THE SPECIFICITY OF BILE SALTS IN THE INTESTINAL ABSORPTION OF MICELLAR CHOLESTEROL IN THE RAT

1. Two aspects of cholesterol absorption; (a) the importance of solubilization and (b) the effects of different bile salts on the mucosal metabolism and lymphatic output of cholesterol, have been investigated using two different in vivo techniques. 2. Bile diverted lymph fistula rats were infused intraduodenally at a steady rate with a constant lipid mixture containing labelled cholesterol, labelled oleic acid and mono-olein. The lipids were completely solubilized in either bile salts or a non-toxic non-ionic detergent, Pluronic F68. Labelled fatty acid was efficiently absorbed from either micellar infusate but virtually no labelled cholesterol appeared in the lymph in the absence of bile salts. 3. Short-term perfusions of the intestine of anaesthetized rats with the same micellar perfusates as above showed approximately 20% of the labelled cholesterol in the mucosa after 30 min perfusion with the bile salt micellar solutions. When the non-ionic micelles were used virtually no isotopic cholesterol left the lumen. 4. Mucosal uptake of labelled cholesterol was linearly dependent on the concentration of solubilized cholesterol in the perfusate and was not dependent on the bile salt concentration. 5. After 30 min the total amount of perfused isotopic cholesterol was recovered from either the lumen or the mucosa, but some fatty acid appeared to have been transported away from the mucosa by this time. 6. The initial rate of mucosal uptake of labelled cholesterol was similar from micellar perfusates using either taurocholate, taurodeoxycholate or taurofusidate. In contrast, after 8 h of infusion, lymphatic output of labelled cholesterol was markedly greater with taurocholate. 7. The increased lymph output with taurocholate was associated with an increase in the esterified fraction of both labelled and unlabelled cholesterol. Fatty acid was absorbed and esterified equally from all three types of perfusate. 8. These results suggested that for the first step in cholesterol absorption, viz. uptake from the lumen, solubilization by a planar detergent was essential. After up take, the more rapid transfer of cholesterol to lymph in the presence of trihydroxy bile acids appeared to be related to a more efficient esterification of cholesterol, but not to a more efficient resynthesis of triglyceride, the other major component of lymph chylomicrons.     

磺胺脒制造过程中“硫化”阶段杂质的分离

在了解生产磺胺脒的过程中,我们发现有许多问题可以作进一步的研究。这些问题的解决可能会对生产上有一定的帮助。其中问题之一就是"硫化"工段产品中杂质的分离。目前生产磺胺脒的步骤如下:     

ROLE OF THE SYMPATHETIC NERVOUS SYSTEM IN THE ONSET OF HYPERTENSION IN THE RAT: THE EFFECT OF 6-OH-DOPAMINE

1. The effect of chemical sympathectomy with 6-OH-dopamine (6-OHDA) on the onset of adrenocorticotrophin (ACTH)-induced hypertension was examined in Sprague-Dawley rats (n = 23). 2. 6-OHDA injection produced a fall in systolic blood pressure (SBP) from 100 +/- 5 mmHg control to 74 +/- 4 mmHg post-6-OHDA Treatment Day 1 (P less than 0.001), but did not alter food or water intake, urine volume or electrolyte excretion. 3. Compared with sham injection, ACTH-treated rats showed an increase in blood pressure (sham: 98 +/- 7 mmHg; ACTH: 123 +/- 9 mmHg on Treatment Day 10; P less than 0.01), loss of bodyweight, and increases in water intake and urine volume. 4. The magnitude of the blood pressure rise on ACTH was greater in 6-OHDA-treated rats than in intact control rats. Metabolic changes were similar. 5. Chemical sympathectomy with 6-OHDA did not delay or block the onset of ACTH hypertension in the rat.     

