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Biomedical subjects

Y Touitou

Publications and source records attributed to Y Touitou.

At least 37 records · Page 2Linked to original sources
PubMed2001

Is melatonin circadian rhythm a physiological feature associated with healthy longevity? A study of long-living subjects and their progeny.

The study investigates the circadian rhythm (CR) of urinary 6-sulphatoxy-melatonin (aMT6s) in long-living (longevous) subjects and their progeny. The aim is to detect whether or not the melatonin CR is a physiological feature associated with healthy longevity. The aMT6s CR was investigated in 10 longevous subjects, 8 of their children and 9 of their grandchildren, all in good health. Control data were obtained respectively from 13 adult subjects and 9 young subjects, in good health, but characterized by a negative family history for longevity. All the subjects were born and living in the same city. The study was performed in the summer of 1996. The aMT6s CR was found to persist in longevous subjects, being characterized by a lower mesor and amplitude. The aMT6s CR was found not to show properties consistently different in children and grandchildren as compared respectively to their adult and young controls. Because of its preservation in longevous subjects, it can be argued that the melatonin CR is a physiological feature associated with healthy longevity. Because of the comparability of aMT6s CR in children and grandchildren, with respect to their controls without a positive family history of longevity, it can be argued that the melatonin CR is not a marker that can be used for an earlier identification of the candidates for longevity.

Adult↗
PubMed2001

Role of school schedule, age, and parental socioeconomic status on sleep duration and sleepiness of Parisian children.

The aim of the study was to assess the duration and quality of sleep of prepubertal (Tanner Scale level 1) physically and mentally healthy children as a function of school schedule (4 versus 4.5 days per week), age and grade (median age of 9.5 years for 4th grade versus median age of 10.5 years for 5th grade), school district (wealthy versus nonwealthy) in Paris, France, and parental socioeconomic status (high, medium, or low). We studied 51 girl and 44 boy volunteer pupils with written parental consent. The study lasted 2 weeks during the month of March. During the first study week, the children attended school 4.5 days, and during the second week, they attended school only 4 days without difference in the length of the school day. A sleep log was used to ascertain time of lights off for sleep and lights on at awakening, nighttime sleep duration, and self-rated sleep quality. A visual analog scale (VAS) was also used by pupils to self-rate the level of perceived sleepiness at four specific times of the school day. Conventional statistical methods (e.g., t and chi2 tests) were used to examine differences in mean values. Sleep duration, self-rated sleepiness, and subjective sleep quality were comparable (P > .05) by gender, school schedule, school district, and parental socioeconomic status. Overall, the sleep of this sample of Parisian children around 10 years of age was rather stable in its duration and timing, suggesting flexibility to adjust to the different school schedules.

Age Factors↗
PubMed2001

The effect of alcohol consumption on the circadian control of human core body temperature is time dependent.

The few controlled studies dealing with the action of alcohol on core body temperature in humans have focused on the effect of a single dose of ethanol and reported that it has a hypothermic effect. No studies report the effects of repeated ethanol intake over a 24-h period, a pattern of consumption much closer to the clinical condition of chronic alcoholism. We therefore designed a trial in which alcohol was repeatedly and regularly administered, with a total dose of 256 g. Nine healthy male volunteers (mean age 23.3 +/- 2.9 yr; range 21-30) each served as his own control. The circadian temperature rhythm was studied by a single-blind, randomized, crossover study that compared a 26-h alcohol session to a 26-h placebo session. The trial controlled for so-called masking effects known to affect temperature. The volunteers were in bed; the ambient temperature was maintained between 20 and 22 degrees C. Meals were standardized. And light was controlled during the night. All sessions took place between November and April. The two sessions were separated by 2 to 5 wk. Rectal temperature was monitored every 20 min throughout the trial. We found the standard hypothermic effect of alcohol in the early hours of the trial, during the daytime, but our principal result is that alcohol consumption induced a very significant hyperthermic effect (+0.36 degrees C) during the night and thereby reduced the circadian amplitude of core body temperature by 43%. The dramatic decrease of the amplitude of circadian temperature rhythm that we observed may explain, at least in part, some clinical signs observed in alcoholic patients, including sleep and mood disorders. We suggest that jet lag, shift work, and aging, which are known to alter body temperature, are aggravated by alcohol consumption.

