尼古丁成瘾者短期戒断对血清骨调素水平的影响

目的：研究发现,尼古丁成瘾是引起骨质疏松和骨折以及增加骨折不愈合的危险因素,而戒烟可以有效降低骨折发生的风险。血清骨调素水平与骨质疏松的发生相关。因此,本研究探索了尼古丁成瘾者短期戒断对血清骨调素水平的影响。方法：将尼古丁成瘾者随机分为两组,要求其中一组受试者戒烟48 h,而另外一组受试者的吸烟量保持不变。检测两组受试者48 h前、后血清骨调素水平的变化。结果：30名尼古丁成瘾者完成了试验。正常吸烟组48 h前、后血清骨调素水平分别为9.57 μg·L-1±s 3.37 μg·L-1和10.5 μg·L-1±s 3.13 μg·L-1,没有显著性差异（n=14,P=0.46）;戒烟组48 h前、后血清骨调素水平分别为8.56 μg·L-1±s 4.5 μg·L-1和5.63 μg·L-1±s 3.32 μg·L-1,有显著性差异（n=16,P=0.04）;两组受试者在48 h前血清骨调素水平没有显著差异（P=0.5）。结论：戒烟后,尼古丁成瘾者血清骨调素水平显著下降。这提示,骨调素可能在尼古丁成瘾影响骨质疏松过程中发挥调节作用。     

青少年期尼古丁暴露对成年大鼠饮酒行为和腹侧被盖区nACh受体表达水平的影响

目的:观察大鼠青少年期尼古丁暴露对成年期大鼠饮酒行为的影响,检测青少年期尼古丁暴露和成年期大鼠饮酒行为对大鼠腹侧被盖区(VTA脑区)烟碱型尼古丁受体(nAChR)部分亚单位mRNA表达的影响。探讨VTA区nAChR受体参与青少年期吸烟和成年期酒依赖形成的可能机制。方法:39只Wistar大鼠出生后35 d(PN35)开始为期10 d的尼古丁(1.0 mg.kg-1/day salt)皮下注射(尼古丁处理组,N组n=20),以生理盐水作为对照处理(生理盐水对照组,C组n=19)。完成后各组随机抽取6只作为空白对照(E)组(分别为CE组n=6,NE组n=6),断头取脑分离VTA区提取mRNA,Real Time-PCR定量检测nAChR受体α4、α5、α7和β2亚单位mRNA。两组余下大鼠作为酒依赖模型(A)组(分别为NA组n=14,CA组n=12)于大鼠出生后60 d(PN60)以Samson糖水递减程序诱导建立乙醇双瓶自由选择饮酒行为实验,观测干预对Wistar大鼠乙醇消费量、酒偏好程度、总饮液量的影响。之后相同程序定量检测VTA标本相同指标。结果:青少年期尼古丁干预对成年期饮酒行为的各项行为学指标无明显影响(P>0.05)。VTA区nAChR亚单位mRNA的表达:未建立酒依赖模型两处理组间α4、α5、α7和β2亚单位mRNA表达无差异(P>0.05);建立酒依赖模型两处理组间α4、α5、α7和β2亚单位mRNA表达都有不同程度的显著性差异(P<0.05或P<0.001),其中尼古丁处理组α4、α5和β2表达上调,生理盐水处理组α7表达下调。因素分析显示:两因素对α4和α5亚单位表达都有调节作用;酒依赖模型因素对β2表达有调节作用;对α5、α7和β2亚单位表达两因素有交互作用。结论:(1)青少年期尼古丁干预可以调节VTA区nAChR亚单位α4、α5、α7、β2的表达,其效应在一定时间后才出现;没有发现青少年期尼古丁干预对成年期酒依赖形成行为学的促进作用,考虑可能有深层的内在原因相继造成了人类青少年期吸烟和此后酒依赖的形成。(2)VTA区多种包含有α4、α5、α7、β2亚单位的nAChR亚型是尼古丁和乙醇共同作用点,推测是众多推动酒依赖形成的因素之一。     

EFFECTS OF CHRONIC NICOTINE INGESTION ON PRESSOR RESPONSE TON-NE2RO- -ARGININE METHYL ESTER ANDEX VIVOCONTRACTION AND RELAXATION RESPONSE OF AORTA TO -ARGININE

Effects of nitric oxide synthase inhibition on blood vessels were studied in nicotine-treated rats. Male Sprague–Dawley rats drank a nicotine solution with a concentration of 25 or 50 μg/ml for 15 days. The blood pressure and heart rate of chloralose-anaesthetized rats and isolated aortic strip contractions were measured.N^ωNitro- -arginine methyl ester ( -NAME)-induced hypertension was significantly reduced after chronic nicotine treatment. TheE_maxof contractions of isolated aortic strips to noradrenaline were dose-dependently enhanced by nicotine and the potentiation was abolished by -arginine. The relaxation of aortic strips to acetylcholine was significantly decreased in nicotine-treated rats, whereas -arginine, but not -arginine, reversed this action. Neither nicotine nor -NAME affected the heart rate. The results show that chronic nicotine treatment reduced the pressor response of -NAME.     