THE POSSIBLE INVOLVEMENT OF ADRENOCEPTORS IN THE INTESTINAL EFFECT OF MORPHINE IN MICE

The inhibitory effect of morphine on intestine was observed by following the intestinal transit of a charcoal meal. This inhibitory effect of morphine was antagonized by naloxone. In addition, the inhibitory effect of morphine was also suppressed by prior administration of yohimbine and phentolamine. However, prazosin, a selective alpha 1-adrenoceptor antagonist, had no effect on the inhibitory effect of morphine on intestinal transit. Furthermore, prior administration of propranolol did not alter this effect of morphine. These adrenoceptor antagonists by themselves, at the doses used, had no effect on the rate of intestinal transit of a charcoal meal in mice. These results suggest that alpha 2-adrenoceptors may be involved in the intestinal effect of morphine while alpha 1- and beta-adrenoceptors do not appear to play any significant role in this aspect of morphine action.     

可乐宁治疗海洛因成瘾临床疗效观察

使用α-受体激动剂可乐宁对60例海洛因成瘾者戒毒治疗,并与亚冬眠疗法对照进行观察。戒毒期间,可乐宁使用有效率为96.6%,与对照组(71.6%)比较,具有非常显著性差异,证明可乐宁的治疗效果可靠。根据海洛因戒断症状的临床表现和体征,本文将可乐宁治疗分为两组,对药物效能进行观察,治疗后72 h两组疗效结果提示,治疗早期配合使用抗焦虑类药物可以明显提高治疗药物的抑制效能,并能缓解与之伴随的主观不适诸症。结果说明可乐宁适用于各种类型的海洛因成瘾者的戒毒治疗。     

mTOR信号通路在大鼠可卡因自身给药复燃中的作用

背景:哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)是一种丝氨酸/苏氨酸激酶,其作用可被雷帕霉素所阻断。mTOR活化后参与调节基因转录、蛋白质翻译起始、核糖体生物合成、细胞凋亡等多个生物学过程。mTOR信号转导通路在学习记忆等神经活动的长期可塑性过程起着重要的作用。药物成瘾的过程是药物作用于中脑多巴胺奖赏系统发挥奖赏效应并使之发生长期神经可塑性改变的过程。长期使用成瘾性药物能产生强烈的心理渴求,使得药物成瘾者在戒断后再次暴露于药物、相关环境或压力时极易发生复吸。目前关于mTOR在药物成瘾中的作用研究较少,已有研究证实mTOR信号转导通路参与了药物作用于中脑边缘多巴胺系统引起的奖赏效应和长期神经可塑性,但mTOR信号通路在药物成瘾后发生复吸中的作用尚不清楚。目的:本研究旨在通过大鼠可卡因自身给药戒断后的复燃模型探讨mTOR信号通路在药物成瘾戒断后发生复吸行为中的作用,从而为成瘾神经生物学机制的研究和临床戒毒治疗提供新的实验依据。方法:(1)建立大鼠可卡因自身给药模型(0.75mg·kg-1 infusion,3h·d-1),经过消退后给予药物相关线索暴露诱导复燃行为,比较经过暴露和未经过暴露大鼠伏隔核中mTOR下游靶蛋白p70s6k磷酸化水平变化;(2)建立大鼠可卡因自我给药模型,经过消退后给予药物相关线索暴露诱导复燃行为。暴露前30min在大鼠伏隔核core/shell部分别微注射mTOR抑制剂雷帕霉素或溶媒,观察其对大鼠的复燃行为的影响,并检测暴露后大鼠伏隔核不同脑区中p70s6k磷酸化水平变化;(3)建立大鼠可卡因自身给药模型,经过消退后给予10mg可卡因点燃诱导复燃行为。可卡因点燃30min前在大鼠伏隔核core/shell部分别微注射雷帕霉素或溶媒,观察其对大鼠的复燃行为的影响;(4)建立大鼠可卡因自身给药模型,当大鼠获得稳定的自身给药行为后,在大鼠伏隔核core/shell部分别微注射雷帕霉素或溶媒,d2继续进行可卡因自身给药训练,观察雷帕霉素对可卡因强化效应的影响。结果:药物线索暴露后伏隔核core部的磷酸化p70s6k水平与未暴露组相比明显上升,说明药物线索暴露诱导的复燃能激活伏隔核的mTOR信号通路。在大鼠伏隔核core部给予雷帕霉素微注射能够抑制药物相关线索诱导的复燃行为,而伏隔核shell部给药无效。大鼠伏隔核core部注射雷帕霉素导致伏隔核core部磷酸化p70s6k水平下降,shell部磷酸化p70s6k水平不变。两个脑区的总p70s6k表达水平均无变化。在大鼠伏隔核shell部给予mTOR抑制剂雷帕霉素微注射能够抑制可卡因点燃诱导的复燃行为,而伏隔核core部给药无效。说明抑制伏隔核mTOR信号通路能够抑制药物相关线索或可卡因诱导的复燃行为,且此作用具有脑区特异性。行为学结果还表明,大鼠获得稳定的可卡因自身给药行为后,在大鼠伏隔核core/shell部微注射雷帕霉素均不能够改变已获得的自身给药行为。说明抑制伏隔核mTOR信号通路不影响可卡因的强化效应,雷帕霉素对大鼠戒断后复燃行为的抑制效应并不是由于其降低了可卡因的强化效应。结论:本研究通过一系列实验证实了在伏隔核shell和core部分别给予雷帕霉素能有效抑制大鼠自身给药戒断后由药物点燃和药物相关线索诱导的复燃行为,这一效应是通过抑制伏隔核的mTOR信号通路实现的。mTOR信号通路脑区特异性的参与了自身给药戒断后的复燃行为。本研究结果为成瘾的神经生物学机制研究和临床开发防复吸药物提供了新的依据。     

