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Biomedical subjects

D Lagarde

Publications and source records attributed to D Lagarde.

At least 19 recordsLinked to original sources

Caffeine or melatonin effects on sleep and sleepiness after rapid eastward transmeridian travel.

We measured the effects of slow-release caffeine (SRC) and melatonin (Mlt) on sleep and daytime sleepiness after a seven-time zone eastbound flight. In a double-blind, randomized, placebo-controlled study, each of three groups of nine subjects was given either 300 mg SRC on recovery day 1 (D1) to D5 (0800) or 5 mg Mlt on preflight D-1 (1700), flight day D0 (1600), and from D1 to D3 (2300), or placebo (Pbo) at the same times. Nighttime sleep was evaluated by polysomnography and daytime sleepiness from measurements of sleep latencies and continuous wrist actigraphy. Compared with baseline, we found a significant rebound of slow-wave sleep on night 1 (N1) to N2 under Pbo and Mlt and a significant decrease in rapid eye movement sleep on N1 (Pbo) and N1-N3 (Mlt). Sleepiness was objectively increased under Pbo (D1-D6) and Mlt (D1-D3). SRC reduced sleepiness but also tended to affect sleep quality until the last drug day. In conclusion, both drugs have positive effects on some jet lag symptoms after an eastbound flight: SRC on daytime sleepiness, and Mlt on sleep.

Adult↗

Cerebral cortical blood flow during loss of consciousness induced by gravitational stress in rhesus monkeys.

We investigated the influence of +Gz acceleration (head-to-foot inertial forces) onset on cerebral cortical blood flow (CBF) of rhesus monkeys to study the mechanisms underlying +Gz-induced loss of consciousness (G-LOC). CBF was measured through a chronic cranial window by laser-Doppler flowmetry and electrodes in contact with the dura mater were used to detect G-LOC (suppression of the cortical electrical activity). The animals were centrifuged up to +12 Gz with different G-onset rate until G-LOC occurred. G-LOC was preceded by a 2-5 s decrease in CBF. At G-LOC detection, CBF was not related to G-onset rate (mean CBF change: -76 +/- 9% of control value). We conclude that G-LOC results from cerebral ischemia rather than from mechanical stresses applied to the brain.

Animals↗

Resynchronization of hormonal rhythms after an eastbound flight in humans: effects of slow-release caffeine and melatonin.

The aim of this work was to investigate the potential chronobiotic properties of slow-release caffeine, in comparison with melatonin, on resynchronization of endogenous melatonin and cortisol secretions after an eastbound flight by jet incurring a time loss of 7 h. A group of 27 reservists of the US Air Force received either slow-release caffeine (300 mg), melatonin (5 mg) or placebo before, during and/or after the transmeridian flight. Saliva and urine were sampled before the flight in the United States (from day -2 to day 0) and after the flight in France (from day 1 to day 10). Saliva was collected once a day on waking to determine saliva melatonin and cortisol concentrations. In addition, concentrations of caffeine in saliva were determined three times a day and of 6-sulphatoxymelatonin in urine collected overnight to check that the treatment regimes had been complied with. From day 3 to day 5, post-flight saliva melatonin concentrations were significantly different from control values in the placebo group only. During treatment with melatonin, the mean urinary 6-sulphatoxymelatonin concentration in the melatonin group was more than twice as high as in the two other groups. In the slow-release caffeine group and the melatonin group, mean saliva cortisol concentrations were significantly lower than control from day 2 to day 5, whereas the placebo group had a mean saliva cortisol concentration significantly lower than the control value from day 2 to day 9. In conclusion, these results indicate that administration of slow-release caffeine, as well as of melatonin, allows a faster resynchronization of hormone rhythms during the 4 days following an eastbound flight incurring the loss of 7 h.

Adjuvants, Immunologic↗

Slow release caffeine and prolonged (64-h) continuous wakefulness: effects on vigilance and cognitive performance.

