Nocturnal Melatonin Concentrations Research Articles

PINEAL GLAND AND PREECLAMPSIA – A MODERN VIEW OF THE PROBLEM (LITERATURE REVIEW)

Preeclampsia is a complex pathological process which development signifi cantly depends on a decrease in melatonin levels of pregnant women as a result of the pineal gland and placenta dysfunction. The most important hormone of the pineal gland is melatonin, which is a derivative of tryptophan – an essential amino acid. Melatonin is a powerful natural antioxidant. When it’s levels are decreased, there is a risk of preeclampsia progression as a pathological condition of pregnant women, accompanied by high blood pressure, systemic multiple- organ failure and even cerebral edema and convulsions.Thus, although preeclampsia is considered a disease of the mother, it should rather be considered as a pathological condition of the placenta that aff ects both mother’s and fetus health. As the key factor of placental diorders is an oxidative stress, many researchers consider melatonin to be a potentially useful option for treating preeclampsia. It is noted that pregnant women with preeclampsia have a decrease in nocturnal concentrations of melatonin in comparison with healthy pregnant women that may indicate about pineal gland dysfunction in preeclampsia. Therefore, the normalization of melatonin levels may be a promising direction in the treatment of pregnant women with preeclampsia.

Efficacy and safety of electroacupuncture combined with Suanzaoren decoction for insomnia following stroke: study protocol for a randomized controlled trial

BackgroundInsomnia is a common but frequently overlooked sleep disorder after stroke, and there are limited effective therapies for insomnia following stroke. Traditional Chinese medicine (TCM), including acupuncture and the Chinese herbal medication (CHM) Suanzaoren decoction (SZRD), has been reported as an alternative option for insomnia relief after stroke in China for thousands of years. Here, this study aims to investigate the efficacy and safety of electroacupuncture (EA) in combination with SZRD in the treatment of insomnia following stroke.MethodsA total of 240 patients with post-stroke insomnia will be included and randomized into four groups: the EA group, SZRD group, EA & SZRD group, and sham group. The same acupoints (GV20, GV24, HT7, and SP6) will be used in the EA group, EA & SZRD group, and sham group, and these patients will receive the EA treatment or sham manipulation every other day for 4 consecutive weeks. SZRD treatments will be given to participants in the SZRD group and EA & SZRD group twice a day for 4 consecutive weeks. The primary outcome measures include Pittsburgh Sleep Quality Index scores and polysomnography. Secondary outcome measures include the Insomnia Severity Index, the National Institutes of Health Stroke Scale, the Hospital Anxiety and Depression Scale, brain magnetic resonance imaging, functional magnetic resonance imaging, and nocturnal melatonin concentrations. The primary and secondary outcomes will be assessed at baseline (before treatment), during the 2nd and 4th weeks of the intervention, and at the 8th and 12th weeks of follow-up. Safety assessments will be evaluated at baseline and during the 4th week of the intervention.DiscussionThis study will contribute to assessing whether the combination of these two therapies is more beneficial for post-stroke insomnia than their independent use, and the results of this clinical trial will improve our understanding of the possible mechanisms underlying the effects of combination therapies.Trial registrationChinese Clinical Trials Register ChiCTR2000031413. Registered on March 30, 2020

Can skyglow reduce nocturnal melatonin concentrations in Eurasian perch?

