前胡丙素对分离的成年鼠正常及肥厚心室肌细胞内游离钙的影响(英文)

目的:研究分离的成年大鼠正常及肥厚左室肌细胞[Ca~(2 )]_i及前胡丙素的作用.方法:用Fura 2-AM测定单细胞[Ca~(2 )]_i.结果:外钙为1.0mmol·L~(-1)时,正常左室肌细胞静息钙87±4 nmol·L~(-1),肥厚细胞123±7 nmol·L~(-1).肥厚心肌细胞中,加入KCl 20,40,60 mmol·L~(-1),[Ca~(2 )]_i增加29％,78％和185％,幅度高于正常细胞.前胡丙素1,10,100 μmol·L~(-1)浓度依赖地抑制KCl及去甲肾上腺素诱导[Ca~(2 )]_i增加.作用与硝苯啶相似.结论:肥厚心肌细胞静息钙高于正常细胞;前胡丙素抑制激动剂引起的[Ca~(2 )]_i升高源于其钙通道阻断作用.     

小檗胺对培养的HeLa细胞内游离钙浓度的作用(英文)

目的:研究Ca~(2 )信号传导是否参与Hela细胞的信号传导过程以及小檗胺(Ber)对HeLa细胞内钙浓度([Ca~(2 )]_i)变化的影响。方法:Fluo 3-AM负载HeLa细胞,共聚焦法测定[Ca~(2 )]_i,结果以荧光强度(FI)表示。结果:(1)有外钙时,HeLa细胞静息FI为186±44,KCl、NE、Cal,及咖啡因均升高HeLa细胞的[Ca~(2 )]_i。(2)Ber处理后,静息FI无影响,但抑制KCl、NE和Cal引起的[Ca~(2 )]_i升高(P<0.01),FI变化的速率减慢,达峰值的时间延长。(3)无外钙时,咖啡因诱导的[Ca~(2 )]_i升高不被Ber抑制。(4)Ber的上述作用与Ver的作用相似。结论:HeLa细胞属于非兴奋性细胞,但部分生物学特征与兴奋性细胞相似,Ca~(2 )同样在其信息转导中发挥重要作用。     

TMB-8抑制神经递质引起的单个脑细胞内游离钙的升高(英文)

目的:研究TMB-8对神经递质引起的单个脑细胞内游离钙升高的作用。方法:应用AR-CM-MIC阳离子测定系统测定游离大鼠单个脑细胞内钙离子浓度。结果:当细胞外液Ca~(2 )浓度为1.3mmol·L~(-1)时,TMB-8 30μmol·L~(-1)能降低谷氨酸,组织胺,5-羟色胺引起的脑[Ca~(2 )]_i浓度的升高。而当细胞外液无钙时,TMB-8能降低细胞内静息[Ca~(2 )]_i;TMB-8 10μmol·L~(-1)则几乎完全抑制了组织胺和5-羟色胺引起的脑[Ca~(2 )]_i升高作用。结论:TMB-8能降低谷氨酸,组织胺,5-羟色胺引起的脑[Ca~(2 )]_i升高。     

钾通道开放剂降低血管平滑肌细胞内游离钙浓度(英文)

目的:研究PCO—Pin,Nic,Lem及RP对VMSC内[Ca~(2 )]_i的改变及其可能机制。方法:VSMC加入Fura-2 AM 2.5μmol·L~(-1)37℃下孵育50min,[Ca~(2 )]_i用荧光分光光度计检测。结果:4种PCO能较弱地抑制K~ 30 mmol·L~(-1)诱导的[Ca~(2 )]_i增加,但明显抑制ATP 0.1mmol·L~(-1)诱导的[Ca~(2 )]_i峰相及持续相增加,且呈剂量依赖性。格列苯脲完全阻断Pin,Lem及RP的作用,只部分抑制Nic的作用。无钙液中先给4种PCO,能显著抑制ATP诱导的[Ca~(2 )]_i峰相增加。结论:4种PCO均抑制ATP诱导的[Ca~(2 )]_i增加,此作用与减少细胞外钙内流及细胞内钙释放有关。     

大蒜新素对分离大鼠脑细胞内游离Ca~(2 )的影响

目的:观察大蒜新素对不同刺激剂所致分离大鼠脑细胞内游离钙的影响。方法:以Fura 2-AM为细胞内游离钙的荧光指示剂,用AR-CM-MIC阳离子测定系统,直接测定了分离新生大鼠脑细胞内游离钙([Ca~(2 )]_i)值,观察了大蒜新素的影响。结果:大蒜新素对脑细胞静息[Ca~(2 )]_i无明显影响,大蒜新素1-100μmol·L~(-1)能剂量依赖性地抑制高K~ 和谷氨酸引起的[Ca~(2 )]_i升高,其中IC_(50)分别为59.7和69.9μmol·L~(-1),高剂量大蒜新素100μmol·L~(-1)能抑制去甲肾上腺素引起的[Ca~(2 )]_i升高。结论:大蒜新素对高K~ 、去甲肾上腺素及谷氨酸引起的[Ca~(2 )]_i升高的抑制作用可能是其抗脑缺血作用机制之一。     

甲基黄酮醇胺对分离的胎鼠脑细胞内游离钙浓度的影响(英文)

