Can supplementation of tryptophan in parenteral nutrition increase melatonin and alleviate inflammatory response?

OBJECTIVE: Endogenous melatonin is produced from tryptophan which is an essential amino acid. Besides its role in the regulation of sleep patterns, melatonin has anti-inflammatory effects. In this case-control study, we aimed to compare tryptophan and melatonin levels and their relationship with the inflammatory response, specifically serum interleukin-1, interleukin-6, and c-reactive protein levels following major abdominal surgery in patients with food restriction and who receive parenteral nutritional therapy. METHODS: We enrolled 40 patients between the ages of 18 and 65 years in the study. We collected blood and urine samples 48 h before the operation and on postoperative days 1, 3, and 5. RESULTS AND CONCLUSION: The tryptophan levels in the experimental group were higher than in the control group but failed to reach any statistical difference. Melatonin levels were increased in both groups following the surgery compared with preoperative levels. The increase in the experimental group was statistically different 3 days after the surgery. The difference in the level of interleukin-1 between the control and the experimental groups was greatest on postoperative day 3. On postoperative day 3, the interleukin-6 level in the treatment group was slightly higher than in the control group. We did not find any difference in the levels of c-reactive protein between the groups. As a result, the levels of tryptophan and melatonin were increased in the parenteral nutrition group, irrespective of the postoperative inflammatory response.

Antioxidant Effect of Melatonin in Preterm Newborns.

INTRODUCTION: Preterm infants are at risk of free radical-mediated diseases from oxidative stress (OS) injury. Increased free radical generation has been demonstrated in preterm infants during the first seven days of life. Melatonin (MEL) is a powerful antioxidant and scavenger of free radicals. In preterm neonates, melatonin deficiency has been reported. Exogenous melatonin administration appears a promising strategy in the treatment of neonatal morbidities in which OS has a leading role. OBJECTIVE: The aim was to evaluate plasma MEL concentrations and OS biomarkers in preterm newborns after early administration of melatonin. METHODS: A prospective, randomized double-blind placebo-controlled pilot study was conducted from January 2019 to September 2020. Thirty-six preterm newborns were enrolled. Starting from the first day of life, 21 received a single dose of oral melatonin 0.5 mg/kg once a day, in the morning (MEL group); 15 newborns received an equivalent dose of placebo (placebo group). Samples of 0.2 mL of plasma were collected at 24 and 48 hours after MEL administration. Plasma concentrations of melatonin, non-protein-bound iron (NPBI), advanced oxidation protein products (AOPP), and F2-isoprostanes (F2-Isopr) were measured. Babies were clinically followed until discharge. RESULTS: At 24 and 48 hours after MEL administration, the MEL concentrations were significantly higher in the MEL group than in the placebo group (52759.30 ± 63529.09 vs. 28.57 ± 46.24 pg/mL and 279397.6 ± 516344.2 vs. 38.50 ± 44.01 pg/mL, respectively). NPBI and AOPP did not show any statistically significant differences between the groups both at 24 and 48 hours. At 48 hours, the mean blood concentrations of F2-Isopr were significantly lower in the MEL group than in the placebo group (36.48 ± 33.85 pg/mL vs.89.97 ± 52.01 pg/mL). CONCLUSIONS: Early melatonin administration in preterm newborns reduces lipid peroxidation in the first days of life showing a potential role to protect high-risk newborns. Trial Registration. This trial is registered with NCT04785183, Early Supplementation of Melatonin in Preterm Newborns: the Effects on Oxidative Stress.

Dietary supplementation of acetate-conjugated tryptophan alters feed intake, milk yield and composition, blood profile, physiological variables, and heat shock protein gene expression in heat-stressed dairy cows.

