Coagulation markers in healthy human subjects exposed to diesel exhaust

BACKGROUND: Ambient particulate matter (PM) is associated with cardiovascular morbidity and mortality. It has been proposed that PM induces a pro-thrombotic process, increasing the risk of cardiovascular events, with some support from epidemiological and laboratory-based models. Diesel exhaust is a major contributor to urban PM, and we conducted a controlled human exposure of diesel exhaust in healthy subjects. OBJECTIVE: To evaluate diesel exhaust exposure effects on fibrinolytic burden (D-dimer), platelet number, and endothelial injury (von Willebrand's factor, VWF), inhibition of the fibrinolytic pathway (plasminogen activator inhibitor-1 [PAI-1]), and inflammation (C-reactive protein, CRP). MATERIALS AND METHODS: Randomized, crossover, double-blinded design, with 13 healthy participants exposed on three different days (>or=2 weeks washout) to diesel exhaust at 0 (filtered air), 100 microg PM(2.5)/m(3) and 200 microg PM(2.5)/m(3). We assessed diesel exhaust-associated changes in D-dimer, VWF, PAI-1 and platelets at 3, 6 and 22 h, and CRP at 22 h, after exposure initiation. RESULT: Significant changes did not occur in any primary endpoints. Among secondary endpoints, diesel exhaust (200 microg PM(2.5)/m(3)) effect on PAI-1 levels at 22 h was of borderline significance, with a 1.32-fold decrease after exposure to diesel exhaust (200 microg PM(2.5)/m(3)), relative to filtered air (CI 1.00 to 1.54). Diurnal patterns in D-dimer and PAI-1 were observed. CONCLUSIONS: In healthy individuals, exposure to 200 microg PM(2.5)/m(3) diesel exhaust did not affect primary pro-thrombotic endpoints. Thus, these data do not support a diesel exhaust-induced pro-thrombotic phenomenon. Replication of these studies should be carried out to ascertain whether or not they inform our mechanistic understanding of air pollution's cardiovascular effects.     

大面积烧伤伴吸入性损伤的治疗

目的总结大面积烧伤并吸入性损伤患者的治疗经验,以探索最佳治疗方法。方法分析2004年至2007年收治的20例大面积烧伤伴吸入性损伤患者的临床资料。结果20例患者中治愈18例;死亡2例;治愈率90％。结论早诊断,早治疗,防止并发症出现,可提高此类患者的治愈率。     

糖皮质激素吸入对哮喘患儿外周血CD4+CD25+ 调节性T细胞水平的影响

目的： 探讨糖皮质激素吸入对哮喘患儿外周血CD4+CD25+ 调节性T细胞（Tr）水平的影响。方法：采用糖皮质激素吸入治疗70例发作期哮喘患儿,应用流式细胞术检测患儿外周血的Tr细胞数。结果：糖皮质激素规则治疗后患儿外周血CD4+CD25+Tr水平（7.05%±1.61%）明显高于治疗前（5.62%±1.29%）,P<0.01。完全控制组患儿外周血CD4+CD25+Tr水平最高（7.56%±1.88%）,部分控制组患儿次之（7.09%±1.23%）,控制不佳组患儿最低（6.11%±1.96%）,差异均显著,P<0.05。经激素规则治疗的患儿外周血Tr水平（7.05%±1.61%）明显高于不规则治疗组患儿（5.91%±1.76%）,P<0.01。结论：规则使用糖皮质激素吸入疗法可明显提高哮喘患儿外周血Tr水平,Tr水平与哮喘的激素治疗效果有关。     

