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。     

高密度脂蛋白受体SR-BI对细胞内胆固醇外流的影响

<正>胆固醇逆向转运(RCT)是清除内源性胆固醇的重要途径,该过程指高密度脂蛋白(HDL)将多余的胆固醇从外周组织、细胞(包括泡沫细胞)通过载体血浆脂蛋白转运至肝脏,以胆酸的形式排泄或形成类固醇激素等再循环的过程。主要包括细胞胆固醇的流出、酯化及清除,而这些途径均需高密     

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。     

有机阴离子转运蛋白在外源化学物毒性中的作用

机体接触各种潜在毒性有机阴离子,包括内源性物质如激素、神经递质和细胞代谢产物;外源性化学物质如多种药物、农药和动植物毒素等。快速有效地清除其中的毒性物质是机体最好的防御方式。有机阴离子转运蛋白介导的跨上皮主动转运通常是其中的限速过程。因此,研究有机阴离子转运蛋白的种类、分布及其转运与表达调控机制具有重要的毒理学意义。     

肾脏转运蛋白的分类及其在抗生素肾脏清除的作用

大多数抗生素在体内通过肾脏排泄清除,而这一过程主要是通过肾小管表达的多种转运蛋白所产生的分泌作用实现的.本文对肾脏转运蛋白的分类、种属差异、以及可能产生的与抗生素有关的药物间相互作用进行综述.     

有机阴离子转运多肽及其对药物吸收、分布和排出的影响

药物在体内的转运正日益被认为是影响药效和药物残留的关键因素.近年来研究表明位于细胞膜上的转运蛋白在药物的吸收、分布和排出中发挥重要作用,药物在组织间的定向运动依赖于药物吸收和排出转运蛋白的协同作用.有机阴离子转运多肽(OATP)是一类药物吸收转运蛋白,在药物吸收、组织分布及其在肝、肾的清除中起重要作用.本文就近年来对OATP结构特点、生物学功能的研究进行综述.     

腹膜透析液添加丹参酮ⅡA对腹膜水清除的影响

目的 观察在腹膜透析液(PDS)中添加丹参酮ⅡA对腹膜透析(PD)患者腹膜水清除的影响.方法 78例置管3个月的PD患者随机均分为两组:试验组在PDS中添加丹参酮ⅡA注射液10 mg/2 L;对照组PDS中不加药.均行持续非卧床PD治疗.用药3周前后行标准腹膜平衡试验(PET)及Mini-PET.结果 与PD前比较,试验组用药后总水清除、自由水清除、4-h尿素氮、肌酐MTAC值均较用药前明显升高(P＜0.05),小孔水清除、葡萄糖D/D0均较用药前明显降低(P＜0.05).结论 在PDS中添加丹参酮ⅡA可以增加PD患者腹膜小分子溶质转运,并增加腹膜自由水清除及总水清除,对腹膜高转运患者作用也很明显.     

从革螨单层细胞培养物中检出和分离出血热病毒

将人工感染EHFV的格氏血厉螨和厩真历螨经紫外线照射、胰酶消化和反复清洗后,作成细胞悬液进行培养。24小时后,可见螨单层细胞贴壁良好,应用IF法见到螨细胞内有特异的荧光颗粒。将螨单层细胞培养物接种VeroE_6细胞分离出EHFV。表明革螨可能是EHF的传播媒介。     

植物药-化学药间基于有机阴离子转运多肽介导的相互作用研究进展

有机阴离子转运多肽(OATPs)是人及动物体内最重要的细胞膜吸收转运蛋白,在肝脏中有大量分布,介导多种内源性物质及临床常用药物的吸收转运,影响着药物在体内的吸收、分布和清除过程.许多植物药及其有效成分是OATPs的底物,它们对OATPs活性表现出抑制或者诱导作用,从而对OATPs介导的其他药物转运产生影响,改变药物生物利用度或产生不良反应.本文概述了基于OATPs介导的植物药-化学药物之间可能发生的相互作用研究进展.     

