大白鼠吸入EHFV气溶胶后病毒在肺巨噬细胞和外周血白细胞内增殖的研究

流行性出血热病毒(EHFV)气溶胶被大白鼠吸入后第5天和第7天,病毒分别在体外培养的肺巨噬细胞和外周血白细胞内增殖,最后定位于肺组织Ⅱ型上皮细胞内。结果表明:EHFV 气溶胶可通过呼吸道使实验大白鼠感染,病毒在体内的传播可能是通过单核巨噬细胞系统。     

流行性出血热病毒Rn9株的毒力研究

流行性出血热Rn9株病毒经脑内接种新生乳小白鼠,适应传代后,可使乳鼠发病死亡,并在乳鼠脑、肺、脾、肝、肾检出病毒抗原,感染后14天血清中亦可检出特异性抗体,滴度为1:20。通过乳鼠脑传5代的病毒毒力测定属于弱毒力株(ID_(50)10~(-6·6~3),LD_(50)10~(-4·95)),乳鼠于接种后16～18天内发病死亡,表现嗜神经性特征。     

流行性出血热病毒糖膜蛋白的纯化

为了提高流行出血热疫苗中糖膜蛋白的纯度。采用调节ＰＨ值使乳鼠脑杂蛋白沉淀的方法，对蔗糖密度梯度区带离心，脱蔗糖后的糖膜蛋白样口进行纯化。结果表明，此方法简便易行，能大幅度降低杂蛋白的含量，提高糖膜蛋白纯度。     

流行性出血热54例的治疗观察

目的探讨流行性出血热的有效治疗方法。方法针对54例流行性出血热患者的发热期、低血压休克期、少尿期、多尿期和恢复期的不同情况,给予相应的综合治疗措施。以支持疗法和对症疗法为主,同时积极做好休克、肾功能衰竭、出血的处理。结果本组54例患者经治疗后,症状与体征消失,血常规、尿常规、生化等各项指标均恢复正常,全部治愈出院。结论在流行性出血热的治疗过程中,不仅要积极治疗原发病,而且要高度注意并发症的出现,并及时处理。根据患者不同病程采用相应的支持疗法和对症疗法等综合措施可以提高疗效,减少并发症和死亡率。     

流行性出血热病毒经伤口传播的研究

本次研究采用实验室和现场相结合的方法，对流行性出血热病毒（EHFV）经伤口传播的有关问题进行一系列的研究。结果表明鼠感染的EHFV通过尿、粪排出体外后在外界环境中（4～15℃）可存活24小时；5ID50／ml的EHFV悬液可通过不显性破损的表皮使实验鼠感染。家鼠、野鼠型疫区调查结果也表明：在鼠间EHF传播因素中以皮肤破损为主要因素，鼠间密切接触和鼠体寄生昆虫叮咬为次要因素。     

Deposition, Clearance, and Shortening of Kevlar Para-aramid Fibrils in Acute, Subchronic, and Chronic Inhalation Studies in Rats

The deposition and clearance of lung-deposited Kevlar paraaramidfibrils (subfibers) have been investigated as part of a subchronicand chronic inhalation toxicity testing program. Fibrils recoveredfrom lung tissue in para-aramid-exposed Sprague-Dawley ratswere microscopically counted and measured after exposures toairborne fibrils which were about 12 µm median length(ML) and <0.3 µm median diameter. In each of threestudies lung-recovered fibrils were progressively shorter withincreasing residence time in the lungs. Twenty-eight days aftera single 6-hr exposure at 400 respirable fibrils per cubic centimeter(f/cm³) the ML of recovered fibrils decreased to about 5 µm.Twenty-four months after a 3-week exposure to 25 or 400 (f/cm³)fibrils reached about 2 µm ML. After 2 years of continuousexposure at 2.5, 25, or 100 f/cm³ or 1 year exposure plus 1year recovery at 400 f/cm fibril ML approached 4 µm. Inthe 2-year study, the lung-fiber accumulation rate/exposureconcentration was similar for the three highest concentrationsand was about 3x greater than that seen at 2.5 f/cm³ indicatingthat concentrations of about 25 f/cm or more may overwhelm clearancemechanisms. Time required for fibrils to be reduced to <5µm in the lung was markedly less at lower exposure concentrationand shorter exposure time. The primary shortening mechanismis proposed to be long fibril cutting by enzymatic attack atfibril defects. However, length-selective fibril depositionand clearance may contribute to shortening in the first fewdays after exposure. The enzymatic cutting hypothesis is supportedby measured increases in numbers of short fibers following cessationof exposures, continued shortening of the fibril length distributionup to 2 years following exposure, and in vitro fibril shorteningafter 3 months in a proteolytic enzyme preparation. The conclusionis that para-aramid fibrils are less durable in the lungs ofrats than expected from the known chemical resistance of commercialyarn. These data suggest that at the low para-aramid fibrilexposures found in the workplace, this fibril-shortening mechanismmay limit the residence time of long fibers in the lungs ofexposed workers. In addition, associated cascade impactor aerodynamicmeasurements indicate that due to their ribbon shape and curlynature, para-aramid fibrils behave aerodynamically larger thanstraight fibers.     

