatment to replace the endogenous levels and circadian rhythmicity of cortisol in AI may impact central circadian timing, resulting in daytime, in addition to nighttime, release of melatonin. This finding suggests that exogenous cortisol replacement that does not mimic a normal 24-h rhythm, may cause central circadian dysfunction and contribute to alterations in mood, vigor and sleepiness. Presentation: Thursday, June 15, 2023

THU315 Sleep And Circadian Regulation, And Intrinsically Photosensitive Retinal Ganglion Cells Function In Diabetic Retinopathy

Abstract Disclosure: S. Reutrakul: None. J.J. McAnany: None. J.C. Park: None. F.Y. Chau: None. K.K. Danielson: None. P. Bharati: None. S. Pannain: None. E. Van Cauter: None. E.C. Hanlon: None. Background: Diabetic retinopathy (DR) is associated with a dysfunction of intrinsically photosensitive retinal ganglion cells (ipRGCs), a crucial component of the entrainment of the circadian system and of the photic entrainment of melatonin secretion. We explored ipRGC function, sleep, 24-h melatonin and cortisol profiles in patients with and without DR. Methods: Type 2 diabetes patients with DR (n=10) and without DR (n=7,) participated. ipRGC function was inferred from the post illumination pupil response (PIPR). Sleep was assessed by 14-day actigraphy. Serum was sampled at hourly intervals for 24hrs for melatonin and cortisol measurement. Results: Mean (SD) age (53.8 (8.1) vs (54.0 (8.6) yr) and mean A1C (7.5 (1.7) vs. 7.1 (0.9)%) did not differ between DR and no-DR patients. PIPR was significantly smaller in DR than no-DR patients (0.14 (0.16) vs. 0.33 (0.10), p=0.001). Nightly sleep duration and efficiency were similar, but sleep variability (standard deviation of daily sleep duration over 7 nights) tended to be larger in DR than no-DR patients (84.1 (29.8) vs. 59.5 (21.8) minutes), p=0.08. Twenty four-hour serum melatonin output was significantly lower in DR than no-DR patients (103.1 (95.4) pg/ml vs. 231.1 (131.3) pg/ml, p=0.034). All no-DR patients exhibited the classical 24-h profile of melatonin with consistently low levels during the day time and a clear nocturnal rise peaking around the middle of the night. In contrast, a normal melatonin rhythm was observed only in 3 of the 10 patients with DR. Six DR patients had 24-h mean melatonin level under 3 pg/ml, five without any evident day-night pattern. One DR patient had a shift in melatonin timing. There was a significant correlation between PIPR and 24-h melatonin output, r= 0.726, p&amp;lt;0.001, but not with sleep variability. In contrast, mean 24-h cortisol profiles and levels, however, were not significantly different between the two groups (mean levels DR 6.18 (1.23) vs no-DR 6.18 (0.73) μg/dL), Conclusion: DR is associated with ipRCGs dysfunction, irregular sleep, and with major disruptions of the 24-hour melatonin rhythm while cortisol rhythm was maintained, suggesting circadian dysfunction in those with type 2 diabetes and retinopathy. Whether melatonin supplementation is beneficial in type 2 diabetes with DR should be explored. Presentation: Thursday, June 15, 2023

Assessment of plasma melatonin profile in summer anestrous buffaloes exhibiting differential fertility following melatonin implants treatment

Plasma melatonin vis-a-vis anestrus or estrus status of buffaloes during summer or winter season (n=50 in each group) suggested its impact on reproductive axis as plasma melatonin activity tended to be higher (P&gt;0.05) in buffaloes exhibiting estrus compared to their anestrous counterparts irrespective of season. The differential reproductive status of these buffaloes was confirmed by history as well as differences (P&lt;0.05) in diameter of largest follicle and luteal profile. Further, for evaluating the impact of melatonin treatment during summer season on reproductive axis, 132 anestrous buffaloes were subcutaneously inserted 2x4 mm absorbable slow-release melatonin implants (18 mg/50 kg b wt) at the base of left ear and 60 buffaloes were used as control. In these buffaloes, ovarian ultrasonography and jugular vein blood sampling was carried out at 7-day interval till day 35 post-treatment or till ovulation, whichever was earlier. Control and implanted buffaloes were subjected to artificial insemination (AI) at overt or induced estrus followed by pregnancy diagnosis at day 90 post-AI. In treatment group, an increase (P&lt;0.05) in plasma melatonin was recorded in all the buffaloes, exhibiting differential fertility status, during post-treatment study period compared to their pre-treatment and control group values. However, within treatment group, there was no difference (P&gt;0.05) in plasma melatonin between ovulatory or non-ovulatory as well as between pregnant or non-pregnant counterparts. Moreover, plasma melatonin within control buffaloes remained similar (P&gt;0.05) throughout the study period irrespective of differential exhibition of fertility. It can be concluded that factors other than circulating melatonin are also involved in the display of differential fertility in terms of initiation of ovarian cyclicity/ovulation or ability to conceive in summer anestrous buffaloes.

