A Bogdan

Pierre and Marie Curie University - Paris 6, Lutetia Parisorum, Île-de-France, France

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Publications (96)256.36 Total impact

  • Yvan Touitou, Andre Bogdan
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    ABSTRACT: Almost all cardiovascular events occur according to a circadian rhythm with a greater frequency in the morning on waking and when resuming activity, the mechanism and precise triggering events for myocardial infarction (MI) are not yet fully known. Multiple biologic functions show a diurnal and/or seasonal variation that may contribute to adverse cardiac outomes. Exogenous factors may also modulates these variations. The MI peak usually occurs between 07:00 and 12:00 h. This timing corresponds to the concurrent increase in platelet aggregability, blood concentration of cortisol, catecholamines, angiotensin II, myocardial oxygen demand and coagulation activity, while fibrinolytic activity is decreased. In this review paper we will point out the biological rhythms of a number of functions involved in acute myocardial infarction e.g. blood pressure, hormonal determinants, cholesterol, among others.
    Biological Rhythm Research 06/2007; 38(3):169-179. · 1.22 Impact Factor
  • Yvan Touitou, André Bogdan
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    ABSTRACT: Chronobiotics are substances that adjust the timing of internal biological rhythms. Many classes of drugs have been claimed to possess such properties and arouse growing interest as the circumstances for their use in sleep disturbances caused by circadian rhythms alterations (delayed or advanced sleep-phase syndromes, non-24-h sleep-wake disorders, jet lag, shift work sleep disorders and so on) have become progressively more frequent. Amongst the substances potentially presenting chronobiotic properties, a consensus seems to be reached on the possible use of melatonin or its agonists to shift the phase of the human circadian clock, but optimizing the dose, formulation and especially the time of administration require further studies.
    Physiology & Behavior 03/2007; 90(2-3):294-300. · 3.03 Impact Factor
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    ABSTRACT: An impairment of immunity is reported after long-haul flights, and the mild hypobaric hypoxia caused by pressurization in the passenger airline cabin may contribute to it. In this controlled crossover study, the effects of two levels of hypoxia, equivalent to 8000 and 12,000 feet above sea level, on the rhythm of CD3, CD4, and CD8 lymphocytes and plasma concentrations of the immunoglobulins A, G, and M were assessed. Fourteen healthy male volunteers, aged 23 to 39 years, spent 8.5 h in a hypobaric chamber (08:00 to 16:30 h), simulating an altitude condition at 8,000 feet. This was followed by an additional 8.5 h study four weeks later simulating altitude conditions at 12,000 feet. The variables were assayed every 2 h over two 24 h cycles (control and hypoxic-exposure cycles). No significant effect of hypoxia on the studied circadian immune profiles were found. Therefore, the authors conclude that mild hypobaric hypoxia does not seem to be responsible for any quantitative changes during long-haul flights in the immune assays commonly used in routine clinical medicine practice.
    Chronobiology International 02/2007; 24(1):87-98. · 2.88 Impact Factor
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    ABSTRACT: The disruption of melatonin secretion has been largely studied since it could provide the missing link between the exposure to 50/60-Hz electric and magnetic fields (EMF) and the occurrence of possible health effects as the "melatonin hypothesis". We analysed the current experimental data from animal (rodents) where contradictory results have been observed, and from human studies conducted with volunteers or with workers in various conditions of exposure, biological endpoints and metrics. In humans, even in long lasting exposures, the overall results of these studies do not support the "melatonin hypothesis". It is unlikely that malignancies or mood disorders reported by people exposed to 50/60-Hz EMF could be related to the disruption of the melatonin levels.
