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Nerve agents are used in civil wars and terrorist attacks, posing a threat to public safety. Acute exposure to nerve agents such as soman (GD) causes serious brain damage, leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation. However, data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited. Here, we evaluated the potential effects of transient receptor vanilloid 4 (TRPV4) in the treatment of soman-induced status epilepticus (SE) and secondary brain injury. We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures. Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity. TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure. Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity. The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1β and IL-18 increased in soman-exposed rat hippocampus. However, TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway. In conclusion, our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation. To our knowledge, this is the first study regarding the “dual-switch” function of TRPV4 in the treatment of soman intoxication.
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Objective:To analyze and summarize the basic characteristics and clinical features of botulism patients caused by cosmetic injection of botulinum toxin.Methods:Retrospective investigation and analysis method were used to analyze the data of botulism patients caused by cosmetic injection of botulinum toxin admitted to the Poisoning Treatment Center of the PLA from March 2016 to June 2019.Results:Total of 380 cases were included in this study, including 114 hospitalized cases and 266 emergency cases. The majority patients (97.4%) were female, and most of them (39.5%) were among 30-39 years old. Most of the cases occurred in beauty salons or beauty studios, and most of the botulinum toxin injected was fake and inferior products. Onset latency were mainly distributed in 3 to 6 days. Common clinical symptoms included dizziness, blurred vision, eyes open weakness, dysphagia, chest tightness of breath, fatigue, diplopia, nausea, bilateral eyelid drooping, and dysarthria. The "4D" sign of cranial nerve injury occurred less frequently, mainly with mild and moderate poisoning; The occurrence rates of dysarthria, dysphagia, eyes open weakness, blurred vision, choking in drinking water, chewing weakness, bilateral eyelid drooping, decreased limb muscle strength, and chest tightness of breath in the hospitalized case were significantly higher than those in the emergency cases (all P < 0.05). Three hundred and nine patients received botulinum antitoxin therapy. The dose of botulinum antitoxin was 20 000 (20 000-30 000) U, with a total treatment duration of 4 (3-7) days in the emergence cases, and 30 000 (30 000-50 000) U with a total treatment time of 8 (5-11) days in the hospitalized cases, and there were significant differences between the two groups ( P < 0.05). All cases were followed up with good prognosis. Conclusions:Cosmetic injection of botulinum toxin has certain risk. If symptoms of poisoning occur such as dizziness, blurred vision, eyes open weakness and dysphagia, patients should be treated promptly, and early treatment with botulinum antitoxin can improve the prognosis.
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Objective To study the similarities and differences on in vitro replication and expression of hepatitis C virus (HCV) between human fetal hepatocytes (HFH) and 7721 cell line. Methods Human fetal hepatocytes and a hepatoma cell line 7721 were incubated with a serum from hepatitis C patient. After incubation, the presence of HCV RNA, the expression of HCV NS3 antigens in cells and/or supernatant were examined by RT-PCR, in situ hybridization and immunohistochemistry, respectively. Results It was found that: ①The intracellular HCV RNA was first detected on d 2～3 post-incubation and then could be intermittently detected in cells and/or supernatant subsequently (HCV RNA could be detected in 7721 cells during a period of at least 66 days. In HFH, HCV RNA could be detected up to 25 days after incubation); ②HCV-NS3 antigen could be expressed in infected cells; ③Minus-strand RNA of HCV was mainly located within cytoplasm by in situ hybridization. Conclusion The results suggest that both the fetal hpatocytes and the hepatoma cell line 7721 are susceptible to HCV, and especially 7721 cell line can stably support HCV replication in vitro and may be used as the target cell for long-term cultures of HCV.