Enantioselective resolution of Rac‐terbutaline and evaluation of optically pure R‐terbutaline hydrochloride as an efficient anti‐asthmatic drug

Terbutaline is a β₂‐adrenoceptor agonist for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among the two isomers of terbutaline (TBT 2), R‐isomer was found to be the potent enantiomer in generating therapeutic effect, while S‐isomer has been reported to show side effects. In this study, R‐terbutaline hydrochloride (R‐TBH 6) was synthesized through chiral resolution from the racemic terbutaline sulfate (rac‐TBS 1) with 99.9% enantiomeric excess (ee) in good overall yield (53.6%). Further, R‐TBH 6 nebulized solution was prepared in half dosage of Bricanyl®, which is a marketed product of racemic terbutaline and evaluated in vitro aerosol performance and in vivo anti‐asthmatic effect on guinea pigs via. pulmonary delivery. From the investigation, it is evident that R‐TBH 6 nebulized solution of half dosage performed similar fine aerosol characteristics and anti‐asthmatic effect with Bricanyl®.     

当归与激素合用对哮喘小鼠的治疗作用及其机制

目的：探讨当归与激素合用对哮喘小鼠的治疗作用及其机制。方法：取BALB/c小鼠随机分为对照组、血瘀模型组、哮喘模型组、氢化可的松组、当归组、氢化可的松与当归合用组（n=12）。采用卵白蛋白致敏、激发,复制哮喘模型;使用氢化可的松复制血瘀模型。观测当归、氢化可的松及其合用对小鼠血液流变学（全血黏度与血清TXB2含量）和哮喘（哮喘行为学、肺功能、肺指数与肺组织含水量）的影响,采用ELISA法、免疫组化法测定相关细胞因子和HMGB1/TLR4/NF-κB蛋白质的表达水平。结果：8 g/kg当归、0.05 g/kg氢化可的松及其合用可明显缓解哮喘行为学指标,提高肺功能,降低肺指数及肺组织含水量,降低BALF中TNF-α、IL-1β及IL-6水平,抑制肺组织HMGB1、TLR4及NF-κB蛋白质的高表达;当归与氢化可的松合用对提高哮喘小鼠肺功能、降低相关细胞因子（TNF-α、IL-1β及IL-6）水平明显优于单独使用当归组,抑制肺组织中TLR4和NF-κB蛋白质表达的作用优于单独使用当归或氢化可的松。二者合用后可缓解氢化可的松所致的小鼠血清TXB2含量升高、血液粘稠度增加。结论：当归与激素及其合用具有明显的平喘作用,抑制HMGB1/TLR4/NF-κB蛋白质合成是其平喘的机制之一。当归与激素合用改善肺功能的作用更强,可能与加强抑制TLR4/NF-κB合成有关。合用当归可缓解激素在治疗哮喘时引起的血液流变学异常变化。     

豚鼠气道及肺组织原癌基因表达与哮喘的相关研究

目的：为研究原癌基因在哮喘发病中的作用。方法：以卵白蛋白致敏豚鼠建立哮喘模型,用Ｄｏｔ－ｂｌｏｔ、Ｎｏｒｔｈ－ｅｒｎ－ｂｌｏｔ分子杂交及免疫组化技术,分别观察正常及哮喘发作后豚鼠气道上皮及肺组织中原癌基因ｃ－ｆｏｓ、ｃ－ｍｙｃ的表达水平。结果：正常豚鼠气道及肺组织中ｃ－ｆｏｓ及ｃ－ｍｙｃｍＲＮＡ无或很少表达,哮喘发作后豚鼠气道上皮及肺组织中ｃ－ｆｏｓ和ｃ－ｍｙｃｍＲＮＡ表达明显增强,３０ｍｉｎ达高峰,发作后４ｈ降至正常水平。地塞米松对ｃ－ｆｏｓ及ｃ－ｍｙｃｍＲ－ＮＡ有部分抑制作用。结论：原癌基因ｃ－ｆｏｓ及ｃ－ｍｙｃ在哮喘发病过程中可能起一定作用。     

支气管哮喘患儿肺功能状态及Th1Th2指标的变化观察

目的:观察支气管哮喘患儿肺功能状态及Th1Th2指标的变化情况。方法:选取2013年10月~2015年8月本院诊治的65例支气管哮喘患儿为观察组,另选择同期接受体检的健康同龄儿童65名为对照组。比较两组患儿肺功能状态及Th1Th2指标,观察不同严重程度及分期支气管哮喘患儿的肺功能状态及Th1Th2指标。结果:观察组患儿肺功能指标及血清Th1Th2指标均低于对照组,差异具有统计学意义(P0.05);观察组患儿发作期肺功能指标及血清Th1Th2指标明显低于缓解期,差异具有统计学意义(P0.05);重度患儿肺功能指标及血清Th1Th2指标均低于轻度及中度患儿,差异具有统计学意义(P0.05);中度患儿肺功能指标及血清Th1Th2指标低于轻度患儿,差异具有统计学意义(P0.05)。结论:支气管哮喘患儿肺功能状态及Th1Th2指标的变化较大,且疾病分期与疾病严重程度对其检测结果也有较大影响。     

