Local examination of skin diffusion using FTIR spectroscopic imaging and multivariate target factor analysis

In the context of trans-dermal drug delivery it is very important to have mechanistic insight into the barrier function of the skin's stratum corneum and the diffusion mechanisms of topically applied drugs. Currently spectroscopic imaging techniques are evolving which enable a spatial examination of various types of samples in a dynamic way. ATR-FTIR imaging opens up the possibility to monitor spatial diffusion profiles across the stratum corneum of a skin sample. Multivariate data analyses methods based on factor analysis are able to provide insight into the large amount of spectroscopically complex and highly overlapping signals generated. Multivariate target factor analysis was used for spectral resolution and local diffusion profiles with time through stratum corneum. A model drug, 4-cyanophenol in polyethylene glycol 600 and water was studied. Results indicate that the average diffusion profiles between spatially different locations show similar profiles despite the heterogeneous nature of the biological sample and the challenging experimental set-up.

Fluoride-releasing composite resins

This paper reviews the literature on fluoride-releasing composite resins. These materials have been available for several years, with fluoride release being achieved by adding soluble or sparingly soluble fluoride salts to the formulation. However, this has been shown to lead to a gradual reduction in the mechanical properties. These materials are also unable to undergo "fluoride recharge". Experimental fluoride-releasing composites have been prepared which supply fluoride by alternative mechanisms that do have the potential for fluoride recharge but, so far, these materials have not been made available for use in patients. Fluoride-releasing composite resins have been shown to be effective in preventing secondary caries in vitro. They have also been shown to reduce the size and depth of carious lesions. However, information on their clinical effectiveness is limited and the paper concludes that there is an urgent need for research on this topic.

Valuation of ecological and amenity impacts of an offshore windfarm as a factor in marine planning

Integrated marine planning, which must take into consideration environmental and social impacts, is being introduced widely in Europe, the USA, Australia and elsewhere. Installation of offshore windfarms creates impacts both on local marine ecosystems and the view of the seascape and is one of multiple activities in the marine area that must be addressed by marine planning. The impacts on people's values (and hence welfare) of changes in ecology and amenity that could arise from the installation of a windfarm in the Irish Sea were assessed using a discrete choice experiment administered through an online survey. The ecological changes investigated were: increased species diversity resulting from artificial reef effects, and the effect of electromagnetic fields from subsea cables on marine life; whilst the amenity change was the visibility of offshore turbines from land. Respondents expressed preferences for ecological improvements but had less clear preferences regarding the height and visibility of the turbines. In particular distance decay effects were observed with respondents further away from the coast being less concerned about visual impact created by offshore turbines. Understanding ecological and amenity impacts and how they are valued by people can support the decisions made within marine planning and licensing.

Museums as a factor for the social integration of art in the community. The experience of cultural volunteering by members of the senior community

After considering museums as cultural institutions responsible for preserving cultural memory and its evolution over time, this article describes the cultural practices within our society that are aimed at disseminating art and at reproducing and transmitting culture, history and identity. Further, it considers the key role that older people are steadily assuming in Spain’s ageing society. New social-empowerment activities based on volunteering by the elderly are linked to generativity because the individual and social groups acquire new skills through those activities, thereby strengthening a society for all ages. Never in the history of social work have so many older people been prepared to participate actively at the community level, and never has a social movement with these features gone so unnoticed by so many social agents.

The Influence of Copper Binding on the Stability of the SCO Protein from Bacillus subtilis

Every aerobic organism expresses cytochrome c oxidase to catalyze reduction of molecular oxygen to water, and takes advantage of this energy releasing reaction to produce an electrochemical gradient used in cellular energy production. The protein SCO (Synthesis of cytochrome c oxidase) is a required assembly factor for the oxidase, conserved across many species. SCO is implicated in the assembly of one of two copper centres (ie., CuA) of cytochrome oxidase. The exact mechanism of SCO’s participation in CuA assembly is not known. SCO has been proposed to bind and deliver copper, or alternatively to act in reductive preparation of the CuA site within the oxidase. In this body of work, the strength and stability of Cu(II) binding to Bacillus subtilis SCO is explored via electronic absorption and fluorescence spectroscopies and by calorimetric methods. An equilibrium dissociation constant (Kd) of 3.5x10-12 M was determined as an upper limit for the BsSCO-Cu(II) interaction, via differential scanning calorimetry. In the first reported case for a SCO homolog, dissociation kinetics of Cu(II) from BsSCO were characterized, and found to be dependent on both ionic strength and the presence of free Cu(II) in solution. Further differential scanning calorimetry experiments performed at high ionic strength support a two-step model of BsSCO and Cu(II) binding. The implications of this model for the BsSCO-Cu(II) interaction are presented in relation to the mechanism of interaction between SCO and the CuA site of cytochrome c oxidase.

Alcohol: a recently identified risk factor for breast cancer

Acknowledgements: I thank Dr. Barbour Warren, arriet Richardson and Alison James for their helpful input.

Role of hypoxia and hypoxia-inducible factor-1 in tumour immune escape

Previous studies revealed that, upon exposure to hypoxia, tumour cells acquire resistance to the cytolytic activity of IL-2-activated lymphocytes. The MHC class I chain-related (MIC) molecules – comprised of MICA and MICB – are ligands for the activating NKG2D receptor on Natural Killer (NK) and CD8+ T cells. MIC-NKG2D interactions lead to the activation of NK and CD8+ T cells and the subsequent lysis of the tumour cells. The study also showed that the mechanism of the hypoxia-mediated immune escape involves the shedding of MIC, specifically MICA, from the tumour cell surface. The objective of the present study was to determine whether the shedding of MICA requires the expression of hypoxia inducible factor-1 (HIF-1), a transcription factor that regulates cellular adaptations to hypoxia. Exposure to hypoxia (0.5% O2 vs. 20% O2) led to the shedding of MIC from the surface of MDA-MB-231 human breast cancer cells and DU-145 human prostate cancer cells as determined by flow cytometry. Knockdown of HIF-1α mRNA using siRNA technology resulted in inhibition of HIF-1α accumulation under hypoxic conditions as determined by Western blot analysis. Parallel study revealed that knockdown of HIF-1α also blocked the shedding of MICA from the surface of MDA-MB-231 cells exposed to hypoxia. These results indicate that HIF-1 is required for the hypoxia-mediated shedding of MICA and, consequently, that HIF-1 may play an important role in tumour immune escape. Ongoing studies aim to determine the HIF-1 target genes involved in the shedding of MICA under hypoxia.