Vanadium pentoxide induces pulmonary inflammation and tumor promotion in a strain-dependent manner

<p>Abstract</p> <p>Background</p> <p>Elevated levels of air pollution are associated with increased risk of lung cancer. Particulate matter (PM) contains transition metals that may potentiate neoplastic development through the induction of oxidative stress and inflammation, a lung cancer risk factor. Vanadium pentoxide (V₂O₅) is a component of PM derived from fuel combustion as well as a source of occupational exposure in humans. In the current investigation we examined the influence of genetic background on susceptibility to V₂O₅-induced inflammation and evaluated whether V₂O₅functions as a tumor promoter using a 2-stage (initiation-promotion) model of pulmonary neoplasia in mice.</p> <p>Results</p> <p>A/J, BALB/cJ (BALB), and C57BL/6J (B6) mice were treated either with the initiator 3-methylcholanthrene (MCA; 10 μg/g; i.p.) or corn oil followed by 5 weekly aspirations of V₂O₅or PBS and pulmonary tumors were enumerated 20 weeks following MCA treatment. Susceptibility to V₂O₅-induced pulmonary inflammation was assessed in bronchoalveolar lavage fluid (BALF), and chemokines, transcription factor activity, and MAPK signaling were quantified in lung homogenates. We found that treatment of animals with MCA followed by V₂O₅promoted lung tumors in both A/J (10.3 ± 0.9 tumors/mouse) and BALB (2.2 ± 0.36) mice significantly above that observed with MCA/PBS or V₂O₅alone (<it>P </it>< 0.05). No tumors were observed in the B6 mice in any of the experimental groups. Mice sensitive to tumor promotion by V₂O₅were also found to be more susceptible to V₂O₅-induced pulmonary inflammation and hyperpermeability (A/J>BALB>B6). Differential strain responses in inflammation were positively associated with elevated levels of the chemokines KC and MCP-1, higher NFκB and c-Fos binding activity, as well as sustained ERK1/2 activation in lung tissue.</p> <p>Conclusions</p> <p>In this study we demonstrate that V₂O₅, an occupational and environmentally relevant metal oxide, functions as an <it>in vivo </it>lung tumor promoter among different inbred strains of mice. Further, we identified a positive relationship between tumor promotion and susceptibility to V₂O₅-induced pulmonary inflammation. These findings suggest that repeated exposures to V₂O₅containing particles may augment lung carcinogenesis in susceptible individuals through oxidative stress mediated pathways.</p

Multi-walled carbon nanotube instillation impairs pulmonary function in C57BL/6 mice

<p>Abstract</p> <p>Background</p> <p>Multi-walled carbon nanotubes (MWCNTs) are widely used in many disciplines due to their unique physical and chemical properties. Therefore, some concerns about the possible human health and environmental impacts of manufactured MWCNTs are rising. We hypothesized that instillation of MWCNTs impairs pulmonary function in C57BL/6 mice due to development of lung inflammation and fibrosis.</p> <p>Methods</p> <p>MWCNTs were administered to C57BL/6 mice by oropharyngeal aspiration (1, 2, and 4 mg/kg) and we assessed lung inflammation and fibrosis by inflammatory cell infiltration, collagen content, and histological assessment. Pulmonary function was assessed using a FlexiVent system and levels of Ccl3, Ccl11, Mmp13 and IL-33 were measured by RT-PCR and ELISA.</p> <p>Results</p> <p>Mice administered MWCNTs exhibited increased inflammatory cell infiltration, collagen deposition and granuloma formation in lung tissue, which correlated with impaired pulmonary function as assessed by increased resistance, tissue damping, and decreased lung compliance. Pulmonary exposure to MWCNTs induced an inflammatory signature marked by cytokine (IL-33), chemokine (Ccl3 and Ccl11), and protease production (Mmp13) that promoted the inflammatory and fibrotic changes observed within the lung.</p> <p>Conclusions</p> <p>These results further highlight the potential adverse health effects that may occur following MWCNT exposure and therefore we suggest these materials may pose a significant risk leading to impaired lung function following environmental and occupational exposures.</p

Ethical implications of the perception and portrayal of dementia

yesThe way we perceive and portray dementia has implications for how we act towards people with dementia and how we address the issue of dementia within society. As a multi-disciplinary working group, established within the framework of the European Dementia Ethics Network of Alzheimer Europe, we aimed to describe the different ways that people with dementia are perceived and portrayed within society and to consider the moral implications of this. In the current paper, we address perceptions of dementia as reflected in explanatory models of its cause and nature, descriptions of characteristics of people with dementia, the use of language, media portrayals and the views of people living with dementia. Academics and professionals could use this exploration to reflect on their behaviour and their use of language regarding people with dementiaThe taskforce’s work arises from the 2013 Work Plan of Alzheimer Europe, which received funding from the European Union in the framework of the Health Programme

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination

Vanadium pentoxide induces pulmonary inflammation and tumor promotion in a strain-dependent manner