Deposition and Fate of Inhaled Ethylene Glycol Vapor and Condensation Aerosol in the Rat

Deposition and Fate of Inhaled Ethylene Glycol Vapor and CondensationAerosol in the Rat. Marshall, T.C. and Cheng, Y.S. (1983). Fundam.Appl. Toxicol. 3:175-181. Fischer-344 rats were exposed by nose-onlyinhalation for 30 min to ethylene glycol-¹⁴C vapor at a concentrationof 32 mg/m³. A second group of rats was exposed for 17 min toan ethylene glycol-¹⁴C aerosol formed by condensation of theglycol on 0.1 m ⁶⁷Ga₂O₃ particles. The mass median aerodynamicdiameter (MMAD) of the condensation aerosol was 2.3 µm (g = 1.8) with an ethylene glycol concentration of 184 mg/m³. Initial radiocarbon body burdens were at glycol levels of0.7 mg/kg for the vapor exposure and 2.4 mg/kg for the aerosolexposure. Estimates indicated that at least 60% of the ethyleneglycol inhaled for both exposures was deposited in rats withthe highest concentration of radioactivity being in the nasalcavities. Distribution from the site of deposition was rapidsince 75 to 80% of the initial body burden was found throughoutthe bodies of rats sacrificed immediately after exposure. Thepredominant routes of elimination during the first 4 days followingexposure were via the expired air as ¹⁴CO₂ (63% for the vaporexposure and 70% for the aerosol exposure) and urine as theunchanged glycol (20% and 11%). The proportion of the dosesexcreted as ¹⁴CO₂ suggested more complete metabolism of ethyleneglycol following inhalation relative to that observed afterintravenous injections reported previously. The half-time forclearance of plasma radiocarbon was 39 and 34 hr for the vaporexposure and aerosol exposure, respectively. The studies suggestedthat ethylene glycol plasma levels following acute exposureto high airborne concentrations of ethylene glycol vapor and/oraerosol would not approach the toxic concentrations associatedwith known dose-dependent changes in the glycol's metabolism.     

雾化吸入柠檬酸对贫铀致大鼠肺成纤维细胞增生的影响

目的:探讨雾化吸入柠檬酸对贫铀(DU)致大鼠肺成纤维细胞增生的影响及其机制。方法:取大鼠随机分为生理盐水组、模型组和柠檬酸组,后2组灌肺给予贫铀建模。柠檬酸组建模30min后雾化吸入20%柠檬酸,流量为1.44mL.min-1,每日1次,每次20min,连续给药7d。采用湿消化法检测各组大鼠建模给药后第7、15、30天(n=13)时肺铀含量,观察肺组织病理学变化及肺间质胶原沉积情况,免疫组化法检测肺泡区基质金属蛋白酶9(MMP-9)及其组织金属蛋白酶抑制物1(TIMP-1)表达情况。结果:与生理盐水组比较,模型组大鼠肺铀含量和MMP-9、TIMP-1表达均明显增加(P<0.05),且随时间延长肺铀含量逐渐降低;与模型组同时间点比较,柠檬酸组3个时间点肺铀含量和15、30d时MMP-9、TIMP-1表达均明显降低(P<0.05或P<0.01),且柠檬酸组15、30d时MMP-9、TIMP-1表达与生理盐水组比较无明显差异(P>0.05);模型组大鼠15、30d时肺成纤维细胞明显增生、肺间质胶原沉积明显,与其相同时间点比较,柠檬酸组15、30d时增生、沉积均减轻。结论:雾化吸入柠檬酸对贫铀致大鼠肺损伤具有保护作用,其可能机制是降低成纤维细胞增生。     