    Cancer Causes and Control 06/2006; 17(4):547-52. · 2.96 Impact Factor
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    ABSTRACT: Mild hypobaric hypoxia caused by pressurisation may contribute to alter rhythmicity after long-haul flights, independently of the number of time zones crossed. In this controlled crossover study, we assessed the effects of two levels of hypoxia, equivalent to 8000 ft and 12,000 ft above sea level, on the rhythm of plasma concentrations of three hormones: testosterone, LH, and FSH. A hypoxia-induced decrease in LH and FSH has often been reported during mountaineering while testosterone is considered a marker of fatigue. Sixteen healthy male volunteers, aged 23-39 years, spent 8 h in a hypobaric chamber (08:00-16:30), simulating conditions at 8000 ft. This was followed by an additional 8 h four weeks later, simulating conditions at 12,000 ft. Plasma hormones were assayed every 2 h over two 24-h cycles (control and hypoxic-exposure cycles). We found no significant effects of hypoxia on the circadian profile of the gonadal axis hormones and, therefore, conclude that these hormones do not serve as valuable markers of post-flight alterations of the circadian system in human.
    Steroids 04/2006; 71(3):214-21. · 2.72 Impact Factor
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    ABSTRACT: Fatigue is often reported after long duration flights. Mild hypobaric hypoxia caused by pressurisation may be involved in this effect through disruption of circadian rhythms, independently of the number of time zones crossed. In this controlled crossover study, we assessed the effects of two levels of hypoxia equivalent to 8000 and 12,000 ft on the circadian rhythm of plasma cortisol, a marker of the circadian time structure. Sixteen healthy young male volunteers (23-39 years) were exposed in a hypobaric chamber for 8 h (08:00-16:00 h) to 8000 ft, followed 4 weeks later to 12,000 ft. Plasma cortisol was assayed during two 24-h cycles (control and hypoxic exposure) every 2h in all subjects. We found a significant change in the pattern of cortisol secretion during both hypoxic exposures, with an initial fall in cortisol followed by a transient rebound, whereas the phase and the 24-h mean level remained unchanged. The change in cortisol pattern followed the alterations in autonomic balance assessed by heart rate variability (HRV) spectral analysis. The normalised high frequencies and the low-to-high frequencies ratio showed a significant shift toward sympathetic dominance with some differences in time course for both altitudes studied. HRV analysis improved the interpretation of cortisol 24-h profiles. Our data, which strongly suggest that prolonged mild hypoxia alters the expression of cortisol circadian rhythm, should be taken into account to interpret secretory rhythm changes after transmeridian flights.
    Steroids 12/2005; 70(12):803-10. · 2.72 Impact Factor
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    André Bogdan, Belal Bouchareb, Yvan Touitou
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    ABSTRACT: Although the effects of short-term fasting on serum leptin concentrations are known, those resulting from long-lasting modifications of food intake schedule, as during the month of Ramadan, have not yet been extensively studied. Therefore, serum concentrations of leptin were measured around the clock at 4-hourly intervals before the beginning of Ramadan and on the twenty-third day of Ramadan daytime fasting in ten male subjects keeping the same usual activity pattern and general synchronisation in both situations. Time series were analysed with repeated measures ANOVA and Cosinor. No significant changes in amplitude or 24 h mean concentration were seen, but significant shifts of 5 h 30 min in peak and trough serum leptin levels were found on the twenty-third day of Ramadan.
    British Journal Of Nutrition 05/2005; 93(4):515-8. · 3.34 Impact Factor
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    ABSTRACT: Adrenal function and aging have been the object of intense interest in recent years. In this study we analyzed morning (08:00 h) serum cortisol concentrations from a sample of Chinese subjects aged from 31 to 110 years. These levels differed according to age, health status and sex, although the sex difference was confirmed only among the healthy elderly. These results suggest that age (older than 60 years), disease and male sex are associated with increased morning serum cortisol levels in a Chinese population.