Some long work or shift work schedules necessitate an elevated and prolonged level of vigilance and performance but often result in sleep deprivation (SD), fatigue and sleepiness, which may impair efficiency. This study investigated the effects of a slow-release caffeine [(SRC) at the daily dose of 600 mg] on vigilance and cognitive performance during a 64 h continuous wakefulness period. Sixteen healthy males volunteered for this double-blind, randomised, placebo controlled, two-way crossover study. A total of 300-mg SRC or placebo (PBO) was given twice a day at 21:00 and 9:00 h during the SD period. Vigilance was objectively assessed with continuous electroencephalogram (EEG), the multiple sleep latency tests (MSLT) and wrist actigraphy. Cognitive functions (information processing and working memory), selective and divided attention were determined with computerised tests from the AGARD-NATO STRES Battery (Standardised Tests for Research with Environmental Stressors). Attention was also assessed with a symbol cancellation task and a Stroop's test; alertness was appreciated from visual analogue scales (VAS). Tests were performed at the hypo (02:00-04:00 h, 14:00-16:00 h) and hypervigilance (10:00-12:00 h, 22:00-00:00 h) periods during SD. Central temperature was continuously measured and safety of treatment was assessed from repeated clinical examinations. Compared with PBO, MSLT showed that SRC subjects were more vigilant from the onset (P=0.001) to the end of SD (P < 0.0001) whereas some cognitive functions were improved till the thirty third of SD but others were ameliorated through all the SD period and alertness was better from the thirteenth hour of SD, as shown by Stroop's test (P=0.048). We showed that 300-mg SRC given twice daily during a 64-h SD is able to antagonize the impairment produced on vigilance and cognitive functions.

Adult↗

Nycthemeral variations in core temperature and heart rate: continuous cycling exercise versus continuous rest.

Circadian rhythms have formed the subject of many researches in man during bed rest or usual routine, but have been little studied during continuous and sustained physical exercise. This study deals with the influence of time of day on biological markers in competitive cyclists during continuous physical exercise versus continuous rest. Ultra-distance cyclists were studied over a 24 h period (13:00 to 13:00 h the next day) in the laboratory. The subjects were requested to maintain a constant speed (set at 65% - 70% of their maximal aerobic speed obtained during a preliminary test) on their own bicycles which were equipped with home trainers. Workload, core temperature and heart rate were monitored continuously. The same measures were also recorded while the athletes were resting awake until 13:00 h the next day. Results show that in both situations, core temperature and heart rate exhibited significant circadian variations (p < 0.001). Furthermore, during exercise, an accentuation of amplitude and mean of every rhythm (p < 0.05) with a phase lag (p < 0.05) were observed. Despite a strenuous and continuous physical exercise requiring special physiological adaptations, the rhythmic variations observed at rest persisted, which highlighted the influence of biological clocks.

Adult↗

Evaluation of pharmacological aids on physical performance after a transmeridian flight.

PURPOSE: The purpose of this study was to evaluate physical performance (static and dynamic) of U.S. Air Force reservists after an eastbound air travel across seven time zones and to estimate the pharmacological aids slow-release caffeine and melatonin versus placebo in attempt to overcome the decline in performance. METHODS: 27 American volunteers were randomly divided into three groups: caffeine 300 mg, melatonin 5 mg, and placebo (lactose capsules). Two days before the flight and 10 d after, three tests were performed: hand grip strength test (static performance), squat jump test (maximal height), and multiple jump test (power and endurance). All measures were repeated twice a day: morning and afternoon. RESULTS: In placebo conditions, the static performance of the dominant hand decreased significantly during the first three mornings and tended to decrease the fourth morning. Simultaneously, the caffeine group's static performance increased significantly, whereas the melatonin group maintained its levels. No significant differences were observed the afternoons. No statistical differences appeared for the nondominant hand in the mornings or afternoons. Dynamic capacities presented no significant degradation after the travel. In the placebo group, for the squat jump test, performance increased from the fourth day. No real explanation can be given about this result. CONCLUSIONS: We demonstrated that slow-release caffeine and melatonin might be used to compensate for jet-lag troubles and particularly for the static physical performance decrease. The slow-release caffeine seems to be the best treatment, but its effects are only demonstrated on previously damaged performance. These preliminary results need further investigation, but we are the first to report a beneficial effect of slow-release caffeine and melatonin on physical performances after jet-lag.