The purpose of this study was to investigate the effects of dietary supplementation of rumen-protected tryptophan (RPT) at four levels on milk yield, milk composition, blood profile, physiological variables, and heat shock protein gene expression in dairy cows under conditions of moderate-severe heat stress (MSHS, THI = 80~89). Sixteen early-lactating dairy cows (body weight = 719 ± 66.4 kg, days in milk = 74.3 ± 7.1, milk yield = 33.55 ± 3.74 kg, means ± SEM) were randomly assigned in a factorial arrangement to one of the four treatments: control group (n = 4, no RPT supplementation), 15 g/d RPT (n = 4), 30 g/d RPT (n = 4), or 60 g/d RPT group per cow (n = 4) supplemented to the TMR. A higher dry matter intake (DMI) and milk yield were found in the 30 g RPT group compared with the other groups, and the 3.5% fat-corrected milk yield, energy-corrected milk yield, milk fat, protein, ß-casein, mono-unsaturated fatty acid, and poly-unsaturated fatty acid contents, and serum glucose content were observed in the 30 g RPT group (p < 0.05). The milk lactose concentration was significantly higher in the 30 g RPT group compared with the control and 60 g RPT groups (p < 0.05). The plasma cortisol level was lower, while the serotonin and melatonin concentrations were higher in the 30 g group compared with the other groups (p < 0.05). Heat shock protein (HSP) 70 expression was downregulated in the control and 15 g RPT groups, whereas the expression of HSP90 and HSPB1 remained unchanged among the groups. In particular, the 30 g RPT group was considered to have an improved DMI, milk yield, and lactose concentration, as well as anti-heat stress effects due to the simulation of serotonin and melatonin during MSHS.

Luffa operculata at a late period of gestation dysregulates melatonin and cytokines interfering with weight of dams and their male offspring.

ETHNOPHARMACOLOGICAL RELEVANCE: The tea made with the fruits of Luffa operculata (L.) Cogn. (Cucurbitaceae; EBN) is popularly used as abortive. AIM OF THE STUDY: The present work aimed at accessing how the exposition of female Wistar rats to 1.0 mg/kg of EBN (experimental group, EG), or distilled water (control group, CG), by gavage, at gestational days (GD) 17-21 interfered with the reproductive performance, and with dams' behavior after weaning. MATERIALS AND METHODS: At post-natal day 2 (PND2), the number of male and female pups was evaluated, as well as their weight. After weaning (PND21), dams were euthanized, and their liver and kidneys were removed for histological and biochemical analyses, while the blood was used in the evaluation of cytokines IL-1α, IL-1ß, IL-6 and TNF-α, corticosterone, adrenocorticotrophic hormone, melatonin, AST, ALT and creatinine levels. RESULTS AND DISCUSSION: Dams that were treated with EBN showed an anxiety-like behavior, weight loss at the end of gestation and weight gain at weaning, accompanied with a significant decrease in pro-inflammatory cytokines and in the melatonin level. No significant histological or biochemical alterations have occurred in the liver or kidneys. The number of female pups was significantly higher in the EG. The male pups showed weight gain at PND60. CONCLUSION: The presence of cucurbitacins is probably involved in the dysregulations that were found, due to their polycyclic steroid triterpene structure.

Circadian Rhythm and Concentration of Melatonin in Breast Cancer Patients.

BACKGROUND: Melatonin is a biomarker of the central circadian clock and its chronobiotic actions entraining circadian rhythms to the light-dark cycle are well known. Reduction in melatonin levels and altered circadian rhythms have been associated with a high risk of breast cancer. Melatonin has also been shown to display anti-proliferative effects on breast cancer growth and proliferation. Evaluation of melatonin circadian rhythm alterations in patients bearing breast cancer may have interesting prognostic and therapeutic applications. OBJECTIVE: To review studies evaluating the circadian rhythm of melatonin in breast cancer patients. The effects of surgery and chemotherapy on melatonin secretion were also reviewed. METHODS: Electronic databases, including PubMed/MEDLINE and Scopus, were searched from their inception to May 2020, using the keywords "Melatonin", "Circadian rhythm" and "Breast cancer". RESULTS: Patients with breast cancer maintain a circadian rhythm of melatonin secretion with relatively high levels during the night and low levels during the day, however, a reduction in nocturnal melatonin peak and decreased amplitude of melatonin circadian rhythms in these patients have also been reported. Melatonin levels can influence estrogen receptor concentrations in hormone-dependent estrogen- positive breast cancer. Chemotherapy alters melatonin levels and breast surgery tends to alter melatonin secretion at first-day post-operation. Melatonin levels correlate with clinical and psychological symptoms of breast cancer, such as sleep quality and depression severity. CONCLUSION: Circadian rhythm and the concentration of melatonin in the blood are altered in patients with breast cancers, and it can modify not only the sleep-wake cycle and, thus, patients' quality of life but due to melatonin's antioxidant effects, the effect of therapies can be modulated. Due to the heterogonous protocols used to assess melatonin and variable environmental factors during sampling, further studies need to control, such variables in order to tailor clinical trials based on melatonin rhythm adjustment and/or supplementation in breast cancer patients.

