Melatonin treatment delays the softening of blueberry fruit by modulating cuticular wax metabolism and reducing cell wall degradation.

The effects of postharvest melatonin (MT) treatment on cuticular wax and cell wall metabolism in blueberry fruit (Vaccinium spp.) were evaluated. The results revealed that MT treatment maintained the cuticular wax rod-like structure and delayed wax degradation. The gas chromatography-mass spectrometry analysis results revealed that MT application changed the cuticular wax composition in blueberries, and 25 metabolic components were screened. The metabolic regulation of wax quality in blueberry fruit may therefore be influenced by MT. Additionally, MT slowed down pectin and cellulose degradation by reducing the activities of cell wall degrading enzymes like pectin methyl esterase polygalacturonase, ß-galactosidase, and cellulose in the later stages of storage. It also downregulated the transcriptional expression of related genes like VcPE, VcPG, VcBG6, and VcGAL1. Thus, MT prevented softening and senescence by postponing the degradation of the cell wall in postharvest blueberry fruit.

Mineral, Nutritional, and Phytochemical Composition and Baking Properties of Teff and Watermelon Seed Flours.

Demonstrated limitations in the mineral and nutritional composition of refined flours have led to calls for the possibility of enriching them with health-promoting supplements, such as high-value non-cereal seeds. Teff and watermelon seeds have been found suitable for the production of gluten-free flour, but so far, their potential to enrich conventional baking flours has not been comprehensively studied. Hence, the present study aimed at farinographic evaluation of dough based on refined wheat flour with additions of whole white teff (TF) and watermelon seed (WSF) and pomace (DWSF) flours (tested levels 10%, 20%, and 30%), as well as possibly extensive chemical characterization of the plant material tested, including LC-MS/MS, GC-MS, total phenolics, flavonoids, melatonin, and antioxidant potential. Most of the rheological traits were improved in the flour mixtures compared to the base white flour: development time and quality number (above 1.6-fold increase), softening and stability time (up to 1.3-fold change), and water absorption (up to 6%). Overall, the best results were achieved after the addition of watermelon seed pomace. The DWSF material was characterized by the highest levels of P, Mg, Na (7.5, 1.7, 0.4 g/kg, respectively), and Fe and Zn (124 and 27 mg/kg), while TF was the richest in Ca (0.9 g/kg) and Mn (43 mg/kg). Protein and fat levels were significantly higher in watermelon seeds compared to teff (about double and up to 10-fold, respectively). Phytochemical analyses highlighted the abundance of phenolics, especially flavones, in TF, WSF and DWSF flours (244, 93, and 721 mg/kg, respectively). However, the value of total polyphenols was low in all materials (<2 mg GAE/g), which also correlates with the low antioxidant potential of the samples. Watermelon seed pomace was characterized by significantly higher melatonin concentration (60 µg/kg) than teff (3.5 µg/kg). This study provides new information on the chemical composition and application opportunities of teff and watermelon seeds.

Impact of Tea Processing on Tryptophan, Melatonin, Phenolic and Flavonoid Contents in Mulberry (Morus alba L.) Leaves: Quantitative Analysis by LC-MS/MS.

Mulberry (Morus alba L.) leaves from two cultivars, Yai-Burirum (YB) and Khunphai (KP), were prepared into green tea (GT) and black tea (BT). Compared to fresh leaf (FL) extract, GT and BT extracts were evaluated for their total phenolic and total flavonoid contents. Total phenolic content (TPCs) in all samples ranged between 129.93 and 390.89 mg GAE/g extract. The processing of tea decreased the levels of TPC when compared to FL extracts in both cultivars. The total flavonoid content (TFCs) in all samples was found in the range of 10.15-39.09 mg QE/g extract and TFCs in GT and BT extracts were higher than FL extracts. The change in tryptophan, melatonin, phenolic and flavonoid contents was investigated by liquid chromatography-mass spectroscopy (LC-MS). The results exhibited that tryptophan contents in all samples were detected in the range 29.54-673.72 µg/g extract. Both GT and BT extracts increased tryptophan content compared to FL extracts. BT extracts presented the highest amounts of tryptophan among others in both cultivars. Phenolic compounds were found in mulberry leaf extracts, including gallic acid, caffeic acid, gentisic acid, protocatechuic acid and chlorogenic acid. Chlorogenic acid presented the highest amount in all samples. Almost all phenolic acids were increased in the processed tea extracts except chlorogenic acid. Rutin was the only flavonoid that was detected in all extracts in the range 109.48-1009.75 mg/g extract. The change in phenolic and flavonoid compounds during tea processing resulted in the change in antioxidant capacities of the GT and BT extracts. All extracts presented acetylcholinesterase enzyme (AChE) inhibitory activity with IC50 in the range 146.53-165.24 µg/mL. The processing of tea slightly increased the AChE inhibitory effect of GT and BT extracts. In conclusion, processed tea from mulberry leaves could serve as a new alternative functional food for health-concerned consumers because it could be a promising source of tryptophan, phenolics and flavonoids. Moreover, the tea extracts also had antioxidative and anti-AChE activities.

