谷氨酰胺衍生物的合成及抑瘤活性

以抗瘤酮 A_(10)和 AS_(2-5)为先导化合物,设计合成了15个谷氨酰胺的衍生物。初步抑瘤试验结果表明,化合物3、6、8、9和10对小鼠肉瘤 S180有较好的抑制作用,抑制率达30.3～64%.     

SKELETAL MUSCLE RESTING METABOLISM IN COLD-ACCLIMATED RATS: EFFECT OF AGE, NORADRENALINE AND HYPEROSMOLARITY

1. A myothermic technique has been used to measure the resting metabolism of small bundles of a fast twitch muscle, extensor digitorum longus (EDL), and a slow twitch muscle, soleus (SOL), in 7-week-old rats. At 27°C, mean (± SEM) resting heat rates were 2.33 ± 0.41 and 2.09 ± 0.37 mW/g in EDL and SOL, respectively (n= 16). 2. Seven-week-old rats were cold acclimatized at 4°C for 1–4 weeks and the metabolic rates of the fast and slow twitch muscles were monitored and compared with 7- and 11-week-old controls. There was a 160% increase in metabolic rate from week 7 to week 11, but the increase also occurred in the control group. 3. In accordance with several literature reports, noradrenaline at concentrations of 10”⁷ and 10”⁶ mol/L had no effect on either the control or cold-acclimatized resting heat rate. 4. The osmolarity of the physiological solution bathing the muscle bundles was increased by lOOmosmol using sodium sulphate. Basal metabolism increased by similar amounts (approximately 250%) in both the fast and slow muscle bundles. Periods of cold exposure had no significant effect on the magnitude of the increment. 5. Bumetanide, a potent inhibitor of Na⁺-Cl^? co-transport, produced only a slight reduction in the heat increments caused by hyperosmolar challenge.     

EFFECTS OF MILD AEROBIC EXERCISE AND A MILD HYPOCALORIC DIET ON PLASMA LEPTIN IN SEDENTARY WOMEN

1. The present study was conducted to investigate whether mild aerobic exercise and a mild hypocaloric diet, instead of severe restrictions on caloric intake, would affect weight reduction and plasma leptin concentrations. 2. Forty-one middle-aged sedentary women (15 obese and 26 non-obese) participated in a 12 week lifestyle-modification programme to reduce cardiovascular risk factors. Bodyweight, body composition, plasma leptin concentrations, serum lipid profiles, fasting plasma glucose and fasting plasma insulin were measured before and after the 12 week intervention. The intervention consisted of aerobic exercise, corresponding to approximately 50% of maximal oxygen consumption, and personal diet counselling. 3. Bodyweight decreased by (mean +/- SD) 3.9 +/- 3.4 kg in the obese group (P < 0.05) and by 1.7 +/- 1.8 kg in the non-obese group (P < 0.05). The plasma leptin concentration decreased significantly from 14.7 +/- 5.3 to 8.9 +/- 3.6 ng/mL in the obese group (P < 0.001) and from 7.6 +/- 3.9 to 5.6 +/- 2.2 ng/mL in the non-obese group (P < 0.01). 4. Overall, for all subjects, both pre- and postintervention, the plasma leptin concentration was significantly correlated with body mass index (BMI; pre-intervention: r = 0.73, P < 0.0001; postintervention: r = 0.67, P < 0.0001), fat mass (FM; pre-intervention: r = 0.74, P < 0.0001; postintervention: r = 0.63, P < 0.0001) and fasting plasma insulin (pre-intervention: r = 0.66, P < 0.001; postintervention: r = 0.45, P < 0.01). The change in plasma leptin concentration was significantly correlated with the respective changes in BMI (r = 0.64, P < 0.0001), FM (r = 0.48, P < 0.01) and fasting plasma insulin (r = 0.58, P < 0.0001). Interestingly, the ratio of plasma leptin concentration to BMI or FM diminished significantly after intervention. In addition, we found that the plasma leptin concentration decreased in participants whose FM did not decrease. These results suggest that the production of leptin per unit FM decreased after intervention. 5. Mild aerobic exercise and a mild hypocaloric intake decreased body mass and the plasma leptin level in Japanese middle-aged sedentary women. This decrease in plasma leptin levels was likely to be associated with weight reduction plus some unknown factor(s).     

