A Jerte valley cherry product provides beneficial effects on sleep quality. Influence on aging.

OBJECTIVE: In the present work, we evaluated the effect of the intake of a Jerte Valley cherry-based product (JVCP), compared to a placebo product, on sleep quality, urinary 6-sulfatoxymelatonin (aMT6-s) levels and the serum concentration of interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α) and interleukin-8 (IL-8). DESIGN: This was a blind, placebo-controlled, randomized, crossover study. SETTING: University of Extremadura (Spain). PARTICIPANTS: Ten young (20-30 years old), ten middle-aged (35-55 years old), and ten elderly (65-85 years old) participants. INTERVENTION: A placebo (Kool-Aid®) or JVCP (patent no. ES 2342141 B1) were consumed twice a day, as lunch and dinner desserts. MEASUREMENTS: Actigraphic monitoring was used to record and display the temporal patterns of the individuals' activity and rest. Urinary aMT6-s and serum cytokines (IL-1ß, TNF-α and IL-8) were also determined. RESULTS: The consumption of the JVCP improved the nocturnal rest, measured by sleep efficiency, number of awakenings, total nocturnal activity, sleep latency, assumed sleep, actual sleep time and immobility. Moreover, it was detected an increase in both the levels of aMT6-s found in first-void morning urine and the concentrations of serum pro-somnogenic cytokines obtained from samples collected at the acrophase of the melatonin rhythm (1.00 am) in all experimental age groups after the JVCP consumption. Generally, better results were obtained with advancing age. CONCLUSION: The ingestion of the JVCP may contribute to establish a high-quality sleep and be used as a potential nutraceutical tool to prevent sleep disorders with the advance of age.

Melatonin reduces body weight gain and increases nocturnal activity in male Wistar rats.

AIM: This study evaluated the effect of the administration of melatonin, the chief secretory product of the pineal gland, on the body weight in male Wistar rats. MAIN METHODS: The animals were housed for 4months in cages equipped to log horizontal activity within a thermostatically-controlled chamber, under a 12h/12h light/dark photoperiod (lights on at 08:00h). After acclimatization, the animals were divided into two groups: (1) control animals, and (2) melatonin-treated animals. Melatonin was administered in tap water (20µg/ml), and fresh drinking fluid was changed twice weekly. Rats were fed a standard diet ad libitum. KEY FINDINGS: Food and water intake, body weight, the amplitude of the activity/rest rhythm (motor activity), and blood melatonin and glucose concentrations were measured. The administration of melatonin did not influence either food or water intake or glucose levels relative to those found in the control animals. However, melatonin administration reduced body weight gain and increased nocturnal locomotor activity. The peak concentration of melatonin was found at night coinciding with the increase in nocturnal activity. SIGNIFICANCE: The results show that exogenous melatonin reduces body weight gain without having marked effects on metabolism. This may be due in part to the increased nocturnal activity shown by the animals treated with the indoleamine.

Tryptophan-enriched cereal intake improves nocturnal sleep, melatonin, serotonin, and total antioxidant capacity levels and mood in elderly humans.

Melatonin and serotonin rhythms, which exhibit a close association with the endogenous circadian component of sleep, are attenuated with increasing age. This decrease seems to be linked to sleep alterations in the elderly. Chrononutrition is a field of chronobiology that establishes the principle of consuming foodstuffs at times of the day when they are more useful for health, improving, therefore, biorhythms and physical performance. Our aim was to analyze whether the consumption of cereals enriched with tryptophan, the precursor of both serotonin and melatonin, may help in the reconsolidation of the sleep/wake cycle and counteract depression and anxiety in 35 middle-aged/elderly (aged 55-75 year) volunteers in a simple blind assay. Data were collected for 3 weeks according to the following schedule: The control week participants consumed standard cereals (22.5 mg tryptophan in 30 g cereals per dose) at breakfast and dinner; for the treatment week, cereals enriched with a higher dose of tryptophan (60 mg tryptophan in 30 g cereals per dose) were eaten at both breakfast and dinner; the posttreatment week volunteers consumed their usual diet. Each participant wore a wrist actimeter that logged activity during the whole experiment. Urine was collected to analyze melatonin and serotonin urinary metabolites and to measure total antioxidant capacity. The consumption of cereals containing the higher dose in tryptophan increased sleep efficiency, actual sleep time, immobile time, and decreased total nocturnal activity, sleep fragmentation index, and sleep latency. Urinary 6-sulfatoxymelatonin, 5-hydroxyindoleacetic acid levels, and urinary total antioxidant capacity also increased respectively after tryptophan-enriched cereal ingestion as well as improving anxiety and depression symptoms. Cereals enriched with tryptophan may be useful as a chrononutrition tool for alterations in the sleep/wake cycle due to age.

Diets enriched with a Jerte Valley cherry-based nutraceutical product reinforce nocturnal behaviour in young and old animals of nocturnal (Rattus norvegicus) and diurnal (Streptopelia risoria) chronotypes.

