肝硬化患者血浆降钙素基因相关肽和内皮素-1含量分析

目的　观察肝硬化患者血浆降钙素基因相关肽 (CGRP)和内皮素 (ET 1)含量变化。方法　选择肝硬化患者 6 0例 (其中腹水患者 4 3例 )、正常对照 30例 ,用放射免疫法检测其血浆CGRP和ET 1含量。结果　肝硬化组血浆CGRP和ET 1明显高于对照组 (P <0 0 1) ;肝硬化腹水患者高于无腹水患者 (P <0 0 1) ;肝功能Child Pugh分级中C级高于B级、B级高于A级。结论　肝硬化患者血浆CGRP和ET 1水平增高 ,CGRP及ET 1在肝功能损伤及肝硬化高动力循环状态的发生中具有重要作用     

依那普利联合卡维地洛对慢性心力衰竭患者心功能与神经内分泌功能及血管内皮功能的影响

目的 探讨依那普利联合卡维地洛治疗慢性心力衰竭(CHF)的临床效果.方法 选取2014年1月～2016年7月我院104例CHF患者,根据治疗方案分组,各52例.在常规治疗基础上,对照组给予依那普利治疗,观察组给予依那普利+卡维地洛治疗.对比两组治疗前后左室射血分数(LVEF)、内皮素(ET)及神经内分泌功能指标[醛固醇(ALD)、血管紧张素Ⅱ(ATⅡ)、肾素活性(PRA)]水平.结果 治疗前,两组LVEF、ET及PRA、ATⅡ、ALD水平差异无统计学意义(P＞0.05),经治疗,观察组LVEF高于对照组,ET及PRA、ATⅡ、ALD低于对照组,差异有统计学意义(P＜0.05).结论 依那普利联合卡维地洛治疗慢性心力衰竭,有利于改善患者心功能及内皮功能,且对神经内分泌功能调节作用显著.     

肝硬化患者凝血功能和纤维蛋白溶解功能变化及其临床意义

目的:探讨肝硬化患者凝血和纤溶功能的变化及其临床意义.方法:对50 例肝硬化患者及20 例正常对照组采用全自动血凝仪测定其血浆D-二聚体(D-dimer)和纤维蛋白原(FIB)含量,测定凝血酶原(PT)和活化部分凝血活酶(APTT)时间,血小板(PLT)采用全自动血球计数仪检测.结果:肝硬化chi1 d B级组、C级组血浆D-二聚体(D-dimer)、PT、APTT、PLT分别与正常对照组比较差异均有显著性(P＜0.05),肝硬化Child B级组、C级组(FIB)分别与正常对照组比较差异无显著性(P＞0.05);肝硬化Child C级组D-dimer、PT、APTT分别与肝硬化Child B级组比较其差异性更显著(P＜0.01),肝硬化Child C级组FIB、PLT与肝硬化Child B级组比较差异无显著性(P＞0.05).结论:联合检测凝血及纤溶指标对判断肝硬化患者肝功能损害程度、出血危险性的D-dimer、预后估计及指导临床治疗有一定参考价值.     

心钠素、肾素-血管紧张素-醛固酮系统在慢阻肺病、肺心病的变化及相互关系

本文应用放免法测定了正常人16例、肺气肿13例、肺心病51例血浆心钠素(ANP)、肾素活性(PRA)、血管紧张素Ⅱ(AT Ⅱ)、醛固酮(Aldo)的浓度,结果发现①肺气肿组血浆 ANP 水平明显低于正常对照组;②肺心病不同心功能血浆 ANP 水平不同,心功能Ⅰ、Ⅱ、Ⅲ级肺心病患者的血浆 ANP 浓度各组之间有明显差异;③肺心病组血浆 PRA,AT Ⅱ、Aldo 的水平明显高于肺气肿组;④血浆 ANP 与 PRA 有一定的正相关。     

肾素-血管紧张素-醛固酮系统与妊娠高血压病的关系

目的探讨肾素-血管紧张素-醛固酮系统(RAAS)与妊娠高血压疾病(HDCP)的关系。方法选取2014年2月~2015年8月在我院住院分娩的孕产妇92例,其中合并HDCP 38例,设为妊高症组,正常孕产妇54例,设为对照组。比较两组孕产妇产前、产后血浆活性肾素(PRA)水平、血管紧张素Ⅱ(AngⅡ)及醛固酮(ALD)水平的差异。结果与对照组比较,妊高症组孕产妇产前血浆PRA、AngⅡ水平均明显降低(P<0.05),ALD水平明显升高(P<0.05);与产前比较,妊高症组孕产妇产后血浆PRA、AngⅡ均明显升高,ALD水平明显降低(P<0.05),而对照组无统计学差异(P>0.05);与对照组比较,妊高症组孕产妇产后AngⅡ水平明显升高(P<0.05),而PRA、ALD水平比较差异无显著性(P>0.05);妊高症组孕产妇胎盘组织中AT1受体表达明显强于对照组(P<0.05),组间肾素表达差异无统计学意义(P>0.05)。结论 HDCP的发病与胎盘组织局部肾素-血管紧张素系统相关,其机制可能与胎盘组织中AT1受体表现显著增多,通过多种途径影响胎盘血流灌注,使胎盘发生缺血缺氧有关。     