THE EFFECTS OF THYROXINE TREATMENT ON SLOW- AND FAST-CONTRACTING SKELETAL MUSCLE CONTRACTIONS OF THE CAT AND THEIR CYCLIC AMP LEVEL

1. The effects of thyroxine treatment on soleus and extensor digitorum longus (EDL) muscle contractions and their cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels were examined in anaesthetized cats. 2. Thyroxine treatment decreased the tension of incomplete tetanic contractions of the soleus as well as the EDL muscles. The effect on tension of these muscles was not associated with an increase in the cyclic AMP level of the muscle as is the case with a beta 2-adrenoceptor agonist effect. 3. The results do not support the involvement of cyclic AMP in the tension depressant effect of thyroxine on contractions of skeletal muscle. 4. It is suggested that the muscle weakness and tremor observed in thyrotoxicosis and during administration of beta 2-adrenoceptor agonists are mediated by different mechanisms.     

山莨菪碱及阿托品对大鼠肝、横纹肌及趾蹠血管的作用

Rats were urethanised and kept in a constant temperature chamber.The surface temperature of various organs including the liver and the armpit skeletal mus-cle were monitored with a special mercury thermometer through a narrow hole on the skincut with scalpel. The temperature of the foot- pad skin were measured using a thermome-ter as reported previously. After iv of anisodamine or atropine at doses of 12. 5 ～50μg/kg the temper-ature of the liver and the armpit skeletal muscle were significantly reduced in adose-dependent manner but the skin temperature was increased. Temperature changeswere observed 5 min after drug administration, reaching peak height at about 15 min andmaintained for one hour or so. Isoprenaline, dopamine and aminophylline iv showed only a tempera-ture-elevating effect, while serotonin and noradrenaline caused only a tempera-ture- decreasing effect in all the three organs mentioned above. Although the functional significance of the opposite effects on the microcirculation ofdifferent tissues remain to be defined, the effects of atropine- like drugs must result in aredistribution of circulating blood and may have beneficial effects on the survival of somevital organs such as brain, lungs, kidneys…especially in shock.     

山莨菪碱及阿托品对大鼠肝、横纹肌及趾蹠血管的作用

阿托品类药物对感染性休克等病有突出疗效,作用机理较复杂,主要是直接促进微循环的作用。以前我们报告了这类药物扩张大鼠皮肤血管的高度活性。本文报告对调节微循环血量有重要作用的肝脏、横纹肌及皮肤(趾跖)对阿托品类药物的同时收缩和扩张两种不同性质的反应。     

维拉帕米、硝苯吡啶对大鼠输卵管活动和卵转运的影响

钙拮抗剂维拉帕米(VER)和硝苯吡啶(NIF)可明显抑制离体大鼠输卵管标本的自发性收缩活动,用求积仪测得的5min收缩曲线面积表明:VER、NIF给药后面积均明显小于给药前,呈剂量依赖性,在整体实验中VER、NIF可使妊娠3d大鼠输卵管内卵的运行加速,与对照组比较,用药组在子宫腔内回收到的卵数明显多于对照组,合笼实验证明VER、NIF没有抗着床作用。     

EFFECT OF EXERCISE ON PLASMA ADRENOMEDULLIN AND NATRIURETIC PEPTIDE LEVELS IN MYOCARDIAL INFARCTION

1. We investigated the effect of exercise on plasma adreno-medullin, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations and studied the relationship between these peptides and haemodynamic parameters in nine patients with old myocardial infarction (MI) and in eight normal subjects. 2. The exercise protocol consisted of two fixed work loads (40 and 80 W) for 4 min each and venous blood samples were taken at rest, during each exercise stage and after exercise while monitoring the mean arterial pressure (MAP) and heart rate (HR). In MI, pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP) and cardiac output (CO) were measured throughout exercise. 3. Adrenomedullin levels did not significantly increase with exercise. Adrenomedullin levels correlated with PAP and PCWP at rest (P < 0.05). Atrial natriuretic peptide levels correlated with PAP, PCWP and LVEDP throughout exercise (P < 0.05) but, on multiple regression analysis, PCWP correlated only with ANP (P < 0.01). Brain natriuretic peptide levels correlated with LVEDP throughout exercise (P < 0.01) and its increment correlated closely with basal BNP levels at rest (P < 0.01). 4. These results suggest that adrenomedullin does not respond to the acute haemodynamic changes of exercise, whereas ANP responds to it and PCWP is the major stimulus factor. Brain natriuretic peptide responds to exercise in proportion to the basal synthesis of BNP in patients with left ventricular dysfunction and LVEDP may play a role in increasing BNP during exercise.     

