The Journal of toxicological sciences
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NOD-like receptor protein 3 (NLRP3) is involved in acute lung injury (ALI), but its exact role in phosgene-induced ALI is not clearly understood. The aim of the study is to explore the potential therapeutic effect of NLRP3 inflammasome modulation in the management of phosgene-induced ALI. ALI was induced in rats by phosgene exposure at 8.33 g/m3 for 5 min, 30 hr before intravenous injection of adenovirus-NLRP3 shRNA (Ad/NLRP3-shRNA). ⋯ Reduced level of pro-inflammatory interleukin (IL)-1β, IL-18, IL-33, and tumor necrosis factor (TNF)-α (all P < 0.05), but not of anti-inflammatory IL-4 and IL-10 (all P > 0.05), were found in serum and BALF from Ad/NLRP3-shRNA rats. NLRP3 gene silencing exerts beneficial effects on phosgene-induced lung injury by inhibiting NLRP3 inflammasome activation and pro-inflammatory factors, but not anti-inflammatory factors. Disruption of NLRP3 inflammasome activation might be used as a therapeutic modality for the treatment of phosgene-induced ALI.
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Recent studies have shown that sevoflurane can cause long-term neurotoxicity and learning and memory impairment in developing and progressively neurodegenerative brains. Sevoflurane is a widely used volatile anesthetic in clinical practice. Late gestation is a rapidly developing period in the fetal brain, but whether sevoflurane anesthesia during late gestation affects learning and memory of offspring is not fully elucidated. ⋯ HDAC2 inhibitor suberoylanilide hydroxamic acid (SAHA) treatment alleviated all of these changes in offspring rats. Therefore, the present study indicates that sevoflurane exposure during late gestation impairs offspring rat's learning and memory via upregulation of the expression of HDAC2 and downregulation of the expression of CREB and NR2B. SAHA can alleviate these impairments.
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Observational Study
Clinical characteristics of patients who overdose on multiple psychotropic drugs in Tokyo.
The purpose of this study was to identify the clinical aspects leading to overdose of multiple psychotropic drugs, in order to determine areas which need attention in the proper treatment of overdose patients. ⋯ Patients who ingested an overdose of more than 60 tablets of psychotropic drugs should be considered a high-risk group requiring intensive care with extended ICU stay. In case of including antipsychotics and/or barbiturates, the patient should be observed carefully due to a higher risk of medical complications.
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Exposure to humidifier disinfectants was identified in 2011 as the potential cause of an outbreak of lung disease in Korea. It is estimated that over 8 million people have been exposed to humidifier disinfectants-chemicals added to the water used in humidifiers to prevent the growth of microorganisms-since their commercial introduction. ⋯ Lesions observed in the lungs of patients were similar to those observed in laboratory animals exposed to PHMG-P. In this review, we outline the physicochemical and toxicological properties of PHMG-P, and introduce a putative mechanism for its lung toxicity based in large part on research findings to date.
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Propofol can induce acute neuronal apoptosis or long-term cognitive dysfunction when exposed at early age in rodents, but it is unclear how the neurotoxicity including neuronal apoptosis and synaptic loss will change in a dynamic manner with brain development after multiple or single exposure of propofol, and the role of neuronal apoptosis and synaptic loss in propofol-induced long-term cognitive impairment needs to be elucidated. In this study, we investigated dynamic changes of neuronal apoptosis, neuronal density, synaptic density in hippocampal CA1 region and the prelimbic cortex (PrL), and long-term cognitive function after multiple or single exposure of propofol in neonatal rats. ⋯ Results suggest that single exposure of propofol only induces transient neuronal apoptosis and deficit, while multiple exposures of propofol induce persistent neuronal apoptosis, neuronal deficit, synaptic loss, and long-term cognitive impairment. Furthermore, persistent neuronal deficit and disturbances in synapse formation but not transient neuronal apoptosis may contribute to long-term cognitive impairment.