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Biomedical subjects

Y Touitou

Publications and source records attributed to Y Touitou.

At least 91 records · Page 5Linked to original sources
PubMed1993

In vitro glucocorticosteroid and mineralocorticosteroid biosynthesis in Conn's adenoma tissues.

The in vitro metabolism of [1,2-3H] deoxycorticosterone (DOC), [1,2-3H] 18-hydroxy-11-deoxycorticosterone (18-OHDOC) and [1,2-3H] 11-deoxycortisol (S) was studied in adrenal adenoma homogenates from patients with primary hyperaldosteronism. Tumor tissues actively converted deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone to 18-hydroxycorticosterone and aldosterone. Yields of cortisol and cortisone were also large showing that the tissues did not lack the zona fasciculata-like 11 beta-hydroxylation ability.

18-Hydroxycorticosterone↗
PubMed1993

Decreased nocturnal plasma melatonin levels in patients with recurrent acute intermittent porphyria attacks.

Acute intermittent porphyria (AIP) is a hereditary disease characterized biochemically by a defect in the heme pathway enzyme porphobilinogen deaminase. There is wide variability in the neurologic clinical expression of AIP, and the disorder remains latent in most gene carriers. The natural history of the disease and results in a porphyric rat model suggest a significant relationship between tryptophan metabolites and clinical expression of the disease. In the present study, we examined urine and blood tryptophan metabolite levels in AIP women before, during and after acute attacks and treatment by heme arginate. Heme arginate treatment promptly decreased total tryptophan levels (from 69 +/- 9, to 44 +/- 5, mean +/- SEM, mumole/l, p < 0.001), serotonin blood levels (from 629 +/- 103, to 356 +/- 80, nmole/l, p < 0.01) and the urinary excretion of 5-HIAA (from 3.9 +/- 0.6, to 2.2 +/- 0.4, mumole/mmole creatinine, p < 0.01). The plasma level of melatonin was found much lower than the normal control level at night (86.2 +/- 70.3, vs the normal range, 409 +/- 78.9, pmole/l +/- SEM) and day time (38.8 +/- 22.0, vs 75 +/- 13.7). Heme arginate treatment did not influence melatonin levels. Our results support the involvement of abnormal tryptophan metabolism in the pathophysiology of AIP acute attacks. Low melatonin plasma levels in porphyric women suggest that the defect of the pineal hormone may be responsible for the recurrent aspect of porphyric attacks. A desynchronization of biological rhythms in AIP patients may increase the inducibility of hepatic ALA synthase to environmental risk factors and, specially, to sex steroid hormones.

Adult↗
PubMed1993

Weekly changes in psychophysiological variables of 8- to 10-year-old school girls.

Three groups of schoolgirls 8, 9, and 10 years of age, respectively, self assessed sleep onset/offset and duration, as well as oral temperature and a set of cognitive measures, at school at 09:00, 11:00, 14:00, and 16:00 h on Mondays, Tuesdays, Thursdays, and Fridays (and/or Saturday) for 2 consecutive weeks (spring 1987 and 1989). The scores of a letter cancellation test exhibited neither daily nor weekly temporal variation at the age of 8 years [analysis of variance (ANOVA), p > 0.05]. In contrast, in the 10-year-olds, changes as a function of both time of day (peak time 14:00-16:00 h) and day of week (peak day Tuesday-Friday) were substantiated. Moreover, the time of best performance on the letter cancellation test varied systematically according to the day of the week (ANOVA, p = 0.000). Day of the week changes in the observed duration of sleep, self-rated fatigue, drowsiness, and attention changes were not detected in any of the age groups. It is hypothesized that temporal performance variations in the girls during the 7-day period was age related.

Age Factors↗
PubMed1993

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent.

Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/l) and magnesium (1.34 mmol/l) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/l) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.

Animals↗
PubMed1993

Kinetic changes of melatonin release in rat pineal perifusions at different circadian stages. Effects of corticosteroids.

