Biomedical subjects

Alain Buguet

Publications and source records attributed to Alain Buguet.

15 recordsLinked to original sources

PubMed2006

Recombinant human erythropoietin prevents the death of mice during cerebral malaria.

Cerebral involvement during malaria is a complication that leads to seizure, coma, and death. The effect of new neuroprotective therapies has not yet been investigated, although cerebral malaria shares some features with neurological stroke. Erythropoietin (EPO) is one of the more promising drugs in this area. We measured the effect of EPO on the survival of mice infected with Plasmodium berghei ANKA and demonstrated that inoculations of recombinant human EPO at the beginning of the clinical manifestations of cerebral malaria protect >90% of mice from death. This drug has no effect on the course of parasitemia. The effect of EPO was not related to either the inhibition of apoptosis in the brain or the regulation of the increase and decrease of nitric oxide production in the brain and blood, respectively. Tumor necrosis factor-alpha and interferon-gamma mRNA overexpression was inhibited by EPO, and treated mice had fewer brain hemorrhages. EPO has been used in patients with chronic diseases for years, and more recently it has been used to treat acute ischemic stroke. The data presented here provide the first evidence indicating that this cytokine could be useful for the symptomatic prevention of mortality during the acute stage of cerebral malaria.

Animals↗

PubMed2005

Sleep structure: a new diagnostic tool for stage determination in sleeping sickness.

Human African trypanosomiasis (HAT), due to the transmission of Trypanosoma brucei (T. b.) gambiense and T. b. rhodesiense by tsetse flies, is re-emerging in inter-tropical Africa. It evolves from the hemolymphatic Stage I to the meningo-encephalitic Stage II. The latter is generally treated with melarsoprol, an arseniate provoking often a deadly encephalopathy. A precise determination of the HAT evolution stage is therefore crucial. Stage II patients show: (i) a deregulation of the 24-h distribution of the sleep-wake alternation; (ii) an alteration of the sleep structure, with frequent sleep onset rapid eye movement (REM) periods (SOREMPs). Gambian HAT was diagnosed in eight patients (four, Stage II; three, Stage I; one, "intermediate" case) at the trypanosomiasis clinic at Viana (Angola). Continuous 48-h polysomnography was recorded on Oxford Medilog 9000-II portable systems before and after treatment with melarsoprol (Stage II) or pentamidine (Stage I and "intermediate" stage). Sleep traces were visually analyzed in 20-s epochs using the PRANA software. Stage II patients showed the complete sleep-wake syndrome, partly reversed by melarsoprol 1 month later. Two Stage I patients did not experience any of these alterations. However, the "intermediate" and one Stage I patients exhibited sleep disruptions and/or SOREMPs, persistent after pentamidine treatment. Polysomnography may represent a diagnostic tool to distinguish the two stages of HAT. Especially, SOREMPs appear shortly after the central nervous system invasion by trypanosomes. The reversibility of the sleep-wake cycle and sleep structure alterations after appropriate treatment constitutes the basis of an evaluation of the healing process.

Adolescent↗

PubMed2005

Clinical assessment of the entry into neurological state in rat experimental African trypanosomiasis.

Human African trypanosomiasis, caused by Trypanosoma brucei (T.b.) gambiense or rhodesiense, evolves in two stages: haemolymphatic stage and meningo-encephalitic stages, the latter featuring numerous neurological disorders. In experimental models infected with diverse T.b. sub-species, body weight (BW) loss, drop in food intake (FI), and hypo-activity after an asymptomatic period suggest the occurrence of a similar two-stage organization. In addition to daily measurement of BW and FI, body core temperature (T(co)) and spontaneous activity (SA) were recorded by telemetry in T.b. brucei-infected rats. After a 10--12-day symptom-free period, a complex clinical syndrome occurred suddenly. If the animal survived the access, the syndrome re-occurred at approximately 5-day intervals until death. The syndrome was made of a drop in FI and BW, a sharp decrease in T(co) and a loss of SA, suggesting a brisk alteration of the central nervous system functioning. Such events confirm the existence of a two-stage disease development in experimental trypanosomiasis. The entry into the second stage is marked by the occurrence of the first access, BW follow-up being essential and often sufficient its determination.

