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1.
Chemosphere ; 362: 142621, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38880256

RESUMEN

BACKGROUND: Biodiesel, a renewable diesel fuel that can be created from almost any natural fat or oil, is promoted as a greener and healthier alternative to commercial mineral diesel without the supporting experimental data to back these claims. The aim of this research was to assess the health effects of acute exposure to two types of biodiesel exhaust, or mineral diesel exhaust or air as a control in mice. Male BALB/c mice were exposed for 2-hrs to diluted exhaust obtained from a diesel engine running on mineral diesel, Tallow biodiesel or Canola biodiesel. A room air exposure group was used as a control. Twenty-four hours after exposure, a variety of respiratory related end point measurements were assessed, including lung function, responsiveness to methacholine and airway and systemic immune responses. RESULTS: Tallow biodiesel exhaust exposure resulted in the greatest number of significant effects compared to Air controls, including increased airway hyperresponsiveness (178.1 ± 31.3% increase from saline for Tallow biodiesel exhaust exposed mice compared to 155.8 ± 19.1 for Air control), increased airway inflammation (63463 ± 13497 cells/mL in the bronchoalveolar lavage of Tallow biodiesel exhaust exposed mice compared to 40561 ± 11800 for Air exposed controls) and indications of immune dysregulation. In contrast, exposure to Canola biodiesel exhaust resulted in fewer significant effects compared to Air controls with a slight increase in airway resistance at functional residual capacity and indications of immune dysregulation. Exposure to mineral diesel exhaust resulted in significant effects between that of the two biodiesels with increased airway hyperresponsiveness and indications of immune dysregulation. CONCLUSION: These data show that a single, brief exposure to biodiesel exhaust can result in negative health impacts in a mouse model, and that the biological effects of exposure change depending on the feedstock used to make the biodiesel.

2.
Exp Lung Res ; 50(1): 118-126, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38683138

RESUMEN

AIM: Treatment options for viral lung infections are currently limited. We aimed to explore the safety and efficacy of inhaled ethanol in an influenza-infection mouse model. MATERIALS AND METHODS: In a safety and tolerability experiment, 80 healthy female BALB/c mice (20 per group) were exposed to nebulized saline (control) or three concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods, with a two-hour break between exposures. In a separate subsequent experiment, 40 Female BALB/c mice were nasally inoculated with 104.5 plaque-forming units of immediate virulence "Mem71" influenza. Infection was established for 48-h before commencing treatment in 4 groups of 10 mice with either nebulized saline (control) or one of 3 different concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods daily over three consecutive days. In both experiments, mouse behavior, clinical scores, weight change, bronchoalveolar lavage cell viability, cellular composition, and cytokine levels, were assessed 24-h following the final exposure, with viral load also assessed after the second experiment. RESULTS: In uninfected BALB/c mice, 3x30-minute exposures to nebulized 40%, 60%, and 80% ethanol resulted in no significant differences in mouse weights, cell counts/viability, cytokines, or morphometry measures. In Mem71-influenza infected mice, we observed a dose-dependent reduction in viral load in the 80%-treated group and potentiation of macrophage numbers in the 60%- and 80%-treated groups, with no safety concerns. CONCLUSIONS: Our data provides support for inhaled ethanol as a candidate treatment for respiratory infections.


Asunto(s)
Modelos Animales de Enfermedad , Etanol , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae , Carga Viral , Animales , Etanol/farmacología , Etanol/administración & dosificación , Femenino , Administración por Inhalación , Ratones , Carga Viral/efectos de los fármacos , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/virología , Infecciones por Orthomyxoviridae/inmunología , Macrófagos/efectos de los fármacos , Citocinas/metabolismo , Líquido del Lavado Bronquioalveolar , Aerosoles , Pulmón/efectos de los fármacos , Pulmón/virología
3.
Am J Physiol Lung Cell Mol Physiol ; 326(6): L713-L726, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38469649

