Cannabinoid CB1 receptor antagonism prevents neurochemical and behavioural deficits induced by chronic phencyclidine.

Clinical and laboratory studies suggest that the endocannabinoid system is involved in schizophrenia disorders. Recent evidence indicates that cannabinoid receptor (CB1) antagonists have a pharmacological profile similar to antipsychotic drugs. We investigated the behavioural and biochemical effects of the CB1 antagonist AM251 in a phencyclidine (PCP) animal paradigm modelling the cognitive deficit and some negative symptoms of schizophrenia. Chronic AM251 (0.5 mg/kg for 3 wk) improved the PCP-altered recognition memory, as indicated by a significant amelioration of the discrimination index compared to chronic PCP alone (2.58 mg/kg for 1 month). AM251 also reversed the PCP-induced increase in immobility in the forced swim test resembling avolition, a negative sign of schizophrenia. In order to analyse the mechanisms underlying these behaviours, we studied the effects of AM251 on the endocannabinoid system (in terms of CB1 receptor density and functional activity and endocannabinoid levels) and c-Fos protein expression. The antagonist counteracted the alterations in CB1 receptor function induced by PCP in selected cerebral regions involved in schizophrenia. In addition, in the prefrontal cortex, the key region in the integration of cognitive and negative functions, AM251 markedly raised anandamide levels and reversed the PCP-induced increase of 2-arachidonoylglycerol concentrations. Finally, chronic AM251 fully reversed the PCP-elicited expression of c-Fos protein in the prefrontal cortical region. These findings suggest an antipsychotic-like profile of the CB1 cannabinoid receptor antagonist which, by restoring the function of the endocannabinoid system, might directly or indirectly normalize some of the neurochemical maladaptations present in this schizophrenia-like animal model

Efficacy and Safety of a Hyaluronic Acid-Containing Gauze Pad in the Treatment of Chronic Venous or Mixed-Origin Leg Ulcers: A Prospective, Multicenter, Randomized Controlled Trial.

International audienceIntroduction: Hyaluronic acid (HA)-containing formulations routinely are utilized along with standard therapy to promote faster healing of chronic wounds; evidence to guide clinical decisions on the use of topical HA in the healing of vascular leg ulcers is limited.Objective: This study compared the efficacy and safety of an HA-impregnated gauze pad with an identical gauze pad without HA in the treatment of chronic leg ulcers of vascular origin.Materials and methods: A prospective, multicenter, multinational, parallel-group, randomized, double-blind, clinical study was conducted between June 13, 2017, and December 31, 2018. Adults with 1 or more chronic leg ulcers of venous or mixed origin between 2 months and 4 years' duration were eligible to participate. Participants were randomized to treatment consisting of standard care (ie, ulcer cleansing, debridement/anesthesia as necessary, and optimized compression) and either application of a gauze pad containing 0.05% HA or a neutral comparator once daily for a maximum of 20 weeks. The primary efficacy endpoint was complete ulcer healing (100% reepithelialization of the wound area centrally assessed by 1 independent and experienced assessor blinded with respect to the treatment applied, as shown on digital photographs taken under standardized conditions at or before 20 weeks and confirmed 3 weeks later). Secondary efficacy endpoints included the percentage of completely healed target ulcers, residual area of target ulcer relative to baseline, the condition of the periulcerous skin, the total amount of analgesics used, the incidence of infection at the ulcer site of the target ulcer, patient adherence to treatment, time to achieve complete healing as centrally assessed, and pain intensity as measured by a visual analog scale.Results: Among the 168 participants (82 in the HA gauze pad group and 86 in the neutral gauze pad group), 33 (39.8%) in the HA group experienced complete healing of the target ulcer, which was significantly higher than the neutral comparator group (15, 18.5%; P = .002). Results in the full analysis and per-protocol sets were consistent with the primary results; no significant difference was noted in outcomes when participants' wounds were stratified according to baseline ulcer size.Conclusions: HA delivered in a gauze pad formulation could be a beneficial treatment for chronic leg ulcers of venous or mixed origin

Coating of Cerium oxide nanoparticles with natural molecules modifies the toxic effects towards Mytilus galloprovincialis

In the framework of a need to properly predict environmental implications of nanoparticles (NPs), an emerging challenge is to address the complex dynamic of physicochemical and biological processes that drive NP’s toxicity once they are released into natural matrices. In particular this study focused on the effects of surface coating, acquired through the interaction with natural biomolecules, on the behaviour and ecotoxicity of NPs. To this aim CeO2NPs were ad hoc synthesized with different coating agents such as Alginate and Chitosan, two abundant polysaccharides in the aquatic environment. The mussel Mytilus galloprovincialis was used as a biological model to test whether these surface modifications could influence NP’s fate, uptake and toxicity. Mussels were exposed to 100 ug/L of CeO2NPs Naked and coated with the two polysaccharides for 7 days and to 1 ug/L for 28 days. A suite of biomarkers related to oxidative stress/damage and energy metabolism was applied. Results showed that the different coating determined different hydrodynamic behavior and stability in water. The coatings affected also CeO2NPs toxicological outcomes as exposure to CeO2NPs coated with Alginate triggered oxidative damage, while mussels exposed to CeO2NPs coated with Chitosan showed increase of antioxidant enzyme activities. Our results highlight that interactions with biomolecules largely present in the aquatic environment could be a driver of NPs’ toxicity