Melatonin secretion patterns are associated with cognitive vulnerability and brain structure in bipolar depression

ABSTRACT Circadian rhythm disruption is a core symptom of bipolar disorder (BD), also reflected in altered patterns of melatonin release. Reductions of grey matter (GM) volumes are well documented in BD. We hypothesized that levels and timing of melatonin secretion in bipolar depression could be associated with depressive psychopathology and brain GM integrity. The onset of melatonin secretion under dim light conditions (DLMO) and the amount of time between DLMO and midsleep (i.e. phase angle difference; PAD) were used as circadian rhythm markers. To study the time course of melatonin secretion, an exponential curve fitting the melatonin values was calculated, and the slope coefficients (SLP) were obtained for each participant. Significant differences were found between HC and BD in PAD measures and melatonin profiles. Correlations between PAD and depressive psychopathology were identified. Melatonin secretion patterns were found to be associated with GM volumes in the Striatum and Supramarginal Gyrus in BD. Our findings emphasized the role of melatonin secretion role as a biological marker of circadian synchronization in bipolar depression and provided a novel insight for a link between melatonin release and brain structure.

Diurnal Variation of L-Arginine and the Cardiovascular Risk Markers Asymmetric and Symmetric Dimethylarginine and Homoarginine in Rotating Night Shift Workers and Controls.

Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) interfere with nitric oxide (NO) formation from L-arginine via different mechanisms. ADMA is a biomarker of cardiovascular disease and mortality, whilst SDMA is a biomarker of mortality after ischemic stroke. Homoarginine, another L-arginine-derived amino acid, is associated with stroke and congestive heart failure. Acute ischemic events like myocardial infarction show a time-of-day variation in the timing of their onset, as do NO-mediated vascular function and blood pressure. We studied whether the plasma concentrations of L-arginine-related amino acid metabolites show diurnal variation in a clinical study comparing 12 non-night shift workers with 60 rotating night shift workers. The plasma concentrations of L-arginine-related biomarkers, melatonin, and cortisol were measured every 3 h during a 24-h period. In addition, 24-h blood pressure recordings were performed. In non-night shift workers, L-arginine and homoarginine plasma concentrations showed diurnal variation with a 12-h period, which were both attenuated in night shift workers. ADMA and SDMA showed a 24-h rhythmicity with no significant differences in phase between night shift and non-night shift workers. The plasma profiles of melatonin and cortisol were not significantly different between both groups, suggesting that the rotating night shift work does not have a major influence on central suprachiasmatic nuclei clock timing. In addition, systolic and diastolic blood pressure patterns were similar between both groups. Our data show diurnal variation of dimethylarginines with the timing of their acrophases corresponding to the published timing of the peak incidence of cardiac ischemic events.

A cysteine-rich secretory protein involves in phytohormone melatonin mediated plant resistance to CGMMV

BackgroundMelatonin is considered to be a polyfunctional master regulator in animals and higher plants. Exogenous melatonin inhibits plant infection by multiple diseases; however, the role of melatonin in Cucumber green mottle mosaic virus (CGMMV) infection remains unknown.ResultsIn this study, we demonstrated that exogenous melatonin treatment can effectively control CGMMV infection. The greatest control effect was achieved by 3 days of root irrigation at a melatonin concentration of 50 μM. Exogenous melatonin showed preventive and therapeutic effects against CGMMV infection at early stage in tobacco and cucumber. We utilized RNA sequencing technology to compare the expression profiles of mock-inoculated, CGMMV-infected, and melatonin+CGMMV-infected tobacco leaves. Defense-related gene CRISP1 was specifically upregulated in response to melatonin, but not to salicylic acid (SA). Silencing CRISP1 enhanced the preventive effects of melatonin on CGMMV infection, but had no effect on CGMMV infection. We also found exogenous melatonin has preventive effects against another Tobamovirus, Pepper mild mottle virus (PMMoV) infection.ConclusionsTogether, these results indicate that exogenous melatonin controls two Tobamovirus infections and inhibition of CRISP1 enhanced melatonin control effects against CGMMV infection, which may lead to the development of a novel melatonin treatment for Tobamovirus control.

