One of the current challenges in wound care is the development of multifunctional dressings that can both protect the wound from external agents and promote the regeneration of the new tissue. Here, we show the combined use of two naturally derived compounds, sodium alginate and lavender essential oil, for the production of bioactive nanofibrous dressings by electrospinning, and their efficacy for the treatment of skin burns induced by midrange ultraviolet radiation (UVB). We demonstrate that the engineered dressings reduce the risk of microbial infection of the burn, since they stop the growth of Staphylococcus aureus. Furthermore, they are able to control and reduce the inflammatory response that is induced in human foreskin fibroblasts by lipopolysaccharides, and in rodents by UVB exposure. In particular, we report a remarkable reduction of pro-inflammatory cytokines when fibroblasts or animals are treated with the alginate-based nanofibers. The down-regulation of cytokines production and the absence of erythema on the skin of the treated animals confirm that the here described dressings are promising as advanced biomedical devices for burn management.

Adenosine, an ubiquitous neuromodulator, and its analogues have been shown to produce ‘depressant’ effects in animal models believed to be relevant to depressive disorders, while adenosine receptor antagonists have been found to reverse adenosine‐mediated ‘depressant’ effect. We have designed studies to assess whether adenosine A_2A receptor antagonists, or genetic inactivation of the receptor would be effective in established screening procedures, such as tail suspension and forced swim tests, which are predictive of clinical antidepressant activity. Adenosine A_2A receptor knockout mice were found to be less sensitive to ‘depressant’ challenges than their wildtype littermates. Consistently, the adenosine A_2A receptor blockers SCH 58261 (1 – 10 mg kg⁻¹, i.p.) and KW 6002 (0.1 – 10 mg kg⁻¹, p.o.) reduced the total immobility time in the tail suspension test. The efficacy of adenosine A_2A receptor antagonists in reducing immobility time in the tail suspension test was confirmed and extended in two groups of mice. Specifically, SCH 58261 (1 – 10 mg kg⁻¹) and ZM 241385 (15 – 60 mg kg⁻¹) were effective in mice previously screened for having high immobility time, while SCH 58261 at 10 mg kg⁻¹ reduced immobility of mice that were selectively bred for their spontaneous ‘helplessness’ in this assay. Additional experiments were carried out using the forced swim test. SCH 58261 at 10 mg kg⁻¹ reduced the immobility time by 61%, while KW 6002 decreased the total immobility time at the doses of 1 and 10 mg kg⁻¹ by 75 and 79%, respectively. Administration of the dopamine D₂ receptor antagonist haloperidol (50 – 200 μg kg⁻¹ i.p.) prevented the antidepressant‐like effects elicited by SCH 58261 (10 mg kg⁻¹ i.p.) in forced swim test whereas it left unaltered its stimulant motor effects. In conclusion, these data support the hypothesis that A_2A receptor antagonists prolong escape‐directed behaviour in two screening tests for antidepressants. Altogether the results support the hypothesis that blockade of the adenosine A_2A receptor might be an interesting target for the development of effective antidepressant agents. British Journal of Pharmacology (2001) 134, 68–77; doi:10.1038/sj.bjp.0704240

After its release, the endocannabinoid anandamide is taken up from the synaptic cleft by internalization by neurons and astrocytes. Although several lines of evidence suggest that the anandamide uptake itself is a carrier-mediated diffusion process, the molecular identity of the transporter was unknown until now. Here Fu et al. show that anandamide uptake is mediated by a novel protein named FAAH-like anandamide transporter (FLAT) that is generated as an alternative splicing product of the fatty acid amide hydrolase-1 (Faah) mRNA. The endocannabinoid anandamide is removed from the synaptic space by a selective transport system, expressed in neurons and astrocytes, that remains molecularly uncharacterized. Here we describe a partly cytosolic variant of the intracellular anandamide-degrading enzyme fatty acid amide hydrolase-1 (FAAH-1), termed FAAH-like anandamide transporter (FLAT), that lacked amidase activity but bound anandamide with low micromolar affinity and facilitated its translocation into cells. Known anandamide transport inhibitors, such as AM404 and OMDM-1, blocked these effects. We also identified a competitive antagonist of the interaction of anandamide with FLAT, the phthalazine derivative ARN272, that prevented anandamide internalization in vitro, interrupted anandamide deactivation in vivo and exerted profound analgesic effects in rodent models of nociceptive and inflammatory pain, which were mediated by CB1 cannabinoid receptors. The results identify FLAT as a critical molecular component of anandamide transport in neural cells and a potential target for therapeutic drugs.