Daily Melatonin Research Articles

The influence of melatonin on the functional state of the human body during desynchronosis

In the article the mechanisms of melatonin action in the human body, exploring its impact on circadian rhythms, sleep, the immune system, and overall physiological function were considered. A focal point is the use of melatonin as a pharmacological tool to address dyssynchrony, particularly in students facing new time zones or geographic latitude changes. The study aims to understand melatonin's potential influence on regulating biological rhythms and the general physiological state in such scenarios. It scrutinizes how melatonin affects circadian rhythms, sleep, activity, and overall physiological balance during disruptions in biorhythmic synchronization. Recent studies were analyzed, revealing promising prospects for melatonin in regulating desynchronization and maintaining human health amid altered biological rhythms. Findings indicated that students in the experimental group, who took melatonin, experienced enhanced academic performance, increased work capacity, and improved mood. That underscored melatonin's positive impact on the functional state of the human body, even in the presence of desynchronosis. A study involving 100 students identified changes in circadian rhythms contributing to seasonal depression, with daily melatonin tablets proving effective in alleviating desynchronization symptoms. The article furnishes vital scientific data and practical recommendations, catering to professionals in biomedicine, biology, and pharmacology, as well as individuals keen on understanding human health and biological rhythms.

КЛИНИЧЕСКОЕ ЗНАЧЕНИЕ СУТОЧНОГО МОНИТОРИРОВАНИЯ АРТЕРИАЛЬНОГО ДАВЛЕНИЯ И ЦИРКАДНОГО СИНТЕЗА МЕЛАТОНИНА В ПРОГНОЗИРОВАНИИ СИНДРОМА ОБСТРУКТИВНОГО АПНОЭ СНА У ПАЦИЕНТОВ С АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ I-II СТЕПЕНИ

Objective. To study the role of 24-hour ambulatory blood pressure monitoring (ABPM) and circadian melatonin (MT) synthesis in predicting obstructive sleep apnea syndrome (OSAS) in patients with grade 1-2 arterial hypertension (AH) and to reveal the relationship between the study findings. Material and methods. 67 patients aged 50.0 (41.0; 56.0) having grade 1-2 AH were examined and divided into 2 groups in regard to the complex of clinical and instrumental research methods: Group 1 – 25 patients having AH and Group – 45 patients having AH associated with OSAS. 24-hour ABPM, anthropometric measurements, and respiratory monitoring were performed. MT levels were evaluated by the content of its metabolite 6-sulfatoxymelatonin (6-COMT) in the urine. Results It has been found that according to ABPM diastolic blood pressure variability during the day was ≥12 mm Hg and had high sensitivity (74.1%) and specificity (91.7%) for predicting the OSAS in patients with hypertension receiving standard antihypertensive therapy. The characteristic feature of the daily MT production in patients with AH in combination with OSAS is an increase in the level of 6-SOMT in daily urine (p=0.031) and its daily portion (p=0.037), correlating with the severity of OSAS (r=0.43; p=0.00065 and r=0.40; p=0.00079, respectively) and independent of the grade of AH (p>0.05). Conclusion. The obtained results allow us to recommend the use of ABPM as a screening, low-cost study to predict OSAS in patients with grade 1-2 AH. The identified changes in the daily rhythm of MT synthesis weakly correlate with the severity of OSAS and the degree of hypertension.

Melatonin Against Aging: Could We Stimulate Melatonin Secretion Through Tahajjud?

