Intrinsic burst generation of preinspiratory neurons in the medulla of brainstem-spinal cord preparations isolated from newborn rats

In brainstem-spinal cord preparations isolated from newborn rats, intrinsic burst-generating properties of preinspiratory (Pre-I) neurons in the rostral ventrolateral medulla, which have been suggested to be primary respiratory rhythm-generating neurons, were studied by perforated whole-cell recordings using the antibiotic nystatin. Nystatin causes small pores to be formed in the cells, through which pass small monovalent ions. For blockade of chemical synaptic transmission, perfusate Ca²⁺ concentration was lowered to 0.2 mM and the Mg²⁺ concentration was increased to 5 mM. In Iow-Ca²⁺, high-Mg²⁺ solution (referred to here as low Ca), 10 of 55 Pre-I neurons generated rhythmic bursts (burst type), 14 fired tonically (tonic type), and 31 were silent (silent type). Burst-type neurons showed periodic depolarization of 5–12 mV in low Ca, at a rate of 12±6.5/min. Hyperpolarization of the membrane caused decrease in or disappearance of the periodic depolarization and prolongation of the cycle period. Thus, the burst generations were voltage dependent. The firing frequency of tonictype neurons was 2.3±1.6 Hz and was decreased by hyperpolarization. In 6 of these neurons, the firing patterns changed to burst patterns during continuous hyperpolarization. Membrane depolarization by continuous outward current injection into some silent-type neurons (3 of 11 tested) induced bursting activity. Activity of C4 and Pre-I neurons was completely silent with 0.1–1 M tetrodotoxin (TTX) added to the standard perfusate. In low Ca, burst-type neurons (n=3) were also silent with 1 M TTX perfusion. Inspiratory neurons either became silent (n=4) or fired tonically (n=1) in low Ca. The present study by perforated whole-cell recordings confirmed that some Pre-I neurons possess intrinsic burst-generating properties, which were not attributable to phasic synaptic inputs.     

Melatonin and adjustment to phase shift

The pineal hormone melatonin has clear circadian phase-shifting effects in humans which have recently been formalized as a phase response curve. Its potential use in circadian rhythm disorders has been investigated in field studies of jet lag and shift work and in simulated phase shift. A substantial amount of information indicates that in the majority of subjects it hastens adaptation of both subjective and objective measures to forced shifts in time cues with few reported side-effects. Field studies of its use in adaptation to shift work are sparse and preliminary but the first indications are positive. In some blind subjects with sleep disturbance it can stabilize sleep onset time without necessarily entraining all circadian rhythms and it can advance sleep timing in delayed sleep-phase insomnia. Acute suppression of core body temperature may be an integral part of the phase-shifting mechanism.     

原发性高血压病人血压昼夜节律变化与心率变异的相关分析

为探讨原发性高血压患者的血压昼夜节律的变化与心率变异的关系,对６５例原发性高血压患者进行了２４ｈ动态血压监测,用时域分析法对心率变异性（ＨＲＶ）各项指标进行了检测,并与３８例正常对照比较。结果：代表心率总变异程度的ＳＤＮＮ（２４ｈ正常ＲＲ间期标准差）,ＳＤＡＮＮＩ（２４ｈ５ｍｉｎ平均ＲＲ间期标准差）明显下降（Ｐ＜０．０５）。按照夜间血压下降百分率将原发性高血压病人分为节律消失组、节律正常组,并分别与正常对照组比较,发现节律消失组ＨＲＶ各项指标下降更为显著,ＳＤＮＮ、ＳＤＡＮＮＩ、ＳＤＮＮＩ（２４ｈ５ｍｉｎ正常ＲＲ间期标准差均值）不但显著低于正常对照组（Ｐ＜０．０５）,也显著低于节律正常组（Ｐ＜０．０５）。说明在原发性高血压患者中,节律消失者的心脏自主神经系统功能损害更为严重。     

吉林省吸血蠓昼夜活动节律观察

笔者对吉林省8种优势种群吸血蠓的昼夜活动节律进行了观察.结果表明:华库蠓、孔库蠓、伊库蠓、原野库蠓、亚单带库蠓、淡角库蠓属于晨昏活动型蠓种;明边库蠓属于夜间活动型蠓种;浑江铗蠓属于白天活动型蠓种.     

