Detection of Light Images by Simple Tissues as Visualized by Photosensitized Magnetic Resonance Imaging

In this study, we show how light can be absorbed by the body of a living rat due to an injected pigment circulating in the blood stream. This process is then physiologically translated in the tissue into a chemical signature that can be perceived as an image by magnetic resonance imaging (MRI). We previously reported that illumination of an injected photosynthetic bacteriochlorophyll-derived pigment leads to a generation of reactive oxygen species, upon oxygen consumption in the blood stream. Consequently, paramagnetic deoxyhemoglobin accumulating in the illuminated area induces changes in image contrast, detectable by a Blood Oxygen Level Dependent (BOLD)-MRI protocol, termed photosensitized (ps)MRI. Here, we show that laser beam pulses synchronously trigger BOLD-contrast transients in the tissue, allowing representation of the luminous spatiotemporal profile, as a contrast map, on the MR monitor. Regions with enhanced BOLD-contrast (7-61 fold) were deduced as illuminated, and were found to overlap with the anatomical location of the incident light. Thus, we conclude that luminous information can be captured and translated by typical oxygen exchange processes in the blood of ordinary tissues, and made visible by psMRI (Fig. 1). This process represents a new channel for communicating environmental light into the body in certain analogy to light absorption by visual pigments in the retina where image perception takes place in the central nervous system. Potential applications of this finding may include: non-invasive intra-operative light guidance and follow-up of photodynamic interventions, determination of light diffusion in opaque tissues for optical imaging and possible assistance to the blind

Picumeterol: Dissociation of improvement in lung function and reduction of airways hyperresponsiveness in asthmatics

Aims The new potent and selective beta(2)-adrenoceptor agonist, GR 114297A (picumeterol) is the R-enantiomer of the racemic form, GR 63411B. Picumeterol has been shown to produce long-lasting relaxation of airways smooth muscle both in vitro and in vivo. We assessed the intrinsic activity of picumeterol by increasing intracellular levels of c-AMP and compared this with isoprenaline and salbutamol. Methods In human atopic asthmatics, we have investigated the duration of action and efficacy of picumeterol and GR 63411B with regard to improvement in resting lung function (i.e. FEV(1)) and airways responsiveness (i.e. PC20) to methacholine (MCh). The study design consists of two clinical parts each for one drug. Different asthmatics participated in the two studies, seven in the first part and eight in the second part. In human bronchial smooth muscle cells in vitro, we have investigated the intrinsic activity of picumeterol in increasing intracellular levels of cyclic AMP and compared it with isoprenaline and salbutamol. Results In vivo, both drugs caused bronchodilatation with similar potency, but, their effects were short-lasting. Despite their bronchodilator activity, neither drug improved PC20, when compared with placebo. lit vitro, picumeterol was found have intrinsic activity lower than the other beta(2)-adrenoceptor agonists tested. Conclusions In the clinical studies, the bronchodilator potencies of picumeterol and GR 63411B were similar. However, both drugs were short-acting, which is at odds with their activity in vitro. Our data suggest that these compounds display dissociation between bronchodilator activity and protection against MCh-induced bronchoconstriction. These findings may be explained by low intrinsic activity and need further conformation

Evidence-Based Recommendations to Improve the Safe Use of Drugs in Patients with Liver Cirrhosis

Contains fulltext : 191902.pdf (publisher's version ) (Open Access

Economic-environmental trade-offs and the conservativeness of the upper partial moment

Probabilistic programming are typically used to model economic-environmental trade-when environmental outcomes are stochastic. Application of available probabilistic programming techniques such as the upper partial moment (UPM) is problematic due to the conservativeness of the estimated the compliance probability. Conservatively estimated trade-offs may result in overregulation of agricultural production practices. Although the conservativeness of the UPM is usually acknowledged by researchers, none of the researchers investigated the size of conservativeness of the UPM. An alternative non-linear trade-off model specification is developed to investigate the conservativeness of the UPM. Meta data from the validated Soil Water Balance (SWB) crop growth simulation model for irrigated maize in South Africa is used to show that the UPM is very conservative in the estimation of the trade-offs comparing to the new method. However, the size of the conservativeness is very situation-specific and varies due to differences in fixed resources, fertilizer application methods and conservativeness measures