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Biomedical subjects

B Claustrat

Publications and source records attributed to B Claustrat.

At least 55 records · Page 3Linked to original sources

Nocturnal plasma melatonin profile and melatonin kinetics during infusion in status migrainosus.

The plasma melatonin profile was significantly disturbed (phase-shift of the maximum melatonin level) in four out of six female sufferers from status migrainosus, compared with nine healthy controls. The number of secretion peaks was similar in both groups. A nocturnal 20 micrograms melatonin infusion (from 21.00 to 01.00 h) evoked plasma melatonin levels slightly higher than a physiological secretion peak. During infusion, the episodes of secretion were reinforced and the endogenous plasma profile was phase-advanced in two patients displaying a phase-delay. These data suggest impaired pineal function in migraine. In the absence of side effects of melatonin infusion, the relief of certain migraine symptoms described by our patients might support a controlled trial of melatonin in migraine.

Adult↗

Rapid shift in peak melatonin secretion associated with improved performance in short shift work schedule.

We studied the performance and adaptability of 40 nurses (median age 35 years), 20 on permanent day shift and 20 on permanent night shift with fast rotation of work and days off, matched for age, gender, and socio-familial responsibilities. For 15 days prior to the study, subjects maintained sleep logs and trained for performance tests. Questionnaires were administered to evaluate adaptability to shift work. During the experimental phase, sleep/wake patterns were monitored using sleep logs and activity/inactivity with wrist actigraphy. Performance levels were measured with the four choice reaction time and memory test for seven letters, eight times/day during the wake period, days on and off. On the last day of work and first day off, 6-sulfatoxy-melatonin levels were assayed from urine samples collected every 2 hours. Estimated total sleep time during the 15-day experimental period was not significantly different in the dayshift and nightshift nurses. Night nurses shifted regularly to daytime activities on days off and, as a group, were significantly sleep deprived on work days with napping on the job in 9 of the 20 night shift nurses (mean of 114+/-45 minutes per shift) and a significant performance decrement during the work period. Further analysis revealed two subgroups of night nurses: The majority (14 nurses) had a mean peak of 6-sulfatoxy-melatonin at 0718 hours on days off and no peak during night work while the other 6 night shift nurses presented a fast melatonin shift with two clear peaks on both work and days off. Comparison of performance scores revealed that all nurses performed similarly on days off. Daytime nurses and fast-shifting night nurses had similar scores on work days, while nonshifting night nurses had significantly lower scores at work. Despite similar gender, age, social conditions, and light exposure levels, a minority of the nurses studied possessed the physiological ability to adapt to a fast-shifting sleep-wake schedule of more than 8 hours and were able to perform appropriately in both conditions. This shift was associated with a change in the acrophase of 6-sulfatoxy-melatonin.

Adult↗

Pharmacokinetically guided melatonin scheduling in rats with circadian system suppression.

To obtain a pharmacologic effect of melatonin in rats kept under prolonged continuous light exposure, conditions known to produce functional suppression of the circadian system, mimicking of the physiologic 24-h pattern of melatonin secretion, a hormonal signal of darkness exposure may be needed. The delivery scheme for melatonin was established in rats in the present studies. First, the plasma pharmacokinetics of [3H]melatonin were determined in rats kept under continuous light and in rats synchronized by exposure to alternating 12 h light and 12 h darkness (LD 12:12) in the early light span. The pharmacokinetics of total radioactivity were similar in both groups. Further quantitation of melatonin by thin-layer chromatography revealed differences dependent on light conditions. The mean plasma clearance and steady-state distribution volume were approximately twice as low with continuous light as with LD 12:12. Plasma protein binding of melatonin was approximately 33%, irrespective of group or sampling time. These pharmacokinetic parameters were used to devise a 24-h periodic delivery schedule consisting of a 6-h constant infusion of exogenous melatonin, followed by an 18-h melatonin-free interval. In a second study, the melatonin 24-h pattern was estimated from the measurement of 2-h fractions of urinary 6-sulfatoxymelatonin excretion for 4 days. 6 unrestrained rats kept under continuous light received melatonin for 2 days from 22:00 to 04:00 h through an indwelling jugular catheter, connected to a reservoir from a programmable pump. Only the administration of low doses (0.01 mg/kg/day) resulted in both a circadian pattern for 6-sulfatoxymelatonin excretion and normal physiological values during the infusion-free intervals. The resynchronizing efficacy of this schedule should be tested in rats with functional suppression of the circadian system.