    Steroids 09/2003; 68(6):551-5. · 2.72 Impact Factor
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    ABSTRACT: The relation of adrenal function and aging has been the subject of intense interest in recent years. The circadian variations of plasma cortisol have been described in Caucasians, but little information is available on such hormone variations among the Chinese population, especially its changes with age. This study was, therefore, designed to examine the effects of age on the circadian variations of serum cortisol, dehydroepiandrosterone sulfate (DHEAS) and the molar ratio of cortisol/DHEAS in Chinese men, stratified by 10-year age-groups (i.e. men in their 30-60s, aged from 31 to 63 years old). Circadian variations of serum cortisol and DHEAS were documented at 2-h intervals from 8:00 to 22:00 and hourly from 22:00 to 8:00 in 26 healthy Chinese men. We found that the serum levels of both hormones showed a statistically significant circadian rhythmicity in all age-groups. The circadian pattern of serum cortisol was characterized by peaks (04:00-06:00) and troughs (18:00-24:00) occurring approximately 2h earlier than those usually reported in Caucasians. Aging did not significantly influence serum cortisol concentrations, but serum DHEAS levels declined significantly with age: subjects in their 60s had significantly lower levels, and their cortisol/DHEAS molar ratios were significantly higher than those in the younger age-groups.
    Steroids 03/2003; 68(2):133-8. · 2.72 Impact Factor
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    ABSTRACT: Although previous reports indicate that nocturnal plasma melatonin secretion declines with age, some recent findings do not support this point. In the present cross-sectional study, we documented serum melatonin concentrations at two time points, 02:00 and 08:00 h, in 144 persons aged 30-110 yr and found a significant age-related decline. It began around the age of 60 and reached a very significantly lower level in subjects in their 70s and over 80 yr of age (P < 0.01, when compared with age <60 yr). Nocturnal melatonin levels were higher among (post-menopausal only) women than men overall (P < 0.05). In the older age-groups, nocturnal melatonin levels did not differ between healthy controls and subjects with high blood pressure or ischemic heart disease. To further check these results, we also assessed the circadian pattern of serum melatonin in four subgroups of healthy men, aged 30-39, 40-49, 50-59, and 60-69 yr: blood samples were taken at 2 h intervals from 08:00 to 22:00 h and hourly from 22:00 to 08:00 h. Our results showed generally similar circadian melatonin patterns that peaked at night with very low levels during the daytime. No significant difference was found among the three younger groups, but nocturnal melatonin levels were significantly lower in the men in their 60s.
    Chronobiology International 11/2002; 19(6):1171-82. · 2.88 Impact Factor
  • C Benstaali, A Bogdan, Y Touitou
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    ABSTRACT: Circadian rhythms of body temperature and motor activity were documented in young and old rats (four 8-week-old and five 22-month-old male Wistars, implanted with telemetric probes and housed in a chronobiological facility) under two different photoperiod conditions. The animals were maintained in a light:dark (LD) cycle of 12 h each (LD 12:12) for 4 weeks and then exposed to a LD 6:18 cycle for 7 weeks to assess the effect of age on the desynchronization of the temporal structure of the rhythms. In old rats under LD 12:12, the power of the 24-h component and the circadian amplitude of body temperature and motor activity were markedly lower than in the young and both rhythms were phase-advanced. After the shift to LD 6:18, the circadian rhythmicity was maintained for both variables and the same phase delay (+5+/-1 h) was observed in both age groups, as was a gradual expansion of the patterns of both functions with the longer night. The photoperiod reduction (6 weeks under LD 6:18) did not modify the power of the 24-h component of body temperature and motor activity in old rats. In young rats, however, the power and amplitude of the 24-h component of motor activity rhythm fell to the levels of those in old rats, while the power of the 24-h component of body temperature rhythm and the amplitude did not change. Our data show that the circadian rhythm of motor activity, but not of body temperature, responds age dependently to a photoperiod reduction.