Background: Islamic instructions suggest waking up near dawn and praying to Allah. This is the time of maximum melatonin secretion, a hormone whose main function is regulating the circadian rhythm. Melatonin secretion declines with age, leading to different clinical consequences. This study investigated the melatonin levels among night vigil prayers, non-prayer late sleepers, and those with regular night sleep. Methods: A questionnaire including information about age, gender, education, and occupation was used to collect the demographic information of the participants. Melatonin was measured with two blood draws (23:00 to 24:00 and 9:00 to 10:00). Results: There was a significant difference between the night vigil prayers’ nocturnal and daily melatonin and the melatonin levels of the other two groups. There was no significant difference in the average daily serum melatonin levels between regular night sleepers and non-praying late sleepers (P=0.306). Moreover, a significant negative relationship was found between age and nocturnal melatonin (r=0.38, P<0.0001) and between age and daily melatonin (r=0.25, P=0.02). Conclusion: Night vigil prayers had higher average nocturnal and daily serum melatonin levels than non-praying late sleepers and regular sleepers. Therefore, waking up at night accompanied by approaching Allah, prayer, supplication, and positive thoughts was related to release in melatonin.

Effects of 12 Weeks of Daily Melatonin Administration on Inflammatory Markers and Adipose Tissue Mass of Rats under Hypoestrogenism.

Background and Objectives: The hormonal state of hypoestrogenism is associated with the accumulation of white adipose tissue, which can induce an increase in pro-inflammatory markers, leading to progressive health complications. Melatonin can act on adipose tissue mass, promoting its reduction and influencing inflammation, reducing IL-6 and releasing IL-10, pro- and anti-inflammatory markers, respectively. However, the role of melatonin regarding such parameters under the context of hypoestrogenism remains unknown. The aim of this study was to determine the effect of 12 weeks of hypoestrogenism and melatonin on white adipose tissue mass and circulating levels of IL-6, IL-10, TGF-β-1, and leukotriene C4 (LTC4). Materials and Methods: The animals (Wistar rats with sixteen weeks of age at the beginning of the experiment) under hypoestrogenism were submitted to the surgical technique of bilateral ovariectomy. The animals received melatonin (10 mg·kg-1) or vehicles by orogastric gavage every day for 12 weeks and administration occurred systematically 1 h after the beginning of the dark period. White adipose tissue (perigonadal, peritoneal, and subcutaneous) was collected for mass recording, while blood was collected for the serum determination of IL-6, IL-10, TGF-β-1, and LTC4. Results: Hypoestrogenism increased the perigonadal and subcutaneous mass and IL-6 levels. Melatonin kept hypoestrogenic animals in physiological conditions similar to the control group and increased thymus tissue mass. Conclusions: Hypoestrogenism appears to have a negative impact on white adipose tissue mass and IL-6 and although melatonin commonly exerts a significant effect in preventing these changes, this study did not have a sufficiently negative impact caused by hypoestrogenism for melatonin to promote certain benefits.

Melatonin and sexual development of adolescents with type 1 diabetes

Objective — to study the level of daily melatonin excretion in adolescents with type 1 diabetes mellitus (DM1) at the stages of puberty, taking into account the course of puberty. Materials and methods. The investigation involved 172 patients with DM1 aged 9—18 years (85 boys and 87 girls), who stayed in the Endocrinology Department of the SI «Institute for Children and Adolescents Health Care of the NAMS of Ukraine» for examinations and treatment. The DM1 duration was 1 to 10 years. With account of the level of sexual development at the time of examination, adolescents were divided into the following subgroups: prepuberty (T1); early puberty (T2); puberty itself (T3); late puberty (T4). The nature of sexual maturation was assessed with account of the norms for the corresponding age. The nature of melatonin production was assessed by the excretion of its main metabolite — 6-­sulfatoxymelatonin in daily urine, which was determined by fluorometric method. Statistical processing of the results was carried out using application packages Microsoft Excel and SPSS 17.0. Results and discussion. The effects of puberty on melatonin production have been determined, with its increase during puberty and late puberty. It has been proven that violation of the puberty course is accompanied with changes in the melatonin levels, corresponding to the degree of sexual development of girls and boys with DM1. In conditions of accelerated puberty, the melatonin level increases, and it decreases in case of slowdown sexual development. In girls of 14—18 years old, the lowest melatonin levels were determined in patients with delayed sexual development and primary amenorrhea. During sexual maturation, formation of epiphyseal­pituitary­gonadal and epiphyseal­pituitary­thyroid links takes place, their nature changes in the course puberty. Conclusions. In adolescents with DM1, the age-related dynamics of daily melatonin excretion during puberty is preserved, with an increase in its levels during late puberty. Melatonin levels in patients with DM1 depend on the sexual maturation course, and they are altered in case of its disorders. Regardless of gender, at delayed sexual development significantly lower melatonin levels were registered in comparison with patients with normal sexual development. The nature of correlations between melatonin and hormonal indicators depends on the level of an adolescent’s sexual development and gender.