Animals↗

PubMed2005

Disruptions of ultradian and circadian organization of core temperature in a rat model of African trypanosomiasis using periodogram techniques on detrended data.

Periodogram techniques on detrended data were used to determine the incidence of Trypanosoma brucei brucei infection on the distribution of the core temperature of rats and the expression of temperature rhythms. In such an animal model, sudden episodic hypothermic bouts were described. These episodes of hypothermia are used here as temporal marks for the purpose of performing punctual comparisons on temperature organization. The experiment was conducted on 10 infected and 3 control Sprague-Dawley rats reared under a 24 h light-dark cycle. Core temperature was recorded continuously throughout the experiment, until the animals' death. Temperature distributions, analyzed longitudinally across the full duration of the experiment, exhibited a progressive shift from a bimodal to unimodal pattern, suggesting a weakening of the day/night core temperature differences. After hypothermic events, the robustness of the circadian rhythm substantially weakened, also affecting the ultradian components. The ultradian periods were reduced, suggesting fragmentation of temperature generation. Moreover, differences between daytime and nighttime ultradian patterns decreased during illness, confirming the weakening of the circadian component. The results of the experiments show that both core temperature distribution and temperature rhythm were disrupted during the infection. These disruptions worsened after each episode of hypothermia, suggesting an alteration of the temperature regulatory system.

Animals↗

PubMed2005

Hypersomnia.

Hypersomnia, a complaint of excessive daytime sleep or sleepiness, affects 4% to 6% of the population, with an impact on the everyday life of the patient Methodological tools to explore sleep and wakefulness (interview, questionnaires, sleep diary, polysomnography, Multiple Sleep Latency Test, Maintenance of Wakefulness Test) and psychomotor tests (for example, psychomotor vigilance task and Oxford Sleep Resistance or Osler Test) help distinguish between the causes of hypersomnia. In this article, the causes of hypersomnia are detailed following the conventional classification of hypersomnic syndromes: narcolepsy, idiopathic hypersomnia, recurrent hypersomnia, insufficient sleep syndrome, medication- and toxin-dependent sleepiness, hypersomnia associated with psychiatric disorders, hypersomnia associated with neurological disorders, posttraumatic hypersomnia, infection (with a special emphasis on the differences between bacterial and viral diseases compared with parasitic diseases, such as sleeping sickness) and hypersomnia, hypersomnia associated with metabolic or endocrine diseases, breathing-related sleep disorders and sleep apnea syndromes, and periodic limb movements in sleep.

Circadian Rhythm↗

PubMed2004

Effects of sleep deprivation on spontaneous arousals in humans.

STUDY OBJECTIVES: The hierarchical definition of arousals from sleep includes a range of physiologic responses including microarousals, delta and K-complex bursts, and variations in autonomic system. Whether patterns in slow-wave electroencephalographic activity and autonomic activation are primary forms of arousal response can be addressed by studying effects of total sleep deprivation. We therefore examined changes in arousal density during recovery sleep in healthy subjects. DESIGN: Participants spent 6 consecutive 24-hour periods in the laboratory. Nights 1 and 2 were baseline nights followed by 64-hour total sleep deprivation, then 2 consecutive recovery nights. SETTING: Sleep-deprivation protocol was conducted under laboratory conditions with continuous behavioral and electrophysiologic monitoring. PARTICIPANTS: Twelve drug-free men aged 27.4 +/- 7.9 years were studied. None reported sleepiness or altered sleep-wake cycle, and none had neurologic, psychiatric or sleep disorders. INTERVENTION: N/A. MEASUREMENTS AND RESULTS: Arousals were classified into 4 levels: microarousals, phases of transitory activation, and delta and K-complex bursts. Sleep deprivation induced changes in the density of considered arousals except phases of transitory activation, with a distinct pattern among the different types. The greatest change was found for microarousals, which showed a significant decrease in the first recovery night (P = .01), with return to baseline thereafter. A fall in K-complex and delta-burst density was noted in the first recovery night, not, however, reaching statistical significance. The phases of transitory activation rate were virtually unaffected throughout the experimental nights. CONCLUSIONS: We conclude that homeostatic sleep processes exert an inhibitory effect on arousal response from sleep with a significant effect only on the microarousal density. Decreased delta and K-complex burst rates, though not significant, support the hypothesis that they may be activating processes, probably modulated by factors independent from those implicated in cortical arousal.

