粉防己碱,Fura2—AM和BayK8644对脂多糖刺激大鼠腹腔巨噬细胞释…

目的：研究化钙与脂多糖（ＬＰＳ）刺激大鼠腹腔巨噬细胞（ＰＭφ）释放血小板活化因子（ＰＡＦ）的关系，方法：通过ＰＡＦ的生物测定法，观察了粉防己碱（Ｔｅｔ），Ｆｕｒａ２－ＡＭ和Ｂａｙｋ８６４４对ＬＰＳ刺激ＰＭφ释放ＰＡＦ的影响，结果，ＬＰＳ刺激ＰＭφ释放ＰＡＦ，但并不使其细胞内钙增高，Ｔｅｔ在０．１，１．０，１０，１００μｍｏｌ．Ｌ＾－１和Ｆｕｒａ２－ＡＭ在０．０１，０．１，１０，１０μｍｏｌ．Ｌ＾－     

四甲基吡嗪对内毒素血症小鼠的保护作用及其与血小板活化因子的关系(英文)

研究四甲基吡嗪（ＴＭＰ）对内毒素血症小鼠的保护作用及其与血小板活化因子（ＰＭ）的关系．方法：给 ＴＭＰ处理的小鼠 ｉｖ　 ＬＰＳ,观察其存活率及血清ＰＡＦ水平．体外用ＬＰＳ刺激小鼠ＰＭφ,测定 ＰＭ及 ＰＬＡ２和乙酰辅酶 Ａ乙酰基转移酶的活性．结果：ＴＭＰ明显提高小鼠存活率和降低血清ＰＡＦ水平．体外,ＴＭＰ（０．０５－５０μｍｏｌ· Ｌ－１）剂量依赖性减少ＰＭφ释放ＰＡＦ［１２．７±１．６）,（８．９±１．２）,（６．９±０．８）,（５．５±１．０）μｇ·Ｌ－１,Ｐ＜０．０１］,降低ＰＬＡ２活性肝（１４９．９±２．８）（１１７．５±２．０）,（８９．６±２．０）,（７５．０±２．８） Ｕ,Ｐ＜０．０１］和乙酰辅酶Ａ乙酰基转移酶活性［ＰＡＦ（９．５±０．７）,（５．２± ０．７）,（２．９±０． ３）,（２．５±０． ３）μｇ· ｇ－１（ｐｒｏｔｅｉｎ）·ｍｉｎ－１, Ｐ＜０．０１］．结论： ＴＭＰ对内毒血症小鼠有保护作用,其机制是通过抑制 ＰＬＡ２和乙酰辅酶Ａ乙酰基转移酶的活性而抑制ＰＡＦ的合成。     

Regulatory role of protein tyrosine phosphorylation in platelet activating factor induced signal transduction in platelets 1

目的：研究蛋白酪氨酸磷酸化（ＰＴＰ）在血小板激活因子（ＰＡＦ）诱导血小板信号传导中的作用．方法：用水洗兔血小板考查Ｇｅｎ抑制聚集及５羟色胺释放,Ｆｕｒａ２和ＢＣＥＣＦ负载测胞内钙及ｐＨ,特异性抗酪氨酸单抗及免疫印迹法检测ＰＴＰ．结果：Ｇｅｎ１００和２００μｍｏｌ·Ｌ－１分别抑制ＰＡＦ诱导的５羟色胺释放为２３７％±２０％及４１％±８％,对胞内钙增加和Ｎａ＋／Ｈ＋交换也有抑制作用．ＰＡＦ增加Ｍｒ为７００００,６００００,５００００,４２０００／４００００,３４０００的ＰＴＰ．Ｇｅｎ２００,４００μｍｏｌ·Ｌ－１明显抑制该效应．用Ｓｔａ２０ｎｍｏｌ·Ｌ－１,ＢＡＰＴＡ２００μｍｏｌ·Ｌ－１,依他酸２ｍｍｏｌ·Ｌ－１,分别阻断ＰＫＣ及胞内钙增加和内流,也减少ＰＴＰ形成．结论：ＰＴＰ参与ＰＡＦ诱导血小板信号传导途径,ＰＫＣ活化和胞内钙动员对ＰＴＰ有调节作用．     