β淀粉样蛋白跨血脑屏障转运机制研究进展

β淀粉样蛋白(amyloid beta-peptides,Aβ)是阿尔茨海默病(Alzheimer’s disease,AD)的主要病理特征。Aβ在患者脑内的积聚由多种因素诱导,其中血脑屏障(blood-brain barrier,BBB)对于Aβ在脑内与血液之间的转运发挥关键作用,而这一转运作用是通过BBB上Aβ受体介导的。在AD患者脑内可检测到Aβ转运及相关受体表达的异常,与脑内Aβ含量的异常升高有关。对BBB结构与功能、Aβ转运相关受体的表达及其转运机制进行了综述,并对可能的脑内Aβ跨BBB清除策略进行了总结。     

Comparative efficacy of different methods of nebulising terbutaline

The efficacy of terbutaline inhaled from different aerosol systems was studied in 13 adult asthmatics. Terbutaline 1 mg was delivered from a pressurised aerosol, 1 and 4 mg were inhaled from a nebuliser, 1 mg was inhaled through a pressurised aerosol with a pear-shaped, 750 ml spacer, and 1 mg was inhaled from a nebuliser with Intermittent Positive Pressure Ventilation (I.P.P.V.). An open, randomized, cross-over design was used. The bronchodilator effect was evaluated by recording hourly flow-volume curves and the FEV1.0 for 5 h after treatment. No significant difference in bronchodilatation was observed after inhalation of 1 mg terbutaline from different aerosol systems, except following use of the nebuliser, which required approximately four times as much terbutaline to obtain the same effect as the ordinary spray.     

Drug delivery via aerosol systems: concept of "aerosol inhaled".

The mass of aerosol inhaled is primarily a function of the patient's breathing pattern and the aerosol delivery system. Once inhaled, deposition is governed by factors related to the properties of the aerosol and the individual characteristics of the patient (e.g., particle size distribution, airway geometry, and residence time). This paper will center upon the actual generation and delivery of clinical aerosols by jet nebulizers and assess variability in aerosol delivery. Because of the practical difficulties in predicting nebulizer function from first principles, it will be advocated that nebulizer function be directly measured for each clinical situation. Terms like "nebulizer output", "efficiency", etc. are to be avoided. The following definition is proposed: "aerosol inhaled" represents that quantity of drug actually delivered by a given nebulizer for a defined breathing pattern and period of time. The concept of "aerosol inhaled" allows a direct comparison of the quantity of drug delivered by different nebulizer systems and adjustment of dose of a given therapeutic agent. Bench testing of aerosol systems and measurement of "aerosol inhaled" can be made in the laboratory if careful attention is paid to the relationship between laboratory conditions and actual use, including the particle distribution and the accuracy of a radiolabel in estimating the quantity of drug nebulized.     

Pulmonary elimination rate of inhaled 99mTc-sestamibi radioaerosol is delayed in healthy cigarette smokers

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Very little is known about the physiology of P-glycoprotein (P-gp) expression in the lungs.
•  Ex vivo evidence based on resected lung tissue suggests that pulmonary P-gp is upregulated by cigarette smoke, but there are no in vivo studies to date.
WHAT THIS STUDY ADDS
• The novel observation that healthy cigarette smokers have a delayed pulmonary elimination rate of inhaled ^99mTc-sestamibi, a P-gp substrate, provides for the first time a potential method for quantifying functional pulmonary P-gp expression that may inform about drug therapy by inhalation as well as provide a non-invasive, quantitative, human biomarker for assessing P-gp modulators.
AIM To explore inhaled technetium-99m-labelled hexakis-methoxy-isobutyl isonitrile (^99mTc-sestamibi) for quantifying pulmonary P-glycoprotein (P-gp) expression.
METHODS The elimination rate from the lungs of ^99mTc-sestamibi was recorded scintigraphically for 30 min following inhalation as an aerosol in healthy smokers, nonsmokers and patients with lung disease.
RESULTS ^99mTc-sestamibi elimination rates [% min⁻¹ (SD; P vs. healthy nonsmokers)] were: healthy nonsmokers, 0.43 (0.083); healthy smokers, 0.19 (0.056; P  < 0.001); chronic obstructive pulmonary disease patients, 0.26 (0.077; P  < 0.001). Elimination rates in three patients with interstitial lung disease were not accelerated.
CONCLUSION Cigarette smoke upregulates lung P-gp. ^99mTc-sestamibi elimination in normal smokers could be used to test new P-gp modulators. The findings also have implications for inhaled drug delivery.     

