
Alain ReinbergFondation A. de Rothschild, Paris France · Chronobiology Un it
Alain Reinberg
MD Ph D
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Publications
Publications (412)
Biologic rhythms of cells and organisms are well documented and have been extensively studied at the physiologic and molecular levels. For the skin, many circadian changes have been investigated but few systematic studies comparing skin at different body sites have been reported. In this study we investigated facial and forearm skin circadian rhyth...
Details of serious injuries to children ≤16 yrs. of age that necessitated urgent surgical intervention by the Department of Pediatric Surgery of the University Hospital of Lausanne, Switzerland were recorded into a database registry. Some 15 110 entries listed the precise time of injury, and 3114 (20.6%) of these resulted from participating in spor...
Purpose:
This study aims to investigate whether valproic acid (VPA) anticonvulsant activity varied according to circadian dosing-time in mice.
Methods:
VPA was administered to mice at four circadian stages (1, 7, 13 and 19h after light onset, (HALO)). The controls received a saline injection followed by a s.c. injection of pentylenetetrazol (PTZ...
This study investigates whether the toxicity in kidneys as well as oxidative stress varied according to the dosing time of an immunosuppressive agent “mycophenolate mofetil (MMF)“ in Wistar Rat. 300 mg/kg of MMF was injected by intraperitonal at four different circadian stages (1, 7, 13 and 19 h after light onset, HALO). Rats were sacrificed after...
Introduction:
This study is designed to investigate whether the pharmacokinetics of the antituberculous agent isoniazid (INH) varied according to the circadian dosing-time.
Methods:
A total of 168 male mice aged 10 weeks and synchronized for 3 weeks to 12h light and 12h dark were used. A single INH (100mg/kg) dose was administered by intraperito...
Immunosuppressive drugs such as Mycophenolate Mofetil (MMF) are used to suppress the immune system activity in transplant patients and reduce the risk of organ rejection. The present study investigates whether the potential cytotoxicity and genotoxicity varied according to MMF dosing-time in Wistar Rat. A potentially toxic MMF dose (300 mg/kg) was...
The circadian time structure of an organism can be desynchronized in a large number of instances, including the intake of specific drugs. We have previously found that propofol, which is a general anesthetic, induces a desynchronization of the circadian time structure in rats, with a 60–80 min significant phase advance of body temperature circadian...
Aims:
Why are some healthy male shift workers (SWers) overweight [body mass index (BMI) >25 and <30] if not obese (BMI >30)? Seven risk factors potentially causing overweight and obesity were evaluated, namely (1) age, (2) physical/sports activity, (3) length of exposure to shift work (SW), (4) speed of shift rotation, (5) tolerance to SW, (6) int...
Biological processes are organized in time as innate rhythms defined by the period (τ), phase (peak [Φ] and trough time), amplitude (A, peak-trough difference) and mean level. The human time structure in its entirety is comprised of ultradian (τ < 20 h), circadian (20 h > τ < 28 h) and infradian (τ > 28 h) bioperiodicities. The circadian time struc...
Cereus peruvianus (Peruvian apple cactus) is a large erect and thorny succulent cactus characterized by column-like (cereus [L]: column), that is, candle-shaped, appendages. For three successive years (1100 days), between early April and late November, we studied the flowering patterns of eight cacti growing in public gardens and rural areas of nor...
Biological rhythmicity is presumed to be an advantageous genetic adaptation of fitness and survival value resulting from evolution of life forms in an environment that varies predictably-in-time during the 24 h, month, and year. The 24 h light/dark cycle is the prime synchronizer of circadian periodicities, and its modulation over the course of the...
This study investigates whether the intestinal toxicity of the immunosuppressive agent "mycophenolate mofetil (MMF)" varied according to the circadian dosing-time in rats. MMF (300 mg/kg) was acutely administered by i.p. route in rats at four different circadian stages (1, 7, 13 and 19 hours after light onset, HALO). The results obtained showed tha...