Adult↗

PubMed2004

Twenty-four-hour disruption of the sleep-wake cycle and sleep-onset REM-like episodes in a rat model of African trypanosomiasis.

STUDY OBJECTIVES: Patients with human African trypanosomiasis (sleeping sickness) due to the inoculation of Trypanosoma brucei gambiense or rhodesiense show a major disruption of the 24-hour sleep-wake distribution, accompanied by the occurrence of sleep-onset rapid-eye-movement (REM) sleep episodes, proportional to the severity of the illness. Although animal models of human African trypanosomiasis have been developed to understand the pathogenic mechanisms leading to immune alterations, the development of an animal model featuring the alterations of endogenous biologic rhythms remains a necessity. ANIMALS: Sprague-Dawley rats (N = 10) entrained to a 12:12-hour dark-light regimen. INTERVENTIONS: Rats were infected with Trypanosoma brucei brucei AnTat 1.1E and instrumented with electrocorticographic and electromyographic electrodes. Polysomnography was recorded continuously from 2 days before infection until the animal's death. MEASUREMENTS AND RESULTS: The analysis of the spontaneous sleep-wake architecture revealed an increased proportion of slow-wave sleep (SWS) and a decreased amount of wakefulness 2 days before death. Considerable sleep fragmentation was observed in the infected rats, with numerous changes in sleep-wake stages and an increased number of episodes of wakefulness and SWS. Infected rats presented a fragmented pattern of SWS and a marked reduction in the mean paradoxical-sleep (PS) latency, resulting in a considerable disruption of the PS-SWS sequences. Abnormal transitions, particularly the appearance of sleep-onset REM episodes, marked the disruption of the internal sleep structure. The electrocorticogram traces were modified during SWS, with the occurrence of abnormal hypersynchronic slow waves and a disappearance of spindles. CONCLUSION: The Trypanosoma brucei brucei-infected rat is a good model of the syndrome seen in human African trypanosomiasis, ie, the 24-hour disruption of the sleep-wake cycle and the occurrence of sleep-onset REM-like sleep episodes.

Animals↗

PubMed2004

Heart rate activation during spontaneous arousals from sleep: effect of sleep deprivation.

OBJECTIVE: Arousal (AR) from sleep is associated with an autonomic reflex activation raising blood pressure and heart rate (HR). Recent studies indicate that sleep deprivation may affect the autonomic system, contributing to high vascular risk. Since in sleep disorders a sleep fragmentation and a partial sleep deprivation occurs, it could be suggested that the cardiovascular effects observed at AR from sleep might be physiologically affected when associated with sleep deprivation. The aim of the study was to examine the effect of sleep deprivation on cardiac arousal response in healthy subjects. METHODS: Seven healthy male subjects participated in a 64 h sleep deprivation protocol. Arousals were classified into four groups, i.e. >3<6 s, >6<10 s, >10<15 s and >15 s, according to their duration. Pre-AR HR values were measured during 10 beats preceding the AR onset, and the event-related HR fluctuations were calculated during the 20 beats following AR onset. As an index of cardiac activation, the ratio of highest HR in the post-AR period over the lowest recorded before AR (HR ratio) was calculated. RESULTS: For AR lasting less than 10 s, the occurrence of AR induces typical HR oscillations in a bimodal pattern, tachycardia followed by bradycardia. For AR lasting more than 10 s, i.e. awakenings, the pattern was unimodal with a more marked and sustained HR rise. The HR response was consistently similar across nights, during NREM and REM sleep, without difference between conditions. CONCLUSIONS: Overall, total sleep deprivation appeared to have no substantial effect on cardiac response to spontaneous arousals and awakenings from sleep in healthy subjects. Further studies are needed to clarify the role of chronic sleep deprivation on cardiovascular risk in patients with sleep disorders. SIGNIFICANCE: In healthy subjects acute prolonged sleep deprivation does not affect the cardiac response to arousal.