Adult↗
PubMed2000

Evidence of prooxidant and antioxidant action of melatonin on human liver cell line HepG2.

The aim of this study was to evaluate melatonin cytotoxicity by measuring its effects on various cellular targets. Cell viability, intracellular reduced glutathione (GSH) level, and reactive oxygen species (ROS) production were assessed in the human liver cell line (HepG2), after incubation with increasing melatonin concentrations (0.1-10,000 microM). The incubation times tested were 24, 72, and 96 h for cell viability and intracellular GSH level, and 15 and 45 minutes for ROS production. Cellular target evaluations were possible in living cells by means of a new microplate cytofluorimeter. This technology was suitable for the assessment of cell viability, GSH level, and ROS overproduction with, respectively, neutral red, monochlorobimane (mBCl), and 2',7'-dichlorofluorescin diacetate (DCFH-DA) fluorescent probes. At the lowest melatonin concentrations (0.1-10 microM) and for a relatively short incubation time (24 h), the antioxidant effect of melatonin was revealed by an increased intracellular GSH level, associated to cell viability improvement. In contrast, after longer incubation (96 h), cell viability significantly decreased with these lowest melatonin concentrations (0.1-10 microM). Moreover, high melatonin concentrations (1,000-10,000 microM) induced GSH depletion. This oxidative stress is associated with ROS overproduction from 10 microM after only 15 minutes of incubation. This dual effect is strong evidence that, in vitro, melatonin can be both antioxidant and prooxidant on the human liver cell line, depending on the concentration and incubation time.

Antioxidants↗
PubMed2000

DHEA-sulfate causes a phase-dependent increase in melatonin secretion: a study of perifused rat pineal glands.

Steroid hormones affect various metabolic activities, including melatonin synthesis, in mammals and nonmammals. We report here the effects of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S), two steroids with weak androgen potency, on the levels of isoproterenol-stimulated melatonin released by perifused rat pineal glands removed in the middle of the light and dark spans [7 and 19 Hours After Light Onset (HALO), respectively] in a L/D 12:12 regimen. DHEA-S but not DHEA was found to have a direct action on beta-adrenergic-stimulated melatonin release. DHEA-S increased melatonin secretion (by 50-80%) dose-dependently in pineals obtained during the light span. This effect depended on the circadian stage, because at night (19 HALO), only the highest concentration (10(-3) M) of DHEA-S increased melatonin secretion (by 25%). In contrast, DHEA had no effect on melatonin release in pineals obtained during the light span. This work shows that DHEA-S but not DHEA was able to stimulate melatonin secretion by adrenergic-stimulated pineals removed during the light phase. It also suggests that the effects observed, or their intensity, or both depend on the circadian stage.

Adrenergic beta-Agonists↗
PubMed2000

Progesterone inhibits, on a circadian basis, the release of melatonin by rat pineal perifusion.

The effects of 10(-6) and 10(-9) M of progesterone were documented on isoproterenol-stimulated melatonin release by perifused pineal glands removed from female rats in diestrous at two different times of a 12 : 12 h light/dark cycle, 7 and 19 h after light onset (which corresponds to daytime and nighttime, respectively), to look for the existence of a circadian stage-dependence of the hormone effects. Three weeks before the experiment, the rats were synchronized with a 12 : 12 lighting regimen. Progesterone decreased by approximately 50% the release of melatonin during the light span, but not during the dark span. These results show the direct effects of this ovarian hormone on pineal melatonin release and strongly suggest a time-related effect of progesterone on pineal function.

Animals↗
PubMed2000

Marked 24-h rest/activity rhythms are associated with better quality of life, better response, and longer survival in patients with metastatic colorectal cancer and good performance status.

