Accumulation of gliotoxin, a cytotoxic mycotoxin from Aspergillus fumigatus, in blue mussel (Mytilus edulis).

A strain of Aspergillus fumigatus has been isolated from sediments of a mussel bed. When cultured in hyper saline conditions (with sea-water), it produces a cytotoxic and immunosuppressive toxin, gliotoxin, which is excreted in an exudate. In order to know if this toxin could represent a risk for shellfish consumers, an experiment of bioaccumulation of gliotoxin in mussel has been carried out. After 6 days of contamination, toxin was accumulated in the meat of the mussels, at a level up to 2.9 microg/mg of extract weight, with a mode of contamination different to the classical digestive process described for a majority of marine toxins, but similar to the contamination mode of domoic acid.     

Brain protection at the blood-cerebrospinal fluid interface involves a glutathione-dependent metabolic barrier mechanism.

The choroid plexuses (CPs) form a protective interface between the blood and the ventricular cerebrospinal fluid (CSF). To probe into the pathways by which CPs provide brain protection, we sought to evaluate the efficiency of glutathione conjugation in this barrier as a mechanism to prevent the entry of blood-borne electrophilic, potentially toxic compounds into the CSF, and we investigated the fate of the resulting metabolites. Rat CPs, as well as human CPs from both fetal and adult brains, displayed high glutathione-S-transferase activities. Using an in vitro model of the blood-CSF barrier consisting of choroidal epithelial cells cultured in a two-chambered device, we showed that glutathione conjugation can efficiently prevent the entry of 1-chloro-2,4-dinitrobenzene (CDNB) into the CSF, a model for electrophilic compounds. The duration of this enzymatic protection was set by the concentration of CDNB to which the epithelium was exposed, and this barrier effect was impaired only on severe epithelial intracellular glutathione and cysteine depletion. The conjugate was excreted from the choroidal cells in a polarized manner, mostly at the blood-facing membrane, via a high-capacity transport process, which is not a rate-limiting step in this detoxification pathway, and which may involve transporters of the ATP-binding cassette c(Abcc) and/or solute carrier 21 (Slc21) families. Supplying the choroidal epithelium at the blood-facing membrane with a therapeutically relevant concentration of N-acetylcysteine sustained this neuroprotective effect. Thus, glutathione conjugation at the CP epithelium coupled with the basolateral efflux of the resulting metabolites form an efficient blood-CSF enzymatic barrier, which can be enhanced by pharmacologically increasing glutathione synthesis within the epithelial cells.     

Extending the capability paradigm to address the complexity of disability

Amartya Sen looks at people's well-being in terms of functioning and freedom, rather than in terms of the amount of goods or services consumed. The capability approach, developed by Sen, deals with what people are able to achieve by using these commodities. Concerning disability, he wrote: “We must take note that a disabled person may not be able to do the many things that an able-bodied individual can, with the same bundle of commodities” [Sen, A. K. (1985). Commodities and capabilities. Oxford: Oxford University Press [1999], p. 7]. The capability approach makes it possible to analyse the economic situation of people with disabilities in a different way. What becomes important is their functioning, i.e. what they are able to achieve within a given context. In fact, the capability set includes not only what a person is effectively able to achieve, but also the potential functionings that he/she can choose. This expresses the degree of freedom that a person with disability benefits from in a given environment. The challenge is therefore to reduce the constraints that the environment adds to a person's impairment in order to expand their capability set and to allow them to live a life which they value. This paper reviews the paradigms that address disability and the ways of assessing a person's capability set within this framework. Achieved functionings are easily measured through cross-sectional surveys, using counterfactual analysis to compare the situations of disabled and non-disabled people. This was done in 2005 in Afghanistan when a national disability survey was carried out on a random sample of households. Measuring detailed capabilities, especially their freedom dimension, is quite complex and requires identifying people's potential choices in an ever-changing environment. This implies a need to extend the philosophical framework and to adopt appropriate statistical methodologies.