弥漫性大B细胞淋巴瘤中Survivin和bcl-2蛋白表达及相互关系

目的探讨Survivin和bcl-2在弥漫性大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）免疫类型中的表达及相互关系。方法采用免疫组化MaxVision法检测凋亡抑制基因Survivin和bcl-2在DLBCL免疫类型中和反应性增生的淋巴结中的表达。结果免疫分型60例弥漫性大B细胞淋巴痛中免疫类型GCB（germinal center-B-cell like）25例,non—GCB（non germinal center-B-cell like）35例：免疫类型GCB中survivin的阳性率为72．0％,non-GCB中survivin的阳性率为42．9％,两者之间P〈0．05;GCB中bcl-2的阳性率为76．0％,non—CCB中bcl-2的阳性率为31．4％。两者之间P〈0．01;survivin阳性弥漫性大B细胞淋巴瘤中bcl-2阳性率为69．7％．Burvivin阴性弥漫性大B细胞淋巴瘤中bcl-2阳性率为25．9％。在DLBCL中,Survivin的表达与bel-2蛋白表达密切相关。结论survivin、bcl-2的表达与弥漫性大B细胞淋巴瘤的免疫学类型相关,C-CB类型中高表达,non—GCB类型中低表达。在DLBCL中Survivin与bcl-2蛋白表达密切相关,两者协同发挥抗凋亡效应。     

胃癌组织PTEN蛋白、VEGF表达和血管形成的关系

目的研究胃癌组织中PTEN蛋白、血管内皮生长因子（VEGF）表达和血管形成的关系。方法采用免疫组织化学S-P法检测20例正常胃黏膜及80例胃癌组织中PTEN、VEGF、微血管密度（MVD）的表达。结果20例正常胃黏膜组织PTEN全部阳性表达，胃癌组织PTEN阳性率为52．5％（40／80）、PTEN蛋白表达水平与组织分化程度、淋巴结转移及TNM分期密切相关（P〈0．05），VEGF在正常胃黏膜阳性率为10％（2／20），胃癌组织阳性率为53．8％（43／80），二者差异有显著性（P〈0．01），VEGF表达与淋巴结转移及TNM分期密切相关（P〈0．05），胃癌组织MVD显著高于正常胃黏膜MVD（P〈0．01），MVD与胃癌组织浸润深度、分化程度、淋巴结转移及TNM分期密切相关（P〈0．01），胃癌组织中VEGF表达与MVD呈显著正相关（P〈0．01），PTEN蛋白表达水平与VEGF表达呈显著负相关（P〈0．01），PTEN蛋白表达水平与MVD呈显著负相关（P〈0．01）。结论PTEN蛋白表达与胃癌的临床病理特征密切相关，胃癌PTEN基因失活可能通过增加VEGF的表达来促进血管形成，导致肿瘤恶性进展。     

COX-2和Survivin蛋白在胃癌组织中的表达及临床意义

目的探讨COX-2和Survivin蛋白在胃癌中的表达及临床意义。方法采用免疫组织化学sP法检测76例胃癌和13例正常胃黏膜中COX-2和survivin蛋白的表达,分析二者与胃癌临床病理特征的关系。结果COX-2和Survivin蛋白在胃癌组织中阳性表达率分别为80．26％和77．63％,均显著高于正常胃黏膜组织（P〈0．01）。COX-2蛋白在胃癌中阳性表达与性别、年龄、分化程度、浆膜侵犯等因素无关（P〉0．05）,但与淋巴转移、TNM分期密切相关（P〈0．05）。Survivin蛋白在胃癌中的阳性表达与性别、年龄无关（P〉0．05）,但与肿瘤分化程度、浆膜侵犯、淋巴结转移、TNM分期密切相关（P〈0．05）。胃癌中COX-2和Survivin蛋白阳性表达呈正相关性（P〈0．05）。结论COX-2和Survivin蛋白在胃癌组织中高表达,可能在胃癌发生发展中起重要作用;COX-2和Survivin蛋白在胃癌中表达呈正相关。联合检测COX-2和Survivin蛋白可作为反映胃癌生物学行为和判断预后的有效指标之一。     

survivin在胃癌中的表达及意义

目的：研究人胃癌组织中凋亡抑制蛋白（IAP）家族survivin的表达与临床病理的关系。方法：采用免疫组化的方法检测28例胃癌患者肿瘤组织及10例慢性胃炎患者胃黏膜中survivin的表达。结果：10例慢性胃炎患者胃黏膜中survivin的表达阳性1例,阳性率为10％;28例胃癌组织中survivin阳性20例,阳性率71．4％。survivin表达与患者年龄、肿瘤浸润深度、淋巴结转移、临床分级等无明显相关性,而与肿瘤组织分型相关（P〈0．05）。结论：胃癌患者survivin高表达导致的凋亡抑制在胃癌的发生、发展中起了重要作用。     