Artificial light at night (ALAN) changes the natural rhythm of light and darkness and can impair the biorhythms of animals, for example the nocturnal melatonin production of vertebrates, which serves as a proxy for daily physiological rhythms. Freshwater fish are exposed to ALAN in large urban and suburban areas in the form of direct light or in the form of skyglow, a diffuse brightening of the night sky through the scattered light reflected by clouds, atmospheric molecules, and particles in the air. However, investigations on the sensitivity of melatonin production of fish towards low intensities of ALAN in the range of typical skyglow are rare. Therefore, we exposed Eurasian perch (Perca fluviatilis) to nocturnal illumination levels of 0.01 lx, 0.1 lx and 1 lx and a control group with dark nights and daylight intensities of 2900 lx in all groups. After ten days of exposure to the experimental conditions, tank water was non-invasively sampled every 3 h over a 24 h period and melatonin was measured by ELISA. Melatonin was gradually reduced in all treatments with increasing intensity of ALAN whereas rhythmicity was maintained in all treatment groups although at 1 lx not all evaluated parameters confirmed rhythmicity. These results show a high sensitivity of Eurasian perch towards ALAN indicating that low light intensities of 0.01 lx and 0.1 lx as they occur in urban and suburban areas in the form of skyglow can affect the physiology of Eurasian perch. Furthermore, we highlight how this may impact perch in their sensitivity towards lunar rhythms and the role of skyglow for biorhythms of temperate freshwater fish.

Blunted Nocturnal Salivary Melatonin Secretion Profiles in Military-Related Posttraumatic Stress Disorder.

Background: Sleep disturbances are a hallmark of posttraumatic stress disorder (PTSD), yet few studies have evaluated the role of dysregulated endogenous melatonin secretion in this condition. Methods: This study compared the sleep quality and nocturnal salivary melatonin profiles of Canadian Armed Forces (CAF) personnel diagnosed with PTSD, using the Clinician Administered PTSD Scale (CAPS score ≥50), with two healthy CAF control groups; comprising, a “light control” (LC) group with standardized evening light exposure and “normal control” (NC) group without light restriction. Participants were monitored for 1-week using wrist actigraphy to assess sleep quality, and 24-h salivary melatonin levels were measured (every 2h) by immunoassay on the penultimate day in a dim-light (< 5 lux) laboratory environment. Results: A repeated measures design showed that mean nocturnal melatonin concentrations for LC were higher than both NC (p = .03) and PTSD (p = .003) with no difference between PTSD and NC. Relative to PTSD, NC had significantly higher melatonin levels over a 4-h period (01 to 05 h), whereas the LC group had higher melatonin levels over an 8-h period (23 to 07 h). Actigraphic sleep quality parameters were not different between healthy controls and PTSD patients, likely due to the use of prescription sleep medications in the PTSD group. Conclusions: These results indicate that PTSD is associated with blunted nocturnal melatonin secretion, which is consistent with previous findings showing lower melatonin after exposure to trauma and suggestive of severe chronodisruption. Future studies targeting the melatonergic system for therapeutic intervention may be beneficial for treatment-resistant PTSD.

Assessment of diurnal melatonin, cortisol, activity, and sleep−wake cycle in patients with and without diabetic retinopathy

ObjectiveTo assess the diurnal melatonin, cortisol, and activity/rest levels, as well as sleep quality, in patients with and without nonproliferative diabetic retinopathy (DR). MethodsWe included 25 diabetic patients with DR and 29 without DR. A total of 21 healthy subjects constituted the control group. We assessed the circadian rhythm by actigraphy and diurnal salivary melatonin and cortisol measurements. Sleep quality was evaluated by actigraphy and the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaires. Light exposure was quantified by actigraphy. The primary outcome was peak salivary melatonin level. Secondary outcomes were mean melatonin and cortisol levels during dark hours, activity−rest rhythm, sleep quality, as well as level of white, red, green, and blue light exposure. ResultsPeak melatonin concentration at 04:00 and mean nocturnal melatonin level were significantly reduced in all diabetic patients, regardless of retinopathy stage (p < 0.001). Levels of light exposures during dark hours were not significantly different in patients with and without DR and healthy controls. Only patients with DR showed increased intradaily variability in their activity−rest interval, indicating circadian misalignment (p = 0.04). Neither the objective actigraphic sleep quality parameters nor the subjective PSQI or ESS scores were significantly different between healthy controls and diabetic patients. ConclusionsReduced nocturnal melatonin concentration and increased fragmentation of activity−rest intervals revealed circadian rhythm disturbance in diabetic patients with DR.