Animals↗

Rapid shift in sleep time and acrophase of melatonin secretion in short shift work schedule.

Tolerance to shift work and adaptability to shifting schedules is an issue of growing importance in industrialized society. We studied 40 registered nurses, 20 on fixed day-shifts and 20 on fixed night-shifts, to assess whether workers with rapidly shifting schedules were able to adapt their melatonin secretion and sleep-wake cycles. The day-shift worked 5 days with 2 days off and the night-shift worked 3 nights with 2 off. All night-shift personnel acknowledged shifting back to daytime schedules on their days off. Sleep-wake was determined by sleep logs and actigraphy. To measure 6-sulfatoxymelatonin levels, urine was collected at 2-hour intervals on the last work day and on the last day off. Night-shift workers slept significantly more on days off. Napping on the job occurred in 9/20 night-shift workers (mean 114 minutes) between 3 and 6 a.m. The acrophase of 6-sulfatoxymelatonin in day-shift nurses occurred at similar times on workdays and off days. In night-shift nurses, the acrophase was about 7 a.m. on days off, but had a random distribution on workdays. Further analysis revealed two subgroups of night-shift nurses: six subjects (group A).demonstrated a rapid shift in melatonin secretion (acrophase at near 12 noon on work days and at near 7 a.m. on days off) while 14 nurses (group B) did not shift. Group A nurses slept more in the daytime on work days and their total sleep time was the same as day-shift nurses. Group A was slightly younger and was composed solely of women (there were nine women and five men in group B). Age may be a factor in the ability to adapt to rapidly shifting schedules.

Adult↗

[Melatonin: from hormone to drug?].

Melatonin is an indole hormone that is produced by the pineal gland, mainly at night, with a peak around 3.00 a.m. under normal environmental conditions. This endogenic secretion cycle is generated by the suprachiasmatic nuclei in response to the day/night alternation. Light either suppresses or entrains melatonin production according to the time of light exposure. Melatonin can be viewed as the "hand" of the internal clock and is regulated via the central nervous and sympathetic systems. Melatonin synchronizes biological cycles, particularly the temperature and sleep/wake cycles. Exogenous melatonin can influence the endogenous secretion of melatonin according to a phase response curve, an effect that provides a rationale for the use of melatonin to treat disorders of biological rhythms (rapid time-zone change syndrome, delayed sleep phase syndrome, desynchronization in blind subjects or shift workers, insomnia in the elderly). Other therapeutic indications are being considered (immune function disorders). Improvements in galenic forms (sustained-release presentations) or the development of analogs would be significant advances.

Body Temperature↗

Induction of muricidal behavior by ACTH or adrenalectomy in young male Wistar rats.

ACTH administered IP induces a muricidal behavior in 52% of male Wistar rats that do not express it before; such behavior is also observed spontaneously in 68% of adrenalectomized animals. This change in behavior is characterized by an exceptionally long duration (several months in some animals), and by its prevention by previous or substitutive treatments with dexamethasone. Data obtained using hypophysectomized or adrenalectomized animals with or without ACTH treatments suggest that the muricidal-inducing effect of ACTH might have, at least partially, a central origin.

Adrenal Glands↗

[Melatonin in humans: a biochemical marker of the circadian clock and an endogenous synchronizer].