IMPORTANCE OF CENTRAL SEROTONIN NEURONS IN THE HYPOTENSIVE ACTION OF METHYLDOPA IN THE RAT

1. Normotensive (WKY) and stroke prone spontaneously hypertensive (SHR-SP) rats were given methyldopa (200 mg/kg i.p.) daily for five days and their brains were then sectioned and processed with the Faglu method for catecholamine fluorescence. 2. This treatment with methyldopa induced a green fluorescence not seen in control animals, in cells coinciding with the B1–B9 groups of serotonin neurons in the brainstem. 3. Pretreatment with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, i.c.v.), which is relatively specific for serotonin neurons, prevented the appearance of this green fluorescence in the serotonin cell groups of rats given methyldopa. 4. Pretreatment with 5,7-DHT, i.c.v. approximately halved the magnitude of the hypotensive response to a single dose of methyldopa (80 mg/kg i.p.). 5. We suggest that central serotonin nerves contribute to the hypotensive action of methyldopa. 6. It is our hypothesis that methyldopa is taken up by these serotonin cells and that the green fluorescence reflects the production of α-methyldopamine, as a result of decarboxylation by the ubiquitous enzyme, L-aromatic amino acid decarboxylase.     

应用不麻醉鸽进行洋地黄的生物检定

自Braun与Lusky两氏在1948年报导了用乙醚麻醉的鸽进行洋地黄的生物检定后,因具有操作简便、动物易于获得而又经济,及实验精密度较猫法为高等优点,已先后被各国药典收载成为法定的检验方法。中国药典1953年版第一增补本亦采用了鸽法。其他含强心甙的毒毛旋花子类植物药亦以鸽法进行效价测定。但此法须用乙醚作麻醉剂,而武汉地区夏季室温常在37°左右,使实验进行很困难。我们注意到鸽子性情温和,是     

