6,6—二甲基—4—苄基—5—羧亚甲基—2—环己烯—1—酮的合成

美丽红豆杉素A(Taxamairin A,1)和美丽红豆杉素B(Taxamairin,B,2),是1985年从美丽红豆杉植物中分离得到的天然产物。它们是新型的含有革酮结构的三环二萜类化合物,体外药理试验发现具     

1—o—乙酰基—2,3,5—三—o—苯甲酰基—4—［9‘—（6’—氢— …

从１－ｏ－乙酰基－２,３,５－三－ｏ－苯甲酰基－４－溴－β－Ｄ－呋喃核糖出发,在溴化汞催化作用下,合成了３个４－取代的核苷化合物,其中２个化合物未见文献报道。     

1—苄基哌啶—4—羧酸的新合成法

设计了一条新颖的１－苄基哌啶－４－羧酸的合成方法,该法以二乙醇胺为起始原料,经过氮烃化、氯代、环合和水解四步反应合成了目的物。并对其中的环缩合反应的后处理方法进行了改进。各步反应的操作简单,收率较高,总率比文献方法提出了１０％以上,较适用于工业化生产。     

立体控制合成外向-1-乙炔基-3-二苯叔丁硅氧基双环[3.1.0]已烷

目的　寻找更有效的 ,可用于工业化生产的 19-失碳 - 1α,2 5 -二羟基维生素 D3 ( 2 )的 A环合成子( - ) -外向 - 1-乙炔基 - 3-二苯叔丁硅氧基双环 [3.1.0 ]已烷 ( 3)的合成方法。方法　以 3-环戊烯 - 1-醇 ( 4)为原料 ,经 9步反应 ,以总收率 2 0 %合成了 (± ) ( 3)。结果　该方法实验操作简单、收率高 ,其光谱数据与我们早期报道的 ( - ) ( 3)一致 ,为进一步合成 ( - ) ( 3)打下了基础。结论　该方法是一个较好的合成 (± ) ( 3)的方法     

Effects of 1alpha, 25-dihydroxyvitamin D3 on the acute immune rejection and corneal neovascularization in high-risk penetrating keratoplasty in rats]

OBJECTIVE: To investigate the effects of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), a hormone that has immunosuppressive properties, on acute rejection and corneal neovascularization in rat keratoplasty model, so as to assess the therapeutic effects and explore the mechanism of 1,25(OH)(2)D(3) as an immunosuppressant in corneal transplantation. METHODS: High risk corneal transplantation was performed orthotopically in SD rat models of high risk penetrating keratoplasty established by placing three 10-0 nylon sutures in the central corneas for two weeks, with the Wistar rats as the donors. The SD rat models were randomly assigned into 5 groups and treated with 1,25(OH)(2)D(3) at varied concentrations and cyclosporine A (CsA). The expressions of interleukin (IL)-1alpha, tumor necrosis factor (TNF)-alpha, and vascular endothelial growth factor (VEGF) mRNA were detected by in situ hybridization (ISH). RESULTS: 1,25(OH)(2)D(3) significantly suppressed acute graft rejection and inhibited corneal neovascularization as compared with saline. 1,25(OH)(2)D(3) showed better immunomodulatory effects when administered along with CsA in rat corneal allotransplants. ISH study demonstrated that 1,25(OH)(2)D(3) strongly suppressed mRNA and protein expressions of the cytokines IL-1alpha and TNF-but not those of VEGF. CONCLUSION: Topical administration of 1,25(OH)(2)D(3) can be effective in suppressing acute corneal graft rejection by inhibiting the expression of proinflammatory cytokines (IL-1alpha and TNF-alpha).     

