8-甲氧基补骨脂素的结构简化类似物的合成

鉴于花椒毒素有钙离子拮抗作用,根据结构特征,我们对其结构进行了简化,合成了5个化合物。有待药理筛选之后,对其构效关系进行研究。     

127名HBsAg携带者e系统的调查报告

病毒性肝炎,尤其是乙型肝炎是目前危害性最大的传染病之一。众多的乙型肝炎表面抗原携带者,又为防治工作带来诸多困难。为作好乙肝的防治工作,探讨HBsAg携带者在儿童中可能造成的传染性,我们对127名HBsAg阳性儿童进行了HBsAg滴度,HBsAg和抗-HBe,PHSA受体,肝功能等进行了检测。 1 方法与结果:①HBeAg和抗-HBe的检测:1990年我们对1989年儿童体检HBsAg阳性127名儿童进行了复检。复检后仍有125名HBsAg携带者。我们对这些儿童进行了     

美人蕉利胆有效部分的初步分离及其利胆作用的实验观察

美人蕉用于急性黄疸型肝炎的治疗,国内已有不少报告。1972年,我们报告了美人蕉对急性黄疸肝炎的临床疗效。在临床应用比较稳定的情况下,我们通过动物实验初步证明美人蕉有明显的利胆作用,松弛肠道平滑肌作用以及促进肝脏 BSP 的廓清功能。为了进一步探讨美人蕉的作用机理,我们对美人蕉的利胆有效部分进行了初步分离,并对其利胆作用进行了实验研究。报道如下。     

佳木斯铁路地区中学生肺结核病调查

多年来,由于大力开展了卡介苗的接种工作和新的强有力的抗痨药物问世,对结核病进行了有效的控制。近年来在世界范围内有上升的趋势。我们在临床工作中也发现青少年患病也占有相多的比例,为了正确评估在中学生中开展结防工作情况,以便采取更有效的措施,保证中学生的身体键康,1993年春季我们对管区内两所初中和一所高中的所有在校生进行了调     

心律宁片(苦参总碱)抗心律失常临床研究

苦参(Sophora flavescens Ait)是一种传统中药,历代本草多有记述。有清热、燥湿、杀虫、利水之功。苦参中含有多种有效成分,我们对其中的生物碱进行了实验性心律失常的研究。证明总生物碱对药物诱发的动物心律失常有较好的治疗和预防作用。为进一步研究苦参总碱抗心律失常作用,我们用苦参总碱制成的片剂(心律宁片)对各种心脏病并发心律失常进行了234例临床疗效观察。     

门诊内科病人的心理特点及护理

为了解门诊内科病人的就诊心理状态,有针对性地对存在负性心理的病人进行心理护理,2003年8～12月,我们对门诊内科500例病人进行了心理问卷调查,发现有450例存在不同程度的负性心理,部分病人存在复合负性心理,主要表现有焦虑、猜疑、怀疑、抑郁、恐惧、愤怒、依赖等.我们认为,加强门诊病人的心理护理,对提高护理质量、减少医疗纠纷、更好地维持门诊医疗秩序具有积极作用.     

血液透析患者水 盐 钾控制的治疗体会

对血液透析患者进行水、盐、钾的控制对防治血液透析患者发生高血压、心力衰竭及心脏骤停有重要意义，我们对此进行了具体研究，现报告如下。     

一些青蒿素衍生物的抗日本血吸虫作用

青蒿素有明显的抗疟作用,对动物血吸虫病亦有一定疗效。为寻找疗效更高的青蒿素衍生物,中国科学院上海药物研究所合成室对青蒿素进行了一系列的结构改造。我们选择了该所合成的部分青蒿素衍生物进行了抗血吸虫筛选试验,以探讨其构效关系。 实验方法     

浅谈病员满意度在预防医疗纠纷中的调查分析

目的通过对住院病员的满意度问卷调查,了解医院各科室、各部门对患者的整体服务情况,从而针对我院的薄弱环节进行整改,提高我院整体服务水平,缓解医患矛盾、预防医疗纠纷。方法自制住院病员满意度问卷调查表,对我院2010年和2011年住院的病员进行随机抽查的问卷调查,比较、分析我们全院对病员的服务情况和患者及家属对我们工作的评价。结果住院病员满意度均有不同程度的提高,我院的整体服务水平有了明显的提高。结论通过住院病员满意度问卷调查,有效缓解了医患矛盾,预防了医疗纠纷的发生。     

采血车ALT检测不合格原因分析

按照GB-18469全血及成分血质量要求,血站要对血液进行ALT的检测,由于影响ALT检测因素较多,为了减少因ALT不合格而造成血液报废,我们在采血车对献血者进行ALT的检测,合格后采血,然后按要求再对血液进行初、复检,但是仍有一定数量的血液因ALT不合格而报废,为此我们进行了调查,报道如下。     