生存素蛋白在胃癌中的表达及意义

目的 观察生存素（survivin）蛋白在不同胃组织中的表达与肿瘤细胞凋亡及增殖的关系。方法 采用免疫组织化学SP法检测生存素蛋白,DNA末端标记法TUNEL技术检测细胞凋亡。结果 150例胃癌标本中有73例生存素蛋白阳性表达,其阳性率48．67％;生存素蛋白阳性表达组中的凋亡指数（0．60％）与其阴性组（0．94％）之间有统计学差异（P〈0．05）;增殖指数也明显高于阴性组（P〈0．05）;生存素蛋白在正常胃黏膜中没有表达,在上皮内瘤变中生存素蛋白有不同程度的表达,与正常胃黏膜之间有统计学意义（P〈0．05）,低级别与高级别上皮内瘤变之间有统计学意义（P〈0．05）,高级别上皮内瘤变与胃癌之间无统计学意义（P〉0．05）。从低级别上皮内瘤变、高级别上皮内瘤变到胃癌的过程中,凋亡指数逐渐减少,增殖指数逐渐增加。结论 生存素蛋白抑制胃癌细胞凋亡,促进胃癌细胞增殖,与肿瘤的发生有关。     

胃癌组织中Survivin基因、COX-2和VEGF表达的相关性研究

目的探讨Survivin,COX-2和VEGF在胃癌中的表达、临床意义及其相关性。方法用免疫组化法检测60例胃癌组织中Survivin,COX-2和VEGF的表达。结果胃癌组织中Survivin,COX-2和VEGF表达阳性率分别为68．3％（41／60）,55．O％（33／60）和66．7％（40／60）;Survivin,COX-2和VEGF在胃癌中表达与浸润深度、淋巴结转移和TNM分期有显著性关系（P〈0．05）,Survivin的表达还与组织分化程度有显著性关系（P〈0．05）。Survivin在胃癌组织中的表达与COX-2和VEGF的表达呈正相关。结论Survivin,COX-2和VEGF在胃癌组织中三者相关,可能在胃癌的发生发展中起相互的协同作用。     

Survivin和p53蛋白在胃癌组织中的表达及意义

目的探讨Survivin和p53蛋白在胃癌组织中的表达及意义。方法应用免疫组化sP法检测60例胃癌组织及10例正常胃黏膜组织中Survivin和p53的表达。结果60例胃癌组织中Survivin和p53阳性率分别为56．7％和65．0％,明显高于对照组（Х^2=7．89,Х^2=8．85,均P〈0．01）;不典型增生组织中,Survivin和p53阳性率分别为44．0％和32．0％（Х^2=1．92,P〈0．05）;胃癌低分化组Survivin和p53阳性率分别为85．2％和81．5％,明显高于高、中分化组39．4％和51．5％（Х^2=4．39,Х^2=4．39,均P〈0．05）;胃癌中有淋巴结转移组Survivin和p53阳性率分别为69．2％和74．4％,明显高于无淋巴结转移组33．3％和47．6％（Х^2=3．98,Х^2=3．98,均P〈0．05）;Ⅰ＋Ⅱ期Survivin和p53阳性率阳性率分别为38．1％和33．3％,明显低于Ⅲ＋Ⅳ66．7％和82．1和82.1% （Х^2=4．55,Х^2=4．55,P〈0．05）;经单因素分析显示,胃癌浸润深度和生存时间相关（Х^2=20．23,P〈0．001）。结论Survivin、p53蛋白的异常表达导致细胞增殖异常与胃癌的发生有关。     

PTEN和survivin在胃癌中的表达及相关性研究

目的研究PTEN与Survivin在胃癌组织中的表达,探讨两者相互作用机制。方法采用免疫组化SP法染色检测60例胃癌组织、10例正常胃黏膜组织中PTEN和Survivin的表达。结果胃癌组织中的nEN蛋白阳性表达率为46．7％．明显低于正常胃黏膜组（P〈0．05）,并与胃癌TNM分期、淋巴结转移显著相关（P〈0．05）,与组织分化程度和浸润深度无关（P〉0．05）;胃癌组织中的Survivin蛋白阳性表达率为71．7％,明显高于正常胃黏膜组（P〈0．05）。并与组织分化程度、胃癌TNM分期和淋巴结转移显著相关（P〈0．05）,与肿瘤浸润深度无关（P〉0．05）;PTEN和Survivin蛋白在胃癌组织中的阳性表达率呈负相关（P〈0．05）。结论在胃癌组织中PTEN表达下调而Survivin表达上调．与胃癌的发生和临床进展关系密切．可作为判断胃癌生物学行为和预后的参考指标。     