RESUMEN

Mucopolysaccharidosis type IIIA (MPS IIIA) is characterized by neurological and skeletal pathologies caused by reduced activity of the lysosomal hydrolase, sulfamidase, and the subsequent primary accumulation of undegraded heparan sulfate (HS). Respiratory pathology is considered secondary in MPS IIIA and the mechanisms are not well understood. Changes in the amount, metabolism, and function of pulmonary surfactant, the substance that regulates alveolar interfacial surface tension and modulates lung compliance and elastance, have been reported in MPS IIIA mice. Here we investigated changes in lung function in 20-wk-old control and MPS IIIA mice with a closed and open thoracic cage, diaphragm contractile properties, and potential parenchymal remodeling. MPS IIIA mice had increased compliance and airway resistance and reduced tissue damping and elastance compared with control mice. The chest wall impacted lung function as observed by an increase in airway resistance and a decrease in peripheral energy dissipation in the open compared with the closed thoracic cage state in MPS IIIA mice. Diaphragm contractile forces showed a decrease in peak twitch force, maximum specific force, and the force-frequency relationship but no change in muscle fiber cross-sectional area in MPS IIIA mice compared with control mice. Design-based stereology did not reveal any parenchymal remodeling or destruction of alveolar septa in the MPS IIIA mouse lung. In conclusion, the increased storage of HS which leads to biochemical and biophysical changes in pulmonary surfactant also affects lung and diaphragm function, but has no impact on lung or diaphragm structure at this stage of the disease.NEW & NOTEWORTHY Heparan sulfate storage in the lungs of mucopolysaccharidosis type IIIA (MPS IIIA) mice leads to changes in lung function consistent with those of an obstructive lung disease and includes an increase in lung compliance and airway resistance and a decrease in tissue elastance. In addition, diaphragm muscle contractile strength is reduced, potentially further contributing to lung function impairment. However, no changes in parenchymal lung structure were observed in mice at 20 wk of age.


Asunto(s)
Resistencia de las Vías Respiratorias , Diafragma , Mucopolisacaridosis III , Alveolos Pulmonares , Animales , Diafragma/fisiopatología , Diafragma/patología , Diafragma/metabolismo , Rendimiento Pulmonar , Ratones , Alveolos Pulmonares/patología , Alveolos Pulmonares/fisiopatología , Alveolos Pulmonares/metabolismo , Mucopolisacaridosis III/patología , Mucopolisacaridosis III/fisiopatología , Mucopolisacaridosis III/metabolismo , Mucopolisacaridosis III/genética , Contracción Muscular/fisiología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Fuerza Muscular , Pulmón/patología , Pulmón/fisiopatología , Pulmón/metabolismo , Masculino
4.
Int J Mol Sci ; 24(6)2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36982203

RESUMEN

Biodiesel, which can be made from a variety of natural oils, is currently promoted as a sustainable, healthier replacement for commercial mineral diesel despite little experimental data supporting this. The aim of our research was to investigate the health impacts of exposure to exhaust generated by the combustion of diesel and two different biodiesels. Male BALB/c mice (n = 24 per group) were exposed for 2 h/day for 8 days to diluted exhaust from a diesel engine running on ultra-low sulfur diesel (ULSD) or Tallow or Canola biodiesel, with room air exposures used as control. A variety of respiratory-related end-point measurements were assessed, including lung function, responsiveness to methacholine, airway inflammation and cytokine response, and airway morphometry. Exposure to Tallow biodiesel exhaust resulted in the most significant health impacts compared to Air controls, including increased airway hyperresponsiveness and airway inflammation. In contrast, exposure to Canola biodiesel exhaust resulted in fewer negative health effects. Exposure to ULSD resulted in health impacts between those of the two biodiesels. The health effects of biodiesel exhaust exposure vary depending on the feedstock used to make the fuel.