Effects of toluene on protein synthesis and the interaction with ethanol in hepatocytes isolated from fed and fasted rats

The effects of three different concentrations (about 10, 100 and 1000 microM) of toluene on protein synthesis were studied in hepatocytes isolated from fed and fasted rats after 60 and 120 min. of incubation. The interaction between ethanol (60 mM) and the low and high toluene concentrations were also tested. To measure protein synthesis, 14C-valine was used as the precursor amino acid. Total valine concentration was 2 mM to ensure near-constant specific radioactivity of precursor. Toluene concentrations were measured by head-space gas chromatography. Protein synthesis was unchanged in the presence of low toluene concentrations. Intermediate toluene concentration decreased protein synthesis by about 20% and high toluene concentration decreased protein synthesis by about 60%. Protein synthesis was similar in cells from fed and fasted rats. Ethanol alone inhibited protein synthesis by 20-30%, more in fasted than in fed rats. Toluene and ethanol in combination inhibited protein synthesis additively. The high toluene concentration with or without ethanol appeared to inhibit synthesis/secretion of export proteins in hepatocytes from fasted rats. In conclusion, our study indicates that toluene in relatively high concentrations inhibits general protein synthesis in isolated rat hepatocytes. Toluene and ethanol seems to inhibit protein synthesis additively.     

Fate of aclacinomycin-A and its metabolites effect on cell growth and macromolecular synthesis

The relationship between the structure and activity of aclacinomycin-A (ACM) metabolites was investigated in vitro in Friend leukaemia cells (FLC). The cytotoxic effect was related to the ease with which ACM and its metabolites accumulate in the nucleus. Cellular uptake and nuclear incorporation are influenced by the hexopyranoses linked to aklavinone (AKV) and by the two methyls linked to the l-rhodosamine amino groups. The effect of ACM and its metabolites on macromolecular synthesis depended on the drug concentrations and the exposure time. ACM was the most active in the inhibition of nucleic acid synthesis whereas it had no direct effect on protein synthesis even at high drug concentrations. When cells were treated for a short time with low drug concentrations (1 μM), RNA synthesis was inhibited to a greater extent than DNA synthesis. But when incubated for longer periods, inhibition of DNA synthesis increased further. RNA and DNA syntheses were both inhibited to about the same extent only when cells were exposed to the higher drug concentrations (10 μM). We conclude therefore that at low drug concentrations the effect on DNA synthesis is probably a consequence of RNA synthesis inhibition. The early DNA synthesis inhibition which occurs at higher drug concentrations may result from the direct action on the cellular genome.     

Inhibition of heparin synthesis by methotrexate in rats in vivo

The content and synthesis of heparin and mast cell-dependent skin oedema (as an indirect evaluation of histamine and serotonin content) were investigated in the rat skin after chronic treatment with compound 48/80, a mast cell degranulating substance. The effect of methotrexate, a folic acid analogue that interrupts the synthesis of DNA and RNA, on heparin synthesis and amine storage also was evaluated in rat skin. The heparin content at 6 and 240 hr after treatment with compound 48/80 was reduced markedly (86 and 64%, respectively). At 6 hr, heparin synthesis increased 3.1-fold compared with control animals; maximal synthesis occurred at 24 hr post-treatment (12.8-fold increase), decaying at 240 hr (2.4-fold increase). The dermatan sulfate content and synthesis were not affected by treatment with compound 48/80. Autoradiographic analysis revealed that methotrexate (2.5mg/kg for 3 consecutive days) abolished heparin synthesis at 6, 24, and 72 hr after compound 48/80 treatment, without affecting dermatan sulfate synthesis. The oedema induced by intradermal injection of compound 48/80 (1 microg/site) into the rat skin was decreased significantly at 6 hr after chronic treatment with this compound, but was restored completely 72 hr post-treatment. This pattern of oedematogenic response was also observed in the methotrexate-treated rats. In conclusion, our results show that methotrexate suppresses heparin synthesis without affecting the synthesis of either dermatan sulfate or the co-stored amines histamine/serotonin (as evaluated by measuring the mast cell-dependent oedema), suggesting that the enzyme system involved in heparin synthesis is inducible.     