The Effect of Melatonin on Increasing the Health Related Quality of Life in Non-Metastatic Breast Cancer Patients: Three-Year Follow up a Clinical Trial.

Although breast cancer is common worldwide, if diagnosed early and treated on time, the probability of recovery is high and patients often experience a long life. Reducing the quality of life is a common side effect in patients. Melatonin may have an important role in fatigue, sleep disorders and, as a result, the health-related quality of life (HRQoL) in people. About 184 patients with breast cancer were enrolled in 2 groups: intervention with daily melatonin intake of 18 mg for 3 years (93 patients) and the control group with placebo intake (91 patients). Health-related quality of life and the effect of melatonin on increasing that were evaluated with the EORTC QLQ-C30 questionnaire, third edition at the beginning, 2 months later and 3 years after the beginning of the study. The general score of the HRQoL was significantly different both in the passage of time and in the comparative study of the 2 groups, and it was better in the melatonin group (P < .05). Long-term use of 18 mg of melatonin for 3 years in patients with non-metastatic breast cancer can lead to an increase in the patients' quality of life.

Seasonal Variations in Melatonin Secretory Rhythms in High-, Middle-, and Low-Latitude Regions

This study aims to measure the daily melatonin secretory rhythms of people living in high-, mid-, and low-latitude regions characterised by different day lengths and global solar-radiation conditions. In Poland, a high-latitude region, the amount of melatonin secretion is greater, with secretion occurring earlier (exemplifying phase advance). On the other hand, in Vietnam, a low-latitude region, the level is lower and occurs later (phase delay). Japan, a mid-latitude region, shows behaviour intermediate between these two. Melatonin secretory rhythm in Vietnam is closely related to Day length and Global Solar Radiation, though no such relationship is observed in Poland or Japan, making it necessary for other factors to be considered. The results of this study have important implications considering the impacts of light pollution and lighting-related conditions of modern life.

Does exposure to moonlight affect day/night changes in melatonin and metabolic parameters in Amazonian fish?

Lunar cycle modulates the rhythmic activity patterns of many animals, including fish. The effect of the moonlight cycle on daily melatonin and metabolic parameters was evaluated in matrinxã (Brycon amazonicus) subjected to external natural lighting. Eighty juvenile were distributed in 4 tanks of 1m3 (20 fish/tank) and divided into two groups. One group was exposed to the full moon and the other group to the new moon for 30 days, which corresponds to the duration of the lunar period. At the end of the lunar phase, 6 fish from each group were anesthetized to collect blood, tissue and eye samples at midday and midnight. The comparison between the light and dark periods revealed a significant increase in plasma and ocular melatonin in the last period. However, there was no significant difference for plasma melatonin between moons. Ocular melatonin presented higher concentrations during the new moon. Glucose, total proteins, cortisol, liver glutathione and gill lipid peroxidation were higher in the full moon compared to in the new moon. Plasma triglyceride was higher during the night for the full moon, and the opposite was found for the new moon. Total cholesterol values were higher at night regardless the moon phase. Glutathione in the gills and lipid peroxidation in the liver showed no significant differences. These results highlight the importance of considering both the day and lunar cycles for melatonin and metabolic parameters in species of commercial interest and susceptible to stressful situations in rearing conditions.

