Combustion-generated nanoparticulates in the El Paso, TX, USA / Juarez, Mexico Metroplex: their comparative characterization and potential for adverse health effects.

In this paper we report on the collection of fine (PM1) and ultrafine (PM0.1), or nanoparticulate, carbonaceous materials using thermophoretic precipitation onto silicon monoxide/formvar-coated 3 mm grids which were examined in the transmission electron microscope (TEM). We characterize and compare diesel particulate matter (DPM), tire particulate matter (TPM), wood burning particulate matter, and other soot (or black carbons (BC)) along with carbon nanotube and related fullerene nanoparticle aggregates in the outdoor air, as well as carbon nanotube aggregates in the indoor air; and with reference to specific gas combustion sources. These TEM investigations include detailed microstructural and microdiffraction observations and comparisons as they relate to the aggregate morphologies as well as their component (primary) nanoparticles. We have also conducted both clinical surveys regarding asthma incidence and the use of gas cooking stoves as well as random surveys by zip code throughout the city of El Paso. In addition, we report on short term (2 day) and longer term (2 week) in vitro assays for black carbon and a commercial multiwall carbon nanotube aggregate sample using a murine macrophage cell line, which demonstrate significant cytotoxicity; comparable to a chrysotile asbestos nanoparticulate reference. The multi-wall carbon nanotube aggregate material is identical to those collected in the indoor and outdoor air, and may serve as a surrogate. Taken together with the plethora of toxic responses reported for DPM, these findings prompt concerns for airborne carbonaceous nanoparticulates in general. The implications of these preliminary findings and their potential health effects, as well as directions for related studies addressing these complex issues, will also be examined.

Cytotoxicity assessment of some carbon nanotubes and related carbon nanoparticle aggregates and the implications for anthropogenic carbon nanotube aggregates in the environment.

Nanotechnology and nanomaterials have become the new frontier world-wide over the past few years and prospects for the production and novel uses of large quantities of carbon nanotubes in particular are becoming an increasing reality. Correspondingly, the potential health risks for these and other nanoparticulate materials have been of considerable concern. Toxicological studies, while sparse, have been concerned with virtually uncharacterized, single wall carbon nanotubes, and the conclusions have been conflicting and uncertain. In this research we performed viability assays on a murine lung macrophage cell line to assess the comparative cytotoxicity of commercial, single wall carbon nanotubes (ropes) and two different multiwall carbon nanotube samples; utilizing chrysotile asbestos nanotubes and black carbon nanoaggregates as toxicity standards. These nanotube materials were completely characterized by transmission electron microscopy and observed to be aggregates ranging from 1 to 2 microm in mean diameter, with closed ends. The cytotoxicity data indicated a strong concentration relationship and toxicity for all the carbon nanotube materials relative to the asbestos nanotubes and black carbon. A commercial multiwall carbon nanotube aggregate exhibiting this significant cell response was observed to be identical in structure to multiwall carbon nanotube aggregates demonstrated to be ubiquitous in the environment, and especially in indoor environments, where natural gas or propane cooking stoves exist. Correspondingly, preliminary epidemiological data, although sparse, indicate a correlation between asthma incidence or classification, and exposure to gas stoves. These results suggest a number of novel epidemiological and etiological avenues for asthma triggers and related respiratory or other environmental health effects, especially since indoor number concentrations for multiwall carbon nanotube aggregates is at least 10 times the outdoor concentration, and virtually all gas combustion processes are variously effective sources. These results also raise concerns for manufactured carbon nanotube aggregates, and related fullerene nanoparticles.

Therapeutic efficacy of an anti-IL-5 monoclonal antibody delivered into the respiratory tract in a murine model of asthma.

BACKGROUND: IL-5 is central to the pathogenesis of airway eosinophilic inflammation and hyperresponsiveness associated with both atopic and nonatopic asthma. The therapeutic potential of IL-5 antagonists in asthma is supported by the inhibition of airway eosinophilia and hyperresponsiveness in animal models receiving neutralizing anti-IL-5 mAbs intravenously or intraperitoneally. OBJECTIVE: The purpose of this study was to test the hypothesis that mAbs against IL-5 delivered by way of the respiratory tract are as effective as those delivered intraperitoneally in diminishing the pulmonary eosinophilic inflammation and airway hyperresponsiveness in a murine model of ovalbumin-induced asthma. METHODS: Ovalbumin-sensitized Balb/c mice were given an anti-IL-5 mAb delivered intranasally or an isotype-matched control mAb delivered intranasally before respiratory challenge with ovalbumin. Outcome variables included respiratory system resistance responses to methacholine, bronchoalveolar lavage fluid cellularity, and lung histopathology. RESULTS: Anti-IL-5 mAbs administered intranasally to ovalbumin-sensitized and challenged mice significantly decreased eosinophil counts in bronchoalveolar lavage fluid and lung tissue and significantly reduced airway hyperresponsiveness relative to ovalbumin-sensitized and challenged mice that received either no mAb treatment or an isotype-matched control mAb. Similar results were obtained when an anti-IL-5 mAb was given intraperitoneally. CONCLUSION: This is the first study to demonstrate that delivery of anti-IL-5 mAbs into the respiratory tract is efficacious in attenuating the asthma phenotype in a murine model. These results provide impetus for the development of inhaled IL-5 antagonists for the treatment of human asthma.

Failure of zafirlukast to prevent ibuprofen-induced anaphylaxis.

BACKGROUND: Anaphylaxis to nonsteroidal anti-inflammatory drugs is thought to depend on cycloxygenase inhibition coupled to upregulation of 5-lipoxygenase-dependent pathways. The introduction of leukotriene-receptor antagonists afforded the opportunity to test this hypothesis. These agents provide at least partial protection against aspirin-induced anaphylaxis during controlled challenges but we did not know whether the level of protection was high enough to block symptoms from ingestion of a full dose of aspirin. METHODS: We report a patient with moderately severe asthma who experienced an episode of anaphylaxis following ingestion of 400 mg of ibuprofen while under therapy with 20 mg of zafirlukast given twice a day. RESULTS: No further episodes of anaphylaxis have been noted following institution of complete avoidance to all nonsteroidal anti-inflammatory drugs. CONCLUSIONS: Patients who are sensitive to cycloxygenase inhibitors should practice complete avoidance of these drugs even while under therapy with leukotriene modifiers.

Behçet's-like syndrome associated with idiopathic CD4+ T-lymphocytopenia, opportunistic infections, and a large population of TCR alpha beta+ CD4- CD8- T cells.

Herein we report a patient with Behçet's like syndrome, idiopathic CD4+ T-lymphocytopenia, opportunistic infections, and a large polyclonal population of TCR alpha beta + CD4- CD8- T cells. Microfluorimetric analysis of peripheral blood mononuclear cells revealed CD4+ T-cell counts of 10 +/- 5/mm3. The CD3+ T cells were 99% TCR alpha beta +, of which 74 +/- 5% were CD4- CD8-. No clonal populations were detected by southern analysis for T-cell receptor V beta gene rearrangements. No evidence of human immunodeficiency virus infection was present, although nocardia, candida, pneumocystis, cytomegalovirus, and herpes infections were documented. The concomitant presence of opportunistic infections and a large population of TCR alpha beta + CD4- CD8- T cells suggests a pathogenic association and an intense immune response to microbial lipid or lipoglycan antigens presented in the context of CD1 molecules. This case demonstrates the potential for idiopathic CD4+ T-lymphocytopenia to occur in Behçet's-like syndrome with lethal consequences.