Sun Avoidance and the Risk of Developing Breast Cancer: A Systematic Review and Meta-Analysis

Background: A relationship has been hypothesized between moderate solar ultraviolet radiation (UVR) exposure and breast cancer. This hypothesis centers on the anti-proliferative and apoptotic properties of vitamin D, as well as increases in nocturnal melatonin concentrations which have been shown to slow cellular proliferation. To date, the literature on the effects of exposure to UVR and breast cancer risk have not been systematically reviewed and synthesized. Furthermore, the effects of sun avoidance (low amounts of time spent in the sun) in different exposure windows (adolescence vs. a period relevant to diagnosis) have not been compared.Methods: We conducted a systematic review and meta-analysis to investigate the association between sun avoidance (defined as less than an hour of sun per day) and the risk of developing breast cancer. Associations were estimated using random effects models. Heterogeneity was investigated through subgroup analyses and I2 statistics.Results: Seven studies were included in this review with the majority (n&amp;#61;5) being conducted in Canada or the US. We observed an increased risk of breast cancer for individuals obtaining less than an hour of sun exposure per day during summer months compared to individuals that obtained greater than an hour (pooled relative risk (RR) &amp;#61; 1.15; 95% CI: 1.09-1.20). Heterogeneity among this body of literature was minimal (I2 &amp;#61; 2.7%) Among studies that measured sun exposure over different life periods, sun avoidance during adolescence appeared to confer a qualitatively greater risk of breast cancer than that closer to diagnosis (pooled RR &amp;#61; 1.18; 95% CI: 1.05-1.30 vs. 1.05; 95% CI: 0.88-1.25).Conclusion: This is the first meta-analysis to estimate the risk of developing breast cancer associated with sun avoidance. The results of this study suggest that obtaining less than one hour of sun per day during summer months, especially in adolescence, could increase the risk of developing breast cancer.

Influence of artificially induced light pollution on the hormone system of two common fish species, perch and roach, in a rural habitat.

Almost all life on earth has adapted to natural cycles of light and dark by evolving circadian and circannual rhythms to synchronize behavioural and physiological processes with the environment. Artificial light at night (ALAN) is suspected to interfere with these rhythms. In this study we examined the influence of ALAN on nocturnal melatonin and sex steroid blood concentrations and mRNA expression of gonadotropins in the pituitary of European perch (Perca fluviatilis) and roach (Rutilus rutilus). In a rural experimental setting, fish were held in net cages in drainage channels experiencing either additional ALAN of ~15 lx at the water surface or natural light conditions at half-moon. No differences in melatonin concentrations between ALAN and natural conditions were detected. However, blood concentration of sex steroids (17β-estradiol; 11-ketotestosterone) as well as mRNA expression of gonadotropins (luteinizing hormone, follicle stimulating hormone) was reduced in both fish species. We conclude that ALAN can disturb biological rhythms in fish in urban waters. However, impacts on melatonin rhythm might have been blurred by individual differences, sampling methods and moonlight. The effect of ALAN on biomarkers of reproduction suggests a photo-labile period around the onset of gonadogenesis, including the experimental period (August). Light pollution therefore has a great potential to influence crucial life history traits with unpredictable outcome for fish population dynamics.

Diurnal and nocturnal serum melatonin concentrations after treatment with continuous positive airway pressure in patients with obstructive sleep apnea.