Melatonin (MLT) is a methoxyindole secreted principally by the pineal gland. It is synthesized at night under normal environmental conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and activated by the light/dark cycle. Light is able to both suppress or activate melatonin production on the light schedule. The nycthohemeral rhythm of this hormone can be determined by repeated measurements of plasma or saliva MLT or urine sulfatoxy-MLT, the main hepatic metabolite. Melatonin can be considered as the output (the hand) of the endogenous clock. Since the regulating system follows a central and sympathetic nervous pathway, an abnormality at any level could unspecifically modify the MLT secretion, especially in patients with sympathalgia or dysautonomia. Melatonin plays the role of an endogenous zeitgeber on core temperature or sleep-wake cycle. Exogenous MLT is able to influence the endogenous secretion of the hormone according to a phase response curve. There are practical implications for this property in situations when biological rhythms are disturbed (jet-lag syndrome, delayed sleep phase syndrome, insomnia in blind people, shift-work, insomnia in elderly people). Improvement of pharmaceutical forms (controlled release preparations) or development of MLT analogs could lead to decisive progress.

Biomarkers↗

Nocturnal melatonin excretion is decreased in patients with migraine without aura attacks associated with menses.

Nocturnal melatonin excretion was studied throughout a complete menstrual cycle in 10 women with migraine without aura attacks associated with menses and 9 women controls. Urine melatonin was determined by radioimmunoassay. The mean nocturnal melatonin excretion throughout the cycle was significantly lower in the migraine patients than in controls. In the control group, melatonin excretion increased significantly from the follicular to the luteal phase, whereas no difference was observed in the migraine group. Results are discussed in view of the role of the pineal gland in the organization of biological rhythms and homeostasis in relation to environmental conditions.

Adult↗

Heterogeneity of human prolactin. Influence on immunoassays (RIA and IRMA).

Plasma hPRL consists of a complex mixture of molecular forms. The monomeric form, derived from the pituitary, is the main form. Others (dimeric or oligomeric) can form de novo in plasma. Recently, BBPRL (big big PRL) has been identified in some cases as an antiPRL autoantibody, but these data require further investigation. The PRL forms are differently recognized by immunoassays (IRMA and RIA) and are a source of inter-assay discrepancy.

Humans↗

Melatonin is able to influence its secretion in humans: description of a phase-response curve.

A single physiological dose of melatonin (20 micrograms for 3 h given intravenously at different times of the day (04.00-12.00, 16.00 and 20.00 h) was able to shift the endogenous plasma melatonin profile of healthy volunteers under entrained conditions according to a phase-response curve (PRC). ANOVA showed an effect of the time of administration on the onset, the acrophase or the offset of the melatonin profiles. These profiles were significantly delayed when the infusion was administered at 12.00 h and advanced when the infusion was given at 20.00 h. Further, the AUCs evaluated on the nocturnal melatonin profiles were increased after the 04.00 h infusion (+20.5%, p < 0.05), whereas they were decreased after the 12.00 h infusion (-20%, p < 0.05). Lastly, no alteration was observed for cortisol rhythm, whatever the time of melatonin administration. These results, which show that according to a PRC the system regulating melatonin secretion is sensitive to a single short-term administration of the hormone given at a low dose, support the paradigm of the endogenous synchronizer melatonin.

Adult↗

Inhibitory effects of the dopamine agonists quinagolide (CV 205-502) and bromocriptine on prolactin secretion and growth of SMtTW pituitary tumors in the rat.