Asunto(s)
Contaminantes Atmosféricos , Masculino , Ratones , Animales , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Biocombustibles/toxicidad , Biocombustibles/análisis , Material Particulado/toxicidad , Material Particulado/análisis , Emisiones de Vehículos/toxicidad , Emisiones de Vehículos/análisis , Azufre , Inflamación
5.
Toxics ; 11(3)2023 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-36977055

RESUMEN

Despite their increasing popularity, and Australia's unique regulatory environment, how and why Australian adults use e-cigarettes and their perceptions of their safety, efficacy and regulation have not been extensively reported before. In this study, we screened 2217 adult Australians with the aim of assessing these questions in a sample of current or former e-cigarette users. A total of 505 out of 2217 respondents were current or former e-cigarette users, with only these respondents completing the full survey. Key findings of this survey included the high proportion of respondents who indicated they were currently using e-cigarettes (307 out of 2217 = 13.8%), and the high proportion of current e-cigarette users that were also smokers (74.6%). The majority of respondents used e-liquids containing nicotine (70.3%), despite it being illegal in Australia without a prescription, and the majority bought their devices and liquids in Australia (65.7%). Respondents reported using e-cigarettes in a variety of places, including inside the home, inside public places (where it is illegal to smoke tobacco cigarettes), and around other people-which has implications for second and third hand exposures. A significant proportion of current e-cigarette users (30.6%) thought that e-cigarettes were completely safe to use long-term, although in general, there was a large amount of uncertainty/ambivalence with respect to perceptions of e-cigarette safety and efficacy as smoking cessation tools. This study shows that e-cigarette use is common in Australia, and that appropriate dissemination of unbiased research findings on their safety and efficacy in smoking cessation is urgently required.

7.
Chemosphere ; 310: 136873, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36252896

RESUMEN

To address climate change concerns, and reduce the carbon footprint caused by fossil fuel use, it is likely that blend ratios of renewable biodiesel with commercial mineral diesel fuel will steadily increase, resulting in biodiesel use becoming more widespread. Exhaust toxicity of unblended biodiesels changes depending on feedstock type, however the effect of feedstock on blended fuels is less well known. The aim of this study was to assess the impact of biodiesel feedstock on exhaust toxicity of 20% blended biodiesel fuels (B20). Primary human airway epithelial cells were exposed to exhaust diluted 1/15 with air from an engine running on conventional ultra-low sulfur diesel (ULSD) or 20% blends of soy, canola, waste cooking oil (WCO), tallow, palm or cottonseed biodiesel in diesel. Physico-chemical exhaust properties were compared between fuels and the post-exposure effect of exhaust on cellular viability and media release was assessed 24 h later. Exhaust properties changed significantly between all fuels with cottonseed B20 being the most different to both ULSD and its respective unblended biodiesel. Exposure to palm B20 resulted in significantly decreased cellular viability (96.3 ± 1.7%; p < 0.01) whereas exposure to soy B20 generated the greatest number of changes in mediator release (including IL-6, IL-8 and TNF-α, p < 0.05) when compared to air exposed controls, with palm B20 and tallow B20 closely following. In contrast, canola B20 and WCO B20 were the least toxic with only mediators G-CSF and TNF-α being significantly increased. Therefore, exposure to palm B20, soy B20 and tallow B20 were found to be the most toxic and exposure to canola B20 and WCO B20 the least. The top three most toxic and the bottom three least toxic B20 fuels are consistent with their unblended counterparts, suggesting that feedstock type greatly impacts exhaust toxicity, even when biodiesel only comprises 20% of the fuel.


Asunto(s)
Biocombustibles , Material Particulado , Humanos , Biocombustibles/toxicidad , Biocombustibles/análisis , Material Particulado/análisis , Factor de Necrosis Tumoral alfa , Aceite de Semillas de Algodón , Emisiones de Vehículos/toxicidad , Emisiones de Vehículos/análisis , Gasolina/toxicidad , Minerales
8.
Microbiol Resour Announc ; 11(12): e0095322, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36416544

RESUMEN

We identified a double-stranded DNA (dsDNA) bacteriophage appearing to belong to Herelleviridae, genus Kayvirus. The bacteriophage, Biyabeda-mokiny 1, was isolated from breast milk using a clinical isolate of Staphylococcus aureus. The genome is 141,091 bp in length and encodes 230 putative coding sequences.

