Two selective 5-HT1A receptor antagonists, WAY-100 635 and NDL-249, stimulate locomotion in rats acclimatised to their environment and alter their behaviour: a behavioural analysis

The aim was to study firstly, the motor effects of a new 5-HT_1A antagonist, NDL-249 [(R)-3-(N-cyclopentyl-N-propylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide hydrochloride] and of the reference 5-HT_1A antagonist WAY-100 635 [N-(2-(1-(4-(2-methoxyphenyl)piperazinyl))ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride], in comparison to the 5-HT_1A agonist (±)-8-OH-DPAT [(8-hydroxy-2-(di-N-propylamino) tetralin, hereafter 8-OH-DPAT], in rats acclimatised to the automated activity cages; secondly, to study whether the behavioural effects of NDL-249 and 8-OH-DPAT are sensitive to the 5-HT depleting effects of p-chlorophenylalanine (PCPA); thirdly, to characterise the nature of the antagonist-induced activation seen in the automatic activity cages with the aid of a behavioural observation analysis; fourthly, to examine the interaction between the 5-HT_1Areceptors mediating the behavioural effects and dopamine (DA) receptors. NDL-249 was found to bind in vitro to rat hippocampal 5-HT_1A receptors with high affinity and selectivity. In second messenger studies, it was devoid of agonist-like effects. In the locomotor activity studies, each antagonist significantly increased the incidence of horizontal activity, peripheral activity and rearing. 8-OH-DPAT, while significantly increasing peripheral and horizontal activities, decreased the incidence of rearing. PCPA blocked the motor effects of NDL-249 but did not affect those of 8-OH-DPAT. Observational analyses indicated that NDL-249 induced significant increases at one or more doses in sniffing, rearing and locomotion together with a significant reduction in stillness. WAY-100 635 significantly increased the incidence of rearing, intense grooming and vacuous chewing. The significant increases in sniffing, grooming and intense grooming and the significant decrease in stillness induced by the DA D₁ agonist, SK&F 38393 [(±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride], were not altered by concomitant pre-treatment with NDL-249. Pre-treatment of rats with either the DA D₁ antagonist SCH-23390 (2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol) or the DA D₂ antagonist, raclopride, blocked the reduced stillness and increased sniffing and rearing induced by NDL-249. In conclusion, 5-HT_1A antagonists including the new selective antagonist, NDL-249, induce mild behavioural activation in rats, which is mediated probably indirectly via DA systems. Received: 3 April 1997/Final version: 23 February 1998     

一种改良的抗氧化活性测定方法

活性氧自由基在生物体内参与生理，病理过程并起重大作用，在筛选和评价抗氧化药物时，越来越需要一种快速，简便，价廉而又可靠的抗氧化活性测定方法，本文发展了一种具备了上述优点新方法，ＳＯＤ（超氧化物歧化酶）及其模拟物的工作已有很多，很多文献报道了其活性一；Ｃｕ（Ⅱ）。本文着重研究了另一个金属辅基，Ｚｎ＾２＋并且发现了Ｚｎ＾２＋独特的，但为人们忽视了的；抗氧化活性加强作用。     

Regional differentiation of sympathetic activity during hypothalamic heating and cooling in anesthetized rabbits

Summary In anesthetized rabbits immobilized with succinyl choline, the discharges of sympathetic efferents supplying cutaneous and visceral regions were simultaneously recorded. The effects of thermal stimulation of the hypothalamic region were tested on the basis of the integrated discharges. During hypothalamic heating cutaneous sympathetic activity decreased, corresponding to increased ear blood flow, while visceral sympathetic activity increased. During hypothalamic cooling there was, on the average, no significant change of regional sympathetic activity. However, in single experimental periods an increase of cutaneous and a decrease of visceral sympathetic activity was found.The observed responses of regional sympathetic activity were compared with findings about regional cutaneous and intestinal blood flow under the same thermal stimulus and further with corresponding former investigations on regional blood flow and regional sympathetic activity during spinal thermal stimulation. It is suggested by this comparison that regional differentiation of sympathetic activity represents a specific thermoregulatory response of the vasomotor system mediated by the hypothalamic thermoregulatory center.     