NEUROPHARMACOLOGY OF NICOTINE: EFFECTS ON THE AUTOREGULATION OF ACETYLCHOLINE RELEASE BY SUBSTANCE P AND METHIONINE ENKEPHALIN IN RODENT CEREBRAL SLICES AND TOXICOLOGICAL IMPLICATIONS

1. The neuronal release of acetylcholine (ACh) and its autoregulation by neuromodulators, substance P (SP) and methionine enkephalin (MEK), have been studied using super-fused rodent cerebral slices. Nicotine exerts significant effects on autoregulation of ACh release, which may have toxicological implications. 2. Positive and negative feedback systems have been postulated for autoregulation of ACh release. The components of the positive feedback system include a muscarinic (Ms) receptor, SP, and activation of Ca²⁺ influx. Low levels of ACh in the biophase of the cholinergic synaptic gap may trigger the positive feedback system, and high levels of ACh may trigger the negative feedback system. 3. There are also neuronal pathways for direct reciprocal regulations of SP and MEK. 4. Low concentrations of nicotine triggers the release of ACh followed by MEK and SP. Release of SP causes neurogenic inflammation. 5. Nicotine and its metabolite, cotinine, activate platelet activating factor (PAF)-hydrolase and thereby enhance the turnover rate of PAF. This effect may contribute to tobacco-induced arterial thrombosis in peripheral and central nervous systems.     

EFFECTS OF OESTROGEN AND PROGESTERONE ON AGE-RELATED CHANGES IN ARTERIES OF POSTMENOPAUSAL WOMEN

1. Hormone replacement therapy (HRT) with oestrogen or oestrogen plus progestin may have different effects on arterial structure and function. To examine this question, carotid artery intima-medial thickness (IMT) and indices of systemic and carotid arterial compliance were measured in groups of older men, postmenopausal women not on HRT (non-HRT) and those women on long-term HRT with oestrogen alone (HRT-E) or oestrogen plus progestin (HRT-EP). 2. Sixty men, 90 postmenopausal women taking HRT and 91 not taking HRT participated in the study. The groups were similar for age, body mass index, numbers of smokers, physical activity, alcohol intake and blood pressure. 3. Plasma total cholesterol was reduced and high-density lipo-protein-cholesterol was increased in the HRT group compared with the non-HRT group; low-density lipoprotein-cholesterol, triglyceride and lipoprotein (a) values were similar in these two groups. Results for HRT-E and HRT-EP subgroups were similar. 4. Carotid IMT was significantly reduced in the HRT group compared with men and non-HRT groups. Results for HRT-E and HRT-EP subgroups were similar. 5. Mean systemic arterial compliance (SAC) was significantly greater in men than in women and was related to age; SAC was higher in both HRT-E and HRT-EP groups compared with the non-HRT group. Indices of carotid stiffness were similar in men and in non-HRT groups. The HRT-EP group showed increased carotid stiffness compared with the HRT-E group. 6. There is an apparent protective effect of long-term oestrogen therapy on carotid IMT and age-related changes in arterial stiffness. Progestin does not alter the IMT effects but may adversely influence arterial stiffness.     

EFFECTS OF ENDOTHELIN-1 ON ARTERIAL PRESSURE AND MYOCARDIAL CONTRACTILITY IN THE CONSCIOUS NORMOTENSIVE RABBIT

1. We studied the effects of an intravenous bolus of endothelin-1 on arterial pressure and myocardial contractility in the conscious rabbit. 2. Endothelin produced an initial fall in arterial pressure accompanied by an increase in heart rate. This was followed by a dose-dependent increase in arterial pressure, peaking about 7 min after injection, accompanied by a reciprocal fall in heart rate. 3. Left ventricular rate of change of pressure (LV dP dt) increased with endothelin except at higher doses (0.8 and 1.6 nmol/kg), where in some animals it decreased.     

