Long-term (up to 20 years) effects of 50-Hz magnetic field exposure on immune system and hematological parameters in healthy men.

OBJECTIVES: The relationship between exposure to 50-Hz magnetic fields and human health is of increasing interest since associations have been found in brain cancer in adults and childhood leukemia. In this study we investigate the possible chronic (up to 20 years) effects of exposure to magnetic fields in humans. DESIGN AND METHODS: We examined the nocturnal profiles of red blood cells, hemoglobin, hematocrit, platelets, mean platelet volume, total white blood cells, lymphocytes, monocytes, eosinophils, basophils, neutrophils, Ig (Immunoglobulin) A, IgM, IgG, CD (cluster of differentiation) 3, CD4, CD8, natural killer cells, B cells, total CD28, CD8+ CD28+, activated T cells, interleukin (IL)-2, IL-6, and IL-2 receptor, in 15 men exposed chronically and daily for a period of 1-20 years, in the workplace and at home, to a 50-Hz magnetic field. The weekly geometric mean of individual exposures ranged from 0.1 to 2.6 µT. The results are compared to those of 15 unexposed men age-matched, with the same synchronization and physical activity that served as controls (individual exposures ranged from 0.004 to 0.092 µT). Blood samples were taken hourly from 20:00 h to 08:00 h. RESULTS: Exposure over a long period and on a daily basis to magnetic fields resulted in no changes in the levels or patterns of hematological and immune system variables. CONCLUSIONS: Our data show that a long-term exposure to 50-Hz magnetic fields does not affect the hematological and immune system functions or their profile in healthy men, at least for the variables studied, and suggest that magnetic fields have no cumulative effects on these functions.

Long-term (up to 20 years) effects of 50-Hz magnetic field exposure on blood chemistry parameters in healthy men.

OBJECTIVES: The potential effects of a chronic exposure to magnetic fields on blood chemistry in humanswere tested. DESIGN: We examined the nocturnal profiles and levels of the following blood parameters: electrolytes (sodium, potassium, chloride, calcium, magnesium, phosphorus), nonprotein nitrogenous compounds (uric acid, urea, creatinine), and glucose, in 15 men (38.0 ± 0.9 years) exposed chronically and daily for a period of 1-20 years, in the workplace and at home, to a 50-Hz magnetic field in search of any cumulative effect from those chronic conditions of exposure. The weekly geometric mean of individual exposures ranged from 0.1 to 2.6 µT. The results are compared to those obtained in our control group: 15 unexposed men of similar age (39.4 ± 1.2 years), with the same synchronization and physical activity that served as controls (individual exposures ranged from 0.004 to 0.092 µT). Blood samples were taken hourly from 20:00 h to 08:00 h. RESULTS: This work shows that subjects exposed over a long period (up to 20 years) and on a daily basis to magnetic fields experienced significant changes in serum sodium, chloride, phosphorus and glucose where an effect for field-hour interaction was noted for exposures greater than 0.3 µT. CONCLUSION: Our data suggest that long-term exposure to 50-Hzmagnetic fields (exposure>0.3 µT) in healthy men could induce some biological modifications of certain blood parameters, though their clinical relevance needs further investigation.

Twenty-four-hour profiles of urinary excretion of calcium, magnesium, phosphorus, urea, and creatinine in healthy prepubertal boys.

OBJECTIVES: Available data on 24-h urinary solute excretion in healthy children are sparse. We thus documented the daily and overnight variations of urinary electrolytes (calcium, magnesium, and phosphorus), urea, and creatinine in prepubertal (Tanner stage I) boys. DESIGN AND METHODS: Nine voluntary healthy prepubertal boys aged 10.8+/-0.11 years participated in this study. Concentrations of variables were quantified in daytime samples (collected between 07:00 h+/-30 min and 21:00 h+/-30 min) and nighttime samples (collected between 21:00 h+/-30 min and 07:00 h+/-30 min) in spring, during a period of 24-h every 3 h. RESULTS: Significant differences were found between daytime and nighttime excretion of calcium (p<0.05), magnesium (p<0.001), phosphorus (p<0.01), and urea (p<0.05), with high concentrations during the night. The 24-h solute/creatinine ratio was 0.072+/-0.008 mg/mg for calcium, 0.069+/-0.008 mg/mg for magnesium, 0.698+/-0.070 mg/mg for phosphorus, and 0.017+/-0.001 g/mg for urea. Statistically significant correlation analyses showed that urea and creatinine were positively associated with body mass index (BMI) (R=0.790, p=0.0113 for urea; R=0.889, p=<0.0013 for creatinine) and weight (R=0.717, p=0.0297 for urea; R=0.978, p=<0.001 for creatinine). The other urinary variables were independent of BMI and body mass. CONCLUSION: These data are of interest for the diagnosis of certain renal disease in prepubertal children.