The decline in melatonin secretion with age seems to be one of the major reasons for increased sleep disruption in older animals. Previously, we showed that the administration with melatonin or its precursor, tryptophan, improved activity/rest rhythms in aged individuals. Here, it was evaluated the effect of a 10-day consumption of a Jerte Valley cherry-based nutraceutical product (patent no. ES2342141B1), which contains high levels of tryptophan, serotonin and melatonin, on the activity/rest rhythms of young and old rats (Rattus norvegicus) and ringdoves (Streptopelia risoria) as representatives of animals with nocturnal and diurnal habits, respectively, and its possible relationship with the serum levels of melatonin and glucose. Total diurnal and nocturnal activity pulses were logged at control, during, and up to 3 days after the treatment. Melatonin and glucose were measured with ELISA and testing kits respectively. In both young and old rats, the intake of the cherry nutraceutical decreased diurnal activity, whereas nocturnal activity increased. The opposite effect was observed for ringdoves. The treatment increased the circulating levels of melatonin in both species and restored the amplitude of the activity rhythm in the old animals to that of the non-treated young groups. The consumption of a Jerte Valley cherry-based nutraceutical product may help to counteract the impaired activity/rest rhythm found in aged animals.

Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity.

A worldwide increase in the incidence of obesity indicates the unsuccessful battle against this disorder. Obesity and the associated health problems urgently require effective strategies of treatment. The new discovery that a substantial amount of functional brown adipose tissue (BAT) is retained in adult humans provides a potential target for treatment of human obesity. BAT is active metabolically and disposes of extra energy via generation of heat through uncoupling oxidative phosphorylation in mitochondria. The physiology of BAT is readily regulated by melatonin, which not only increases recruitment of brown adipocytes but also elevates their metabolic activity in mammals. It is speculated that the hypertrophic effect and functional activation of BAT induced by melatonin may likely apply to the human. Thus, melatonin, a naturally occurring substance with no reported toxicity, may serve as a novel approach for treatment of obesity. Conversely, because of the availability of artificial light sources, excessive light exposure after darkness onset in modern societies should be considered a potential contributory factor to human obesity as light at night dramatically reduces endogenous melatonin production. In the current article, the potential associations of melatonin, BAT, obesity and the medical implications are discussed.

Effect of melatonin and tryptophan on humoral immunity in young and old ringdoves (Streptopelia risoria).

Melatonin is involved in the regulation of both cellular and humoral immunity. In the present study we have evaluated the effect of the oral administration of melatonin and its precursor, the amino acid tryptophan, on humoral immune response in ringdoves (Streptopelia risoria) from different age groups. Male and female ringdoves of 4-5years of age (young) and 12-14years of age (old) were used in this study. The animals received a single capsule of 300mg/kg b.w. of tryptophan (old animals) for 3 consecutive days 1h after lights on or a single oral dose (0.25 or 2.5mg/kg body weight/0.1ml per animal/day, young and old animals, respectively) of melatonin, for 3 consecutive days 1h before lights off. Blood samples were taken before beginning the treatment (basal values) and at the end of the treatment. Immunoglobulins, bactericidal and haemolytic activity were measured. Our results show that in old animals the humoral immune response was reduced with respect to the young. Both melatonin and tryptophan treatment increased the immunoglobulin concentration, with the nocturnal values being significantly higher than diurnal values and with a major effect in old animals. The bactericidal activity of the S. risoria serum against Staphylococcus aureus, after the treatment with melatonin or tryptophan, was increased at night with a greater effect in old animals. No significant differences were observed in the haemolytic activity of the serum in young animals, but there was an increase in old animals, with higher values at night after treatment with melatonin. In general, the oral administration of melatonin or tryptophan produced a stimulation of humoral immune response with greater effects in old ringdoves.

Melatonin in relation to the "strong" and "weak" versions of the free radical theory of aging.

That free radicals and the damage they inflict are related to deteriorative cellular and organismal changes associated with aging and also with the development of a variety of age-related diseases is widely debated. There seems to be little doubt that free radical mutilation of essential molecules contributes to these conditions. Numerous investigators, on the basis of their experimental results, have drawn this conclusion. If the free radical theory of aging and disease development has validity, antioxidants could presumably be successfully used to delay the molecular destruction, cellular loss, and organismal death. In the current review we summarize the experimental data related to the utility of melatonin in protecting against reactive oxygen and reactive nitrogen species-induced cellular damage. While the data supporting a role for melatonin in forestalling aging and prolonging life span per se is not compelling, the findings related to melatonin's ability to reduce the severity of a variety of age-related diseases that have as their basis free radical damage is convincing. To date, the bulk of these investigations have been performed in experimental models of diseases in animals. It is now imperative that similar studies be conducted using humans whose quality of life may benefit from treatment with melatonin.

Hydrogen peroxide increases the phagocytic function of human neutrophils by calcium mobilisation.