Anti-inflammatory and Protective Effects of Melatonin on Rats Exposed to Anticancer Drugs

ABSTRACT This study was aimed to investigate the effects of Melatonin at )10mg/kg) on liver function enzymes AST,ALT,ALP activity and determination the inflammatory marker CRP activity and total counting of WBC on rats exposed to anticancer drugs Gemcitabine, and protective effects of melatonin in the liver tissue.Materials and Methods: sixty four adult male albino rats were used in this study, weighing (250-350) gm at temperature 22±20C , The animals were feeding and drinking water as needed . the animals were divided into 5 main groups as follow : Group A( Control group n=8 ) given a daily D.W. Group B:(melatonin group n=8)given a daily melatonin 10mg/kg/orally. Group C (Gemcitabine n=16) this group was divided into two group according to Gemcitabine dose (25 and 50 mg/kg). Group D (protective group n=16): this group was divided into two group according to Gemcitabine dose (25 and 50 mg/kg ) together with given a daily melatonin in dose (10mg /kg) orally.Group E (protective and treatment group n=16) : this group was divided into two group according to Gemcitabine dose (25 and 50 mg/kg ). This group was given a daily melatonin in dose (10mg /kg) orally as a treatment. The results showed that melatonin reduced the activity of AST, ALT enzymes compare with gemcitabine treated groups, While increased the activity of ALP in A, B groups compare with gemcitabine treated groups , that induced by chemotherapy drug ,While decreased the activity of CRP inflammatory marker in A, B groups compare with another groups that treated with anticancer drug. Melatonin given protective effect on liver enzymes and tissues from damaged that happened by Gemcitabine in two different dose (25,50 mg/kg ) .

Melatonin Supplementation during the Late Gestational Stage Enhances Reproductive Performance of Sows by Regulating Fluid Shear Stress and Improving Placental Antioxidant Capacity

In this study, the effects of daily melatonin supplementation (2 mg/kg) at the late gestational stage on the reproductive performance of the sows have been investigated. This treatment potentially increased the litter size and birth survival rate and significantly increased the birth weight as well as the weaning weight and survival rate of piglets compared to the controls. The mechanistic studies have found that these beneficial effects of melatonin are not mediated by the alterations of reproductive hormones of estrogen and progesterone, nor did the glucose and lipid metabolisms, but they were the results of the reduced oxidative stress in placenta associated with melatonin supplementation. Indeed, the melatonergic system, including mRNAs and proteins of AANAT, MTNR1A and MTNR1B, has been identified in the placenta of the sows. The RNA sequencing of placental tissue and KEGG analysis showed that melatonin activated the placental tissue fluid shear stress pathway to stimulate the Nrf2 signaling pathway, which upregulated its several downstream antioxidant genes, including MGST1, GSTM3 and GSTA4, therefore, suppressing the placental oxidative stress. All these actions may be mediated by the melatonin receptor of MTNR1B.

CasEcR and CasMIH Genes in the Blue Crab, Callinectes sapidus: A Temporal Evaluation and Melatonin Effects

Environmental cues synchronize endogenous rhythms of many physiological processes such as hormone synthesis and secretion. Little is known about the diurnal pattern of hormones and gene expression of the Callinectes sapidus molt cycle. We aimed to investigate in the eyestalk and hepatopancreas of premolt and intermolt C. sapidus the following parameters: 1) the diurnal expression of the ecdysteroid receptor CasEcR isoforms, and the molt inhibiting hormone CasMIH; 2) the diurnal hemolymph ecdysteroid and melatonin levels; and 3) melatonin effects on the transcripts of the above-mentioned genes in intermolt C. sapidus. Ecdysteroid levels were higher in the premolt than the intermolt animals at all time points evaluated (ZTs). Premolt crabs displayed a variation of ecdysteroid concentration between time points, with a reduction at ZT17. No difference in the melatonin level was seen in either molt stage or between stages. In the eyestalk of intermolt animals, CasEcR expression oscillated, with a peak at ZT9, and premolt crabs have a reduction at ZT9; CasMIH transcripts did not vary along 24 h in either molt stage. Moreover, the evaluated eyestalk genes were more expressed at ZT9 in the intermolt than the premolt crabs. In the hepatopancreas, CasEcR expression showed a peak at ZT9 in premolt crabs. Exogenous melatonin (10−7 mol/animal) reduced the expression of both genes in the eyestalk at ZT17. In the hepatopancreas, melatonin markedly increased the expression of the CasEcR gene at ZT9. Taken altogether, our results are pioneer in demonstrating the daily oscillation of gene expression associated to molt cycle stages, as well as the daily ecdysteroid and melatonin levels and the remarkable influence of melatonin on the molt cycle of C. sapidus.

