地塞米松、盐酸氨溴索对胎兔组织器官重量及体重的影响

目的:了解产前使用地塞米松、盐酸氨溴索对胎兔肺表面活性物质合成及体重和各器官重量的影响.方法:随机选取30只雌兔分为地塞米松组、盐酸氨溴索组及对照组,每组均为10只.地塞米松组、盐酸氨溴索组于兔妊娠第24 d开始分别给予地塞米松、盐酸氨溴索耳缘静脉注射,对照组给予等剂量生理盐水耳缘静脉注射,连续3 d,妊娠第27 d取出胎兔,检测胎兔肺的磷脂水平;称量胎兔体重及胎肺、胎肝、胎肠及胎盘的湿重.结果:地塞米松组、盐酸氨溴索组及对照组胎兔肺磷脂含量分别为(0.70±0.45)mmoL/g、(0.69±0.41)mmol/g、(0.35±0.13)mmol/g.地塞米松组、盐酸氨溴索组与对照组胎肺的磷脂水平比较差异均有统计学差异(P<0.05).地塞米松组妊娠胎兔的总体重(128.05±34.34)g,低于盐酸氨溴索组(154.90±61.74)g及对照组(159.55+50.03)g,差异有统计学意义(P<0.05);地塞米松组妊娠胎兔的平均体重(19.10±5.74)g,低于盐酸氨溴索组(23.47±6.26)g及对照组(23.81±6.02)g,差异有统计学意义(P<0.05);地塞米松组妊娠胎盘的总重量和平均体重低于盐酸氨溴索组及对照组,而胎肝、胎肠、胎肺各组间比较差异无统计学意义(P>0.05).结论:产前应用盐酸氨溴索能促进胎兔肺表面活性物质合成,且与地塞米松作用效果相似;地塞米松可降低胎兔体重和胎盘重量,盐酸氨溴索组则对胎兔体重影响不明显.     

氨溴索联合地塞米松对脂多糖诱导的急性肺损伤大鼠肺表面活性蛋白A的影响

目的观察氨溴索和地塞米松联用对脂多糖诱导的急性肺损伤(ALI)大鼠肺表面活性蛋白A(SP-A)表达的影响。方法 SD大鼠42只,随机分成六组,每组7只。空白对照组无处理,阴性对照组自尾静脉注入生理盐水2 mL。其余四组均给予脂多糖5 mg·kg-1,在此基础上氨溴索组予氨溴索100 mg·kg-1,地塞米松组予地塞米松6 mg·kg-1,联合用药组予氨溴索60 mg·kg-1+地塞米松4 mg·kg-1。检测各组血气分析指标、肺组织湿干重比及病理学改变,采用免疫组化和RT-PCR测定各组肺组织SP-A含量及mRNA表达。结果空白对照组和阴性对照组各项指标均无显著差异(P>0.05)。与对照组比较,模型组大鼠动脉血pH值和PaO2降低,肺组织湿干重比增高,SP-A含量及其mRNA表达均下降,差异均有显著意义(P<0.05),病理损伤明显。与模型组比较,各给药组pH值和PaO2增高,肺组织湿干重比降低,SP-A含量及其mRNA表达均升高(P<0.05),病理损伤明显改善,联合用药组改善优于氨溴索组和地塞米松组(P<0.05)。结论氨溴索与地塞米松可能通过提高肺组织SP-A含量对ALI大鼠起保护作用,两药合用效果更佳。     

盐酸氨溴索、地塞米松对大鼠胎肺TGF-β3表达的影响

目的 比较产前给药盐酸氨溴索、地塞米松对大鼠胎肺转化生长因子-β3(TGF-β3)基因和蛋白表达的影响.方法 9只孕鼠随机分为生理盐水对照组、地塞米松组、盐酸氨溴索组,每组3只.孕16、17、18 d腹腔注射给药3剂.孕19 d取胎鼠肺, RT-PCR法检测TGF-β3基因表达水平;免疫组织化学法检测TGF-β3蛋白表达水平.结果 地塞米松组和盐酸氨溴索组TGF-β3基因和蛋白的表达均明显高于对照组 (P＜0.05).地塞米松组TGF-β3基因和蛋白的表达高于盐酸氨溴索组(P＜0.05).结论 产前给药盐酸氨溴索、地塞米松均能促进胎肺发育相关因子TGF-β3基因及蛋白的表达,从而促进胎肺功能的发育.     