Adult↗

PubMed2004

Megazol combined with suramin improves a new diagnosis index of the early meningo-encephalitic phase of experimental African trypanosomiasis.

In human African trypanosomiasis (HAT), the parasites invade the central nervous system (CNS), leading to the development of meningo-encephalitis and an irreversible demyelinating process, which kills the patient unless specific treatment is undertaken. Among the experimental trypanocides, the nitroimidazole derivative megazol alone at optimal doses does not cure late-stage disease tested in mouse models, however the combination of suramin and megazol is able to cure infected mice without CNS involvement. We recently developed an experimental model of HAT with a sharp decrease in both the food intake and the body weight which may constitute an effective index of the early meningo-encephalitic phase. Using this model, we tested this hypothesis by the exclusive effectiveness of a megazol and suramin combination treatment to eliminate CNS trypanosomes. Sprague-Dawley rats were infected with Trypanosoma brucei brucei AnTat 1.1E. Food intake and body weight were measured daily from the day of infection to death. Haematocrit was measured twice a week. Treatment consisted of 20 mg suramin per kg body weight administered intraperitoneally (i.p.) alone, or three daily doses (80 mg/kg) of megazol given per os, or suramin (20 mg/kg, i.p.) followed 24 h later by three daily doses (80 mg/kg) of megazol given per os. Treatment was followed by an increase in daily body weight and food intake similar to those of the control animals, 2 weeks after treatment. The anaemia developed after infection is also cleared as shown by the haematocrit measurements. The rats treated with megazol alone died about 29 days after treatment and those treated with suramin, after about 26 days. Seven months later, no signs of relapse were seen in 10 of 12 rats treated with the therapeutic combination, indicating that this chemotherapy regimen was curative. The results support our previous finding, i.e. the decrease in body weight may constitute a diagnosis index of the early meningo-encephalitic phase.

Anemia↗

PubMed2003

Behavioural changes after an acute stress: stressor and test types influences.

Behavioural consequences of different acute stressors (30 min of restraint, 20 min of forced swim stress, 15 min of inescapable footshocks) applied at the beginning of the active period were assessed in using two behavioural tests: a 20 min light extinction test 24 h after the stressor exposure in order to explore the psychomotor ability and a 10 min open field session within the dark period 48 h after the stressor exposure to estimate the emotional status and the locomotor activity of the rat. Different behavioural responses were observed depending on the nature of the applied stressor. In the light extinction test, the footshock-stressed rats developed a very low activity independent on light conditions whereas the rats submitted to forced swim and restraint exhibited an activity level depending on the strain. Moreover, restrained rats had a higher transient activity than forced swim rats under light condition. In the open field test, none of the stressed rats did develop differences in behaviour. The efficacy of a 24 h recovery period on the behavioural response to an acute stressor exposure depends on the intensity of the applied stressor and the behavioural demands.

Adaptation, Psychological↗

PubMed2003

Distinctive effects of modafinil and d-amphetamine on the homeostatic and circadian modulation of the human waking EEG.