Scorpion toxin of Androctonus australis garzonii induces neuropeptide Y release via bradykinin stimulation in rat atria and kidneys.

The ability of scorpion toxins to produce hemodynamic alterations is well documented but all mediators implied in cardiovascular disturbances are not known. In the present investigation we studied the effect of North African Androctonus australis garzonii scorpion toxin on neuropeptide Y (NPY) release from rat atria and kidneys by a perifusion system in vitro. To further understand the mechanisms of the scorpion toxin action on NPY release, the effects of icatibant (HOE 140, a selective bradykinin-B2 receptor antagonist), tetrodotoxin (TTX, a sodium channel antagonist) and diltiazem (a calcium channel antagonist), and the effect of the scorpion toxin on bradykinin (BK, a potent vasorelaxant peptide of the kinin group) release were studied in both tissues. We showed that the scorpion toxin (10(-6)M) increased the NPY release from both atria (35%) and kidneys (40%). This increase was significantly (p<0.001) inhibited by HOE 140 (10(-5)M). The scorpion toxin (10(-6)M) enhanced BK secretion in both atria (52%) and kidneys (55%). Diltiazem (10(-5)M) and TTX (10(-5)M) decreased by 45-75% NPY levels induced by scorpion toxin in both organs. The results show that A. australis garzonii scorpion toxin stimulates NPY release from both rat atria and kidneys, and suggest that the toxin induces NPY release via BK stimulation through B2 receptors. This effect appears to involve calcium and sodium channel activation.

Daily profiles of salivary and urinary melatonin and steroids in healthy prepubertal boys.

The aim of this study was to assess the circadian hormonal profile of two circadian markers, melatonin and cortisol, as well as other steroids in prepubertal boys (Tanner stage I). Nine volunteer healthy prepubertal boys aged 10.8 +/- 0.11 years participated in this study. Concentrations of daily salivary and urinary hormones were quantified around 24-hours, every 3 hours, in daytime samples (collected between 07.00 h +/- 30 min and 21.00 h +/- 30 min) and night-time samples (collected between 21.00 h +/- 30 min and 07.00 h +/- 30 min). Significant differences (p < 0.01) were found between day- and nighttime secretion of salivary melatonin and urinary 6-sulphatoxymelatonin, whereas no significant differences were found between day- and nighttime secretion of salivary and urinary cortisol nor between day- and nighttime secretion of 17-hydroxycorticosteroids (17-OHCS). The circadian profiles of salivary melatonin and cortisol showed large amplitude with a peak occurring at night (approximately 03.00 h) for melatonin and in the early morning (between 06.00 and 09.00 h) for cortisol. The curve patterns of the urinary 6-sulphatoxymelatonin and steroids (free cortisol and 17-OHCS) were coherent with data on saliva. The pattern of salivary androstenedione and testosterone were undetectable due to the very low concentrations of these steroids in the saliva of the prepubertal children. A strong significant positive correlation was observed between the daily salivary melatonin levels and the daily urinary 6-sulphatoxymelatonin excretion (R = 0.968, p < 0.001), and between free urinary cortisol and urinary 17-OHCS (R = 0.733, p = 0.025). The salivary and urinary hormones studied were independent of body mass index. This study shows the relevance of salivary cortisol and melatonin, although lower than in plasma, in testing adrenal and pineal function as markers of circadian rhythms. The data are of interest for the diagnosis and treatment of chronobiological disorders in prepubertal children.