The Effects of Melatonin Supplementation on Sleep Quality and Assessment of the Serum Melatonin in ICU Patients: A Randomized Controlled Trial.

OBJECTIVES: To evaluate whether the use of exogenous melatonin affects sleep, reduces the prevalence of delirium, and decreases the need for analgosedation and to assess whether serum melatonin indices correlate with exogenous administration in critically ill patients. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: Multicenter ICUs of two tertiary hospitals. PATIENTS: A total of 203 adult patients who were admitted to the ICU and administered with analgesics and/or sedatives. INTERVENTIONS: Oral melatonin (10 mg) or placebo for up to seven consecutive nights. MEASUREMENTS AND MAIN RESULTS: The number of observed sleeping hours at night was assessed by the bedside nurse. Sleep quality was evaluated using the Richards Campbell Questionnaire Sleep (RCSQ). The prevalence of delirium, pain, anxiety, adverse reactions, duration of mechanical ventilation, length of ICU and hospital stays, and doses of sedative and analgesic drugs administered were recorded. The use of analgesics and sedatives was assessed daily. Melatonin levels were determined by enzyme-linked immunosorbent assay. Based on the RCSQ results, sleep quality was assessed to be better in the melatonin group than that in the placebo group with a mean (SD) of 69.7 (21.2) and 60.7 (26.3), respectively (p = 0.029). About 45.8% and 34.4% of participants in the melatonin and placebo groups had very good sleep (risk ratio, 1.33; 95% CI, 0.94-1.89), whereas 3.1% and 14.6% had very poor sleep (risk ratio, 0.21; 95% CI, 0.06-0.71), respectively. No significant difference was observed regarding the days free of analgesics or sedatives, the duration of night sleep, and the occurrence of delirium, pain, and anxiety. Melatonin serum peak levels at 2 AM were 150 pg/mL (range, 125-2,125 pg/mL) in the melatonin group and 32.5 pg/mL (range, 18.5-35 pg/mL) in the placebo group (p < 0.001). CONCLUSIONS: Melatonin was associated with better sleep quality, which suggests its possible role in the routine care of critically ill patients in the future.

Yokukansankachimpihange, a traditional Japanese (Kampo) medicine, enhances the adaptation to circadian rhythm disruption by increasing endogenous melatonin levels.

The traditional Japanese (Kampo) medicines yokukansan (YKS) and yokukansankachimpihange (YKSCH) have similar formulas and the same indications. In animals or cultured cells, the neuropharmacological actions of YKS are sometimes more beneficial than those of YKSCH. Since both drugs are used to treat sleep disorders in Japan, we examined the ameliorative effects of YKS and YKSCH on circadian rhythm disturbance and compared their efficacy using a mouse model of circadian rhythm disruption. Ramelteon was used as the positive control. Ramelteon treatment significantly reversed decreased running wheel activity during the advanced dark phase, indicating facilitation of circadian adaptation. YKS treatment also reversed the activity in the early period of drug treatment; however, it was not statistically significant. YKSCH treatment significantly reversed the decreased activity during the advanced dark phase. Plasma melatonin (MT) levels were significantly increased in the YKSCH but not in the YKS group. The ameliorative effect of YKSCH on rhythm disruption was significantly inhibited by coadministration of the MT2 receptor antagonist. Therefore, the therapeutic effect of YKSCH on circadian rhythm disruption would be attributable, to elevated endogenous MT levels. Taken together, YKS and YKSCH have different pharmacological properties and may be more precisely prescribed depending on patients' psychological symptoms.

Melatonin down-regulates steroidal hormones, thymocyte apoptosis and inflammatory cytokines in middle-aged T. cruzi infected rats.