Efectsofmoxonidineinjectedintorostralventrolateralmedulaonbloodpressure,heartrate,andrenalsympatheticnerveactivityinrats

目的：观察延髓腹外侧头端（ＲＶＬＭ）注射莫索尼定（Ｍｏｘ）对麻醉大鼠血压（ＢＰ）、心率（ＨＲ）及肾交感神经放电（ＲＳＮＡ）的影响．方法：麻醉大鼠ＲＶＬＭ注射１μＬＭｏｘ１，１０，１００μｍｏｌ·Ｌ－１，同步记录ＢＰ，ＨＲ及ＲＳＮＡ．结果：Ｍｏｘ１，１０，１００μｍｏｌ·Ｌ－１分别使ＢＰ从１３９±１０ｋＰａ降至１３０±１７ｋＰａ（Ｐ＜００５），１３８±１８ｋＰａ至１１４±１５ｋＰａ（Ｐ＜００１），ａｎｄ１３９±１９ｋＰａ至９４±１７ｋＰａ（Ｐ＜００１）．Ｍｏｘ不影响ＨＲ．Ｍｏｘ１μｍｏｌ·Ｌ－１增加ＲＳＮＡ５０％（Ｐ＜００５），１０μｍｏｌ·Ｌ－１对ＲＳＮＡ无影响（Ｐ＞００５），１００μｍｏｌ·Ｌ－１则降低ＲＳＮＡ２３％（Ｐ＜００５）．在缓冲神经切断大鼠，Ｍｏｘ１０μｍｏｌ·Ｌ－１抑制ＲＳＮＡ５０％（Ｐ＜００５），明显不同于缓冲神经完整的动物（Ｐ＜００１）．结论：麻醉大鼠ＲＶＬＭ注射Ｍｏｘ可降低ＢＰ，但不影响ＨＲ，且ＲＳＮＡ变化与其降压作用并不平行     

Detection of DNA damage in peripheral lymphocytes by 7 compounds using comet assay

目的：检测过氧化氢（Ｈ２Ｏ２）、甲磺酸乙酯（ＥＭＳ）、丝裂霉素Ｃ（ＭＭＣ）、二甲基亚硝胺（ＤＭＮＡ）、苯并（ａ）芘（ＢａＰ）、２氨基芴（２ＡＦ）和环磷酰胺（ＣＰ）诱发小鼠、大鼠及人外周血淋巴细胞ＤＮＡ单链断裂．方法：体外单细胞微量凝胶碱性电泳试验（慧星试验）．结果：除ＥＭＳ０９７ｍｍｏｌ·Ｌ－１在小鼠淋巴细胞，ＭＭＣ３０μｍｏｌ·Ｌ－１在小鼠、人淋巴细胞中呈阴性外，其余均为阳性．最低可检测浓度分别为Ｈ２Ｏ２１μｍｏｌ·Ｌ－１，ＥＭＳ０４８ｍｍｏｌ·Ｌ－１，ＢａＰ５０μｍｏｌ·Ｌ－１，ＣＰ２０ｍｍｏｌ·Ｌ－１，ＭＭＣ１０μｍｏｌ·Ｌ－１，ＤＭＮＡ２７３ｍｍｏｌ·Ｌ－１，２ＡＦ６２５μｍｏｌ·Ｌ－１．ＣＰ、ＢａＰ、２ＡＦ需经Ｓ９Ｍｉｘ代谢活化才显示毒性．结论：彗星试验检测出ＭＭＣ诱导大鼠，ＥＭＳ诱导大鼠和人，以及Ｈ２Ｏ２、ＤＭＮＡ、ＢａＰ、ＣＰ和２ＡＦ诱导小鼠、大鼠和人外周血淋巴细胞ＤＮＡ单链断裂损伤．     