3D-printed electrochemical pestle and mortar for identification of falsified pharmaceutical tablets.

Falsified medicines and healthcare supplements provide a major risk to public health and thus early identification is critical. Although a host of analytical approaches have been used to date, they are limited, as they require extensive sample preparation, are semi-quantitative and/or are inaccessible to low- and middle-income countries. Therefore, for the first time, we report a simple total analysis system which can rapidly and accurately detect falsified medicines and healthcare supplements. We fabricated a poly-lactic acid (PLA) pestle and mortar and using a commercial 3D printer, then made carbon black/PLA (CB/PLA) electrodes in the base of the mortar using a 3D printing pen to make an electrochemical cell. The pestle and mortar were able to crush and grind the tablets into a fine powder to the same consistency as a standard laboratory pestle and mortar. Using melatonin tablets to characterise the device, the 3D-printed pestle and mortar was able to detect the concentration of melatonin in the presence of insoluble excipients. The calibration plot showed a linear response from 37.5 to 300 µg/mL, where the limit of detection was 7 µg/mL. Electrochemical treatment was able to regenerate the CB/PLA working electrode allowing for repeated use of the device. In a blinded study, the device was able to accurately determine falsified melatonin tablets with recovery percentages between 101% and 105%. This was comparable to HPLC measurements. Overall, these findings highlight that our 3D-printed electrochemical pestle and mortar is an accessible and effective total analysis system that can have the ability to identify falsified medicines and healthcare supplements in remote locations.

Acutely applied melatonin prevents CCl4-induced testicular lesions in rats: the involvement of the oxidative capacity and arginine metabolism

Abstract Carbon tetrachloride (CCl4) represents an organic chemical that causes reactive oxygen species derived organ disturbances including male infertility. Melatonin (MLT) is a neurohormone with strong antioxidant capacity, involved in numerous physiological processes. In this study we evaluated the capability of MLT, administered in a single dose of 50 mg/kg, to preserve the testicular tissue function after an acute administration of CCl4 to rats. The disturbance in testicular tissue and the effects of MLT after CCl4 exposure were estimated using biochemical parameters that enabled us to determine the tissue (anti)oxidant status and the intensity of arginine/nitric oxide metabolism. Also, the serum levels of testosterone and the histopathological analysis of tissue gave us a better insight into the occurring changes. A significant diminution in tissue antioxidant defences, arginase activity and serum testosterone levels, followed by the increased production of nitric oxide and extensive lipid and protein oxidative damage, was observed in the CCl4-treated group. The application of MLT after the CCl4 caused changes, clearly visible at both biochemical and histological level, which could be interpreted mainly as a consequence of general antioxidant system stimulation and a radical scavenger. On the other hand, the application of MLT exerted a limited action on the nitric oxide signalling pathway.

Plant-derived melatonin from food: a gift of nature.

In recent years, people have become increasingly interested in bioactive ingredients from plants, especially antioxidant molecules such as melatonin, which are beneficial to human health. The purpose of this article is to provide new information on plant-derived foods with a high content of melatonin. We comprehensively summarize the content of melatonin in plant-derived foods and discuss the factors that influence melatonin levels to provide new ideas on enhancement. Additionally, we describe the biosynthetic pathway of melatonin and identify its major functions. Medicinal herbs are often rich in melatonin while many vegetables and fruits exhibit somewhat lower levels with wide variations among species. The genetic traits of plants, the phenological stage of the cultivar, the photoperiod, the level of stress to which the plants are exposed at the time of harvest, exposure to agrochemicals and determination methods are the main factors affecting the melatonin content. To date, standardization of uniform sampling times and the use of suitable pretreatments as well as determination methods have not been achieved. The results of the studies reviewed highlight the potentially important role of plant melatonin in influencing the progression of human diseases. Based on the health promotional aspects of melatonin, consuming foods containing higher concentrations of tryptophan and melatonin is suggested.