Melatonin and environmental lighting regulate ALA-S gene expression and So porphyrin biosynthesis in the rat harderian gland.

The main porphyrin in rodent Harderian glands (HGs) is the heme precursor protoporphyrin IX (PPIX). Rhythmic variations in PPIX levels have yet to be studied in rodent HGs. Moreover, the mode of regulation of heme biosynthesis in this organ is poorly documented in the rat. The aim of this study was to determine day-night PPIX levels as well as day-night activity and mode of expression of the porphyrinogenic enzymes delta-aminolevulinate synthase (ALA-S) and ferrochelatase (Fech) in the rat HG. The mRNA expression of ABCG2/Bcrp1 was also investigated. Male Wistar rats acclimatized to 12 h light (L): 12 h dark (D) cycles were sacrificed in the middle of both the L and D spans, and HG and liver tissues were collected. We report here that the HG contains an extremely high level of PPIX, 630- to 670-fold higher than in the liver, without a day-night difference, which is the consequence of both low Fech gene expression (5- to 7-fold lower than in the liver) and ALA-S over-expression (4- to 7-fold higher in the HG than liver). Fech and PPIX transporter ABCG2/Bcrp1 do not exhibit day-night variation, whereas HG ALA-S levels are significantly higher during the scotophase. Interestingly, when melatonin (10 mg/kg) is administered in the middle of the light phase, it increases ALA-S mRNA levels in the HG to the ones observed during the middle of the D span. Continuous light exposure abolishes the day-night ALA-S variation in the HG that is observed under standard 12 L:12 D conditions. Our results suggest that melatonin and environmental lighting regulate ALA-S gene expression in the rat HG.

Influence of electromagnetic fields emitted by GSM-900 cellular telephones on the circadian patterns of gonadal, adrenal and pituitary hormones in men.

The potential health risks of radiofrequency electromagnetic fields (RF EMFs) emitted by mobile phones are currently of considerable public interest. The present study investigated the effect of exposure to 900 MHz GSM radiofrequency radiation on steroid (cortisol and testosterone) and pituitary (thyroid-stimulating hormone, growth hormone, prolactin and adrenocorticotropin) hormone levels in 20 healthy male volunteers. Each subject was exposed to RF EMFs through the use of a cellular phone for 2 h/day, 5 days/ week, for 4 weeks. Blood samples were collected hourly during the night and every 3 h during the day. Four sampling sessions were performed at 15-day intervals: before the beginning of the exposure period, at the middle and the end of the exposure period, and 15 days later. Parameters evaluated included the maximum serum concentration, the time of this maximum, and the area under the curve for hormone circadian patterns. Each individual's pre-exposure hormone concentration was used as his control. All hormone concentrations remained within normal physiological ranges. The circadian profiles of prolactin, thyroid-stimulating hormone, adrenocorticotropin and testosterone were not disrupted by RF EMFs emitted by mobile phones. For growth hormone and cortisol, there were significant decreases of about 28% and 12%, respectively, in the maximum levels when comparing the 2-week (for growth hormone and cortisol) and 4-week (for growth hormone) exposure periods to the pre-exposure period, but no difference persisted in the postexposure period. Our data show that the 900 MHz EMF exposure, at least under our experimental conditions, does not appear to affect endocrine functions in men.

Effect and mechanisms underlying scorpion toxin action from Androctonus australis garzonii on atrial natriuretic peptide in rat atria: an in vitro study.