1,25双羟维生素D3及转化生长因子β1对人胚成骨细胞增殖和分化的影响

目的　研究 1,2 5双羟维生素D3 [1,2 5 (OH) 2 VD3 ]及人转化生长因子 β1(hTGF β1)对人胚成骨细胞增殖和分化的影响。方法　体外培养人胚成骨细胞 ,经 1,2 5 (OH) 2 VD3 及hTGF β1作用后 ,通过四唑盐 (MTT)比色法观察细胞增殖 ;检测细胞培养液中碱性磷酸酶 (ALP)活性及骨钙素 (OC)含量 ;逆转录 聚合酶链反应 (RT PCR)方法观察细胞中TGF β信号传导关键蛋白 SMAD蛋白mRNA水平的变化。结果　MTT比色发现 1,2 5 (OH) 2 VD3 组的吸光度值 (OD值 )较对照组下降 30 6 % (0 0 86±0 0 2 2比 0 12 4± 0 0 31,P <0 0 5 )。细胞培养液中ALP活性在 1,2 5 (OH) 2 VD3 组、hTGF β1组以及二者联合应用组均有显著增高 ,为对照组的 1 3～ 2 0倍 (P <0 0 5 )。其中 ,当hTGF β1浓度为 1× 10 -6g/L时 ,1,2 5 (OH) 2 VD3 及hTGF β1对人胚成骨细胞ALP的分泌存在协同刺激作用。 1,2 5 (OH) 2 VD3 与 1×10 -6g/L和 1× 10 -5g/L浓度的hTGF β1合用使得细胞培养液中OC水平增加 (P <0 0 5 ) ,但未发现二者的协同作用。当 1,2 5 (OH) 2 VD3 与 1× 10 -6g/L的hTGF β1合用时SMAD3mRNA水平达高峰 ,约为对照组的 6倍。结论　 1,2 5 (OH) 2 VD3 抑制人胚成骨细胞增殖 ,促进其分化。 1,2 5 (OH) 2 VD3 及hTGF β1     

CD147通过Beclin-1抑制前列腺癌PC-3细胞自噬

目的: 通过建立饥饿诱导的自噬模型,探讨CD147对前列腺癌PC-3细胞自噬作用的影响,并阐明其作用机制。 方法: 通过饥饿诱导方式建立自噬细胞模型。实验分为阴性对照组和RNAi干扰CD147组(PC-3/shCD147组)。GFP-LC3质粒转染观察细胞自噬斑点形成情况,免疫印迹技术检测自噬蛋白LC3和Beclin-1表达,台盼蓝排斥实验检测细胞死亡率。 结果: 与阴性对照组比较,PC-3/shCD147组GFP-LC3斑点细胞数增加(P<0.01),自噬相关蛋白LC3-Ⅱ(P<0.01)和Beclin-1(P<0.05)表达水平升高;与阴性对照组(22.3%±3.5%)比较,PC-3/shCD147组细胞死亡率(38.4%±3.1%)明显升高(P<0.05)。 结论: 在前列腺癌PC-3细胞中,CD147通过Beclin-1抑制饥饿诱导的自噬过程,减少细胞自噬的发生。     

Modulation of endothelin-1 on pulmonary surfactant synthesis of cultured alveolar type II cells]

The effects of endothelin-1(ET-1) on pulmonary surfactant(PS) synthesis of cultured AT II cells were observed. The results showed that: 1. ET-1(10(-11)-10(-8) mol.L-1) enhanced PS synthesis of cultured AT II cells in a dose-dependent manner. 2. The minimum effective concentration of ET-1 enhanced PS synthesis of cultured AT II cells was higher than that of lung explants. 3. ETA antagonist BQ123 decreased the effect of ET-1 on PS synthesis, but ETB antagonist BQ788 did not change the effect. 4. ET-1 (10(-12) and 10(-10) mol.L-1) had no effect on the proliferation of AT II cells. These results confirmed that ET-1 can enhance directly and indirectly on the PS synthesis of AT II cells mediated via ETA receptor. The effect of ET-1 on PS synthesis was not induced by changing the number of AT II cells.     

黑色素瘤抗原-1、3基因在肝内胆管细胞癌中的表达及临床意义

目的研究黑色素瘤抗原(MAGE)-1和MAGE-3基因在肝内胆管细胞癌(IHCC)组织中的表达,探讨MAGE-1、MAGE-3基因与IHCC患者临床指标的关系。方法RT-PCR方法检测20例IHCC患者癌组织及相应癌旁组织MAGE-1、MAGE-3基因表达,对全部RT-PCR扩增产物中目的基因片段进行DNA测序以证实其为MAGE-1、MAGE-3基因。分析MAGE-1、MAGE-3基因表达与患者性别、年龄、肿瘤直径、有无包膜、肿瘤形态以及乙肝病毒表面抗原等临床指标的关系。结果20例IHCC患者癌组织中MAGE-1、MAGE-3基因表达的阳性率分别为35%和45%,显著高于癌旁组织(0)(P<0·01)。IHCC患者癌组织中MAGE-1、MAGE-3基因表达的阳性率与患者性别、年龄、肿瘤直径、有无包膜以及乙型肝炎病毒感染等指标均无关(P>0·05);MAGE-3基因表达的阳性率与肿瘤形态有关(P<0·05)。结论MAGE-1、MAGE-3基因在IHCC患者肝癌组织中特异性高表达,MAGE-1、MAGE-3基因可能成为IHCC患者免疫治疗的攻击靶点。     

Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection: a randomized clinical trial.

