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The Journal of Spinal Cord Medicine Sep 2020Pineal melatonin production is mediated by afferent signaling pathways that navigate through the cervicothoracic spinal cord. Melatonin profiles in individuals with... (Review)
Review
Pineal melatonin production is mediated by afferent signaling pathways that navigate through the cervicothoracic spinal cord. Melatonin profiles in individuals with complete cervical spinal cord injury (SCI) have not been systematically reviewed despite this proposed pathway. The primary objective was to understand melatonin profiles in individuals with complete cervical SCI, as compared to healthy controls and those with thoracolumbar and incomplete cervical SCI. Secondary objectives were to understand the impact of injury chronicity and melatonin supplementation on melatonin values in adults with complete cervical SCI. This review (PROSPERO ID: CRD42017073767) searched several databases and gray literature sources from January 1978 to August 2017. Studies were eligible if they evaluated melatonin levels (blood, saliva or urinary metabolite measurements) in adults with complete cervical SCI. 390 studies were screened and 12 studies met final selection criteria. Given the heterogeneity in study designs, a narrative analysis was performed. There is evidence that adults with complete cervical SCI have absent diurnal melatonin rhythms as compared to healthy controls and individuals with thoracolumbar SCI below T3. There is limited evidence comparing levels in individuals with incomplete tetraplegia. There is insufficient evidence describing profiles immediately (<2 weeks) after cervical SCI. Based on a limited number of studies, melatonin supplementation does not appear to improve sleep outcomes in adults with long-standing complete cervical SCI. Future research should explore melatonin levels acutely after cervical SCI and the impact of supplementation on non-sleep outcomes.
Topics: Adult; Cervical Cord; Circadian Rhythm; Humans; Melatonin; Spinal Cord Injuries
PubMed: 30132738
DOI: 10.1080/10790268.2018.1505312 -
BMC Anesthesiology Nov 2023Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its analogs and the incidence of pediatric EA, yielding conflicting results. This meta-analysis aims to assess the effects of premedication with melatonin or its analogs on preventing EA in children after general anesthesia.
METHODS
PubMed, EMBASE, the Cochrane Library, ProQuest Dissertations & Theses Global, Web of Science, CNKI, Wanfang Data, clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched until 25 November 2022. We included randomized controlled trials that assessed EA in patients less than 18 years old who underwent general anesthesia. We excluded studies that did not use a specific evaluation to assess EA.
RESULTS
Nine studies (951 participants) were included in this systematic review. Melatonin significantly reduced the incidence of EA compared with placebos (risk ratio 0.40, 95% CI 0.26 to 0.61, P < 0.01) and midazolam (risk ratio 0.48, 95% CI 0.32 to 0.73, P < 0.01). Dexmedetomidine remarkably decreased the incidence of EA compared with melatonin (risk ratio 2.04, 95% CI 1.11 to 3.73, P = 0.02).
CONCLUSIONS
Melatonin premedication significantly decreases the incidence of EA compared with placebos and midazolam. Dexmedetomidine premedication has a stronger effect than melatonin in preventing EA. Nevertheless, further studies are warranted to reinforce and validate the conclusion on the efficacy of melatonin premedication in mitigating EA in pediatric patients.
Topics: Child; Humans; Adolescent; Midazolam; Dexmedetomidine; Emergence Delirium; Melatonin; Sevoflurane; Methyl Ethers; Premedication
PubMed: 38037000
DOI: 10.1186/s12871-023-02356-x -
Nutrients Aug 2023Mild traumatic brain injury (mTBI) represents a significant burden for individuals, economies, and healthcare systems worldwide. Recovery protocols focus on medication... (Review)
Review
Mild traumatic brain injury (mTBI) represents a significant burden for individuals, economies, and healthcare systems worldwide. Recovery protocols focus on medication and physiotherapy-based interventions. Animal studies have shown that antioxidants, branched-chain amino acids and omega-3 fatty acids may improve neurophysiological outcomes after TBI. However, there appears to be a paucity of nutritional interventions in humans with chronic (≥1 month) symptomology post-mTBI. This systematic literature review aimed to consolidate evidence for nutrition and dietary-related interventions in humans with chronic mTBI. The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021277780) and conducted following the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three reviewers searched five databases (PubMed/MEDLINE, Web of Science, SPORTDiscus, CINAHL Complete and Cochrane), which yielded 6164 studies. Nine studies met the inclusion criteria. The main finding was the lack of interventions conducted to date, and a quality assessment of the included studies was found to be fair to good. Due to heterogeneity, a meta-analysis was not feasible. The six nutrition areas identified (omega-3 fatty acids, melatonin, Enzogenol, MLC901, ketogenic diet and phytocannabinoids) were safe and well-tolerated. It was found that these nutritional interventions may improve cognitive failures, sleep disturbances, anxiety, physical disability, systolic blood pressure volume and sport concussion assessment tool scores following mTBI. Potential areas of improvement identified for future studies included blinding, reporting compliance, and controlling for confounders. In conclusion, further research of higher quality is needed to investigate the role of nutrition in recovery from mTBI to reduce the burden of chronic outcomes following mTBI.