多剂量地塞米松和盐酸氨溴索对孕鼠和胎鼠的不良影响

目的探讨多剂量地塞米松和盐酸氨溴索对孕鼠和胎鼠的不良影响。方法选择18只妊娠16d SD孕鼠,随机分为生理盐水对照组、地塞米松组和盐酸氨溴索组3组,每组6只。于孕16、17、18 d尾静脉分别注射生理盐水2 m l/d、地塞米松0.8 m g.kg-1.d-1和盐酸氨溴索75 m g.kg-1.d-1,于孕第19天时剖宫取胎。观察孕鼠体重、胎鼠肝脏、肾脏及肾上腺结构,比较多剂量地塞米松和盐酸氨溴索对孕鼠和胎鼠的不良影响。结果多剂量地塞米松组孕鼠体重呈下降趋势,3组孕鼠体重于用药前(妊娠16 d)和用药后第1天各组体重差异无统计学意义(P>0.05);用药后第2天和第3天,地塞米松组孕鼠体重明显低于对照组和盐酸氨溴索组,差异有统计学意义(P<0.05);多剂量地塞米松组12只胎鼠中有5只的肝脏呈不同程度的坏死,盐酸氨溴索组和对照组肝脏结构未见异常。结论产前应用多剂量地塞米松对孕鼠和胎鼠均有不同程度的副作用,而大剂量盐酸氨溴索未见明显的不良影响。     

孕期地塞米松暴露对大鼠生长发育的影响

目的:探讨孕期地塞米松暴露对孕鼠和胎鼠心脏、肾脏、肝脏和肺脏质量的影响.方法:妊娠期SD大鼠分为对照组和地塞米松组,在孕9～20 d期间,对照组大鼠肌注0.9％的氯化钠注射液0.2 mL·d-1,地塞米松组大鼠肌注地塞米松磷酸钠注射液0.2 mL·kg-1·d-1.妊娠20 d麻醉后剖腹取胎,测量孕鼠和胎鼠的体质量、心...     

盐酸氨溴索支气管肺泡灌洗术治疗胎粪吸入综合征疗效观察

目的评价盐酸氨溴索支气管肺泡灌洗术治疗胎粪吸入综合征的有效性和安全性。方法对照组采用常规治疗,治疗组在常规治疗的基础上加用盐酸氨溴索支气管肺泡灌洗术。结果通过不同体位多次盐酸氨溴索支气管肺泡灌洗,实现清除吸入的胎粪颗粒,增加肺表面活性物质的生成。两组治疗前后比较PaCO2、PaO2、SaO2、pH值、治愈率等各项指标差异均有显著性。未发现明显药物不良反应。结论盐酸氨溴索支气管肺泡灌洗术治疗胎粪吸入综合征安全有效。     