INTRODUCTION Melatonin secretion, one of the main factors controlling the sleep-wake rhythm, may be disrupted in patients with sleep disorders. OBJECTIVES The aim of the study was to evaluate the profile of circadian melatonin secretion in patients with obstructive sleep apnea (OSA) and to assess the impact of 2-day and 3-month treatment with continuous airway pressure (CPAP) on diurnal and nocturnal serum melatonin levels. PATIENTS AND METHODS Serum melatonin levels were evaluated in 71 untreated patients with OSA and 18 healthy controls at 6 time points: 10 AM, 2 PM, 6 PM, 10 PM, 2 AM, and 6 AM. The measurements were repeated after 2 days and 3 months of CPAP treatment. RESULTS Melatonin secretion rhythm was altered in 25.4% of the patients with OSA. In patients with preserved secretion rhythm, the serum melatonin level was significantly lower at 2 AM and 6 AM, compared with healthy controls: 68.2 pg/ml (interquartile range [IQR], 30.1-109.8 pg/ml) vs 109.1 pg/ml (IQR, 63-167.9 pg/ml), P = 0.02 and 40.8 pg/ml (IQR, 20.8-73.2 pg/ml) vs 67.7 pg/ml (IQR, 32.7-131.7 pg/ml), P = 0.04, respectively. Melatonin levels did not change significantly after the 2-day and 3-month CPAP treatment. However, at 3 months, a shift of the peak melatonin concentration to 2 AM was observed in patients with an altered secretion rhythm. CONCLUSIONS OSA has a significant effect on serum melatonin levels. Neither short-term nor long-term CPAP treatment significantly changes melatonin concentrations; however, our results seem to indicate that a 3-month CPAP treatment may be helpful in restoring the physiological rhythm of melatonin secretion in patients with OSA.

Relationship of nocturnal concentrations of melatonin, gamma-aminobutyric acid and total antioxidants in peripheral blood with insomnia after stroke: study protocol for a prospective non-randomized controlled trial.

Melatonin and gamma-aminobutyric acid (GABA) have been shown to regulate sleep. The nocturnal concentrations of melatonin, GABA and total antioxidants may relate to insomnia in stroke patients. In this prospective single-center non-randomized controlled clinical trial performed in the China Rehabilitation Research Center, we analyzed the relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke. Patients during rehabilitation of stroke were recruited and assigned to the insomnia group or non-insomnia group. Simultaneously, persons without stroke or insomnia served as normal controls. Each group contained 25 cases. The primary outcome was nocturnal concentrations of melatonin, GABA and total antioxidants in peripheral blood. The secondary outcomes were Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale, Fatigue Severity Scale, Morningness-Eveningness Questionnaire (Chinese version), and National Institute of Health Stroke Scale. The relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke was analyzed and showed that they were lower in the insomnia group than in the non-insomnia group. The severity of stroke was higher in the insomnia group than in the non-insomnia group. Correlation analysis demonstrated that the nocturnal concentrations of melatonin and GABA were associated with insomnia after stroke. This trial was registered at ClinicalTrials.gov, identifier: NCT03202121.

Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease.

Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. The circadian rhythm of intrarenal RAS activation leads to renal damage and hypertension, which are associated with diurnal blood pressure (BP) variation. The activation of intrarenal RAS following reactive oxygen species (ROS) activation, sympathetic hyperactivity and nitric oxide (NO) inhibition leads to the development of renal damage. Melatonin is a hormone regulating the circadian rhythm, and has multiple functions such as anti-oxidant and anti-adrenergic effects and enhancement of NO bioavailability. Nocturnal melatonin concentrations are lower in CKD patients. However, it is not known if impaired endogenous melatonin secretion is related to BP, intrarenal RAS, or renal damage in CKD patients. We recruited 53 CKD patients and conducted 24-h ambulatory BP monitoring. urine was collected during the daytime and nighttime. We investigated the relationship among the melatonin metabolite urinary 6-sulphatoxymelatonin (U-aMT6s), BP, renal function, urinary angiotensinogen (U-AGT), and urinary albumin (U-Alb). Patients' U-aMT6s levels were significantly and negatively correlated with clinical parameters such as renal function, systolic BP, U-AGT, and U-Alb, during both day and night. Multiple regression analyses for U-aMT6s levels were performed using age, gender, renal function, and each parameter (BPs, U-AGT or U-Alb), at daytime and nighttime. U-aMT6s levels were significantly associated with U-AGT (β=-0.31, p=0.044) and U-Alb (β=-0.25, p=0.025) only at night. Impaired nighttime melatonin secretion may be associated with nighttime intrarenal RAS activation and renal damage in CKD patients.