The SMtTW tumor, a spontaneous PRL-secreting transplantable tumor, is the only available animal model sensitive to dopamine agonists. This model has been used to compare the long term in vivo effects of CV 205-502 (CV) and bromocriptine (BR) on PRL secretion and tumor growth. These two drugs were given for 2 months to female Wistar-Furth rats bearing either small or large tumors 4 and 6 months after the graft. Untreated grafted rats served as control. In all rats treated with 5 or 10 mg/kg.day BR or 0.3 mg/kg.day CV, a normalization of plasma PRL levels was observed whatever the pretreatment levels (plasma PRL or CV or BR-treated rats, < 15 ng/ml vs. 28253 ng/ml in control rats 8 months after graft). An inhibition of tumor growth was found for both small and large tumors, but the tumors never disappeared completely (mean tumor weights at autopsy, 440 and 660 mg in BR and CV groups vs. 5270 mg in control group 8 months after graft). Experiments performed with increasing doses of BR (0.15-5 mg/kg.day) or CV (0.03-0.6 mg/kg.day) indicated that CV is effective at doses 5-10 times lower than those of BR. A shrinkage under treatment and a regrowth after drug withdrawal were demonstrated for large tumors by in vivo ultrasonographic measurements of tumor size. Histological and ultrastructural effects were similar for the two drugs: decrease in hemorrhage, reduction of the cell size and secretory activity, increase in immunoreactive PRL cellular content, and inhibition of exocytosis. There was no difference in the PRL mRNA content of treated and untreated tumors, as assessed by in situ hybridization. In conclusion, CV and BR exhibit similar inhibitory effects on tumor growth and PRL secretion. These effects are rapidly and fully reversible after drug withdrawal. The present results give a complete account of the actions of the two dopamine agonists under conditions comparable to those used in the treatment of human prolactinomas.

Aminoquinolines↗

[The nyctohemeral rhythm of melatonin is preserved in human African trypanosomiasis].

We studied plasma melatonin profiles by radioimmunoassay in nine patients suffering from human african trypanosomiasis and six healthy controls matched according to the age and the photoperiodic conditions. The circadian periodicity of the sleep-wake cycle was disturbed proportionally to the degree of severity of the disease. On the contrary, the patients' plasma melatonin profile was similar to the controls' one. These results suggest that, beside the master clock generating the main circadian rhythms (sleep-wake, melatonin and core temperature rhythms), an additional regulating system of the melatonin rhythm could be involved.

Adolescent↗

Long-term isolation of Wistar rats alters brain monoamine turnover, blood corticosterone, and ACTH.

In this work, we investigated neurochemical parameters in the brain of male Wistar rats after isolation times (13 weeks) longer than those previously reported with this strain: a large majority of animals became muricidal under these conditions. Changes in monoamines turnover in hippocampus, cortex, and cerebellum and, in the blood, ACTH, and corticosterone were investigated. Monoamine turnover was analysed using two different approaches: first, by measuring neurotransmitter and metabolite levels and second, by measuring rate of accumulation of the precursor after decarboxylase. Both methods revealed a significant increase in catecholamine turnover in the three regions studied after the 13-week isolation; in contrast, only a modest elevation of 5-hydroxytryptophan accumulation was obtained in cortex and cerebellum of isolated rats. We also observed a decrease in corticosterone levels in blood concomitant with an increase of ACTH.

5-Hydroxytryptophan↗

European isolation and confinement study. Blood pressure, volume-regulating hormones, and electrolytes.

In the ISEMSI confinement experiment we observed three main reactions concerning blood volume regulation: first, a stress activation produced by the high workload that the subjects had to accomplish, both before the isolation period and during the two first weeks of isolation; second, a typical defense reaction to the environment occurred, at least during the two initial days of isolation and later perhaps between crew members themselves; and third, a change in blood volume regulating hormone levels may have been the result of the increase of sympathetic system activity and of dehydration. Confinement is certainly a good and valid method to simulate space station life (with the absence of weightlessness). So, it is interesting to use these confinement studies to perform biological and physiological experiments to obtain greater knowledge, but also to prepare and validate new scientific protocols or new scientific equipment suitable for spaceflights. Even more so, confinement is a good way to prepare and train crew members for long-term space missions. It would seem desirable to confirm the scientific results obtained during the ISEMSI campaign, and especially those for the regulation of the blood volume. This will be done during the next confinement experiment, called EXEMSI, in which four subjects will be subjected to 60 days of confinement.

Adult↗

Platelet serotonin content and free and total plasma tryptophan in healthy volunteers during 24 hours.

The determination of platelet serotonin (5-HT) and plasma tryptophan concentrations is useful in the diagnosis, investigation of etiologies, and treatment of psychiatric disorders. To determine the usual circadian variations in platelet 5-HT and free and total tryptophan concentrations, we measured these variables during 24 h at 1-h intervals and every 30 min from 2000 to 0800 in seven clinically healthy young men with an HPLC method. No common circadian rhythm for platelet serotonin concentrations was observed in our subjects; however, there was a distinct rhythm for both free and total plasma tryptophan: Concentrations were maximal in the afternoon and minimal during the night.