9.
Microbiol Resour Announc ; 11(12): e0095422, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36409081

RESUMEN

Two lytic double-stranded DNA (dsDNA) bacteriophages, belonging to the family Herelleviridae, were isolated from wastewater in Western Australia. Biyabeda-mokiny 2 appears to belong to the genus Kayvirus, and Koomba-kaat 1 to Silviavirus.

10.
Sci Total Environ ; 832: 155016, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-35381248

RESUMEN

Biodiesel is created through the transesterification of fats/oils and its usage is increasing worldwide as global warming concerns increase. Biodiesel fuel properties change depending on the feedstock used to create it. The aim of this study was to assess the different toxicological properties of biodiesel exhausts created from different feedstocks using a complex 3D air-liquid interface (ALI) model that mimics the human airway. Primary human airway epithelial cells were grown at ALI until full differentiation was achieved. Cells were then exposed to 1/20 diluted exhaust from an engine running on Diesel (ULSD), pure or 20% blended Canola biodiesel and pure or 20% blended Tallow biodiesel, or Air for control. Exhaust was analysed for various physio-chemical properties and 24-h after exposure, ALI cultures were assessed for permeability, protein release and mediator response. All measured exhaust components were within industry safety standards. ULSD contained the highest concentrations of various combustion gases. We found no differences in terms of particle characteristics for any of the tested exhausts, likely due to the high dilution used. Exposure to Tallow B100 and B20 induced increased permeability in the ALI culture and the greatest increase in mediator response in both the apical and basal compartments. In contrast, Canola B100 and B20 did not impact permeability and induced the smallest mediator response. All exhausts but Canola B20 induced increased protein release, indicating epithelial damage. Despite the concentrations of all exhausts used in this study meeting industry safety regulations, we found significant toxic effects. Tallow biodiesel was found to be the most toxic of the tested fuels and Canola the least, both for blended and pure biodiesel fuels. This suggests that the feedstock biodiesel is made from is crucial for the resulting health effects of exhaust exposure, even when not comprising the majority of fuel composition.


Asunto(s)
Contaminantes Atmosféricos , Biocombustibles , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Biocombustibles/análisis , Biocombustibles/toxicidad , Células Epiteliales , Gasolina/análisis , Humanos , Material Particulado/análisis , Emisiones de Vehículos/análisis , Emisiones de Vehículos/toxicidad
11.
Am J Physiol Lung Cell Mol Physiol ; 322(5): L683-L698, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35348023

RESUMEN

Excessive production, secretion, and retention of abnormal mucus is a pathological feature of many obstructive airways diseases including asthma. Azithromycin is an antibiotic that also possesses immunomodulatory and mucoregulatory activities, which may contribute to the clinical effectiveness of azithromycin in asthma. The current study investigated these nonantibiotic activities of azithromycin in mice exposed daily to intranasal house dust mite (HDM) extract for 10 days. HDM-exposed mice exhibited airways hyperresponsiveness to aerosolized methacholine, a pronounced mixed eosinophilic and neutrophilic inflammatory response, increased airway smooth muscle (ASM) thickness, and elevated levels of epithelial mucin staining. Azithromycin (50 mg/kg sc, 2 h before each HDM exposure) attenuated HDM-induced airways hyperresponsiveness to methacholine, airways inflammation (bronchoalveolar lavage eosinophil and neutrophils numbers, and IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, and RANTES levels), and epithelial mucin staining (mucous metaplasia) by at least 50% (compared with HDM-exposed mice, P < 0.05). Isolated tracheal segments of HDM-exposed mice secreted Muc5ac and Muc5b (above baseline levels) in response to exogenous ATP. Moreover, ATP-induced secretion of mucins was attenuated in segments obtained from azithromycin-treated, HDM-exposed mice (P < 0.05). In additional ex vivo studies, ATP-induced secretion of Muc5ac (but not muc5b) from HDM-exposed tracheal segments was inhibited by in vitro exposure to azithromycin. In vitro azithromycin also inhibited ATP-induced secretion of Muc5ac and Muc5b in tracheal segments from IL-13-exposed mice. In summary, azithromycin inhibited ATP-induced mucin secretion and airways inflammation in HDM-exposed mice, both of which are likely to contribute to suppression of airways hyperresponsiveness.


