Search PubMed⌕ Search

Biomedical subjects

O Van Reeth

Publications and source records attributed to O Van Reeth.

51 records · Page 3Linked to original sources

Administering triazolam on a circadian basis entrains the activity rhythm of hamsters.

A single injection of the short-acting benzodiazepine, triazolam, can induce permanent phase shifts in the circadian rhythm of locomotor activity in free-running hamsters, with the direction and magnitude of the phase shifts being dependent on the circadian time of treatment. The shape of the "phase-response curve" to triazolam injections is totally different from that for light pulses. These findings raise the possibility that repeated injections of triazolam on a circadian basis might be capable of entraining the circadian pacemaker underlying the activity rhythm of hamsters and that the entrainment pattern might differ from that observed in animals entrained to light pulses. To test this hypothesis, blind hamsters received intraperitoneal injections of triazolam (or vehicle) every 23.34, 23.72, 24.00 or 24.66 h for 19-20 days, and the effect of these injections on the period of the rhythm of wheel-running behavior was determined during and after treatment. Repeated injections of 0.1 mg triazolam at these time intervals resulted in the entrainment of the activity rhythm in 36 of 40 animals, whereas 0 of 40 animals entrained to vehicle injections. Importantly, the phase relationship between triazolam injections and the circadian activity rhythm was dependent on the period of drug treatment and could be predicted from the phase-response curve to single injections of triazolam. These phase relationships are dramatically different from those observed between the activity rhythm and 1-h light pulses presented at similar circadian intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Use of benzodiazepines to manipulate the circadian clock regulating behavioral and endocrine rhythms.

Extensive studies have now been carried out demonstrating that the systemic administration of the short-acting benzodiazepine, triazolam, can have pronounced effects on both behavioral and endocrine circadian rhythms. For example, three daily injections of triazolam can phase-advance the circadian rhythm of pituitary luteinizing hormone release and locomotor activity by about 2-3 h in female hamsters maintained in constant light. Triazolam has also been found to facilitate the rate of reentrainment of the activity rhythm following an 8-hour advance or delay in the light-dark cycle. Limited studies with other short-acting benzodiazepines indicate that the effects of triazolam on the circadian system of hamsters can be generalized to this class of drugs. Recent studies in humans indicate that treatment with triazolam can alter the time it takes for human endocrine rhythms to become reentrained following an 8-hour delay in the sleep-wake and light-dark cycle. Such findings raise the possibility that short-acting benzodiazepines may prove useful in reducing the symptoms associated with 'jet-lag' and rotating shift-work schedules as well as in the treatment of various physical and mental illnesses that have been associated with a disorder of biological timekeeping.

Animals↗

A benzodiazepine antagonist, Ro 15-1788, can block the phase-shifting effects of triazolam on the mammalian circadian clock.

A single injection of the short acting benzodiazepine, triazolam, can induce permanent phase advances as well as phase delays in the onset of the circadian rhythm of wheel running behavior in hamsters free-running under constant environmental conditions. If the phase shifting effects of triazolam on the circadian system are mediated through the benzodiazepine-GABA receptor complex, then it should be possible to block these effects with RO 15-1788, a selective benzodiazepine antagonist, which acts at the benzodiazepine-GABA receptor level. To test this hypothesis, hamsters free running in constant light received an intraperitoneal injection of various doses of Ro 15-1788 15 min before a single i.p. injection of 0.5 mg of triazolam. This dose of triazolam is known to induce maximal phase shifts in the circadian rhythm of wheel running behavior in hamster. Treatment with Ro 15-1788 totally blocked both the phase advancing and phase delaying effects of triazolam, while the administration of Ro 15-1788 alone did not phase shift the activity rhythm. These results support the hypothesis that the phase shifting effects of triazolam are mediated through the benzodiazepine-GABA receptor complex. The absence of any phase shifting effects of Ro 15-1788 when delivered alone suggests that Ro 15-1788 has no partial agonist properties in this experimental paradigm.

Animals↗

Manipulation of the circadian clock with benzodiazepines: implications for altering the sleep-wake cycle.

Abnormal circadian rhythms have been linked to at least some forms of depression and to disturbances in the sleep-wake cycle. In addition, mental and physical disorders associated with rapid travel across time zones (i.e. the jet-lag syndrome) and with rotating shift-work schedules, are thought to involve a disruption of normal circadian rhythmicity. It might be possible to alleviate some of the adverse effects associated with abnormal circadian rhythms if pharmacological agents could be used to manipulate the central circadian pacemaker(s) that regulates these rhythms. Recent findings indicate that treatment with a short-acting benzodiazepine, triazolam, can induce major shifts in the circadian clock of golden hamsters. In the absence of a synchronizing light-dark cycle (i.e. during exposure to constant light or constant dark), a single injection of triazolam can induce a permanent phase shift in the circadian rhythm in locomotor activity. In addition, following a shift in the light-dark cycle, a single injection of triazolam can facilitate the time it takes for the activity rhythm to be resynchronized to the new lighting schedule. Triazolam, or drugs with similar phase-shifting effects on the mammalian circadian system, might be useful in the treatment of various sleep and mental disorders that have been associated with a disorder in circadian time-keeping in humans.