RATIONALE: Modafinil is a wake-promoting agent that affects hypothalamic structures involved in the homeostatic and circadian regulation of vigilance. Administered during sleep deprivation, it reduces the need for prolonged recovery sleep and decreases the rebound in EEG slow-wave activity. These diachronic effects suggest an action of modafinil on a homeostatic sleep regulatory process. OBJECTIVES: The aim of this study was to determine whether modafinil, in comparison to the d-amphetamine reference psychostimulant and to placebo, interferes with the vigilance regulatory processes reflected in the EEG during waking. METHODS: Thirty-three healthy subjects were investigated during 60 h of sustained wakefulness in a double-blind placebo-controlled parallel-design study. A 4-min maintenance-of-wakefulness test administered hourly allowed the concomitant assessment of alertness and waking EEG activity. The effects of equipotent psychostimulant dosages (modafinil 300 mg and d-amphetamine 20 mg) were evaluated at the beginning of the first sleep deprivation night, at the end of the second sleep deprivation night and in the afternoon preceding the first recovery night. RESULTS: One hour following ingestion, both psychostimulants increased alertness during 10-12 h, independently of the time of administration. At the level of the waking EEG, d-amphetamine attenuated the natural circadian rhythm of the different frequency bands and suppressed the sleep deprivation-related increase in low frequency (0.5-7 Hz) powers. In contrast, modafinil, which exhibited a transient amphetamine-like effect, had slight effect on circadian rhythms. Its selective action was characterized by maintenance of the alpha(1) (8.5-11.5 Hz) EEG power, which under placebo exhibited a homeostatic decrease paralleling that of alertness with a circadian trough at night. CONCLUSIONS: These findings demonstrate that the alertness-promoting effects of modafinil and d-amphetamine involve distinct EEG activities and do not reside on the same vigilance regulatory processes. While d-amphetamine inhibits the expression of a sleep-related process, probably through a direct cortical activation masking EEG circadian rhythms, modafinil, through a synchronic effect, preferentially disrupts the homeostatic down-regulation of a waking drive.

Adolescent↗

PubMed2003

Daytime sleepiness during Ramadan intermittent fasting: polysomnographic and quantitative waking EEG study.

During the lunar month of Ramadan, Muslims abstain from eating, drinking and smoking from sunrise to sunset. We reported previously that Ramadan provokes a shortening in nocturnal total sleep time by 40 min, an increase in sleep latency, and a decrease in slow-wave sleep (SWS) and rapid eye movement (REM) sleep duration during Ramadan. During the same study, the effects of Ramadan intermittent fasting on daytime sleepiness were also investigated in eight healthy young male subjects using a quantitative waking electroencephalograph (EEG) analysis following the multiple sleep latency test (MSLT) procedure. This procedure was combined with subjective alertness and mood ratings and was conducted during four successive experimental sessions: (1) baseline (BL) 15 days before Ramadan, (2) beginning of Ramadan (R11) on the 11th day of Ramadan, (3) end of Ramadan (R25) on the 25th day of Ramadan, (4) recovery 2 weeks after Ramadan (AR). During each session, four 20-min nap opportunities (MSLTs) were given at 10:00, 12:00, 14:00 and 16:00 h and were preceded by rectal temperature readings. Nocturnal sleep was recorded before each daytime session. Subjective daytime alertness did not change in R25 but decreased in R11 at 12:00 h, and subjective mood decreased at 16:00 h, both in R11 and R25. During the MSLT, mean sleep latency decreased by an average of 2 min in R11 (especially at 10:00 and 16:00 h) and 6 min in R25 (especially at 10:00 and 12:00 h) compared with BL. There was an increase in the daily mean of waking EEG absolute power in the theta (5.5-8.5 Hz) frequency band. Significant correlations were found between sleep latency during the MSLT and the waking EEG absolute power of the fast alpha (10.5-12.5 Hz), sigma (11.5-15.5 Hz) and beta (12.5-30 Hz) frequency bands. Sleep latency was also related to rectal temperature. In conclusion, Ramadan diurnal fasting induced an increase in subjective and objective daytime sleepiness associated with changes in diurnal rectal temperature.

Adult↗

PubMed2003

Modafinil--medical considerations for use in sustained operations.

An understanding of the consequences of sustained operations involving prolonged sleep deprivation is important to the military. Losses in cognitive performance of the order of 30% after one night and 60% after two nights of sleep loss have been shown to occur in several studies. Napping strategies have been proposed as one coping strategy for these performance decrements. An alternate solution is the use of stimulants. Modafinil may offer a safer alternative to more commonly used psychostimulants. It has been shown to counteract the effects of sleep deprivation with fewer side effects than amphetamine. Recent studies on the effects of modafinil during sleep deprivation are reviewed and compared with those of other stimulants such as amphetamine and caffeine, and to prophylactic naps. Recommendations are proposed for the use of modafinil in sustained military missions. For missions of about 24 h, modafinil is preferable to naps. For longer missions, naps should be considered, along with the concomitant use of modafinil to help maintain performance levels. The authors discuss apparent 'overconfidence' and hyperthermia-inducing effects of modafinil, and advise that these effects be taken into account if modafinil is to be used in any mission conducted in the field or in hot environments. It is also recommended that individual sensitivity to the drug should be tested before any mission of a sustained nature, especially if it involves small operational groups or combat aircrew, where the impact of such effects on individuals would be more critical.