Chagas disease, triggered by the flagellate protozoan Trypanosoma cruzi (T. cruzi) plays a potentially threat to historically non-endemic areas. Considerable evidence established that the immuno-endocrine balance could deeply influence the experimental T. cruzi progression inside the host's body. A high-resolution multiple reaction monitoring approach (MRMHR) was used to study the influence of melatonin on adrenal and plasma steroidal hormones profile of T. cruzi infected Wistar rats. Young (5 weeks) and middle-aged (18 months) male Wistar rats received melatonin (5 mg/Kg, orally) during the acute Chagas disease. Corticosterone, 11-dehydrocorticosterone (11-DHC), cortisol, cortisone, aldosterone, progesterone and melatonin concentration were evaluated. Interleukin-1 alpha and ß (IL-1α and ß), IL-6 and transforming growth factor beta (TGF-ß) were also analyzed. Our results revealed an increased production of corticosterone, cortisone, cortisol and aldosterone in middle-aged control animals, thus confirming the aging effects on the steroidal hormone profile. Serum melatonin levels were reduced with age and predominantly higher in young and middle-aged infected rats. Melatonin treatment reduced the corticosterone, 11-DHC, cortisol, cortisone, aldosterone and progesterone in response to T. cruzi infection. Decreased IL-1 α and ß concentrations were also found in melatonin treated middle-aged infected animals. Melatonin treated middle-aged control rats displayed reduced concentrations of TGF-ß. Melatonin levels were significantly higher in all middle-aged rats treated animals. Reduced percentages of early and late thymocyte apoptosis was found for young and middle-aged melatonin supplemented rats. Finally, our results show a link between the therapeutic and biological effects of melatonin controlling steroidal hormones pathways as well as inflammatory mediators.

Sleep deprivation aggravated lipopolysaccharide/D-galactosamine-induced acute liver injury by suppressing melatonin production.

OBJECTIVE: Sleep loss is common in patients with liver injury, but the effects of sleep deprivation (SD) on liver injury remain unclear. In the present study, the potential effects of SD on acute liver injury and the underlying mechanisms have been investigated. METHODS: The sleep of male BALB/c mice has been deprived by using a modified multiple platform water bath for 3 days and acute liver injury was induced by intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-Gal). The degree of liver injury was detected by aminotransferase determination, histopathology and survival rate analysis. Inflammatory response and melatonin (MT) were measured by enzyme-linked immunosorbent assay (ELISA). In addition, hepatocyte apoptosis was determined by caspase activity measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: We observed that SD increased plasma aminotransferases, TUNEL-positive hepatocytes, histological abnormalities and mortality rates in mice with LPS/D-Gal treatment. SD also promoted LPS/D-Gal-induced production of TNF-α and upregulated hepatic caspase-8, caspase-9, and caspase-3 activities in LPS/D-Gal-exposed mice. In addition, SD significantly decreased MT contents in plasma of mice with acute liver injury, but supplementation with MT reversed these SD-promoted changes. CONCLUSION: Our data suggested that SD exacerbated LPS/D-Gal-induced liver injury via decreasing melatonin production.

[Effect of transcutaneous electrical acupoint stimulation on postoperative olfactory memory disorder and plasma melatonin in patients with general anesthesia of sevoflurane].

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative olfactory memory disorder in patients with general anesthesia of sevoflurane and to explore its possible mechanism. METHODS: Forty patients who were scheduled to have gynecological and urological procedures under general anesthesia were randomly divided into an observation group and a control group, 20 cases in each group. The patients in the observation group were treated with TEAS (dilatational wave, 2 Hz/100 Hz) at Yingxiang (LI 20) and Yintang (GV 29) 10 min before anesthesia induction until the end of operation; the patients in the control group received general anesthesia directly. The changes of mean arterial pressure (MAP), heart rate (HR) and blood oxygen saturation (SpO2) were recorded before treatment, 30 min after operation and at the end of operation; smell identification score was measured by Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test before treatment (T0) and when Aldrete recovery score reached 10 points at the end of anesthesia (T1); the concentration of melatonin in plasma was measured by ELISA method in the two groups. RESULTS: The between-group differences and within-group differences of MAP, HR and SpO2 were not significant at each time point (P>0.05). Compared with T0, the score of smell identification and plasma concentration of melatonin were not significantly different at T1 in the observation group (P>0.05), however, the score of smell identification and plasma concentration of melatonin were reduced in the control group (P<0.05). At T1, the score of smell identification and plasma concentration of melatonin in the observation group were higher than those in the control group (P<0.05). CONCLUSION: TEAS could improve the postoperative olfactory memory disorder in patients with general anesthesia of sevoflurane, and its mechanism may be related to the increase of plasma concentration of melatonin.