Animals↗

Effect of amiodarone on serum T4 and T3 levels in hyperthyroid patients treated with methimazole.

We investigated the course of thyroid hormones levels in the serum of hyperthyroid patients acutely treated with amiodarone. Ten patients were treated either with amiodarone, 3 X 400 mg daily for 3 days in addition to methimazole, 3 X 20 mg daily for 10 days (Group I; n = 5) or with a placebo plus methimazole at the same doses (Group II; n = 5). Basal T3, T4 and rT3 serum concentrations were: 297 ng/dl, 16.6 micrograms/dl and 507 pg/dl, respectively in Group I and 377 ng/dl, 17.6 micrograms/dl and 362 pg/dl in Group II (NS). Compared with basal values, the drop in serum T3 concentration became significant on Day 1 in Group I, but not until day 5 in Group II. The decrease in serum T3 concentration was significantly higher in Group I than in Group II from Day 1 to Day 7. In Group I, T4 concentration was significantly lower on Days 2, 4 and 6; the percentage drop in T4 calculated from the areas under the curves was higher and the T3/T4 ratio lower on Days 3-5, 7 and 9; rT3 was higher on Days 4 and 5 and its rise was significant on Days 1, 3 and 4. During the follow-up period a transient rise in T4 and T3 concentrations was observed in two patients in Group I when the methimazole dosage was tapered or stopped because of agranulocytosis. In conclusion, in our hyperthyroid patients, amiodarone in conjunction with methimazole induced a greater fall in T3 and T4 than did methimazole alone.

Adult↗

Demonstration of a neuropeptide Y (NPY)-like immunoreactivity in the pigeon retina.

The distribution of neuropeptide Y (NPY)-like immunoreactivity in the pigeon retina was investigated by fluorescence immunohistochemistry. NPY-positive cells were found in central and peripheral retina. NPY somata were located in the proximal portion of the inner nuclear layer and their processes directed to the inner plexiform layer where they ramified in 3 immunoreactive bands. NPY might play a role as a neurotransmitter or neuromodulator in the pigeon retina.

Animals↗

Co-existence of cholecystokinin- or gastrin-like peptides with other peptides in the hypophysis and the hypothalamus.

The presence of cholecystokinin and gastrin has been reported in the hypothalamohypophyseal system. These peptides present a peculiar distribution in the hypothalamic nuclei, the median eminence, and the neurohypophysis. CCK and gastrin have close relationships with other peptides like oxytocin, CRF, vasopressin, and the enkephalins; these relationships vary in different projecting areas and in different types of hypothalamic neurons. The functional role of G-CCK in neurosecretion seems to be linked to the role of these closely associated peptides and certainly deserves further investigation.

Animals↗

What is emergency? Analysis of a population presenting to an emergency room.

The population presenting at emergency rooms is increasing in Belgium. What is emergency in 1983 and why do people come? From a study of the emergency room population in a relatively new university hospital it emerges that more than 30% of those patients are in critical conditions or require in hospital treatment and about 50% are in acute discomfort. Our results confirm the impression that inappropriate use of emergency rooms is more an impression than a real problem. For socio-economic and cultural reasons, people go to emergency rooms when they need or think they should have medical help. Some emergency rooms are well able to cope with this situation. Others, less well-equipped in staff and facilities are dangerous and should be improved or closed. Unfortunately education and training programs for emergency physicians are still unknown in many parts of the French-speaking Belgium.

Adult↗

Distribution of neuropeptide Y immunoreactivity in human visual cortex and underlying white matter.

Immunocytochemical techniques have been used to study neuropeptide Y (NPY) distribution in the human visual cortex (Brodman's areas 17, 18 and 19) NPY cell bodies belong mostly to inhibitory (multipolar and bitufted) but also to excitatory (bipolar and some pyramidal) neuronal types. Their distribution is similar in the three cortical areas studied: 20 to 40% of the NPY perikarya are located in the cortical gray matter, mostly in the deep layers, while the remaining 60 to 80% are located in the underlying white matter. Immunoreactive NPY processes form a rich network of intersecting fibers throughout the entire visual cortex. A superficial plexus (layers I and II) and a deep plexus (deep layer V and layer VI) of NPY fibers are present in areas 17, 18 and 19. In area 17, an additional well developed plexus is present in layers IVb and IVc. These plexuses receive branches from long parallel fibers arising from deep cortical layers or underlying white matter and terminating in superficial layers. Local or extrinsic NPY terminals wind around vessels in the cortex as well as in the white matter, and either penetrate them or form clusters of club endings on their walls. Our results suggest a role for NPY in human visual circuitry and in cortical blood flow regulation.

Aged↗

Prenatal stress and long-term consequences: implications of glucocorticoid hormones.