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.

Optimization of Light Intensity, Temperature, and Nutrients to Enhance the Bioactive Content of Hyperforin and Rutin in St. John's Wort.

St. John's wort (Hypericum perforatum L.) is a medicinal plant that alleviates depression and other disorders due to its abundance of active ingredients. Hyperforin, rutin, and melatonin are the main active, and important, ingredients in St. John's wort that alleviate depression. In order to investigate the optimal conditions for accumulating these active ingredients, design of experiments and response surface methodology (RSM) was employed in this study. Two-month-old St John's wort plants were cultivated in growth chambers at varying temperatures, light intensities, and nutrient solution concentrations before analysis by HPLC, for determining differences in hyperforin, rutin, and melatonin content. The results showed that hyperforin and rutin contents were significantly influenced by temperature (18-23 °C) and light intensity (49-147 µmol m-2 s-1 photosynthetic photon flux density (PPFD)), whereas Hoagland's nutrient solution concentration (25-75%) had little effect. The accumulation of melatonin might not be influenced by cultivation conditions. Light intensity and temperature are easily controlled environmental factors in artificial cultivation, both of which are related to secondary metabolite production in the plant. Based on RSM, the optimal conditions for the accumulation of hyperforin and rutin were obtained. The maximum content of hyperforin was 5.6 mg/g, obtained at a temperature of 19 °C, a nutrient solution concentration of 45%, and a light intensity of 49 µmol m-2 s-1 PPFD. The maximum content of rutin was 3.8 mg/g obtained at a temperature of 18 °C, a nutrient solution concentration of 50%, and a light intensity of 147 µmol m-2 s-1 PPFD. This evaluation of suitable conditions for the accumulation of bioactive compounds in St. John's wort can be applied to plant factories on a large scale.

Melatonin Content of Human Milk: The Effect of Mode of Delivery.

Objective: Cesarean section rates are increasing in developed countries and could be performed as an emergency or elective procedure. Our research aim was to determine whether elective cesarean section influences the melatonin content, the main circadian hormone, in human milk. Methods: Twenty-one women after vaginal delivery and 18 women after elective cesarean section were included. Only healthy mothers with normal newborns exclusively breastfed were recruited. Two samples of human milk were collected for each woman at three stages of lactation: colostrum, transitional milk, and mature milk; at each stage, one daytime sample and another nighttime sample were obtained. In total, 228 milk samples were studied. The melatonin content was analyzed by enzyme-linked immunosorbent assay. Results: Melatonin rhythmicity with higher melatonin content at night was maintained at each of the three stages of lactation, regardless of the type of delivery. A higher melatonin content was found in daytime colostrum after cesarean section with respect to colostrum obtained from mothers after vaginal delivery (30.3 pg/mL versus 14.7 pg/mL, p = 0.020). Melatonin content decreased progressively throughout the course of lactation in both groups. This decrease was significant when comparing transitional milk to colostrum in the cesarean group, both in the daytime (p = 0.016) and nighttime samples (p = 0.048). Conclusions: Cesarean section is associated with an increase in daytime colostrum melatonin. No difference was observed in mature milk with respect to vaginal delivery. Melatonin values in human milk decrease during the first month of lactation and circadian rhythmicity was observed irrespective of the mode of delivery.

Influence of Dietary Sources of Melatonin on Sleep Quality: A Review.

Sleep is an essential biological phenomenon, being a physiological and behavioral process necessary for quality of life. Melatonin is a circadian hormone produced at night by the pineal gland, regulated by the light/dark cycle, under the control of the suprachiasmatic nucleus. Melatonin is an indoleamine, synthesized from the essential amino acid tryptophan via serotonin. Melatonin is also found in plants, where it helps fight oxidative stress. To present a systematic review on the ability of food sources of melatonin to promote healthy sleep. A literature search was performed on the PubMed, Scopus, and ScienceDirect databases, including only randomized, placebo-controlled trials published in English between 2005 and 2019. The methodological quality of the trials was assessed by the Jadad scale. Of the 25 eligible articles, eight met the inclusion criteria. They addressed the intake of milk or cherry juice in children, adults, and elderly subjects and evaluated sleep quality by questionnaires, sleep diary, actigraphy, or polysomnography. The analysis of the studies presented limitations, including lack of homogeneity of treatment dosage and duration. Nonetheless, the results indicated that the consumption of milk and sour cherries, sources of melatonin, may improve sleep quality in humans. These results pointed out to the potential suitability of food sources of melatonin as adjuvants in the prevention and treatment of sleep disorders. Further studies are necessary to better ascertain the aspects relevant to their use.

