Decreased nocturnal synthesis of melatonin in patients with coronary artery disease

In human beings, cardiovascular activity has a distinct circadian variation: Heart rate, blood pressure, and vascular tone decrease at night. Nocturnal cardiovascular blunting is at least partially linked to the autonomic activity and increased risk of cardiac and cerebral events. To assess whether decreased nocturnal melatonin synthesis and secretion in coronary artery disease (CAD), we investigated nocturnal secretion pattern of melatonin in patients with CAD and healthy subjects. The present study performed in 16 patients with angiographically documented CAD (aged 46-71 years) and in nine healthy controls (aged 36-66 years). Blood samples were collected every 2 h between 22:00 and 08:00 h. Melatonin levels were measured with a commercially available radioimmunoassay kit. We found large interindividual variation in the pattern of melatonin secretion in both groups. Patients with CAD secreted less nocturnal melatonin at 02:00, 04:00 and 08:00 h than control subjects (P=0.014, P=0.04 and P=0.025, respectively). Peak and Delta melatonin (peak-lowest melatonin) were found lower in patients with CAD (48.6 [19.1-75.4] vs. 131.4 [67.8-137.2] pg/ml, P=0.006 and 43 [10.5-68.5] vs. 107.6 [55.7-113.1] pg/ml, P=0.002, respectively). Peak time of melatonin secretion was observed earlier in patients with CAD (02:00 h [23:00-02:00 h] vs. 03:45 h [02:00-05:00 h], P=0.04). Our study provides useful and preliminary information about decreased nocturnal melatonin synthesis and release in patients with CAD might help physicians in managing these patients.     

Effects of oxygen administration on the circulating vascular endothelial growth factor (VEGF) levels in patients with obstructive sleep apnea syndrome

OBJECTIVE: Repeated nocturnal hypoxia is implicated in the pathogenesis of cardiovascular complications in obstructive sleep apnea syndrome (OSAS). We hypothesized that circulating vascular endothelial growth factor (VEGF) levels are affected by nocturnal hypoxemia in patients with OSAS. METHODS: We examined the serum VEGF levels in patients with OSAS and in control subjects. We also tested the effects of oxygen or air administration on the subjects' VEGF levels. PATIENTS AND MATERIALS: Twenty-four OSAS patients (mean age 54.2 +/- 3.6 years) and 24 age-matched control subjects (53.2 +/- 3.6 years). Their serum samples were tested. RESULTS: Serum VEGF levels at 8:00 AM were significantly higher in OSAS patients than in controls (p<0.01). VEGF levels decreased from 515 +/- 31 (pg/ml) to 178 +/- 16 (pg/m) (p<0.01) in OSAS patients whose nocturnal hypoxemia was found to be improved by administration of 2 l/min of oxygen during the night. However, the administration of compressed air affected neither the VEGF level nor nocturnal oxygen desaturation in OSAS patients. CONCLUSION: These results indicate that circulating VEGF levels are elevated in OSAS patients, primarily due to nocturnal hypoxemia.     

The effects of light exposure on plasma concentrations of melatonin, LH, FSH and prolactin in women