Selective inhibition of herpesvirus DAN synthesis by foscarnet

The inhibition of cellular and herpesvirus DNA synthesis by phosphonoformate (INN; foscarnet sodium) has been determined after isopycnic separation of cellular and viral DNA in CsCl gradients. The DNA synthesis was determined as the incorporation of ortho[³²P]phosphate and [³H]thymidine into DNA. A 50% inhibition of herpes simplex virus DNA synthesis was observed at 50 μM phosphonoformate. At this concentration cellular DNA synthesis was not inhibited. At 500 μM phosphonoformate more than 95% of the viral DNA synthesis was inhibited, while the cellular DNA synthesis in infected and uninfected cells were inhibited to about 10%. The same results were obtained in both Vero and GMK cells and using either ortho[³²P]phosphate or [³H]thymidine to label the newly synthesized DNA. The 50% inhibitory concentration of phosphonoformate was similar for inhibition of herpes DNA synthesis and plaque reduction.     

Cellular targets of adriamycin-induced damage in Escherichia coli

The cellular targets of adriamycin (ADR) activity were studied in Escherichia coli by following colony forming ability and various cellular functions. The parameter exhibiting the best correlation with mortality was inhibition of RNA synthesis. Total DNA synthesis was inhibited to a lesser extent, but may reflect a concurrent inhibition of replication and stimulation of DNA repair activity. Protein synthesis, membrane function and rate of oxygen consumption were affected later. No extensive DNA fragmentation was observed. The inhibition of RNA synthesis was independent of the stringent response and of inhibition of DNA synthesis induced by nalidixic acid. ADR activated the SOS repair system, and the lesions induced by the drug could be repaired by recA dependent functions. These results indicate that the primary activity of ADR was directed against the DNA and interfered with the DNA template function.     

Non-selective decrease of collagen synthesis by cultured fetal lung fibroblasts after non-lethal doses of ethanol

Addition of ethanol to cultured fetal lung fibroblasts resulted in decreases of both collagen and noncollagen protein syntheses. The inhibitory effect of ethanol on protein synthesis was dependent on the concentration of ethanol and the number of treatments with ethanol. Significant inhibition of collagen and noncollagen protein synthesis was observed 3 hr after a single treatment in 0.25% (v/v) ethanol. The maximum inhibitory effect of ethanol on protein synthesis was observed at 6 hr after drug addition. Inhibition of protein synthesis was observed when either proline or glycine was used as the precursor amino acid. An inhibition of alcohol dehydrogenase did not block the ethanol-mediated inhibition of protein synthesis. Ethanol, added to cell cultures throughout the log phase, inhibited cell growth during the late log and stationary phases. Ethanol inhibition of collagen and noncollagen protein synthesis was reversed when the cell cultures were washed and suspended in fresh media for 24 hr. These inhibitory effects of ethanol on macromolecular syntheses were not engendered by killing of cells. The viability of the cells, as indicated by trypan blue exclusion, was not affected significantly at the concentrations of ethanol used. The inhibitory effect of ethanol on protein synthesis also did not originate from drug-mediated inhibition of precursor amino acid uptake. Polysomes isolated from ethanol-treated fibroblasts incorporated proline into protein at a rate which was reduced commensurate with cellular protein synthesis. The resultant inhibition by ethanol of protein synthesis was not attributable to a direct effect of drug on polysomes. Treatment of fetal lung fibroblasts with ethanol also caused a marked inhibition of radioactive thymidine and uridine incorporation, indicating a reduction of both total cellular DNA and RNA synthesis. Accordingly, the decrease of protein synthesis resulted from inhibition of RNA synthesis. Furthermore, messenger RNA synthesis may have decreased since polysomes isolated from ethanol-treated fibroblasts synthesized less protein in the wheat germ cell-free system. Unlike other biochemical variables that were inhibited by ethanol treatment, the level of prolyl hydroxylase activity was elevated significantly. The elevated level of prolyl hydroxylase activity, however, was related neither to the rate of collagen polypeptide synthesis nor to the degree of proline hydroxylation of cellular collagen. The data suggest that the growth-retarding effects of nonlethal doses of ethanol on fetal development may result from inhibition of macromolecular synthesis in fetal fibroblasts.     

Influence of repeated treatment with buspirone on central 5-hydroxytryptamine and dopamine synthesis.

The anxiolytic agent buspirone was administered subcutaneously twice a day for 10 days to Sprague-Dawley rats, at a dose of 3 mg kg-1. Controls were given saline. On the eleventh day, the rats were given an injection of NSD-1015, an aromatic L-amino acid decarboxylase inhibitor, 30 min before decapitation. To another group of rats, only one injection of buspirone was given, followed 30 min later by NSD-1015. After a further 30 min the animals were decapitated. The brains were rapidly removed and the raphe nuclei, striatum, hippocampus and cerebellum were dissected out on to dry ice. With the use of HPLC, the four regions of the brain were assayed for 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine, reflecting the synthesis of 5-HT and dopamine, respectively. In those rats which had received an acute dose of buspirone, the synthesis of 5-HT was substantially reduced in all four regions of the brain. However, in those rats which had received buspirone for 10 days, no such alterations in the synthesis of 5-HT were observed. The synthesis of dopamine was unchanged in any of the regions of the brain, after the acute dose of buspirone. After 10 days of treatment with buspirone, however, the synthesis of dopamine in the striatum was significantly reduced. These findings suggest that repeated treatment with buspirone reduces the synthesis of dopamine in the striatum but that the synthesis of 5-HT is unaffected.     