A Multi-Response Analysis of Learned Heart Rate Control

Thirty college students were classified on the basis of cold-pressor blood pressure responses and then randomly assigned to one of three treatment groups. One group merely tracked a visual analog display of their heart rate (tracking group). A second group attempted to increase and decrease its heart rate without the visual display (no-feedback group). A third group attempted to increase and decrease their heart rates with the aid of the visual heart rate display (feedback group). Results indicated that the heart rate changes produced by both the feedback and no-feedback groups were significantly greater than those observed in the tracking group. There was no significant difference between the former two groups. Results also demonstrated that high cold-pressor reactors were able to produce significantly larger heart rate changes than the low reactor subjects. A correlational analysis of physiological responses accompanying heart rate change suggested that the response topographies of the high and low cold-pressor reactors differed as well. Finally, results indicated no relationship between coronary-prone personality characteristics, as measured by the Jenkins Activity Scale, and either cold-pressor reactivity or heart rate control performance.     

Local blood flow and metabolism of the tongue before and during panting in the dog

Summary The effects of hyperthermia on blood flow and oxygen consumption of the tongue were investigated in anesthetized dogs. For comparison, blood flow through the skin and deep muscle of the hind leg was also measured in some animals. Increasing blood temperature revealed a biphasic response of lingual blood flow. At 41°C blood temperature respiratory frequency was twice that of control and there was a reduction of lingual blood flow, while resistance of the lingual bed was increased significantly. The arterio-venous oxygen difference (AVDO₂) of lingual blood was markedly increased at this level and the of the tongue was like-wise significantly greater than control. At 41.9°C, the steep increase of respiratory frequency was accompanied by a marked fall in lingual resistance as evidenced by a four-fold increase of lingual blood flow. The systemic AVDO₂ rose at this temperature, while the lingual AVDO₂ fell dramatically. There was no further increase of lingual . At both temperature levels the blood flow through the skin did not change substantially, while the deep muscle blood flow slightly increased. The mean arterial pressure showed a progressive fall during hyperthermia. It is assumed that the decrease of lingual blood flow at elevated blood temperature without panting is due to a redistribution of cardiac output to areas other than the tongue. The increase of lingual blood flow without an additional increase of lingual during panting may be explained solely as a mechanism for heat dissipation. The fact that the decrease of lingual resistance was demonstrated in immobilized animals concomitant with high frequency phrenic burst activity suggests that the decrease of lingual resistance and panting may be induced by a common central integrating mechanism.     

Heart rate recorder

We describe the design of an instrument that can acquire and store the average heart rate of a subject over 256 time intervals of predetermined length (1 or 6 min) during normal daily activities. The instrument consists of two units: a portable recorder, worn by the patient, detects and counts heart beats, and stores their average in memory, and a display later retrieves the contents of that memory. C.M.O.S. technology and programmable operational amplifiers resulted in low power consumption (20 mW). The results obtained from this instrument were accurate to about 1 beat/min compared with Holter monitoring and telemetry.     

Physical fitness of blind and sighted children

Summary Twenty-seven children (age 7–17 years) with varying degrees of blindness but with no other known disorder were assessed for physical fitness. Twenty-seven randomly selected children with normal eyesight were also assessed. Maximum oxygen uptake ( ) was measured directly during a progressive exercise test on a treadmill. There was a significant and substantial reduction in in totally blind children (mean ± standard deviation 35.0±7.5 ml · min^–1 · kg^–1) compared with normal children (45.9±6.6 ml · min^–1 · kg^–1). Partially sighted children had a significant but smaller reduction in . Fitness assessed by a step-test was significantly reduced in the visually impaired children, and skin-fold thickness was also significantly greater in totally blind children.The level of habitual physical activity for each child, as assessed by a questionnaire, correlated with (r=0.53,p<0.0001). Blind children were significantly less active than normal children, and the difference between mean for blind and normal children became non-significant when their different activity levels were taken into account. It is concluded that totally blind children are less fit than other children at least partly because of their lower level of habitual activity.     

