气功外气对人鼻咽癌细胞株的抑制作用和DNA合成影响的初步探讨

为寻找祖国医学治疗鼻咽癌的新途径,我们进行了气功外气对体外培养的人鼻咽低分化鳞癌细胞株(CNE—2)的抑制作用试验,实验共进行了三次,光镜观察受功组比对照组生长缓慢,外气对细胞生长的抑制率分别为33％(P<0.05);43％(P<0.05);55％(P<0.001)。同时进行了~3H—TdR掺入试验,观察外气对CNE—2细胞株DNA合成的影响。实验进行了四次,其抑制率分别为:34％(P<0.01);35％(P<0.01);39％(P<0.01),53％(P<0.001),模仿者为17％(P>0.05)。     

Assessment of immunosuppression by serum inhibition of alloreaction and measurement of cyclosporin A (CyA) serum levels in kidney graft recipients under CyA

The immunosuppressive effect of kidney graft recipient sera was studied on T-lymphocyte alloreactive line (4H) proliferation and compared to native cyclosporin A (CyA) and CyA metabolite concentrations determined by radioimmunoassay (RIA) using specific or nonspecific monoclonal antibodies. Three clinical groups were studied: (1) patients experiencing acute renal rejection episodes (CyA-R), (2) patients experiencing CyA-dependent nephrotoxicity episodes (CyA-TOX) and (3) patients in a clinically steady state (CyA-ST), according to their therapeutic regimen i.e., monotherapy (CyA alone) or polytherapy (CyA associated with prednisolone and/or azathioprine). Regardless of the clinical state, sera of patients in polytherapy displayed more inhibitory activity than those of monotherapy patients (24% and 40% inhibition of 4H proliferation, respectively, at sera dilution of 1:2), something which was no doubt due to the inhibitory activity of prednisolone on T-lymphocyte growth. In the two therapeutic regimens, CyA-ST patient sera exhibited the lowest inhibitory activity on the 4H line (45% and 65% inhibition of 4H proliferation in mono-and polytherapy, respectively, at sera dilution of 1:2). Sera from CyA-TOX patients were highly inhibitory (74% and 86% inhibition of 4H proliferation in mono-and polytherapy, respectively, at sera dilution of 1:2), in agreement with RIA assays showing increased native circulating CyA and CyA metabolites and daily CyA intake in this group as compared to CyA-St. Surprisingly, CyA-R patient sera were no less inhibitory than those of CyA-ST patients on 4H-line, antigen-induced proliferation. This clinical group did not differ from others for CyA intake or level of circulating immunosuppressive molecules, suggesting that rejection could be associated with a state of interindividual variation in sensitivity to CyA. In addition, a polytherapeutic regimen seemed to modify CyA bioavailability in CyA-ST group patients, with a decreased CyA metabolite level as compared to their monotherapy counterparts (native CyA plus metabolite/native CyA ratio being 2.73 and 3.73, respectively). In contrast, in the CyA-R patient group, polytherapy appeared to be associated with an increase in CyA metabolite circulating levels (ratio 4.79). In view of the low inhibitory activity of CyA metabolites, this profile might lead to rejection.     

Modulation of paired-pulse responses in the dentate gyrus: effects of prenatal protein malnutrition

Since our major hypothesis is that prenatal protein malnutrition significantly affects hippocampal neuroplasticity, this study examined the effects of prenatal protein malnutrition on the modulation of dentate granule cell excitability in freely moving rats at 15, 30 and 90 days of age across the vigilance states of quiet waking (QW), slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Using paired-pulse stimulation, the paired-pulse index (PPI), a measure of the type and degree of modulation of dentate granule cell excitability elicited by stimulation of the medial perforant path, was obtained for each vigilance state at each stage of development. Four specific measures of granule cell excitability were computed, namely, PPI using both population spike amplitude (PSA) and EPSP slope measures, absolute values of PSA(1) and EPSP(1) slope. PPI values obtained at 15, 30 and 90 days of age, however, were altered during normal ontogenetic development, but not by vigilance state. At 15 days of age, the malnourished group exhibits greater early inhibition of the PPI using the PSA measure at IPIs between 20 and 30 ms regardless of vigilance state, while at 30 days of age, the malnourished group exhibits greater facilitation at IPIs between 50 and 70 ms during QW and SWS, but not during REM sleep. In the control adult (PND90) and juvenile (PND30) animal, PSA(1) values are significantly higher during SWS than in QW or REM sleep. However, for the younger malnourished animals (PND15 and PND30), PSA(1) values were found to be significantly greater during REM sleep rather than SWS. Therefore, as the animal matures, there appears to be a shift in vigilance state dependent synaptic transmission through the hippocampal trisynaptic circuit from REM sleep to SWS in both control and malnourished animals, with the change occurring later in malnourished animals when compared to control ones. Furthermore, our findings suggests that prenatal protein malnutrition significantly alters modulation of dentate granule cell excitability (i.e., PPI values using the PSA measure) during the earlier stages of development but not in adulthood.     