Asunto(s)
Asma , Pyroglyphidae , Adenosina Trifosfato , Alérgenos , Animales , Asma/patología , Azitromicina/farmacología , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Interleucina-13 , Metaplasia , Cloruro de Metacolina , Ratones , Mucinas , Moco
12.
Respir Physiol Neurobiol ; 298: 103846, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35063696

RESUMEN

A significant proportion of chronic obstructive pulmonary disease exacerbations are strongly associated with rhinovirus infection (HRV). In this study, we combined long-term cigarette smoke exposure with HRV infection in a mouse model. Our aim was to better understand the effects of HRV infection on such exacerbations, using a realistic method for generating a COPD-like phenotype. After 12-weeks of cigarette smoke exposure, adult female BALB/c mice were infected with HRV-1A and three days later we assessed a range of outcomes including lung volume and function, collected lung tissue for measurement of viral titre, bronchoalveolar lavage for assessment of pulmonary inflammation and levels of key mediators, and fixed lungs for stereological structural analyses. Cigarette smoke exposure alone significantly increased total cells and macrophages, and reduced MIP-2 in bronchoalveolar lavage. HRV-1A infection alone increased neutrophilic inflammation, IP-10 and total protein in lavage and also increased specific airway resistance measured at functional residual capacity. Cigarette smoke and HRV-1A together impacted various lung structural parameters including increasing stereological lung volume. Our results show that long-term cigarette smoke exposure and HRV-1A infection both individually impact respiratory outcomes and combine to alter aspects of lung structure in a mouse model, thus providing insight into the development of future mechanistic studies and appropriate interventions in human disease.


Asunto(s)
Fumar Cigarrillos/efectos adversos , Exposición por Inhalación/efectos adversos , Infecciones por Picornaviridae/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/patología , Rhinovirus/patogenicidad , Brote de los Síntomas , Animales , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos BALB C , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo
13.
J Physiol ; 600(6): 1439-1453, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34731494

RESUMEN

Atmospheric carbon dioxide (CO2 ) levels are currently at 418 parts per million (ppm), and by 2100 may exceed 900 ppm. The biological effects of lifetime exposure to CO2 at these levels is unknown. Previously we have shown that mouse lung function is altered by long-term exposure to 890 ppm CO2 . Here, we assess the broader systemic physiological responses to this exposure. Mice were exposed to either 460 or 890 ppm from preconception to 3 months of age, and assessed for effects on developmental, renal and osteological parameters. Locomotor, memory, learning and anxiety-like behaviours of the mice were also assessed. Exposure to 890 ppm CO2 increased birthweight, decreased female body weight after weaning, and, as young adults, resulted in reduced engagement in memory/learning tasks, and hyperactivity in both sexes in comparison to controls. There were no clear anxiety, learning or memory changes. Renal and osteological parameters were minimally affected. Overall, this study shows that exposure of mice to 890 ppm CO2 from preconception to young adulthood alters growth and some behaviours, with limited evidence of compensatory changes in acid-base balance. These findings highlight the potential for a direct effect of increased atmospheric CO2 on mammalian health outcomes. KEY POINTS: Long-term exposure to elevated levels of atmospheric CO2 is an uncontrolled experiment already underway. This is the first known study to assess non-respiratory physiological impacts of long-term (conception to young adulthood) exposure of mice to CO2 at levels that may arise in the atmosphere due to global emissions. Exposure to elevated CO2 , in comparison to control mice, altered growth patterns in early life and resulted in hyperactive behaviours in young adulthood. Renal and bone parameters, which are important to balance acid-base levels to compensate for increased CO2 exposure, remained relatively unaffected. This work adds to the body of evidence regarding the effects of carbon emissions on mammalian health and highlights a potential future burden of disease.


