Rebound hyperthermia follows ethanol-induced hypothermia in rats

We have recently described a telemetry/micro-computer system to monitor core temperatures in rats. We implant a miniature transmitter (Mini-mitter) into the peritoneal cavity of the rat, allowing us to obtain temperatures around the clock without handling the animals or disturbing the light-dark cycle. In the present study we describe the temperature effects of ethanol doses ranging from 2 to 6 g/kg. Baseline temperatures were collected for 2 days before drug was administered. Subsequent computer analysis then allowed us to compare experimental results in each animal with its own baseline temperature to allow for individual and circadian temperature differences. In preliminary studies we observed the well-known dose-dependent hypothermic effect of ethanol. However, by observing animals continually over 4 days we also observed a period of rebound hyperthermia beginning at about the time of complete ethanol elimination and persisting for several days. During this period daytime temperatures remained at the normally high night-time level. This may be evidence of a mild abstinence syndrome, or alternatively, may be due to a disruption of the normal circadian temperature rhythm.Preliminary work presented at the 33rd Fall Meeting of the American Society of Pharmacology and Experimental Therapeutics, Louisville, KY, August 1982, and at the 28th Annual Meeting of the Western Pharmacology Society, Jan. 20–25, 1985, Tahoe City, CA     

自拟降压汤辅治高血压对患者血压昼夜节律的影响研究

目的研究自拟降压汤辅治高血压(EH)对患者血压昼夜节律的影响。方法按随机数表法将120例EH患者分成自拟降压汤组(研究组,n=60)和常规组(对照组,n=60),于治疗前(T1)及治疗4周后(T2)检测两组24 h动态血压[24 h收缩压(24 h SBP)、24 h舒张压(24 h DBP)、白昼(D)SBP、DDBP、夜间(N)SBP、NDBP]和夜间血压下降率[平均SBP下降率、平均DBP下降率],观察两组患者红细胞免疫相关指标[红细胞受体花环率(RBC-C3bRR)、红细胞免疫复合物花环(RBC-ICR)]和外周血T淋巴细胞亚群(CD4~+、CD8~+)分布改善情况。结果 T2时,两组24 h动态血压水平、RBC-ICR均较T1时降低,且研究组低于对照组(P0.05);两组夜间平均SBP和DBP下降率、RBCC3bRR、CD4~+、CD8~+均较T1时上升,且研究组高于对照组(P0.05)。结论自拟降压汤可显著改善EH患者24 h动态血压、夜间血压下降情况、红细胞免疫相关指标水平和T淋巴细胞亚群分布情况,对调节其血压昼夜节律、增强其免疫功能有一定帮助,于病情转归有利。     

昼夜节律在调控免疫系统功能中的作用

昼夜节律使机体生理、生化、行为等生命现象表现为以大致24 h为周期的振荡规律,受一系列生物钟基因(bmal1、clock、cry、per)和钟控基因(rev-erbα、rorα、dbp、tef、hlf等)调控.生物钟基因广泛存在于机体各免疫器官、组织和细胞中,使免疫细胞功能(迁移和趋化、吞噬、杀伤活性等)及多种免疫参数(循环免疫细胞及其亚群的相对和绝对数量、细胞因子水平等)呈现显著的昼夜节律性变化,从而在维持免疫稳态中发挥重要作用.此外,一些免疫相关疾病也与昼夜节律和生物钟系统异常密切相关.该文将着重阐述昼夜节律及生物钟系统对免疫细胞功能的影响及其在一些免疫相关疾病中的作用.     