Adult↗

Slow-release caffeine: a new response to the effects of a limited sleep deprivation.

STUDY OBJECTIVES: The aim of this study is to assess the interest of the intake of a new galenic form of caffeine called "slow-release" caffeine (SR caffeine) during a decrease of vigilance due to a limited sleep deprivation. DESIGN: The controlled method used compared three doses of SR caffeine (150, 300 and 600 mg) with a placebo. Tests were performed 2, 9 and 13 hours after each treatment. Wakefulness level was assessed subjectively through questionnaires and analog visual scales, and objectively with the Multiple Sleep Latency Test. Performance level was also assessed regularly with an attention test, a grammatical reasoning test, a spatial recognition test, a mathematical processing test, a visual tracking test, a memory search test, and a dual task. The motor activity was evaluated by wrist actimeter and safety of treatment was observed by regular clinical examination. SETTING: NA. PARTICIPANTS: Twenty-four young and healthy volunteers (12 men and 12 women) participated in a 32-hour sleep deprivation. INTERVENTIONS: NA. RESULTS: The results show a significant effect of slow-release caffeine vs. placebo, and on vigilance and performance when subjects became tired. The effects of SR caffeine lasted 13 hours after treatment. SR caffeine 300 and 600 mg are efficacious doses but the optimal dose (maximum effect without any side effects) for both men and women is after all 300 mg. Globally, there is no difference between placebo and caffeine during the recovery night period. CONCLUSIONS: SR caffeine (300 mg) seems to be an efficient and safety substance to maintain a good level of vigilance and performance during limited sleep deprivation.

Adolescent↗

Effect of modafinil on cerebral blood flow of anaesthetised rats. Comparison with amphetamine.

This experiment compares the cardio- and cerebrovascular effects of modafinil and amphetamine administered to rats. Injections of 300 mg/kg and 600 mg/kg modafinil i.p. had no major effect. In contrast, injection of D-amphetamine sulfate (5 mg/kg i.v.) induced a long-lasting rise in heart rate and in mean arterial blood pressure (MABP). Amphetamine administration also elicited a 70-min-long increase in cortical cerebral blood flow which was proportional to the increase in MABP. We conclude that, contrary to amphetamine, modafinil has no effect on perfusion in the cerebral cortex of anaesthetised rats.

Amphetamine↗

Circadian rhythms in human muscular efficiency: continuous physical exercise versus continuous rest. A crossover study.

This study deals with the influence of time of day on neuromuscular efficiency in competitive cyclists during continuous exercise versus continuous rest. Knee extension torque was measured in ultradistance cyclists over a 24h period (13:00 to 13:00 the next day) in the laboratory. The subjects were requested to maintain a constant speed (set at 70% of their maximal aerobic speed obtained during a preliminary test) on their own bicycles, which were equipped with cyclosimulators. Every 4h, torque developed and myoelectric activity were estimated during maximal isometric voluntary contractions of knee extensors using an isokinetic dynamometer. Mesenteric temperature was monitored by telemetry. The same measures were also recorded while the subjects were resting awake until 13:00 the next day. During activity, torque changed within the 24h period (p < .005), with an acrophase at 19:10 and an amplitude of 7.8% around the mean of 70.7%. At rest, a circadian rhythm was observed in knee extensor torque (p < .05), with an acrophase at 19:30 and an amplitude of 6% around the mean of 92.3%. Despite the standardized conditions, the results showed that isometric maximal strength varied with time of day during both a submaximal exercise and at rest without prior exercise. The sine waves representing these two rhythms were correlated significantly. Although at rest the diurnal rhythm followed muscular activity (i.e., neurophysiological factors), during exercise, this rhythm was thought to stem more from fluctuations in the contractile state of muscle.