七氟烷吸入麻醉对老年肿瘤患者认知功能的影响

目的观察七氟烷吸入麻醉对老年肿瘤患者手术后认知功能的影响,为临床合理选择麻醉方法和麻醉药物提供参考。方法选择2008年2月至2010年12月我院收治的老年肿瘤手术患者126例,随机分为对照组和观察组各63例。对照组患者麻醉诱导后静脉靶控输注2～4μg/ml丙泊酚维持麻醉,观察组患者麻醉诱导后给予吸入1.0%～3.0%七氟烷维持麻醉。麻醉深度维持脑电双频指数(BIS)45～55;血压、心率控制在基础值的±20%以内。观察患者麻醉恢复过程,于麻醉前、应答后1 h、3 h、6 h、24 h采用简易精神状态量表(MMSE)评价患者的认知功能。结果两组患者应答后1 h、3 h时MMSE评分较麻醉前明显降低,差异有统计学意义(P<0.05);对照组患者应答后6h时MMSE评分与麻醉前MMSE评分比较,差异无统计学意义(P>0.05);观察组患者应答后6h时MMSE评分明显低于麻醉前MMSE评分,差异有统计学意义(P<0.05);两组患者应答后24 h时MMSE评分与麻醉前MMSE评分比较,差异无统计学意义(P>0.05)。提示对照组患者认知功能术后6 h时恢复至麻醉前水平;观察组术后24 h时恢复至麻醉前水平。结论丙泊酚静脉麻醉和七氟烷吸入麻醉均可引起老年肿瘤患者术后短期认知功能下降,并具有可逆性。七氟烷吸入麻醉患者认知功能的恢复时间较丙泊酚长。     

Dry powder inhalations containing thymopentin and its immunomodulating effects in Wistar rats

Thymopentin (TP5), a synthetic pentapeptide, has been used in clinic as a modulator for immunodeficiences through intramuscular administration. The purpose of this study was to design and evaluate dry powder inhalations (DPIs) for pulmonary delivery of TP5. Dry powder inhalations containing leucine (a dispersibility enhancer), mannitol, and lactose (bulking agents) were prepared by spray-drying from aqueous formulations. The formulation components on the aerosolisation characteristics of spray-dried powders were investigated through the use of various amount of leucine, lactose and mannitol. Following spray-drying, resultant powders were characterized using scanning electron microscopy, laser diffraction and tapped density measurements, and the aerosolisation performance was determined using Twin Stage Impinger. The immunosuppression Wistar rats model was constructed to evaluate the immunomodulating effects of TP5 DPIs in vivo. The results of T-lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+ ratio) analyses suggest that TP5 DPIs have modulating effects. On an overall evaluation, TP5 pulmonary delivery DPIs may be feasible for the future clinical application.     

Lipid nanocapsules: Ready-to-use nanovectors for the aerosol delivery of paclitaxel

Aerosol drug delivery permits the development of dose-intensification strategies in severe, malignant lung diseases. The aim of the study was to demonstrate that the encapsulation of paclitaxel in lipid nanocapsules (LNCs), a novel drug nanocarrier for lipophilic components, allows one to provide pulmonary drug delivery of paclitaxel by nebulisation, thereby allowing preclinical and clinical studies. LNC dispersions are made into aerosols with commercial nebulisers. The structure, drug payload and cytotoxicity of nebulised LNCs were compared to fresh LNCs. The results demonstrated that LNC dispersions could be made into aerosols by using mesh nebulisers without altering the LNC structure. Only eFlow^® rapid-produced aerosols are compatible with human use: the mean duration to nebulise 3 ml of LNC dispersion is less than 9 min, with an aerosol mass median aerodynamic diameter equal to 2.7 ± 0.1 μm and a fine-particle fraction (between 1.0 and 5.0 μm) of 81.5 ± 3.1%. No modifications of drug payload or cytotoxicity effects of paclitaxel-loaded LNC (PTX–LNC) were observed. In order to carry out preclinical studies, a scaled-up LNC formulation protocol was used. Chemical parameters, such as acidity and osmolarity, were optimised, and a storage procedure for PTX–LNC batches was set-up. Animal studies are now needed to determine the tolerance and therapeutic potential of LNC dispersion aerosols.     