The kinetic characteristics of melatonin release were documented in perifused pineal glands removed from rats sacrificed at six circadian stages (light/dark = 12:12): three during the light phase, i.e. 3, 7 and 11 hours after light onset (HALO), and three during the dark phase, i.e. 15, 19 and 23 HALO. Whatever the circadian stage, the melatonin release decreased during the first 3-4 h and then remained fairly constant and roughly similar up to 8 h of perifusion. However, the kinetics of the release in the first 3 h differed in perifusions of pineal glands removed during the light (progressive decline during 3 h) as compared to perifusions of pineal glands removed during the dark (sharp decline during the first hour and then a progressive decline until reaching a constant level after 3 h). As the effects of steroid administration on melatonin secretion are a matter of controversy, we also studied the direct effects and their circadian stage dependence, if any, of corticosterone, deoxycorticosterone and dexamethasone on melatonin secretion by pineal glands removed 7 HALO (about the middle of the light phase) and 19 HALO (about the middle of the dark phase). High concentrations of corticosterone (0.8 x 10(-3) mol/l) and dexamethasone (0.4 x 10(-3) mol/l) resulted in a significant (p < 0.001) inhibitory effect on melatonin production (about a 50% and a 30% decrease, respectively) whatever the circadian stage, whereas lower concentrations (10(-4)-10(-5) mol/l) of both steroids did not affect melatonin production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of a two-hour early awakening and of bright light exposure on plasma patterns of cortisol, melatonin, prolactin and testosterone in man.

Bright light is a synchronizing agent that entrains human circadian rhythms and modifies various endocrine and neuroendocrine functions. The aim of the present study was to determine whether and how the exposure to a bright light stimulus during the 2 h following a 2 h earlier awakening could modify the disturbance induced by the the sleep deprivation on the plasma patterns of hormones whose secretion is sensitive to light and/or sleep, namely melatonin, prolactin, cortisol and testosterone. Six healthy and synchronized (lights on: 07.00-23.00) male students (22.5 +/- 1.1 years) with normal psychological profiles volunteered for the study in winter. The protocol consisted of a baseline control night (customary sleep schedule) followed by three shortened nights with a rising at 05.00 and a 2 h exposure to either dim light (50 lux; one week) or bright light (2000 lux; other week). Our study showed a phase advance of the circadian rhythm of plasma cortisol without significant modifications of the hormone mean or peak concentration. Plasma melatonin concentration decreased following bright light exposure, whereas no obvious modifications of plasma testosterone or prolactin patterns could be observed in this protocol.

Adult↗
PubMed1992

Concurrent adrenocortical carcinoma and Conn's adenoma in a man with primary hyperaldosteronism. In vivo and in vitro studies.

This is a report of a rare and unusual case of adrenal pathology. A patient presented with clinical and biological signs of primary aldosteronism and computed body tomography scan led to our suspecting the presence of a left adrenocortical carcinoma. The in vitro studies performed on the resected tumour showed very low synthesis of mineralocorticoids and glucocorticoids. The patient could not be reexamined until 15 months later, when he still suffered hypertension; another tomography scan revealed a mass on the right adrenal gland. The studies performed on this second tumour confirmed the diagnosis of Conn's adenoma: active in vitro biosynthesis of 18-hydroxy-corticosterone and aldosterone from exogenous tritiated precursors.

Adenoma↗
PubMed1992

The in vitro effect of metyrapone on steroid synthesis in mice adrenals at different circadian stages.

The circadian rhythm of the in vitro biosynthesis of cortisol and cortisone in mice adrenals has been documented in the absence and presence of 0.1 mumol metyrapone, an inhibitor of steroid 11 beta-monooxygenase. After 3 weeks of synchronization with 12 h light:12 h darkness, adrenalectomy was performed at eight circadian stages: 0, 4, 9, 10, 13, 16, 21, and 22 h after light onset (HALO). Because it has been shown that mice adrenals could convert exogenous 11-deoxycortisol, the synthesis of 11-oxysteroids (cortisol+cortisone) in adrenal homogenates was studied from tritiated precursor. The pattern of steroid synthesis showed a maximum around the end (10 HALO) and a minimum at the beginning of the resting period (0 HALO); the variation was approximately 10%. A similar pattern was observed in the presence of a approximately 50% inhibiting dose of metyrapone. On the other hand, the percent inhibition of 11-oxysteroids synthesis was greater at the beginning of the resting period (0 HALO) and minimum around the end of the activity span (21 HALO), with an overall variation of 20%. However, the variations were statistically insignificant (unpaired t test).

