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Melatonin and Caffeine Supplementation Used, Respectively, as Protective and Stimulating Agents in the Cryopreservation of Human Sperm Improves Survival, Viability, and Motility after Thawing compared to Traditional TEST-Yolk Buffer.
Pariz, JR, Ranéa, C, Monteiro, RAC, Evenson, DP, Drevet, JR, Hallak, J
Oxidative medicine and cellular longevity. 2019;:6472945
Abstract
Cryopreservation processes can damage spermatozoa and impair structural and functional cell characteristics. Plasma, nuclear membranes, and cellular organelles can suffer from the freeze and thaw process. This study evaluates the protective and stimulant effect of melatonin and caffeine supplementation on the functional characteristics of human spermatozoa before and after freezing. Thirty seminal samples from normozoospermic men aged 19-45 years old collected between October 2012 and May 2017 were included. Semen samples were supplemented with either 2 mM melatonin (MEL) prior to cryopreservation, 2 mM caffeine (CAF) in postthaw, or CAF and MEL (CM) in precryopreservation and postthaw, respectively. Kinetics and seminal parameters, mitochondrial activity, DNA fragmentation, and reactive oxygen species (ROS) levels were analyzed before and after cryopreservation. A significant reduction in sperm concentration, total and progressive motility, sperm kinetics, and mitochondrial activity, as well as a significant increase in DNA fragmentation and ROS production in postthaw samples compared to fresh samples, was identified. After administration of a caffeine and/or melatonin supplement, there was a significant increase in progressive motility in the CAF (p = 0.005) and CM (p = 0.048) groups, as well as mitochondrial activity in the CM group (p < 0.05). Cryopreservation has negative effects on overall sperm quality and increases ROS production. A combination of caffeine and melatonin in prefreeze and postthaw sperm samples has proven to be a very effective and simple way to improve semen quality. This will be particularly useful for initial low-quality semen samples, those which suffer the most from the freezing/thawing process.
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Characterizing the temporal Dynamics of Melatonin and Cortisol Changes in Response to Nocturnal Light Exposure.
Rahman, SA, Wright, KP, Lockley, SW, Czeisler, CA, Gronfier, C
Scientific reports. 2019;(1):19720
Abstract
We studied the dynamics of melatonin suppression and changes in cortisol levels in humans in response to light exposure at night using high-frequency blood sampling. Twenty-one young healthy participants were randomized to receive either intermittent bright (~9,500 lux) light (IBL), continuous bright light (CBL) or continuous dim (~1 lux) light (VDL) for 6.5 h during the biological night (n = 7 per condition). Melatonin suppression occurred rapidly within the first 5 min and continued until the end of each IBL stimuli (t1/2 = ~13 min). Melatonin recovery occurred more slowly between IBL stimuli (half-maximal recovery rate of ~46 min). Mean melatonin suppression (~40%) and recovery (~50%) were similar across IBL stimuli. Suppression dynamics under CBL were also rapid (t1/2 = ~18 min), with no recovery until the light exposure ended. There was a significant linear increase of cortisol levels between the start and end of each IBL stimulus. Under CBL conditions cortisol showed trimodal changes with an initial linear activating phase, followed by an exponential inhibitory phase, and a final exponential recovery phase. These results show that light exposure at night affects circadian driven hormones differently and that outcomes are influenced by the duration and pattern of light exposure.
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Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism.