The circadian time is an important process affecting both pharmacokinetics and pharmacodynamics of drugs. Consequently, the desired and/or undesired effects vary according to the time of drug administration in the 24 h scale. This study investigates whether the toxicity in liver as well as oxidative stress varies according to the circadian dosing-t...
Simon Folkard in 1997 introduced the phrase black time to draw attention to the fact that the risk of driving accidents (DA) is greater during the night than day in usually diurnally active persons. The 24 h temporal pattern in DA entails circadian rhythms of fatigue and sleep propensity, cognitive and physical performance, and behavior that are co...
Background. We aimed to determine if the risk of work related injuries (WRI) of French Volunteer Firefighters (VFF) and their severity are greater during the night than day. Studies on VFF are a major interest of the French civil security program since they constitute 78% of the total number of 244 900 French firefighters. VFF maintain a regular jo...
This study aims to investigate whether hepatic and renal Valproic acid (VPA) toxicities varied according to the dosing-time in the 24-h scale in mice. VPA was administered by i.p. route to different groups of animals at four different circadian stages (1, 7, 13 and 19 Hours After Light Onset (HALO)). Biochemical study and histopathological examinat...
Introduction:
Isoniazid (INH) is a widely used drug in the prophylaxis and treatment of tuberculosis. In the present study, isoniazid (INH)-induced toxicity was investigated according to the dosing-time in the 24-h scale in mice.
Methods:
Two studies were carried out on a total of 180 male Swiss mice synchronized for 3 weeks to 12-hour light (re...
The aim of our study was to understand how the biological, psychological and socio-ecological rhythms could affect the firefighters’ (FF) profession, as regards to prevention of work related incident, and protection of the population.
A retrospective study enabled us to analyse the rhythm of the FF’s interventions, the circadian pattern of a collec...
Circadian cognitive and physical rhythms plus 24 h patterns of accidents and work-related injuries (WRI) have been verified in numerous studies. However, rarely, if ever, have 24 h temporal differences in both work performance and risk of WRI been assessed in the same group of workers. We explored in a homogenous group of French firemen (FM) 24 h p...
The present work aims to investigate whether the pharmacokinetics of the active metabolite mycophenolic acid (MPA) varies according to the circadian dosing-time of Mycophenolate Mofetil (MMF). A total of 180 male Wistar rats aged 8 weeks and synchronized for 3 weeks to 12 h light and 12 h dark were used. A single dose of 200 mg/kg of MMF was admini...
Antiepileptic drugs may have varying toxicity or efficacy depending on administration time. VPA administration could be associated with a great deal of haematological toxicity and can cause aplasic anaemia or peripheral cytopenia affecting one or more cell lines. The objective of this study is to experimentally verify if VPA-induced haematological...
The yurt is the traditional home of the nomadic Turkmen, the Kyrgyz, the Kazakhs, the Uzbeks, the Kalmyks, the Buryats and the Mongolians. As the impact of the western modern world, in terms of technological and behavioural changes, is slower than anywhere else, the use of the yurt is widespread in the Mongolian steppes, where nomadic life has been...
Dr. Erhard Leo Anton Haus was born in Vienna, Austria to Leo Anton and Marianne Haus, and was the grandson of Anton Haus, the last Grand Admiral of the Austrian-Hungarian Empire. Erhard was educated in internal medicine at the University of Innsbruck and was certified in Laboratory Medicine and Pathology at the University of Minnesota where he also...
*This work is dedicated to the memories of Drs. Israel Ashkenazi and Erhard Haus, outstanding pioneers of medical chronobiology, dear colleagues, and distinguished gentlemen of exceptional human qualities. We investigated the circadian synchronization/desynchronization (by field-study assessment of differences in period, τ, of 16 coexisting and wel...
Bec ause of biological rhythms, drug efficiency and toxicity vary according to the time of administration of the drug. This study investigates whether the haematological toxicity of the immunosuppressive agent Mycophenolate Mofetil varies according to the circadian dosing-time in rats. 300 mg/kg of Mycophenolate Mofetil was injected by i.p. route t...
