Multi-walled carbon nanotube-induced inhalation toxicity: Recognizing nano bis-demethoxy curcumin analog as an ameliorating candidate

Human beings and ecosystems are being possibly exposed to CNTs, as there is a rise in global production rate of carbon nanotubes (CNTs). This may affect the health of humans and increases the environmental risk. We have already reported the pulmonary toxicity due to the inhalation of MWCNTs. We claim that a compound with anti-inflammatory and antioxidant activity may ameliorate the CNT-induced toxic effect. With this view, we have investigated the ameliorative effect of intravenously-administered nano bis-demethoxy curcumin analog (NBDMCA) against MWCNTs-induced inhalation toxicity by examining the lung histopathology for inflammatory cell dynamics, pulmonary remodeling and estimating the inflammatory biomarkers in the broncho-alveolar lavage fluid. We observed that NBDMCA could ameliorate the injury as evidenced by the decline in the levels of markers of inflammation, cell damage, and the histopathological changes induced by MWCNTs. We conclude that NBDMCA may be used to reduce the risk of MWCNTs-induced inhalation toxicity.     

支气管肺泡灌洗液中肿瘤相关物质群对肺部孤立结节鉴别诊断的意义

目的探讨血清和支气管肺泡灌洗液(BALF)中肿瘤相关物质群(TSGF)对周围型肺部孤立结节(SPN)良恶性鉴别诊断的价值。方法对40例周围型SPN患者行血清和健患双侧支气管肺泡灌洗液TSGF、CEA检测并与40例良性病变进行对照。结果恶性SPN患者血清和健患双侧支气管肺泡灌洗液TSGF、CEA均高于良性患者及对照组，恶性SPN组患侧支气管肺泡灌洗液TSGF、CEA检测值亦高于健侧，患侧BALF中TSGF测定对恶性SPN诊断的特异性达100％，亦高于CEA的73.3％及血清TSGF的86．7％。结论支气管肺泡灌洗液及血清TSGF测定对周围型SPN的良恶性鉴别诊断有一定的价值，尤其健患双侧BALF中TSGF检测对肿瘤有一定的定位诊断作用。     

虚证慢性支气管炎不同中医证型支气管肺泡灌洗液中免疫相关指标的比较研究

目的:探索虚证慢性支气管炎各证型组现代医学检测指标结果与证型的相关性,以及证型轻重的相关指标的动态变化,为临床中医辨证分型提供试验依据。方法:对136例慢性支气管炎患者进行中医辨证分型,并对上述患者进行支气管肺泡灌洗液(BALF)免疫相关指标的观察。结果:各证型组支气管肺泡灌洗液的免疫相关指标结果存在显著性差异。结论:随着证型的逐渐加重,患者机体局部及全身免疫功能逐渐下降,其指标结果与证型的动态变化呈正相关性。     

Experimental hypersensitivity pneumonitis: role of MCP-1

Inhalation of Saccharopolyspora rectivirgula causes "farmer's lung" disease, a classic example of hypersensitivity pneumonitis (HP). Monocyte chemoattractant protein-1 (MCP-1) is increased in the bronchoalveolar lavage fluid of mice challenged with S rectivirgula, and S rectivirgula induces MCP-1 secretion by alveolar macrophages. We tested the hypothesis that MCP-1 and its receptor CC chemokine receptor-2 (CCR2) are essential to the development of experimental HP by treating mice with MCP-1 antibody and using CCR2(-/-) mice. Administration of anti-MCP-1 did not change the response to intratracheally administered S rectivirgula. CCR2(-/-) animals responded in a fashion similar to that of wild-type animals to intratracheally administered.S rectivirgula. To determine the influence of the MCP-1-CCR2 interaction in vitro, we transferred S rectivirgula-cultured spleen cells from S rectivirgula-sensitized mice, to na?ve recipients. Later, challenge of the recipients with intratracheal S rectivirgula and examination of both lung histology and bronchoalveolar lavage fluid characteristics were used to determine whether adoptive transfer had occurred. We found that cultured cells from CCR2(-/-) animals were fully capable of adoptive transfer. We conclude that interaction of MCP-1 with CCR2 is not necessary for the development of pulmonary inflammation in response to intratracheally administered S rectivirgula or cells able to adoptively transfer experimental HP.     