The effects of light exposure on plasma concentrations of melatonin, LH, FSH and prolactin were studied in 11 normal cycling women during their follicular phases. Blood samples were obtained via an indwelling venous catheter every 10 min. for 2.5 hours starting at 9:30 and 21:30h. For the blood samplings taken at night, six women were kept in a dark room and were permitted to sleep. Their blood samples were obtained using a flashlight (5-10 lux) without their rest being disturbed. However, the other five women were exposed to light (3,000 lux at eye level) and awakened from 22:40 to 24:00h. Plasma melatonin concentrations in the morning decreased from 48.7 +/- 11.6 pg/ml at 9:30h to 24.7 +/- 4.0 pg/ml at 12:00h. On the other hand, plasma melatonin concentrations at night increased from 65.4 +/- 9.6 pg/ml at 21:30h to 138.2 +/- 28.6 pg/ml at 24:00h. The pulsatile LH secretion was changed from the type of "high frequency, low amplitude" in the morning to the type of "low frequency, high amplitude" at night. Nocturnal FSH concentrations were lower than diurnal ones, but nocturnal prolactin concentrations were higher than diurnal ones. Nocturnal concentrations of melatonin were suppressed 40 min. after the light exposure (from 117.4 +/- 11.4 pg/ml at 22:40h to 74.6 +/- 13.9 pg/ml at 23:20h). On the the other hand, the light exposure increased plasma prolactin concentrations from 10.9 +/- 4.1 ng/ml at 22:40h to 17.0 +/- 4.4 ng/ml at 22:50h, maintained those higher levels for 20 min. and decreased them gradually after 23:20h. With the light exposure, mean values of nocturnal LH concentrations were increased from 11.9 +/- 1.5 mIU/ml before exposure to 14.2 +/- 1.8 mIU/ml after exposure, and those of FSH were also increased from 5.9 +/- 0.4 mIU/ml to 6.3 +/- 0.4 mIU/ml. These results showed that the secretion of melatonin, as well as LH, FSH and prolactin had daily rhythms and that melatonin and prolactin showed different responses to light exposure, suggesting different control mechanisms for the secretion of those two hormones.     

Decreased plasma levels of orexin-A in sleep apnea

BACKGROUND: Orexin-A, also known as hypocretin, is a neuropeptide implicated in appetite and sleep regulation. Because the obstructive sleep apnea syndrome (OSAS) is characterized by obesity and excessive daytime sleepiness, we hypothesized that orexin-A levels may be abnormal in patients with OSAS. Further, since treatment with continuous positive airway pressure (CPAP) in patients with OSAS is very effective in normalizing daytime sleepiness, we also hypothesized that the chronic use of CPAP may influence plasma levels of orexin-A in these patients. OBJECTIVE: To evaluate plasma levels of orexin-A in patients with OSAS and the effect of CPAP treatment. PATIENTS AND METHODS: We compared the plasma levels of orexin-A in 13 healthy controls, 27 untreated patients with OSAS and 14 patients treated with CPAP during at least 1 year (4.5 +/- 0.5 h/night; mean +/- SEM). All patients had severe OSAS (apnea-hypopnea index, 57 +/- 4 h(-1)). Results: Orexin-A plasma levels were significantly lower in untreated (9.4 +/- 1.9 pg.ml(-1), p < 0.01) and treated patients with OSAS (4.2 +/- 1.5 pg.ml(-1), p < 0.001) than in healthy subjects (20.6 +/- 4.5 pg.ml(-1)). In untreated patients, orexin-A levels were not significantly related to daytime somnolence assessed by Epworth scale (r = -0.18, p = 0.37) or the body mass index (r = -0.13, p = 0.52). CONCLUSIONS: Orexin-A plasma levels are abnormally low in patients with OSAS, independently of the level of somnolence and/or presence of obesity. These results suggest that these low orexin-A levels may be related to the pathogenesis of OSAS.     

Estimation of frequently sampled nocturnal melatonin production in humans by deconvolution analysis: evidence for episodic or ultradian secretion

In order to investigate nocturnal melatonin production and clearance rates, we applied deconvolution analysis to plasma melatonin concentration time series obtained every 20 min for 12 hr from 20:00 h to 08:00 h in two groups of healthy subjects at rest (group 1, 12 male subjects, 22-26 yr; group 2, ten female subjects, 31-42 yr). The estimated melatonin production rate from group 1 (0.55 +/- 0.21 microg/kg/night) was significantly higher than that of group 2 (0.26 +/- 0.19 microg/kg/night), as well as the mass of melatonin released per burst (275 +/- 110 vs. 145 +/- 130 pg/mL for groups 1 and 2, respectively), the amplitude of secretory bursts (7.8 +/- 3.2 vs. 4.7 +/- 3.5 pg/mL/min), and the pulsatile melatonin production rate (2.76 +/- 1.14 vs. 1.27 +/- 0.97 ng/mL/night). These differences could reflect alterations related to age and or gender. No differences were observed between the two groups in the secretory burst half-duration and frequency and the interburst interval. Melatonin production rates, as estimated by deconvolution analysis, are in agreement with other independent estimates, especially the isotopic method, and disclose an ultradian rhythmicity.     