Topics: Animals; Humans; Brain Concussion; Amino Acids, Branched-Chain; Antioxidants; Anxiety; Anxiety Disorders
PubMed: 37686758
DOI: 10.3390/nu15173726 -
Frontiers in Endocrinology 2023Environmental pollution and infertility are two modern global challenges that agonize personal and public health. The causal relationship between these two deserves... (Meta-Analysis)
Meta-Analysis
Protective effects of melatonin against the toxic effects of environmental pollutants and heavy metals on testicular tissue: A systematic review and meta-analysis of animal studies.
BACKGROUND
Environmental pollution and infertility are two modern global challenges that agonize personal and public health. The causal relationship between these two deserves scientific efforts to intervene. It is believed that melatonin maintains antioxidant properties and may be utilized to protect the testicular tissue from oxidant effects caused by toxic materials.
METHODS
A systematic literature search was conducted in PubMed, Scopus, and Web of Science to identify the animal trial studies that evaluated melatonin therapy's effects on rodents' testicular tissue against oxidative stress caused by heavy metal and non-heavy metal environmental pollutants. Data were pooled, and standardized mean difference and 95% confidence intervals were estimated using the random-effect model. Also, the risk of bias was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool. (PROSPERO: CRD42022369872).
RESULTS
Out of 10039 records, 38 studies were eligible for the review, of which 31 were included in the meta-analysis. Most of them showed beneficial effects of melatonin therapy on testicular tissue histopathology. [20 toxic materials were evaluated in this review, including arsenic, lead, hexavalent chromium, cadmium, potassium dichromate, sodium fluoride, cigarette smoke, formaldehyde, carbon tetrachloride (CCl4), 2-Bromopropane, bisphenol A, thioacetamide, bisphenol S, ochratoxin A, nicotine, diazinon, Bis(2-ethylhexyl) phthalate (DEHP), Chlorpyrifos (CPF), nonylphenol, and acetamiprid.] The pooled results showed that melatonin therapy increased sperm count, motility, viability and body and testicular weights, germinal epithelial height, Johnsen's biopsy score, epididymis weight, seminiferous tubular diameter, serum testosterone, and luteinizing hormone levels, testicular tissue Malondialdehyde, glutathione peroxidase, superoxide dismutase, and glutathione levels. On the other hand, abnormal sperm morphology, apoptotic index, and testicular tissue nitric oxide were lower in the melatonin therapy arms. The included studies presented a high risk of bias in most SYRCLE domains.
CONCLUSION
In conclusion, our study demonstrated amelioration of testicular histopathological characteristics, reproductive hormonal panel, and tissue markers of oxidative stress. Melatonin deserves scientific attention as a potential therapeutic agent for male infertility.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022369872.
Topics: Animals; Male; Melatonin; Environmental Pollutants; Semen; Testis; Antioxidants
PubMed: 36793277
DOI: 10.3389/fendo.2023.1119553 -
European Journal of Obstetrics,... Nov 2022Placental insufficiency affects about 10% of pregnancies and can lead to pre-eclampsia, fetal growth restriction, and preterm birth. Despite significant advances in... (Review)
Review
Placental insufficiency affects about 10% of pregnancies and can lead to pre-eclampsia, fetal growth restriction, and preterm birth. Despite significant advances in early prediction and prevention of preterm pre-eclampsia with aspirin, the effects of prophylaxis on fetal growth restriction are less certain, and the rates of late-onset pre-eclampsia are not influenced by aspirin treatment. Pregnancies complicated by placental insufficiency are characterized by increased oxidative stress, and recent studies suggest that melatonin has antioxidant properties and contributes to maintaining placental homeostasis. We aimed to systematically review the available literature about melatonin in pregnancies complicated by placental insufficiency, specifically preeclampsia and fetal growth restriction, exploring three different aspects: 1) maternal melatonin levels; 2) expression and activity of melatonin placental receptors; 3) effects of maternal melatonin administration. PubMed (Medline) and Scopus were searched until December 2020. Identified studies were screened and assessed independently by two authors. Data were extracted and compiled in qualitative evidence synthesis. The circadian pattern of melatonin secretion seems to be altered in pregnancies complicated by placental insufficiency reflected by lower production of melatonin, with consequent lower systemic and placental concentrations and lower expression of melatonin receptors, thus reducing the local release of the indole and its autocrine function. Small intervention studies also suggest that treatment is safe and may lead to prolongation of pregnancy and better outcomes, but double-blind, randomized placebo-controlled trials are lacking.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Placental Insufficiency; Pre-Eclampsia; Melatonin; Fetal Growth Retardation; Placenta; Antioxidants; Receptors, Melatonin; Premature Birth; Aspirin; Randomized Controlled Trials as Topic