Background Elevated levels of air pollution are associated with increased risk of lung cancer. Particulate matter (PM) contains transition metals that may potentiate neoplastic development through the induction of oxidative stress and inflammation, a lung cancer risk factor. Vanadium pentoxide (V2O5) is a component of PM derived from fuel combustion as well as a source of occupational exposure in humans. In the current investigation we examined the influence of genetic background on susceptibility to V2O5-induced inflammation and evaluated whether V2O5 functions as a tumor promoter using a 2-stage (initiation-promotion) model of pulmonary neoplasia in mice. Results A/J, BALB/cJ (BALB), and C57BL/6J (B6) mice were treated either with the initiator 3-methylcholanthrene (MCA; 10 µg/g; i.p.) or corn oil followed by 5 weekly aspirations of V2O5 or PBS and pulmonary tumors were enumerated 20 weeks following MCA treatment. Susceptibility to V2O5-induced pulmonary inflammation was assessed in bronchoalveolar lavage fluid (BALF), and chemokines, transcription factor activity, and MAPK signaling were quantified in lung homogenates. We found that treatment of animals with MCA followed by V2O5 promoted lung tumors in both A/J (10.3 ± 0.9 tumors/mouse) and BALB (2.2 ± 0.36) mice significantly above that observed with MCA/PBS or V2O5 alone (P BALB&gt;B6). Differential strain responses in inflammation were positively associated with elevated levels of the chemokines KC and MCP-1, higher NF?B and c-Fos binding activity, as well as sustained ERK1/2 activation in lung tissue. Conclusions In this study we demonstrate that V2O5, an occupational and environmentally relevant metal oxide, functions as an in vivo lung tumor promoter among different inbred strains of mice. Further, we identified a positive relationship between tumor promotion and susceptibility to V2O5-induced pulmonary inflammation. These findings suggest that repeated exposures to V2O5 containing particles may augment lung carcinogenesis in susceptible individuals through oxidative stress mediated pathways

Vanadium pentoxide induces pulmonary inflammation and tumor promotion in a strain-dependent manner

Background: Elevated levels of air pollution are associated with increased risk of lung cancer. Particulate matter (PM) ontains transition metals that may potentiate neoplastic development through the induction of oxidative stress and nflammation a lung cancer risk factor. Vanadium pentoxide (V2O5) is a component of PM derived from fuel ombustion as well as a source of occupational exposure in humans. In the current investigation we examined the nfluence of genetic background on susceptibility to V2O5-induced inflammation and evaluated whether V2O5 unctions as a tumor promoter using a 2-stage (initiation-promotion) model of pulmonary neoplasia in mice. esults: A/J BALB/cJ (BALB) and C57BL/6J (B6) mice were treated either with the initiator 3-methylcholanthrene (MCA; 0 μg/g; i.p.) or corn oil followed by 5 weekly aspirations of V2O5 or PBS and pulmonary tumors were enumerated 20 eeks following MCA treatment. Susceptibility to V2O5-induced pulmonary inflammation was assessed in ronchoalveolar lavage fluid (BALF) and chemokines transcription factor activity and MAPK signaling were quantified n lung homogenates. We found that treatment of animals with MCA followed by V2O5 promoted lung tumors in both /J (10.3 ± 0.9 tumors/mouse) and BALB (2.2 ± 0.36) mice significantly above that observed with MCA/PBS or V2O5 lone (P BALB&gt;B6). Differential strain responses in inflammation were positively associated with levated levels of the chemokines KC and MCP-1 higher NFκB and c-Fos binding activity as well as sustained ERK1/2 ctivation in lung tissue. onclusions: In this study we demonstrate that V2O5 an occupational and environmentally relevant metal oxide unctions as an in vivo lung tumor promoter among different inbred strains of mice. Further we identified a positive elationship between tumor promotion and susceptibility to V2O5-induced pulmonary inflammation. These findings uggest that repeated exposures to V2O5 containing particles may augment lung carcinogenesis in susceptible ndividuals through oxidative stress mediated pathways. Originally published Particle and Fibre Toxicology Vol. 7 No. 9 Apr 201

Vanadium pentoxide (V2O5) induced mucin production by airway epithelium

Exposure to environmental pollutants has been linked to various airway diseases and disease exacerbations. Almost all chronic airway diseases such as chronic obstructive pulmonary disease and asthma are caused by complicated interactions between gene and environment. One of the major hallmarks of those diseases is airway mucus overproduction (MO). Excessive mucus causes airway obstruction and significantly increases morbidity and mortality. Metals are major components of environmental particulate matters (PM). Among them, vanadium has been suggested to play an important role in PM-induced mucin production. Vanadium pentoxide (V2O5) is the most common commercial source of vanadium, and it has been associated with occupational chronic bronchitis and asthma, both of which are MO diseases. However, the underlying mechanism is not entirely clear. In this study, we used both in vitro and in vivo models to demonstrate the robust inductions of mucin production by V2O5. Furthermore, the follow-up mechanistic study revealed a novel v-raf-1 murine leukemia viral oncogene homolog 1-IKK-NF-κB pathway that mediated V2O5-induced mucin production. Most interestingly, the reactive oxygen species and the classical mucin-inducing epidermal growth factor receptor (EGFR)-MAPK pathway appeared not to be involved in this process. Thus the V2O5-induced mucin production may represent a novel EGFR-MAPK-independent and environmental toxicant-associated MO model. Complete elucidation of the signaling pathway in this model will not only facilitate the development of the treatment for V2O5-associated occupational diseases but also advance our understanding on the EGFR-independent mucin production in other chronic airway diseases

Staff experiences of providing support to students who are managing mental health challenges: A qualitative study from two Australian universities (vol 12, pg 192, 2014)

Margaret McAllister, Dianne Wynaden, Brenda Happell, Trudi Flynn, Victoria Walters, Ravani Duggan, Louise Byrne, Karen Heslop & Cadeyrn Gaskin (2014) Staff experiences of providing support to students who are managing mental health challenges: A qualitative study from two Australian universities. Advances in Mental Health: Promotion, Prevention and Early Intervention, 12(3), pp. 192-201. http://dx.doi.org/10.1080/18374905.2014.11081897 When the above article was first published, Victoria Walters’, Ravani Duggan’s and Karen Heslop’s names were spelled incorrectly. This has now been corrected online