The effect of the decoy molecule PA401 on CXCL8 levels in bronchoalveolar lavage fluid of patients with cystic fibrosis

Background

The chemokine interleukin-8 (CXCL8) is a key mediator of inflammation in airways of patients with cystic fibrosis (CF). Glycosaminoglycans (GAGs) possess the ability to influence the chemokine profile of the CF lung by binding CXCL8 and protecting it from proteolytic degradation. CXCL8 is maintained in an active state by this glycan interaction thus increasing infiltration of immune cells such as neutrophils into the lungs. As the CXCL8-based decoy PA401 displays no chemotactic activity, yet demonstrates glycan binding affinity, the aim of this study was to investigate the anti-inflammatory effect of PA401 on CXCL8 levels, and activity, in CF airway samples in vitro.

Methods

Bronchoalveolar lavage fluid (BALF) was collected from patients with CF homozygous for the ΔF508 mutation (n = 13). CXCL8 in CF BALF pre and post exposure to PA401 was quantified by ELISA. Western blot analysis was used to determine PA401 degradation in CF BALF. The ex vivo chemotactic activity of purified neutrophils in response to CF airway secretions was evaluated post exposure to PA401 by use of a Boyden chamber-based motility assay.

Results

Exposure of CF BALF to increasing concentrations of PA401 (50–1000 pg/ml) over a time course of 2–12 h in vitro, significantly reduced the level of detectable CXCL8 (P < 0.05). Interestingly, PA401 engendered release of CXCL8 from GAGs exposing the chemokine susceptible to proteolysis. Subsequently, a loss of PA401 was observed (P < 0.05) due to proteolytic degradation by elastase like proteases. A 25% decrease in neutrophil chemotactic efficiency towards CF BALF samples incubated with PA401 was also observed (P < 0.05).

Conclusion

PA401 can disrupt CXCL8:GAG complexes, rendering the chemokine susceptible to proteolytic degradation. Clinical application of a CXCL8 decoy, such as PA401, may serve to decrease the inflammatory burden in the CF lung in vivo.     

染矽尘大鼠BALF中炎性细胞改变研究

[目的]探讨不同染尘剂量大鼠矽肺模型支气管肺泡灌洗液(BALF)中炎性细胞的变化规律,为矽肺的发病机制提供可靠依据。[方法]2009年5～8月采用一次性气管内灌注二氧化硅(SiO2)粉尘的方法制作大鼠矽肺模型。大鼠随机分为对照组和模型组(15、30、60mg/ml),分别在1、3、7、14、21、28d将大鼠处死,采用在体全肺灌洗法收集BALF,光学显微镜下计数白细胞总数,瑞士吉姆萨染色法进行白细胞分类计数。[结果]模型组大鼠BALF中白细胞总数在大鼠染尘1、3、21、28d较对照组均增高,其中高剂量组和中剂量组较对照组差异有统计学意义(P<0.05);在7、14d仅高剂量组较对照组差异有统计学意义(P<0.05)。各剂量组在大鼠染尘1、3、7、14、21、28d,巨噬细胞、中性粒细胞和淋巴细胞均较对照组增高,巨噬细胞在染尘1、3、7、21、28d均增高;中性粒细胞在1～14d显著增高(P<0.05),淋巴细胞在7～28d明显增高(P<0.05);各剂量组在染尘1、3、7、14、21、28d尘细胞数均增高。[结论]染尘大鼠早期主要表现为炎症反应,炎症细胞(巨噬细胞、中性粒细胞、淋巴细胞和尘细胞)呈规律变化,且尘细胞具有较好的剂量-反应关系,对矽肺的预防和早期诊断具有很大的意义。