PubMed: 36108451
DOI: 10.1016/j.ejogrb.2022.08.029 -
Journal of Clinical Medicine Jan 2023Melatonin modulates the circadian rhythm and has been studied as a preventive measure against the development of delirium in hospitalized patients. Such an effect may be... (Review)
Review
Melatonin modulates the circadian rhythm and has been studied as a preventive measure against the development of delirium in hospitalized patients. Such an effect may be more evident in patients admitted to the ICU, but findings from the literature are conflicting. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We assessed whether melatonin or ramelteon (melatonin agonist) reduce delirium incidence as compared to a placebo in ICU patients. Secondary outcomes were ICU length of stay, duration of mechanical ventilation (MV) and mortality. Estimates are presented as risk ratio (RR) or mean differences (MD) with 95% confidence interval (CI). Nine RCTs were included, six of them reporting delirium incidence. Neither melatonin nor ramelteon reduced delirium incidence (RR 0.76 (0.54, 1.07), = 0.12; I = 64%), although a sensitivity analysis conducted adding other four studies showed a reduction in the risk of delirium (RR = 0.67 (95%CI 0.48, 0.92), = 0.01; I = 67). Among the secondary outcomes, we found a trend towards a reduction in the duration of MV (MD -2.80 (-6.06, 0.47), = 0.09; I = 94%) but no differences in ICU-LOS (MD -0.26 (95%CI -0.89, 0.37), = 0.42; I = 75%) and mortality (RR = 0.85 (95%CI 0.63, 1.15), = 0.30; I = 0%). Melatonin and ramelteon do not seem to reduce delirium incidence in ICU patients but evidence is weak. More studies are needed to confirm this finding.
PubMed: 36675363
DOI: 10.3390/jcm12020435 -
Frontiers in Medicine 2023The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide, with cytokine storm leading to exaggerating immune response, multi-organ dysfunction...
BACKGROUND
The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide, with cytokine storm leading to exaggerating immune response, multi-organ dysfunction and death. Melatonin has been shown to have anti-inflammatory and immunomodulatory effects and its effect on COVID-19 clinical outcomes is controversial. This study aimed to conduct a meta-analysis to evaluate the impact of melatonin on COVID-19 patients.
METHODS
PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched without any language or publication year limitations from inception to 15 Nov 2022. Randomized controlled trials (RCTs) using melatonin as therapy in COVID-19 patients were included. The primary outcome was mortality, and the secondary outcomes included were the recovery rate of clinical symptoms, changes in the inflammatory markers like C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR). A random-effects model was applied for meta-analyses, and further subgroup and sensitivity analyses were also conducted.
RESULTS
A total of nine RCTs with 718 subjects were included. Five studies using melatonin with the primary outcome were analyzed, and the pooled results showed no significant difference in mortality between melatonin and control groups with high heterogeneity across studies identified (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.47-1.11, = 0.14, = 82%). However, subgroup analyses revealed statistically significant effects in patients aged under 55 years (RR 0.71, 95% CI 0.62-0.82, < 0.01) and in patients treated for more than 10 days (RR 0.07, 95% CI 0.01-0.53, = 0.01). The recovery rate of clinical symptoms and changes in CRP, ESR, and NLR were not statistically significant. No serious adverse effects were reported from melatonin use.
CONCLUSION
In conclusion, based on low certainty of evidence, the study concluded that melatonin therapy does not significantly reduce mortality in COVID-19 patients, but there are possible benefits in patients under 55 years or treated for more than 10 days. With a very low certainty of evidence, we found no significant difference in the recovery rate of COVID-19 related symptoms or inflammatory markers in current studies. Further studies with larger sample sizes are warranted to determine the possible efficacy of melatonin on COVID-19 patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022351424.