Adult↗

Increased production of zeaxanthin and other pigments by application of genetic engineering techniques to Synechocystis sp. strain PCC 6803.

The psbAII locus was used as an integration platform to overexpress genes involved in carotenoid biosynthesis in Synechocystis sp. strain PCC 6803 under the control of the strong psbAII promoter. The sequences of the genes encoding the yeast isopentenyl diphosphate isomerase (ipi) and the Synechocystis beta-carotene hydroxylase (crtR) and the linked Synechocystis genes coding for phytoene desaturase and phytoene synthase (crtP and crtB, respectively) were introduced into Synechocystis, replacing the psbAII coding sequence. Expression of ipi, crtR, and crtP and crtB led to a large increase in the corresponding transcript levels in the mutant strains, showing that the psbAII promoter can be used to drive transcription and to overexpress various genes in Synechocystis. Overexpression of crtP and crtB led to a 50% increase in the myxoxanthophyll and zeaxanthin contents in the mutant strain, whereas the beta-carotene and echinenone contents remained unchanged. Overexpression of crtR induced a 2.5-fold increase in zeaxanthin accumulation in the corresponding overexpressing mutant compared to that in the wild-type strain. In this mutant strain, zeaxanthin becomes the major pigment (more than half the total amount of carotenoid) and the beta-carotene and echinenone amounts are reduced by a factor of 2. However, overexpression of ipi did not result in a change in the carotenoid content of the mutant. To further alter the carotenoid content of Synechocystis, the crtO gene, encoding beta-carotene ketolase, which converts beta-carotene to echinenone, was disrupted in the wild type and in the overexpressing strains so that they no longer produced echinenone. In this way, by a combination of overexpression and deletion of particular genes, the carotenoid content of cyanobacteria can be altered significantly.

Bacterial Proteins↗

The zeaxanthin biosynthesis enzyme beta-carotene hydroxylase is involved in myxoxanthophyll synthesis in Synechocystis sp. PCC 6803.

Beta-carotene hydroxylase is known to be involved in zeaxanthin synthesis. Disruption of the crtR gene encoding beta-carotene hydroxylase in Synechocystis sp. PCC 6803 resulted in the absence of both zeaxanthin synthesis and myxoxanthophyll accumulation in the mutant strain. A new carotenoid was detected in this strain. Its chemical structure was close to that of myxoxanthophyll, but the hydroxyl group on the beta-ring was lacking. This compound, deoxy-myxoxanthophyll, most likely is an intermediate in the myxoxanthophyll biosynthesis pathway. Therefore, beta-carotene hydroxylase is involved not only in zeaxanthin synthesis but also in myxoxanthophyll synthesis in Synechocystis. Furthermore, myxoxanthophyll in Synechocystis was found to have a higher molecular mass than what was determined in other species. This difference is likely to be due to a difference in the sugar moiety.

Cyanobacteria↗

Effects of GABA-transaminase inhibition on brain metabolism and amino-acid compartmentation: an in vivo study by 2D 1H-NMR spectroscopy coupled with microdialysis.

The aim of this work was to study the neurochemical effects in the brain of GABA-transaminase inhibition by systemic administration of gabaculine (100 mg/kg, i.a.) in the rat. In order to investigate neurotransmitter and related amino-acid compartmentation and metabolism, we have developed an original tool: the coupling, in vivo, on the same animal, of 2D COSY 1H-NMR spectroscopy with intracerebral microdialysis. The main result is a continuous increase in GABA levels, both in the intracellular compartment (up to 3000+/-450%; P<0.001) and extracellular compartment (up to 808+/-82%; P<0.01) at the sixth hour. The intracellular increase in GABA level became significant at the first hour following gabaculine administration, whereas the extracellular level increased as of the second hour, probably indicating that accumulation of GABA in nerve endings precedes its release in synaptic clefts. Moreover, the levels of the excitatory amino acids, glutamate and aspartate, were decreased both in the intra- and extracellular compartments, thus enhancing sedative effects of the drug. We also observed a decrease in the global energetic creatine-phosphocreatine pool, which also could be related to the sedative properties of gabaculine, measurable by the diminution of cortical electrical activity and mean arterial blood pressure. Finally, the coupling between 2D 1H-NMR spectroscopy and intracerebral microdialysis appears to be an original tool for investigating the cerebral metabolic effects induced by pharmacological agents, in situ, in living animals.