Skene, DJ, Skornyakov, E, Chowdhury, NR, Gajula, RP, Middleton, B, Satterfield, BC, Porter, KI, Van Dongen, HPA, Gaddameedhi, S
Proceedings of the National Academy of Sciences of the United States of America. 2018;(30):7825-7830
Abstract
Misalignment between internal circadian rhythmicity and externally imposed behavioral schedules, such as occurs in shift workers, has been implicated in elevated risk of metabolic disorders. To determine underlying mechanisms, it is essential to assess whether and how peripheral clocks are disturbed during shift work and to what extent this is linked to the central suprachiasmatic nuclei (SCN) pacemaker and/or misaligned behavioral time cues. Investigating rhythms in circulating metabolites as biomarkers of peripheral clock disturbances may offer new insights. We evaluated the impact of misaligned sleep/wake and feeding/fasting cycles on circulating metabolites using a targeted metabolomics approach. Sequential plasma samples obtained during a 24-h constant routine that followed a 3-d simulated night-shift schedule, compared with a simulated day-shift schedule, were analyzed for 132 circulating metabolites. Nearly half of these metabolites showed a 24-h rhythmicity under constant routine following either or both simulated shift schedules. However, while traditional markers of the circadian clock in the SCN-melatonin, cortisol, and PER3 expression-maintained a stable phase alignment after both schedules, only a few metabolites did the same. Many showed reversed rhythms, lost their rhythms, or showed rhythmicity only under constant routine following the night-shift schedule. Here, 95% of the metabolites with a 24-h rhythmicity showed rhythms that were driven by behavioral time cues externally imposed during the preceding simulated shift schedule rather than being driven by the central SCN circadian clock. Characterization of these metabolite rhythms will provide insight into the underlying mechanisms linking shift work and metabolic disorders.
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Evaluation of Melatonin Secretion and Metabolism Exponents in Patients with Ulcerative and Lymphocytic Colitis.
Chojnacki, C, Błasiak, J, Fichna, J, Chojnacki, J, Popławski, T
Molecules (Basel, Switzerland). 2018;(2)
Abstract
Inflammatory bowel diseases, particularly ulcerative colitis (UC) and lymphocytic colitis (LC), affect many people. The role of melatonin in the pathogenesis of UC is precisely determined, whereas in LC it remains unknown. The aim of this study was to compare the expression of the melatonin-synthesizing enzymes tryptophan hydroxylase (TPH1), arylalkylamine-N-acetyltransferase (AANAT), and N-acetylserotonin methyltransferase (ASMT) in the colonic mucosa and urinary excretion of 6-sulfatoxymelatonin in patients with ulcerative and lymphocytic colitis. The study included 30 healthy subjects (group C), 30 patients with severe ulcerative colitis (group UC), and 30 patients with lymphocytic colitis (group LC). The diagnosis was based on endoscopic, histological, and laboratory examinations. Biopsy specimens were collected from right, transverse, and left parts of the colon. The levels of mRNA expression, TPH1, AANAT, and ASMT were estimated in the colonic mucosa with RT-PCR. The urine concentration of aMT6s was determined by the photometric method. The expression of TPH1, AANAT, and ASMT in colonic mucosa in UC and LC patients was significantly higher than in healthy subjects. Significant differences were found in the urinary aMT6s excretion: group C-13.4 ± 4.8 µg/24 h, group UC-7.8 ± 2.6 µg/24 h (p < 0.01), group LC-19.2 ± 6.1 µg/24 h (p < 0.01). Moreover, a negative correlation was found between fecal calprotectin and MT6s-in patients with UC - r = -0.888 and with LC - r = -0.658. These results indicate that patients with UC and those with LC may display high levels of melatonin-synthesizing enzymes in their colonic mucosa, which could possibly be related to increased melatonin synthesis as an adaptive antioxidant activity.
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The role of melatonin to attain electroencephalograms in children in a sub-Saharan African setting.
Ibekwe, R, Jeaven, L, Wilmshurst, JM
Seizure. 2017;:87-94
Abstract
PURPOSE Limited access to electroencephalograms (EEGs) in sub-Saharan Africa results in a high patient load attending the few neurophysiology units. The state of sleep in children improves yield and reduces artefact of EEGs. Melatonin induces "natural sleep" without the risk of airway compromise. This study evaluated the effectiveness of oral melatonin to attain electroencephalograms in South African children. METHOD Children undergoing EEG who were unable to cooperate or required sleep EEG, received oral melatonin (3mg<15kg; 6mg>15kg). A retrospective control group received chloral hydrate. Outcome measures were the proportion of children who slept, useful EEG study data, sleep latency and duration, artefacts and EEG study abnormalities. RESULTS 173 children were recruited, 88 (51%) male, median age 4 years 9 months (range 0-14 years). 87% achieved stage 2 sleep. Median sleep latency was 44.5min and duration of sleep was 25min (range 18.5-29min). Children had no post-sedation irritability, persistent drowsiness, nor any other adverse events or deferments for inter-current illnesses. Sedation with melatonin was less successful in children with developmental and behavioural problems (χ2=6.18, P=0.046), with a higher rate of artefacts (χ2=5.83, P=0.05). 33.5% (n=58) had abnormal EEG studies, which was comparable to a historical cohort sedated with chloral hydrate (45.5%) (χ2=1.22, P=1.27). Also for artefacts (79% melatonin group versus 86% chloral hydrate group) (χ2=0.63, P=0.42). CONCLUSIONS Melatonin is effective and safe in inducing sleep for EEG recording in our setting.