Effect of Chronic Cigarette Smoke Exposure on Lung Clearance of Tracer Particles Inhaled by Rats

Cigarette smoking can influence the pulmonary disposition ofother inhaled materials in humans and laboratory animals. Thisstudy was undertaken to investigate the influence of cigarettesmoke exposures of rats on the pulmonary clearance of inhaled,relatively insoluble radioactive tracer particles. Following13 weeks of whole-body exposure to air or mainstream cigarettesmoke for 6 hr/day, 5 days/week at concentrations of 0, 100,or 250 mg total particulate matter (TPM)/m³, rats were acutelyexposed pernasally to ⁸⁵Sr-labeled fused aluminosilicate (⁸⁵Sr-FAP)tracer particles, then air or smoke exposures were resumed.A separate group of rats was exposed to the ⁸⁵Sr-FAP then seriallyeuthanized through 6 months after exposure to confirm the relativeinsolubility of the tracer particles. We observed decreasedtracer particle clearance from the lungs that was smoke concentration-dependent.By 180 days after exposure to the tracer aerosol, about 14,20, and 40% of the initial activity of tracer was present incontrol, 100 mg TPM/m³, and 250 mg TPM/m³ groups, respectively.Body weight gains were less in smoke-exposed rats than in controls.Smoke exposure produced lung lesions which included increasednumbers of pigmented alveolar macrophages distributed throughoutthe parenchyma and focal collections of enlarged alveolar macrophageswith concomitant alveolar epithelial hyperplasia and neutro-philicalveolitis. The severity of the lesions increased with smokeexposure duration and concentration to include interstitialaggregates of pigmented macrophages and interstitial fibrosis.Our data confirm previous findings that exposure to cigarettesmoke decreases the ability of the lungs to clear inhaled materials.We further demonstrate an exposure-concentration related magnitudeof effect, suggesting that the cigarette smoke-exposed rat constitutesa useful model for studies of the effects of cigarette smokeon the disposition of inhaled particles.     

Comparison of Nasal Deposition and Clearance of Aerosol Generated by a Nebulizer and an Aqueous Spray Pump

Pharmaceutical Research -     

Deposition and Clearance Modeling of Inhaled Kaolin Refractory Ceramic Fibers (RCF) in Hamsters—Comparison Between Species

Abstract

A dosimetry model of refractory ceramic fibers in the hamster lung has been developed based upon the data from recent exposure and recovery experiments conducted by the Research and Consulting Company in Geneva, Switzerland. The modeling results of hamsters showed significant differences from those of an earlier study in rats regarding deposition and clearance of these fibers in the lung. Despite smaller airway size of hamsters, alveolar deposition per breathing cycle in the hamster was found to be higher than that in the rat due to the higher upper airway deposition in rats. The calculated mean deposited fiber size was found to be larger in the hamster, and there were more thin and long fibers deposited in the hamster lung. It was also found that alveolar clearance of refractory ceramic fibers was faster in the hamster. The clearance rate in the hamster did not appear to be fiber size dependent but it varied with lung burden. The higher clearance rate in the hamster resulted in a lower fiber accumulation per unit weight of lung after a long period of exposure. The results of the dosimetry model presented here may contribute to an explanation of different tumorigenic responses observed in the hamster and rat.     

热毒宁治疗流行性出血热的研究

目的 观察热毒宁注射液治疗流行性出血热的疗效及不良反应.方法 将98例流行性出血热患者随机分为两组.治疗组给予热毒宁注射液,对照组给予利巴韦林注射液.比较两组的疗效、病情转归和不良反应.结果 治疗组退热疗效明显优于对照组(x2 =6.41,P＜0.05),退热时间、少尿期时间、总病程明显缩短(t =2.356,2.071,5.125,均P＜0.05).两组均未见明显不良反应.结论 热毒宁注射液治疗流行性出血热疗效好,安全,值得推广应用.     

速效心痛气雾剂中牡丹皮的提取工艺研究

目的优选速效心痛气雾剂中牡丹皮的提取精制工艺.方法以芍药苷的提取率为指标,比较了不同提取方法对牡丹皮提取效率的影响,并探讨了不同的精制方法.结果牡丹皮的提取冷浸法优于渗漉法.结论该工艺提取有效成分多,适于实际生产.