A Randomized, Double-Blind, Crossover Study to Investigate the Pharmacokinetics of Extended-Release Melatonin Compared to Immediate-Release Melatonin in Healthy Adults

Exogenous melatonin can be helpful for treatment of some sleep disorders. However, immediate-release formulations are rapidly absorbed and cleared from the body making it difficult to provide coverage for an entire sleep period. Extended-release melatonin formulations can better mimic the naturally occurring melatonin profile and increase efficacy, but few studies have reported on their pharmacokinetics. To assess the pharmacokinetics of extended-release melatonin, we conducted a randomized, double-blind, crossover study of extended-release melatonin (4 mg) compared to immediate-release melatonin (4 mg) in 18 healthy adults, ages 18–65 years. Participants received immediate-release or extended-release melatonin in clinic after an 8 h fast, and blood samples were taken over a 10-h period. After a 7-day washout period, the same procedures were repeated with the melatonin form not previously received. Extended-release melatonin had a longer time to peak concentration (1.56 vs 0.6 h) and elimination half-life (1.63 vs 0.95 h) compared with immediate-release melatonin. Maximum concentration was lower for extended-release melatonin compared with immediate-release melatonin (7581 pg/mL vs 13120 pg/mL). Extended-release melatonin raised melatonin levels in as little as 15 min and sustained elevated melatonin levels (>300 pg/mL) for 6 h before falling below 50 pg/mL by 9 h. No clinically relevant adverse events were observed, and safety parameters remained within normal ranges for both formulations. The pharmacokinetic profile of this extended-release melatonin formulation suggests that it could be used for future efficacy studies of melatonin and sleep outcomes. This trial is registered at ClinicalTrials.gov, NCT04067791.

Age-Related Gross and Histomorphometrical Dynamics of Pineal Gland (Epiphysis cereberi) Associated with Melatonin Profile in Beetal Goat (Capra aegagrus hircus) of Pakistan

Age-Related Gross and Histomorphometrical Dynamics of Pineal Gland (Epiphysis cereberi) Associated with Melatonin Profile in Beetal Goat (Capra aegagrus hircus) of Pakistan

Phenotypic divergence in sleep and circadian cycles linked by affective state and environmental risk related to psychosis.

Environmental cues influence circadian rhythm timing and neurochemicals involved in the regulation of affective behavior. How this interplay makes them a probable nonspecific risk factor for psychosis is unclear. We aimed to identify the relationship between environmental risk for psychosis and circadian timing phenotypes sampled from the general population. Using an online survey, we devised a cumulative risk exposure score for each of the 1898 survey respondents based on 23 empirically verified transdiagnostic risks for psychosis, three dimensions of affect severity, psychotic-like experiences, and help-seeking behavior. Quantitative phenotyping of sleep and circadian rhythms was undertaken using at-home polysomnography, melatonin and cortisol profiles, and 3-week rest-activity behavior in individuals with a high-risk exposure load (top 15% of survey respondents, n = 22) and low-risk exposure load (bottom 15% of respondents, n = 22). Psychiatric symptoms were present in 100% of the high-load participants and 14% of the low-load participants. Compared to those with a low-load, high-load participants showed a later melatonin phase which was reflected by a greater degree of dispersion in circadian timing. Phase relationships between later circadian melatonin phase and later actigraphic sleep onsets were maintained and these were strongly correlated with self-reported sleep mid-points. No differences were identified from polysomnography during sleep between groups. Distinguishing circadian timing from other sleep phenotypes will allow adaptation for dosage of time-directed intervention, useful in stabilizing circadian timekeeping physiology and potentially reducing the multisystemic disruption in mental health disorders.