CARDIOVASCULAR EFFECTS OF NICOTINE DURING PHYSICAL ACTIVITY AND FOLLOWING MEAL CONSUMPTION

1. In two separate studies using healthy male smokers as subjects, the acute cardiovascular effects of a measured dose of nicotine (15 micrograms/kg) were examined in conjunction with light physical activity and following consumption of a meal, conditions typical of nicotine intake via smoking. 2. Increases in heart rate and systolic blood pressure attributable to nicotine were similar during rest, physical activity, and following eating, demonstrating additivity with the cardiovascular effects of activity and a caloric load. Diastolic blood pressure was less affected by nicotine. 3. These results indicate that cardiovascular activity is acutely increased following nicotine (smoking) regardless of other influences on the cardiovascular system. Such effects may help explain increased risks of acute cardiac abnormalities due to smoking.     

不同年龄组急性心肌梗塞溶栓治疗的对比研究

４７例急性心肌梗塞（ＡＭＩ）患者按发病年龄随机分成三组，进行尿激酶（ＵＫ）溶栓疗效的对比研究。结果表明，１２小时内溶栓的４７例ＡＭＩ患者再通率、死亡率和并发症发生率分别为５５．３％、１４．９％和８．５％。６小时内溶栓再通率老年组（５０％）明显低于青年组（８０％）和老年前期组（７０％）。老年组住院病死率为２５．９％，且有出血并发症发生，而青年组和老年前期组无一例死亡且无一例出血并发症发生。提示ＵＫ溶栓疗效与患者年龄有关，老年人溶栓疗效较差，病死率和出血并发症发生率较高。     

EFFECTS OF CHRONIC NICOTINE INGESTION ON PRESSOR RESPONSE TON-NE2RO-L-ARGININE METHYL ESTER ANDEX VIVOCONTRACTION AND RELAXATION RESPONSE OF AORTA TOL-ARGININE

Effects of nitric oxide synthase inhibition on blood vessels were studied in nicotine-treated rats. Male Sprague–Dawley rats drank a nicotine solution with a concentration of 25 or 50 μg/ml for 15 days. The blood pressure and heart rate of chloralose-anaesthetized rats and isolated aortic strip contractions were measured.N^ωNitro-L-arginine methyl ester (L-NAME)-induced hypertension was significantly reduced after chronic nicotine treatment. TheE_maxof contractions of isolated aortic strips to noradrenaline were dose-dependently enhanced by nicotine and the potentiation was abolished byL-arginine. The relaxation of aortic strips to acetylcholine was significantly decreased in nicotine-treated rats, whereasL-arginine, but notD-arginine, reversed this action. Neither nicotine norL-NAME affected the heart rate. The results show that chronic nicotine treatment reduced the pressor response ofL-NAME.     

肝动脉栓塞微球的动物体内行为和药效学研究

肝动脉栓塞微球是用于治疗中晚期肝癌的新剂型。通过动脉插管即可将微球栓塞至肝癌邻近的末梢动脉血管,起阻断血流和在局部缓释药物的双重作用。本文结合几年来对MTX明胶微球和顺铂-乙基纤维素微球的基础研究工作,综述微球栓塞后在动物体内的行为和药效学,并介绍了初期临床结果。     

THE EFFECT OF FOOD ON THE PHARMACOKINETICS OF MULTIPLE-DOSE TERBINAFINE IN YOUNG AND ELDERLY HEALTHY SUBJECTS

Pharmacokinetic (PK) parameters for terbinafine were assessed in 15 elderly and 15 young healthy subjects randomized to receive 250 mg Lamisil^™ once daily for 15 d in a two-period, two-treatment, two-sequence, crossover (fed versus fasted) design within age groups. On each treatment day except days 8 and 15, subjects took Lamisil^™ with food at 8:00 a.m. On days 8 and 15, subjects took the drug under either fed or fasting conditions according to treatment sequence, and 24 h PK profiles were obtained. Two analyses of the pharmacokinetic data were undertaken. In a noncompartmental analysis, AUC_{0–24 h} , C_max , C_{0 h} , and t_max were computed for each subject on each of days 8 and 15, and the influences of food condition and age on these variables were assessed by analysis of variance. AUC_{0–24 h} and C_{0 h} were found to be larger (p <0·5) among elderly subjects than young subjects on day 15, and t_max was prolonged (p <0·05) under the fed condition on day 15. Similar trends on day 8, as well as generally higher exposures under the fed condition on both days, were not statistically significant. A three-compartment model fitted to the complete sequence of 33 terbinafine concentrations measured over 29 d for each subject separately permitted a within-subject assessment of the food effect that confirmed prolonged absorption and increased bioavailability (p <0·05) under the fed condition. Across-subject comparisons of oral clearances estimated with the model also confirmed the increased exposures (lower clearances) among the elderly (p <0·05). The drug was well tolerated in both age groups. In particular, greater drug exposure in the elderly did not result in greater toxicity, as indicated by the safety evaluations in the study. © 1997 by John Wiley & Sons, Ltd.     