Valproic acid (VPA) is currently one of the most commonly used antiepileptic drugs. This study aims to investigate whether VPA pharmacokinetics varied according to circadian dosing-time. A single dose of VPA (350 mg kg⁻¹) was administered by intraperitonally (i.p.) route to a total of 132 mice synchronized for 3 weeks to 12 h light (rest span) and...
Based on group experiments it was assumed that the rhÿhm of nocturnar peak time of work-related injuries
(WRI) (Riedel et al. 2010) is related to nocturnal trough in performance: e.g. lag time to respond to call
(Brousse et al. 2010). The individual quantification of rhythms parameters, including T, of cognitive
variables was mandatory to test this...
As a rule Ambulatory Blood Pressure Monitoring (AMBP) dealing wirh systolic (SBP) and Diastolic (DBP) blood pressure and heart rate (HR) is restricted to a 24h recording span. In so doing it is assumed that: a) for each of the 3 variables the period is T = 24h b) there is no change of T from one variabre to another (no desynchronization) and c) the...
The aim of the study was to document the desynchronization.(co-existing rhythms with difference in Ts)
of healthy subjects, exposed to irregular nocturnal activity wiih randomly distributed hard and stressing
work hours but with an excellent clinical tolerance (allochronism). Thirty firemen (FM) were divided into
3 groups. A: 12 FM on ward Day & Ni...
Firefighters (FF) are submitted to high temperature levels. We documented changes in the body temperature
24h rhythm (BT) of FF exposed to a fire mimicking that of their work conditions. Six professional male
FF, 27.7 ± 3 years of age, wearing fire shielded cloths -- including special helmet gloves and boots --
were, as a rule, trained to stay a 40...
A well tolerated desynchronisation of 16 rhythms (allochronism) with T differing among themselves
was observed in some of the 30 firemen involved in the study. It is likely that the propensity of a given
subject to desynchronize his rhythms is inherited. The pertinent question is: which non-rhythmic factor(s) may be involved in the desynchronizatio...
Valproic acid (VPA) is an antiepileptic drug widely used for the treatment of absence seizures and generalized tonic-clonic seizures. The present work aims to study whether VPA-induced toxicity varies according to the dosing-time in the 24 hour-scale.
The influence of dosing-time on tolerance to VPA was investigated in 120 male Swiss mice synchroni...
The present work aims to investigate whether the tolerance to mycophenolate mofetil (MMF) varies according to the circadian dosing time in rats. A total of 120 male Wistar rats were synchronized for three weeks to 12 h light/12 h dark. A potentially lethal dose of MMF (450 mg/kg, i.p.) was injected to different groups of animals at six different ci...
The first aim of the study was to assess clock-time patterning of work-related injuries (WRIs) of firemen (FM) of Saône et Loire-71 (France) during the 4-yr span of 1 January 2004 to 31 December 2007. FM of this service are legally required to log every WRI and seek its evaluation by the medical service, whether the WRI was the result of worksite d...
The aim of the study was to assess the group 24-h pattern of lag time (LT) in response by regular and volunteer firemen (RFM and VFM) to calls for medical help (CFMH), specifically calls for out-of-hospital cardiac arrest (OHCA). LT, duration in min between a CFMH and departure of service vehicle equipped with a semiautomated defibrillator and gene...
The authors studied longitudinally four healthy young adults to explore if habitual evening intake of a "moderate" amount of wine alters parameters, including period (τ) of circadian rhythms. Subjects, synchronized by diurnal activity from 07.30 h ± 60 min to 23.00 h ± 90 min and nocturnal rest, were studied during a continuous 22-day span: 11 days...
Aims: Document, as a group phenomenon,the 24 h Lag Tirne (LT) rhythm in response to calls for medical emergencies.
Methods: Firemen (FM) residing in Mâcon (South of Burgundy), >104,000 population suburban area included. FM spent 53% ± 9 (SEM) of their total activity rendering aid to individuals calling for a medical ernergency.
LT = duration (in mi...