Adrenal Glands↗
PubMed1991

Evidence for a new biologic pathway of androstenedione synthesis from 11-deoxycortisol.

17-Hydroxyprogesterone is a well-known precursor of androstenedione in adrenal biosynthesis. This study using sheep adrenal incubations demonstrates that 11-deoxycortisol, the precursor of cortisol synthesis, also can be a precursor of androstenedione. Indeed, our data show that androstenedione synthesis is negatively correlated to the synthesis of cortisol and cortisone. This fact allowed us to infer that this new pathway is closely related to the activity of the 11 beta-hydroxylase that is responsible for the synthesis of cortisol. Indeed, when the activity of this enzyme is impaired, 11-deoxycortisol follows the pathway that leads to androstenedione synthesis in the adrenals. This pathway could explain, at least in part, the marked increase of androstenedione observed in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency.

Adrenal Glands↗
PubMed1991

Diurnal changes in psychophysiological variables of school girls: comparison with regard to age and teacher's appreciation of learning.

Ninety-five nonresident girls of a private school volunteered for the study with the teachers' help as well as parental consent. Ages were approximately 8, 9, and 10 years. They were synchronized with diurnal activity from 0730 to 2100 h and nocturnal rest. Fatigue, drowsiness, and attention were self-rated using visual analogue scales; oral temperature was self-measured and a letter cancellation test was performed. Each of these variables was measured at school at 0900, 1100, 1400, and 1600 h on Mondays, Thursdays, Fridays, and Saturdays for two consecutive weeks in 1987 (March 30-April 11) and again in 1989 (March 13-25) when the youngest group had become 10 years old. According to conventional teacher evaluation of learning (learning performance) within each group, three subgroups were formed: top third, middle third, and bottom third. Time series (more than 50,000 data) were analyzed according to several statistical methods, but mainly chronograms with ANOVA. Similar diurnal changes in oral temperature were validated for each group and subgroups. The occurrence of a diurnal change in self-rated variables (fatigue and drowsiness) and score in letter cancellation was age related: no detection in the 8-year-old group (and subgroups) and validation (p less than 0.002) in 9- and 10-year-old groups (and respective subgroups). A good learning performance was associated with a reduced drowsiness in school girls of 9 and 10 years. Age-related, time-of-day differences in drowsiness (when detected) as well as learning performance effect were not associated with observed duration of sleep. Validated changes in self-rated fatigue were close to that of drowsiness. At 0900 h, girls of 9 and 10 years were more tired when belonging to the bottom third than top third subgroup. Whatever the time of day, self-rated attention was greater in the top than in the bottom third for these girls. Differences related to learning performance were validated in each grade. However, best scores were recorded for the bottom third in the 8-year-old group, while best scores were provided by top third subgroups in 10-year-old girls. It seems that in girls around 8 years of age, critical changes can be detected with regard to the (ontogenic?) occurrence of time-of-day differences in a set of psychophysiologic variables as well as influential effects of learning performance on the same variables. Reported finding are compatible with the hypothesis of circadian oscillators working at the level of the cortex of the human brain.

Age Factors↗
PubMed1990

Growth hormone (GH) and GH-releasing hormone response to ACTH 1-17 at different times of day. Evidence of a circadian stage dependence.

The effect of injection of ACTH 1-17 on the secretion of GH has been examined at three different circadian stages (07, 14 and 21 h) in the winter. Each week for six consecutive weeks the subjects were investigated before and after I.M. injection either of saline (controls) or 100 micrograms ACTH 1-17. Each subject was his own control. The peak plasma concentration of GH was always found 40 min after the injection. The larger absolute increase and the greater AUC curve were seen following the injections at 14.00 h and 21.00 h. The findings could not be attributed to an effect on GH-RH, since secretion of it remained unchanged during the test.