CONTEXT: Attachment of most rhinovirus subtypes to cells depends on a cellular receptor, the intercellular adhesion molecule 1 (ICAM-1). A recombinant soluble ICAM-1 (tremacamra, formerly BIRR 4) has shown possible efficacy in early studies. OBJECTIVE: To determine the efficacy and safety of intranasal administration of tremacamra in experimental rhinovirus colds in humans. DESIGN: Four randomized, double-blind, placebo-controlled trials conducted in January to March 1996. SETTING AND SUBJECTS: Volunteers between the ages of 18 and 60 years who had an antibody titer of 1:4 or less to the challenge virus. Subjects were isolated in a hotel room during study days 0 to 8; symptoms were recorded through day 14. A total of 198 subjects were randomized, of whom 196 received drug or placebo and were included in the safety analysis. A total of 177 subjects were included in the efficacy analysis. INTERVENTIONS: Tremacamra or placebo was given beginning 7 hours before inoculation with rhinovirus type 39 (preinoculation studies) or 12 hours after (postinoculation studies). Tremacamra as an inhaled solution or as a powder (each given preinoculation and postinoculation for a total of 4 studies) and placebo were given in 6 doses at 3-hour intervals daily during days 1 through 7. Recipients of active treatment received 367 microg of tremacamra per nostril per dose for a total of 4.4 mg/d. MAIN OUTCOME MEASURES: Effect of tremacamra on infection, as determined by virus isolation and seroconversion, and on illness, as determined by symptom scores, clinical colds, and nasal mucus weights. Treatment-by-study interaction was not significant, so results were pooled for the main analysis. RESULTS: A total of 88 (92%) of the 96 subjects in the placebo groups and 69 (85%) of the 81 subjects in the active treatment groups were infected (P=.19). For placebo vs tremacamra, respectively, the total symptom score (+/- 95% confidence interval [CI]) was 17.6 (+/- 2.7) vs 9.6 (+/- 2.9), the proportion of clinical colds was 64/96 (67% +/- 9%) vs 36/81 (44% +/- 11%), and the nasal mucus weight was 32.9 (+/- 8.8) g vs 14.5 (+/- 9.4) g (P<.001 for all comparisons). Tremacamra was not associated with adverse effects or evidence of absorption through the nasal mucosa and did not interfere with development of neutralizing antibody. CONCLUSION: Tremacamra reduced the severity of experimental rhinovirus colds. Whether tremacamra will be useful clinically will require further study.     

内皮素—1对肺组织肺表面活性物质合成的调控

采用无血清成年大鼠肺组织培养，观察ＥＴ－１对ＰＳ合成的影响。结果显示：（１）ＥＴ－１促进肺组织＾３－Ｈ胆碱掺入，量效和时效关系显著。１０＾－１０ｍｏｌ．Ｌ＾－１ＥＴ－１可显著提高肺组织总磷脂及ＰＳ主要组分ＰＣ和ＰＧ的含量，而细胞膜特征性磷脂组分ＰＥ，ＰＩ，Ｐｓｅ和ＳＭ均无显著变化，（２）ＥＴＡ受体阻断剂ＢＱ１２３（１０＾－６ｍｏｌ．Ｌ＾－１）可使１０＾－１２和１０＾－１０ｍｏｌ．Ｌ＾－１ＥＴ－１组     

1-alpha-hydroxyvitamin D3 in chronic renal failure. A potent analogue of the kidney hormone, 1,25-dihydroxycholecalciferol.

In chronic renal disease, the synthesis of the kidney hormone, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), is impaired, thus contributing to the development of renal osteodystrophy. The clinical use of 1,25-(OH)2D3 is limited, due to the complexity and expense of its chemical synthesis. This study reports the use of 1-alpha-hydroxyvitamin D3 (1-alpha-OH-D3), an active analogue of 1,25-(OH)2D3, in eight patients with chronic renal failure, five of whom were undergoing long-term hemodialysis. The drug was given orally for 6 to 260 days at a dosage of 1mug to 4mug/day. Short-term (21 days) balance studies showed an increase in intestinal calcium absorption and a simultaneous fall in serum parathyroid hormone levels during administration of 1-alpha-OH-D3. In two long-term studies (160 and 260 days), roentgenographic improvement of renal osteodystrophy was seen after 45 and 185 days, respectively. The data indicate that 1-alpha-OH-D3 holds considerable promise for the prevention and treatment of renal osteodystrophy.