166 results found
Calderon L, Han TT, McGilvery CM, et al., 2017, Release of airborne particles and Ag and Zn compounds from nanotechnology-enabled consumer sprays: Implications for inhalation exposure, ATMOSPHERIC ENVIRONMENT, Vol: 155, Pages: 85-96, ISSN: 1352-2310
Chung KF, Seiffert J, Chen S, et al., 2017, Inactivation, Clearance, and Functional Effects of Lung-Instilled Short and Long Silver Nanowires in Rats, ACS NANO, Vol: 11, Pages: 2652-2664, ISSN: 1936-0851
Conforti F, Davies ER, Calderwood CJ, et al., 2017, The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis., Oncotarget
Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials. The anti-fibrotic effects of romidepsin were evaluated both in vitro and in vivo together with any harmful effect on alveolar type II cells (ATII). Bronchoalveolar lavage fluid (BALF) from IPF or control donors was analyzed for the presence of lysyl oxidase (LOX). In parallel with an increase in histone acetylation, romidepsin potently inhibited fibroblast proliferation, myofibroblast differentiation and LOX expression. ATII cell numbers and their lamellar bodies were unaffected. In vivo, romidepsin inhibited bleomycin-induced pulmonary fibrosis in association with suppression of LOX expression. LOX was significantly elevated in BALF of IPF patients compared to controls. These data show the anti-fibrotic effects of romidepsin, supporting its potential use as novel treatment for IPF with LOX as a companion biomarker for evaluation of early on-target effects.
Mohamed NA, Davies RP, Lickliss PD, et al., 2017, Chemical and biological assessment of metal organic frameworks (MOFs) in pulmonary cells and in an acute in vivo model: relevance to pulmonary arterial hypertension therapy., Pulm Circ, ISSN: 2045-8932
Robinson RK, Birrell MA, Adcock JJ, et al., 2017, Mechanistic link between diesel exhaust particles and respiratory reflexes., J Allergy Clin Immunol
BACKGROUND: Diesel exhaust particles (DEPs) are a major component of particulate matter in Europe's largest cities, and epidemiologic evidence links exposure with respiratory symptoms and asthma exacerbations. Respiratory reflexes are responsible for symptoms and are regulated by vagal afferent nerves, which innervate the airway. It is not known how DEP exposure activates airway afferents to elicit symptoms, such as cough and bronchospasm. OBJECTIVE: We sought to identify the mechanisms involved in activation of airway sensory afferents by DEPs. METHODS: In this study we use in vitro and in vivo electrophysiologic techniques, including a unique model that assesses depolarization (a marker of sensory nerve activation) of human vagus. RESULTS: We demonstrate a direct interaction between DEP and airway C-fiber afferents. In anesthetized guinea pigs intratracheal administration of DEPs activated airway C-fibers. The organic extract (DEP-OE) and not the cleaned particles evoked depolarization of guinea pig and human vagus, and this was inhibited by a transient receptor potential ankyrin-1 antagonist and the antioxidant N-acetyl cysteine. Polycyclic aromatic hydrocarbons, major constituents of DEPs, were implicated in this process through activation of the aryl hydrocarbon receptor and subsequent mitochondrial reactive oxygen species production, which is known to activate transient receptor potential ankyrin-1 on nociceptive C-fibers. CONCLUSIONS: This study provides the first mechanistic insights into how exposure to urban air pollution leads to activation of guinea pig and human sensory nerves, which are responsible for respiratory symptoms. Mechanistic information will enable the development of appropriate therapeutic interventions and mitigation strategies for those susceptible subjects who are most at risk.