The effects of daylight exposure on melatonin levels, Kiss1 expression, and melanoma formation in mice.

AIM: To determine how daylight exposure in mice affects melatonin protein expression in blood and Kiss1 gene expression in the hypothalamus. The second aim was to assess the relationship between skin cancer formation, daylight exposure, melatonin blood level, and kisspeptin gene expression level. METHODS: New-born mice (n=96) were assigned into the blind group or daylight group. The blind group was raised in the dark and the daylight group was raised under 12 hours light/12 hours dark cycle for 17 weeks. At the end of the 11th week, melanoma cell line was inoculated to mice, and tumor growth was observed for 6 weeks. At the end of the experiment, melatonin level was measured from blood serum and Kiss1 expression from the hypothalamus. RESULTS: The blind group had significantly higher melatonin and lower Kiss1 expression levels than the daylight group. Tumor volume was inversely proportional to melatonin levels and directly proportional to Kiss1 expression levels. Tumor growth speed was lower in the blind than in the daylight group. CONCLUSION: Melatonin and Kiss1 were shown to be nvolved in tumor suppression. They were affected by daylight and were mutually affected by each other.

Acupoint combination effect of Shenmen (HT 7) and Sanyinjiao (SP 6) in treating insomnia: study protocol for a randomized controlled trial.

BACKGROUND: Insomnia is a global disease with a high incidence and acupuncture therapy is a well appropriate method to treat insomnia. Shenmen (HT 7) and Sanyinjiao (SP 6) are the acupoints most commonly used to treat insomnia. Although they can obviously relieve the clinical symptoms of insomnia, it is unclear whether they must be used together, whether the combination of two acupoints may have a synergistic or antagonistic effect, and whether there is a primary or secondary relationship between the two points in the treatment of insomnia. Further studies are needed. Therefore, in this study, we are exploring the acupoint combination effect and biological mechanism of HT 7 and SP 6 in treating insomnia. METHODS/DESIGN: This will be a parallel group randomized controlled trial. The study will recruit 120 patients with insomnia randomly assigned to a control group, an electroacupuncture on HT 7 group, an electroacupuncture on SP 6 group, and an electroacupuncture on HT 7 and SP 6 group. The allocation ratio is 1:1:1:1, with 30 subjects in each group. Meanwhile, ten healthy subjects who meet the study criteria will be recruited as the healthy control group. Patients in the intervention groups will be given ten rounds of electroacupuncture stimulation on the corresponding acupoints for 2 weeks, five times per week, with 2 days of rest between the two treatment courses. Patients in the control group will also receive the same two courses of ten rounds of compensatory acupuncture therapy after a 2-week waiting period for treatment. The major outcome measures of this study include the Sleep Dysfunction Rating Scale, the Insomnia Severity Index, Epworth Sleepiness Scale, the Zung Self-Rating Anxiety Scale, and the Zung Self-Rating Depression Scale, combined with the Measure Your Medical Outcome Profile, to evaluate insomnia and the emotional state of patients with insomnia. The secondary outcome measures include sleep composition monitored by polysomnography and measurements of acetylcholine, serotonin, dopamine, norepinephrine, melatonin, gamma-aminobutyric acid, and metabolic biomarkers in serum. DISCUSSION: In this study, we are exploring the acupoint combination effect and biological mechanism of HT 7 and SP 6 in treating insomnia, which may provide evidence for the clinical application of acupuncture and acupoint selection in the treatment of insomnia. TRIAL REGISTRATION: Chinese Clinical Trial Registry, Chi-CTR-1800017483. Registered on 1 August 2018.