4-Aminobutyrate Transaminase↗

[Evaluation of the attention span of 10,000 school children 8-11 years of age].

AIM: This study was conducted in order to evaluate the attention capacity during the school day and week, taking school life and others factors into account in 10,000 children (8 to 11 years old) in public Parisian schools. MATERIAL AND METHODS: The test used to measure attention was a paper and pencil test validated from the Zazzo test. The children answered a questionnaire before each test to obtain information concerning the time and day of the test, and concerning also the different life styles of children, particularly quantity and quality of sleep and composition of breakfast. The evaluation was performed four times in the morning and four times in the afternoon every day, to measure exactly the fluctuations of attention. This study lasted four weeks. The last evaluation week took place after the summer time change. RESULTS: The results showed the existence of an ultradian fluctuation of attention during the day, with the lowest level between 08.00 a.m. and 09.30 a.m. and the highest level between 04.00 p.m. and 04.30 p.m. The attention levels on Monday and Thursday, after a day without school, were not lowered. Furthermore, after a 2 days weekend the attention level was higher than after a 1 day and half weekend. The summer time change also worsened the attention capacity of children all along the next week. Finally, there was a statistical relationship between children attention capacity and their sleep practice. CONCLUSION: These results confirm the ultradian fluctuation of attention capacity and show the importance of the regularity in the child's life style with respect to their mental functioning.

Attention↗

Influence of the composition of a meal taken after physical exercise on mood, vigilance, performance.

The metabolic and behavioral effects of nutrients after exercise on vigilance level, performance, and mood have been minimally studied and have given contradictory results. In order to increase the understanding of the relationships between nutrition, exercise and performance, this experiment compared the effects on mood and performance of a protein- rich meal and a protein- poor meal, eaten just after an acute session of exercise. Vigilance and mood were evaluated by visual analog scales, and memory was measured by memory search task from the AGARD STRES battery, based on the Sternberg paradigm. Forty-two subjects were involved in this experiment. All subjects participated in the study of the effect of exercise after two kinds of meals (protein and nonprotein). Two groups of fourteen subjects we used to evaluate the effect of the exercise and the effect of the delay of meal intake after exercise in the two kinds of diet. The results show no difference in memory performance between exercise and rest conditions, nor between "protein" and "no protein" meal groups. They do show, however, that subjects feel happier after a meal with protein than after a meal without protein. The effects of the "no protein" meal on drowsiness differ with the glucide content of the meal. Subjects are less drowsy when they eat between 125 and 150 g of glucide than when they eat more than 150 g. The rousing effect induced by physical exercise is counterbalanced when subjects eat more than 150 g of carbohydrate. The anxiolytic effect of glucide is re-established.

Adult↗

Scoring of sleep and wakefulness by behavioral analysis from video recordings in rhesus monkeys: comparison with conventional EEG analysis.