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Morning melatonin ingestion and diurnal variation of short-term maximal performances in soccer players.
Ghattassi, K, Hammouda, O, Graja, A, Boudhina, N, Chtourou, H, Hadhri, S, Driss, T, Souissi, N
Physiology international. 2016;(1):94-104
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Abstract
Aim Very few studies have investigated the temporal specificity of melatonin (MEL) ingestion upon short-term maximal athletic performances. The aim of the present study was to explore the effect of morning MEL ingestion on cognitive and physical performances measured in the afternoon. Methods Twelve soccer players from a Tunisian squad (17.9 ± 1.3 years, 1.74 ± 0.06 m and 62.0 ± 8.8 kg) participated in the present study. They performed two testing sessions at 08:00 h, 12:00 h and 16:00 h after either MEL (5mg) or placebo (PLA) ingestion, in a randomized order. During each period, the participants performed the following cognitive and physical tests: reaction time and vigilance tests, medicine-ball throw (MBT), five jumps, handgrip strength (HG), and agility tests. Results cognitive and physical performances were significantly higher at 16:00 h compared to 08:00 h during the two conditions (p < 0.05). Moreover, performances of MBT and HG were lower in the morning with MEL in comparison to PLA (p < 0.05). However, MEL ingestion did not affect physical and cognitive performances measured at 12:00 h and 16:00 h. Conclusion morning MEL ingestion has no unfavourable effect on afternoon physical and cognitive performances in soccer players.
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Protective role of melatonin in progesterone production by human luteal cells.
Taketani, T, Tamura, H, Takasaki, A, Lee, L, Kizuka, F, Tamura, I, Taniguchi, K, Maekawa, R, Asada, H, Shimamura, K, et al
Journal of pineal research. 2011;(2):207-13
Abstract
This study investigated whether melatonin protects luteinized granulosa cells from reactive oxygen species (ROS) as an antioxidant to enhance progesterone production in the follicle during ovulation. Follicular fluid was sampled at the time of oocyte retrieval in women undergoing in vitro fertilization and embryo transfer (IVF-ET). Melatonin concentrations in the follicular fluid were positively correlated with progesterone concentrations (r = 0.342, P < 0.05) and negatively correlated with the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker (r = -0.342, P < 0.05). The progesterone and 8-OHdG concentrations were negatively correlated (r = -0.246, P < 0.05). Luteinized granulosa cells were obtained at the time of oocyte retrieval in women undergoing IVF-ET. Cells were incubated with H(2)O(2) (30, 50, 100 μm) in the presence or absence of melatonin (1, 10, 100 μg/mL). Progesterone production by luteinized granulosa cells was significantly inhibited by H(2)O(2). Melatonin treatment overcame the inhibitory effect of H(2) O(2) . Twenty-five patients who had luteal phase defect (serum progesterone concentrations <10 ng/mL during the mid-luteal phase) were divided into two groups during the next treatment cycle: 14 women were given melatonin (3 mg/day at 22:00 hr) throughout the luteal phase and 11 women were given no medication as a control. Melatonin treatment improved serum progesterone concentrations (>10 ng/mL during the mid-luteal phase) in nine of 14 women (64.3%), whereas only two of 11 women (18.1%) showed normal serum progesterone levels in the control group. In conclusion, melatonin protects granulosa cells undergoing luteinization from ROS in the follicle and contributes to luteinization for progesterone production during ovulation.