SPECTROSCOPIC STUDY OF THE CONFORMATIONS OF PROLINE-CONTAINING OLIGOPEPTIDES IN THE CRYSTALLINE STATE AND IN SOLUTION

A conformational study has been carried out on a series of linear proline-containing oligopeptides (ZGP, ZGPL, ZGPLG and ZGPLGP) in both the crystalline state and in DMSO-d₆, solution, using Raman and n.m.r. spectroscopy. The amide I and HI bands in the Raman spectra of the crystalline forms indicate the presence of a type I β-bend conformation in ZGPLG and ZGPLGP, but not in ZGP and ZGPL. This result is in agreement with X-ray data on these mole cules. The Raman spectra of these peptides in solution indicate that more than one conformation is present, i.e. that the β-bend structure of the solid form of ZGPLG and ZGPLGP is destabilized by DMSO-d₆. ¹³C and ¹H n.m.r. data also demonstrate the presence of more than one conformation in ZGP, ZGPL, ZGPLG and ZGPLGP in DMSO-d₆ solution. These isomers differ in their con formation (cis and trans) about their Gly-Pro peptide bonds and possibly about the Cα-C' bond of the C-terminal proline in ZGPLGP. For ZGP, ZGPL, ZGPLG and ZGPLGP, the ensemble of conformations in DMSO-d₆ includes C₅ and C₇ hydrogen-bonded rings; in addition, ZGPLGP may contain a small percentage of a β-bend conformation (at Pro₂-Leuj₃) with trans peptides in both Gly-Pro moieties.     

THE INFLUENCE OF ALTERATIONS IN THE CARDIAC LOADING CONDITIONS ON INDICES OF MYOCARDIAL CONTRACTILITY IN THE ANAESTHETIZED DOG

1. An online analogue computer was used to measure myocardial contractility as the ratio dP/dt/IIT where dP/dt is maximum rate of change of left ventricular pressure and IIT is integrated isometric tension. 2. In the open thorax anaesthetized dog, max (dP/dt) and dP/dt/IIT were compared during alterations in preload, by partial vena caval occlusion, and changes in after-load obtained by acetylcholine injections and by partial occlusion of the descending thoracic aorta. 3. A fall in preload lowered max (dP/dt) but did not alter dP/dt/IIT A rise and fall in afterload produced respectively an increase and decrease in max (dP/dt) but dp/dt/IIT was unaltered. 4. From expanded time base recordings, the time from the start of aortic flow (EM flowmeter) to max (dP/dt) was measured to indicate the relationship between valve opening and rnax (dP/dt). At low preload or elevated afterload the aortic valve opened well after max (dP/dt) had been reached. When the afterload fell, max (dP/dt) occurred after the opening of the aortic valve. 5. Positive inotropic stimulation following intravenous isoprenaline caused a marked elevation in dP/dt/IIT. However, the rise in max (dP/dt) was attenuated in comparison to dP/dt/IIT by a marked fall in afterload and thus early opening of the aortic valve. 6. It is concluded that max (dP/dt) is very sensitive to alterations in preload or afterload but the index——-dP/dt/IIT is normalized so that changes in end diastolic fibre length do not alter this index. When the afterload falls max (dP/dt) is no longer determined in the isovolumic phase of contraction so that magnitude of rnax (dP/dt) is reduced. However, it is an empirical finding that IIT also falls so that the ratio is unaltered. dP/dt/IIT is a useful index of myocardial contractility that is insensitive to changes in preload or afterload.     

杏丁注射液细菌内毒素检测

目的:建立杏丁注射液细菌内毒素的检查方法。方法:按中国药典2000版二部附录ⅪE、ⅪⅩ F进行实验和结果判断。结果:用标示灵敏度为0.5EU·ml~(-1)的鲎试剂,杏丁注射液在≤最大有效稀释倍数(6—MVD)时,对细菌内毒素检查无干扰作用。13批杏丁注射液中细菌内毒素量均小于3EU·ml~(-1)。结论:可以用细菌内毒素检查法(凝胶法)代替家兔热原检查法控制其热原。     

INFLUENCE OF EXTRA-INTESTINAL INFLAMMATION ON THE IN VITRO ABSORPTION OF 14C-GLUCOSE AND THE EFFECTS OF ANTIINFLAMMATORY DRUGS IN THE JEJUNUM OF RATS

Inflammation was induced in the hind legs of rats by formalin injection and the in vitro jejunal absorption of ¹⁴C-glucose was studied. Treatment of rats with formalin caused a reduction in the in vitro absorption of glucose from the jejunum. Oral administration of oxyphenbutazone or a herbal anti-inflammatory drug (Withania somnifera) prior to formalin injection, resulted in no alteration in the jejunal absorption of glucose.     

