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ional development.Oral inhalation results in pulmonary drug targeting and thereby reduces systemic side effects, making it the preferred means of drug delivery for the treatment of respiratory disorders such as asthma, chronic obstructive pulmonary disease or cystic fibrosis. selleck chemicals llc In addition, the high alveolar surface area, relatively low enzymatic activity and rich blood supply of the distal airspaces offer a promising pathway to the systemic circulation. This is particularly advantageous when a rapid onset of pharmacological action is desired or when the drug is suffering from stability issues or poor biopharmaceutical performance following oral administration. Several cell and tissue-based in vitro and ex vivo models have been developed over the years, with the intention to realistically mimic pulmonary biological barriers. It is the aim of this review to critically discuss the available models regarding their advantages and limitations and to elaborate further which biopharmaceutical questions can and cannot be answered using the existing models.Many animal studies and early clinical trials suggested that N-acetylcysteine (NAC) may benefit addiction treatment. The present study tried to evaluate whether chronic administration of systemic NAC during the extinction period and acute administration of systemic NAC on the reinstatement day could reduce the maintenance of the morphine rewarding properties in the conditioned place preference (CPP) paradigm in the rats. Ninety-six adult male Wistar rats (190-220 g) were examined with morphine (7 mg/kg; sc) and saline (1 mL/kg; sc) during the 3-day conditioning phase in the CPP paradigm. After the acquisition of morphine CPP, different doses of NAC were daily administered during the extinction period (5, 10, 25, and 50 mg/kg; ip), or 30 min before the CPP test on the reinstatement day (2, 5, 10, 25, and 50 mg/kg; ip). Conditioning score and locomotor activity were recorded by the video tracking system and Ethovision software after acquisition on the post-conditioning day, the extinction period, and reinstatement day. Daily NAC administration in high doses (25 and 50 mg/kg; ip) reduced extinction-responding compared with the vehicle-control group during the extinction period. Although a single injection of NAC in doses 10, 25, 50 mg/kg decreased the reinstatement of morphine-induced CPP, two lower doses (2 and 5 mg/kg) could not significantly reduce the CPP scores. These are the first data suggesting that NAC's application during the extinction period could attenuate the morphine reward-associated behaviors in the rats. Moreover, NAC could inhibit the reinstatement of morphine CPP, which adds to the growing appreciation that the NAC may have potential therapeutic use in combating morphine dependence. It can be consistent with the hypothesis of the involvement of the glutamatergic system in the pathophysiology of addiction.The present work focuses on the ecotoxicological effects of montelukast sodium (MTL) and its photoproducts, obtained under environmentally-like conditions. Despite of the potential presence in surface waters and the common use of MTL as asthma drug, limited data has been published for its photodegradation, while no information is available for its ecotoxicity. Light-induced degradation is an effective way for drugs to degrade in aquatic environments, and MTL is highly photosensitive, even by exposure to sunlight. In this study, solar-simulated irradiation of the drug in water was investigated. The drug was quickly converted into a series of photoproducts that were spectroscopically characterized. The possible photoreaction pathways were proposed. Ecotoxicity tests were performed on parent compound and mixture of photoproducts towards two bioindicators (Raphidocelis subcapitata and Daphnia magna). Results evidenced that effects of MTL on D. magna (EC50 = 16.4 mg/L) were greater than effects on R. subcapitata (EC50 = 195.7 mg/L). Microscopy observations revealed that MTL had mainly accumulated in the gut of daphnia. Toxicity data on photolysed solutions highlighted the presence of residual toxicity in all samples, evidencing that no complete mineralization occurred. Future research should focus on monitoring of MTL concentrations in the environment and study its effects in bioaccumulation tests.The use of electronic cigarettes (e-cigarettes) has increased due to the belief that they are healthier than tobacco cigarettes. E-cigarettes contain a metallic heating coil (composed of Ni, Cr, Al and other metals) to heat a solution (commonly called e-liquid) and convert it into an aerosol. This aerosol is inhaled (vaped) by the users who can be potentially exposed to a wide variety of metals. We investigated the possible transfer of metals from the coil to the e-liquid and the generated aerosol, and how the exposure to this aerosol can increase metal body burden in e-cigarette users. We recruited 75 e-cigarette users (50 who only vaped and 25 dual users who vaped and smoked) and 25 controls who neither vaped nor smoked. E-liquid samples before (dispenser e-liquid) and after (tank e-liquid) being added to their devices were collected. Aerosol samples were collected using a condensation method. All participants provided urine and hair samples. All samples were analyzed for metals by ICP-MS. We observed highethe device, likely the heating resistance, as their concentrations were low in the dispenser e-liquid and higher in the aerosol and the e-liquid left in the tank. Although the exposure to e-cigarette aerosol can have an influence in the body burden of metals, aerosol metal levels were not clearly associated with metal levels in biological samples such as urine or hair in e-cigarette users in this study.Mangrove soils with high organic carbon (Corg) content are likely to contain Corg that is vulnerable to remineralization during land use changes. Mangrove conversion to different land uses might deplete soil Corg stocks causing variable carbon dioxide emissions, but the extent of these emissions and the fraction of soil Corg (i.e., labile or stable/recalcitrant) that is mostly lost is poorly understood. Here, we study mangrove soil Corg degradability and its susceptibility to mineralization after mangrove disturbance. We measured changes in soil properties, organic matter (OM) stability and Corg pools and sources across a mangrove disturbance gradient (i.e., pristine forests, degraded mangroves receiving domestic sewage and shrimp farm effluents, and shrimp ponds). Results showed that the conversion of mangroves to shrimp ponds caused the most severe changes in soil properties, OM and Corg characteristics. Shrimp pond soils contained the lowest OM-Corg pools, consisted mostly of stable OM (i.e., recalcitrant and refractory; 36.