Differential bioreactivity of neutral, cationic and anionic polystyrene nanoparticles with cells from the human alveolar compartment: robust response of alveolar type 1 epithelial cells

BACKGROUND: Engineered nanoparticles (NP) are being developed for inhaled drug delivery. This route is non-invasive and the major target; alveolar epithelium provides a large surface area for drug administration and absorption, without first pass metabolism. Understanding the interaction between NPs and target cells is crucial for safe and effective NP-based drug delivery. We explored the differential effect of neutral, cationic and anionic polystyrene latex NPs on the target cells of the human alveolus, using primary human alveolar macrophages (MAC) and primary human alveolar type 2 (AT2) epithelial cells and a unique human alveolar epithelial type I-like cell (TT1). We hypothesized that the bioreactivity of the NPs would relate to their surface chemistry, charge and size as well as the functional role of their interacting cells in vivo. METHODS: Amine- (ANP) and carboxyl- surface modified (CNP) and unmodified (UNP) polystyrene NPs, 50 and 100 nm in diameter, were studied. Cells were exposed to 1–100 μg/ml (1.25-125 μg/cm(2); 0 μg/ml control) NP for 4 and 24 h at 37 °C with or without the antioxidant, N-acetyl cysteine (NAC). Cells were assessed for cell viability, reactive oxygen species (ROS), oxidised glutathione (GSSG/GSH ratio), mitochondrial integrity, cell morphology and particle uptake (using electron microscopy and laser scanning confocal microscopy). RESULTS: ANP-induced cell death occurred in all cell types, inducing increased oxidative stress, mitochondrial disruption and release of cytochrome C, indicating apoptotic cell death. UNP and CNP exhibited little cytotoxicity or mitochondrial damage, although they induced ROS in AT2 and MACs. Addition of NAC reduced epithelial cell ROS, but not MAC ROS, for up to 4 h. TT1 and MAC cells internalised all NP formats, whereas only a small fraction of AT2 cells internalized ANP (not UNP or CNP). TT1 cells were the most resistant to the effects of UNP and CNP. CONCLUSION: ANP induced marked oxidative damage and cell death via apoptosis in all cell types, while UNP and CNP exhibited low cytotoxicity via oxidative stress. MAC and TT1 cell models show strong particle-internalization compared to the AT2 cell model, reflecting their cell function in vivo. The 50 nm NPs induced a higher bioreactivity in epithelial cells, whereas the 100 nm NPs show a stronger effect on phagocytic cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0091-7) contains supplementary material, which is available to authorized users

Culture and activity in aging

The cumulative effects of illness and disability in older age can lead to individuals being less able to make positive decisions about involvement in activities for pleasure and socialization. This lowered self-efficacy can in turn lead to erosion of confidence and ultimately to social exclusion. Older tenants in sheltered housing schemes are at particular risk of isolation and exclusion as the move to age-specific housing is usually triggered by a sudden or gradual decline in ability and/or personal circumstances. In conjunction with this, assumptions that social networks naturally occur in communal retirement communities and that people will individually or collectively arrange activities can lead to peoples' aspirations for meaningful activities in later life being overlooked. This problem is further compounded as housing staff find their time is taken up building maintenance and ensuring that tenants receive basic housing and environmental services. This chapter reports on the findings from a needs analysis that aimed to identify the activities that older tenants in a sheltered housing scheme had enjoyed during their lifetime, were no longer able to do but wanted to resume, and any new interests they were interested in pursuing. This is followed by a description of a one-year activity and culture program developed out of this needs analysis, underpinned by previous work conducted in Sweden

Community care in Scotland

This ethnological perspective of Community Care in Scotland will focus on historical, political, and social contexts and their influences on the community care arrangements for individuals within various types of communities in Scotland today

Older People, Telematics and Care

About the book: What are the implications of current economic, social and political trends in Britain for older people? Social and demographic changes have led to traditional areas of welfare being transformed. The contributors to this book take a critical look at the current situation and assess the implications for future practice. They debate the assumptions and values underlying established welfare programmes and consider the case for change as growing demands put health and social services under increasing pressure. The second part of the book discusses specific areas in detail, ranging from the organisation of effective domiciliary social care to the impact of new technologies on older people's lives. This book provides a comprehensive and practical overview of the provision of services for older people and will be a valuable and thought-provoking resource for anyone involved in caring for and supporting them

The Himalaya Clause, “stipulation pour autrui”. Non-Responsibility Clauses and Gross Negligence under the Civil Code

L'imputation de la responsabilité des pertes et dommages subis par la cargaison des navires dans les ports québécois est une question non encore tranchée. Le problème se complique du fait de l'introduction, dans la plupart des contrats de transport maritime international par connaissement, de la clause dite « Himalaya ». Cette clause représente à peu près en common law l'équivalent de la stipulation pour autrui. La validité de ces clauses a souvent été contestée avec succès devant les tribunaux de plusieurs pays, notamment de Grande-Bretagne, des États-Unis et du Canada. Par ailleurs, en droit civil, si la stipulation pour autrui est admise, ce n'est qu'à titre d'exception et sous des conditions très précises. L'auteur recense la jurisprudence des pays de common law relativement à la clause Himalaya, et examine ensuite la validité de cette clause en droit civil à titre de stipulation pour autrui. Il traite également du contrat de porte fort, et de la validité des clauses de non-responsabilité en cas de faute lourde. Enfin, il analyse cinq décisions québécoises récentes, ainsi qu'une importante décision de la High Court australienne

The 10 February 1977 lunar occultation of Uranus. Radius, limb darkening, and polar brightening at 6900 A

Contact timings, corrected for lunar limb effects, indicate an equatorial radius of 25700 + or - 500 km for the visible disk for Uranus. A modified Minnaert function is used to model limb darkening and polar brightening. Least squares fits to the observed light curve indicate that Uranus is slightly limb darkened in the passband of the observations (450 A FWHM centered near 6900 A) and that polar brightening is present

Liposomes encapsulating polymeric chitosan based vesicles - a vesicle in vesicle system for drug delivery

Drug delivery systems comprising vesicles prepared from one amphiphile encapsulating vesicles prepared from a second amphiphile have not been prepared previously due to a tendency of the bilayer components of the different vesicles to mix during preparation. Recently we have developed polymeric vesicles using the new polymer-palmitoyl glycol chitosan and cholesterol in a 2:1 weight ratio. These polymeric vesicles have now been encapsulated within egg phosphatidylcholine (egg PC), cholesterol (2:1 weight ratio) liposomes yielding a vesicle in vesicle system. The vesicle in vesicle system was visualised by freeze fracture electron microscopy. The mixing of the different bilayer components was studied by monitoring the excimer fluorescence of pyrene-labelled polymeric vesicles after their encapsulation within egg PC liposomes or hexadecyl diglycerol ether niosomes. A minimum degree of lipid mixing was observed with the polymeric vesicle-egg PC liposome system when compared to the polymeric vesicle-hexadecyl diglycerol ether niosome system. The polymeric vesicle-egg PC vesicle in vesicle system was shown to retard the release of encapsulated solutes. 28% of 5(6)-carboxyfluorescein (CF) encapsulated in the polymeric vesicle compartment of the vesicle in vesicle system was released after 4 h compared to the release of 62% of encapsulated CF from plain polymeric vesicles within the same time period

Ultrastructural studies on parasitic flagellates

Summary available: p.4