目的:观察甲基黄酮醇胺(MFA)对胎鼠脑细胞内游离钙浓度在静息以及激动剂存在时的作用。方法:用钙离子荧光染料Fura 2-AM负载后,测定分离的胎鼠脑细胞内游离钙浓度([Ca~(2 )]_i)及其变化。结果:在含钙1.3mmoL·L~(-1)的Hanks’液中,[Ca~(2 )]_i为197±20nmol·L~(-1)(n=44)。MFA0.15mmol·L~(-1)对静息脑细胞内钙浓度无明显影响。在细胞外钙1.3mmol·L~(-1)条件下,MFA(0.03—0.3 mmoL·L~(-1))浓度依赖性地抑制高钾去极化导致的[Ca~(2 )]_i升高,IC_(50)为0.14(95％可信限:0.05—0.42)mmoL·L~(-1)。在较高浓度时,MFA(0.15—0.3mmoL·L~(-1))也可抑制谷氨酸兴奋所引起的[Ca~(2 )]_i,IC_(50)为0.20(95％可信限:0.01—3.40)mmoL·L~(-1)。结论:MFA抑制高钾去极化引起的[Ca~(2 )]_i升高,在较高浓度时也拮抗谷氨酸兴奋所致的[Ca~(2 )]_i升高。     

甘草次酸钠对乳鼠心肌细胞的影响(英文)

目的:研究甘草次酸钠(SG)对乳鼠心肌细胞的作用。方法:体外培养乳鼠心肌细胞,用放射免疫法和荧光法分别测定cAMP和[Ca~(2 )]_i。结果:SG 0.4mmol·L~(-1)于5,10和15min使心肌细胞搏动频率由73±9min~(-1)分别降至62±5,59±7和56±6min~(-1)。SG0.1和0.2mmol·L~(-1)分别在15和10,15min呈现以上相似的结果。SG0.2和0.4mmol·L~(-1)与心肌细胞37℃共孵10,15min,cAMP浓度和[Ca~(2 )]_i均被降低。SG 0.2mmol·L~(-1)处理组的cAMP含量低于对照组(1.09±0.18,1.12±0.35pmol per vial,P<0.05);[Ca~(2 )]_i的变化也类似(30±4nmol·L~(-1),P<0.01,28±6nmol·L~(-1)P<0.05)。SG 0.1和0.2mmol·L~(-1)提高心肌细胞悬液氧分压变化率(87％±5％,75％±4％,P<0.01),但SG0.4mmol·L~(-1)降低氧分压变化率(31％±2％,P<0.01)。结论:SG可保护心肌或治疗缺血性心脏病。     

尼卡地平升高小鼠胸腺细胞胞浆钙浓度(英文)

研究尼卡地平(nicardipine,Nic)对小鼠胸腺细胞胞浆钙浓度([Ca~(2 )]_i)及增殖的影响.方法:用Fura-2掺入细胞的荧光测定法测定[ca~(2 )]_i;用[~3H]thymidine掺入法测定胸腺淋巴细胞的增殖.结果:无论在含Ca~(2 )或无Ca~(2 )介质中,Nic 1—30 μmol·L~(-1),以浓度依赖的方式升高静息胸腺细胞的[Ca~(2 )]_i.丝裂原Con A 5 mg·L~(-1)也从细胞内库释放Ca~(2 ),而Nic抑制Con A引起的[Ca~(2 )]_i升高.在上述升高[Ca~(2 )]_i的浓度中,Nic不刺激静息胸腺淋巴细胞增殖,但显著抑制Con A的增殖反应.结论:Nic升高[Ca~(2 )]_i,干扰了细胞Ca~(2 )稳态,因而抑制淋巴细胞对丝裂原的反应.     

L-焦谷氨酸对抗谷氨酸钠诱发的大鼠皮层神经元损伤

目的:在大鼠皮层神经元研究L-吡咯烷酮羧酸(L-PGA)对谷氨酸钠(Glu)诱发神经毒性的拮抗作用。方法:原代培养的皮层神经元取自16d龄的胎鼠,与Glu作用30分钟,24小时后测定神经元的存活及培养介质中亚硝酸盐的浓度;以Fura 2-AM为细胞内[Ca~(2 )]_i荧光探针,AR-CM-MIC阳离子测定系统测定[Ca~(2 )]_i。结果:L-PGA 10-80μmol·L~(-1)浓度依赖地抑制Glu 500μmol·L~(-1)引起的神经损伤,其IC_(50)为(41±9)μmol·L~(-1),95％可信区间:(30.3-54.7)μmol·L~(-1)。L-PGA也能浓度依赖地降低Glu引起的NO释放。L-PGA 1,3,10,30,100μmol·L~(-1)对Glu 100μmol·L~(-1)引起的[Ca~(2 )]_i升高的抑制率分别为20.5％,34.4％,47.7％,70.6％,80.4％。结论:L-PGA可能通过抑制NO形成或细胞内Ca~(2 )浓度的升高而拮抗Glu的神经毒性。     

MK-447对家兔凝血酶诱导的血小板聚集,ATP释放及细胞内游离钙动员的影响(英文)

目的:研究MK-447对家兔凝血酶诱导的血小板聚集释放反应及单细胞内钙水平的影响.方法:利用浊度法及测定PRP中ATP的含量评价聚集和释放反应,以荧光图像法分析细胞内钙浓度.结果:MK-447仅使兔多血小板血浆(PRP)透光度降低(DLT),即血小板变形,单血小板[Ca~(2 )]_i轻度增加(160 nmol·L~(-1)),并不被依他酸3 mmol·L~(-1)抑制.MK-447消除凝血酶诱导的DLT,聚集和ATP释放增强,呈剂量依赖性,且凝血酶介导的[Ca2 ]_i由369 ±45 nmol·L~(-1)增加到621±121 nmol·L~(-1).结论:MK-447的血小板变形与其[Ca~(2 )]_i释放有关.MK-447增强凝血酶的血小板聚集和ATP释放.MK-447的这一作用可能于[Ca2 ]_i的协同作用有关.     

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.