The rest/activity circadian cycle has been used as a reference for chemotherapy administration at specific times to improve tolerability and efficacy. Because cancer processes may be associated with alterations of circadian rhythms, the rest/activity cycle was monitored noninvasively to assess its relationship with tumor response, survival, and quality of life in 200 patients with metastatic colorectal cancer. Patients wore an actigraph, a wristwatch that records the number of accelerations per minute, for 3 days before receiving chronomodulated chemotherapy. The circadian rhythms in activity were estimated by two robust parameters: the autocorrelation coefficient at 24 h (r24), and the dichotomy index (I<O) for comparing amounts of activity when in bed and out of bed. Accurate data for inclusion, quality of life, response, and survival were available for 192 patients. Survival at 2 years was 5-fold higher (P = 10(-4)) in patients with marked activity rhythm (I<O in upper quartile) than in those with rhythm alteration (I<O in lower quartile). These results were supported by the multivariate Cox analysis. Multivariate regression analysis showed that circadian rhythms in activity (I<O; P = 3 x 10(-4)) and in WBCs (P = 0.03) as well as performance status (P = 0.02) were jointly prognostic of response. Patients with marked rest/activity rhythms also had better quality of life and reported significantly less fatigue. The individual rest/activity cycle provides a novel independent prognostic factor for cancer patients' survival and tumor response as well as a quantitative indicator for quality of life.

Adult↗
PubMed1999

Obsessive-compulsive disorder: evaluation of clinical and biological circadian parameters during fluoxetine treatment.

RATIONALE: Many biological abnormalities have been found in obsessive-compulsive disorder (OCD). The circadian rhythm investigations of different clinical and biological parameters may provide a comparison with depression. Fluoxetine is one of the efficient drugs in alleviating symptoms of OCD. The effect of fluoxetine can highlight some clues to the neurotransmitter alterations in the disorder. OBJECTIVE: The present study investigated clinical and biological circadian modifications in OCD patients during a fluoxetine treatment. METHODS: Daily clinical symptoms, and circadian rhythms of axillary temperature, plasma cortisol and plasma melatonin were assessed in eight patients suffering from OCD. These parameters were compared in the same patients, before and after an 8-week fluoxetine treatment period. RESULTS: A therapeutic effect of fluoxetine was obtained. No significant differences were observed either in daily clinical variations or in biological circadian rhythms measured before and after treatment. CONCLUSION: The therapeutic efficacy of fluoxetine was not related to the biological parameters assessed.

Adult↗
PubMed1999

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.

Acetylserotonin O-Methyltransferase↗
PubMed1999

Body temperature and locomotor activity as marker rhythms of aging of the circadian system in rodents.

Most biological functions present rhythmic variations. These rhythms are distinguished by their period and concern all the levels of biological life. Circadian rhythms follow a periodicity close to 24-h, they allow individuals to survive via adaptation to the periodic variations of environment. Throughout the aging process, modifications in circadian rhythms of endocrinological, metabolical and behavioural fields have been found in many animal species. This review updates the body of knowledge on aging-related alterations of the circadian rhythms of body temperature and locomotor activity: modifications in circadian profiles, modifications in the period of free-running rhythms, internal desynchronisations and modifications in entrainment ability of these rhythms.

Aging↗
PubMed1999

Evaluation in humans of the effects of radiocellular telephones on the circadian patterns of melatonin secretion, a chronobiological rhythm marker.

A decrease in melatonin secretion has been observed in small mammals under exposure to extremely low frequency electromagnetic fields. As there is some concern about possible health effects of the increasing use of radiocellular telephones emitting radiofrequency electromagnetic fields, we examined whether such fields would alter melatonin levels in the human. Volunteers were two groups totalling 38 men, 20-32 yr old. Exposures were to commercially available cellular telephones of the GSM 900 type (Global System for Mobile communication at 900 MHz) or DCS 1800 type (Digital Communication System at 1800 MHz), for 2 hr/day, 5 days/wk, for 4 wk, at their maximum power. Attention of the volunteers was sustained by TV projection of movies. Blood samples were collected hourly during the night and every 3 hr in the daytime. 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 to evaluate the persistence or late appearance of potential effects. Evaluated parameters were the maximum serum concentration, the time of this maximum, and the area under the curve of the hormone profile. Melatonin circadian profile was not disrupted in 37 young male volunteers submitted to a typical pattern of exposure to the electromagnetic fields generated by two common types of cell phones.

Adult↗
PubMed1999

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.

Adult↗
PubMed1998

Non-invasive estimation of the circadian rhythm in serum cortisol in patients with ovarian or colorectal cancer.