Further studies on the extraneuronal uptake and metabolism of isoprenaline in the perfused rat heart

Summary To simultaneously determine the kinetics of removal, O-methylation and accumulation of ³H-isoprenaline, isolated rat hearts were perfused for 4 min with various concentrations of ³H-isoprenaline. The apparent K _m for the O-methylation of ³H-isoprenaline (3.3±0.5 M) was more than one order of magnitude lower than the corresponding value for the accumulation of unchanged amine (71.3±7.1 M). The apparent K _m for removal was very similar to that for accumulation (63.2±5.9 M). At perfusion concentrations higher than 25 M, i.e. when O-methylation was saturated, removal virtually equalled accumulation. However, at low substrate concentrations removal of ³H-isoprenaline was overwhelmingly followed by O-methylation; this led to a marked difference between rates of removal and those of accumulation.When initial rates of uptake of ³H-isoprenaline were determined after 1.5 min of perfusion of the hearts by the method of Graefe et al. (1978), the uptake of ³H-isoprenaline consisted of two components: a nonsaturable and a saturable (after subtraction of the nonsaturable component from the total uptake).The kinetic constants of the saturable component of uptake were higher than those obtained after 4 min perfusion (see above) (K _m : 110±19 M; V _max: 80±4 nmoles·g^–1·min^–1).Corticosterone competitively inhibited the saturable component of uptake of ³H-isoprenaline (K _m : 1.2 M).During wash out of accumulated ³H-isoprenaline, O-methylation took place predominantly in one of the two extraneuronal compartments. The efflux of 3-O-methyl-³H-isoprenaline (³H-OMI), the O-methylated metabolite of ³H-isoprenaline, was characterized by a half time of about 1.2 min. O-methylation accelerated the loss of radioactivity from the tissue during wash out.The extraneuronal uptake of ³H-isoprenaline was characterized as a pump and leak system by means of steady-state kinetics of accumulation of ³H-isoprenaline. Half saturation of the steady-state accumulation was observed at a concentration of 104.5 ±18.5 M ³H-isoprenaline; the leak component was characterized by a rate constant of 0.0359 min^–1.This study was supported by the Deutsche Forschungsge-meinschaftA preliminary account was presented at the 6th International Congress of Pharmacology (Graefe et al., 1975)     

异种(牛)脱细胞真皮基质-游离空肠复合体构建实验研究

目的 研究异种(牛)脱细胞真皮基质-游离空肠复合体的构建技术,以期解决游离空肠移植重建长段气管术后肠腺分泌的问题。 方法 选择10只杂种犬,制备去上皮游离空肠段,将剪成合适大小的异种(牛)脱细胞真皮基质覆盖于游离空肠基底膜表面,并用覆膜镍钛合金支架支撑固定,将构建好的复合体移至腹膜外与腹部皮肤之间,分别于术后7 d、14 d、1个月、3个月和6个月后取出,查看复合体的生长情况。 结果 10只实验犬中,有1只因肠粘连和伤口感染死亡而未能完成实验,余9只实验犬术后存活良好。术后7 d、14 d肉眼观察和病理检查,在游离空肠内表面均见有异种(牛)脱细胞真皮基质成分,表面黏膜层可见部分鳞状上皮化生;术后1个月、3个月、6个月肉眼和病理检查均未再发现异种(牛)脱细胞真皮基质成分,游离空肠内表面几乎全部化生为复层鳞状上皮。 结论 合适大小的异种(牛)脱细胞真皮基质覆盖在去上皮游离空肠内表面,可以促进游离空肠内表面的鳞状上皮化生,抑制肠腺分泌。覆膜镍钛记忆合金支架有一定的弹性,可以很好的对异种(牛)脱细胞真皮基质-去上皮游离空肠复合体起到支撑固定作用。     

姜黄素的作用研究进展

姜黄素属于多酚类化合物,是多年生草本植物姜黄的活性成分。姜黄的研究历史悠久,在医学中用于治疗各种疾病。本文就姜黄素的分子结构及性质,姜黄素在抑制炎症、抗氧化、降脂、抗肿瘤等方面的研究进展做一综述。     