Asunto(s)
Dióxido de Carbono , Fenómenos Fisiológicos Respiratorios , Animales , Femenino , Masculino , Mamíferos , Ratones
15.
MethodsX ; 8: 101561, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34754823

RESUMEN

The method outlined in this article is a customization of the whole exhaust exposure method generated by Mullins et al. (2016) using reprogrammed primary human airway epithelial cells as described by Martinovich et al. (2017). It has been used successfully to generate recently published data (Landwehr et al. 2021). The goal was to generate an exhaust exposure model where exhaust is collected from a modern engine, real-world exhaust concentrations are used and relevant tissues exposed to assess the effects of multiple biodiesel exposures. Exhaust was generated, gently vacuumed into a dilution chamber where it was diluted 1/15 with air and then vacuumed into an incubator containing the primary cell cultures for exposure. Exhaust physico-chemical properties including combustion gas concentrations and particle spectra were then analyzed using a combustion gas analyzer and a Universal Scanning Mobility Particle Sizer. 24 h after exposure, cellular viability and mediator release were measured using Annexin-V/PI staining and meditator multiplexing kits respectively. This method was generated to test biodiesel exhaust exposures but can be easily adapted for any type of engine exhaust exposure or even potentially other respirable environmental exposures such as woodsmoke. The main customization points for this method are:•Exhaust generated by a diesel engine equipped with EURO VI exhaust after treatment devices including diesel particulate filter and diesel oxidation catalyst.•The generated exhaust was diluted 1/15 with air to replicate real world exposure concentrations.•Used primary human airway epithelial cells obtained from bronchoscope brushings from multiple volunteers and reprogrammed to allow multiple, comparative exposures from the same individual.

16.
Viruses ; 13(9)2021 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-34578390

RESUMEN

The emergence of multi-drug resistant (MDR) bacteria is recognised today as one of the greatest challenges to public health. As traditional antimicrobials are becoming ineffective and research into new antibiotics is diminishing, a number of alternative treatments for MDR bacteria have been receiving greater attention. Bacteriophage therapies are being revisited and present a promising opportunity to reduce the burden of bacterial infection in this post-antibiotic era. This review focuses on the current evidence supporting bacteriophage therapy against prevalent or emerging multi-drug resistant bacterial pathogens in respiratory medicine and the challenges ahead in preclinical data generation. Starting with efforts to improve delivery of bacteriophages to the lung surface, the current developments in animal models for relevant efficacy data on respiratory infections are discussed before finishing with a summary of findings from the select human trials performed to date.


Asunto(s)
Infecciones Bacterianas/terapia , Farmacorresistencia Bacteriana Múltiple , Terapia de Fagos/métodos , Infecciones del Sistema Respiratorio/terapia , Animales , Bacteriófagos/fisiología , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Humanos , Pulmón/microbiología , Ratones
17.
Front Immunol ; 12: 699633, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34367159

RESUMEN

High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high (BN) versus low susceptibility (PVG) to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype. We also investigated potential risk mitigation via pretreatment with the immune training agent OM-85. Virus/allergen coexposure in low-risk PVG rats resulted in rapid and transient airways inflammation alongside IRF7 gene network formation. In contrast, responses in high-risk BN rats were characterized by severe airways eosinophilia and exaggerated proinflammatory responses that failed to resolve, and complete absence of IRF7 gene networks. OM-85 had more profound effects in high-risk BN rats, inducing immune-related gene expression changes in lung at baseline and reducing exaggerated airway inflammatory responses to virus/allergen coexposure. In low-risk PVG rats, OM-85 boosted IRF7 gene networks in the lung but did not alter baseline gene expression or cellular influx. Distinct IRF7-associated asthma risk immunophenotypes have dichotomous responses to virus/allergen coexposure and respond differentially to OM-85 pretreatment. Extrapolating to humans, our findings suggest that the beneficial effects OM-85 pretreatment may preferentially target those in high-risk subgroups.