The variability in toxicity or efficacy of cancer chronotherapy among patients may be due to differences in circadian rhythm. Adequate assessment of circadian rhythm often requires repeated blood sampling over at least a 24-hr period; this cannot be a routine procedure. We attempted to assess the reliability of a 2-timepoint estimate of the 24-hr rhythm of serum cortisol in 19 healthy subjects, 19 women with ovarian cancer and 18 patients with metastatic colorectal cancer. The difference between daily maximum and minimum values (MAX-MIN) was compared with that observed between values at 08.00 and at 16.00 (H8-H16). As significant correlations were found between both variables in all groups, we conclude that the magnitude of circadian changes in serum cortisol may be estimated from blood samples collected at 08.00 and at 16.00. The clinical relevance and the prognostic value of this method of assessment are currently under evaluation in a larger-scale clinical trial.

Adult↗
PubMed1998

Plasma melatonin and cortisol in patients with obsessive-compulsive disorder: relationship with axillary temperature, physical activity, and clinical symptoms.

BACKGROUND: Many studies have found biological abnormalities in obsessive-compulsive disorder (OCD), although most of them have not been replicated. The investigation of melatonin rhythm may thus provide an indirect clue to neurotransmitter alterations, and allow a biological comparison with depression. METHODS: The circadian variations of plasma melatonin, plasma cortisol, axillary temperature, motor activity, and obsessive-compulsive symptoms have been documented on a circadian basis in 8 patients with OCD compared to 8 paired healthy volunteers. RESULTS: The circadian pattern of axillary temperature was slightly different in OCD patients when compared to control subjects. No significant difference between the two groups could be observed for any other variable studied. CONCLUSIONS: The discrepancies with previous studies are discussed on the basis of the methods used (patients and control subjects samples, biological measurement procedures). An alteration of temperature circadian rhythm hypothesis is suggested.

Adult↗
PubMed1998

[Melatonin: hormone and medication].

Melatonin (N-Acetyl-5-methoxytryptamine) is a hormone secreted mainly by the pineal gland or epiphyse and in smaller amounts by the retina. It is biosynthesized from tryptophan, the critical enzymatic step depends upon N-Acetyl-transferase (NAT). The circadian rhythm of melatonin is the same in man and all the laboratory animals studied until now with nocturnal plasma concentrations 3-10 times greater than during daytime. The secretion and release of melatonin depend upon a large number of exogenous and endogenous factors as e.g. sex, age, pubertal stage, menstrual cycle, drugs, season.... Light is the major regulating factor which acts through the retino-hypothalamic tract. Melatonin is considered as a transducer of the light signal forwarding to the organism the information about day length (relative length of day and night). It is a time-clue provider used by the organism to adapt itself to its environment.

Acclimatization↗
PubMed1997

Serum thymidine kinase levels are elevated and exhibit diurnal variations in patients with advanced ovarian cancer.

Deoxythymidine kinase (TK) is an enzyme involved in DNA synthesis whose serum activity reflects the proliferative activity of tumors and correlates with prognosis in various malignancies. In ovarian cancer, the value of s-TK has not been studied so far. Therefore the serum levels of TK were investigated in patients with advanced ovarian cancer. Because considerable diurnal fluctuations of s-TK levels were reported previously, repeated determinations were performed over a 48-h time span. Fourteen patients (mean age +/- S.D., 56.1 +/- 8.0 years) with advanced ovarian cancer and five healthy volunteers (30.2 +/- 3.5 years) were studied. Serial determinations of s-TK and serum CA 125 (s-CA 125) levels were performed over a 48-h time period. S-TK and s-CA 125 were elevated (> 4.7 U/l and > 35 U/ml) in 10 patients at least once over the 48-h period, respectively. Linear regression analysis showed a strong correlation between s-TK and s-CA 125. However, three patients with consistently normal s-CA 125 values (< or = 35 U/ml) had elevated s-TK levels, indicating that these two parameters may be independent in some patients. Both s-TK and s-CA 125 levels showed considerable diurnal changes over the 24-h period in individual patients, in marked contrast to normal subjects. Individual peak-trough differences ranged from 0.1-8.5 U/l or 5-268% for s-TK, and from 4-75 U/ml or 15-100% for s-CA 125. Peak-trough differences of s-TK > or = 100% were found in five patients. The circadian fluctuations of s-TK and CA 125 did not show a regular circadian pattern nor any temporal covariation. This study demonstrates for the first time that s-TK levels may be elevated in ovarian cancer. In some patients, s-TK levels may exhibit considerable, irregular diurnal fluctuations. Repeated determinations should therefore be performed in situations where this marker is relevant for patient monitoring.

Adult↗