连花清瘟胶囊对脂多糖致急性肺损伤小鼠炎症因子和连接蛋白表达的影响

目的研究连花清瘟胶囊(LHQW)对脂多糖(LPS)致急性肺损伤小鼠肺组织连接蛋白表达的影响。方法雄性KM小鼠随机分为6组,正常对照组、模型组、模型+地塞米松5 mg·kg-1组、模型+LHQW 2,4和8 g·kg-1组,每组20只。地塞米松和LHQW均ig给药,每天1次,共7 d。末次给药24 h后,除正常对照组外其余5组气管内滴注LPS溶液,制备小鼠急性肺损伤模型。造模24 h后,处死小鼠。光镜下观察肺组织病理形态变化,透射电镜下观察肺泡上皮超微结构,流式细胞术检测外周血T细胞中肿瘤坏死因子α(TNF-α)阳性表达细胞百分率,免疫组化法检测肺组织间隙连接蛋白43(Cx43)、闭锁蛋白和闭锁小带蛋白(ZO-1)的表达。结果光镜下观察发现,模型组小鼠肺内出现大量炎症细胞浸润,肺泡壁增厚;模型+地塞米松组、模型+LHQW 2,4和8 g·kg-1组较模型组炎症细胞浸润减少,肺泡壁增厚减轻。电镜下可见,模型组肺泡上皮细胞出现损伤,模型+地塞米松组、模型+LHQW 2,4和8 g·kg-1组较模型组均不同程度减轻。正常对照组、模型组、模型+地塞米松组、模型+LHQW 2,4和8 g·kg-1组外周血T细胞中TNF-α阳性表达细胞百分率分别为(3.6±0.9)%,(6.4±0.8)%,(2.8±0.7)%,(4.7±1.6)%,(4.0±1.5)%和(3.6±1.2)%,模型组明显高于正常对照组(P<0.01),其余各组均低于模型组(P<0.05,P<0.01)。模型组肺组织中Cx43、闭锁蛋白和ZO-1表达均低于正常对照组(P<0.01),模型+地塞米松、模型+LHQW 4和8 g·kg-1组3种蛋白表达均高于模型组(P<0.05)。结论 LHQW可能通过抑制炎症细胞浸润,改善肺泡上皮细胞和肺血管内皮细胞连接蛋白的表达,缓解LPS导致的急性肺损伤。     

盐酸氨溴索在促胎肺成熟中的应用价值

目的探讨产前应用盐酸氨溴索与地塞米松在促胎肺成熟中的应用价值。方法回顾性分析孕28～36周因早产或计划早产分娩的孕妇180例,分为盐酸氨溴索组和地塞米松组,产前应用盐酸氨溴索或地塞米松促胎肺成熟治疗,观察不同孕周早产儿RDS的发生率。结果盐酸氨溴索组孕31周前出生的早产儿RDS发生率显著低于地塞米松组(P<0.05),两组在孕31～36周出生的早产儿RDS发生率无显著性差异(P>0.05)。结论产前应用盐酸氨溴索促胎肺成熟,在预防31周前出生的早产儿发生RDS方面显著优于地塞米松。     

盐酸氨溴索联合地塞米松在早产促胎肺成熟中的疗效观察

目的：探讨产前应用盐酸氨溴索联合地塞米松在早产孕妇中促胎肺成熟的效果。方法78例先兆早产孕妇,随机分为研究组和对照组,各39例。两组均用地塞米松6 mg,肌内注射,每12小时1次,连续2 d,研究组同时静脉滴注盐酸氨溴索30 mg/次,2次/d,连续4 d。对两组新生儿呼吸窘迫综合征的发生情况进行比较。结果通过治疗,孕周≤32周孕妇,研究组与对照组相比,新生儿呼吸窘迫综合征的发生率明显降低,差异有统计学意义(P<0.05)。结论产前应用盐酸氨溴索联合地塞米松对促胎肺成熟效果显著,可显著降低新生儿呼吸窘迫综合征的发生风险。     

盐酸氨溴索联合地塞米松雾化吸入预防出血性脑卒中术后肺感染的疗效观察

目的：探讨盐酸氨溴索联合地塞米松对高血压出血性脑卒中术后预防肺感染的作用。方法：474例患者随机分为治疗组和对照组,治疗组用盐酸氨溴索联合地塞米松进行雾化吸入,对照组用传统的化痰药进行雾化吸入,其余治疗两组相同。结果：应用盐酸氨溴索联合地塞米松的治疗组在预防肺感染和降低气管切开率方面均优于对照组。结论：盐酸氨溴索联合地塞米松通过雾化吸入的方法直接作用于肺部,能有效的预防肺感染,有利于患者的康复。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.