The Effects of Melatonin Supplementation on Parameters of Mental Health, Glycemic Control, Markers of Cardiometabolic Risk, and Oxidative Stress in Diabetic Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: This study evaluated the effects of melatonin supplementation on parameters of mental health, glycemic control, markers of cardiometabolic risk, and oxidative stress in diabetic hemodialysis (HD) patients. DESIGN: A randomized, double-blind, placebo-controlled clinical trial was conducted in 60 diabetic HD patients, 18-80 years of age. Participants were randomly divided into 2 groups to take either melatonin (2 x 5mg/day) (n = 30) or placebo (n = 30) 1 hour before bedtime for 12 weeks. The effects of melatonin on mental health, metabolic status, and gene expression related to metabolic status were assessed using multiple linear regression adjusting for age and BMI. RESULTS: Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (P = .007), Beck Depression Inventory index (P = .001), and Beck Anxiety Inventory index (P = .01) compared with the placebo. Additionally, melatonin administration significantly reduced fasting plasma glucose (ß = -21.77 mg/dL, 95% CI -33.22 to -10.33, P < .001), serum insulin levels (ß = -1.89 µIU/mL, 95% CI -3.34 to -0.45, P = .01), and homeostasis model of assessment-insulin resistance (ß = -1.45, 95% CI -2.10 to -0.80, P < .001), and significantly increased the quantitative insulin sensitivity check index (ß = 0.01, 95% CI 0.007-0.02, P < .001) compared with placebo treated subjects. In addition, melatonin administration resulted in a significant reduction in serum high sensitivity C-reactive protein (ß = -1.92 mg/L, 95% CI -3.02 to -0.83, P = .001) and plasma malondialdehyde (ß = -0.21 µmol/L, 95% CI -0.36 to -0.06, P = .005); also, significant rises in plasma total antioxidant capacity (ß = 253.87 mmol/L, 95% CI 189.18-318.56, P < .001) and nitric oxide levels (ß = 2.99 µmol/L, 95% CI 0.71-5.28, P = .01) were observed compared with the placebo. CONCLUSION: Overall, melatonin supplementation for 12 weeks to diabetic HD patients had beneficial effects on mental health, glycemic control, inflammatory markers, and oxidative stress.

Estimating Representative Group Intrinsic Circadian Period from Illuminance-Response Curve Data.

The human circadian pacemaker entrains to the 24-h day, but interindividual differences in properties of the pacemaker, such as intrinsic period, affect chronotype and mediate responses to challenges to the circadian system, such as shift work and jet lag, and the efficacy of therapeutic interventions such as light therapy. Robust characterization of circadian properties requires desynchronization of the circadian system from the rest-activity cycle, and these forced desynchrony protocols are very time and resource intensive. However, circadian protocols designed to derive the relationship between light intensity and phase shift, which is inherently affected by intrinsic period, may be applied more broadly. To exploit this relationship, we applied a mathematical model of the human circadian pacemaker with a Markov-Chain Monte Carlo parameter estimation algorithm to estimate the representative group intrinsic period for a group of participants using their collective illuminance-response curve data. We first validated this methodology using simulated illuminance-response curve data in which the intrinsic period was known. Over a physiological range of intrinsic periods, this method accurately estimated the representative intrinsic period of the group. We also applied the method to previously published experimental data describing the illuminance-response curve for a group of healthy adult participants. We estimated the study participants' representative group intrinsic period to be 24.26 and 24.27 h using uniform and normal priors, respectively, consistent with estimates of the average intrinsic period of healthy adults determined using forced desynchrony protocols. Our results establish an approach to estimate a population's representative intrinsic period from illuminance-response curve data, thereby facilitating the characterization of intrinsic period across a broader range of participant populations than could be studied using forced desynchrony protocols. Future applications of this approach may improve the understanding of demographic differences in the intrinsic circadian period.

The effect of aromatherapy with lavender (Lavandula angustifolia) on serum melatonin levels.

