Abstract:
:Antisense oligonucleotides (ASOs) bind and facilitate degradation of RNA and inhibit protein expression in pathways not easily targeted with small molecules or antibodies. Interleukin (IL)-4 and IL-13 potentiate signaling through the shared IL-4 receptor-α (IL-4Rα) subunit of their receptors. ASO targeting of IL-4Rα mRNA in a mouse model of asthma led to attenuation of airway hyperactivity, demonstrating potential benefit in asthma patients. This study focused on tolerability of inhaled IL-4Rα-targeting ASOs. Toxicity studies were performed with mouse- (ISIS 23189) and human-specific (ISIS 369645) sequences administered by inhalation. Four week (monkey) or 13 week (mouse) repeat doses at levels of up to 15 mg/kg/exposure (exp) and 50 mg/kg/exp, respectively, demonstrated dose-dependent effects limited to increases in macrophage size and number in lung and tracheobronchial lymph nodes. The changes were largely non-specific, reflecting adaptive responses that occur during active exposure and deposition of ASO and other material in the lung. Reversibility was observed at a rate consistent with the kinetics of tissue clearance of ASO. Systemic bioavailability was minimal, and no systemic toxicity was observed at exposure levels appreciably above pharmacological doses and doses proposed for clinical trials.
journal_name
Inhal Toxicoljournal_title
Inhalation toxicologyauthors
Fey RA,Templin MV,McDonald JD,Yu RZ,Hutt JA,Gigliotti AP,Henry SP,Reed MDdoi
10.3109/08958378.2014.907587subject
Has Abstractpub_date
2014-07-01 00:00:00pages
452-63issue
8eissn
0895-8378issn
1091-7691journal_volume
26pub_type
杂志文章abstract::To elucidate dose-response and other effects of diesel particles in guinea pigs chronically exposed to diesel exhaust, various biomarkers for chronic obstructive lung diseases were studied using bronchoalveolar lavage (BAL) fluid and blood specimens. Guinea pigs were exposed 16 h/day, 6 days/wk, for 6, 12, 18, or 24 m...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370290084773
更新日期:2002-10-01 00:00:00
abstract::Species differences in the handling of particles are topics of interest for setting ambient particulate matter standards as well as for studies involving the phenomenon of lung overload and the implications, if any, of such studies for workplace dust exposure standards. The dosimetry of inhaled particles differs among...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958378.2000.11463250
更新日期:2000-01-01 00:00:00
abstract::This paper summarizes available data on worker exposures to asphalt fume (soluble fraction), total particulate matter, and respirable crystalline silica (quartz) [hereinafter RCS] over a 30-year period in Owens Corning's asphalt production and roofing manufacturing plants. For the period 1977 through 2006, the air-mon...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.3109/08958378.2011.604107
更新日期:2011-09-01 00:00:00
abstract::With growing evidence of the association between daily mortality and air pollution in adults, it is important to investigate whether infants are also susceptible to the adverse health effects of ambient air pollutants. The purpose of this study is to examine the relationship between air pollution and postneonatal mort...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370500434214
更新日期:2006-03-01 00:00:00
abstract:CONTEXT:Sulfur mustard (SM) causes skin blistering and long-term pulmonary dysfunction. Its adverse effects have been studied in battlefield-exposed humans, but lack of knowledge regarding confounding factors makes interpretation challenging. Animal studies are critical to understanding mechanisms, but differences betw...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.3109/08958378.2010.493901
更新日期:2010-09-01 00:00:00
abstract::NASA is planning to build a habitat on the Moon and use the Moon as a stepping stone to Mars. JSC-1, an Arizona volcanic ash that has mineral properties similar to those of lunar soil, is used to produce lunar environments for instrument and equipment testing. NASA is concerned about potential health risks to workers ...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370701821219
更新日期:2008-01-01 00:00:00
abstract::It is well documented that inhalation of sulfur mustard causes injury of the respiratory system. While all of the reports and surveys thoroughly document long-term pulmonary effects after significant exposure to mustard, there is no direct evidence that addresses the issue of long-term respiratory effects in individua...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370490442421
更新日期:2004-07-01 00:00:00