Adult↗

Melatonin and jet lag: confirmatory result using a simplified protocol.

This study replicates the alleviation of jet-lag with melatonin in a simplified protocol for eastward flight. At 22-n hr (n is the time-lag between the North American departure point and France), subjects took either melatonin (8 mg, n = 15), or placebo (n = 15) on the day of the return flight and for 3 consecutive days. On day 8, self-ratings significantly discriminated between melatonin and placebo for global treatment efficacy, morning fatigue, and evening sleepiness.

Adult↗

Inter-relationships between pituitary-adrenal hormones and catecholamines during a 6-day Nordic ski race.

The aim of the study was to investigate the inter-relationships between pituitary-adrenal hormones and catecholamines during a prolonged competition over 6 days. Plasma adrenocorticotropic hormone (ACTH), cortisol (C), beta-endorphin (beta EP), free and sulphated adrenaline (A) and noradrenaline (NA) were measured in 11 volunteer male subjects during a national Nordic-ski race (323 km). Blood samples were obtained before the competition in the evening as control (D0), and before and after each day's racing (D1-D6). The mean daily heart rate (fc) was calculated from fc values recorded every minute during the race. The results showed the following: changes in mean fc [from 147 (SEM 3) to 156 (SEM 3) beats.min-1 according to the day] were not significant during the race. Diurnal variations in ACTH, beta EP and C were no longer apparent after the race: evening levels were higher than their respective D0 values during the race, except on D3 when there was a lack of response to exercise in the three hormones. Unlike ACTH and beta EP, pre- and postexercise C values on D1 and D2 were higher than those on the subsequent days (P less than 0.001). In contrast, there was a progressive accumulation of A and NA in pre- and postrace concentrations which reached a plateau in about 4 days. Positive correlations between exercise responses in ACTH, C and beta EP were found especially on D3 and D6 (P less than 0.001) but there were no significant correlations between catecholamines and the other three hormones. Thus, prolonged competition over 6 days evoked different control mechanisms for hormones of the pituitary-adrenal axis and catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

Hemodynamic and hormonal responses to hypothermic and normothermic cardiopulmonary bypass.

Normothermic cardiopulmonary bypass (CPB) is used in cardiac surgery at some institutions. To compare hemodynamic and hormonal responses to hypothermic (29 degrees C) and normothermic nonpulsatile CPB, 20 adults undergoing coronary artery bypass graft and/or aortic valve replacement were studied. Hemodynamic measurements and plasma hormone concentrations were obtained from preinduction to the third postoperative hour. The two groups were given similar amounts of anesthetics and vasodilators. Systemic vascular resistance increased only during hypothermic CPB, and heart rate was higher at the end of hypothermic CPB. Postoperative central venous pressure and pulmonary capillary wedge pressure were lower after hypothermic CPB. Oxygen consumption decreased by 45% during hypothermic CPB, did not change during normothermic CPB, but increased similarly in the two groups after surgery; mixed venous oxygen saturation (SvO2) was significantly lower during normothermic CPB. Urine output and composition were similar in the two groups. In both groups, plasma epinephrine, norepinephrine, renin activity, and arginine vasopressin concentrations increased during and after CPB. However, epinephrine, norepinephrine, and dopamine were 200%, 202%, and 165% higher during normothermic CPB than during hypothermic CPB, respectively. Dopamine and prolactin increased significantly during normothermic but not hypothermic CPB. Atrial natriuretic peptide increased at the end of CPB and total thyroxine decreased during and after CPB, with no difference between groups. This study suggests that higher systemic vascular resistance during hypothermic CPB is not caused by hormonal changes, but might be caused by other factors such as greater blood viscosity. A higher perfusion index during normothermic CPB might have allowed higher SvO2.

Aortic Valve↗