The Effects of Kidney Transplantation on Sleep, Melatonin, Circadian Rhythm and Quality of Life in Kidney Transplant Recipients and Living Donors

Background: Sleep disturbance is an important medical problem in patients with end-stage renal disease. It might be related to the disruption of the body's circadian clock since nocturnal levels of its key biomarker melatonin are markedly reduced. We aimed at investigating whether a change in renal function due to kidney transplantation or donation would modify sleep, melatonin levels, circadian rhythmicity, and quality of life in kidney transplant recipients (KTR) and living donors (LD). Methods: In KTR, we assessed saliva melatonin concentrations, sleep quality and daytime sleepiness prior to and at 2 weeks and 3 months after transplantation. In LD, we assessed these parameters prior to and at 3 months after donation. We additionally assessed 24-hour core body temperature (cBT), 24-hour blood pressure profile, and quality of life (QoL) prior to and 3 months after transplantation. Results: Twenty-three KTR and 23 LD completed the study. Regarding sleep, the amount of nighttime awake minutes tended to be reduced in recipients after transplantation (p = 0.05). Nocturnal melatonin concentrations did not change with transplantation or donation. Blood pressure dipping profile and the two circadian markers dim-light melatonin onset and time of core body temperature minimum did not change. Nevertheless, KTR reported that daytime sleepiness and QoL had improved. Conclusion: Objectively nocturnal sleep quality marginally improved after transplantation. Subjectively patients reported improved QoL and daytime sleepiness scores. Changes in renal function were not associated with modified melatonin secretion or circadian rhythmicity.

Can the season of birth risk factor for schizophrenia be prevented by bright light treatment for the second trimester mother around the winter solstice?

The season of birth risk factor for schizophrenia exerts a pervasive effect on the global population, particularly at northerly latitudes. The winter infection hypothesis and the low vitamin D hypothesis are both compelling but lack conclusive clinical data. The present work develops a maternal–fetal chronobiological hypothesis for this season of birth risk factor and its prevention by maternal bright light treatment. Around the winter solstice, due to decreased sunlight, the chronobiological apparatus of the at-risk second trimester mother is characterized by a reduced amplitude circadian pacemaker, and a reduced maximum of her nocturnal plasma melatonin concentrations (MTmax) and an increased minimum of her nocturnal core body temperatures (Tmin)—both of which exert adverse effects on the fetal hippocampus and dorsal striatum. The consequences for the fetus include reduced volume and increased excitability of the hippocampus, ventral striatal dysfunction, increased presynaptic nigrostriatal dopamine transmission, and increased propensity for pathological nigrostriatal neuronal phasic firing. Thus, the maternal–fetal chronobiological hypothesis fully accounts for the fetal precursors of the major pathognomonic abnormalities in adults with schizophrenia. Bright light treatment for the second trimester mother around the winter solstice, by increasing maternal circadian amplitude, could possibly prevent the fetal hippocampal and striatal abnormalities and eliminate the season of birth risk factor for schizophrenia.

Melatonin ameliorates chronic mild stress induced behavioral dysfunctions in mice

Melatonin, a neurohormone, is known to regulate several physiological functions, especially the circadian homeostasis, mood and behavior. Chronic exposure to stress is involved in the etiology of human affective disorders, and depressed patients have been reported to show changes in the circadian rhythms and nocturnal melatonin concentration. The present study was conducted to evaluate a possible beneficial action of chronic night-time melatonin treatment against chronic mild stress (CMS) induced behavioral impairments. As expected in the present study, the stress exposed mice showed reduced weight gain, hedonic deficit, cognitive deficits and decreased mobility in behavioral despair test. Interestingly, CMS exposed mice showed less anxiety. Chronic night-time melatonin administration significantly ameliorated the stress-induced behavioral disturbances, especially the cognitive dysfunction and depressive phenotypes. In conclusion, the present findings suggest the mitigating role of melatonin against CMS-induced behavioral changes, including the cognitive dysfunctions and reaffirm its potential role as an antidepressant.