Cell-free nucleic acids and melatonin levels in human follicular fluid predict embryo quality in patients undergoing in-vitro fertilization treatment.

Despite many advances in assisted reproductive technology (ART), the most viable embryo selection remains a challenge for infertility treatment. This study was designed to investigate whether intra-follicular circulating cell-free DNA (cfDNA) fragments and Melatonin levels predict embryo quality in patients undergoing IVF treatment. A total of eight hundred and ninety-five follicular fluid (ff) samples were collected from 325 infertile patients undergoing IVF treatment. Patients were enrolled from August 2017 to December 2018 in the infertility center of a tertiary care hospital. A clear non-hematic follicular fluid was aspirated after the removal of eggs from the dominant follicles (>18mm) of each patient. Melatonin and E2 levels in each follicular sample were estimated by immune-chemiluminescence using commercially available kits. ALU-qPCR evaluated cfDNA levels in individual follicular fluid samples. Our study presented a significant and negative relationship between intra-follicular cfDNA and melatonin concentration (-0.541: P<0.001). Each individual follicle contains measurable copy number of cfDNA [mean: 1.85±2.98ng/µl (median; 1.86ng/µl (95% Cl: 0.96-2.87)]. In pregnant women cfDNA copy number was significantly decreased in follicular fluid samples(ff) aspirated from matured oocytes than in immature ones [p<0.01; ß = -0.42±0.49; median; 1.45ng/ml (95% Cl: 0.36-2.97) vs. 3.57ng/µl (95% Cl: 0.37-4.01) respectively. While melatonin concentration in ff samples corresponding to mature oocytes was significantly higher than in ff samples related to immature oocytes (p<0.001). Moreover, in pregnant women cfDNA level was significantly lower in ff samples related to oocytes which produces top-quality embryos versus low quality embryos [p<0.001; ß=1.81±0.91; median; 1.25ng/µl (95% Cl: 0.35-1.97)] vs. [(median; 3.65ng/ml (95% Cl: 1.23-6.36)] respectively. Likewise, in non-pregnant women melatonin levels were significantly decreased in ff samples related to embryos with high fragmentation rate (≥25%) than embryos with low fragmentation rate (<25%; p<0.001). Conclusively, this study indicates that Intra-follicular cfDNA and melatonin concentration possibly a new supplemental tool that supports to establish an advanced non-invasive early prognostic test for the patients undergoing IVF/ICSI procedure.

Variations in melatonin levels in preterm and term human breast milk during the first month after delivery.

The objectives of the present study were to examine the dynamic changes in breast milk melatonin throughout the course of lactation and to explore factors associated with changes in melatonin concentrations and rhythms in both preterm and term breast milk. Breast milk was collected sequentially at 03:00, 09:00, 15:00, and 21:00 in one day. Melatonin was analyzed in 392 breast milk samples from 98 healthy nursing mothers at 0 to 30 days postpartum. In both preterm and term breast milk, the melatonin concentration presented a circadian rhythm with the acrophase at around 03:00. Subgroup analysis showed the peak melatonin concentrations differed significantly across lactation stages, with the highest concentration in the colostrum, followed by transitional and mature breast milk. At 03:00, preterm breast milk had a higher concentration of melatonin than term breast milk in the colostrum (28.67 pg/mL vs. 25.31 pg/mL, p < 0.022), transitional breast milk (24.70 pg/mL vs. 22.55 pg/mL), and mature breast milk (22.37 pg/mL vs. 20.12 pg /mL). Further studies are warranted for their roles and significance on melatonin in breast milk in nutrition and metabolism of neonates.

Melatonin Action on the Activity of Phagocytes from the Colostrum of Obese Women.