Smyth E, Solomon A, Birrell MA, et al., 2017, Influence of inflammation and nitric oxide upon platelet aggregation following deposition of diesel exhaust particles in the airways., Br J Pharmacol
BACKGROUND AND PURPOSE: Exposure to nanoparticulate pollution has been implicated in platelet-driven thrombotic events such as myocardial infarction. Inflammation and impairment of NO bioavailability have been proposed as potential causative mechanisms. It is unclear, however, whether airways exposure to combustion-derived nanoparticles such as diesel exhaust particles (DEP) or carbon black (CB) can augment platelet aggregation in vivo and the underlying mechanisms remain undefined. We aimed to investigate the effects of acute lung exposure to DEP and CB on platelet activation and the associated role of inflammation and endothelial-derived NO. EXPERIMENTAL APPROACH: DEP and CB were intratracheally instilled into wild-type (WT) and eNOS(-/-) mice and platelet aggregation was assessed in vivo using an established model of radio-labelled platelet thromboembolism. The underlying mechanisms were investigated by measuring inflammatory markers, NO metabolites and light transmission aggregometry. KEY RESULTS: Platelet aggregation in vivo was significantly enhanced in WT and eNOS(-/-) mice following acute airways exposure to DEP but not CB. CB exposure, but not DEP, was associated with significant increases in pulmonary neutrophils and IL-6 levels in the bronchoalveolar lavage fluid and plasma of WT mice. Neither DEP nor CB affected plasma nitrate/nitrite concentration and DEP-induced human platelet aggregation was inhibited by an NO donor. CONCLUSIONS AND IMPLICATIONS: Pulmonary exposure to DEP and subsequent platelet activation may contribute to the reports of increased cardiovascular risk, associated with exposure to airborne pollution, independent of its effects on inflammation or NO bioavailability.
Botelho DJ, Leo BF, Massa CB, et al., 2016, Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity, NANOTOXICOLOGY, Vol: 10, Pages: 118-127, ISSN: 1743-5390
Chen S, Goode AE, Skepper JN, et al., 2016, Avoiding artefacts during electron microscopy of silver nanomaterials exposed to biological environments, JOURNAL OF MICROSCOPY, Vol: 261, Pages: 157-166, ISSN: 0022-2720
Robinson RK, Birrell MA, Wortley MA, et al., 2016, Diesel Activates Airway Sensory Nerves To Initiate Respiratory Symptoms, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Ruenraromgsak P, Chen S, Hu S, et al., 2016, Translocation of Functionalized Multi-Walled Carbon Nanotubes across Human Pulmonary Alveolar Epithelium: Dominant Role of Epithelial Type 1 Cells, ACS NANO, Vol: 10, Pages: 5070-5085, ISSN: 1936-0851
Sarkar S, Carranza C, Theodorou I, et al., 2016, Impact of Silver and Carbon Nanoparticle Exposures on Macrophage Responses to Mycobacterium tuberculosis (M.tb), Annual Meeting of the American-Association-of-Immunologists (AAI), Publisher: AMER ASSOC IMMUNOLOGISTS, ISSN: 0022-1767
Seiffert J, Buckley A, Leo B, et al., 2016, Pulmonary effects of inhalation of spark-generated silver nanoparticles in Brown-Norway and Sprague-Dawley rats, RESPIRATORY RESEARCH, Vol: 17, ISSN: 1465-993X
Serrano-Mollar A, Gay-Jordi G, Guillamat-Prats R, et al., 2016, Safety and Tolerability of Alveolar Type II Cell Transplantation in Idiopathic Pulmonary Fibrosis, CHEST, Vol: 150, Pages: 533-543, ISSN: 0012-3692
Sweeney S, Hu S, Ruenraroengsak P, et al., 2016, Carboxylation of multiwalled carbon nanotubes reduces their toxicity in primary human alveolar macrophages, ENVIRONMENTAL SCIENCE-NANO, Vol: 3, Pages: 1340-1350, ISSN: 2051-8153
Sweeney S, Leo BF, Chen S, et al., 2016, Pulmonary surfactant mitigates silver nanoparticle toxicity in human alveolar type-I-like epithelial cells, COLLOIDS AND SURFACES B-BIOINTERFACES, Vol: 145, Pages: 167-175, ISSN: 0927-7765
Theodorou IG, Ruenraroengsak P, Gow A, et al., 2016, Effect of pulmonary surfactant on the dissolution, stability and uptake of zinc oxide nanowires by human respiratory epithelial cells, NANOTOXICOLOGY, Vol: 10, Pages: 1351-1362, ISSN: 1743-5390
Zhang JJ, Lee K-B, He L, et al., 2016, Effects of a nanoceria fuel additive on the physicochemical properties of diesel exhaust particles, ENVIRONMENTAL SCIENCE-PROCESSES & IMPACTS, Vol: 18, Pages: 1333-1342, ISSN: 2050-7887