Melatonin inhibits in vitro serotonergic phase shifts of the suprachiasmatic circadian clock

The suprachiasmatic (SCN) circadian pacemaker generates 24 h rhythms of spontaneous neuronal activity when isolated in an acute brain slice preparation. The isolated pacemaker also retains its capacity to be reset, or phase-shifted by exogenous stimuli. For example, serotonin (5-HT) agonists advance the SCN pacemaker when applied during mid subjective day, while neuropeptide Y (NPY) agonists and melatonin advance the pacemaker when applied during late subjective day. Previous work has demonstrated interactions between NPY and 5-HT agonists, such that NPY can block 5-HTergic phase advances, while 5-HT agonists do not prevent NPY-induced advances. Due to a number of similarities in the actions of melatonin and NPY in the SCN, it seemed possible that melatonin and 5-HT might interact in the SCN as well. Therefore, in this study potential interactions between melatonin and 5-HT agonists were explored. Melatonin inhibited phase advances by the 5-HT agonist, (+)DPAT, and this inhibition was decreased by co-application of tetrodotoxin. Conversely, melatonin was unable to block phase advances by the cyclic AMP analog, 8BA-cAMP. Finally, neither 5-HT agonists nor 8BA-AMP were able to block melatonin-induced phase advances. These results demonstrate a clear interaction between melatonin and 5-HT in the SCN, and suggest that melatonin and NPY may play similar roles with respect to modulating the phase of the SCN circadian pacemaker in rats.     

Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway

In view of mounting evidence that the suprachiasmatic nucleus (SCN) is directly involved in the setting of sensitivity of the adrenal cortex to ACTH, the present study investigated possible anatomical and functional connections between SCN and adrenal. Transneuronal virus tracing from the adrenal revealed first order labelling in neurons in the intermedio-lateral column of the spinal cord that were shown to receive an input from oxytocin fibres and subsequently second-order labelling in neurons of the autonomic division of the paraventricular nucleus. The latter neurons were shown to receive an input from vasopressin or vasoactive intestinal peptide (VIP) containing SCN efferents. The true character of this SCN input to second-order neurons was also demonstrated by the fact that third-order labelling was present within the SCN, vasopressin or VIP neurons. The functional presence of the SCN-adrenal connection was demonstrated by a light-induced fast decrease in plasma corticosterone that could not be attributed to a decrease in ACTH. Using intact and SCN-lesioned animals, the immediate decrease in plasma corticosterone was only observed in intact animals and only at the beginning of the dark period. This fast decrease of corticosterone was accompanied by constant basal levels of blood adrenaline and noradrenaline, and is proposed to be due to a direct inhibition of the neuronal output to the adrenal cortex by light-mediated activation of SCN neurons. As a consequence, it is proposed that the SCN utilizes neuronal pathways to spread its time of the day message, not only to the pineal, but also to other organs, including the adrenal, utilizing the autonomic nervous system.     

The Effect of Modifying Dietary Calcium Intake Pattern on the Circadian Rhythm of Bone Resorption

In order to assess day-to-day variations of the circadian rhythm of biochemical bone resorption markers, urinary morning (6–8 a.m.) and evening (7–10 p.m.) samples from 35 individuals were monitored during 3 subsequent days. The bone-specific deoxypyridinoline (DPD) crosslinks of type I collagen followed a circadian rhythm in all individuals. In contrast, no such pattern was observed in the urinary hydroxyproline/creatinine and calcium/creatinine measurements. The DPD crosslink measurements showed a much larger difference between the morning and evening samples collected within 1 day compared with the variation between the samples collected in the morning or evening on subsequent days, indicating the importance of adequate timing of urine sampling for clinical trials aiming to monitor effects on bone resorption. The analysis of DPD crosslinks was then used to evaluate the effects of different patterns of dietary calcium intake on the circadian rhythm of bone resorption in osteoporotic patients. No significant effect on the circadian rhythm of the DPD crosslinks was found after concentrating the normal daily calcium intake to the evening (6–10 p.m.) during 8 days (n = 7). Ingestion of a dietary calcium supplement (600 mg) at 10 p.m. during 8 days (n = 7) resulted in an increased urinary calcium excretion in the morning, and a flattening of the circadian peak and nadir concentrations of urinary DPD/creatinine. The absolute levels of DPD/creatinine in the morning and evening urine samples, respectively, were not significantly altered compared with the control day. We conclude that dietary calcium supplementation in the evening only marginally affects the circadian rhythm of urinary DPD crosslinks in established osteoporosis patients. Received: 23 December 1996 / Accepted: 1 November 1998     