    Pflügers Archiv - European Journal of Physiology 06/2002; 444(1-2):73-9. · 3.07 Impact Factor
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    ABSTRACT: Cancer patients may exhibit normal or altered circadian rhythms in tumor and healthy tissues. Four rhythms known to reflect circadian clock function were studied in 18 patients with metastatic colorectal cancer and good performance status. Rest-activity was monitored by wrist actigraphy for 72 h before treatment, and its circadian rhythm was estimated by an autocorrelation coefficient at 24h and a dichotomy index that compared the activity level when in and out of bed. Blood samples (9-11 time points, 3-6 h apart) were drawn on day 1 and day 4 of the first course of chronochemotherapy (5-fluorouracil: 800 mg/m2/day; folinic acid: 300 mg/m2/day; oxaliplatin: 25 mg/m2/day). Group 24h rhythms were validated statistically for plasma concentrations of melatonin, 6-alpha-sulfatoxymelatonin, and cortisol and for lymphocyte counts. Significant individual 24h rhythms were displayed in melatonin by 15 patients, cortisol by seven patients, lymphocytes by five patients, and prominent circadian rhythms in activity were displayed by 10 patients; only one patient exhibited significant rhythms in all the variables. The results suggest the rhythms of melatonin, cortisol, lymphocytes, and rest/activity reflect different components of the circadian system, which may be altered differently during cancer processes. Such 24h rhythm alterations appeared to be independent of conventional clinical factors.
    Chronobiology International 02/2002; 19(1):141-55. · 2.88 Impact Factor
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    ABSTRACT: Leptin, the product of the ob gene, is secreted by the adipocyte and is involved in the regulation of body weight, energy homeostasis and a wide spectrum of biological activities. We studied how variations in circadian serum leptin levels change as people age. Serum leptin levels were studied on a circadian basis in 26 men, 6 overweight (BMI >27.8) and 20 with normal weight. The normal-weight men were divided into four age groups: (A) in their 30s, (B) in their 40s, (C) in their 50s, and (D) in their 60s. Serum samples were drawn at 2-hour intervals from 8:00 to 22:00 and hourly from 22:00 to 8:00 for a total of 24 h. A significant circadian variation of leptin levels was found whatever the age with a peak at night and a trough around noon. The circadian leptin levels were higher in the older normal-weight groups (50s and 60s) and in the groups with a BMI >27.8. Our study demonstrates that changes in the characteristics of the circadian rhythm of serum leptin in healthy men are associated with both advancing age and increased BMI.
    Gerontology 01/2002; 48(5):309-14. · 2.68 Impact Factor
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    ABSTRACT: In healthy humans, cortisol displays marked 24-hour rhythms in serum and saliva, with a strong correlation between both fluids; the circadian variation of salivary cortisol is prognostic of longer survival in patients with metastatic breast cancer. In order to confirm these results in a non-hormone-dependent cancer, cortisol concentrations in serum and saliva were compared at different circadian stages, in patients with metastatic colorectal cancer. Patients and A first study consisted of round-the-clock sampling for two 24-hour periods, in 18 patients. A second study consisted of blood and salivary sampling at 8:00h and 16:00h, on 2 consecutive days, in 192 patients. Group circadian variations were validated in both body fluids. Cortisol concentrations in the serum and in saliva were significantly correlated in only 62% of the 18 patients in the first study. In the second study, the average cortisol concentrations were higher at 8:00h than at 16:00h, in serum as well as in saliva. Measures from both body fluids were correlated in patients with a marked 24-hour rhythm, but plasma and salivary cortisol did not correlate in patients with a damped diurnal variation. The patient's performance status and extent of liver involvement, as well as the patient's rest activity cycle were influential on cortisol average concentration, but not on its circadian variation. The circadian variation in cortisol was prognostic of neither response, nor survivaL CONCLUSION: These results indicate that the assessment of salivary cortisol cannot substitute for that of serum cortisol in metastatic colorectal cancer. This study suggests that the clinical relevance of cortisol circadian rhythm for patient outcome may differ according to the hormonal dependency of the tumor.