Three months of melatonin treatment reduces insulin sensitivity in patients with type 2 diabetes-Arandomized placebo-controlled crossover trial.

The use of the sleep‐promoting hormone melatonin is rapidly increasing as an assumed safe sleep aid. During the last decade, accumulating observations suggest that melatonin affects glucose homeostasis, but the precise role remains to be defined. We investigated the metabolic effects of long‐term melatonin treatment in patients with type 2 diabetes including determinations of insulin sensitivity and glucose‐stimulated insulin secretion. We used a double‐blinded, randomized, placebo‐controlled, crossover design. Seventeen male participants with type 2 diabetes completed (1) 3 months of daily melatonin treatment (10 mg) 1 h before bedtime (M) and (2) 3 months of placebo treatment 1 h before bedtime (P). At the end of each treatment period, insulin secretion was assessed by an intravenous glucose tolerance test (0.3 g/kg) (IVGTT) and insulin sensitivity was assessed by a hyperinsulinemic‐euglycemic clamp (insulin infusion rate 1.5 mU/kg/min) (primary endpoints). Insulin sensitivity decreased after melatonin (3.6 [2.9–4.4] vs. 4.1 [3.2–5.2] mg/(kg × min), p = .016). During the IVGTT, the second‐phase insulin response was increased after melatonin (p = .03). In conclusion, melatonin treatment of male patients with type 2 diabetes for 3 months decreased insulin sensitivity by 12%. Clinical use of melatonin treatment in dosages of 10 mg should be reserved for conditions where the benefits will outweigh the potential negative impact on insulin sensitivity.

The severity of endothelial dysfunction, oxidative stress, lipid metabolism disorders, decreased elastic properties and tone of peripheral vessels in patients with different POAG course variants, depending on the polymorphism of the genes of the biological clock

The purpose is to find out the relations of the vascular endothelium dysfunction, atherosclerotic damage to the vessels of the upper and lower limbs, the state of the antioxidant and prooxidant systems, and the lipid profile in patients with different POAG course — carriers of biological clock gene polymorphism.Materials and methods. 47 patients with advanced POAG underwent an examination that included visometry, biomicroscopy, ophthalmoscopy, perimetry, tonometry, thermometry, as well as determination of lipid metabolism, indicators of oxidative stress and antioxidant system. All patients were also tested for the degree of endothelial dysfunction by reactive hyperemia method, and the elastic properties and vascular wall tone by the volumetric sphygmomanometry method. POAG progression was determined by static automated perimetry and optical coherence tomography. The hospitalized patients were examined for daily melatonin profile and key biological clock genes typed by real-time polymerase chain reaction. The genetic material was taken by buccal scraping. Polymorphic variants were identified for CLOCK rs1801260 3111T/C and MTNR1B genes. 16 patients (S-POAG — 8, A-POAG — 8) were tested for melatonin taken from saliva samples at different times of the day in laboratory conditions with controlled nutrition and lighting using the DLMO protocol.Results. The predictors of glaucoma progression were found to be pronounced endothelial dysfunction and oxidative stress, which contribute to the acceleration of atherogenesis and a decrease in the elastic properties of the vascular wall of peripheral vessels. Clock 3111t-c circadian gene polymorphism was found to be interrelated with lipid metabolism disorders and increased lipid peroxidation in patients with POAG progression. Carriers of the G allele of the MTNR1B gene tend to have a higher level of triglyceride (TG) which grows in the evening hours if glaucoma is progressing. We showed that the phasal and amplitude characteristics of daily melatonin level, rather than its average level, may affect the state of the vascular wall of peripheral vessels in POAG patients.Conclusion. POAG progression is associated with pronounced oxidative stress, weakened antioxidant protection and dyslipoproteinemia. Differences in the lipid profile (dyslipidemia) and the indicators of oxidative stress and antioxidant protection in patients with stable and progressing glaucoma course are mutually related with Clock 3111t-c gene polymorphism (CG genotype).