Computerized equipment for the delivery of inhaled doses of solid particles in specific bronchial challenge.

An apparatus to generate solid particles was tested for use in diagnosing occupational asthma. This equipment measures the inhaled dose of dry particles during specific inhalation challenge. It includes an aerosol generator, a cyclone type particle size selector, and an inhalation chamber to which a patient breathing at tidal volume can be connected for the test. It is fully controlled by a standard personal computer in automatic mode, acting on the flow rate and the aerosol generator to maintain the concentration at a fixed value, usually 3 mg/m3. The dose of aerosol delivered to the patient was calculated from the aerosol concentration, and the inhaled volume was calculated by integration of the corresponding signals. The coefficient of variation for this measurement was estimated to be 12%. The mass median aerodynamic diameter (MMAD) of aerosol inside the inhalation chamber was measured for three substances: lactose, wheat flour, and buckwheat flour. The MMAD of the aerosol inside the chamber was also estimated from the particle size distribution of the raw powder. The relative difference between the measured MMAD and the calculated value was less than 15%. The corresponding relative difference between the measured geometrical SD and the calculated value was found to be less than 26%.     

Deposition of sidestream cigarette smoke in the human respiratory tract. II. Deposition of ultrafine smoke particles

Sidestream cigarette smoke was generated into an inhalation chamber from which five normal male volunteers inhaled the smoke. Size distribution of the smoke aerosol was: count median diameter, 0.11 micron, mass median diameter 0.43 micron. Deposition fraction measured as concentration difference for each size fraction between inhaled and exhaled aerosol for each size interval was: 0.075 micron, 0.24 +/- 0.04; 0.13 micron, 0.15 +/- 0.04; 0.24 micron, 0.10 +/- 0.04; and 0.42 micron, 0.07 +/- 0.02. The declining deposition fraction as size approaches 0.5 micron is consistent with previous theoretical and experimental data.     

Effects of equipment dead space and pediatric breathing patterns on inhaled mass of nebulized budesonide.

Inhaled mass, the quantity of aerosolized drug actually inhaled by a patient, can be estimated in vitro by using a piston pump and an inhaled mass filter in a manner that simulates in vivo aerosol delivery. For pediatric patients, measurement with an inhaled mass filter with a large equipment dead space (VDEQ) in relation to a small tidal volume (VT) may underestimate the inhaled mass. The present study investigated the impact of VDEQ on the accuracy of in vitro measured inhaled mass of budesonide suspension for nebulization using Spira Module 1 jet nebulizers (Respiratory Care Center, H?meenlinna, Finland), inhaled mass filters, VDEQs of different sizes, and pediatric breathing patterns. The VDEQ varied between 14 and 108 mL, and the breathing patterns corresponded to a VT between 50 and 500 mL, to breathing frequencies of 40 to 12 per min-1, to a duty cycle of 0.5 for all breathing patterns, and to a nebulization time of 2 minutes. The results showed that the inhaled mass was a function of the VDEQ for each breathing pattern as defined by the inspiratory minute volume (VI). For a large VT, a small VDEQ affected the inhaled mass of budesonide only marginally, but as the VDEQ increased, the measured inhaled mass decreased to the point that for a VDEQ larger than the VT, the inhaled mass was zero. When the inhaled mass was expressed as a function of an effective volume (VEFF) (i.e., VI corrected for VDEQ), the results showed a linear correlation (R2 = 0.921) between the volume of aerosol inhaled through the nebulizer and the inhaled mass of budesonide. The results of the study indicate that VDEQ has a critical effect on the measurement of inhaled mass in vitro for conventional jet nebulizers using pediatric breathing patterns. This means that the in vitro measured inhaled mass of drug can seriously underestimate the in vivo value. When pediatric breathing patterns are used in vitro, a correction of the VT by the VDEQ should be made in order to more accurately reflect the in vivo inhaled mass of drug.     