    Anticancer research 01/2002; 22(2B):1243-9. · 1.87 Impact Factor
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    ABSTRACT: Although previous reports indicate that nocturnal plasma melatonin secretion declines with age, some recent findings do not support this point. In the present cross-sectional study, we documented serum melatonin concentrations at two time points, 02:00 and 08:00h, in 144 persons aged 30–110 yr and found a significant age-related decline. It began around the age of 60 and reached a very significantly lower level in subjects in their 70s and over 80 yr of age (P
    Chronobiology International 01/2002; 19(6):1171-1182. · 2.88 Impact Factor
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    ABSTRACT: In rodents, the alternation of light and dark is the main synchronizer of circadian rhythms. The entrainment abilities of the LD cycle could be estimated by experimental modifications of the photoperiod and by following the subsequent temporal distribution of a circadian rhythm. The rate of reentrainment of a rhythm is determined by the nature of the studied variable, by the direction (advance or delay) and the magnitude (or value) of the phase shift. In rodents, core body temperature and motor activity are known to be well synchronized with each other under L:D 12:12 and under constant conditions (LL or DD). There are clear evidences that the circadian pattern of motor activity is generated by two oscillators, one from dusk signal and the other from dawn signal. Whether the circadian rhythms of body temperature and motor activity are generated by a common circadian mechanism or controlled by separate ones still remains unknown. The purpose of this review is to summarize the results obtained on the circadian rhythms of body temperature and motor activity throughout the daily cycle in order to clarify the relationships between these two functions.
    Life Sciences 06/2001; 68(24):2645-56. · 2.30 Impact Factor
  • André Bogdan, Yvan Touitou
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    ABSTRACT: Homeostatic mechanisms are not the only ones implied in metabolic balances. Any living organism, whatever its complexity, presents biologic rhythms. They can have a periodicity of about 24 h (circadian rhythms) ; shorter than 21 h (ultradian rhythms, less than a second up to several hours) ; or longer than 27 h (infradian rhythms : mensual, circannual or seasonal).Biologic rhythms have an endogenous (genetic) origin and are driven by biologic clocks, mainly by the suprachiasmatic nuclei of the anterior hypothalamus. Besides, biologic rhythms are entrained to environmental changes by exogenous factors called synchronizers such as the activity-rest cycle and day-night alternance…The spontaneous food intake behavior, the various processes involved in digestion and the metabolism of nutrients are, as all other biologic variables, submitted to rhythmic variations — but the number and nature of the oscillators responsible for their generation and control are still poorly understood and a matter of controversy, because of the complex and multifactorial character of food consumption.
    Revue Française des Laboratoires 06/2001; 2001(334):59-63.
  • André Bogdan, Belal Bouchareb, Yvan Touitou
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    ABSTRACT: Muslims must refrain from eating, drinking, smoking, and sexual relations from sunrise to sunset during the month of Ramadan. Serum concentrations of melatonin, steroid hormones (cortisol, testosterone), pituitary hormones (prolactin, LH, FSH, GH, TSH) and thyroid hormones (free thyroxin and free triiodothyronine) were documented around the clock at six 4-hourly intervals before Ramadan began and on the twenty-third day of Ramadan (daytime fasting). Time series were analysed with repeated measures ANOVA. Statistically significant differences were found in some variables: the nocturnal peak of melatonin was diminished and may have been delayed; there was a shift in the onset of cortisol and testosterone secretion; the evening peak of prolactin was enhanced, FSH and GH rhythmic patterns were affected little or not at all by Ramadan fasting and only the serum TSH rhythm was blunted over the test time span. These data show that daytime fasting, modifications in sleep schedule and psychological and social habits during Ramadan induce changes in the rhythmic pattern of a number of hormonal variables.
    Life Sciences 03/2001; 68(14):1607-15. · 2.30 Impact Factor
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    ABSTRACT: 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.
    Chronobiology International 02/2001; 18(1):99-107. · 2.88 Impact Factor
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    ABSTRACT: 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.
    Life Sciences 01/2001; 68(4):387-99. · 2.30 Impact Factor

Publication Stats

2k Citations
256.36 Total Impact Points


  • 2006–2007
    • Pierre and Marie Curie University - Paris 6
      • Faculté de médecine Pierre et Marie Curie
      Lutetia Parisorum, Île-de-France, France
  • 2002
    • Shandong Academy of Sciences
      Chi-nan-shih, Shandong Sheng, China
  • 1998–2002
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 1997
    • Faculté de Medecine et de Pharmacie de Casablanca
      Anfa, Grand Casablanca, Morocco
  • 1996
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France