Plasma and tissue vitamin E depletion in sheep with burn and smoke inhalation injury

Oxidants are involved in the pathogenesis of many disorders caused by burn and smoke inhalation; α- and γ-tocopherols are major tissue antioxidants, and their depletion should reflect oxidant injury. To determine whether plasma and tissue vitamin E levels would thus be depleted in severe burn, prepared sheep were randomly divided into the following groups: non-injured, burn- and smoke-exposed, burned only and smoke-exposed only. All were resuscitated with Ringer's lactate solution, mechanically ventilated and sacrificed at various time intervals. Immediately following injury plasma, lung, trachea, heart and liver tocopherols/lipids were measured and found to be significantly depleted except in the heart. Reduction of tissue γ-tocopherol appeared earlier than reduction of α-tocopherol. Thus animals receiving combined burn and inhalation injury underwent marked oxidative stress, suggesting that vitamin E might be depleted also in humans with burn and smoke inhalation injury, and that appropriate supplementation should be evaluated.     

DETECTION OF POLY(ADP-RIBOSE) SYNTHETASE ACTIVITY IN ALVEOLAR MACROPHAGES OF RATS EXPOSED TO NITROGEN DIOXIDE AND OZONE

The toxic effects of nitrogen dioxide (NO₂) and ozone (O₃) are mediated through the formation of free radicals, which can cause DNA strand breaks. The present study demonstrates that exposure to NO₂ and O₃ causes a stimulation of poly (ADP-ribose) (poly ADPR) synthetase in alveolar macrophages of rats. Three-month-old male Sprague-Dawley rats, specific pathogen free, were exposed to either 1.2 ppm NO₂ or 0.3 ppm O₃ alone or a combination of these 2 oxidants continuously for 3 days. The control group was exposed to filtered room air. To evaluate whether exposure to these two oxidants (NO₂ and O₃) caused DNA damage to lung cells, the activity of poly ADPR synthetase was measured. Cellular DNA repair is dependent upon the formation of poly (ADP-ribose) polymerase, which is catalyzed by poly ADPR synthetase. Poly ADPR synthetase is known to be activated in response of DNA damage. The results showed that the enzyme activity was stimulated after exposure to O₃ or exposure to NO₂ + O₃. Ozone exposure caused a 25% increase in the enzyme activity as compared to the control. Combined exposure to NO₂ + O₃ showed a 53% increase in the enzyme activity. These results were statistically significant as compared to the control and NO₂ exposure groups. Other parameters such as total cell count, cell viability, and differential cell count were also determined. The stimulation of poly ADPR synthetase activity after O₃ exposure or NO₂ + O₃ exposure reflects a response to lung cellular DNA repair, which may be used as an indicator for assessing DNA damage caused by oxidant injury.     

普米克令舒吸入佐治小儿毛细支气管炎疗效观察

目的探讨普米克令舒雾化吸入佐治小儿毛细支气管炎(毛支)的疗效.方法将54例毛支患儿随机分为两组,两组均采用综合治疗,观察组加用普米克令舒雾化吸入,对治疗前后症状、体征持续时间、气道阻力参数进行比较.结果观察组在治愈率、缓解喘憋、缩短哮鸣音及咳嗽持续时间、改善肺功能、降低气道阻力的作用均明显优于对照组(P＜0.05).结论普米克令舒雾化吸入治疗小儿毛支,可缩短病程,改善肺功能,疗效确切,且方便、安全,可作为佐治毛支的主要药物.     

儿童哮喘糖皮质激素吸入依从性观察

目的：观察儿童哮喘长期吸入糖皮质激素的依从性。方法：收治哮喘患儿168例，给予糖皮质激素吸入治疗，通过电话、短信、复诊、问卷调查形式，记录不依从原因。结果：168例患儿中不依从65例（38．69％），其主要原因：家长害怕激素不良反应28例（43．08％）；自行中断15例（23．08％）；吸入方法不当14例（21．54％）；不合作6例（9．23％）；因经济原因2例（3．08％）。结论：儿童哮喘长期吸入糖皮质激素依从性不高，是哮喘控制不理想的主要原因。