Caffeine↗

PubMed2002

Effect of modafinil on core temperature during sustained wakefulness and exercise in a warm environment.

BACKGROUND: Previous studies have revealed that modafinil elevates resting core temperature during periods of sustained wakefulness. The purpose of this study was to examine the effects of modafinil on core temperature during rest and exercise throughout 40 h of sustained wakefulness in a warm environment. METHODS: Ten males performed a drug session (three 100 mg doses per day) and a placebo session that involved a control day, 40 h of sustained wakefulness, and a recovery sleep. For 38 h of the sustained wakefulness, subjects were exposed to 30 degrees C with 50% relative humidity. During the afternoon of both days of wakefulness and during the early morning of the second day, subjects performed 2 h of exercise at 60% VO2max while exposed to the warm environment. RESULTS: The data revealed that rectal temperature (Tre) was elevated at rest 0.15-0.2 degrees C following modafinil ingestion throughout the period of sustained wakefulness. This increase in body temperature at rest was due to an increase in heat production during the first day of wakefulness followed by a lower evaporative heat loss during the second day. During exercise, an inconsistent effect of the drug on Tre was observed throughout the 38-h period. On the first afternoon, the impact of modafinil on Tre was no longer evident after 20 min of exercise. In contrast, during the early morning and afternoon of the second day, the effects of the drug on Tre at rest remained during exercise. For seven subjects who had Tre data for 80 min during all exercise periods, Tre during the placebo session was 38.9, 38.4, and 38.7 degrees C after 80 min of exercise for periods one, two and three, respectively, whereas the corresponding values during the modafinil session were 38.8, 38.7, and 38.9 degrees C. CONCLUSION: With a greater cumulative dose of the drug, Tre remained elevated throughout the exercise period to an extent similar to the increase observed under resting conditions when compared with the placebo condition.

Adult↗

PubMedDate not supplied

[The sleep of Africans and Europeans in the Ivory Coast: questionnaire study].

Sleep behaviour has been extensively studied with questionnaires in industrialised countries to investigate the epidemiology of sleep-wake disorders. However, only few attempts have yet been made to examine sleep behaviour of people living in Africa. Although, a large number of studies in hot or cold environments have used short-term exposures, reporting disrupted sleep for most of them, long-term exposures to stressful thermal environments are rare in the literature. Prior to the present investigation, we used questionnaires to analyse the effects of seasonal heat increase on perceived sleep behaviour and sleep quality in young native African students in Niger [7], even though these methods of investigation are by no means as accurate as polysomnographic recordings. The hypothesis was that sleep behaviour may be influenced by climatic variations in a hot dry tropical climate. Such climatic variations have been shown to induce seasonal heat acclimatisation marked by changes in body temperature rhythms in the hot versus the cool season [13]. Sleep behaviour was examined during two 7-day periods in January ("cool-dry" season, 88 subjects) and May ("hot-dry" season, 53 subjects). The questionnaire was completed after night sleep and/or naps. The subjects slept an average of 7 1/2 hours a day, most of them having afternoon naps. They experienced no major seasonal variation in their sleep behaviour, but for an increased number of awakenings during the hot season. Restorative quality of sleep scored lower after a nap than after nocturnal sleep. Therefore, general sleep characteristics were not modified by seasonal temperature variations in African native students, perhaps because of the limited changes in daylight under the low latitude of Niamey. Another investigation was carried out using the same 12-item questionnaire in Abidjan on 78 medical students who did not have a nap [9]. Contrary to the Niamey students, the Abidjan subjects adopted short duration sleep schedules, without any effect on the subjective quality of the restorative properties of their sleep.

Adult↗