丙戊茶碱的合成

目的　选择丙戊茶碱的合成路线,考察其重要中间体 6 -溴 - 2 -己酮的合成工艺。方法　以 1,3-二溴丙烷、乙酰乙酸乙酯缩合得 2 -甲基 - 3-吡喃酸乙酯,再与 6 3%氢溴酸反应得 6 -溴 - 2 -己酮,总收率:6 3 1%。以 3-甲基黄嘌呤为原料,经与溴丙烷、6 -溴 - 2 -己酮两步缩合,得到丙戊茶碱,总收率:73 96 %。结果　产品质量合格,收率达到文献水平。结论　6 -溴 - 2 -己酮和丙戊茶碱的合成工艺适用于工业生产。     

Relationship between the oxidation potential of benzene metabolites and their inhibitory effect on DNA synthesis in L5178YS cells

The effects of benzene and its metabolites on the rate of DNA synthesis were measured in the mouse lymphoma cell line, L5178YS. The direct toxicity of benzene could be distinguished from that of its metabolites since bioactivation of benzene in L5178YS cells was not observed. Cells were exposed to benzene, phenol, catechol, hydroquinone, p-benzoquinone, or 1,2,4-benzenetriol over the range of 1.0 X 10(-7) to 1.0 X 10(-2) M for 30 min, and the rate of DNA synthesis was measured at various times after chemical washout. Cell viability and protein synthesis were determined by trypan blue dye exclusion and [3H]leucine incorporation, respectively. Effects were designated as "DNA specific" when DNA synthesis was inhibited in the absence of discernible effects on cell membrane integrity and protein synthesis. Concentrations of benzene as high as 1 mM had no effect on DNA synthesis. Comparison of the effects at the maximum nontoxic dose for each compound showed that catechol and hydroquinone were the most effective, inhibiting DNA synthesis by 65%. Phenol, benzoquinone, and benzenetriol inhibited DNA synthesis by approximately 40%. Maximum inhibition was observed 60 min after metabolite washout in each case. Benzoquinone was the most potent inhibitor of DNA synthesis, followed by hydroquinone, benzenetriol, catechol, and phenol with ED50 values of 5 X 10(-6), 1 X 10(-5), 1.8 X 10(-4), 2.5 X 10(-4), and 8.0 X 10(-4), respectively. Cyclic voltammetric experiments were performed on the hydroxylated metabolites of benzene to assess the possible involvement of a redox-type mechanism in their inhibition of DNA synthesis. The ease of oxidation of these metabolites correlated with their ED50 values for inhibition of DNA synthesis (r = 0.997). This suggests that oxidation of phenol or one of its metabolites may be necessary for production of the species involved in inhibition of DNA synthesis.     

Development and applications of new reactions for construction of basic structures of natural products]

This review deals with the development of efficient methods to construct the basic structure of natural products and the versatile methods to control the stereochemistry, and these methods were applied to the synthesis of natural compounds. The photochemical spirodienone formation reaction was applied to the synthesis of proaporphine alkaloids. The alternative spirodienone formation reactions by the metal-catalyzed degradation reaction of phenolic alpha-diazoketones were applied to many natural spirocyclic compounds, such as chamigrane type sesquiterpenes, spirovetivane type phytoalexins, marine natural products, and so on. Lewis acid mediated spirocyclization reaction of cyclohexene bis-acetal derivative was developed, and this reaction was applied to the synthesis of aphidicolane and stemodane diterpenes. The regioselective cleavage reaction of the cyclopropane ring of tricyclooctanone derivatives was used for the syntheses of diquinane and triquinane compounds. A chiral pool synthesis of several aromadendrane sesquiterpenes was achieved via common tricyclic enone intermediates. The synthesis of macrocarpals, coupling products of aromadendrane skeleton and isopentylphloroglucinol dialdehyde, was also accomplished for the first time using an arene Cr(CO)3 complex as a chiral benzyl cation equivalent. The Fe(diene)(CO)3 complexes were used for the highly stereoselective asymmetric synthesis of several natural products, such as insect pheromones and alkaloid, as a versatile mobile chiral auxiliary.