Increased melatonin concentrations in children with growth hormone deficiency

A relationship between melatonin and growth hormone (GH) is poorly understood. We compare circadian melatonin rhythms in short children with normal and decreased GH secretion. The analysis included 22 children (20 boys and 2 girls) aged 11.1-16.9 yr (mean +/- S.E.M. = 14.1 +/- 0.3 yr) with short stature (height SDS below -2.0). Based on the GH peak in stimulation tests patients were divided into two groups: idiopathic short stature (ISS, n = 11; GH peak > or = 10 ng/mL) and GH deficiency (GHD, n = 11; GH peak < 10 ng/mL). In all patients the circadian melatonin rhythm was assessed on the basis of nine blood samples, collected in 4-hr intervals during the daytime and 2-hr intervals at night, with dark period lasting from 22:00 to 06:00 hr. Magnetic resonance imaging examination excluded organic abnormalities in central nervous system in all patients. Melatonin concentration at 24:00, 02:00 and 04:00 hr as well as the area under curve of melatonin concentrations (AUC) were significantly higher in the patients with GHD than in individuals with ISS. Significant correlations between GH secretion and melatonin concentrations at 24:00, 02:00 and 04:00 hr, and AUC were also observed. On the basis of these data it seems that the assessment of nocturnal melatonin secretion might be a valuable diagnostic tool used for the improvement of the difficult diagnosis of short stature in children.     

Platelet function in patients with obstructive sleep apnoea syndrome.

Patients with obstructive sleep apnoea syndrome (OSAS) are subject to an increased cardiovascular morbidity including myocardial infarction and stroke. Platelets play an important role in the pathogenesis and triggering of acute cardiovascular syndromes. So far, the influence of OSAS on platelet function is not fully understood. Platelet aggregability to epinephrine, collagen, arachidonic acid, and adenosine diphosphate in vitro was measured in 17 consecutive male patients (53.0+/-2.1 yrs) with polysomnographically verified OSAS and compared with that of 15 male controls (50.1+/-3.6 yrs) at 20:00 h, 24:00 h, and 06:00 h. In addition, the long-term effects of continuous positive airway pressure (CPAP) therapy on platelet aggregability was assessed after 6 months. Platelet aggregation in vitro induced by epinephrine showed a slight increase overnight in the untreated OSAS patients (NS) whereas it decreased slightly (NS) in the controls and in the treated OSAS patients. Pretherapeutic platelet aggregability was significantly lowered by CPAP therapy both at 24:00 h (64.0+/-6.5 versus 55.3+/-6.7%, p<0.05) and at 06:00 h (64.1+/-6.5 versus 45.8+/-7.6%; p=0.01). Platelet aggregability during sleep in the controls resembled that found in patients with OSAS during CPAP therapy. The results suggest that obstructive sleep apnoea syndrome contributes, at least in part, to platelet dysfunction and that long-term continuous positive airway pressure treatment may reduce platelet aggregability.     

Light/dark patterns of soluble vascular cell adhesion molecule-1 in relation to melatonin in patients with ST-segment elevation myocardial infarction