粉防己碱、颅通定对兔窦房结动作电位及豚鼠心室肌单细胞钙电流的协同作用

采用标准微电极技术和膜片钳记录技术，分别研究了粉防己碱（Ｔｅｔ）和颅通定（ｒｏｔｕｎｄｉｎｅ）对家兔窦房结动作电位及豚鼠心室肌单细胞钙电流的影响。结果表明：Ｔｅｔ１～２００μｍｏｌ·Ｌ－１，ｒｏｔｕｎｄｉｎｅ３～３００μｍｏｌ·Ｌ－１能浓度依赖性地降低兔窦房结动作电位的ＡＰＡ，Ｖｍａｘ和ＳＰ４，延长ＳＣＬ。Ｔｅｔ０．３μｍｏｌ·Ｌ－１与ｒｏｔｕｎｄｉｎｅ１μｍｏｌ·Ｌ－１合用亦有作用。在膜片钳实验中Ｔｅｔ０．１μｍｏｌ·Ｌ－１和ｒｏｔｕｎｄｉｎｅ１μｍｏｌ·Ｌ－１合用能有效抑制豚鼠心室肌单细胞钙电流，抑制率为１９．２％。提示，两种植物源性抗钙剂有良好的协同效果。     

Elevation of an endogenous inhibitor of nitric oxide synthase in diabetic rat serum

目的：测定糖尿病大鼠血中内源性ＮＯ合酶抑制物二甲基精氨酸（ＤＭＡ）的含量．方法：在链佐星诱发的糖尿病大鼠测定血清ＤＭＡ的含量和乙酰胆碱（ＡＣｈ）诱导血管内皮依赖性舒张．结果：与对照组相比，糖尿病大鼠ＤＭＡ血清浓度显著增加（５４±１０ｖｓ０７±０３μｍｏｌ·Ｌ－１，Ｐ＜００１）；丙二醛含量也高于对照组（２５±０３ｖｓ１５±０１μｍｏｌ·Ｌ－１，Ｐ＜００１）；糖尿病大鼠ＡＣｈ舒血管效应减弱，其作用可被左旋精氨酸所改善．结论：链佐星诱发糖尿病大鼠高血糖症引起内源性ＤＭＡ含量升高，同时血管内皮依赖性舒张功能被削弱．     

炎性刺激剂对小鼠腹腔巨噬细胞NF-κB的诱导

目的：建立炎性刺激剂诱导细胞核因子κＢ（ＮｕｃｌｅａｒｆａｃｔｏｒκＢ,ＮＦκＢ）的模型,研究传统非甾体抗炎药阿斯匹林（ａｓｐｉｒｉｎ）作用机理。方法：用脂多糖（ＬＰＳ）和佛波酯（ＰＭＡ）刺激小鼠腹腔巨噬细胞,用电泳迁移率改变检测法（ｅｌｅｃｔｒｏｐｈｏｒｅｔｉｃｍｏｂｉｌｉｔｙｓｈｉｆｔａｓａｙ,ＥＭＳＡ）检测。结果：ＬＰＳ１μｇ·ｍＬ－１及３μｇ·ｍＬ－１,ＰＭＡ２ｎｇ·ｍＬ－１均能诱导细胞核内ＮＦκＢ的含量。阿斯匹林１０－５ｍｏｌ·Ｌ－１可以显著抑制ＬＰＳ（１μｇ·ｍＬ－１）和ＰＭＡ（ＰＭＡ２ｎｇ·ｍＬ－１）对细胞核内ＮＦκＢ的活化。结论：所建立的以ＬＰＳ和ＰＭＡ为刺激剂,诱导细胞核内ＮＦκＢ的模型,可用于非甾体抗炎药的抗炎机理的研究。     

Effects of dexamethasone, cyproheptadine, anisodamine, and dinoprostone on TNF_α production in endotoxic shock