Seasonal differences in melatonin concentrations and heart rates during sleep in obese subjects in Japan

During the past several decades, obesity has been increasing globally. In Japan, obesity is defined by a BMI of 25 kg/m² or over; 28.6 % of men and 20.6 % of women are obese. Obese people have an increased incidence of developing cardiovascular, renal, and hormonal diseases and sleep disorders. Obese people also have shortened sleep durations. We investigated seasonal differences in melatonin concentrations, heart rates, and heart rate variability during sleep in obese subjects in Japan. Five obese (BMI, 32.0 ± 4.9 kg/m²) and five non-obese (BMI, 23.2 ± 2.9 kg/m²) men participated in this study in the summer and winter. Electrocardiograms were measured continuously overnight in a climatic chamber at 26 °C with a relative humidity of 50 %. Saliva samples for melatonin were collected at 2300 hours, 0200 hours, and 0600 hours. We found that melatonin concentrations during sleep in obese subjects were significantly lower than those in non-obese subjects in the winter. Heart rate during sleep in winter was significantly higher than that in summer in both obese and non-obese subjects. Heart rate variability was not significantly different in the summer and winter in both obese and non-obese subjects. Our results show that decreased nocturnal melatonin concentrations during winter in obese men may be related to higher heart rates, and this may suggest that obese men are at an increased risk of a cardiovascular incident during sleep, especially in the winter.

Melatonin, A Natural Programmed Cell Death Inducer in Cancer

Melatonin, an indolamine derived from the amino-acid tryptophan, participates in diverse physiological functions and has great functional versatility related to the regulation of circadian rhythms and seasonal behaviour, sexual development, retinal physiology, tumour inhibition, as an antioxidant, immunomodulatory and anti-aging properties. In relation to its oncostatic properties, there is evidence that tumor initiation, promotion or progression may be restrained by the night-time physiological surge of melatonin in the blood or extracellular fluid. In addition, depressed nocturnal melatonin concentrations or nocturnal excretion of the main melatonin metabolite, 6-sulfatoxymelatonin, were found in individuals with various tumor types. In the majority of studies, melatonin was shown to inhibit development and/or growth of various experimental animal tumors and some human cell lines in vitro. Many tumors do not respond to drug treatment due to their resistance to undergo apoptosis thereby contributing to the development of cancer. Thus, given the importance of the apoptotic program in cancer treatment, the role of melatonin in influencing apoptosis in tumor cells attracted attention because it seems that it actually promotes apoptosis in most tumor cells, in contrast to the obvious inhibition of apoptotic processes in normal cells. Thus, this paper is also intended to provide to the reader an up-date of all the researches that have been carried out to date, which investigate the proapoptotic effects of melatonin in experimental preclinical models of cancer (in vitro and in vivo) and the underlying proposed action mechanism of this effects. If melatonin uniformly induces apoptosis in cancer cells, the findings could have important clinical implications to improve the quality of live while preventing the appearance of cancer.

Daily Rhythms of Plasma Melatonin, but Not Plasma Leptin or Leptin mRNA, Vary between Lean, Obese and Type 2 Diabetic Men