CROSSOVER COMPARISON BETWEEN THE DEPRESSOR EFFECTS OF LOW AND HIGH WORK-RATE EXERCISE IN MILD HYPERTENSION

1. The relationship between work-rate and the antihypertensive effect of exercise in hypertensives, and the mechanism of that effect, were investigated by a crossover clinical trial. 2. Ten mild hypertensives were randomly divided into two groups. One group performed low work-rate exercise (LWE) on a cycle ergometer for 10 weeks (blood lactate threshold; ～50% of maximum oxygen consumption [V?_O2max]). After a 10 week interval without exercise training, these subjects were then switched to a high work-rate exercise (HWE) regimen (4 mmol/ L of blood lactate; ～75% of V?_O2max) for another 10 weeks. In the other group, the order of exercise training was reversed. Since two patients withdrew from the protocol during HWE periods, statistical analysis was performed on the data from the remaining eight patients. There were no order effects observed in any of the data from the two groups. 3. During both LWE and HWE, resting blood pressure (BP) fell significantly after the initiation of exercise therapy (P<0.05). Furthermore, the overall effects of 10 weeks of LWE and HWE on BP were not significantly different. 4. The work-rate at the lactate threshold, which reflects physical fitness, had increased significantly by 16 W (P<0.01) after the LWE period and by 11 W (P<0.01) after the HWE. 5. During the LWE period, changes in haemodynamic and humoral variables were not significant, except for a reduction in plasma norepinephrine at week 10 (P<0.05). In the HWE period, changes in haemodynamic and humoral variables were not significant. 6. Based on these findings, LWE is recommended for mild hypertensives because of its safety.     

全腹照射后大鼠的肠粘膜病理损害及防治

６０只大鼠分为四组：未接受照射的Ａ组口服谷氨酰胺，Ｂ组口服甘氨酸，接受照射的Ｃ组口服谷氨酰胺，Ｄ组口服甘氨酸，均为标准颗粒饲料喂养，一周后杀死动物，无菌取肠系膜淋巴结，肝和脾制成匀浆，行细菌培养，统计细胞移位率。对回肠粘膜进行光镜检查，光镜切片用显微图象分析仪进行计算机图象分析，结果说明：大鼠全腹照射可引起肠粘膜损伤，并由此引起细菌位移，而口服谷氨酰胺能预防大鼠全腹照射后的肠粘膜病理损害，而减少细菌移位的发生。     

AMG-1和腺苷对大鼠脑突触体谷氨酸释放的影响

观察了腺苷类化合物AMG-1对大鼠脑突触体前膜谷氨酸(glu)释放的影响。AMG-1在0.1～0.3 mmol·L^-1能明显抑制突触前膜Ca²⁺-依赖性glu的释放,并呈现剂量—效应关系。其作用强度与腺苷基本相似。提示AMG-1对脑保护作用可能与它激活腺苷A₁受体,从而抑制兴奋性氨基酸释放有关。     

INFLUENCE OF MUSCLE BLOOD FLOW ON FATIGUE DURING INTERMITTENT HUMAN HAND-GRIP EXERCISE AND RECOVERY

1. The influence of muscle blood flow on fatigue and recovery was studied in the forearm muscles of eight male subjects performing a powerful isometric hand-grip exercise. The exercise was performed with the exercising forearm normally perfused and, on a separate occasion, with its blood flow occluded with a sphygmomanometer cuff. 2. In the no cuff condition, peak force declined to an initial plateau at 40–50% of the maximal voluntary grip force (MVC). When perfusion was occluded, the force decline was similar during the first minute of exercise, then force fell rapidly to exhaustion. 3. In a separate experiment to investigate the mechanisms underlying the plateau in force loss, occlusion of blood flow during the force plateau phase resulted in a rapid decline in force to exhaustion. 4. Recovery of peak force after the cuff exercise was significantly greater during the initial 3.5 min of recovery than after no-cuff exercise. After this time, recovery was similar for both conditions. 5. Muscle blood flow occlusion during intermittent exercise profoundly reduces endurance without prolonging recovery. Recovery time may depend on the duration and energy cost of the exercise rather than on the degree of force loss. 6. The present study suggests that the fall in muscle force induced by a continuous MVC is a combination of profound short-term fatigue in anaerobic muscle fibres due to the consumption of their short-term energy supplies, plus a decline in force production by aerobic muscle fibres that is the consequence of hypoxia. Thus, MVC may not be a good model of fatigue occurring under submaximal conditions, as hypoxia of type I fibres is unlikely to occur under physiological conditions in which muscle contractions are usually intermittent.     