OBJECTIVE: Physiologically, blood melatonin levels decrease as a person ages and the older adult commonly presents with insomnia and other types of sleep disorders. Alternative therapies can be used to attenuate sleep disturbances. The aim of the present study was to analyze the effect of aromatherapy with lavender on serum melatonin levels in the noninstitutionalized older adult (OA). DESIGN AND SETTING: A pre-experimental, quantitative study with a pre-test - post-test design was conducted on 67 OAs that included both sexes. MAIN OUTCOME MEASURES: Serum melatonin levels were measured before and after eight sessions of aromatherapy with lavender that lasted 4 weeks. The results were expressed as mean ±â€¯standard deviation of melatonin levels (pg/ml). The differences were compared using the Student's t-test and statistical significance was set at a p ≤ 0.05. RESULTS: Blood melatonin levels significantly increased in the total population after the intervention with aromatherapy (pg/ml): 102.3 ±â€¯33.4 VS 132.5 ±â€¯42.3, p = 0.000004. There were significant differences in the pre-test and post-test phases in the women and men measured as separate groups (p = 0.00005 and p = 0.026), respectively. However, those differences were not observed when the measurements were compared between the two sexes, before (p = 0.64) or after (p = 0.31) the intervention. CONCLUSION: Aromatherapy with lavender essential oil similarly favors an increase in blood melatonin levels in both older adult men and women.

Case report of sudden death in a twin infant given melatonin supplementation: A challenging interpretation of postmortem toxicology.

Melatonin (MEL) is a neurohormone in humans produced in a number of locations. Starting with the amino acid tryptophan, MEL is produced through a number of enzymatic steps that includes serotonin as an intermediate compound. The primary production of MEL is in the pineal gland located in the brain. It is directly associated with the the suprachiasmatic nucleus (SCN) located in the hypothalamus. In young and adult humans, the blood levels of MEL are typically in the picogram levels and produced in a cyclic schedule highly regulated by light detected in the retina by intrinsically photosensitive retinal ganglion cells (ipRGCs), resulting in production primarily during periods of darkness. During periods of light, MEL levels are typically very low or undetectable. Basal levels of MEL in infants have been observed to be either undetectable or also in the picogram levels, although some medical treatment has involved administration of exogenous MEL resulting in peak levels in the nanogram range. MEL is considered to be well tolerated and there have been limited reports of toxicity. In this case, an infant was found unresponsive and cause of death was ruled as Undetermined. Melatonin was detected in the peripheral blood at a concentration of 1,400ng/mL.

A carbon paste electrode modified with Al2O3-supported palladium nanoparticles for simultaneous voltammetric determination of melatonin, dopamine, and acetaminophen.

The authors have modified a carbon paste electrode with Al2O3-supported palladium nanoparticles (PdNP@Al2O3) to obtain a sensor for simultaneous voltammetric determination of melatonin (MT), dopamine (DA) and acetaminophen (AC). The PdNP@Al2O3 was characterized by scanning electron microscopy and energy-dispersive X-ray spectra. The sensor can detect DA, AC, MT and their mixtures by giving distinct signals at working voltages of typically 236, 480 and 650 mV (vs. Ag/AgCl), respectively. Differential pulse voltammetric peak currents of DA, AC and MT increase linearly in the 50 nmol L-1 - 1.45 mmol L-1, 40 nmol L-1 -1.4 mmol L-1, and 6.0 nmol L-1 - 1.4 mmol L-1 concentration ranges. The limits of detection are 36.5 nmol L-1 for DA, 36.5 nmol L-1 for AC, and 21.6 nmol L-1 for MT. The sensor was successfully used to detect the analytes in (spiked) human serum and drug samples. Graphical abstract Schematic presentation of Al2O3-supported palladium nanoparticles (PdNP@Al2O3) for modification of a carbon paste electrode (CPE) to develop a voltammetric sensor for the simultaneous determination of dopamine (DA), acetaminophen (AC) and melatonin (MT).

Melatonin Levels in Preterm and Term Infants and Their Mothers.