VEGF反义寡核苷酸抑制大鼠胶质瘤生长的时间与剂量的效应关系

目的在大鼠脑内原位注射反义寡核苷酸观察胶质瘤的生长抑制情况的时间与剂量的效应关系。方法所有大鼠均在立体定向导引下右尾状核区接种1×106C6胶质瘤细胞。不同时间和剂量VEGF反义寡核苷酸均在立体定向导引下原穿刺靶点注射。其中实验Ⅰ组在接种细胞的同时原位注射1000μmol/L的VEGF反义寡核苷酸,而实验Ⅱ组则同时注射2000μmol/L的VEGF反义寡核苷酸。对照Ⅰ组为对照。实验Ⅲ和Ⅳ组在细胞接种后的1和2周各原位注射1次,共2次,每次实验Ⅲ组为1000μmol/L、实验Ⅳ组为2000μmol/L的VEGF反义寡苷核酸。对照Ⅱ组为对照。实验V组仅在接种后2周注射1次2000μmol/L的VEGF反义寡核苷酸,并设对照Ⅲ组为对照。实验3周时处死所有的大鼠,解剖出全脑标本,观察肿瘤的生长情况,测量肿瘤大小。结果实验Ⅰ组的抑瘤率为94.5％,实验Ⅱ组的抑瘤率为100％。实验Ⅲ组的抑瘤率为91.5％,实验Ⅳ组为100％,实验Ⅴ组抑瘤率为87.8％。实验组和对照组的肿瘤体积比较有非常显著的差异。结论 原位应用VEGF反义寡核苷酸能取得很好的抗血管生成的治疗效果,抑瘤效果有明显的浓度依赖性。原位早期使用足量反义核酸能取得更好的效果。     

7种中草药粗提液对肺成纤维细胞增殖抑制作用的比较研究

目的观察7种中草药粗提液对肺成纤维细胞增殖的作用,为中药治疗肺纤维化筛选苗头药物.方法根据肺纤维化的病理机制,确定赤芍、毛冬青、莲子心、瑞香狼毒、猫眼草、千金子、蒲公英粗提物为备筛药物,利用大鼠原代培养肺成纤维细胞,加入不同浓度的提取液,采用细胞形态学观察、MTT比色法,比较其对细胞增殖的抑制作用,并以乳酸脱氢酶（LDH）的测定来观察其细胞毒性.结果莲子心、狼毒、千金子对大鼠肺成纤维细胞有显著的抑制作用,其中效果最佳、细胞毒作用最小的为莲子心提取物.结论莲子心是一种有希望的治疗肺纤维化的苗头药物.     

何首乌提取物对人乳腺癌细胞脂肪酸合酶的抑制研究

目的 研究何首乌提取物对人乳腺癌MCF7细胞脂肪酸合酶(fatty acid synthase，FAS)的抑制作用。方法 MTT法测定人乳腺癌MCF7细胞增殖速度，采用超速离心技术部分纯化人乳腺癌MCF7细胞FAS。不同浓度何首乌提取物与FAS相互作用不同时间后，加入底物，用分光光度法观察何首鸟提取物对FAS的抑制作用。结果 何首鸟提取物对人乳腺癌MCF7细胞的增殖有一定的抑制作用。人乳腺癌MCF7细胞FAS被部分纯化，三种浓度何首乌提取物(0．1，0．5，1g／L)与FAS在催化前相互作用0、5和10min，对FAS活性的抑制率分别为24．60％、27．30％、and42．75％(0．1g／L)；43．50％、50．30％、and94．03％(O．5g／L)；98．60％、97．30％ and97．05％(1g／L)。结论 何首乌提取物对人乳腺癌MCF7细胞FAS具有抑制作用；作用强度既依赖于抑制剂浓度，又依赖于抑制剂与酶相互作用时间。     

An Update on the Status of Potent Inhibitors of Metallo-β-Lactamases

The production of metallo-β-lactamases is the most important strategy by which pathogenic bacteria become resistant to currently known β-lactam antibiotics. The emergence of these enzymes is particularly concerning for the future treatment of bacterial infections. There are no clinically available drugs capable of inhibiting any of the metallo-β-lactamases, so there is an urgent need to find such inhibitors. In this review, an up-to-date status of the inhibitors investigated for the inhibition of metallo-β-lactamases has been given so that this rich source of structural information of presently known metallo-β-lactamases could be helpful in generating a broad-spectrum potent inhibitor of metallo-β-lactamases.