视觉模拟标尺评估吸烟者尼古丁渴求强度的能力初探

目的:探讨视觉模拟标尺(VAS)评估吸烟者尼古丁渴求强度的能力。方法:在知情同意的前提下,采用VAS和Fagerstrm尼古丁依赖检验量表(FTND)对广告招募的北京市区211例吸烟史≥1a、每日吸烟≥10支,并有戒烟动机的吸烟者进行横断面现场调查,以VAS分和FTND总分的相关分析评估VAS评估吸烟者尼古丁渴求强度的能力,并以吸烟者吸烟量、吸烟深度、呼气一氧化碳(CO)浓度和尿中可替宁浓度等指标来验证。结果:VAS与FTND呈线性正相关(P=0.000);VAS与日吸烟量、吸烟深度、呼气CO浓度、尿液可替宁浓度呈正相关(P均<0.01)。饮酒组与非饮酒组中VAS与FTND皆呈正相关(P=0.000)。非饮酒组中VAS与日吸烟量、吸烟深度、呼气CO浓度都呈正相关(P均<0.05)。饮酒组中VAS与日吸烟量、尿液可替宁浓度呈正相关(P均<0.01)。结论:VAS对吸烟者中尼古丁渴求强度有较好的评估能力,推荐该量表可以用来作为评价尼古丁渴求强度的工具。同时,在VAS结合自报吸烟深度评价饮酒者的尼古丁渴求程度时,应当考虑饮酒因素的影响。     

大鼠烟碱依赖对脑皮层M、N胆碱能受体的影响

采用放射配体结合实验，研究大鼠对烟碱形成依赖后脑皮层Ｍ、Ｎ胆碱能受体的变化，结果显示，形成烟碱依赖后脑皮层Ｍ－受体的亲和力与密度均无改变；Ｎ－受体亲和力也无明显变化，而Ｎ－受体密度则从对照组的９０ｆｍｏｌ·ｍｇ－１±ｓ５ｆｍｏｌ·ｍｇ－１蛋白上调到１３１ｆｍｏｌ·ｍｇ－１±ｓ９ｆｍｏｌ·ｍｇ－１蛋白。表明烟碱依赖与脑Ｎ－受体上调相关。     

FACTORS INFLUENCING THE EFFECTS OF INTRAVENOUS NALOXONE ON ARTERIAL PRESSURE AND HEART RATE AFTER HAEMORRHAGE IN CONSCIOUS RABBITS

The circulatory responses to different intravenous doses of naloxone were studied in conscious rabbits before and after haemorrhage, under different conditions including prior ganglion blockade. Unless there had been blood loss, naloxone elicited no pressor response, even in high dose. After bleeding so that arterial pressure fell to 40 mmHg, the dose-response relationship for naloxone had two components. Over a low-dose range (threshold 0.3 mg/kg) naloxone had a modest pressor effect but did not affect heart rate. Over a much higher dose range (threshold 0.6 mg/kg) naloxone caused a marked rise in arterial pressure and a profound bradycardia. The highest dose of naloxone examined (25 mg/kg) caused a rise in arterial pressure of 70 mmHg and a reduction in heart rate of 160 beats/min. The pressor and bradycardic effects of naloxone were the same whether post-haemorrhagic hypotension lasted 5, 10, 20 or 30 min. The responses to naloxone in low or high dose depended much more closely on the volume of blood removed than on the level to which arterial pressure fell. Even after non-hypotensive haemorrhage a high dose of naloxone had marked pressor and bradycardic effects. Ganglion blockade prior to haemorrhage abolished the pressor response to a low, but not to a high, dose of naloxone. It was concluded that prolonged and severe hypotension are not necessary to 'prime' the cardiovascular system to respond to naloxone after haemorrhage. In a high dose its pressor effects appear to be mediated post-ganglionically, but in a low dose it may act within the central nervous system.     