Adolescent↗
PubMed1990

Effect of shift work on the night-time secretory patterns of melatonin, prolactin, cortisol and testosterone.

In a study of the internal desynchronization of circadian rhythms in 12 shift workers, 4 of them, aged 25-34 years, agreed to be sampled every 2 h during their night shift (0000 hours to 0800 hours). They were oil refinery operators with a fast rotating shift system (every 3-4 days). We found marked changes in the secretory profiles of melatonin, prolactin and testosterone. Melatonin had higher peak-values resulting in a four-times higher amplitude than in controls. With respect to prolactin and testosterone, peak and trough times were erratic and the serum concentrations were significantly decreased in shift workers. Serum cortisol presented a decreased rhythm amplitude together with higher concentrations at 0000 hours in shift workers. This study clearly shows that fast rotating shift-work modifies peak or trough values and rhythm amplitudes of melatonin, prolactin, testosterone and cortisol without any apparent phase shift of these hormones. Whether the large rhythm amplitude of melatonin may be considered as a marker of tolerance to shift work, as reported for body temperature and hand grip strength, since it would help the subjects to maintain their internal synchronization, needs further investigation.

Adult↗
PubMed1990

Psychophysiological effects of early morning bright light exposure in young adults.

The effects of bright light on circadian rhythms in man are well documented. Nevertheless the theoretical basis and the rules for the practical utilization of light exposure as therapy need still to be better defined. The present study determined to what extent a 2-hr bright light exposure (0500-0700 h) improved the adjustment to an early rising in normal adults. Phase changes were assessed in subjective alertness, performance in several search tasks, time estimation, and a visual discrimination task, as well as in body motility, plasma cortisol concentrations, and body temperature. In comparison with a dim light exposure, the bright light resulted in increased motor activity during waking, in earlier peak of subjective alertness, and an improvement in performance speed in three out of five tasks in the morning. Cortisol and body temperature also were phase-advanced. In summary, light applied to a portion of the circadian cycle sensitive to phase advance shifts influenced rhythms with strong endogenous components (temperature and cortisol), while other rhythms with strong exogenous components were more sensitive to sleep deprivation caused by the early rising time.

Adult↗
PubMed1990

Cortisol and cortisone production in rat and mouse adrenal incubations.

The presence of 17 alpha-hydroxylase in rodent adrenals is debated. The presence in blood of mice of 11-deoxycortisol together with the absence of cortisol is well known. We demonstrated here the in vitro synthesis of 17 alpha-hydroxyprogesterone and cortisol from [3H]progesterone in rat and mouse adrenals. We have shown that these syntheses represented 45 and 28% of those of 11-deoxycorticosterone and corticosterone, respectively, from progesterone. These data clearly suggest the presence of a 17 alpha-hydroxylase activity in vitro in these rodents adrenals. In addition, a noticeable synthesis of cortisol (0.87-1.57% per mg tissue, i.e. 52-64% per incubation flask) from 11-deoxycortisol was also observed and was inhibited by 0.1-0.3 mumol of Metyrapone and SKF 12185. These results allow to underline that the adrenals of rat and mouse, two species commonly used in laboratory experiments, may be used for in vitro investigations on cortisol metabolism from exogenous radioactive precursors.

Adrenal Cortex Hormones↗
PubMed1990

[Legal time shifting and biologic rhythms: summer hour in question?].

In France daylight saving time is set on last sunday of march (legal time becomes GMT + 2 h instead of GMT + 1h) and set off last sunday of september. Fifteen years ago when it was established this change of time was generally welcomed by the public. Since then strong rejection reflexes have appeared and an association against the summer daylight saving time has been founded. The arguments sustained by the oponents to this system are based on economical, agricultural and/or health considerations. A growing number of individuals claim they cannot withstand the change of legal time and suffer from various troubles mainly fatigue and sleep disturbances. An alteration of biologic rhythms has been put forward by some to explain these troubles. We will here discuss the problems related to the change of legal time and especially those in the field of health. For the latter we will show that troubles when they are present can not ascribed to a desynchronization.

Biological Clocks↗