目的：研究地塞米松（Ｄｅｘ）、噻庚啶（Ｃｙｐ）、山莨菪碱（Ａｎｉ）和地诺前列酮（Ｄｉｎ）对脂多糖（ＬＰＳ）诱导的肿瘤坏死因子（ＴＮＦα）基因表达的影响和抑制ＴＮＦα产生的抗休克作用．方法：Ｗｉｓｔａｒ大鼠静脉注射ＬＰＳ（ＥｃｏｌｉＯ１１１Ｂ４,５ｍｇ·ｋｇ－１）复制内毒素休克模型．Ｎｏｒｔｈｅｒｎ印迹杂交分析肝脏ＴＮＦαｍＲＮＡ表达,放射免疫法测定血浆ＴＮＦα的含量．结果：ＬＰＳ攻击后２ｈ肝脏ＴＮＦαｍＲＮＡ表达水平显著增高（放射性自显影扫描分析３８±１０ｖｓ盐水对照组１１±８,Ｐ＜００１）;血浆ＴＮＦα水平明显升高［（２２±３）μｇ·Ｌ－１ｖｓ盐水对照组（２２±１０）μｇ·Ｌ－１,Ｐ＜００１］．静脉注射ＬＰＳ后立即静脉注射Ｄｅｘ５,Ｃｙｐ５,Ａｎｉ１０及Ｄｉｎ２ｍｇ·ｋｇ－１均能显著降低大鼠肝脏ＴＮＦαｍＲＮＡ水平和血浆ＴＮＦα含量,提高ＬＰＳ２０ｍｇ·ｋｇ－１攻击的小鼠２４ｈ的存活率．结论：Ｄｅｘ,Ｃｙｐ,Ａｎｉ和Ｄｉｎ均能显著抑制ＬＰＳ诱导的ＴＮＦα基因表达,具有较强的抗休克作用．     

Electrophysiologic effect of enalapril on guinea pig papillary muscles in vitro

目的：研究依那普利（Ｅｎａ）对豚鼠乳头状肌电生理特性，哇巴因诱发的延迟后除极（ＤＡＤ）和触发电活动（ＴＡ）的直接作用．方法与结果：采用标准玻璃微电极技术记录豚鼠乳头状肌动作电位．Ｅｎａ呈浓度依赖性增加静息膜电位（ＲＰ）和动作电位幅度（ＡＰＡ），而对０期最大除极，超射，和动作电位时程无明显影响．Ｅｎａ１０μｍｏｌ·Ｌ－１则可明显抑制哇巴因０５μｍｏｌ·Ｌ－１诱发的ＤＡＤ和ＴＡ，ＤＡＤ幅度分别由５３±２３，５９±２８，７４±２１和８９±１３降至２６±０７，３１±１０，３７±１５和５３±１１（ｍＶ）（Ｐ均＜００１），刺激周长为２００ｍｓ时ＴＡ数目由３６±０７降至０８±０２（Ｐ＜００５）．结论：Ｅｎａ通过增加心肌细胞ＲＰ和ＡＰＡ抑制哇巴因诱发豚鼠乳头状肌ＤＡＤ和ＴＡ．     

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。     

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。     

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.     

Strength of drug habits: For heroin,morphine, methadone,alcohol, barbiturates,pentobarbital, benzedrine,cocaine, and marijuana

The drug habits for 78 confirmed opiate addicts were studied on eight scales from the Process Association Test of Addiction (PATA) for many drug names. Through cluster analysis eight stages of addiction were defined: “to be clean”, “to learn about drugs”, “to hustle”, “to chip” (also “to be high”), to be psychologically dependent or “to need a shot”, “to be hooked”, “to kick a habit” and “to be in treatment”. Associations stimulated by the words heroin and morphine were very similar over the eight stages of addiction in opiate addicts. The subjects were especially inclined to associate morphine and heroin with the most severe level of addiction, “to be hooked”. Associations to both methadone and cocaine were elevated at the “hooked” stage, but in other respects associations to these drugs were opposite. Thus, associations to cocaine were focused on the stage of psychological dependence and the lower intermediate stage of addiction, “to chip” and “to be high”, whereas associations to methadone suggested a turning away from addiction as indicated by avoidance associations (“to come down” and “to kick a habit”) as well as associations to “treatment” and “to be clean”. Marijuana, Benzedrine, “goofball” (barbiturates) and alcohol habits were prominent at an intermediate stage of addiction (“to chip” and “to be high”). Avoidance associations were common for Benzedrine and “goofballs” (also pentobarbital) but not for marijuana or alcohol. “Hustling” associations were frequent for marijuana but not for alcohol.