EFFECTS OF ACUTE VERSUS CHRONIC DELETION OF ARTERIAL BARORECEPTOR INPUT ON THE CARDIOVASCULAR RESPONSES TO EXERCISE IN THE RABBIT

These experiments were designed to confirm that at the onset of treadmill exercise in rabbits the tonic reflex depressor effects of input to the central nervous system from arterial baroreceptors is abolished, thus contributing to the rise of systemic arterial pressure (SAP) and heart rate (HR). An inflatable cuff was placed around one common carotid artery after the remaining arterial baroreceptors had been surgically denervated. Transient inflation of the cuff caused reflex rises of SAP and HR, which were much reduced during the first minute of exercise. Deflation of the cuff caused a brisk fall of HR, which was completely abolished by exercise. A snare was placed around one carotid sinus nerve after the remaining arterial baroreceptors had been surgically denervated. Where the snare was tightened all arterial baroreceptor reflexes were immediately and permanently abolished. This allowed the reflex effects of baroreceptor input to be calculated by difference. The magnitude of these calculated effects, at rest and during exercise, diminished according to how long after barodenervation the observations were made. We conclude from the above experiments that the resting tonic reflex depression of SAP and HR caused by baroreceptor input is much reduced, rather than completely abolished, at the onset of exercise. We also conclude, from the effects of partial surgical barodenervation, and of unloading the carotid baroreceptors prior to exercise by inflating the carotid cuff, that resting input from the arterial baroreceptors must be near zero before the cardiovascular response to exercise is grossly altered.     

甘糖酯对鹌鹑肝脏和动脉壁胆固醇及丙二醛含量的影响

甘糖酯(PGMS)是类肝素海洋药物。本文以鹌鹑高脂血症为模型观察了PGMS对鹌鹑肝脏和动脉壁胆固醇及丙二醛含量(MDA)的影响。结果表明,口服PGMS 6周,能明显抑制高脂饮食所致TC、(LDL VLDL)-C水平的升高,提高HDL-C/TC及HDL_2-C/HDL_3-C值;明显减少鹌鹑肝脏和动脉壁胆固醇含量,特别是减少胆固醇酯在动脉壁的沉积和脂质过氧化物的终末产物MDA的生成。     

硝苯吡啶缓释片的人体药物动力学及生物利用度

用ＨＰＬＣ法测定血中硝苯吡淀浓度，对进口的硝苯吡啶务产的硝苯吡啶缓释片进行健康人药物动力学和生物利用度研究，所得数据经３Ｐ８７软件处理。结果显示：硝苯吡啶以二室模型进行分布和消除，进口硝苯吡啶的生物利用度明显优于国产硝苯吡啶，消除半衰期长于国产硝苯吡啶。     

四肽KRDS对犬血小板功能及动脉血栓形成的抑制作用

来自人乳转铁蛋白的四肽(赖—精—门冬—丝氨酸,K RDS)能抑制ADP诱导的犬血小板聚集反应(IC_(50):350μmol/L)和花生四烯酸诱导的血栓烷B_2的产生(IC_(50):175μmol/L),同时,KRDS能抑制凝血酶诱导的血小板表面α—颗粒膜蛋白(GMP-140)的表达(IC_(50):350μmol/L及5—羟色胺的释放(IC_(50):525μmol/L)。另外,KRDS能抑制犬股动脉实验血栓的形成,制备血栓模型4h后,离体血栓的重量为对照组的50%,以~(125)Ⅰ—SZ-51(抗GMP-140的单抗)为示踪剂,离体血栓与血液的放射活性比值仅为对照组的16%。结果提示:四肽KRDS不仅能抑制犬血小板的聚集和释放功能,对体内血栓的形成也有明显的抑制作用,为一生理性抗血栓寡肽。     

EFFECT OF GRADED ADRENALINE INFUSION ON ARTERIAL ADRENALINE CLEARANCE IN NORMOTENSIVE AND HYPERTENSIVE MAN

1. Arterial adrenaline (ADR) levels were measured during graded ADR infusions in normotensives (NT) and in mild hypertensives (HT), in order to test the hypothesis that ADR enhances its own clearance in NT. 2. Although infusion of ADR resulted in similar arterial ADR levels in NT and HT, increases in systolic blood pressure (SBP) and heart rate (HR) and decreases in diastolic blood pressure (DBP) were greater during ADR infusion in HT than in NT. 3. Twenty minutes after cessation of infusion, SBP and HR remained elevated in HT but not in NT. 4. No evidence was found supporting enhanced ADR clearance during increasing ADR levels in NT or HT.