一氧化氮与内皮素在肝硬化发生发展中的作用

目的 :研究一氧化氮和内皮素在肝硬化发生发展中的作用。方法 :用放射免疫法 ,镀铜镉还原法和火箭电泳法测定 74例肝硬化患者和 5 1例正常对照组血浆内皮素 (ET)、肿瘤坏死因子 α(TNFα)、一氧化氮 (NO)和纤维联结蛋白 (FN)的含量。结果 :肝硬化患者血浆 ET和 NO明显升高 ,二者均与 TNFα呈正相关 ,与 FN呈负相关。ET和 NO水平随肝功能受损加重、腹水量增加和食管静脉曲张程度加重而增加 ,正常对照组和肝硬化 A级时 ,ET与 NO无相关性 ,而 B级和 C级 ,中大量腹水组及食管静脉曲张组 ET和 NO呈明显正相关。结论 :NO和 ET在肝硬化发生发展中均具有重要作用 ,二者共同促进了肝硬化的失代偿及并发症发生     

直立倾斜试验中肾素—血管紧张素—醛固酮变化

30例不明原因晕厥病人及15例无晕厥史的健康人行直立倾斜试验（HUT）检查，并取血测定血浆肾素活性（PRA）、血管紧张素Ⅱ（ATⅡ）及醛固酮（ALD）。结果示平卧位、倾斜后5分钟阳性、阴性及对照组PRA、ATⅡ、ALD浓度及其变化相似，三组间无显著差异（P＞0.05）。检查结束时三组PRA、ATⅡ及ALD均较倾斜后5分钟又有所增加（P＜0.05）；但阳性组PRA、ATⅡ、ALD显著高于阴性及对照组（P＜0．01）。研究表明血浆肾素、ATⅡ及ALD均参与体位改变后维持循环稳定方面的快速调节，它们的增加不是引起血管迷走性晕厥的原因而是对血压下降的一种代偿反应。     

心钠素对肝硬化患者血浆内皮素血管紧张素Ⅱ的影响

目的：应用外源性心钠素（ANP），观察其对直硬化患者血浆内皮素（ET）、血管紧张素Ⅱ（ATⅡ）等缩血管物质的影响。方法：应用心血通注射液（心钠素）治疗41例肝硬化患者，用放免法分别检测治疗前后血浆ANP、ET、ATⅡ的水平，同时检测20例健康人，结果：肝硬化组比正常组血浆ANP、ET、ATⅡ水平明显升高（P＜0．05），肝硬化患者血浆ANP与ET呈负相关，与ATⅡ无显著相关。外源性心钠素能降低childA级和／或B级ET、ATⅡ的水平（P＜0．05，P＜0．01），对childC级无抑制作用。结论：肝硬化患者血管扩张因子与血管收缩因子之间失衡，促进腹水及门脉高压的形成，外源性心钠素能部分调节它们之间的紊乱关系，对肝硬化失代偿期的治疗有重要价值。     

培哚普利对充血性心力衰竭患者血液动力学、肾素血管紧张素系统和内皮素的影响

目的:观察培哚普利对充血性心力衰竭(CHF)患者血液动力学及神经内分泌系统的影响。方法:23例病情相对稳定的CHF患者给予培哚普利4mg口服,Qd,于用药前及用药后1小时,6小时,24小时分别以超声心动图检测并计算左室射血分数(LVEF)、左室短轴缩短率(LVFS)、心输出量(CO)、心脏指数(CI)、外周血管阻力(SVR);以放免法检测血浆肾素活性(PRA)、血管紧张素Ⅱ(AT Ⅱ)及内皮素(ET)的变化;同期检测20例健康人上述指标作为对照。结果:治疗组治疗前LVEF、LVFS、CO、CI均显著低于对照组(P<0.01),SVR明显高于对照组(P<0.01);PRA、AT Ⅱ、ET均高于对照组(P<0.01)。用培哚普利治疗6小时后,LVEF、LVFS、CO、CI均较用药前显著增高(P<0.01),SVR显著下降(P<0.01);PRA无显著变化(P>0.05).AT Ⅱ及ET均显著下降(P<0.01)。结论:培哚普利能够调整CHF患者紊乱的神经内分泌及血液动力学指标。     

1,6-二磷酸果糖对老年慢性心衰患者血浆TNF、ET、RAS的影响

目的探讨1,6-二磷酸果糖(FDP)对老年慢性心力衰竭患者血浆肾素血管紧张素系统(RAS)、内皮素(ET)、细胞因子(TNF)水平的影响。方法67例老年慢性心衰患者(CHF)随机分为A组(33例)B组(34例),A组采用常规抗心衰药物治疗,B组在常规治疗的基础上加用FDP10g静脉滴注,1次/d,疗程14d,采用放免法测定两组治疗前后血浆肾素(PRA)、血管紧张素Ⅱ(AgⅡ)、内皮素(ET)和血清肿瘤坏死因子(TNF)水平,超声心动图测定治疗前后心功能,并以30例健康老人为对照(对照组)。结果A、B两组CHF患者治疗前PRA、AgⅡ、ET、TNF水平与对照组比较均显著升高,治疗后PRA、AgⅡ水平明显上升,ET、TNF水平显著下降;左室短轴缩短率(FS),E峰速度(PEV),E/A比值亦明显改善。但B组较A组改善更明显,并且差异有统计学意义(P<0.05)。结论AgⅡ、ET、TNF等神经激素、细胞因子参与了老年慢性心衰的发生发展过程,1,6-二磷酸果糖可通过调节内皮细胞舒缩功能,改善心功能。     

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.