Survivin、VEGF、β—catenin在子宫内膜癌组织及腹腔冲洗液中的表达及意义

目的研究子宫内膜癌组织及腹腔冲洗液细胞中凋亡抑制蛋白（Survivin）、血管内皮生长因子（VEGF）及β-连环素（β-catenin）的表达和意义。方法用免疫组织化学SP法检测Survivin、VEGF和β-catenin在49例子宫内膜癌组织及腹腔冲洗液细胞标本中的表达。结果在子宫内膜癌组织中,Survivin蛋白的表达与组织和子宫肌层浸润深度有关（P〈0．05）;VEGF的表达与子宫肌层的浸润深度有关（P〈0．05）;β—catenin的表达与组织病理分级及子宫肌层浸润深度有关。三者具有相关性（r值分别为0．580、0．663、27．104,P〈0．01）。在子宫内膜癌腹腔冲洗液细胞中,Survivin与组织病理分级、子宫肌层浸润有关（X^2值分别为8．075、9．323,P〈0．01）;VEGF与子宫肌层浸润和手术病理分期有关（X^2值分别为11．617,10．597,P〈0．01）;在子宫内膜癌腹腔冲洗液细胞中Survivin与VEGF具有相关性（r=6．282。P〈0．05）。结论Survivin、VEGF和β-catenin与子宫内膜癌的发展侵袭相关;三者共同作用促进子宫内膜癌的发展和侵袭。     

MMP-9和VEGF的表达与胃癌组织生长、侵袭及转移的关系

目的分析血管内皮生长因子（vascular endothelial growthfactor,VEGF）和基质金属蛋白酶（matrix metalloproteinase-7,MMP-9）在胃癌中的表达,探讨血管生成在肿瘤侵袭转移中的差别及意义。方法选取70例胃癌及其癌旁组织、正常组织标本,应用免疫组化方法检测VEGF、MMP-9表达和微血管密度（microvessel density,MVD）计数,并结合病理特点进行分析。结果VEGF、MMP-9表达阳性率胃癌组织较癌旁组织、正常组织差异有统计学意义（VEGF：77．14％VS5．71％,12．86％,P〈0．01;MMP-9：68．57％VS8．57％,5．71％,P〈0．01）;在大小为〈2cm、2～5cm和〉5cm肿瘤VEGF的阳性率分别为42．86％、92．86％和78．57％,MMP-9的阳性率分别为28．57％、75．00％和83．33％;分化程度高、中、低肿瘤VEGF的阳性率分别为71．43％、70．59％和90．91％,MMP-9的阳性率分别为71．43％、64．71％和72．73％,差异均有统计学意义（P〈0．05）。VEGF、MMP-9阳性率在淋巴转移阳性组分别为100％、95．24％,胃癌VEGF、MMP-9阳性组与阴性组MVD平均值比较,差异均有统计学意义（t=3．23,P〈0．01;t=3．89,P〈0．01）。结论VEGF、MMPO与胃癌的高血管生成活性相关,VEGF、MMPO有望成为抗胃癌侵犯转移治疗的靶蛋白。     

Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.     

HPLC法测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱

目的 采用高效液相色谱（HPLC）法同时测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱10种活性成分。方法 采用InerSustain AQ-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,流动相A：乙腈–无水乙醇（80∶20）,流动相B：0.1%磷酸溶液,梯度洗脱,检测波长220 nm,体积流量1.0 mL/min,柱温30℃,进样量10 μL。结果 木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱分别在2.69～134.50、1.95～97.50、0.63～31.50、0.86～43.00、11.95～597.50、0.59～29.50、6.08～304.00、4.85～242.50、1.66～83.00、19.79～989.50 μg/mL线性关系良好（r≥0.999 3）;平均回收率分别为99.11%、98.23%、96.95%、97.78%、100.02%、97.21%、99.66%、99.52%、98.81%、100.08%,RSD值分别为1.04%、1.23%、1.37%、1.65%、0.70%、1.28%、0.65%、0.81%、1.11%、0.63%。结论 建立的HPLC法可用于抗妇炎胶囊中10种活性成分的测定,作为抗妇炎胶囊质量控制方法。     