ROLE OF UTERINE FACTORS IN THE DEVELOPMENT OF HYPERTENSION IN SHR

1. To examine whether the uterine environment plays a role in the development of hypertension in the spontaneously hypertensive rats (SHR), we have compared fetal weight, placental weight, and amniotic fluid composition of SHR and Wistar-Kyoto (WKY) rats after 20 days of gestation. 2. Pregnant SHR and WKY were anaesthetized at 20 days of gestation and the uterus and embryonic sacs removed. Fetal and placental weights were recorded and amniotic fluid collected for measurement of volume, osmolality and electrolyte composition. 3. No significant difference was found in litter size and placental weight between SHR and WKY. Total embryonic sac weight and fetal weight of SHR were significantly lower than WKY. Amniotic fluid volume, sodium concentration and osmolality of SHR were significantly higher than WKY, while amniotic fluid potassium concentration of SHR was significantly lower than WKY. 4. Thus, the SHR foetus was significantly underweight compared to the WKY and was bathed in amniotic fluid with a significantly higher osmolality and sodium concentration. As the mature foetus is known to drink amniotic fluid, it is hypothesized that the elevated Na/K ratio in SHR amniotic fluid may instigate or accelerate the hypertensive process.     

西沙比利治疗老年人功能性消化不良的疗效

607例门诊老年功能性消化不良患者随机分为治疗组和对照组.治疗组(317例)中po西沙比利5mp tid×4wk;对照组(290例)po多福立酮10mgtid×4wk.结果:西沙比利对餐后饱胀、上腹胀满、恶心及呕吐等症状的缓解作用明显优于多潘立酮(P<0.01).治疗组总有效率为86.1%,对照组为77.6%,差异有显著性.西沙比利的主要不良反应为腹泻、肠鸣和腹痛,但患者可以耐受.结果表明西沙比利对老年人功能性消化不良有良好的疗效.     

芍药甙在芍药属植物中的存在

本文报道了赤芍的有效成分芍药甙在芍药属植物中的存在情况。从植物亲缘角度来看,高含量芍药甙的种类主要分布在本属的芍药组(sect.Paeonia)植物中,含量以目前商品赤芍的主要来源:芍药(Paeonia lactiflora)和川赤芍(P.veitchii)为高。从生长动态来看,在北京地区栽培的芍药根中芍药甙的含量以显蕾期为高。从药材角度来看,来源于芍药属的三种中药:赤芍、白芍及牡丹皮,含量以赤芍为高。对本属药用植物的资源利用提出了几点意见。     

西咪替丁对大鼠体内呋喃氟脲嘧啶药代动力学的影响

本文用交叉实验设计法研究了西咪替丁(Cim)对9只大鼠口服呋喃氟脲嘧啶(FT—207)药代动力学的影响。反相HPLC法测定血清FT-207浓度,其药时曲线符合一室开放模型。单次口服Cim80mg/kg或连用Cim80 mg/kg·d~(-1)×5d,均增加血清FT—207浓度和AUC。连用时,FT-207的C_(max)和AUC分别增加21.0%(P<0.05)和34.1%(P<0.025),Te_(1/2)缩短(P<0.005);单次服Cim时,FT-207的药代学改变与连用时相似,但差异无显著性。文中讨论了二药相互作用的机制及临床意义。     

吗啡依赖动物戒断后的焦虑情绪变化

本文采用高架十字迷宫模型和Vogel's饮水冲突模型观察吗啡依赖动物自然戒断后18、24、48、72、96、120h的焦虑情绪 ,结果表明吗啡依赖动物自然戒断后48h时的焦虑症状在两种模型上都最为明显 ,丁螺环酮可明显缓解吗啡所致的焦虑情绪。提示高架十字迷宫模型和Vogel's饮水冲突模型可较为客观和准确地反映吗啡所致焦虑情绪。