鼻窦功能性手术治疗慢性鼻窦炎合并支气管哮喘的远期疗效评估

目的:评价鼻窦功能性手术(FESS)治疗慢性鼻窦炎合并支气管哮喘的远期疗效。方法:选择自2011年1月至2013年1月我院收治的慢性鼻窦炎患者65例,行FESS治疗。根据是否合并患有支气管哮喘将患者分为观察组(慢性鼻窦炎合并支气管哮喘)和对照组(慢性鼻窦炎),选择同期健康志愿者作为正常组。采用酶联免疫吸附测定测定白细胞介素4(IL-4)、干扰素-γ(IFN-γ)水平、可溶性白细胞介素2受体(sIL-2R)和可溶性Ig E低亲和力受体(sCD23)的水平,并术后随访2年观察对比慢性鼻窦炎和支气管哮喘改善情况。结果:对照组和观察组患者手术后的IL-4、sIL-2R及sCD23水平降低,IFN-γ水平升高,且与手术前的差异均有统计学意义(P0.05);两组患者术后2年的慢性鼻窦炎治愈率均高于术后1年;观察组患者术后1年和术后2年的哮喘完全控制率明显高于术前,且差异具有统计学意义(P0.05),且术后2年哮喘完全控制率显著高于术后1年之间(P0.05);观察组患者术后1年、2年哮喘平均发作率显著低于术前,且术后2年的哮喘平均发作率明显低于术后1年(P0.05)。结论:FESS用于治疗慢性鼻窦炎合并支气管哮喘具有良好的临床疗效,能够显著改善患者的IL-4、IFN-γ、sIL-2R及sCD23水平,且随着时间的延长,其远期疗效较满意。     

Long-term effects of biofeedback-induced facial relaxation on measures of asthma severity in children

We studied the effects of electromyographic biofeedback on measures of asthma severity in children. Fifteen children received biofeedback training to reduce facial tension, and 14 children, who served as controls, received biofeedback training to maintain facial tension at a stable level. Assignment to experimental condition was random. As a result of training, electromyographic levels decreased in children trained in facial relaxation and remained fairly constant in children trained in facial tension stability. Biofeedback training was augmented for children in both groups by having them practice their facial exercises at home. Each child's condition was followed for a five-month period subsequent to biofeedback training. Throughout the experiment, the following measures of asthma severity were monitored: lung function, self-rated asthma severity, medication usage, and frequency of asthma attacks. In addition, standardized measures of attitudes toward asthma, self-concept, and chronic anxiety were recorded at regular intervals. As compared to the facial stability subjects, the facial relaxation subjects exhibited higher pulmonary scores, more positive attitudes toward asthma, and lower chronic anxiety during the followup period. Subjects in the two groups, however, did not differ on self-rated asthma severity, medication usage, frequency of asthma attacks, or self-concept. Based on the improvements we observed in pulmonary, attitude, and anxiety measures, we concluded that biofeedback training for facial relaxation contributes to the self-control of asthma and would be a valuable addition to asthma self-management programs.This research was supported by NIH grant No. HL27402. We are grateful to Anita D. Baker, Lisa Barclay, Deborah L. Harm, and Douglas J. Miller for serving as experimenters and to Constance K. Cottrell and Cindy Stout for compiling summaries of the data.     

Microbial contributions to bronchial asthma occurrence in children: A metagenomic study

Bronchial asthma, a common chronic respiratory disease in children, is traditionally regarded as a noninfectious disease. Current hypotheses, however, argue that asthma can be caused by microbial infection. We, therefore, hypothesize that a variety of microbes are more commonly found in the sputum of children with asthma, and these microbes may contribute to the occurrence and development of asthma. The present study proposes to use metagenomic approach to explore microbial diversity and to identify the microbial community characteristics of sputum from children with asthma. We found that microbial communities in the sputum of children differed significantly between asthmatics and controls. Kruskal-Wallis testing showed that 16 phyla, 104 genera, and 159 species were significantly downregulated, whereas two phyla including Platyhelminthes phylum and Chordata phylum, two genera including Spirometra genus and Homo sapiens, and the Spirometra erinaceieuropaei species were significantly upregulated in asthma patients compared with controls (P < 0.05). Among them, H. sapiens and S. erinaceieuropaei exhibited 2.3- and 2.0-fold overabundance in asthmatics vs controls, respectively. Meanwhile, metastats assay demonstrated that 31 phyla, 400 genera, and 813 species were significantly downregulated, whereas two phyla, 10 genera, and 16 species were significantly upregulated in asthma patients compared with controls (P < 0.05). Among them, Tetrahymena thermophila and Candidatus Zinderia insecticola exhibited 4.7-fold overabundance in asthmatics vs controls. Our study establishes a link between microbial infection and the mechanisms leading to asthma development, which will be useful for developing novel diagnostic biomarkers and aiding in the prevention and control of asthma.