Arformoterol: (R,R)-eformoterol, (R,R)-formoterol, arformoterol tartrate, eformoterol-sepracor, formoterol-sepracor, R,R-eformoterol, R,R-formoterol

Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the beta(2)-adrenoceptor agonist formoterol [eformoterol]. This isomer contains two chiral centres and is being developed as an inhaled preparation for the treatment of respiratory disorders. Sepracor believes that arformoterol has the potential to be a once-daily therapy with a rapid onset of action and a duration of effect exceeding 12 hours. In 1995, Sepracor acquired New England Pharmaceuticals, a manufacturer of metered-dose and dry powder inhalers, for the purpose of preparing formulations of levosalbutamol and arformoterol. Phase II dose-ranging clinical studies of arformoterol as a longer-acting, complementary bronchodilator were completed successfully in the fourth quarter of 2000. Phase III trials of arformoterol began in September 2001. The indications for the drug appeared to be asthma and chronic obstructive pulmonary disease (COPD). However, an update of the pharmaceutical product information on the Sepracor website in September 2003 listed COPD maintenance therapy as the only indication for arformoterol. In October 2002, Sepracor stated that two pivotal phase III studies were ongoing in 1600 patients. Sepracor estimates that its NDA submission for arformoterol, which is projected for the first half of 2004, will include approximately 3000 adult subjects. Sepracor stated in July 2003 that it had completed more than 100 preclinical studies and initiated or completed 15 clinical studies for arformoterol inhalation solution for the treatment of bronchospasm in patients with COPD. In addition, Sepracor stated that the two pivotal phase III studies in 1600 patients were still progressing. In 1995, European patents were granted to Sepracor for the use of arformoterol in the treatment of asthma, and the US patent application was pending.     

欧洲刺柏（Juniper）

活性成分与药理作用欧洲刺柏药用部位是其浆果，具有促水排泄、防腐、抗胃肠胀气和抗风湿作用，还可改善胃功能。用作促水排泄药可增加尿量（水丢失），但不增加钠排泄。成分萜品烯-4-醇可增加肾小球滤过率，但刺激肾。欧洲刺柏浆果对单纯疱疹病毒体外显示抗病毒活性，并具抗真菌活性。动物实验显示，欧洲刺柏浆果提取物具有堕胎、抗生育、抗炎、抗胚胎植入、降血压、升血压和降血糖作用。欧洲刺柏浆果油具有兴奋子宫的活性，以及利尿、胃肠道抗菌和刺激作用，该油对平滑肌有阻止解痉作用。     

Oral Presentations (LDD, LPES, LNM, LPAT, LNT, LPPT, LPM)

Probiotic microorganisms have been shown to provide specific health benefits when consumed as food supplements or as food components. The main problem of such products is the poor survival of the probiotic bacteria in the low pH of gastric fluid. However the use of synthetic excipients for enteric coating to prevent the exposure of microorganisms to gastric fluid is limited in food supplementary industry. Therefore the aim of this study was to develop an enteric coating formulation containing shellac as a natural polymer. Shellac possesses good resistance to gastric juice; the major disadvantage of this polymer is its low solubility in the intestinal fluid [1, 2]. Thus films containing different ratios of shellac and water-soluble polymers (sodium alginate, hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidon (PVP)) or plasticizers (glycerol and glyceryl triacetate (GTA)) were prepared in order to analyse the films’ melting temperatures (T_m), the changes in enthalpy (ΔH), their capability of taking up water, and their solubility in different media. The release characteristics of the films were studied by loading pellets with Enterococcus faecium M74 and coating them with formulations containing different amounts of shellac and polymer or plasticized shellac. Using dissolution tests, performed according to USP XXXI paddle method, the resistance of the coatings to simulated gastric fluid (SGF, pH 1.2) and the release of cells in simulated intestinal fluid (SIF, pH 6.8) was investigated.The trials showed that an increasing amount of plasticizer results in a decrease of T_m and ΔH of the films whereat glycerol had a superior plasticization effect to GTA. The compatibility of films made of water-soluble polymers and shellac was also concentration dependent. HPMC and PVP showed superior compatibility with shellac compared to sodium alginate, since films containing shellac and more than 10% [w/w] sodium alginate tended to separate into two phases. In the end five formulations containing shellac and either 5% [w/w] glycerol, 10% [w/w] PVP, 20% [w/w] PVP, 10% [w/w] HPMC, or 5% [w/w] sodium alginate emerged as feasible for enteric coating purposes.