Background: Omalizumab, mepolizumab, benralizumab, and dupilumab are the currently available biologics used to treat asthma in Japan. Anaphylaxis following treatment with mepolizumab or benralizumab is considered rare. Case presentation: We report the case of a 35-year-old woman with severe asthma, who experienced anaphylaxis following the administration of benralizumab, mepolizumab, and omalizumab, separately. The therapy with biologics was chosen to avoid the repeated use of systemic corticosteroids for asthma exacerbations. The mechanisms underlying anaphylaxis caused by these three biologics remain unclear. The patient's asthma symptoms and lung function improved after treatment with bronchial thermoplasty. Conclusions: To our knowledge, this is the first report of an asthmatic patient developing anaphylaxis after commencement of benralizumab, mepolizumab, and omalizumab therapy. These three biologics should be administered carefully, and patients should be monitored for anaphylaxis.
Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder and the most common cause of dementia in the elderly. An excessive accumulation of amyloid β peptide (Aβ), derived from amyloid precursor protein (APP). APP is sequentially cleaved by membrane bound protease called α-, β-and γ-secretase, which is being explored as a target for therapy and prevention of AD. Although previous reports indicated that these secretases have a significant role in development, these functions in developed neurons and synapses are still largely unknown.We investigated the roll of these secretase in synaptic formation and maturation using organotypic hippocampal slice cultures because they have advantages over both in vivo and in vitro platforms. The hippocampal slices were obtained from anaesthetized rats at postnatal day 7-8 and placed on a polytetrafluoroethylene membrane filter, and culture medium (50% MEM, 25% HBSS, 25% horse serum) was added up to the bottom surface of the filter. For the analysis of synapse formation and maturation, we evaluated the expression level of synaptic proteins and synaptic activity. In this study, we utilized hippocampal slice cultures as an ex vivo model that enabled continuous and long-term analysis for secretases. Furthermore, we suggested that 3-20 days in vitro were a critical period of synapse formation and maturation in hippocampal slice cultures. During the period of synapse formation and maturation, pharmacological inhibition of secretases changed the expression levels of synaptic proteins. After synaptic maturation, secretase inhibition did not affect the synaptic protein, except for APP. Our results and previous reports indicate that secretase activity is important for synaptogenesis and maturation. Furthermore, we suggest that cultured hippocampal slices are useful tools for understanding physiological functions of membrane associated protease. This report is the first step toward ex vivo continuous analysis of APP and secretases.
Electrical injuries induce ventricular arrhythmias, which are lethal. Therefore, it is important to evaluate the risk of arrhythmias at initial presentation to the emergency department in cases of electrical injuries. Here, we report two cases with electrical injuries, where current flowed between the upper limbs, requiring 24-h hospitalization for arrhythmia monitoring. The patients were 57- and 30-year-old men, who sustained separate electrical injuries (6600 V, line voltage), with current flow from one hand to the other. They did not develop any ventricular arrhythmias during hospitalization and were discharged. The risk for ventricular arrhythmias is lower for electrical injuries occurring between the upper limbs than for those occurring between the upper and lower limbs. We conclude that 24-h hospitalization for monitoring of patients with electrical injuries of the upper limbs may be sufficient.
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