Elevated levels of soluble cellular adhesion molecules have been reported in patients with acute coronary syndromes. Likewise, a relation between decreased nocturnal melatonin levels and coronary artery disease has been suggested. The aim of the present study was to investigate the day-night variations in the concentration of soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with ST-segment elevation myocardial infarction (STEMI) in relation to the light/dark melatonin pattern. Ninety consecutive patients with STEMI who were admitted to the Coronary Care Unit of our institution were studied. We also recruited 70 age- and gender-matched healthy normal subjects. Blood samples were drawn at 09:00 and 02:00 hr, while patients were at rest, for the assessment of sVCAM-1 and melatonin, which were measured using commercially available ELISA. In STEMI patients, melatonin concentrations maintained a diurnal variation, but the difference between nocturnal and diurnal levels was less than that in healthy subjects (P < 0.0001). In contrast to findings with melatonin, sVCAM-1 levels showed no diurnal variations in control subjects. In the STEMI group, however, sVCAM-1 concentration at 02:00 hr was significantly higher than that during the light phase (09:00 hr; 1391 +/- 38 versus 1200 +/- 43 ng/mL, P < 0.05). The results suggest that diurnal variations in endogenous sVCAM-1 production in STEMI patients might be related to an attenuated circadian secretion of melatonin.     

Melatonin levels decrease in type 2 diabetic patients with cardiac autonomic neuropathy

The present study has been designed to determine melatonin levels in type 2 diabetic patients and test the relationship between the autonomic nervous system and melatonin dynamics. Thirty-six type 2 diabetic patients and 13 age-matched healthy subjects were recruited for the study. Circadian rhythm of melatonin secretion was assessed by measuring serum melatonin concentrations between 02:00-04:00 and 16:00-18:00 hr. Melatonin dynamics were re-evaluated with respect to autonomic nervous system in diabetic patients with autonomic neuropathy who were diagnosed by the cardiovascular reflex tests, heart rate variability (HRV), and 24-hr blood pressure monitoring. Nocturnal melatonin levels and the nocturnal melatonin surge were low in the diabetic group (P = 0.027 and 0.008 respectively). Patients with autonomic neuropathy revealed decreased melatonin levels both at night and during day when compared with healthy controls (P < 0.001 and 0.004 respectively) while the melatonin dynamics were similar to controls in patients without autonomic neuropathy. Nocturnal melatonin level was positively correlated with nocturnal high and low frequency components of HRV (P = 0.005 and 0.011 respectively) and systolic and diastolic blood pressures at night (P = 0.002 and 0.004 respectively) in patients with autonomic neuropathy. We found a negative correlation between nocturnal melatonin levels and the degree of systolic blood pressure decrease at night (r = -0.478, P = 0.045). As a conclusion this study has shown that circadian rhythm of melatonin secretion is blunted in type 2 diabetic patients and there is a complex relationship between various components of autonomic nervous system and melatonin secretion at night. Among the patients with autonomic neuropathy those with more preserved HRV and the systolic nondippers (<10% reduction in blood pressure during the night relative to daytime values) have more pronounced melatonin surge at night.     

Serum melatonin circadian profiles in women suffering from cervical cancer

Although there is an increasing evidence that the pineal gland may play a role in human malignancy, the studies on melatonin concentrations in different types of malignant tumors brought about controversial results. However, changes in melatonin concentrations have been observed in some types of human malignant tumors. Therefore, we decided to study the circadian melatonin rhythm in patients suffering from cervical cancer in different stages of progression and to compare them with those in subjects free from neoplastic disease. A total of 45 women were analyzed in this study. The subjects were divided into two groups. The first group consisted of 31 patients [mean age 52.1 +/- 1.8 yr (mean +/- S.E.M.), range 32-77 yr] with cervical cancer in various stages of the disease. The second group consisted of 14 healthy volunteers [mean age 53.5 +/- 2.0 yr (mean +/- S.E.M.), range 42-63] who served as the control group. Blood samples were collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00, and 08:00 hours. Melatonin concentration was measured by immunoenzymatic method. There were significant differences in circadian melatonin profiles as well as in the area under curve among the two studied groups. Melatonin concentrations were significantly lower in cancer patients in comparison with healthy individuals. Taking into consideration stage of the cervical cancer significantly lower melatonin secretion has been found in all subgroups of patients in comparison with that of tumor-free control group. Additionally, nocturnal melatonin concentrations as well as area under curve were significantly lower in advanced stage of cancer (stages 3 and 4) in comparison with patients with preinvasive cancer (stage 0) at 24:00, 02:00, and 04:00 hours and patients with stage 1 disease at 02:00 and 04:00 hours. The results of the present study indicate that the presence of cervical cancer influences melatonin levels in women. Moreover, stage dependence in reduction of melatonin concentrations has been found.     