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Melatonin as a potential tool against oxidative damage and apoptosis in ejaculated human spermatozoa.
Espino, J, Bejarano, I, Ortiz, A, Lozano, GM, García, JF, Pariente, JA, Rodríguez, AB
Fertility and sterility. 2010;(5):1915-7
Abstract
It is assumed somatic cells can die in the apoptotic, the autophagic, or the necrotic way; however, the mechanisms of sperm death are not clear. Here, ejaculated human spermatozoa were evaluated for apoptosis and reactive oxygen species production in the absence or presence of melatonin, and we concluded that melatonin reverses sperm apoptosis due to its free radical scavenging actions.
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Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status.
Norsa, A, Martino, V
Cancer biotherapy & radiopharmaceuticals. 2006;(1):68-73
Abstract
BACKGROUND The prognosis of low performance status (PS) patients with advanced non-small-cell-lung cancer (NSCLC) is dismal. In these patients, we have determined the survival, clinical benefits, and toxicity of a multidrug regimen, based on cyclophosphamide and biotherapeutical agents. METHODS Patients with a diagnosis of stage IIIB or stage IV NSCLC, no previous surgery or chemoradiotherapy, and an Eastern Cooperative Oncology Group (ECOG) PS equal to or greater than 2 received a daily combination of somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide. RESULTS Twenty-eight (28) patients were enrolled. The median age was 64 years (range, 35-74). The PS was 2 and 3 in 78.6% and 21.4% of patients, respectively. The median overall survival (intent-to-treat analysis) was 12.9 months (range, 1.5-33.5 months), The overall survival rates at 1 and 2 years were 51.2% and 21.1%, respectively. The side-effects were very mild, mostly consisting of diarrhoea, nausea/vomiting, and drowsiness of grade 1-2. Most patients experienced an improvement of both respiratory (cough and dyspnoea) and general (pain, fatigue, and insomnia) symptoms. CONCLUSIONS Low PS patients with advanced NSCLC may benefit from a combination of somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide, in terms of survival and quality of life, with very low side-effects.
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[The influence of melatonin supplementation on circadian pattern of blood pressure in patients with coronary artery disease--preliminary report].
Rechciński, T, Kurpesa, M, Trzos, E, Krzeminska-Pakuła, M
Polskie Archiwum Medycyny Wewnetrznej. 2006;(6):520-8
Abstract
UNLABELLED Melatonin--sleep-inducing remedy was reported to be implicated in "biological clock" of circulatory system. The deficits of this pineal hormone were observed in patients with coronary artery disease (CAD) and those with abnormal circadian pattern of blood pressure (BP). We hypothesize that melatonin supplementation could be beneficial for this group of patients thanks to return from "non-dippers" to physiological "dippers" group, which is characterized by lower rate of left ventricle hypertrophy and/or number of ischemic episodes, in comparison with "non-dippers". The aim of this study was to assess safety and the effects of melatonin treatment in patients with CAD and impaired circadian pattern of BP. INVESTIGATED GROUP AND METHODS Thirty-nine ambulatory patients (69% males, mean age 61+/-5,0), with CAD confirmed by coronary angiography and with circadian pattern of BP classified in 24 hour ambulatory blood pressure monitoring (ABPM) as "non-dippers" were included into the study. All study participants, apart of previous treatment, started to use 5 mg melatonin before sleep. Control 24h ABPM was performed after 30 days of such cure. The results of both ABPMs were compared using statistical methods. RESULTS Melatonin supplementation improved circadian pattern of BP in one third (30,8%) of study group - they were classified in the second ABPM as "dippers". Despite a tendency to increase a day/night difference of average BP for 5,9%--a percentage of patients who remained in the group of "non-dippers" was 46,2%. Unfavourable effect of melatonin treatment was observed in 23% of patients: 15,4%--"extreme-dippers", 7,6% --"reverse-dippers". CONCLUSION Twenty-four hour noninvasive blood pressure monitoring performed before and during melatonin cure is crucial by considering benefits and dangers of this treatment begun in purpose to modify impaired pattern of blood pressure in patients with coronary artery disease.