“深海龙”的抗疲劳作用及对人体运动能力的影响

深海龙是由海龙、海马、鹿茸、人参、肉苁蓉、当归、枸杞以及另外十几味中药组成的复方中药制剂。为了控索深海龙的抗疲劳作用和对人体运动能力的影响,对４０名中长跑运动员进行了历时一个月的大强度训练。其中２０名服用深海龙,另外２０名不服药者作为对照组。服药训练前后分别测试运动员的最大有氧能力和最大无氧能力。结果显示,经过一个月的训练,服药组的最大平均无氧功率、最大有氧功率和最大乳酸值比对照组有明显提高。服药     

THE EFFECT OF OXYTOCIN ON PORCINE MALIGNANT HYPERPYREXIA SUSCEPTIBLE SKELETAL MUSCLE

1. Certain commercial preparations of oxytocin have been reported to reverse the development of pale soft exudative meat and malignant hyperpyrexia (MH) in pigs in vitro. 2. In this study it is shown that preservative-free oxytocin has no significant effect on the characteristic contractures of MH susceptible (MHS) muscle to halothane, caffeine, succinylcholine and KCl in vitro. 3. Whilst a commercial preparation of oxytocin, Syntocinon (containing chlorbutol as preservative), reversed and prevented the MHS characteristic responses, this study demonstrates conclusively that this was entirely due to the preservative chlorbutol.     

粉防己碱抑制血管平滑肌细胞胶原合成

目的　观察粉防己碱(Tet)对血管壁胶原沉积和血管平滑肌细胞胶原蛋白合成的影响。方法　用羟脯氨酸含量反映主动脉胶原沉积状况,用[³H]-脯氨酸参入反映细胞胶原蛋白合成。结果　与伪手术组相比,肾血管性高血压大鼠主动脉壁羟脯氨酸含量明显增加;粉防己碱可有效降低主动脉壁胶原含量,并呈浓度依赖性抑制[³H]-脯氨酸参入AngII或NE诱导的血管平滑肌细胞。结论　粉防己碱抑制血管平滑肌细胞胶原合成和动脉壁胶原沉积是其逆转血管重构作用的重要机制之一     

EFFECT OF TEMOCAPRIL ON HAEMODYNAMIC AND HUMORAL RESPONSES TO EXERCISE IN PATIENTS WITH MILD ESSENTIAL HYPERTENSION

1. This study was carried out to evaluate the effect of temocapril on haemodynamic and humoral responses to exercise in nine patients with mild essential hypertension (WHO stages I and II). 2. After a 4-week placebo period, temocapril was administered at a dose of 1.0 mg once daily for 2–4 weeks. Graded submaximal bicycle ergometer exercise was performed before and after temocapril treatment, and the changes in arterial blood pressure, heart rate, cardiac output (CO), and systemic vascular resistance (SVR) were evaluated. In addition, the plasma norepinephrine (NE) level was determined both at rest and peak exercise before and after temocapril treatment. 3. Both the systolic and diastolic blood pressure were reduced at rest and during exercise by temocapril treatment. No significant change in the resting heart rate and CO was observed, and the exercise-induced increase of these parameters was also not affected by temocapril. In contrast, the resting SVR was significantly decreased by temocapril, although the exercise SVR was similar during both temocapril and placebo treatment. 4. Although there was no significant change in the plasma NE level with temocapril treatment, the exercise-induced increase of plasma NE was significantly suppressed by temocapril. 5. These results indicate that temocapril reduces the blood pressure without causing any significant changes in the heart rate and CO at rest, and that it does not produce any changes in the haemodynamic response to exercise.     