Chronotherapeutics: The Relevance of Timing in Cancer Therapy

Background Cell physiology is regulated along the 24-h time scale by a circadian timing system composed of molecular clocks within each cell and a central coordination system in the brain. The mammalian molecular clock is made of interconnected molecular loops involving at least 12 circadian genes. The cellular clocks are coordinated by the suprachiasmatic nuclei, a hypothalamic pacemaker which also helps the organism adjust to environmental cycles. The rest–activity rhythm is a reliable marker of the circadian system function in both rodents and man. This circadian organization is responsible for predictable changes in the tolerability and efficacy of anticancer agents, and possibly also in tumor promotion or growth. Methods Expected least toxic times of chemotherapy were extrapolated from experimental models to human subjects with reference to the rest–activity cycle. The clinical relevance of the chronotherapy principle, i.e. treatment administration as a function of rhythms, has been demonstrated in randomized multicenter trials. Results Chronotherapeutic schedules have been used to safely document the activity of the association of oxaliplatin, 5-FU and leucovorin against metastatic colorectal cancer and to set up a new medicosurgical management of this disease which achieved unprecedented long term survival. Conclusion The chronotherapy concept offers further promises for improving current cancer treatment options as well as for optimizing the development of new anticancer or supportive agents     

原发性高血压患者血压变异性及昼夜节律与左室肥厚的关系

目的 探讨原发性高血压患者血压变异性及血压昼夜节律与心室肥厚的关系.方法 连续入选2010 年8 月至2012 年1 月,于中国医科大学附属第一医院心血管内科住院的原发性高血压患者共93例,根据超声心动图测量指标计算所得的左心室重量指数(LVMI)分为左心室肥厚(LVH)组与无LVH 组;再根据24 h 动态血压监测获得的结果分为血压晨峰组与无血压晨峰组,杓型血压组与非杓型血压组.分析比较24 h 血压、白昼和夜间血压均值、血压变异性、血压昼夜节律及晨峰与心室肥厚的相关性.结果 ①与无LVH 组相比,LVH 组24 小时收缩压(24 h SBP)、24 小时舒张压(24 h DBP)、白昼收缩压(dSBP)、白昼舒张压(dDBP)、夜间收缩压(nSBP)和夜间舒张压(nDBP)均升高,P<0.01;LVH 组24 小时平均收缩压标准差(24 hSSD)高于无LVH 组,P<0.05,但两组24 小时平均舒张压标准差(24 h DSD)无差别;与无LVH 组相比,LVH组夜间收缩压标准差(nSSD)和夜间舒张压标准差(dDSD)升高,P<0.01;但白昼收缩压标准差(dSSD)和白昼舒张压标准差(dDSD)无差别.②血压晨峰组LVMI 高于无血压晨峰组,P<0.05;血压晨峰组LVH 比率也高于无血压晨峰组,P<0.01;与无血压晨峰组相比,血压晨峰组24 h SBP、dSBP 和nSBP 均增高,P<0.05,但两组24 h DBP、dDBP 和nDBP 无差别.③杓型血压组LVMI 低于非杓形血压组,P<0.05;杓型血压组LVH 比率低于非杓形血压组,P<0.01;与非杓形血压组相比,杓型血压组nSBP、nDBP 均降低,P<0.01;而两组24 hSBP、24 h DBP、dSBP、dDBP 差异无统计学意义.结论 原发性高血压患者LVH 的发生与血压变异性和血压晨峰密切相关.具有血压晨峰的患者和血压昼夜节律消失的非杓型高血压患者更易出现LVH.     

老年高血压患者血压昼夜节律与腔隙性脑梗死、脑白质病变的关系

目的 研究老年高血压患者血压昼夜节律变化与腔隙性脑梗死(LI) 和脑白质病变(WML)的关系。方法 选择2011年4月～2014年2月河北医科大学附属哈励逊国际和平医院门诊及住院年龄≥60岁的高血压病人126例,进行动态血压监测及头颅MRI检查,并同时收集患者的临床和实验室资料。将患者分为杓型组（48例）和非杓型组（78例）。结果 非杓型组24hSBP（136.39±12.45）mmHg、dSBP（138.78±11.67）mmHg、nSBP（133.56±11.7）mmHg明显高于杓型组,非杓型组ASBP%为3.38±1.96,明显低于杓型组11.54±2.41, 两组患者24hSBP、dSBP、nSBP、ASBP%比较差异有统计学意义（P＜0.05）;非杓型组LI46例（58.97%）、WML41例（52.56%）,杓型组LI13例（27.08%）、WML11例（22.92%）,非杓型组LI、WML的发生率明显高于杓型组,两组比较有统计学差异（P＜0.01）。结论 在老年高血压患者中,非杓型高血压可增加LI和WML的发生率。有效地降低夜间血压,恢复杓型节律有助于减轻靶器官损害。     