γ—辐射对T淋巴细胞环核苷酸昼夜节律的毒效应

测定了小鼠外周血Ｔ淋巴细胞中ｃＡＭＰ和ｃＧＭＰ含量及其比值的昼夜节律各峰值时相分别位于１２：２０时、０１：１２时和１３：０４时,经５．０Ｇｙγ－射线照射后,ｃＡＭＰ含量升高,ｃＧＭＰ一降低,ｃＡＭＰ／ｃＧＭＰ比值增大。而０．５Ｇｙ照射引起比值下降。这些变化在０４：００时较为明显,而在１２：００时则观察不到,表现出明显的昼夜时相差异。另一方面,照射后ｃＡＭＰ／ｃＧＭＰ比值节律的峰值位相发生延迟或提前     

Effects of continuous oral nicotine administration on brain nicotinic receptors and responsiveness to nicotine in C57Bl/6 mice

 The route of drug delivery is an important consideration in studies that evaluate the long-term biobehavioral adaptations that occur in response to chronic drug administration. Continuous infusions (intravenous or subcutaneous) or intermittent intraperitoneal (or subcutaneous) injections are the most commonly utilized routes of chronic drug delivery in these studies. The purpose of the present study was to determine the effects of chronic oral nicotine exposure on sensitivity to nicotine and brain nicotinic cholinergic receptors in female C57Bl/6 mice. Mice were randomized to different treatment groups that received 2% saccharin, containing 0–200 μg/ml nicotine (free base). In preliminary experiments, radiotelemetry devices were implanted in the mice; consumption of the nicotine-containing drinking solution caused a significant increase in home-cage nocturnal (but not diurnal) activity and also altered circadian alterations in body temperature. Oral nicotine exposure resulted in dose-related elevations in plasma levels of cotinine, a primary nicotine metabolite. Continuous exposure (30 days) to oral nicotine (200 μg/ml) resulted in the expression of significant tolerance to the locomotor depressant and hypothermic actions of acute nicotine challenge. This tolerance was accompanied by a significant increase in brain nicotinic receptor number assessed by quantitative autoradiography using [³H]-cytisine (α4 nAChr) and [¹²⁵I]-α-bungarotoxin (α7 nAChr) as radioligands. These results suggest that chronic oral nicotine delivery to female C57Bl/6 mice results in behavioral and biochemical changes that resemble changes that occur following other routes of chronic nicotine delivery. Received: 30 January 1998 / Final version: 25 June 1998     

Early nocturnal blood pressure changes in diabetic autonomic neuropathy assessed by Fourier series

The 24 h periodic pattern of blood pressure was studied in 44 patients with diabetes mellitus (14 type 1, 30 type 2; mean duration of disease 6.5 ± 1.8 years) in good metabolic control but with abnormal cardiovascular reflex responses; of these 21 were normotensive and 23 hypertensive. All had abnormal responses to at least two out of four tests: deep breathing, lying to standing, Valsalva manoeuvre and postural hypotension. Two sex- and agematched groups, consisting of 20 normotensive and 20 hypertensive diabetic patients without dysautonomia, were studied as controls. Each patient underwent ambulatory blood pressure monitoring for at least 24 h, using an auscultatory automatic device. Data were analysed using the sum of three periodic functions (Fourier partial sum). In the diabetic normotensive groups, the absolute blood pressure fell to its night-time minimum more rapidly, and increased to its morning maximum more slowly, in those with abnormal cardiovascular reflexes than in the controls (nightly blood pressure decrease –5.8/–4.7 vs. –3.8/–4.0 mmHg/h; increase 4.7/3.6 vs. 5.9/6.1 mmHg/h). The same behaviour was found in both hypertensive groups but the amplitude of the differences was more marked (blood pressure nocturnal decrease –7.7/–7.1 vs. –4.3/–3.9 mmHg/h; increase 3.2/2.1 vs. 5.8/4.3 mmHg/h). This analysis of 24 h ambulatory blood pressure data may be of value in diagnosis and evaluation of autonomic deficits.