Scorpion envenomation is considered public health problem in Northern African countries. The mechanisms of cardiac dysfunction following scorpion envenomation are not fully understood. This study examined the effect and mechanisms underlying scorpion toxin action from Androctonus australis garzonii on atrial natriuretic peptide (ANP) release from rat atrium using in vitro organ perifusion. Male Sprague Dawley rats were used in this study. Three experiments were conducted. In experiment 1, atrial tissues were exposed either to Krebs-bicarbonate buffer medium (control) or to scorpion toxin (10(-8) M to 10(-6) M). In experiment 2, animals were chemically sympathectomized with a single intraperitoneal injection of 6-hydroxydopamine (6-OHDOPA) at a dose of 40 microg/g 24 h before sacrifice. Vehicle-treated rats served as control. Atrial tissues were collected and perifused in the presence of 10(-6) M scorpion toxin. In experiment 3, atrial tissues were exposed to 10(-6) M scorpion toxin either in the absence or presence of 10(-6) M propranolol (a beta-adrenoceptor blocker), or 10(-6) M tetrodotoxin (a sodium channel blocker). ANP levels released in the perifusion medium were determined by radioimmunoassay. The scorpion toxin at 10(-6) M induced a significant (p<0.01) increase (106%) in ANP levels. This effect was decreased (20%) by 6-OHDOPA. Propranolol and tetrodotoxin significantly (p<0.01) inhibited 55% and 60%, respectively, the toxin-induced ANP release. The data show that the North African scorpion toxin from Androctonus australis garzonii increases the ANP release in rat atrium through stimulation of sympathetic cardiac nerves and sodium channels activation.

Aging and photoperiod affect the daily rhythm pattern of atrial natriuretic peptide in the rat atrium.

This study investigates the release characteristics of atrial natriuretic peptide (ANP) from young (10 weeks) and old (22 months) rat atrium. Levels of ANP release from samples of atrium were studied by organ perifusion. Rats were exposed to light:dark (LD) cycles of 12:12 or 18:6 and sacrificed at different zeitgeber time (ZT) points: ZT0, ZT6, ZT8, ZT12, ZT16, and ZT19 for LD 12:12 or ZT0, ZT9, ZT16, ZT18, ZT20, and ZT 21.5 for LD 18:6. The heart was collected, and the right atrium was removed, weighed, and perifused with Krebs-bicarbonate buffer for 100 min, including a period of 50 min for stabilization of secretion rate. ANP concentrations released by atrium did not differ between the two age groups either under LD 12:12 or under LD 18:6, except at the light:dark transition under LD 12:12 conditions where ANP levels were significantly (P<0.05) lower in young compared to old rats. ANP exhibited daily variations in concentrations under LD 12:12, with a peak during the beginning of photophase (ZT0) in young rats and a peak at the beginning of scotophase (ZT12) in old animals. These variations were strongly modified under LD 18:6, where the pattern of the release exhibited a peak during the light phase at ZT16 in both young and old rats. This strongly suggests that the atrial ANP rhythm is dependent on the environmental light:dark cycle. Moreover, the total ANP levels released by atria in old rats were significantly increased under LD 18:6 compared to standard LD 12:12. This observation strongly suggests that old animals are more sensitive to a photoperiodic change. In conclusion, our results show that ANP concentrations in the rat atrium exhibit daily variations which are significantly affected by the daylength (photoperiod) change in aged rats.

Epidemiological and aetiological study on tinea pedis and onychomycosis in Algeria.

Epidemiological studies on tinea pedis and onychomycosis, common fungal infections, have been conducted in many parts of the world. There are currently no studies of tinea pedis and/or onychomycosis in Algeria. The aim of this paper was to study the epidemiology of foot diseases, including tinea pedis and onychomycosis and to identify the aetiological factors of these infections in outpatients attending the Department of Dermatology of the Central Hospital of Army in Algiers, Algeria. A total of 1300 male subjects, mean age 35.9 +/- 16 years (range: 16-80) were recruited during the period November 2003 to November 2004 and were clinically examined. A complete dermatological examination was performed on all subjects, and skin and nail specimens of the feet were taken from those patients presenting signs of tinea pedis and/or onychomycosis for microscopy and fungal culture. Clinical diagnosis for tinea pedis and onychomycosis was suspected in 249 and 72 subjects, respectively, and confirmed in 197 and 60 cases, respectively, by positive cultures, resulting in a global prevalence of tinea pedis and toenail onychomycosis of 15% and 4.6% respectively. The age groups most commonly infected were 50-59 and 20-29 years. The yeast species Candida parapsilosis and the dermatophytic species Trichophyton rubrum were shown to be the most common pathogens in both tinea pedis (C. parapsilosis 20.4%; T. rubrum 17%) and onychomycosis (T. rubrum 35%; C. parapsilosis 28.3%). This is the first investigation dealing with fungal foot diseases in Algeria. The clinical and epidemiological data collected would serve as reference for future research and may be useful in the development of preventive and educational strategies.