Sleep disturbance associated with Smith-Magenis syndrome

Smith-Magenis syndrome (SMS) (OMIM #182290) is a rare genetic disorder with a prevalence of 1 in 25 000 live births. Approximately 90% of SMS patients have harbored a 3.7 Mb interstitial 17p11.2 deletion involving the RAI1 gene, while 10% of cases have carried pathogenic variants of the RAI1 gene. SMS is characterized by sleep disturbance, intellectual impairment, developmental delay, craniofacial and cardiovascular anomalies, obesity, self injury, aggressive and autistic-like behaviors. Most SMS patients have sleep disorders such as short total sleep time, frequent night waking, short sleep onset, and early morning waking. The sleep disturbance may aggravate with age and persist throughout life. Three mechanisms have been delineated. The first concern was the abnormal secretion of melatonin, with high levels during daytime and low levels at night. Evaluation of the integrity of the intrinsically photosensitive retinal ganglion cell (ipRGC)/melanopsin system has found that SMS patients showed dysfunction in the sustained component of the pupillary light responses to blue light. Synchronization of daily melatonin profile and its photoinhibition are dependent on the activation of melanopsin. Dysfunction of the retina-melanin system may be one of the causes of melatonin spectrum disorders. Secondly, dysregulation of circadian rhythm gene expression has also been noted in mice and SMS patients. Finally, there may be association between sleep deprivation symptoms and DNA methylation patterns, which has provided new insights for SMS-associated sleep disorders and symptoms alike. Treatment for SMS-related sleep disorders is administered primarily through medications like melatonin tablets, which can alleviate insomnia-related sleep difficulties, in particular externalizing behavior in children. Researchers are also actively exploring other treatments for SMS currently.

Peculiarities of hormonal regulation of the blood antioxidant system of adolescents with obesity

The study is designed to establish the relationship between the rate of the induced blood lipid peroxidation and production of some hormones in adolescents. The investigations have not shown any significant alteration in the blood insulin content as well as in the daily catecholamines and melatonin excretion in the urine of adolescents in early puberty with the I–II degree of neuroendocrine obesity and without insulin resistance. The rate of the induced blood lipid peroxidation in them remains to be at the initial level. In adolescents of the same age group hyperinsulinemia and an increased urinary excretion of catecholamines and melatonin occur against the background of the concomitant insulin resistance. The rate of the induced blood lipid peroxidation in such cases remains at the level of control values. Formation of hyperinsulinemia and an increased urinary excretion of norepinephrine and melatonin have been registered in late puberty in adolescents with neuroendocrine obesity of the I–II degree without insulin resistance. The emergence of these changes is accompanied by the maintenance of control values of the induced blood lipid peroxidation. The similar changes in the endocrine parameters with attendant increase in the rate of the induced blood lipid peroxidation are occurred in adolescents of the above-mentioned age group with neuroendocrine obesity against the background of insulin resistance.

Effects of Daily Melatonin Supplementation on Visual Loss, Circadian Rhythms, and Hepatic Oxidative Damage in a Rodent Model of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases characterized by a progressive loss of visual function that primarily affect photoreceptors, resulting in the complete disorganization and remodeling of the retina. Progression of the disease is enhanced by increased oxidative stress in the retina, aqueous humor, plasma, and liver of RP animal models and patients. Melatonin has beneficial effects against age-related macular degeneration, glaucoma, and diabetic retinopathy, in which oxidative stress plays a key role. In the present study, we used the P23HxLE rat as an animal model of RP. Melatonin treatment (10 mg/kg b.w. daily in drinking water for 6 months) improved the parameters of visual function and decreased the rate of desynchronization of the circadian rhythm, both in P23HxLE and wild-type rats. Melatonin reduced oxidative stress and increased antioxidant defenses in P23HxLE animals. In wild-type animals, melatonin did not modify any of the oxidative stress markers analyzed and reduced the levels of total antioxidant defenses. Treatment with melatonin improved visual function, circadian synchronization, and hepatic oxidative stress in P23HxLE rats, an RP model, and had beneficial effects against age-related visual damage in wild-type rats.