Multidimensional Ultrasound Doppler Signal Analysis for Fetal Activity Monitoring

Fetal activity parameters such as movements, heart rate and the related parameters are essential indicators of fetal wellbeing, and no device provides simultaneous access to and sufficient estimation of all of these parameters to evaluate fetal health. This work was aimed at collecting these parameters to automatically separate healthy from compromised fetuses. To achieve this goal, we first developed a multi-sensor–multi-gate Doppler system. Then we recorded multidimensional Doppler signals and estimated the fetal activity parameters via dedicated signal processing techniques. Finally, we combined these parameters into four sets of parameters (or four hyper-parameters) to determine the set of parameters that is able to separate healthy from other fetuses. To validate our system, a data set consisting of two groups of fetal signals (normal and compromised) was established and provided by physicians. From the estimated parameters, an instantaneous Manning-like score, referred to as the ultrasonic score, was calculated and was used together with movements, heart rate and the associated parameters in a classification process employing the support vector machine method. We investigated the influence of the sets of parameters and evaluated the performance of the support vector machine using the computation of sensibility, specificity, percentage of support vectors and total classification error. The sensitivity of the four sets ranged from 79% to 100%. Specificity was 100% for all sets. The total classification error ranged from 0% to 20%. The percentage of support vectors ranged from 33% to 49%. Overall, the best results were obtained with the set of parameters consisting of fetal movement, short-term variability, long-term variability, deceleration and ultrasound score. The sensitivity, specificity, percentage of support vectors and total classification error of this set were respectively 100%, 100%, 35% and 0%. This indicated our ability to separate the data into two sets (normal fetuses and pathologic fetuses), and the results highlight the excellent match with the clinical classification performed by the physicians. This work indicates the feasibility of detecting compromised fetuses and also represents an interesting method of close fetal monitoring during the entire pregnancy.     

Rhythm Control in Heart Failure Patients With Atrial Fibrillation : Contemporary Challenges Including the Role of Ablation

Because nonpharmacological interventions likely alter the risks and benefits associated with rhythm control, this paper reviews the role of current rhythm control strategies in atrial fibrillation. This report also focuses on the specific limitations of pharmacological interventions and the utility of percutaneous ablation in this growing population of patients with concomitant atrial fibrillation and heart failure.     

Evidence for an internal and functional circadian clock in rat pituitary cells

In primary cultures of rat pituitary cells and in a pituitary sommatolactotroph cell line (GH4C1), endogenous core-clock- as well as hormone-genes such as prolactin displayed a rhythmic expression pattern, fitted by a sinusoidal equation in which the period value was close to the circadian one. This is consistent with the presence of a functional circadian oscillator in pituitary cells whose importance was ascertained in GH4C1 cell lines stably expressing a dominant negative mutant of BMAL1. In these cells, both endogenous core-clock- and prolactin-genes no more displayed a circadian pattern. Some genes we recently identified as mouse pituitary BMAL1-regulated genes in a DNA-microarray study, lost their circadian pattern in these cells, suggesting that BMAL1 controlled these genes locally in the pituitary. The intra-pituitary circadian oscillator could then play a role in the physiology of the gland that would not be seen anymore as a structure only driven by hypothalamic rhythmic control.     

时间药理学在临床用药中的合理运用

本文将结合时间药理学的相关知识,对时间药理学与自然生物节律之间的联系、以及时间药理学在临床用药中的运用进行分析。