EFFECT OF DIETARY SALT LOADING AND HIGH-CALCIUM DIET ON VASCULAR SMOOTH MUSCLE RESPONSES AND ENDOTHELIUM FUNCTION IN RATS

1. The present study examined the effects of concurrent manipulation of dietary calcium and salt on contractile responses of vascular smooth muscle (VSM) and endothelial function of aortic rings from Sprague-Dawley rats. 2. Salt loading enhanced the contractile response of the aortic rings to noradrenaline (NA), an effect that was blunted by a high calciu. intake. 3. Removal of the endothelium and incubation of aortic rings in physiological salt solution containing methylene blue increased the sensitivity of the rings t. NA. 4. The increase in the sensitivity of aortic rings induced by endothelium removal was more pronounced in aortic rings from salt-loade. rats. 5. Acetylcholine caused similar degrees of relaxation in all experimental groups, but the relaxation to histamine was smalle. (P < 0.05) in salt-loaded rats than in other groups of rats; however, after removal of the endothelium, the contractile response to histamine was higher in salt-loaded rats. 6. The results indicate that the hypersensitivity of isolated aortic rings to agonists, as observed in salt-loaded rats, is due to altered responses of the VSM and not as a result of changes in the endothelium. In addition, salt loading tends to increase the synthesis of endothelium-dependent relaxing factor. The ability of salt loading to enhance the contractile responses of VSM to agonists can be prevented by supplementing the diet with high calcium.     

AP对正常和内毒素化大鼠脾细胞体外分泌细胞因子的影响

从分子免疫水平探讨了巴巴多斯芦荟多糖提取物(AP)对免疫系统的作用.结果表明巴巴多斯芦荟多糖提取物对体外正常大鼠脾细胞分泌IL-1、IL-6、TNFα等细胞因子均有一定的促进作用,而对内毒素诱导脾细胞分泌的细胞因子IL-1、IL-6、TNFα有显著抑制作用.对IL-2的分泌在以上两种情况下均表现促进作用.显示巴巴多斯芦荟多糖提取物对细胞因子的分泌可产生双向调控作用.     

INFLUENCE OF WORKLOAD ON THE ANTIHYPERTENSIVE EFFECT OF EXERCISE

1. The relation between workload and the antihypertensive effect of exercise therapy in hypertensive patients, and the mechanism of that effect, were investigated. 2. Twenty-six patients participated in the study and were randomly assigned to 10 weeks of either low or high workload exercise. In the low workload group, 16 mild hypertensive patients were treated with bicycle ergometer exercise at approximately 50% of their maximum oxygen consumption (VO2max) for 60 min three times a week for 10 weeks. In the high workload group, 10 mild hypertensive patients exercised on the same schedule, but at approximately 75% of VO2max. 3. After 10 weeks of exercise, the low workload group had significantly lower systolic (9 mmHg), mean (6 mmHg) and diastolic (6 mmHg) blood pressures. In the high workload group, decreases in systolic (3 mmHg), mean (4 mmHg) and diastolic (5 mmHg) blood pressure were not statistically significant. 4. In the low workload group, changes in haemodynamic and humoral variables were not significant, except for a reduction in plasma norepinephrine at week 7. Cardiac index and plasma norepinephrine tended to decrease. In the high workload group, plasma norepinephrine and the renin-angiotensin system were transiently stimulated after 4 weeks of exercise. Stroke volume significantly increased (+26.4%) after 10 weeks of high workload exercise. 5. Based on these results and better patient compliance with the exercise programme in the low workload group than in the high workload group, low workload exercise therapy was recommended to mild hypertensive patients.     

EFFECT OF DILTIAZEM, VERAPAMIL AND DANTROLENE ON THE CONTRACTILITY OF ISOLATED MALIGNANT HYPERPYREXIA-SUSCEPTIBLE HUMAN SKELETAL MUSCLE

1. Diltiazem (10 mumol/L) and verapamil (10 mumol/L) inhibited the hypercontractility induced by 3% halothane and 2 mmol/L caffeine in malignant hyperpyrexia susceptible (MHS) muscle. Diltiazem also inhibited 80 mmol/L KCl contractures. 2. Like the skeletal muscle relaxant dantrolene sodium (6 mumol/L), diltiazem not only prevented but reversed the abnormal contractures induced by halothane and caffeine. 3. The effect on caffeine contractures of diltiazem and dantrolene in combination was additive. 4. The ability of diltiazem and verapamil to inhibit the hypercontractility of MHS muscle suggests that Ca2+ influx across the transverse tubular membrane may be important in the aetiology of the malignant hyperpyrexia syndrome. 5. These results also suggest an abnormality in transverse tubule-sarcoplasmic reticulum communication.