We have studied the effect of exogenous administration of hydrogen peroxide (H(2)O(2)) on phagocytic activity of human neutrophils. The treatment of cells with increasing concentrations of H(2)O(2) evoke a significant elevation of phagocytic function assayed as phagocytic index, percentage and efficiency; and was similar to that induced by the calcium mobilising agonist formyl-methionyl-leucyl-phenylalanine (fMLP). This stimulatory effect was reduced by pre-treatment of neutrophils with catalase and abolished in neutrophils loaded with the intracellular calcium quelator dimethyl BAPTA. In the absence of extracellular calcium, treatment of cells with H(2)O(2) resulted in a increase in [Ca(2+)]( i ), indicating the release of calcium from intracellular stores. H(2)O(2) abolished the typical calcium release stimulated by the physiological agonist fMLP, while depletion of agonist-sensitive calcium pools by fMLP was able to prevent H(2)O(2)-induced calcium release. We conclude that H(2)O(2) induces calcium release from agonist-sensitive stores and consequently increase the phagocytosis process.

Melatonin, lipid peroxidation, and age in heterophils from the ring dove (Streptopelia risoria).

Numerous recent studies have shown the ability of physiological as well as all pharmacological concentrations of melatonin to prevent oxidative stress. We have found that incubating avian heterophils from young birds with a pharmacological concentration of 100 microM (23x10(6) pg/ml) melatonin reduced superoxide anion levels by modulating the activity of superoxide dismutase while also enhancing phagocytosis. There was also a decline in lipid peroxidation levels with both physiological and pharmacological concentrations of this indolamine. In the present work, we evaluated malonaldehyde (MDA) levels as an indicator of lipid peroxidation (both basal and antigen-induced) in young and old animals (ring doves) at different times of day (16:00 and 00:00) and with two incubation times (15 and 60 min). The lipid peroxidation was also measured in heterophils from old animals, incubated with the physiological concentrations of melatonin measured in young animals (50 and 300 pg/ml, diurnal and nocturnal, respectively). The results, expressed as nmol MDA/mg protein, show that MDA levels were higher in heterophils of old animals than in the young birds in all the experimental groups studied at both 16:00 and 00:00 (00:00 is the time at which the lowest peroxidation levels were obtained). Incubation with melatonin was found to reduce MDA levels, with the maximum reduction being after the 60?min incubation time and the nocturnal melatonin concentration. At both concentrations (diurnal and nocturnal), melatonin also counteracted the enhancement of MDA levels caused by latex beads, with the effect being greater at the longer incubation time. In conclusion, the results are further evidence of the antioxidant effect of melatonin even at physiological concentrations, and suggest its utility as a therapeutic agent in some pathological processes associated with age.

Comparative study of the heterophil phagocytic function in young and old ring doves (Streptopelia risoria) and its relationship with melatonin levels.

A functional connection between the pineal gland (via the hormone melatonin) and the immune system has been suggested. In our previous results in the ring dove, we observed diurnal oscillations in the levels of this neurohormone in young animals and a decline in its plasma levels with advancing age (which is accompanied by the absence of diurnal rhythm). We also noted enhanced phagocytic activity of heterophils from old animals after in vitro incubation with both physiological and pharmacological doses of melatonin. Here, we evaluate the functional capacity of ring dove (Streptopelia risoria) heterophils in young (2 years of age) and old (8 years and more) animals at different times of day (0:00, 10:00 and 16:00, the times when the maximum, minimum, and mean values, respectively, of melatonin levels are observed in young animals). The phagocytic capacities for the ingestion of latex beads and Candida albicans were evaluated, as well as the oxidative metabolism which accompanies phagocytosis. At all three times of day studied, the heterophil phagocytic function with both latex and C. albicans was significantly greater in the young than in the old animals, and in the young animal cells it was significantly higher at 0:00. In addition, in the presence of latex beads, there was a significant decline at 10:00 and 0:00 of superoxide anion levels in the young animals relative to the old. In the young animals, there was a decline at 0:00 in comparison with both 10:00 and 16:00, and in the old animals there was a decline at both 0:00 and 16:00 compared with 10:00. These results could be due, at least in part, to the absence of a diurnal rhythm of melatonin in old animals, and to an enhancing effect of that hormone on young animals' heterophil phagocytic function, which would also neutralize the oxidative stress deriving from this immune function.

Nurse/parent role perceptions in care of neonatal intensive care unit infants: implications for the advanced practice nurse.

This study compared parent and nurse perceptions of the nurse's roles regarding responsibilities toward infants in the neonatal intensive care unit (NICU). It also examined the attitudes of nurses and parents regarding the extent to which parents should participate in the care of their infants in the NICU, as well as the role of the advanced practice nurse (APN). The convenience sample of 25 parents of infants in the NICU and 35 nurses who cared for the infants was surveyed regarding perceptions of nurses and parents about nurse responsibilities and parent roles in the NICU. Results suggest parents and nurses have different perceptions about role expectations and that nurses perceive themselves to lack comfort and knowledge in providing support to parents. The findings support a role of the APN as fostering a nursing NICU philosophy to facilitate role transition for parents of infants in the NICU.