The phasing of circadian rhythms in mice kept under normal or short photoperiods.

Mammals represent a multi-oscillatory system. Not only different rhythmic function but also a certain rhythmic function may be controlled by several oscillators. Also, the LD cycle, though being the main zeitgeber, may have different effects on different rhythmic functions. The aim of the present study was to investigate putative changes of internal phase relationships between different rhythms and their phase relationship with respect to the light-dark cycle following a gradual lengthening of the dark time. The investigations were carried out on adult female mice (HaZ:ICR). Animals were initially kept in a 12:12 h LD cycle. The dark time was then lengthened once a week by delaying the time of lights-on by 1 h until an L/D=6:18 h was reached. The motor activity was recorded continuously. The daily profiles of food intake, liver glycogen and melatonin in the serum and the pineal gland were estimated as transverse studies under L/D=12:12 h and L/D=6:18 h. Under short-day conditions (L/D=6:18 h), the evening onset of the main maximum of motor activity and food intake was delayed in relation to lights-off and the onset of the secondary maximum in the morning was advanced in relation to lights-on. Similar phase changes were found with respect to the onset of glycogen synthesis and its breakdown. In the case of melatonin, the rise and the fall occurred earlier or later, respectively, and the phase differences with respect to lights-off and lights-on became smaller. If the mid-point between the evening and morning onsets of activity and food intake and between the rises and falls of glycogen and melatonin concentrations are considered, then the changes in all rhythmic functions were similar. Consequently, the phase relationships between different rhythmic functions and with respect to the light-dark cycle, and thus the internal and the external temporal order, were preserved under different light-dark ratios. Also, the results are in good accordance with a modified two-oscillator model where lights-off triggers advances of an evening oscillator and lights-on delays a morning oscillator.

Old rats are more sensitive to photoperiodic changes. A study on pineal melatonin.

After having previously demonstrated that beta-adrenergic stimulation of melatonin under a standard light:dark (LD) cycle regimen of 12:12 is more effective in young than in old pineal glands, we have now studied how the daylength change LD 18:6 affects pineal melatonin secretion and its regulation by the beta-adrenergic system. Young (10 weeks) and old (22 months) male Wistar rats were synchronized with either a standard LD 12:12 for 4 weeks, or acclimatized under the same LD conditions for 4 weeks, then subjected to a long LD 18:6 photoperiod for 1 week. The rats were sacrificed at three time samplings: 0, 4, and 7h after dark onset (HADO) for LD 12:12 or 0, 2, and 3.5 HADO for LD 18:6. Pineal glands were collected and perifused for 480 min. Isoproterenol (10(-4)M) was infused for 20 min, 4h 10 min after the beginning of the perifusion. Basal levels of melatonin production in the young rats displayed a 1.5-2.5-fold increase compared to those in the old rats. Interestingly, mean basal melatonin levels in old rats under standard LD 12:12 conditions were significantly higher (P<0.05) than mean levels at the same relative dark phase intervals under LD 18:6 conditions. Isoproterenol stimulated melatonin production in both young and old rat pineal glands, regardless of time sampling or photoperiodic conditions. The magnitude of the response to 10(-4)M isoproterenol infusion in old pineals was approximately half that found in young glands (P<0.001), and tended to be higher under LD 12:12, in both young and old rat pineal glands, although no significant difference was found in melatonin response between the two photoperiods (P>0.05). This study shows that basal pineal melatonin levels in old rats are more sensitive to photoperiod changes than in young rats. These results also demonstrate that isoproterenol can stimulate both young and old rat pineal glands irrespective of time or photoperiod and confirm previous findings, showing that the melatonin response to isoproterenol is age-dependent and that pineal gland response to isoproterenol is not photoperiod-dependent, at least under our experimental conditions.

Lack of effect of ghrelin treatment on melatonin production in rat pineal and Harderian glands.

