Circadian Carbamazepine Toxicity

Summary: Owing to marked fluctuations in plasma con-centrations, circadian CNS toxicity (maximum in the early afternoon) occurred in a 69-year-old female patient being treated with an instant-release formulation of carbamazepine (CBZ). The neurologic syndrome was reversible after administration of the same daily dose as sustained-release formulation. This case illustrates the importance of correct timing of blood sampling to detect drug-induced toxicity and of use of sustained-release for-mulations in antiepileptic therapy with CBZ.     

Nitric oxide synthase inhibitor blocks light-induced phase shifts of the circadian activity rhythm, but not c-fos expression in the suprachiasmatic nucleus of the Syrian hamster

Circadian rhythms in mammals are entrained to the environmental light cycle by daily adjustments in the phase of the circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Brief exposure of hamsters maintained under constant darkness to ambient light during subjective nighttime produces both phase shifts of the circadian activity rhythm and characteristic patterns of c-fos protein (Fos) immunoreactivity in the SCN. In this study, we demonstrate that light-induced phase shifts of the circadian activity rhythm are blocked by intracerebroventricular (i.c.v.) injection of the competitive nitric oxide synthase (NOS) inhibitor,N-nitro-l-arginine methyl ester (l-NAME), but not by the inactive isomer,d-NAME. The effects ofl-NAME are reversible and dose-related, and are countered by co-injection of arginine, the natural substrate for NOS. While effects on behavioral rhythms are pronounced, similar treatment does not alter the pattern of light-induced Fos immunoreactivity in the SCN. These results suggest that nitric oxide is a component of the signal transduction pathway that communicates photic information to the SCN circadian pacemaker, and that nitric oxide production is either independent of, or downstream from, pathways involved in induction of c-fos expression.     

Endogenous melatonin signal does not mediate the effect of photoperiod on the rat suprachiasmatic nucleus

The duration of the nocturnal interval during which light can induce high Fos-like immunoreactivity in the suprachiasmatic nucleus is a function of the photoperiod to which rats are exposed. The effect of photoperiod is not altered by pinealectomy indicating that day length affects the functional state of the suprachiasmatic nucleus circadian pacemaking system in the rat directly, not via the pineal melatonin signal.     

Can a population of suprachiasmatic nucleus neurons with different period lengths produce a stable circadian rhythm?

The firing rate of a population of SCN neurons in vivo exhibits stable circadian oscillations, but the period length of individual neurons is not known and may be different or similar to the population rhythm. To address this question we used published data from Bos and Mirmiran [Brain Res., 511 (1990) 158–162] that reported different period lengths and amplitudes for individual neurons recorded in explant cultures of the SCN. We reconstructed the individual rhythms for several cycles, calculated the population rhythm, and then tested its stability. The period and amplitude of the rhythm of groups of neurons with different period lengths were unstable. Furthermore, the stability of the rhythm was reduced as the number of sampled neurons increased. These results suggest that the stable circadian rhythm reported for neuron populations in the intact SCN emerges from the identical period length of individual neurons. The possible intercellular interactions in the SCN that may underlie the stable circadian rhythm are discussed.     

Circadian rhythm abnormalities in adrenoleukodystrophy and methyl B12 treatment

A 13-year-old male with adrenoleukodystrophy (ALD) developed a sleep-wake disorder after complete vision loss. He had a 25-h sleep-wake cycle. After methyl B₁₂ therapy, circadian rhythms in his plasma melatonin and β-endorphin levels approximated those of healthy volunteers, and his peak cortisol time shifted backward. Daily deep body temperature (DBT) amplitude was smaller than in healthy males before and after the treatment, and his acrophase did not change. However, his sleep-wake rhythm became normal. Methyl B₁₂ is considered useful for treating circadian rhythm disturbances in patients having central nervous system disorders and blindness.     

Circadian rhythm of serotonin transport in human platelets

The circadian rhythm of serotonin active transport in human platelets was investigated in ten healthy men, aged 27–35 years. Blood was collected at 08.00, 14.00, 20.00, 02.00 and 08.00 hours the next morning. Simultaneous evaluation of the mean platelet volume, platelet distribution width, platelet distribution skewness and platelet number in whole blood was performed. K _m and V _max for serotonin transport varied considerably among individuals over 24 h. However, the mean values and distribution of these kinetic parameters were reduced at 02.00 hours. All platelet size or number parameters were stable and normal over 24 h; therefore, the reduction in mean K _m and V _max values at 02.00 h is not related to morphological platelet differences but either to platelet intrinsic factors or plasmatic variables. Knowledge of the affinity and capacity of serotonin transport throughout the diurnal cycle is important for future comparisons with depressed patients as well as other hormonal rhythms in patients and healthy humans.     

免疫系统的昼夜生理节律

本文从时间生理学的角度，探讨免疫系统的生理节律。在稳定的环境条件下，小鼠外周血白细胞总数及其类细胞均存在着昼夜节律，其峰值位于从下午至傍晚的时点。血清白蛋白和球蛋白含量周期性涨落的位相，与白细胞相似。反映机体体液免疫和细胞免疫功能的两个指标，特异性抗绵羊红细胞抗体（ＩｇＧ）的含量和Ｔ淋巴细胞酸性α－醋酸萘酯酸的活性，也呈昼夜性波动。免疫系统昼夜节律的揭示，对于深入理解免疫本质、指导生理实验和临床检     

Violence in hospitalized psychiatric patients: Diurnal and seasonal patterns

The use of four-point physical restraints on a single occasion or repeatedly in psychiatric inpatients was followed prospectively during 1993 in Beer Sheva Mental Health Center. Mood-disordered patients had significantly more restraints per patient than did schizophrenic and schizoaffective patients. The monthly rates of restraints of mood-disordered and schizophrenic patients were found to be negatively correlated with the duration of the daily photoperiod, which was phase-advanced by a month. The findings suggest that seasonality (the duration of the daily photoperiod) should be taken into account in attempts to predict the potential dangerousness of psychiatric patients.     

Weak 50-Hz electromagnetic fields activate rat open field behavior

Rats were tested in an open field after previous exposure to a weak, 50-Hz electromagnetic field of the same order of magnitude as the earth's magnetic field. Animals exposed to the artificial field at the beginning of the light phase showed 40% more rearing activity than controls, together with a slight increase in ambulation and a tendency towards less defecation and a shortened rearing latency. A replication experiment yielded the same results. Animals exposed at the beginning of the dark phase manifested no significant changes in open field activity. The results show that weak electromagnetic stimuli can modify some behavioral responses, and that these responses are sensitive to circadian phase.