Brahim Selmaoui

Magnetic fields and pineal function in humans: evaluation of nocturnal acute exposure to extremely low frequency magnetic fields on serum melatonin and urinary 6-sulfatoxymelatonin circadian rhythms.

Exposure to a 50/60-Hz electromagnetic field can decrease the nocturnal production of melatonin in rodents. Melatonin is considered to be a marker of circadian rhythms, and abnormalities in its secretion are associated with clinical disorders, including fatigue, sleep disruption, mood swings, impaired performance, and depression, which are consequences of desynchronisation. Interestingly, some epidemiological studies have been reported finding most of these clinical disorders in individuals living or working in an environment exposed to electromagnetic fields. This experiment was designed to look for the possible effects of acute exposure (9 hours) to 50-Hz linearly polarized magnetic fields (10 mu T) on the pineal function. Thirty-two young men (20-30 years old) were divided into two groups (control group, i.e., sham-exposed: 16 subjects; exposed group: 16 subjects). All subjects participated in two 24-hour experiments to evaluate the effects of both continuous and intermittent exposure to linearly polarized magnetic fields. They were synchronized with a diurnal activity from 08:00 to 23:00 and nocturnal rest. The experiment lasted two months (mid-February to mid-April). The subjects were exposed to the magnetic fields (generated by three Helmholtz coils per bed) from 23:00 to 08:00, while lying down. Blood samples were collected during each session at 3-hour intervals from 11:00 to 20:00 and hourly from 22:00 to 08:00. Total urine was collected every 3 hours from 08:00 to 23:00 and once during the night, from 23:00 to 08:00. The levels of serum melatonin and its metabolite in urine (6-sulfatoxymelatonin) in exposed men did not differ significantly from those in control (sham-exposed) subjects. This study shows that nocturnal acute exposure to either continuous or intermittent 50-Hz linearly polarized magnetic fields of 10 mu T does not affect melatonin secretion in humans.

Sinusoidal 50-HZ magnetic fields depress rat pineal NAT activity and serum melatonin. Role of duration and intensity of exposure

The purpose of this study was to determine whether the exposure to a 50-Hz sinusoidal magnetic field could influence serum melatonin concentration and pineal enzymes activities in rats. The effects of both duration and intensity of exposure were also looked at. Two groups of Wistar male rats were exposed to 50-Hz magnetic fields of either 1, 10 or 100 microT. The first group was exposed for 12 hours and the second for 30 days (18 hours per day). During this time the animals were kept under a standard 12:12 light: dark cycle with a temperature of 25 degrees C and a relative humidity of 45 to 50%. Control (Sham-exposed) animals were kept in a similar environment but without exposure to a magnetic field. The animals were sacrificed under red dim light. Serum melatonin concentration and pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) activities were studied. Long-term exposure to a magnetic field (10 and 100 microT) significantly depressed the nocturne peak of serum melatonin concentration and pineal NAT activity whereas no effect was observed on HIOMT activity. Short-term exposure depressed both pineal NAT activity and nocturnal serum melatonin concentration but only with the highest intensity used (100 microT). Our results suggest that sinusoidal magnetic fields alter the production of melatonin through an inhibition of pineal NAT activity. Both duration and intensity of exposure play an important role in this effect. This work shows that, 1) sinusoidal magnetic field depresses NAT activity as static magnetic field does whereas HIOMT activity remains unaltered whatever the type of experiment and the intensity used, 2) the effect observed is related to both the duration of exposure and the intensity of magnetic fields, 3) the sensitivity threshold to magnetic fields vary with the duration of exposure which strongly suggests a cumulative effect of sinusoidal magnetic fields on pineal function.

Effects of caffeine on daytime recovery sleep: A double challenge to the sleep–wake cycle in aging

BACKGROUND AND OBJECTIVE Caffeine is the most widely used stimulant to counteract the effects of sleepiness, but it also produces important detrimental effects on subsequent sleep, especially when sleep is initiated at a time when the biological clock sends a strong waking signal such as during daytime. This study compares the effects of caffeine on daytime recovery sleep in young (20-30 y.) and middle-aged subjects (45-60 y.). METHODS Subjects participated in both caffeine (200mg) and placebo conditions (double-blind cross-over design), spaced one month apart. For each condition, subjects initially came to the laboratory for a nocturnal sleep episode. Daytime recovery sleep started in the morning after 25h of wakefulness. Subjects were administered either one caffeine (100mg) or placebo capsule three hours before daytime recovery sleep and the remaining dose one hour before daytime recovery sleep. RESULTS Middle-aged subjects showed greater decrements of sleep duration and sleep efficiency than young subjects during daytime recovery under placebo compared to nocturnal sleep. Caffeine decreased sleep efficiency, sleep duration, slow-wave sleep (SWS) and REM sleep during daytime recovery sleep similarly in both age groups. Caffeine also reduced N-REM sleep EEG synchronization during daytime recovery sleep (reduced delta, theta, and alpha power, and greater beta power). CONCLUSIONS The combined influence of age and caffeine made the sleep of middle-aged subjects particularly vulnerable to the circadian waking signal. We propose that lower brain synchronization due to age and caffeine produces greater difficulty in overriding the circadian waking signal during daytime sleep and leads to fragmented sleep. These results have implications for the high proportion of the population using caffeine to cope with night work and jet lag, particularly the middle-aged.