Botelho D, Shaffer M, Porter A, et al., 2015, Lung Lining Interaction Determines the Fate of Multi-Walled Carbon Nanotubes (MWCNTs) in vivo, Experimental Biology Meeting, Publisher: FEDERATION AMER SOC EXP BIOL, ISSN: 0892-6638
Cryer AM, Ruenraroengsak P, Tetley TD, et al., 2015, SYNTHESIS OF GOLD-BASED NANOMEDICINES TO TREAT NON-SMALL CELL LUNG CANCER, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A58-A59, ISSN: 0040-6376
Marchetti M, Shaffer MSP, Zambianchi M, et al., 2015, Adsorption of surfactant protein D from human respiratory secretions by carbon nanotubes and polystyrene nanoparticles depends on nanomaterial surface modification and size, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 370, ISSN: 0962-8436
McKenzie Z, Kendall M, Mackay R-M, et al., 2015, Nanoparticles modulate surfactant protein A and D mediated protection against influenza A infection in vitro, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 370, ISSN: 0962-8436
Melbourne J, Clancy A, Seiffert J, et al., 2015, An investigation of the carbon nanotube - Lipid interface and its impact upon pulmonary surfactant lipid function., Biomaterials, Vol: 55, Pages: 24-32, ISSN: 1878-5905
Multiwalled carbon nanotubes (MWCNTs) are now synthesized on a large scale, increasing the risk of occupational inhalation. However, little is known of the MWCNT-pulmonary surfactant (PS) interface and its effect on PS functionality. The Langmuir-Blodgett trough was used to evaluate the impact of MWCNTs on fundamental properties of PS lipids which influence PS function, i.e. compression resistance and maximum obtainable pressure. Changes were found to be MWCNT length-dependent. 'Short' MWCNTs (1.1 μm, SD = 0.61) penetrated the lipid film, reducing the maximum interfacial film pressure by 10 mN/m (14%) in dipalmitoylphosphatidylcholine (DPPC) and PS, at an interfacial MWCNT-PS lipid mass ratio range of 50:1 to 1:1. 'Long' commercial MWCNTs (2.1 μm, SD = 1.2) caused compression resistance at the same mass loadings. 'Very long' MWCNTs (35 μm, SD = 19) sequestered DPPC and were squeezed out of the DPPC film. High resolution transmission electron microscopy revealed that all MWCNT morphologies formed DPPC coronas with ordered arrangements. These results provide insight into how nanoparticle aspect ratio affects the interaction mechanisms with PS, in its near-native state at the air-water interface.
Mukherjee D, Porter A, Ryan M, et al., 2015, Modeling In Vivo Interactions of Engineered Nanoparticles in the Pulmonary Alveolar Lining Fluid, NANOMATERIALS, Vol: 5, Pages: 1223-1249, ISSN: 2079-4991
Nyga A, Hart A, Tetley TD, 2015, Importance of the HIF pathway in cobalt nanoparticle-induced cytotoxicity and inflammation in human macrophages, NANOTOXICOLOGY, Vol: 9, Pages: 905-917, ISSN: 1743-5390
Ruenraroengsak P, Tetley TD, 2015, Differential bioreactivity of neutral, cationic and anionic polystyrene nanoparticles with cells from the human alveolar compartment: robust response of alveolar type 1 epithelial cells, PARTICLE AND FIBRE TOXICOLOGY, Vol: 12, ISSN: 1743-8977
Sarkar S, Leo BF, Carranza C, et al., 2015, Modulation of Human Macrophage Responses to Mycobacterium tuberculosis by Silver Nanoparticles of Different Size and Surface Modification, PLOS ONE, Vol: 10, ISSN: 1932-6203
Seiffert J, Hussain F, Wiegman C, et al., 2015, Pulmonary Toxicity of Instilled Silver Nanoparticles: Influence of Size, Coating and Rat Strain, PLOS ONE, Vol: 10, ISSN: 1932-6203
Smyth E, Solomon A, Vydyanath A, et al., 2015, Induction and enhancement of platelet aggregation in vitro and in vivo by model polystyrene nanoparticles, NANOTOXICOLOGY, Vol: 9, Pages: 356-364, ISSN: 1743-5390
Sweeney S, Berhanu D, Ruenraroengsak P, et al., 2015, Nano-titanium dioxide bioreactivity with human alveolar type-I-like epithelial cells: Investigating crystalline phase as a critical determinant, NANOTOXICOLOGY, Vol: 9, Pages: 482-492, ISSN: 1743-5390
Sweeney S, Grandolfo D, Ruenraroengsak P, et al., 2015, Functional consequences for primary human alveolar macrophages following treatment with long, but not short, multiwalled carbon nanotubes, International Journal of Nanomedicine, Vol: 10, Pages: 3115-3129, ISSN: 1178-2013
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