Differences in period (T) length of a variety of arcadian rhythms of a given subject (internal desynchronization or circadian dyschronism) have been demonstrated in shift workers and subjects exposed to natural environmental Zeitgebers. The aims of the present study were to compare the frequency distributions of circadian TS of the oral temperature...
The concept of homeostasis (i.e., constancy of the milieu interne) has long dominated the teaching and practice of medicine. Concepts and findings from chronobiology, the scientific study of biological rhythms, challenge this construct. Biological processes and functions are not at all constant; rather, they are organized in time as rhythms with pe...
As part of the Journal's strategy to foster communication among authors and readers, the editors have encouraged a special type of report on matters pertaining to biological rhythm research seldom published, but which nonetheless contributes to critical developments in chronobiology.
Intolerance to shift work may result from individual susceptibility to an internal desynchronization. Some shift workers (SW) who show desynchronization of their circadian rhythms (e.g., sleep-wake, body temperature, and grip strength of both hands) exhibit symptoms of SW intolerance, such as sleep alteration, persistent fatigue, sleep medication d...
Rhodanese (thiosulfate sulfurtransferase) is a ubiquitous enzyme that accelerates the transformation of cyanide into the very less toxic thiocyante. Influence of cerebral rhodanese level on cyanide toxicity has already been shown in mice. However, age-related changes in rhodanese activity have not been previously examined. The aim of the experiment...
Study of the chronobiology of allergic rhinitis (AR) and bronchial asthma (BA) and the chronopharmacology and chronotherapy of the medications used in their treatment began five decades ago. AR is an inflammatory disease of the upper airway tissue with hypersensitivity to specific environmental antigens, resulting in further local inflammation, vas...
Ondansetron (Zophren((R))) is a serotonin 5HT(3)-receptor antagonist used primarily to control nausea and vomiting caused by cytotoxic chemo-and radio-therapy. Tolerance to this drug shows both 24 and 8 h periodicities. In this framework, this study aimed to determine whether these ondansetron tolerance rhythms are modulated by season. The chronoto...
The authors define a subject as euchronic when the circadian parameters--tau (tau=period), Ø (acrophse or peak time), A (amplitude), and M (MESOR=24 h rhythm-adjusted mean)--of a set of circadian variables are within the confidence limits of appropriate reference values of healthy subjects (HS). We define internal desynchronization as a state in wh...
In aerobic organisms, the use of oxygen (O(2)) to produce energy is associated with the production of Reactive Oxygen Species (ROS), which reacts with biological molecules to produce oxidized metabolites such as malondialdehyde (MDA). This experiment focused on male Swiss mice 12 weeks of age synchronized for 3 weeks by the 12 h light (rest)/12 h d...
To protect tissues from damaging effects of reactive oxygen species (ROS), organisms possess enzymatic and non-enzymatic antioxidant systems. Cytosolic-enzyme catalase (CAT) is a component of the antioxidant defence system that reduces hydrogen peroxide (H2O2) to water (H2O). The aim of this study was to assess the variation of antioxidant enzyme C...
Résumé
L’utilisation thérapeutique du Cortisol et de ses dérivés, les corticoïdes anti-inflammatoires, pose des problèmes délicats à résoudre en raison des rôles physiologiques du Cortisol et de ses rythmes circadiens. Le Cortisol et la plupart de ses dérivés ont des effets désirés et indésirables qui varient en fonction des heures de leur administ...
The therapeutic use of cortisol and its derivatives, anti-inflammatory corticoids, sets delicate problems to resolve because of cortisol's physiological roles and its circadian rhythms. Cortisol and the majority of its derivatives have desirable and undesirable effects that are time-related administration. The chronotherapeutic optimisation to incr...
Thiosulfate sulfurtransferase (TST) is an important 'enzyme of protection,' that accelerates the detoxification of cyanide, converting it into thiocyanate. The TST physiological rhythm was investigated at wks 2, 4, and 8 of post-natal development (PND) in the mouse. The results revealed a statistically significant gender-related difference, with th...