Light Suppression of Melatonin in the Squirrel Monkey (Saimiri sciureus)

This study examined plasma melatonin levels and the suppressant effect of light on melatonin production in the squirrel monkey. Monkeys were maintained on a 12:12 light-dark cycle (LD 12:12) with lights on from 07:00 to 19:00. Plasma levels of melatonin were determined by gas chromatography negative chemical ionization mass spectrometry. Melatonin levels at 00:00 (99.5 +/- 18.9 pg/ml) were significantly higher than at 02:00 (57.21 +/- 7.7 pg/ml; Student's t = 2.859; P less than or equal to 0.021). Baseline values at 02:00 were compared with levels at the same time of day after exposure to 2 hours of 200 lux of light (30.6 +/- 13.1 pg/ml), which caused an average suppression of 54.8% in melatonin levels. One animal did not show light suppression. Results indicated that the squirrel monkey suppressant response to light, as well as baseline values of melatonin, varied between animals.     

8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may compromise oxidative balance. Oxidative stress is increased in the blood and in the airways of OSA patients. DESIGN: The aim of this study was to investigate whether oxidative stress is determined by nocturnal apneas and could be reduced by CPAP therapy, and whether there is a relation between local and systemic oxidative stress in these patients. PATIENTS AND METHODS: Eighteen patients with OSA (13 men; mean [+/- SD] age, 48 +/- 3 years) and 12 healthy age-matched and weight-matched subjects (8 men; mean age, 46 +/- 7 years) were recruited. 8-Isoprostane was measured in exhaled breath condensate and blood by a specific enzyme immunoassay. Measurements and results: Higher concentrations of 8-isoprostane were found in the morning exhaled condensate (9.5 +/- 1.9 pg/mL) and plasma (9.7 +/- 1.5 pg/mL) of OSA patients compared to healthy obese subjects (6.7 +/- 0.2 and 7.1 +/- 0.3 pg/mL, respectively; p < 0.0001). Elevated mean concentrations of exhaled 8-isoprostane were observed in the OSA patients at 8:00 AM (9.5 +/- 1.9 pg/mL) but not at 8:00 PM (7.6 +/- 0.8 pg/mL; p < 0.0005), and a significant reduction was seen after continuous positive airway pressure (CPAP) therapy (7.7 +/- 0.9 pg/mL; before treatment, 9.6 +/- 1.7 pg/mL; p < 0.005). A positive correlation was found between morning exhaled 8-isoprostane levels and the apnea-hypopnea index (r = 0.8; p < 0.0001), and 8-isoprostane levels and neck circumference (r = 0.6; p < 0.0001). CONCLUSIONS: These findings suggest that systemic and local oxidative stress are increased in OSA patients, and that they are higher after nocturnal apnea and reduced by CPAP therapy.     

Atrial natriuretic peptide levels in geriatric patients with nocturia and nursing home residents with nighttime incontinence