The prevention of perinatal brain damage following preterm birth remains a public health priority. Melatonin has been shown to be a promising neuroprotectant in neonatal preclinical models of brain damage, but few studies have investigated melatonin secretion in newborns. We hypothesized that melatonin circulating levels would be lower in preterm compared to term infants. We conducted a prospective, longitudinal, multicenter study to assess melatonin, and 6-sulfatoxy-melatonin (aMT6s) concentrations, measured by radioimmunoassay. Among 209 neonates recruited, 110 were born before 34 gestational weeks (GW) and 99 born after 34 GW. Plasma melatonin concentrations, measured at birth and on Day 3 were below detectable levels (≤7 pg/mL) in 78% and 81%, respectively, of infants born before 34 GW compared to 57% and 34%, respectively, of infants born after 34 GW. The distribution of plasma melatonin concentrations was found to be correlated with gestational age at both time-points (p < 0.001). Median urine aMT6s concentrations were significantly lower in infants born before 34 GW, both on Day 1 (230 ng/L vs. 533 ng/L, p < 0.0001) and on Day 3 (197 ng/L vs. 359 ng/L, p < 0.0001). In conclusion, melatonin secretion appears very low in preterm infants, providing the rationale for testing supplemental melatonin as a neuroprotectant in clinical trials.

Different routes and formulations of melatonin in critically ill patients. A pharmacokinetic randomized study.

BACKGROUND AND OBJECTIVES: Critically ill patients present reduced endogenous melatonin blood levels, and they might benefit from its exogenous supplementation. The aim of this research was to evaluate the feasibility of different routes of administration and drug formulations of melatonin. The efficiency of absorption was assessed as well as the adequacy in achieving and maintaining the physiological nocturnal blood peak. METHODS: Twenty-one high-risk critically ill patients were randomly assigned to receive melatonin either: (a) per os, as a standard tablet (ST-OS), (b) per os, as a suspension in solid lipid nanoparticles (SLN-OS) or c) transdermal (TD), by applying a jellified melatonin microemulsion (µE) on the skin (µE-TD). SLN-OS and µE-TD were lipid-based colloidal systems. The endogenous melatonin blood values were observed for 24 hours; subsequently, melatonin 3 mg was administered and pharmacokinetics was studied for 24 hours further. RESULTS: In both groups that received ST-OS and SLN-OS, the median time-to-peak blood concentration was 0.5 hours; however, the area under the curve (AUC) after administration of SLN-OS was significantly higher than after ST-OS (157386 [65732-193653] vs 44441 [22319-90705] pg/mL*hours, P = 0.048). µE-TD presented a delayed time-to-peak blood concentration (4 hours), a lower bioavailability (AUC: 3142 [1344-14573] pg/mL*hours) and reached pharmacological peak concentration (388 [132-1583] pg/mL). CONCLUSIONS: SLN-melatonin enterally administered offers favourable pharmacokinetics in critically ill patients, with higher bioavailability with respect to the standard formulation; µE-TD provided effective pharmacological blood levels, with a time-concentration profile more similar to the physiological melatonin pattern.

The effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 diabetes mellitus patients with chronic periodontitis: a double-blind, placebo-controlled trial.

BACKGROUND: Diabetes mellitus (DM) and periodontitis are two common chronic diseases with bidirectional relationship. Oxidative stress plays a key role in the pathogenesis of these two diseases. The aim of this study was to investigate the effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 DM patients with chronic periodontitis (CP). MATERIALS AND METHODS: In this double-blind clinical trial study, 50 type 2 DM patients with CP were randomly allocated to the intervention and control groups. The intervention and control groups received either 6 mg melatonin or placebo (2 tablets) once a day. Serum levels of melatonin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), hs-C-reactive protein (hs-CRP), clinical attachment loss (CAL), pocket depth (PD), bleeding on probing (BOP) and plaque index were evaluated in all subjects pre- and post-intervention. RESULTS: Melatonin supplementation significantly increased the mean serum levels of melatonin after intervention. The mean changes of melatonin were significantly higher in intervention group compared with control group. IL-6 and hs-CRP levels were significantly (p = 0.008 and p = 0.017, respectively) reduced in the intervention group. The mean changes of IL-6 were significantly lower in the intervention group compared with the control group (p = 0.04). In the intervention group, PD and CAL were significantly decreased after intervention (p < 0.001). There were significant differences in the mean change of PD and CAL between the intervention and control groups after intervention (p < 0.001). CONCLUSIONS: Melatonin supplementation in adjunct with non-surgical periodontal therapy might improve inflammatory and periodontal status in T2DM with CP.