We have shown that prenatal restraint stress (PNRS) induces higher levels of anxiety, greater vulnerability to drugs, a phase advance in the circadian rhythm of locomotor activity and an increase in the paradoxical sleep in adult rats. These behavioral effects result from permanent modifications to the functioning of the brain, particularly in the feedback mechanisms of the hypothalamic-pituitary-adrenal (HPA) axis: the secretion of corticosterone is prolonged after stress and the number of the central glucocorticoid receptors is reduced. These abnormalities are associated with modifications in the synthesis and/or release of certain neurotransmitters. Dysfunction of the HPA axis is due, in part, to stress-induced maternal increase of glucocorticoids, which influences fetal brain development. Some biological abnormalities in depression can be related to those found in PNRS rats reinforcing the idea of the usefulness of PNRS rats as an appropriate animal model to study new pharmacological approaches.

Animals↗

[Biologic rhythms. Circadian, ultradian and seasonal rhythms].

CIRCADIAN RHYTHMS: Our knowledge of the genetic and molecular mechanisms regulating the principal circadian clock located in the suprachiasmatic nuclei is progressing. The clock's intrinsic period varies from one species to another and to a lesser degree from one individual to another. In humans, the intrinsic period is slightly over 24 hours. The clock is capable of synchronizing itself to the surrounding environment by reacting to outside factors or zeitgebers (time-givers). Light-dark cycles are the main zeitgebers; meals, the social environment, and locomotor activity also affect the circadian clock. In addition, the circadian clock acts as an internal timer, providing the organism with a means of synchronizing the function of multiple biochemical and physiological systems. ULTRADIAN RHYTHMS: The frequency of ultradian rhythms varies considerably form one species to another and from one parameter to another. In humans, several functions oscillate at 60-120 minute intervals, rhythms which are sometimes superimposed on other functions oscillating at 3 to 5 minute intervals. SEASONAL RHYTHMS: Several mechanisms allow living organisms to adapt to seasonal variations in the environment. In certain species, reproduction functions are stimulated at appropriate moments in the yearly cycle, optimizing the newborn's chances of survival. Such seasonal variations are much less marked in humans.

Biological Clocks↗

[Biologic rhythms. Nyctemeral variation in man].

CORTICOTROPIC AXIS: The nycthemeral pattern of cortisol is a good marker of the circadian clock. Cortisol levels fluctuate between a peak level, observed in the early hours of the morning, and a minimal level around midnight. This variability is considerably reduced or even abolished in Cushing s syndrome. THYREOTROPIC AXIS: The nycthemeral pattern of TSH secretion is dependent on both the circadian clock and sleep (which inhibits hormone secretion). The moment of the evening rise is a reliable marker of the circadian rhythmicity. SOMATOTROPIC AXIS: Growth hormone is essentially pulsatile. GH levels are often undetectable between pulses. The circadian rhythmicity plays only a minor role in the regulation of growth hormone secretion. LACTOTROPIC AXIS: Nycthemeral variations in prolactin secretion are mainly regulated by wake-sleep cycles; peak levels occur in the middle of the night. Prolactin secretion is also modulated by the circadian rhythmicity. GONADOTROPIC AXIS: Gonadotropins are secreted in pulses, following the pulses of GnRH secretion. In adult women, nycthemeral variations in LH are strongly modulated by the menstrual cycle. MELATONIN: The nychtemeral pattern of melatonin is an excellent marker of the circadian clock. Diurnal concentrations are low and vary little whereas peak levels are observed in the middle of the night. Melatonin rhythmicity is not influenced by sleep, but is dependent on exposure to light and darkness.

Adolescent↗

[Biologic rhythms. Effect of aging on the desynchronization of endogenous rhythmicity and environmental conditions].

CIRCADIAN AND PULSATILE RHYTHMICITY IN THE AGING PROCESS: The aging process produces morphological and neurochemical alterations in the suprachiasmatic nuclei as well as major alterations in the quality of sleep. In addition, aging is frequently accompanied by changes in life style due to different, often less demanding, social and occupational activities, leading to an attenuation of the synchronizing effects of the light-dark and activity-rest cycles. Together, these different elements contribute to a decline in temporal organization in the elderly, a phenomenon which starts in the third decade for some variables. There is a characteristic phase shift with age: in an 80-year-old individual, the circadian cortisol peak occurs about 3 hours earlier than in a 20 year-old-individual. JET LAG AND NIGHT SHIFT WORK: The circadian rhythm and environmental conditions can become desynchronized after transmeridian flights, a phenomenon commonly called jet lag. In night shift workers, such desynchronization creates an important public health problem. The impact may be underestimated since 15 to 20% of the work force in industrialized countries work permanently or occasionally on night shifts. The resulting dissociation between environmental signals and the wake-sleep cycle leads to various health problems. No truly effective therapeutic strategy has been developed although ongoing research, particularly on the use of light and/or melatonin, provides some promising perspectives.

Circadian Rhythm↗