The effects of ghrelin, a peptide hormone secreted from the stomach, on melatonin remain unknown. The aim of the study was to investigate possible ghrelin-melatonin interactions by studying the effect of ghrelin treatment on melatonin production in rat pineal and Harderian glands. Young (9 weeks) and old (20 months) male Wistar rats, maintained under a light:dark cycle regimen of 12:12, were assigned randomly to either a single subcutaneous (s.c.) injection of saline or ghrelin (1 microg/rat or 15 microg/rat) 1 h before sacrifice in the middle of the dark phase, or repeated s.c. saline or ghrelin injections (15 microg/rat), 3, 2 and 1 h before sacrificed in the middle of the dark phase. Neither ghrelin doses (1 microg/rat or 15 microg/rat) nor type of treatment (acute or repeated) influenced melatonin levels or the melatonin synthesizing enzymes N-acetyltransferase and hydroxyindole-O-methyltransferase activities, either in pineal gland or in Harderian glands. At the concentrations used, ghrelin does not influence melatonin production in rat pineal and Harderian glands, and therefore is not involved in the regulation of melatonin secretion, at least under our experimental conditions.

Diazepam affects both level and amplitude of rat locomotor activity rhythm but has no effect on core body temperature.

The present study investigates the effects of a chronic administration of diazepam, a benzodiazepine widely used as an anxiolytic, on locomotor activity and body core temperature rhythms in male Wistar rats housed under 12 : 12 light : dark (LD) cycle conditions. Diazepam was administered subcutaneously for 3 wks in a dosage of 3 mg/kg body weight/day, 1 h before the onset of darkness. Diazepam increased the level of locomotor activity from the first day until the end of treatment, and also increased the amplitude of the activity circadian rhythm, but only on the third wk of treatment. Diazepam exerted no effects on the length of the period and did not affect the phase of the locomotor activity rhythm. The body temperature rhythm of rats was affected neither by short-term (a single injection) nor by long-term (every day for 3 wks) diazepam treatment. Diazepam lacked effect on body core temperature even on the first day of administration, thereby ruling out the possibility of drug tolerance development. The fact that diazepam affects locomotor activity, but not core body temperature, suggests that different mechanisms mediate the actions of diazepam on locomotor activity and on core body temperature.

Isoproterenol-stimulated melatonin production by perifused rat pineal glands: age- and time-related effects.

OBJECTIVES: The purpose of this study was to investigate and compare the effects of the beta-adrenergic agonist, isoproterenol, on induced increase in melatonin production in the pineal gland of young and old rats, at different circadian stages. MATERIALS AND METHODS: We report here the effects of 10(-6) M isoproterenol-stimulated melatonin production by perifused pineal glands obtained from young (55 day old) and old (21 month old) male Wistar rats acclimatised to light:dark cycles regimen of 12:12 for 3 weeks. Pineal glands were collected at different circadian stages: 3, 7, 11, 15, 19 and 23 hours after light onset (HALO), and perifused for 510 min. RESULTS: The basal levels of melatonin production in the young rats were approximately twice greater than those of the old rats. Isoproterenol stimulated melatonin production in both young and old rat pineal glands, whatever the circadian stage. The intensity of the response to 10(-6) M isoproterenol infusion was greater in young than in old rat pineal glands (P<0.001), with a trend towards an increase during the light phase, at 7 HALO, in both young and old rat pineal glands, although this trend towards increased melatonin response did not reach statistical significance (P>0.05). CONCLUSIONS: These results show that isoproterenol is able to stimulate both young and old rat pineal glands whatever the circadian stage. The magnitude of isoproterenol stimulation is greater in young than in old glands. Our results also suggest that the pineal gland response to isoproterenol is not dependent on circadian stage, at least, under our experimental conditions.

Daily variation in the concentration of neuropeptide Y in the rat atrium: effects of age and photoperiodic conditions.

