Metaphors in Nanomedicine: The Case of Targeted Drug Delivery

International audienceThe promises of nanotechnology have been framed by a variety of metaphors, that not only channel the attention of the public, orient the questions asked by researchers, and convey epistemic choices closely linked to ethical preferences. In particular, the image of the 'therapeutic missile' commonly used to present targeted drug delivery devices emphasizes precision, control, surveillance and efficiency. Such values are highly praised in the current context of crisis of pharmaceutical innovation where military metaphors foster a general mobilization of resources from multiple fields of cutting-edge research. The missile metaphor, reminiscent of Paul Ehrlich's 'magic bullet', has framed the problem in simple terms: how to deliver the right dose in the right place at the right moment? Chemists, physicists and engineers who design multi-functional devices operating in vitro can think in such terms, as long as the devices are not actually operating through the messy environment of the body. A close look at what has been done and what remains to be done suggests that the metaphor of the "therapeutic missile" is neither sufficient, nor even necessary. Recent developments in nanomedicine suggest that therapeutic efficacy cannot be obtained without negotiating with the biological milieu and taking advantage of what it affords. An 'oïkological' approach seems more appropriate, more heuristic and more promising than the popular missile. It is based on the view of organism as an oikos that has to be carefully managed. The dispositions of nanocapsules have to be coupled with the affordances of the environment. As it requires dealing with nanoparticles as relational entities (defined by their potential for interactions) rather than as stable substances (defined by intrinsic properties) this metaphor eventually might well change research priorities in nanotechnology in general

Erosive cola-based drinks affect the bonding to enamel surface: an in vitro study

Objective: This study aimed to assess the impact of in vitro erosion provoked by different cola-based drinks (Coke types), associated or not with toothbrushing, to bonding to enamel. Material and methods: Forty-six bovine enamel specimens were prepared and randomly assigned into seven groups (N=8): C- Control (neither eroded nor abraded), ERO-RC: 3x/1-minute immersion in Regular Coke (RC), ERO-LC: 3x/1-minute immersion in Light Coke (LC), ERO-ZC: 3x/1-minute immersion in Zero Coke (ZC) and three other eroded groups, subsequently abraded for 1-minute toothbrushing (EROAB-RC, EROAB-LC and EROAB-ZC, respectively). After challenges, they were stored overnight in artificial saliva for a total of 24 hours and restored with Adper Single Bond 2/Filtek Z350. Buildup coronal surfaces were cut in 1 mm2 -specimens and subjected to a microtensile test. Data were statistically analyzed by two-way ANOVA/Bonferroni tests (α=0.05). Failure modes were assessed by optical microscopy (X40). The Interface of the restorations were observed using Confocal Laser Scanning Microscopy (CLSM). Results: All tested cola-based drinks significantly reduced the bond strength, which was also observed in the analyses of interfaces. Toothbrushing did not have any impact on the bond strength. CLSM showed that except for Zero Coke, all eroded specimens resulted in irregular hybrid layer formation. Conclusions: All cola-based drinks reduced the bond strength. Different patterns of hybrid layers were obtained revealing their impact, except for ZC

Limits on the production of scalar leptoquarks from Z (0) decays at LEP

A search has been made for pairs and for single production of scalar leptoquarks of the first and second generations using a data sample of 392000 Z0 decays from the DELPHI detector at LEP 1. No signal was found and limits on the leptoquark mass, production cross section and branching ratio were set. A mass limit at 95% confidence level of 45.5 GeV/c2 was obtained for leptoquark pair production. The search for the production of a single leptoquark probed the mass region above this limit and its results exclude first and second generation leptoquarks D0 with masses below 65 GeV/c2 and 73 GeV/c2 respectively, at 95% confidence level, assuming that the D0lq Yukawa coupling alpha(lambda) is equal to the electromagnetic one. An upper limit is also given on the coupling alpha(lambda) as a function of the leptoquark mass m(D0)

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Metal insulator transitions in the triclinic reduced Molybdenum oxides.

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Study of homogenization treatments of cast 5xxx series ai-mg-mn alloy modified with zn

Microstructural changes of DC-cast 5xxx series AI-Mg-Mn alloy modified with Zn addition occurring during the homogenization treatments were studied through the thickness of a rolling ingot. The homogenization treatments included: low temperature annealing at 430 degrees C for 12h and high temperature homogenization at 550 degrees C for 16h. Microstructure evolution was followed by electrical resistivity measurements, optical microscopy, SEM and TEM characterization and microanalysis. During the homogenization, decomposition of the supersaturated solid solution, present in the as-cast state, occurred. Distribution of the precipitates was dictated by segregations and could be related to the partition coefficients of alloying elements. It was found that during the high temperature homogenization not only dissolution processes occurred, but also precipitation of new phases