Toxicity and behavioural effects of ocfentanil and 2-furanylfentanyl in zebrafish larvae and mice.

The introduction of the so-called New Psychoactive Substances represents a problem of global concern due to several factors, including multiplicity of structures, poorly known activity, short half-life in the market, lack of pure standards etc. Among these problems, of the highest relevance is also the lack of information about metabolism and adverse effects, which must be faced using simple and low-cost animal models. On these grounds, the present work has been carried out on 5 days post fertilization zebrafish (Danio rerio) larvae in comparison with adult mice (Mus musculus). Ocfentanil and 2-furanylfentanyl were administered at different concentrations to zebrafish larvae (1, 10 µM) and mice (0.1, 1, 6, 15 mg/kg). The behavioural assay showed a decrease in basal locomotor activity in zebrafish, whereas in mice this effect was evident only after the mechanical stimulus. Larva extracts and mice urine were analysed by using liquid chromatography coupled to high resolution mass spectrometry to identify the metabolic pathways of the fentanyl analogs. For 2-furanylfentanyl, the most common biotransformations observed were hydroxylation, hydration and oxidation in zebrafish larvae, whereas mice produced mainly the dihydrodiol metabolite. Hydroxylation was the major route of metabolism for ocfentanil in zebrafish larvae, while in mice the O-demethylated derivative was the main metabolite. In addition, a study was conducted to evaluate morphological effects of the two drugs on zebrafish larvae. Malformations were noticeable only at the highest concentration of 2-furanylfentanyl, whereas no significant damage was observed with ocfentanil. In conclusion, the two animal models show similarities in behavioral response and in metabolism, considering the different biological investigated.

Zebrafish larvae: A new model to study behavioural effects and metabolism of fentanyl, in comparison to a traditional mice model.

In an effort to find alternatives to study in vivo the so-called New Psychoactive Substances (NPS), the present work was undertaken to investigate the use of zebrafish larvae as animal model in pharmaco-toxicology, providing behavioural and metabolism information. For this purpose, fentanyl, the progenitor of an extremely dangerous group of NPS, was administered at different doses to zebrafish larvae (1, 10, 50, 100 µM) in comparison to mice (0.1, 1, 6, 15 mg/kg), as a well-established animal model. A behavioural assay was performed at the time of the peak effect of fentanyl, showing that the results in larvae are consistent with those observed in mice. On the other hand, several morphological abnormalities (namely yolk sac edema, abnormal pericardial edema, jaw defect and spinal curvature) were found in larvae mostly at high fentanyl doses (50, 100 µM). Larva extract and mice urine were analyzed by using liquid chromatography coupled to high resolution mass spectrometry to identify the metabolic pathways of fentanyl. The main metabolites detected were norfentanyl and hydroxyfentanyl in both the tested models. In conclusion, the present study provides evidence that fentanyl effects on zebrafish larvae and metabolism are similar to rodents and consequently support the hypothesis of using zebrafish larvae as a suitable rapid screening tool to investigate new drugs, and particularly NPS.

[Introducing marketing strategies and techniques into the field of voluntary blood donation, to meet the rise in blood demand]. / Techniques du marketing au service de la fidélisation des donneurs.

Social marketing uses marketing principles and techniques to induce a target audience to voluntary accept, reject, change or abandon a behaviour for the benefit of individuals, groups, or society as a whole. Thus, individual or societal gain is the primary goal of social marketing. This kind of marketing is frequently used in the United States or in Canada in several fields such as healthcare, social work, or the environment. In 2008, we introduced these strategies and techniques in the field of blood donation in France. This article describes what has been achieved in the last three years and outlines the main steps in the social marketing planning process: analyzing the social marketing environment, defining target audiences and objectives, building and implementing strategies and action plans, evaluating and monitoring. On the way to self-sufficiency, while respecting donors, social marketing is additional to the work done by the blood collection staffs, communication teams, and volunteers. Social marketing is a complementary tool to the work done by the blood collection staff, communication teams and blood donation organizations and can help to meet the challenge of self-sufficiency while still allowing for the privacy and rights of donors.