Several adult chronobiologic studies have shown that accidents do not occur at random. Comparing a large cohort of injured children with uninjured children living in an urban setting, we evaluated the rhythmicity of pediatric injury occurrence.
A data review of a prospective cohort study of child trauma over an 8-year period was recorded in a Swiss...
Cetirizine is a second generation histamine H(1) receptor antagonist used to provide symptomatic relief of allergic signs caused by histamine release. The aim of the study was to learn whether the survival and the motor incoordination (ataxia) side effect of cetirizine administration is dosing time-dependent.
A total of 240 male Swiss mice, 10 week...
Cetirizine is a second generation histamine H1 receptor antagonist used to provide symptomatic relief of allergic signs caused by histamine release. The aim of the study was to learn whether the survival and the motor incoordination (ataxia) side effect of cétirizine administration is dosing time-dependent.Materials and methods. – A total of 240 ma...
Loratadine is a second-generation histamine H(1)-receptor antagonist used in the treatment of allergic diseases. The aim of the study was to assess whether lethal toxicity and motor incoordination (neurotoxicity) of loratadine is circadian rhythm-dependent. A total of 210 male Swiss mice, aged 10 wk, were synchronized for 3 wk to 12 h light (rest s...
24 h patterns with high frequency components in the incidence of pediatric trauma were validated and quantified in one of our earlier studies. Herein, we further explored the temporal--high frequency, 24 h, weekly (7d), hemi-weekly (3.5d), and annual--patterns in traumatic (1990-1997; n = 15,110 events) and non-traumatic pediatric surgical emergenc...
Biological processes and functions in women are well organized in time, as evidenced by the expression of ultradian (high frequency), circadian ( approximately 24-hour), circamensual ( approximately monthly), and circannual ( approximately yearly) rhythms and by the changes that occur with menarche, reproduction, and menopause. Attributes of women'...
The aim of this study was to determine the effect of consuming alcoholic vs. nonalcoholic beverages on performance of psycho-technical tasks (attentional and general nonverbal intelligence tasks) and social behavior at different times of day. Both alcoholic and nonalcoholic consumption took place in a largely festive situation. The experiment was c...
Biological rhythms and their temporal organization are adaptive phenomena to periodic changes in environmental factors linked to the earth's rotation on its axis and around the sun. Experimental data from the plant and animal kingdoms have led to many models and concepts related to biological clocks that help describe and understand the mechanisms...
The aim of the study was to learn whether the lethal and the motor incoordination (ataxia) side effect of ondansetron (Zophren) administration is dosing-time dependent. Ondansetron is a serotonin 5-HT3 receptor antagonist used primarily to control nausea and vomiting arising from cytotoxic chemo- and radiotherapy. A total of 210 male Swiss mice 10...
In healthy mature subjects simple reaction time (SRT) to a single light signal (an easy task) is associated with a prominent rhythm with tau = 24 h of dominant (DH) as well as nondominant (NDH) hand performance, while three-choice reaction time (CRT), a complex task, is associated with tau = 24 h of the DH but tau < 24 h of the NDH. The aims of the...
This study investigates if the serotoninergic system plays a role in chronotoxic effects of the anticancer agent oxaliplatin (l-OHP). Four groups of female rats (120 in total) synchronized with light-dark (12 h:12 h) were treated with: (i) saline, (ii) para-chlorophenylalanine (pCPA, an inhibitor of serotonin biosynthesis: 300 mg/kg/d, i.p. for two...
In a prospective study, 15,110 childhood traumas were recorded by the Pediatric Surgery Service (CHUV, Lausanne) between January 1, 1990 and December 31, 1997. The exact clock hour when the injury occurred and other germane data were obtained. Time series thus obtained were analyzed by several statistical (ANOVA, cosinor, chi2, Table Curve, etc.) m...
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 nonwea...
Biologic rhythms of cells and organisms are well documented and have been extensively studied at the physiologic and molecular levels. For the skin, many circadian changes have been investigated but few systematic studies comparing skin at different body sites have been reported. In this study we investigated facial and forearm skin circadian rhyth...