Effects of daily administration of melatonin before bedtime on fasting insulin, glucose and insulin sensitivity in healthy adults and patients with metabolic diseases. A systematic review and meta-analysis.

Melatonin is increasingly used as a pharmacological sleep aid but it is also emerging as a regulator of glucose homoeostasis. Yet, previous research has been ambiguous with reports of both positive and negative effects of melatonin on glucose metabolism. To assess the effect of daily treatment with melatonin on fasting glucose, insulin, insulin sensitivityand haemoglobin A1c (HbA1c) levels. MEDLINE, EMBASE, CENTRAL, clinicaltrials.govand clinicaltrialsregister.eu were systematically searched. All randomized, placebo-controlled studies with melatonin treatment were assessed. We included studies with daily melatonin treatment (≥2 weeks) of healthy adults or patients with metabolic diseases. Hedges' g differences were calculated for the metabolic parameters of the included studies, heterogeneity was assessed with χ2 and I2 testsand meta-analyses were performed with the random-effects model. Long-term treatment with melatonin did not change fasting glucose significantly compared with placebo (g: -0.07 [-0.22 to 0.08], n = 603)but it reduced fasting insulin levels slightly (g: -0.27 [-0.50 to -0.04], n = 278) and trended towards reduced insulin resistance (HOMA-IR) (g:-0.20 [-0.44 to 0.03], n = 278). HbA1c levels were largely unaffected by melatonin treatment compared with placebo (g: 0.14 [-0.19 to 0.46],n = 142). With the available literature, melatonin seems to be a glucose-metabolic safe sleep aid in patients with metabolic diseases and in healthy adults. It may even have beneficial glucose-metabolic effects as fasting insulin levels were reduced in this meta-analysis, but the confidence intervals of the meta-analyses are wide, underscoring the need for further research within this field.

Effects of photoperiod and light intensity on milk production and milk composition of dairy cows in automatic milking system.

The purpose of this study was to determine the effects of photoperiod and light intensity on milk production, milk composition, hormones levels and blood metabolites indices of Korean Holstein dairy cows in automatic milking system (AMS). A total of 24 Holstein dairy cows were selected and used to four subsequent treatments for the experimental periods of 60 days. The light programs consisted of (1) Control: the natural photoperiod with 14.2 h of the light period and 9.4 h of the dark period (below 10 Lux); (2) T1: 16 h of the long day photoperiod (LDPP) with 50 Lux of light; (3) T2: 16 h of LDPP with 100 Lux of light; and (4) T3: 16 h of LDPP with 200 Lux of light, respectively. Importantly, there was a significant difference in the thurl activity of dairy cows between the different light intensity programs (p < 0.05). Milk yield was higher in T1 and T2 (40.80 ± 1.71 and 39.90 ± 2.02 kg/d, respectively) than those of Control and T3 (32.18 ± 1.51 and 35.76 ± 2.80 kg/d, respectively) (p < 0.05), but DMI was lower in T1, T2, and T3 compared to Control (p < 0.05). Also, milk fat percentage, the contents of milk fat and total solids were higher in T2 than those in the others (p < 0.05). The average daily melatonin level in milk was high to T3 (28.20 ± 0.43 pg/mL), T2 (24.62 ± 0.32 pg/mL), T1 (19.78 ± 0.35 pg/mL), and Control (19.36 ± 0.45 pg/mL) in order (p < 0.05). Also, the cortisol levels in milk and blood were lower in treatment groups than in Control (p < 0.05). The results of this study showed that it will be effective to improve the milk yield and milk composition, and to reduce the stress of dairy cows when the light conditions regulate to extend the photoperiod to 16 h at a light emitting diode (LED) intensity of 100 Lux under the AMS in dairy farm.