Asunto(s)
Alérgenos/inmunología , Asma/inmunología , Infecciones por Cardiovirus/inmunología , Extractos Celulares/farmacología , Factor 7 Regulador del Interferón/inmunología , Animales , Asma/etiología , Inmunofenotipificación , Masculino , Ratas
18.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-34445491

RESUMEN

In this study we assessed the effects of antigen exposure in mice pre-sensitized with allergen following viral infection on changes in lung function, cellular responses and tight junction expression. Female BALB/c mice were sensitized to ovalbumin and infected with influenza A before receiving a second ovalbumin sensitization and challenge with saline, ovalbumin (OVA) or house dust mite (HDM). Fifteen days post-infection, bronchoalveolar inflammation, serum antibodies, responsiveness to methacholine and barrier integrity were assessed. There was no effect of infection alone on bronchoalveolar lavage cellular inflammation 15 days post-infection; however, OVA or HDM challenge resulted in increased bronchoalveolar inflammation dominated by eosinophils/neutrophils or neutrophils, respectively. Previously infected mice had higher serum OVA-specific IgE compared with uninfected mice. Mice previously infected, sensitized and challenged with OVA were most responsive to methacholine with respect to airway resistance, while HDM challenge caused significant increases in both tissue damping and tissue elastance regardless of previous infection status. Previous influenza infection was associated with decreased claudin-1 expression in all groups and decreased occludin expression in OVA or HDM-challenged mice. This study demonstrates the importance of the respiratory epithelium in pre-sensitized individuals, where influenza-infection-induced barrier disruption resulted in increased systemic OVA sensitization and downstream effects on lung function.


Asunto(s)
Hiperreactividad Bronquial/tratamiento farmacológico , Cloruro de Metacolina/administración & dosificación , Infecciones por Orthomyxoviridae/complicaciones , Ovalbúmina/inmunología , Pyroglyphidae/inmunología , Resistencia de las Vías Respiratorias/efectos de los fármacos , Animales , Hiperreactividad Bronquial/etiología , Claudina-1/metabolismo , Regulación hacia Abajo , Femenino , Virus de la Influenza A/patogenicidad , Cloruro de Metacolina/farmacología , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/inmunología , Ovalbúmina/administración & dosificación , Resultado del Tratamiento
19.
J Hazard Mater ; 420: 126637, 2021 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-34329109

RESUMEN

BACKGROUND: Biodiesel is promoted as a sustainable replacement for commercial diesel. Biodiesel fuel and exhaust properties change depending on the base feedstock oil/fat used during creation. The aims of this study were, for the first time, to compare the exhaust exposure health impacts of a wide range of biodiesels made from different feedstocks and relate these effects with the corresponding exhaust characteristics. METHOD: Primary airway epithelial cells were exposed to diluted exhaust from an engine running on conventional diesel and biodiesel made from Soy, Canola, Waste Cooking Oil, Tallow, Palm and Cottonseed. Exhaust properties and cellular viability and mediator release were analysed post exposure. RESULTS: The exhaust physico-chemistry of Tallow biodiesel was the most different to diesel as well as the most toxic, with exposure resulting in significantly decreased cellular viability (95.8 ± 6.5%) and increased release of several immune mediators including IL-6 (+223.11 ± 368.83 pg/mL) and IL-8 (+1516.17 ± 2908.79 pg/mL) above Air controls. In contrast Canola biodiesel was the least toxic with exposure only increasing TNF-α (4.91 ± 8.61). CONCLUSION: This study, which investigated the toxic effects for the largest range of biodiesels, shows that exposure to different exhausts results in a spectrum of toxic effects in vitro when combusted under identical conditions.


Asunto(s)
Contaminantes Atmosféricos , Biocombustibles , Células Epiteliales/efectos de los fármacos , Emisiones de Vehículos/toxicidad , Contaminantes Atmosféricos/análisis , Biocombustibles/toxicidad , Células Cultivadas , Culinaria , Gasolina , Humanos
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