Body composition,work capacity,and work efficiency of active and inactive young men

On 46 healthy young men, of whom 18 took part in strenuous sport at least once a week, height, weight, total body fat (as % of body mass) and lean body mass (LBM) were determined. The subjects performed submaximal exercise on a bicycle ergometer and climbing on an upwardly inclined treadmill at work loads of 60, 110, and 140 watts. Oxygen consumption ( ), respiratory quotient (RQ), energy expenditure (), and heart rate (f _H) were measured at rest and at each work load, and maximum oxygen intake ( max) and physical work capacity (PWC₁₅₀, PWC₁₇₀) were calculated.Anthropometric parameters did not differ significantly between sportsmen and sedentary subjects. max, PWC₁₅₀, and PWC₁₇₀ had higher correlations with LBM than with the other anthropometric parameters. max expressed in terms of LBM (ml/kg LBM/min) was the parameter which showed the clearest distinction between sportsmen and sedentary individuals. The sportsmen had higher max on the treadmill test than on the bicycle ergometer. PWC₁₅₀ and PWC₁₇₀ were higher on the bicycle than on the treadmill and had high correlations with max. Work efficiency was of the same order in both groups and showed negative correlation with the degree of obesity on the bicycle ergometer and positive correlation on the treadmill.     

AML患者端粒酶逆转录酶mRNA的表达与端粒酶活性的检测

目的:建立一种实时荧光RT-PCR方法,定量检测急性髓细胞白血病(AML)患者外周血单个核细胞端粒酶逆转录酶(hTERT)mRNA的表达水平,观察其与AML发生及复发的关系,探讨hTERT mRNA的表达水平与端粒酶活性的相关关系。方法:采用实时荧光RT-PCR与Lightcycler荧光PCR仪定量检测hTERT mRNA的表达水平,采用PCR-ELISA检测端粒酶活性。结果:①AML首治患者、复发患者、完全缓解期患者以及健康体检者NhTERT分别为299.2±292.8、550.1±441.3、14.0±9.2和12.3±6.7,与健康体检者和完全缓解期患者比较,AML首治患者、复发患者hTERT mRNA表达水平显著升高,而且AML复发患者hTERT mRNA的表达水平显著高于首治患者;②AML首治患者、AML复发患者、AML完全缓解期患者以及健康体检者端粒酶的活性分别为32.8%±24.3%4、8.6%±31.4%、7.4%±5.1%和7.6%±3.6%,AML首治患者、复发患者端粒酶活性显著升高,而且AML复发患者端粒酶活性显著高于首治患者;③hTERT mRNA表达水平与端粒酶的活性呈现良好的相关性,相关系数为0.78。结论:hTERT mRNA表达水平与端粒酶活性的上调是AML发生与复发的一个重要因素,且hTERT mRNA表达水平与端粒酶活性呈良好的正相关。     

Design of a multichannel solid-state recorder and its application to temperature measurement

The development of a multichannel unconstrained memory system for monitoring physiological information is described. The system comprises a portable recorder, worn by the subject, to detect and store data in memory and a readout unit for transferring the data to a microcomputer. Using the microcomputer, the physiological data are displayed, retrieved and analysed. The portable recorder consists of a memory control unit, an instrumentation unit, an LCD timer and batteries. In the memory-control unit the data are transferred to EPROM (erasable programmable read-only memory), which is a nonvolatile memory. This memory, removed from the protable recorder, can be delivered to the laboratory and its contents analysed without interrupting the field experiment. In connection with the instrumentation unit, an 8-channel skin thermometer was designed and tested. It was accurate to within ±0.08°C compared with a standard thermometer.