Respiration-Based Measurement of Lung Deposition of a Fluorescent Dextrane Aerosol in a Marmoset Monkey

A technique for measurement of respiration-based lung deposition of an aerosol was investigated and subsequently applied in a pilot study with a marmoset monkey. The technique consisted of an aerosol exposure system for a marmoset using a face mask and a previously constructed monkey chair, a method for recovery of fluorescent dextrane from lung material, and respiration measurement of the marmoset by whole-body plethysmography. In the pilot study, a ketamine-anesthetized marmoset was exposed for 20 min to an FITC–dextrane aerosol atmosphere (200 μg/L air, particle size 1.5 μm mass median aerodynamic diameter [MMAD]). It was found that 3.4% of the inhaled aerosol was deposited in the lungs; the aerosol was distributed over the lung lobes with an higher concentration at the distal side.     

Respiration-based measurement of lung deposition of a fluorescent dextrane aerosol in a marmoset monkey

A technique for measurement of respiration-based lung deposition of an aerosol was investigated and subsequently applied in a pilot study with a marmoset monkey. The technique consisted of an aerosol exposure system for a marmoset using a face mask and a previously constructed monkey chair, a method for recovery of fluorescent dextrane from lung material, and respiration measurement of the marmoset by whole-body plethysmography. In the pilot study, a ketamine-anesthetized marmoset was exposed for 20 min to an FITC-dextrane aerosol atmosphere (200 microg/L air, particle size 1.5 microm mass median aerodynamic diameter [MMAD]). It was found that 3.4% of the inhaled aerosol was deposited in the lungs; the aerosol was distributed over the lung lobes with an higher concentration at the distal side.     

Corrections in dose assessment of 99mTc radiolabeled aerosol particles targeted to central human airways using planar gamma camera imaging

The dose of inhaled radiolabeled aerosols is usually assessed using gamma (GC) camera imaging. Because of the complex and inhomogeneous structure of the lung, consisting of soft tissue, the thoracic skeleton, blood vessels, and air spaces, proper attenuation correction coefficients are difficult to evaluate and the estimated doses bear high uncertainty. One hundred milliliters of aerosol boli composed of 100 nm diameter (99m)Tc radiolabeled carbon particles (Technegas) were targeted either to the airways (AW) or to 800-mL volumetric lung depth (alveoli, AL) in 11 healthy volunteers. In addition, 750-mL full breaths (FB) of aerosol were inhaled to a 800-mL lung depth. The deposited dose was measured by collecting aerosol from inhaled and exhaled air stream on filters, which were analyzed for radioactivity. Lung imaging was performed using a planar GC (posterior). Ratios of GC counts to deposited dose (GC/DD) were similar after FB and AL administration, but twofold lower after AW administration (p < 0.01). Associated attenuation correction factors (ACF) were 2.5 +/- 0.5 (FB), 2.2 +/- 0.4 (AL), and 5.5 +/- 1.6 (AW, p < 0.01). Both GC/DD and ACF were highly correlated to the aerosol distribution index (central to peripheral ratio, C/P). After shallow bolus administration there was a negative correlation between body mass index and GC/DD. Inhalation of radioaerosols used in medical diagnosis and therapy in combination with high central airway deposition results in an underestimation of the deposited dose based on planar GC imaging. The aerosol distribution index C/P may provide one suitable indicator for corrections, which should be confirmed in future studies by individual attenuation analysis based on radiotracer transmission measurements.