Melatonin and leptin exhibit daily rhythms that may contribute towards changes in metabolic physiology. It remains unclear, however, whether this rhythmicity is altered in obesity or type 2 diabetes (T2DM). We tested the hypothesis that 24-hour profiles of melatonin, leptin and leptin mRNA are altered by metabolic status in laboratory conditions. Men between 45–65 years old were recruited into lean, obese-non-diabetic or obese-T2DM groups. Volunteers followed strict sleep-wake and dietary regimes for 1 week before the laboratory study. They were then maintained in controlled light-dark conditions, semi-recumbent posture and fed hourly iso-energetic drinks during wake periods. Hourly blood samples were collected for hormone analysis. Subcutaneous adipose biopsies were collected 6-hourly for gene expression analysis. Although there was no effect of subject group on the timing of dim light melatonin onset (DLMO), nocturnal plasma melatonin concentration was significantly higher in obese-non-diabetic subjects compared to weight-matched T2DM subjects (p<0.01) and lean controls (p<0.05). Two T2DM subjects failed to produce any detectable melatonin, although did exhibit plasma cortisol rhythms comparable to others in the group. Consistent with the literature, there was a significant (p<0.001) effect of subject group on absolute plasma leptin concentration and, when expressed relative to an individual’s 24-hour mean, plasma leptin showed significant (p<0.001) diurnal variation. However, there was no difference in amplitude or timing of leptin rhythms between experimental groups. There was also no significant effect of time on leptin mRNA expression. Despite an overall effect (p<0.05) of experimental group, post-hoc analysis revealed no significant pair-wise effects of group on leptin mRNA expression. Altered plasma melatonin rhythms in weight-matched T2DM and non-diabetic individuals supports a possible role of melatonin in T2DM aetiology. However, neither obesity nor T2DM changed 24-hour rhythms of plasma leptin relative to cycle mean, or expression of subcutaneous adipose leptin gene expression, compared with lean subjects.

Melatonin Effects on Plasmodium Life Cycle: New Avenues for Therapeutic Approach

Malaria remains a global health problem affecting more than 515 million people all over the world including Malaysia. It is on the rise, even within unknown regions that previous to this were free of malaria. Although malaria eradication programs carried out by vector control programs are still effective, anti-malarial drugs are also used extensively for curtailing this disease. But resistance to the use of anti-malarial drugs is also increasing on a daily basis. With an increased understanding of mechanisms that cause growth, differentiation and development of malarial parasites in rodents and humans, new avenues of therapeutic approaches for controlling the growth, synchronization and development of malarial parasites are essential. Within this context, the recent discoveries related to IP3 interconnected signalling pathways, the release of Ca2+ from intracellular stores of Plasmodium, ubiquitin protease systems as a signalling pathway, and melatonin influencing the growth and differentiation of malarial parasites by its effects on these signalling pathways have opened new therapeutic avenues for arresting the growth and differentiation of malarial parasites. Indeed, the use of melatonin antagonist, luzindole, has inhibited the melatonin's effect on these signalling pathways and thereby has effectively reduced the growth and differentiation of malarial parasites. As Plasmodium has effective sensors which detect the nocturnal plasma melatonin concentrations, suppression of plasma melatonin levels with the use of bright light during the night or by anti-melatonergic drugs and by using anti-kinase drugs will help in eradicating malaria on a global level. A number of patients have been admitted with regards to the control and management of malarial growth. Patents related to the discovery of serpentine receptors on Plasmodium, essential for modulating intra parasitic melatonin levels, procedures for effective delivery of bright light to suppress plasma melatonin levels and thereby arresting the growth and elimination of malarial parasites from the blood of the host are all cited in the paper. The purpose of the paper is to highlight the importance of melatonin acting as a cue for Plasmodium faciparum growth and to discuss the ways of curbing the effects of melatonin on Plasmodium growth and for arresting its life cycle, as a method of eliminating the parasite from the host.