BACKGROUND AND OBJECTIVES: Breastfeeding promotion is an important public health strategy for counter-balancing the negative effects of maternal overweight and obesity. Colostrum contains melatonin, which can attenuate the impacts of excessive maternal weight and boost the infant's immune system. Therefore, the objective of this study was to analyze the effects of melatonin on mononuclear (MN) phagocytes from the colostrum of women with pre-gestational obesity. Materials and Methods: Colostrum samples were collected postpartum from 100 women at a public hospital in São Paulo, Brazil. The donors were divided into two groups: the control group and the high body mass index (BMI) group. Melatonin levels in the colostrum were determined by an ELISA Kit, and the functional activity of MN cells was assessed using the phagocytosis assay by flow cytometry, and reactive oxygen species (ROS), intracellular calcium, and apoptosis were assessed by fluorimetry using a microplate reader. RESULTS: The colostrum of mothers with pre-gestational high BMI exhibited higher melatonin levels (p < 0.05) and lower phagocytosis (p < 0.05) and ROS release (p < 0.05). Superoxide release was similar between the normal and high BMI groups (p > 0.05). Intracellular calcium release and apoptosis were also higher in the high BMI group (p < 0.05). Melatonin levels likely increased the phagocytosis rate and reduced intracellular calcium release and the apoptosis index (p < 0.05). CONCLUSIONS: The results suggest that melatonin is a possible mechanism for maternal-infant protection against obesity and restores the functional activity of colostrum phagocytes in obese mothers.

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 in Medicinal and Food Plants: Occurrence, Bioavailability, and Health Potential for Humans.

Melatonin is a widespread molecule among living organisms involved in multiple biological, hormonal, and physiological processes at cellular, tissue, and organic levels. It is well-known for its ability to cross the blood-brain barrier, and renowned antioxidant effects, acting as a free radical scavenger, up-regulating antioxidant enzymes, reducing mitochondrial electron leakage, and interfering with proinflammatory signaling pathways. Detected in various medicinal and food plants, its concentration is widely variable. Plant generative organs (e.g., flowers, fruits), and especially seeds, have been proposed as having the highest melatonin concentrations, markedly higher than those found in vertebrate tissues. In addition, seeds are also rich in other substances (lipids, sugars, and proteins), constituting the energetic reserve for a potentially growing seedling and beneficial for the human diet. Thus, given that dietary melatonin is absorbed in the gastrointestinal tract and transported into the bloodstream, the ingestion of medicinal and plant foods by mammals as a source of melatonin may be conceived as a key step in serum melatonin modulation and, consequently, health promotion.

Resetting the late timing of 'night owls' has a positive impact on mental health and performance.

BACKGROUND: There is conflict between living according to our endogenous biological rhythms and our external environment, with disruptions resulting in negative consequences to health and performance. This is often documented in shift work and jet lag, but 'societal norms' (eg, typical working hours) can create profound issues for 'night owls', people whose internal biological timing predisposes them to follow an unusually late sleep-wake cycle. Night owls have also been associated with health issues, mood disturbances, poorer performance and increased mortality rates. METHODS: This study used a randomized control trial design aimed to shift the late timing of night owls to an earlier time (phase advance), using non-pharmacological, practical interventions in a real-world setting. These interventions targeted light exposure (through earlier wake up/sleep times), fixed meals times, caffeine intake and exercise. RESULTS: Overall, participants demonstrated a significant advance of ∼2 h in sleep/wake timings as measured by actigraphy and circadian phase markers (dim light melatonin onset and peak time of the cortisol awakening response), whilst having no adverse effect on sleep duration. Notably, the phase advance was accompanied by significant improvements to self-reported depression and stress, as well as improved cognitive (reaction time) and physical (grip strength) performance measures during the typical 'suboptimal' morning hours. CONCLUSIONS: Our findings propose a novel strategy for shifting clock timing towards a pattern that is more aligned to societal demands that could significantly improve elements of performance, mental health and sleep timing in the real world.

Anti-inflammatory effects of Melatonin: A mechanistic review.

N-acetyl-5-methoxy-tryptamine (melatonin) is a natural substance produced both by plants, as a secondary metabolite, and animals, by the pineal gland and other tissues. In humans, melatonin participates in numerous functions including the regulation of mood, sleep, reproduction, promotion of immunomodulation, antioxidant defense and as an anti-inflammatory agent. The anti-inflammatory activity of melatonin could yield beneficial effects on intake, particularly against the chronic inflammation which underlies many chronic diseases. This review aims to provide an assessment of the literature data on the anti-inflammatory activity of melatonin, with a particular focus on the mechanisms responsible for this behavior. We can conclude that many in vitro studies and in vivo studies in experimental animal model systems show that melatonin exerts anti-inflammatory activity in a number of chronic diseases which affect different organs in different circumstances. Clinical trials, however, often fail to reach positive results and are thus far inconclusive. Thus, in the future, long-term well-designed investigations on melatonin-rich foods or melatonin food supplements could provide valuable information towards public health recommendations on melatonin, taking into account both the nature of the compound and the optimal dose, for protection from long-term inflammation linked to chronic diseases.