OBJECTIVES: To determine if nocturnal polyuria in geriatric patients with nocturia and nocturnal incontinence is associated with elevated plasma atrial natriuretic peptide (ANP) levels. DESIGN: Case series. SETTING: Four nursing homes and two board and care facilities. PARTICIPANTS: Fifty-four nursing home residents and 26 board and care residents with a mean age of 86. MEASUREMENTS: Daytime (7:00 a.m. to 7:00 p.m.) and nighttime (7:00 p.m. to 7:00 a.m.) urine volumes of incontinent nursing home residents were measured over 3 days and 3 nights by reweighing preweighed adults diapers and toileting inserts emptied by research staff for the board and care group. Blood was drawn in the early morning (5:00 a.m. to 7:00 a.m.) before subjects arose and in the evening after an hour of lying in bed (8:00 p.m. to 11:00 p.m.), and plasma ANP levels were determined by radioimmunoassay. RESULTS: Forty-nine (61%) of the subjects had nocturnal polyuria as defined by night/total urine volume ratios > or = 50%. There was no significant difference between those with night/total ratios > or = 50% versus < 50% in plasma levels of ANP in the early morning (44.2+/-33.3, median 35.7 pg/mL vs 40.9+/-39.2, median 28.5; P = .36 by Mann Whitney U) or in the evening (43.4+/-28.8, median 36.4 pg/mL vs 49.6+/-53.1, median 34.4; P = .58). Nor was there any significant correlation between night/total urine volume ratio and morning or evening ANP levels (r = .01, P = .96 and r = .23, P = .31, respectively). CONCLUSIONS: In this sample of geriatric patients with nocturia and nursing home residents with nighttime urinary incontinence, ANP levels were elevated, but increased nighttime urine production was not associated with higher levels. Because of the variability in ANP levels, our power to detect such an association was low, and we cannot draw any definitive conclusions. Although high plasma ANP levels are unlikely to be a primary cause of nocturia and nighttime incontinence, they may, when combined with other factors such as low antidiuretic hormone levels, sleep disorders, and low functional bladder capacity, contribute to these symptoms in some geriatric patients.     

阻塞性睡眠呼吸暂停低通气综合征患者血清褪黑素的变化及其意义

目的 研究阻塞性睡眠暂停低通气患者血清褪黑素的变化及其临床意义.方法 选择在兰州大学第一医院就诊,经多导睡眠监测确诊的OSAHS患者30例和健康对照10名,并用Epworth嗜睡量表进行评估.用高效液相色谱法检测血清褪黑素浓度.分别在22:30时、02:00时和07:00时测OSAHS患者和健康对照者血清褪黑素浓度.结...     

Overdrive atrial pacing does not improve obstructive sleep apnoea syndrome.

The aim of this study was to assess the ability of overdrive atrial pacing to reduce sleep apnoea severity. A total of 17 unselected patients (12 males; mean+/-SD age 71+/-10 yrs; body mass index 27+/-3 kg x m(-2)) who had received permanent atrial-synchronous ventricular pacemakers for symptomatic bradyarrhythmias and not known to have central or obstructive sleep apnoea syndrome (OSAS) were studied. Using a crossover study design, patients were or were not in pacing mode with atrial overdrive (15 beats x min(-1) faster than mean baseline nocturnal cardiac frequency) for 1 month. Patients were paced only during sleep periods, identified by a specific algorithm included in the pacemaker. Patients underwent three overnight polysomnographic evaluations 1 month apart. The first was performed for baseline evaluation. The patients were then randomly assigned to either 1 night in spontaneous rhythm or to 1 night in pacing mode with atrial overdrive. Two patients refused to continue the study after the first polysomnographic evaluation. OSAS was highly prevalent in this population: 10 of the 15 (67%) patients exhibited an apnoea-hypopnoea index of >30 events x h(-1). The nocturnal spontaneous rhythm was 59+/-7 beats x min(-1) at baseline, compared to 75+/-10 beats x min(-1) with atrial overdrive pacing. The apnoea-hypopnoea index was 46+/-29 events x h(-1) in spontaneous rhythm, compared to 50+/-24 events x h(-1) with atrial overdrive pacing. Overdrive pacing changed none of the respiratory indices, or sleep fragmentation or sleep structure parameters. In conclusion, atrial overdrive pacing has no significant effect on obstructive sleep apnoea.     

Increased sympathetic activity during sleep and nocturnal hypertension in Type 2 diabetic patients with diabetic nephropathy.