PubMed: 37181363
DOI: 10.3389/fmed.2023.1171294 -
Brain Sciences May 2023The pineal gland (PG) is a small interhemispheric brain structure that influences human physiology in many ways, most importantly via secretion of the hormone melatonin... (Review)
Review
The pineal gland (PG) is a small interhemispheric brain structure that influences human physiology in many ways, most importantly via secretion of the hormone melatonin which is known to regulate sleep and wakefulness. Here, we systematically reviewed existing neuroimaging studies of PG structure, and/or melatonin release (MLT) in psychosis and mood disorders. Medline, PubMed, and Web of Science databases were searched (on 3 February 2023), yielding 36 studies (8 PG volume, 24 MLT). The findings showed smaller-than-normal PG volume in people with schizophrenia, regardless of symptom severity and illness stage; and smaller-than-normal PG volume in major depression, with some indication of this being present only in certain subgroups, or in those with high scores on the 'loss of interest' symptom. There was considerable evidence of lower-than-normal MLT as well as aberrant MLT secretion pattern in schizophrenia. A similar picture, though less consistent than that seen in schizophrenia, emerged in major depression and bipolar disorder, with some evidence of a transient lowering of MLT following the initiation of certain antidepressants in drug-withdrawn patients. Overall, PG and MLT aberrations appear to represent transdiagnostic biomarkers for psychosis and mood disorders, but further work is needed to establish their clinical correlates and treatment implications.
PubMed: 37239299
DOI: 10.3390/brainsci13050827 -
Journal of Neurosciences in Rural... Jan 2022Triclofos and melatonin are commonly used oral sedatives in children for obtaining a sleep electroencephalogram (EEG) record. There has been no systematic review...
Triclofos and melatonin are commonly used oral sedatives in children for obtaining a sleep electroencephalogram (EEG) record. There has been no systematic review till now to compare the efficacy and safety of these two medications. The review intended to compare the efficacy of oral triclofos and melatonin in children <18 years of age for inducing adequate sedation for obtaining a sleep EEG record. We also attempted to compare the adverse effects, impact on EEG record, the yield of epileptiform abnormalities, and sleep onset latency in both groups. A systematic search was conducted on "MEDLINE/PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, and Google Scholar" till November 30, 2020, with the following keywords/the Medical Subject Headings (MESH) terms while searching: "sleep EEG," "electroencephalogram," "triclofos," "melatonin" OR "ramelteon" AND "epilepsy," "seizure," OR "convulsion." ROB 2.0 and ROBINS-I tool was used to determine the risk of bias. To assess heterogeneity in studies, Higgins and Thompson's method was utilized. When was more than 50%, a random effects model was utilized and a fixed-effect model was used for other parameters. To assess the presence of publication bias, Egger's test was used. For describing the efficacy of triclofos in 1,284 and melatonin in 1,532 children, we selected 16 articles. The indirect comparison between the pooled estimate of all children receiving individual medications revealed comparable efficacy in obtaining successful sleep EEG record with a single dose (90 vs. 76%, = 0.058) and repeat dose ( = 0.054), detection of epileptiform abnormalities ( = 0.06), and sleep onset latency ( = 0.06), but more proportion of children receiving triclofos had adverse effects ( = 0.001) and duration of sleep was also higher with triclofos ( = 0.001). Efficacy of triclofos and melatonin are comparable in inducing sleep for recording EEG in children, although triclofos is more likely to cause adverse effects. However, the level of evidence is low for this conclusion and the weak strength of recommendation for the results of this review is likely to change in the future after completion of controlled trials exploring these two medications.
PubMed: 35110915
DOI: 10.1055/s-0041-1736511 -
Sports (Basel, Switzerland) Jul 2023The use of saliva to monitor immune and hormonal responses in training, competitions, and during recovery is an easy and non-invasive alternative means of collecting... (Review)
Review
The use of saliva to monitor immune and hormonal responses in training, competitions, and during recovery is an easy and non-invasive alternative means of collecting samples compared to serum collection. Saliva can provide insight into a number of interesting biomarkers such as cortisol, testosterone, immunoglobulins, alpha-amylase, and melatonin, among others. High-intensity and exhaustive exercises, such as training or competition, provide variations in immune, protein and hormonal markers. An adequate recovery period, calming down, and recovery methods can contribute to a fast normalization of these markers, decreasing illness, as well as the likelihood of overtraining and injuries, but their effectiveness is still inconclusive. The aim of this review was to investigate the evidence of salivary markers in post-exhaustive exercise during the recovery period. This study is a systematic review from three electronic databases with studies from 2011 to 2021 within healthy humans. The search found 213 studies, and after applying the inclusion and exclusion criteria, while excluding duplicated studies, 14 studies were included in this review. The most cited salivary markers were cortisol and testosterone, as well as their ratio, alpha-amylase and IgA. Half of the studies applied a variety of recovery methods that showed controversial results over salivary markers' impact. However, they showed an impact on the markers from the exercise, which was still dependent on exercise intensity, methodology, and duration.
PubMed: 37505624
DOI: 10.3390/sports11070137