abstract:CONTEXT:Ambient particulate matter (PM) is associated with acute exacerbations of airflow obstruction. Additionally, elderly individuals are more susceptible to increased functional morbidity following acute PM exposure. OBJECTIVE:The purpose of this study is to determine the aging effects of PM exposure on the respon...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.3109/08958378.2012.731436
更新日期:2012-12-01 00:00:00
abstract::This study was designed to investigate effects of sulfur dioxide (SO(2)) and its derivatives (bisulfite and sulfite) on the rat blood pressure. The blood pressures of male Wistar rats exposed to SO(2) and its derivatives at various doses were measured. Findings were that: (1) with acute-one time exposure to SO(2) for ...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370390215785
更新日期:2003-08-01 00:00:00
abstract::Increased levels of C-reactive protein (CRP) and heat-shock protein-70 (Hsp70) in plasma are known to be associated with an increased risk of cardiovascular disease. In this study we have investigated the effects of environmental air pollution particles (PM10) and ultrafine carbon black (ufCB) on the expression of CRP...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370490439614
更新日期:2004-06-01 00:00:00
abstract:BACKGROUND:Gastroesophageal reflux of bile acids plays an important role in the development of Barrett's esophagus (BE)-associated esophageal adenocarcinoma (EAC). Cigarette smoke has been demonstrated to exacerbate the effects of reflux and thus the initial stages of EAC carcinogenesis. To date, no in vivo studies hav...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.3109/08958378.2011.568977
更新日期:2011-04-01 00:00:00
abstract::Measurement strategies as well as results from measurements at workplaces are presented. Measurements were performed in research laboratories as well as by companies producing small amounts of nanostructured materials. The work was done in the frame of a BAuA (Bundesanstalt für Arbeitsschutz und Arbeitsmedizin) resear...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370902962317
更新日期:2009-07-01 00:00:00
abstract::Mexico City children are chronically exposed to significant concentrations of air pollutants and exhibit chronic respiratory-tract inflammation. Epidemiological, controlled human exposures, laboratory-based animal models, and in vitro/in vivo studies have shown that inflammatory, endothelial dysfunction, and endotheli...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370701864797
更新日期:2008-03-01 00:00:00
abstract::Inhalation exposure systems are necessary tools for determining the dose-response relationship of inhaled toxicants under a variety of exposure conditions. The objective of this project was to develop an automated computer controlled system to expose small laboratory animals to precise concentrations of airborne multi...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370802712713
更新日期:2009-10-01 00:00:00
abstract::Concurrent exposure to SO(2) and benzo(a)pyrene (B(a)P) resulted in an increased incidence of lung tumors in rodents compared to exposure to B(a)P alone. A synergistic effect on the expression of c-fos and c-jun between SO(2) and B(a)P was observed in lungs after SO(2) and B(a)P exposure. However, tumorigenesis occurs...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.3109/08958370903341891
更新日期:2010-03-01 00:00:00
abstract::Pulmonary tissue injury and repair processes involve complex and coordinated cellular events such as necrosis, inflammation, cell growth/differentiation, apoptosis, and remodeling of extracellular matrix. These processes are regulated by expression of multiple mediator genes. Commercially available microarray blots an...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370050198566
更新日期:2000-12-01 00:00:00
abstract::The lung toxicity of inhalable polymer materials is normally carried out by evaluation of the histopathology responses of rat lungs to repeat, nose-only, exposures of an inhalable aerosol of material in a 13-wk subchronic repeat dose toxicity study. The introduction of transcriptomics into toxicology has allowed the c...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370500444304
更新日期:2006-04-01 00:00:00
abstract::The C9 alkylbenzenes, composed mostly of ethyltoluenes and trimethylbenzenes, comprise 75-90% of the naphtha fraction of crude oil. Occupational and environmental exposure to C9 alkylbenzenes occur via inhalation. We conducted short-term inhalation studies on the ethyltoluene isomers (2-, 3- or 4-) to select one isome...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958378.2018.1430190
更新日期:2017-01-01 00:00:00
abstract:CONTEXT:There have been no animal studies of the health effects of repeated inhalation of mixtures representing downwind pollution from coal combustion. Environmental exposures typically follow atmospheric processing and mixing with pollutants from other sources. OBJECTIVE:This was the fourth study by the National Env...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.3109/08958378.2011.572932