AIMS: To elucidate the putative factors involved in the blunted nocturnal blood pressure reduction in hypertensive Type 2 diabetic patients with diabetic nephropathy. METHODS: Extracellular fluid volume and fluid shift from interstitial to plasma volume (haematocrit), sympathetic nervous activity (plasma noradrenaline and adrenaline) and the internal 'body clock' (serum melatonin) were investigated in 31 hypertensive Type 2 diabetes mellitus (DM) patients with diabetic nephropathy (24 males, age 60 (45-73) years). All variables, except extracellular volume, were measured repeatedly with the patients lying awake in bed from 21:30 to 23:00 h (baseline) and during sleep from 23:00 to 07:00 h. Using the median nocturnal blood pressure reduction (8.4%) as a guide, the patients were divided into groups; group 1 with the highest and group 2 with the lowest nocturnal blood pressure reduction. RESULTS: Haematocrit decreased from baseline to the sleep period in group 1 by a mean (95% confidence interval (CI)) of 1.7 (0.3-3.1)%, but it increased by 0.5 (-1.0-1.9)% in group 2, mean difference (95% CI), -2.1 (-4.0 to -0.2)% (P = 0.029). Noradrenaline decreased from baseline to the sleep period, mean (95% CI), by 13.3 (0.0-25.0)% in group 1 but rose by 7.7 (-9.7-28.4)% in group 2, mean difference (95% CI), -19.6 (-35-0.0)% (P = 0.049). The nocturnal blood pressure change correlated to the nocturnal change in both noradrenaline (r = 0.51, P = 0.004) and haematocrit (r = 0.42, P = 0.018). Adrenaline remained constant in both groups. Extracellular fluid volume and plasma melatonin levels were comparable in the two groups. CONCLUSION: Sustained adrenergic activity during sleep is associated with blunted nocturnal blood pressure reduction in hypertensive Type 2DM patients with diabetic nephropathy, probably mediated through a lack of peripheral vasodilatation whereas changes in extracellular fluid volume distribution and melatonin secretion have no impact.     

A study of melatonin levels and stress in female shift workers

The aim of this study was to determine the relationship between saliva melatonin and stress levels in Thai female shift workers. Five older (38.4 +/- 1.82) and five younger (21.4 +/- 0.55) female workers voluntarily participated in this study. All participants worked both morning and night shifts at a glass manufacturing factory. Saliva was collected every three hours at the workplace and at the subjects' houses to examine melatonin profiles. The Mann-Whitney U test and the Wilcoxon signed ranks test were used. There was a significant (p < 0.05) difference between melatonin levels in younger and older subjects when measured during the night shift at 19:00. Differences between melatonin levels during the morning and night shifts in the older group were significant at 07:00 and at 19:00 in younger subjects (p < 0.05). Normal stress and mild stress were found. No significant differences in melatonin levels were found between workers with normal and mild stress levels. The onset time of increasing saliva melatonin was at 19:00, both in women working the morning shift and in those working the night shift. Peak melatonin production occurred at 22:00 for the night shift in both groups. During the morning shifts, the peak times were at 04:00 and 01:00 (in the younger and older groups, respectively), usually between 02:00 and 04:00. These findings show that melatonin levels in female shift workers adapted according to the shift worked, especially in the older group. Health surveillance programs should therefore be established to prevent further negative health effects for female shift workers.     

Plasma melatonin and insulin-like growth factor-1 responses to dim light at night in dairy heifers

The effect of dim (5, 10 and 50 1x) light at night on night plasma melatonin level (NML) and night plasma insulin-like growth factor-1 (IGF-1) level was determined in 12 prepubertal Holstein heifers (245 +/- 16 days age) using a 4 x 4 Latin Square design with 14-day treatment and 14-day recovery periods. Blood samples were collected at 23:00 hr (prior to the 8 hr night treatment which commenced at mid-night) on days 0, 3 and 13, and throughout the night at 01:00, 02:00, 03:00, 04:00, 06:00 and 08:00 hr on days 1, 4 and 14 of treatment. Plasma was analysed by radioimmunoassay for melatonin (all samples) and IGF-1 (samples for day 14, 04:00 hr only). Treatment (P = 0.03) and treatment x time (P = 0.02) were significant for NML. Exposure to 50 lx suppressed NML by 50% during the initial 2 hr of the night, but not thereafter. Exposure to 5 and 10 lx had no effect on NML. The NML response to 50 lx was found on all treatment days studied (treatment x time x day; P = 0.99). There was no treatment effect on plasma IGF-1 level (P = 0.89), but plasma IGF-1 level was higher (P = 0.001) during period 4. Plasma IGF-1 level and NML tended (P = 0.10) to be negatively correlated. Light intensities of 10 lx or less appear safe for use at night in dairy barns where darkness is recommended.     