Age-related differences in serum melatonin and pineal NAT activity and in the response of rat pineal to a 50-HZ magnetic field

In a previous study we have shown that exposure to a 50-Hz sinusoidal magnetic field decreased serum melatonin concentration and pineal enzyme activities in young rats (9 weeks). In the present study we looked for the effect of a magnetic field of 100 microT on serum melatonin and pineal NAT activity in aged rats and compared them to young rats. We hypothesized that aging may change sensitivity of rats to a magnetic field. Two groups of Wistar male rats [aged rats (23 months) and young rats (9 weeks)] were exposed to 50-Hz magnetic fields of 100 microT for one week (18h/day). The animals were kept under a standard 12:12 light: dark cycle with a temperature of 25 degrees C and a relative humidity of 45 to 50%. Control (sham-exposed) animals were kept in a similar environment but without exposure to a magnetic field. The animals were sacrificed under red dim light. Serum melatonin concentration and pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) activities were studied. Our results showed that sinusoidal magnetic fields altered the production of melatonin (28% decrease; P <0.05) through an inhibition of pineal NAT activity (52% decrease; P <0.05) in the young rats whereas no effect was observed in aged ones. On the other hand, when comparing data from control animals between young and aged rats, we observed that serum melatonin level and NAT activity, but not HIOMT activity, decreased in aged rats (decrease by about 38% and 36% respectively). Our data strongly suggest that old rats are insensitive to the magnetic field.

Are Modifications of Melatonin Circadian Rhythm in the Middle Years of Life Related to Habitual Patterns of Light Exposure

The mechanisms underlying age-related changes in the signal from the biological clock have yet to be determined. The authors sought to determine if the phase advance of circadian melatonin rhythm during the middle years of life is related to different patterns of habitual light exposure. Forty-one healthy subjects between the ages of 22 and 58 y were studied. Habitual light exposure was measured by a wrist monitor for 7 days. Participants underwent a 25-h constant routine. They provided saliva samples every 30 min, and melatonin concentration was determined by radioimmunoassay to assess salivary dim light melatonin onset (S-DLMO1.3). Aging was associated with earlier S-DLMO1.3. Increasing age was not related to the time spent at different light intensities. However, it was associated with lower percentage of light exposure during the night (between 0200-0400, 0600-0700, and 2300-2400 h) and with higher percentage of light exposure in the morning (between 0800-1100 h). Earlier S-DLMO1.3 was associated with lower percentage of light exposure early on in the night (between 2200-0000, 0000-0100, and 0200-0300 h) as well as in the afternoon (between 1500-1600 h) and with higher percentage of light exposure in the morning (between 0800-1100 h). When the effects of age were controlled, there was no significant relationship between S-DLMO1.3 and percentages of light exposure. Yet increasing age was associated with earlier S-DLMO1.3 regardless of light exposure patterns. Earlier habitual wake time explained the earlier light exposure patterns of older subjects. Both habitual wake time and age contributed to the prediction of S-DLMO1.3. The results suggest a phase advance of circadian rhythms in the middle years of life. Whereas a clear change in habitual light exposure patterns was associated with aging and with shifts in S-DLMO1.3, it did not explain entirely the age-related advance of melatonin circadian phase.

Assessment of the effects of nocturnal exposure to 50-Hz magnetic fields on the human circadian system. A comprehensive study of biochemical variables.

The proposed laboratory investigation was designed to evaluate the effects of acute exposure to both continuous and intermittent magnetic fields (MFs) (50 Hz-10 microT) on the circadian rhythm of clinical chemistry variables in humans: electrolytes (magnesium, calcium, phosphorus, sodium, potassium, and chloride), enzymes (amylase, lipase, aldolase, gamma glutamyl-transferase [GGT], lactate dehydrogenase [LDH], aspartate aminotransferase [ASAT], and alkaline phosphatase [ALP]), lipids (cholesterol, high-density lipoprotein [HDL], apolipoprotein A1 [ApoA1], and ApoB), proteins (total proteins and albumin), nitrogen substances (uric acid, urea, and creatinine), iron, glycemia, and transferrin. Young volunteers (32 subjects; 16 exposed and 16 sham exposed) were selected according to the screening criteria. Each subject participated in two sessions held within a 4-week period. In the first session, one group of volunteers (16 subjects) was exposed to a continuous MF and then, in the second session, to an intermittent MF. The second group (16 subjects) served as a control for both sessions. At each session, blood samples were collected at 3 h intervals from 11:00 to 20:00 and hourly from 22:00 to 08:00. The results indicate that both continuous and intermittent 50-Hz linearly polarized MFs of 10 microT intensity have no effects on the circadian rhythms or on the levels of the variables studied here.

