Antihistaminic drug

  • 文章类型: Journal Article
    在过敏反应的后期,体液中发现了翻译控制的肿瘤蛋白(TCTP)的分泌,TCTP与过敏性疾病有关。此外,在动物模型中,阻断TCTP已被证明有助于治疗哮喘和过敏.本研究的目的是产生抗TCTP单克隆抗体(mAb),测试它们在体外抑制二聚体TCTP(dTCTP)的细胞因子样功能的能力,并评估它们在卵清蛋白(OVA)诱导的气道炎症的小鼠模型中的治疗效果。我们首先验证了4种抗TCTPmAb对dTCTP诱导的BEAS-2B细胞分泌IL-8的抑制作用。探讨抗TCTP单克隆抗体对过敏性气道炎症的抗炎作用,我们在OVA攻击前用抗TCTPmAb治疗OVA致敏小鼠。支气管肺泡灌洗液(BALF)细胞的变化,BALF和肺匀浆中IL-4、IL-5和IL-13水平,OVA特异性IgE的血浆水平,并对肺组织进行分析。我们发现JEW-M449抗TCTPmAb与TCTP的柔性环结合,并显着抑制dTCTP诱导的IL-8释放,使其成为我们研究中最有效的抑制剂。我们还发现,用JEW-M449治疗可显着减少炎症细胞的浸润,并以剂量依赖性方式抑制OVA诱导的BALF和肺匀浆中2型细胞因子的上调。此外,JEW-M449可显着减弱杯状细胞增生和粘液分泌的程度。我们的结果表明,TCTP柔性环的特异性靶向是治疗气道炎症性疾病的有效策略。
    Secretion of translationally controlled tumor protein (TCTP) was found in body fluids during the late phase of allergic reactions, implicating TCTP in allergic diseases. Furthermore, blocking TCTP has been shown to be helpful in treating asthma and allergies in animal models. The objectives of this study were to produce anti-TCTP monoclonal antibodies (mAbs), test their ability to inhibit the cytokine-like function of dimeric TCTP (dTCTP) in vitro and to assess their therapeutic effects in a murine model of ovalbumin (OVA)-induced airway inflammation. We first verified the inhibitory effects of 4 anti-TCTP mAbs on dTCTP-induced secretion of IL-8 in BEAS-2B cells. To investigate the anti-inflammatory effect of anti-TCTP mAbs on allergic airway inflammation, we treated OVA-sensitized mice with anti-TCTP mAbs before OVA challenge. The changes in bronchoalveolar lavage fluid (BALF) cells, IL-4, IL-5, and IL-13 levels in both BALF and lung homogenates, plasma levels of OVA-specific IgE, and lung tissues were analyzed. We found that JEW-M449 anti-TCTP mAb bound to the flexible loop of TCTP and significantly inhibited dTCTP-induced IL-8 release, making it the most effective inhibitor in our study. We also found that treatment with JEW-M449 significantly reduced the infiltration of inflammatory cells and suppressed the OVA-induced upregulation of type 2 cytokines in both BALF and lung homogenates in a dose-dependent manner. In addition, JEW-M449 significantly attenuated the degree of goblet cell hyperplasia and mucus secretion. Our results demonstrate that specific targeting of the flexible loop of TCTP is a potent strategy for treating airway inflammatory diseases.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Randomized Controlled Trial
    飞行模拟器在机组人员培训中起着至关重要的作用。偶尔,晕动病的症状,定义为模拟器疾病,在这些会议期间发展。晕动病的预防方法已经被彻底调查,然而,只有少数研究检查了模拟疾病的预防性治疗。这项研究的目的是研究东pol碱(抗胆碱能药)与桂利嗪(抗组胺药)预防直升机模拟器疾病的功效。在这项研究中,使用了经过验证的模拟器疾病问卷(SSQ)评分来确定模拟器疾病症状的严重程度。计算初步SSQ分数和每次排序后的SSQ分数。每个参与者都被给予东pol碱,在每个训练日的第一次训练前,以双盲随机方式服用桂利嗪或安慰剂。41名直升机飞行员参加了审判。平均年龄为30.5±7.1。在服用桂利嗪两小时后,SSQ值从初步SSQ问卷的平均值73.30显著提高到平均值30.92(p=0.012,95%CI[8.071,76.703])。在缓解模拟器疾病症状方面,东莨菪碱的效果不如桂利嗪和安慰剂。这项研究是第一个比较东pol碱与cinnarizine预防模拟器疾病的研究。根据这项研究的结果,我们建议使用桂利嗪而不是东pol碱预防模拟器疾病。本文受版权保护。保留所有权利。
    Flight simulators have an essential role in aircrew training. Occasionally, symptoms of motion sickness, defined as simulator sickness, develop during these sessions. Preventive methods for motion sickness have been investigated thoroughly; however, only a few studies have examined preventive treatments for simulator sickness. The aim of this study was to examine the efficacy of scopolamine (an anticholinergic drug) compared with cinnarizine (an antihistaminic drug) for helicopter simulator sickness prevention. A validated simulator sickness questionnaire (SSQ) score was used to determine the severity of simulator sickness symptoms in this study. Preliminary SSQ scores and SSQ scores after each sortie were calculated. Each participant was given scopolamine, cinnarizine, or a placebo in a double-blind randomized manner before the first sortie of each training day. Forty-one helicopter pilots participated in the trial. The average age was 30.5 ± 7.1 years. SSQ values significantly improved from an average of 73.30 in the preliminary SSQ questionnaire to an average of 30.92 after 2 hours following the administration of cinnarizine (P = .012, 95%CI 8.071-76.703). Scopolamine was found to be less effective than both cinnarizine and the placebo in the alleviation of simulator sickness symptoms. This study is the first to compare scopolamine with cinnarizine for simulator sickness prevention. Based on the results of this study, we recommend the use of cinnarizine over scopolamine for simulator sickness prevention.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    Loratadine and desloratadine are second-generation antihistaminic drugs. Because of human administration, they are continuously released via excreta into wastewater treatment plants and occur in surface waters as residues and transformation products (TPs). Loratadine and desloratadine residues have been found at very low concentrations (ng/L) in the aquatic environment but their toxic effects are still not well known. Both drugs are light-sensitive even under environmentally simulated conditions and some of the photoproducts have been isolated and characterized. The aim of the present study was to investigate the acute and chronic ecotoxicity of loratadine, desloratadine and their light-induced transformation products in organisms of the aquatic trophic chain. Bioassays were performed in the alga Pseudokirchneriella subcapitata, the rotifer Brachionus calyciflorus and in two crustaceans, Thamnocephalus platyurus and Ceriodaphnia dubia. Loratadine exerted its acute and chronic toxicity especially on Ceriodaphnia dubia (LC50: 600 µg/L, EC50: 28.14 µg/L) while desloratadine showed similar acute toxicity among the organisms tested and it was the most chronically effective compound in Ceriodaphnia dubia and Pseudokirchneriella subcapitata. Generally, transformation products were less active in both acute and chronic assays.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Sci-hub)

公众号