Clearance of melatonin and 6-sulfatoxymelatonin by hemodialysis in patients with end-stage renal disease

Patients with end-stage renal disease (ESRD) suffer from a number of related disorders. These include endocrine abnormalities, sleep disturbances, and depression. Melatonin is involved in the synchronization of exogenous zeitgebers with the endogenous rhythms, and it has effects on various psychological factors. As the concentrations of melatonin and the effects of dialysis have only occasionally been investigated in ESRD, we performed a study involving 35 patients, measuring the serum concentrations of melatonin, and of its major metabolite 6-sulfatoxymelatonin (aMT6s), before and after hemodialysis. Serum samples taken during morning hours from a control group (n=11) with intact kidneys served as controls. Patients were dialyzed for approximately 4 hr between 07:00 and 13:00 hr (S1), between 13:00 and 20:00 hr (S2), or between 18:30 and 22:30 hr (S3). Mean melatonin concentrations before hemodialysis were highly elevated when compared with the controls (40.6 vs. 6.7 pg/mL; P<0.001). Although melatonin levels were decreased to 20.3 pg/mL after dialysis, they were still well above the control levels. Likewise, aMT6s concentrations before dialysis were highly elevated in ESRD patients before dialysis when compared with controls (39.5 vs. 2.0 pg/mL; P<0.001), and also decreased by dialysis to levels still well above control levels (25.3 pg/mL). Clearance efficacy was better for melatonin (48.9%) than for aMT6s (36.6%; P<0.05). In ESRD patients, a diurnal rhythm for melatonin was observed (S1, 45.1 pg/mL; S2, 31.5 pg/mL; S3, 48.7 pg/mL; P<0.05), indicating that the normal synthesis rhythm is maintained. None of the following secondary disorders were correlated with melatonin concentrations: insomnia, delayed sleep onset, night-time arousals, and restless-leg syndrome. The reason for this observation is probably the melatonin concentrations, which were so high that no sub-classification could be identified. It is concluded that in ESRD patients, hemodialysis is unable to decrease elevated levels of melatonin and aMT6s to normal values. It is speculated that some of the secondary disorders in ESRD are caused by supraphysiological concentrations of melatonin.     

A Once-Repeated Study of Nocturnal Plasma Melatonin Patterns and Sleep Recordings in Six Normal Young Men

The concentration of melatonin was determined, using a sensitive and reliable radioimmunoassay, in plasma samples obtained at 20 min intervals during a 12 hr period (from 20.00 to 8.00) from six normal men. Polygraphic sleep recording was simultaneously performed. Each subject was studied twice at a 1 week interval. For each session, the plasma melatonin profile showed an episodic secretion: a mean frequency of 4.5 peaks and 4.0 troughs per night in the first study and a mean frequency of 4.0 peaks and 3.5 troughs in the second study. The two nocturnal melatonin profiles obtained from each subject were very similar. However, considerable interindividual variation was found (areas under the curve [AUC] from 15.3 to 125 pg X hr/ml). No relationship could be obtained between AUC and body weight. Apparent melatonin half-life calculated from the semilogarithmic plots of the melatonin pattern was 57 +/- 34 min. Chi-square testing revealed that the nocturnal pattern of melatonin levels was not related to sleep stages. Our data do not favor a direct relationship between melatonin secretion and the sleep-waking cycle in humans.