Radiofrequency signal affects alpha band in resting electroencephalogram

The aim of the present work was to investigate the effects of the radiofrequency (RF) electromagnetic fields (EMFs) on human resting EEG with a control of some parameters that are known to affect alpha band, such as electrode impedance, salivary cortisol, and caffeine. Eyes-open and eyes-closed resting EEG data were recorded in 26 healthy young subjects under two conditions: sham exposure and real exposure in double-blind, counterbalanced, crossover design. Spectral power of EEG rhythms was calculated for the alpha band (8-12 Hz). Saliva samples were collected before and after the study. Salivary cortisol and caffeine were assessed by ELISA and HPLC, respectively. The electrode impedance was recorded at the beginning of each run. Compared with the sham session, the exposure session showed a statistically significant (P < 0.0001) decrease of the alpha band spectral power during closed-eyes condition. This effect persisted in the postexposure session (P < 0.0001). No significant changes were detected in electrode impedance, salivary cortisol, and caffeine in the sham session compared with the exposure one. These results suggest that GSM-EMFs of a mobile phone affect the alpha band within spectral power of resting human EEG.

Effects of GSM 900 MHz on Middle Cerebral Artery Blood Flow Assessed by Transcranial Doppler Sonography

Mobile phone use has increased worldwide but its possible effects on the brain remain unclear. The aim of the present study was to investigate the effect of acute exposure to a radio frequency electromagnetic field (RF EMF) generated by a mobile phone operating in the Global System for Mobile Communication (GSM) 900 MHz on cerebral blood flow. Twenty-nine volunteers attended two experimental sessions: a sham exposure session and a real exposure session in a cross-over double-blind study in which a mobile phone was positioned on the left side of the head. In one session, the mobile phone was operated without RF radiation (sham phone) and in the other study it was operated with RF radiation (real phone) for 20 min. Thus, each subject served as its own control. Middle cerebral artery blood flow was monitored noninvasively by transcranial Doppler sonography to measure middle cerebral artery blood flow velocity. Pulsatility index and resistance index were also evaluated. A voluntary breath holding physiological test was carried out as a positive control for testing cerebral vasoreactivity. Hemodynamic variables were recorded and analyzed before, during and after mobile phone exposure. No significant changes were detected in studied variables in middle cerebral arteries during sham or real exposure. In the exposed side the cerebral blood flow velocity, the pulsatility index and the resistance index during sham and real exposure were respectively: [61.9 ± 1.3, 61.7 ± 1.3 cm/s (P = 0.89)]; [0.93 ± 0.03, 0.90 ± 0.02 (P = 0.84)] and [0.58 ± 0.01, 0.58 ± 0.01 (P = 0.96)] at baseline; and [60.6 ± 1.3, 62 ± 1.6 cm/s (P = 0.40)]; [0.91 ± 0.03, 0.87 ± 0.03 (P = 0.97)]; [0.57 ± 0.01, 0.56 ± 0.01 (P = 0.82)] after 20 min of exposure. Twenty minutes of RF exposure to a mobile phone does not seem to affect the cerebral circulation.

Food ingestion and circadian rhythmicity

Abstract Feeding is organised within the 24-h of the light – dark (LD) cycle. Food is ingested in a circadian manner in nature and in laboratory animals kept under constant conditions. The circadian rhythmicity in food ingestion is driven by a biological clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The circadian organisation of food ingestion not only allows animals to live in harmony with their environment but food intake could also act as a zeitgeber for other rhythmic functions. Lesions in the area of the SCN result in the loss of most rhythmic functions as well as to a disrupted circadian rhythmicity of food and water intake. These findings, together with observations from daytime feeding experiments conducted in nocturnal animals, suggest that food intake may serve as a temporal signal for some peripheral organs to oscillate in phase with the SCN. This paper overviews and discusses how food intake interacts with the circadian system.

A population Pharmacokinetic Turnover and Surge‐Function Model for Describing Melatonin Biological Rhythm in Healthy Male Subjects

A turnover model in combination with an empirical surge function based on a chromatographic peak detection algorithm was used to model the population pharmacokinetics of melatonin in 32 healthy males (aged 20-30 years, weight 62-85 kg) who had 15 blood samples drawn (11:00 to 08:00) on three occasions, separated by 2-4 weeks. Serum melatonin concentrations were measured by RIA. A pharmacokinetic model with a surge function was fitted to the data; dA/dt = K(IN) [1 + (AMP/(((t - T(0))/WID)(N) + 1))] - K(OUT) A, using NONMEM. Estimates were sought for the typical population parameter values and the intersubject variability (CV%) of; baseline amount of melatonin (A(B)), elimination rate constant (K(OUT)), peak amplitude (AMP), peak width (WID), acrophase (T(0)). The model stability was validated using a nonparametric bootstrap (100 samples with replacement). Population typical values (CV%) were: A(B); 103 ng (103%), K(OUT); 0.255 h(-1) (57.8%), AMP; 34.9 (108%), WID; 2.3 h (20.9%), T(0); 14.8 h (4.4%). Interoccasion variability (CV%) for; A(B) (12.3%), K(OUT) (29.5%) and AMP (9.1%) was much less than the corresponding intersubject variability. This approach has potential for application in clinical studies designed to characterize abnormal melatonin rhythms.