Spectroscopic Analysis of Melatonin in the Terahertz Frequency Range.

There is a need for fast and reliable quality and authenticity control tools of pharmaceutical ingredients. Among others, hormone containing drugs and foods are subject to scrutiny. In this study, terahertz (THz) spectroscopy and THz imaging are applied for the first time to analyze melatonin and its pharmaceutical product Circadin. Melatonin is a hormone found naturally in the human body, which is responsible for the regulation of sleep-wake cycles. In the THz frequency region between 1.5 THz and 4.5 THz, characteristic melatonin spectral features at 3.21 THz, and a weaker one at 4.20 THz, are observed allowing for a quantitative analysis within the final products. Spectroscopic THz imaging of different concentrations of Circadin and melatonin as an active pharmaceutical ingredient in prepared pellets is also performed, which permits spatial recognition of these different substances. These results indicate that THz spectroscopy and imaging can be an indispensable tool, complementing Raman and Fourier transform infrared spectroscopies, in order to provide quality control of dietary supplements and other pharmaceutical products.

Diagnostic and Treatment Challenges of Sighted Non-24-Hour Sleep-Wake Disorder.

STUDY OBJECTIVES: To report the diagnostic and treatment challenges of sighted non-24-hour sleep-wake disorder (N24SWD). METHODS: We report a series of seven sighted patients with N24SWD clinically evaluated by history and sleep diaries, and when available wrist actigraphy and salivary melatonin levels, and treated with timed melatonin and bright light therapy. RESULTS: Most patients had a history of a delayed sleep-wake pattern prior to developing N24SWD. The typical sleep-wake pattern of N24SWD was seen in the sleep diaries (and in actigraphy when available) in all patients with a daily delay in midpoint of sleep ranging 0.8 to 1.8 hours. Salivary dim light melatonin onset (DLMO) was evaluated in four patients but was missed in one. The estimated phase angle from DLMO to sleep onset ranged from 5.25 to 9 hours. All six patients who attempted timed melatonin and bright light therapy were able to entrain their sleep-wake schedules. Entrainment occurred at a late circadian phase, possibly related to the late timing of melatonin administration, though the patients often preferred late sleep times. Most did not continue treatment and continued to have a non-24-hour sleep-wake pattern. CONCLUSIONS: N24SWD is a chronic debilitating disorder that is often overlooked in sighted people and can be challenging to diagnose and treat. Tools to assess circadian pattern and timing can be effectively applied to aid the diagnosis. The progressive delay of the circadian rhythm poses a challenge for determining the most effective timing for melatonin and bright light therapies. Furthermore, once the circadian sleep-wake rhythm is entrained, long-term effectiveness is limited because of the behavioral and environmental structure that is required to maintain stable entrainment.

Human colostrum action against Giardia lamblia infection influenced by hormones and advanced maternal age.

Children are more susceptible to Giardia lamblia infection. Cells and hormones contained in human colostrum have an immunoprotective action against giardiasis, but the effects of advanced maternal age on these components are poorly understood. This study analyzed the colostrum of older women to determine melatonin and cortisol levels besides the participation of these hormones on the functional activity of phagocytes against G. lamblia. Colostrum samples were collected from younger (18 to 35 years old) and older (over 36 years old) lactating women. Colostrum samples were subjected to melatonin and cortisol determination, immunophenotyping, quantification of superoxide release, and assessment of phagocytic rate and microbicidal activity of phagocytes treated with hormones and in the presence of G. lamblia. Colostrum from mothers of advanced age contained higher melatonin and cortisol levels and a lower rate of cells expressing CD14+ and CD15+. In the colostru of these older mothers, melatonin increased superoxide release by phagocytes. In both groups, superoxide release by phagocytes treated with cortisol was higher in the presence of G. lamblia. In colostrum from mothers of advanced age, mononuclear (MN) phagocytes treated with melatonin showed higher phagocytosis of G. lamblia and higher microbicidal index. In younger mothers, MN and polymorphonuclear (PMN) colostrum phagocytes exhibited higher rates of G. lamblia elimination when treated with both melatonin and cortisol. In older mothers, cortisol and melatonin regulation for the functional activity of colostrum phagocytes against G. lamblia may represent an additional defense mechanism, relevant for the protection and treatment of parasitic infections in breastfed children.