ОСОБЛИВОСТІ ЗАПАЛЕННЯ БУРОЇ ЖИРОВОЇ ТКАНИНИ У ЩУРІВ З РОЗВИТКОМ ІНДУКОВАНОГО ДІЄТОЮ ОЖИРІННЯ ПІСЛЯ РІЗНИХ РЕЖИМІВ УВЕДЕННЯ МЕЛАТОНІНУ

One of the prominent obesity-related changes is the development of systemic low-grade proinflammatory state. Brown adipose tissue (BAT) may serve as a potential target for activation by melatonin to facilitate heat production and simultaneously stimulate lipolysis during obesity development. At the same time, melatonin is known to have immunomodulatory properties, which are performed via endocrine and paracrine signal pathways in variety cell types (including brown adipocytes)and change significantly during the day. Therefore, it can be used in a wide range of doses and at different times of the day (chronotherapeutic approach). Thus, the main goal of our research was to analyze the inflammation state of brown adipose tissue of rats during high-calorie diet induced-obesity development after different daily melatonin application in different regimes. Melatonin was administered by gavage for 7 weeks in dose 30 mg/kg 1 h before lights-off (HCD ZT11, M ZT11, evening), or 1 h after lights-on (HCD ZT01, M ZT01, morning). Tissue collagen content and leukocyte infiltration levels in BAT, detected by Van Gieson trichrome staining, were used as markers for the assessment of BAT inflammation state BAT. Propagation of obesity resulted in the increase of BATfibrosis level (the relative area occupied by collagen fibers) and tissue leukocyte infiltration in comparison to control rats. BAT fibrosis level after melatonin administrations to obese rats of HCD ZT01 and HCD ZT11 groups decreased to control values. Similar effects were observedinBAT tissue leukocyte infiltration after both regimes (HCD ZT01 and HCD ZT11 groups) of melatonin intake: this parameter decreased significantly, comparing to obese rats, but was still elevated, comparing to controls. At the same time, melatonin treatmentin morning or evening regimes did not have any impact on BAT fibrosis propagation and leukocyte infiltration in animals that consumed standard diet (M ZT01 and M ZT11 groups). To sum up, we suggest corrective properties of melatonin in context of chronic low-grade inflammation in obese rats BAT and suppose its wide potential for the therapeutic use combined with virtually absent side effects on BAT histophysiology of non-obese rats.

The Effects of Daily Melatonin Gavage on Reproductive Activity in the Male Syrian Hamsters.

The proper administration of melatonin has well been documented to induce testicular regression in seasonal breeding animals. The subcutaneous injections of melatonin in the afternoon, not in the morning, consistently occurred testicular involution in the male Syrian (golden) hamsters whose reproductive activity is regulated by the photoperiod. But the effects of daily melatonin via gavage have not been estimated. Golden hamsters housed in long photoperiod (LP) were divided into 5 groups: the control animals housed in LP or in short photoperiod (SP) and animals treated daily with low (15 μg), middle (150 μg), and high dosages (1,500 μg) of pure melatonin by using gavage in the evening for 8 weeks. As results, LP control animals had large testes and SP controls displayed small and entirely regressed testes. The animals treated with various dosages of melatonin showed collectively degenerating effects on the weights of testes, epididymides, and seminal vesicles in the middle and high dosage groups, with the individual differences as well. The high dosages induced testicular regression in more proportion than the middle dosages did. The low dosage had large testes like the LP control animals. The small and inactive testes shown in some animals of both middle and high groups presented the complete regression as those of the animals maintained in SP. These results strongly suggest that the administrations of melatonin lead to testicular involution in the male golden hamsters when it is administered through gavage.