Extensive work on sleep-wake cycles in non-human primates has been carried out using conventional EEG scoring. In this study, simultaneous somnopolygrams and video recordings at 1 frame/s were performed on 6 adult rhesus monkeys (Macaca mulatta) during a 24 h period. Wakefulness, NREM sleep and REM sleep were scored by analysis of animal behavior from video data, using characteristic criteria for each state of vigilance. Results were then compared with those of conventional EEG scoring. Values of the total amount for each state obtained by the two scoring methods during the light and the dark periods were significantly closely related (P < 0.001) with a high correlation coefficient for wakefulness (r1 = 0.99956), for NREM sleep (r1 = 0.99641) and for REM sleep (r1 = 0.98708). Moreover, the epoch by epoch analysis between both methods showed a high concordance with percent agreement values of 95.68% for wakefulness, 93.52% for NREM sleep and 94.02% for REM sleep. The number of REM sleep episodes was similarly defined. The patterns of successive sleep-wake cycles determined from both scorings were superimposable, as were the frequent state changes for the same time segments. The video method's main limitation was that the 4 stages of NREM sleep could not be differentiated. Reliability and advantages of sleep-wake scoring by behavioral analysis are discussed. These results suggest that the video methodology is relevant as a non-invasive technique complementary to conventional EEG analysis for sleep studies in rhesus monkeys.

Animals↗

[Role of the pharmacopoeia in the prevention of jet-lag].

Long-haul flights allow rapid crossing of times zones. When four time zones are crossed, the transmeridian flight induce jet-lag syndrome. Jet-lag is essentially composed of digestive and behavioural disturbances (insomnia and/or drowsiness). It is due to an immediate conflict between external time cues, which have been phase-advanced or phase-delayed by eastward or westward flight, respectively, and the endogenous clock. This conflict induces a desynchronization of the biological rhythms. Different counter-measures could be advised, but the most used is the pharmacological one. Hypnotics like benzodiazepines, cyclopyrones or imidazopyridines induce a recovery sleep but could also induce secondary effects in case of chronic use. Melatonin secreted by pineal gland needs more studies before a safety use for jet-lag treatment. Psychostimulants are able to induce a prolonged wakefulness. But amphetamine-like substances have to be forbidden because of the importance of side effects. New researches are studying a new galenic form of caffeine: the time release caffeine, which permits to induce a long and good quality wakefulness.

Caffeine↗

[Jet lag].

Desynchronization of circadian rhythmicity resulting from rapid travel through at least four time zones leads to symptoms known in everyday English as jet-lag. The most detrimental effect of jet-lag is fatigue with poor alertness and psychomotor performance. Severity is subject to individual variation in susceptibility (morning/evening typology, age,...) and environmental factors (direction of travel, number of time zones crossed, psychosocial environment...). Many measures used to prevent or reduce jet lag are inappropriate or ineffective and some may even be dangerous, such as use of melatonin. One of the most reliable preventive techniques consists of reinforcing social synchronizers by maintaining exposure to sunlight and social activity. Only two drugs currently available on the market can be recommended, i.e. non-benzodiazepinic hypnotics which induce high quality sleep to allow quick recovery and a new time-release caffeine agent which has been shown to prolong psychomotor performance.

Caffeine↗

Tissue-specific expression of Arabidopsis AKT1 gene is consistent with a role in K+ nutrition.

AKT1, a putative inwardly directed K+ channel of Arabidopsis, restores long-term potassium uptake in a yeast mutant defective in K+ absorption. In this paper, the expression pattern of the gene encoding AKT1 is described. Northern blots indicate that AKT1 transcripts are preferentially accumulated in Arabidopsis roots. Owing to the difficulties in producing large quantities of Arabidopsis roots under hydroponic conditions, experiments were undertaken with Brassica napus, a related species. Potassium starvation experiments on B. napus plants show that changes in the K+ status of the organs do not modify AKT1 mRNA accumulation. Western blot analysis of B. napus proteins confirms the presence of AKT1 at the root plasma membrane. Tissue-specific expression directed by the Arabidopsis AKT1 gene promoter was investigated by analysis of beta-glucuronidase (GUS) activity in transgenic Arabidopsis containing an AKT1-GUS gene fusion. As determined by fluorimetric and histochemical tests, the AKT1 promoter directs preferential expression in the peripheral cell layers of root mature regions. The discrete activity found in leaves relates to leaf primordia and to small groups of cells, hydathodes, found on toothed margins of the Arabidopsis leaf lamina. These data are discussed with regard to a possible role of AKT1 in K+ nutrition of plants.

Arabidopsis↗