更新日期:2011-05-01 00:00:00
abstract::Objective: To develop a physiologically based pharmacokinetic (PBPK) model for chloroprene in the mouse, rat and human, relying only on in vitro data to estimate tissue metabolism rates and partitioning, and to apply the model to calculate an inhalation unit risk (IUR) for chloroprene.Materials and methods: Female B6C...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958378.2020.1715513
更新日期:2019-01-01 00:00:00
abstract::This article addresses the importance of blood pressure as a covariate in studies of long-term associations between air quality and mortality. We focus on a cohort of about 50,000 U.S. veterans who had been diagnosed as hypertensive at some time and whose survival rates were predicted by blood pressure (BP) and ambien...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370304463
更新日期:2003-04-25 00:00:00
abstract::Nonhuman primates are often the animal models of choice to study the infectivity and therapy of inhaled infectious agents. Most animal models for inhaled infectious diseases use aerosol/droplets generated by an atomization technique such as a Collison nebulizer that produces particles in the size range of 1 to 3 micro...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370802105413
更新日期:2008-09-01 00:00:00
abstract:CONTEXT:Cocoa-derived ingredients are used in cigarette tobacco. OBJECTIVE:A battery of tests was used to compare toxicity of mainstream smoke from experimental cigarettes containing different added levels of cocoa-derived ingredients. MATERIALS AND METHODS:Five cocoa-derived ingredients chocolate (CH), cocoa (COC), ...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.3109/08958378.2010.542580
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Nanoparticles are being rapidly assimilated into numerous research fields and consumer products. A concurrent increase in human exposure to such materials is expected. Magnetic nanoparticles (MNPs) possess unique and beneficial features, increasing their functionality and integrative potential. However, MNP ...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.3109/08958378.2011.592869
更新日期:2011-08-01 00:00:00
abstract::Diagnosis of an exposure to airborne toxicants can be problematic. Phosgene is used widely in industry for the production of many synthetic products, such as polyfoam rubber, plastics, and dyes. Although nearly 100% of the gas is consumed during processing, there is the potential problem of accidental or even intentio...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370390197254
更新日期:2003-06-01 00:00:00
abstract::Objectives: This follow-up study set out to evaluate the natural course and radiographic progression of silicosis among ceramic workers and describe the risk factors related with disease progression. Materials and methods: We retrospectively analyzed the data of ceramic workers with silicosis who were referred to our ...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958378.2019.1613459
更新日期:2019-02-01 00:00:00
abstract::AKR/J mice were exposed to cigarette smoke (CS) and/or lipopolysaccharide (LPS) via inhalation for 3 wk and pulmonary responses were evaluated. The objective was to explore the feasibility of coexposing LPS with cigarette smoke under a subacute exposure, as a surrogate for viral or bacterial insults, that would mimic ...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370600985784
更新日期:2007-01-01 00:00:00
abstract::Nano-sized particles (NSPs) have a diameter of less than 100 nm. When inhaled, they preferentially deposit in the deeper lung, where pulmonary surfactant covers the thin aqueous lining layer. Thus, pulmonary surfactant is the initial contact where NSPs impinge. This can lead to various consequences. For example, bindi...
journal_title:Inhalation toxicology
pub_type: 杂志文章,评审
doi:10.1080/08958370903005744
更新日期:2009-07-01 00:00:00
abstract::Elastolysis, collagenolysis and gelatinolysis are essential in the pathogenesis of tobacco smoke-induced emphysema; however, these activities have been scantily studied in emphysema secondary to woodsmoke. The aim of this study was to analyze elastolysis, collagenolysis and gelatinolysis, MMP-1, MMP-2, and MMP-9 expre...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370802419145
更新日期:2009-02-01 00:00:00
abstract::A subchronic, nose-only inhalation study compared the effects of mainstream smoke from a 1R4F research cigarette to that of a 2R4F research cigarette. Male and female rats were exposed for 1 h/day, 5 days/wk, for 13 wk to mainstream smoke at 0, 0.06, 0.20, or 0.80 mg wet total particulate matter per liter of air. Clin...
journal_title:Inhalation toxicology
pub_type: 杂志文章
doi:10.1080/08958370490271340
更新日期:2004-01-01 00:00:00