This study investigates the release characteristics of neuropeptide Y (NPY) from young (10 weeks) and old (22 months) rat atrium. Levels of NPY release from samples of atrium were studied by organ perifusion. Rats were exposed to light:dark (LD) cycles of 12:12 or 18:6 and sacrificed at different circadian stages: 0, 4, 7, 12, 18, and 20 h after dark onset (HADO) for LD 12:12 or 0, 2, 3.5, 6, 15, and 22 HADO for LD 18:6. The heart was collected, and the right atrium was removed, weighed, and perifused with Krebs-bicarbonate buffer for 100 min, including a period of 50 min for stabilization of secretion rate. NPY concentrations released by atrium did not differ between the two age groups. NPY exhibited daily variations in concentrations in LD 12:12, with a peak during the end of scotophase, at 12 HADO, in both the young and old rats. These variations were strongly modified in LD 18:6, where the pattern of the release exhibited two peaks occurring during the two thirds of dark (3.5 HADO) and light (22 HADO) periods. This strongly suggests that the NPY rhythm is dependent on the environmental light:dark cycle. In this paper we show that NPY concentrations in the rat atrium exhibit daily variations, which are maintained with ageing. Moreover, photoperiod greatly influences NPY levels in the atrium.

Ex vivo studies on the acute and chronic effects of DHEA and DHEA-sulfate on melatonin synthesis in young- and old-rat pineal glands.

This study investigates the effects of acute and chronic injections of the neurosteroid dehydroepiandrosterone (DHEA) and its sulfate DHEA-S on pineal gland melatonin synthesis. Pineal melatonin production and plasma melatonin levels were investigated in young (9-week-old) and old (27-month-old) male Wistar rats. DHEA or DHEA-S have been administered acutely in a single intraperitoneal injection at a dosage of 50, 250, or 500 microg per animal, or on a long-term basis, i.e., for 8 days at a dosage of 100 microg per animal, 1 h before the onset of darkness. DHEA, at a dose of 50, 250, or 500 microg per animal, administered acutely to rats had no significant effects on pineal melatonin production whatever the age of the animals. In contrast, 500 microg DHEA-S induced a significant increase in the pineal melatonin content (15% in young animals and 35% in old animals) and the activity of N-acetyltransferase, the rate-limiting enzyme for melatonin synthesis in the pineal gland, (40% in young animals and 20% in old animals), without altering the activity of hydroxyindole-O-methyltransferase whatever the age of the animals. At lower concentrations (50 or 250 microg) DHEA-S had no effect on pineal melatonin production regardless of the age of the rats. Chronic injection of DHEA or DHEA-S at a dose of 100 microg had no effect on pineal melatonin or NAT and HIOMT activities in the two age groups. This work shows that DHEA-S (and not DHEA) is able, at pharmacological concentrations, to stimulate melatonin production by rat pineal glands regardless of the age of the animals.

Effects of diazepam and its metabolites on nocturnal melatonin secretion in the rat pineal and Harderian glands. A comparative in vivo and in vitro study.

We investigated the effects of diazepam (DZP) and its three metabolites: nordiazepam (NZP), oxazepam (OZP), and temazepam (TZP) on pineal gland nocturnal melatonin secretion. We looked at the effects of benzodiazepines on pineal gland melatonin secretion both in vitro (using organ perifusion) and in vivo in male Wistar rats sacrificed in the middle of the dark phase. We also examined the effects of these benzodiazepines on in vivo melatonin secretion in the Harderian glands. Neither DZP (10(-5)-10(-6)M) nor its metabolites (10(-4)-10(-5)M) affected melatonin secretion by perifused rat pineal glands in vitro. In contrast, a 10(-4)M suprapharmacological concentration of DZP increased melatonin secretion of perifused pineal glands by 70%. In vivo, a single acute subcutaneous administration of DZP (3 mg/kg body weight) significantly affected pineal melatonin synthesis and plasma melatonin levels, while administration of the metabolites under the same conditions did not. DZP reduced pineal melatonin content (-40%), N-acetyltransferase activity (-70%), and plasma melatonin levels (-40%), but had no affects on pineal hydroxyindole-O-methyltransferase activity. Neither DZP nor its metabolites affected Harderian gland melatonin content. Our results indicate that the in vivo inhibitory effect of DZP on melatonin synthesis is not due to the metabolism of DZP. The results also show that the control of melatonin production in the Harderian glands differ from that observed in the pineal gland.