Melatonin status in pediatric intensive care patients with sepsis*

Considering the potential immunomodulatory role of melatonin and its direct antioxidant activity, disturbances of the melatonin secretion pattern in the septic conditions could be particularly unfavorable. The aim of this study was to evaluate the nocturnal melatonin concentration and total 24-hr excretion of 6-sulfatoxymelatoninsulfate, melatonin's major urinary metabolite, in children with sepsis in the pediatric intensive care unit. Prospective observational pilot study. A pediatric intensive care unit. Twenty septic and 20 nonseptic children admitted between February 2008 and January 2010. None. Blood and urine samples were obtained from each patient on days 1, 2, 3, 5, and 10. There were no significant differences between the groups concerning age and gender. The median nocturnal melatonin concentrations were not significantly different between septic and nonseptic patients during the study period (p > .05). A subgroup analysis in septic patients showed that the nocturnal melatonin concentrations in nonsurvivors were significantly higher than in survivors, whereas total 6-sulfatoxymelatoninsulfate excretions in nonsurvivors were significantly lower than in survivors (p = .001 and p = .015, respectively). Furthermore, nocturnal melatonin concentrations of septic patients in septic shock state were statistically significantly higher than those of septic patients without septic shock state (p = .002). The 24-hr 6-sulfatoxymelatoninsulfate excretions in septic patients with liver dysfunction were found significantly lower than those in septic patients without liver dysfunction (p = .015). The presence of sedation and mechanical ventilation had no effect on the nocturnal melatonin concentrations in septic patients (p = .953 and p = .922, respectively). The present study shows that, in contradiction to results in adult patients, the nocturnal melatonin concentrations are not decreased in septic pediatric intensive care unit patients despite severe disease. Further investigations are needed to identify whether treatment with melatonin may have beneficial effects in pediatric intensive care unit patients with sepsis/septic shock.

Microdialysis of melatonin in the confluens sinuum of the rat following quantification by gas chromatography-mass spectrometry in the negative chemical ion mode.

In this study, an original surgical implantation technique in the confluens sinuum via the superior sagittal vein was developed to quantify melatonin secretion by the pineal gland. Melatonin (CAS 73-31-4) was determined using gas chromatography couples to negative ion chemical ionisation mass spectrometry following liquid extraction and derivatisation by penta-fluoropropionic acid anhydride (PFPA). The minimum detectable amount was 40 fg per injection, corresponding to 1 pg.ml-1 in dialysate. The assay was linear in the range 20-1000 pg.ml-1. This method was suitable for routine melatonin determination in dialysats of peripheral and central circulation with coefficients of variation of 11.2 and 24.6%, respectively for within and between analyses. Profiles of melatonin concentration were obtained (n = 3 rats) over a 2-day experimentation with a slowly diminution of the filtration capacity of the probe during the second day. The nocturnal concentrations of melatonin in the confluens sinuum dialysat ranged from 1003.9 to 2345 pg.ml-1 in the dialysat, indicating wide interindividual variations in the melatonin levels.

Impact of photoperiod manipulation on day/night changes in melatonin, sex steroids and vitellogenin plasma levels and spawning rhythms in Senegal sole, Solea senegalensis

Photoperiod and temperature are known as the main synchronizers of seasonal reproduction in fish. This paper studied the role of photoperiod on the synchronization of F1 Senegal sole reproduction rhythms. Fish were maintained under constant short-photoperiod (9L:15D) from the winter solstice onwards (experimental group) or under naturally-changing photoperiod (control group), and water temperature naturally oscillated in both groups. Blood samples were collected during the reproduction season at pre-spawning (March), spawning (April) and post-spawning (May) to determine the endocrine status. Spawning events and egg quality parameters were also monitored. The results revealed a significant increase in nocturnal melatonin concentration from March to May in the control group, while in the experimental group such seasonal change did not occur. As to plasma levels of vitellogenin, testosterone, estradiol and 11keto-testosterone, differences between groups were found mostly in March, while in April and May levels were often similar. Spawning was observed in both groups, although the experimental group started slightly earlier and also finished earlier than the control group, perhaps as a result of the increase in sex steroids and VTG observed at pre-spawning. Briefly, reproduction rhythms persisted in the absence of the natural lengthening of photoperiod, although photoperiod manipulation altered the seasonal modulation of melatonin, increased sex steroids and vitellogenin at pre-spawning, and slightly advanced the timing of spawning.