Interactions on Cerium oxide nanoparticles with natural biomolecules affect toxicity for aquatic biota

While societal benefits and improvements of nanotechnology are well established, several concerns have raised regarding the potential risk of nanoparticles (NPs) for the environment and human health. In the framework of a need to properly predict environmental implications of NPs, an emerging challenge is to address the complex dynamic of physicochemical and biological processes that drive NPs toxicity once they are released into natural matrices. Therefore the objective of this study was to perform an ecotoxicological evaluation of CeO2NPs with different surface modifications, representative of NPs bio-interaction with molecules naturally occurring in water environment, to identify the role of biomolecule coating on nanoceria toxicity for aquatic organisms. Ad hoc synthesis of CeO2NPs with different coating agents such as Alginate and Chitosan was performed and the NPs were fully characterized. The crustacean Daphnia magna and the bivalve Dreissena polymorpha were used as biological models to test the different ecotoxicity of the CeO2NPs. Several endpoints were evaluated at different level of biological organization such as: the imbalance of the oxidative status by the measurement of some antioxidant enzyme activities, oxidative damage, genotoxicity and behavioral responses. Overall results show that the coating with chitosan increases CeO2NPs stability in exposure media. The different coating influenced also significantly the toxic effects of CeO2NPs in species-specific way. Our findings emphasize that environmental modifications affect significantly the environmental fate and ecotoxicity of NPs

Interactions with natural biomolecules affect the ecotoxicity Cerium oxide nanoparticles for aquatic biota

The ongoing development of nanotechnology have raised several concerns regarding the potential risk of nanoparticles (NPs) for the environment, in particular the aquatic ecosystems. In the framework of a need to properly predict environmental implications of NPs, an emerging challenge is to address the complex dynamic of physicochemical and biological processes that drive NPs toxicity once they are released into natural matrices. Therefore the objective of this study was to perform an ecotoxicological evaluation of CeO2NPs with different surface modifications, representative of NPs bio-interaction with molecules naturally occurring in water environment, to identify the role of biomolecule coating on nanoceria toxicity for aquatic organisms. Ad hoc synthesis of CeO2NPs with different coating agents such as Alginate and Chitosan was performed and the NPs were fully characterized. The freshwater species Daphnia magna and Dreissena polymorpha were used as biological models to test the different ecotoxicity of the CeO2NPs. Several endpoints were evaluated at different level of biological organization, from the molecular to the entire organism. Overall results show that the different coating affects the hydrodynamic behavior of CeO2NPs in exposure media. The different coating influenced also significantly the toxic effects of CeO2NPs in species-specific way. Specifically, in D. magna none of the CeO2NPs triggered a significant oxidative stress, but behavioural assay showed that CeO2NPs coated with chitosan determined hyperactivity. In zebra mussel the CeO2NPs coated with alginate seems to behave as ROS scavenger. Our findings emphasize that the eco-corona is able to influence the environmental fate and ecotoxicity of NPs

Environmental biomolecules affect the fate and toxicity of Cerium oxide nanoparticles for aquatic biota

The ongoing development of nanotechnology have raised several concerns regarding the potential risk of nanoparticles (NPs) for the environment, in particular the aquatic ecosystems. In the framework of a need to properly predict environmental implications of NPs, an emerging challenge is to address the complex dynamic of physicochemical and biological processes that drive NPs toxicity once they are released into natural matrices. Therefore, the objective of this study was to perform an ecotoxicological evaluation of CeO2NPs with different surface modifications, representative of NPs bio-interaction with molecules naturally occurring in water environment, to identify the role of biomolecule coating on nanoceria toxicity for aquatic organisms. Ad hoc synthesis of CeO2NPs with different coating agents such as Alginate and Chitosan was performed, and the NPs were fully characterized. The marine bacteria Aliivibrio fischeri, the freshwater crustacean Daphnia magna and the freshwater bivalve Dreissena polymorpha were used as biological models to test the different ecotoxicity of the CeO2NPs. Several endpoints were evaluated at different level of biological organization, from the molecular to the entire organism. Overall results show that the different coating affects the hydrodynamic behavior of CeO2NPs in exposure media. The different coating influenced also significantly the toxic effects of CeO2NPs in species-specific way. Specifically, in D. magna none of the CeO2NPs triggered a significant oxidative stress, but behavioral assay showed that CeO2NPs coated with Chitosan determined hyperactivity. In zebra mussel the CeO2NPs coated with Alginate affected significantly the antioxidative stress machinery. Our findings emphasize the role of environmental modification in determining the NP effects on aquatic organisms