Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis – a GA2LEN study

Chronic rhinosinusitis is one of the most common health care challenges, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. The diagnosis of chronic rhinosinusitis (CRS) currently is based on clinical signs, nasal endoscopy and CT scanning, and therapeutic recommendations are focussing on 2 classes of drugs, corticosteroids and antibiotics. A better understanding of the pathogenesis and the factors amplifying mucosal inflammation therefore seems to be crucial for the development of new diagnostic and therapeutic tools. In an effort to extend knowledge in this area, the WP 2.7.2 of the GA²LEN network of excellence currently collects data and samples of 1000 CRS patients and 250 control subjects. The main objective of this project is to characterize patients with upper airway disease on the basis of clinical parameters, infectious agents, inflammatory mechanisms and remodeling processes. This collaborative research will result in better knowledge on patient phenotypes, pathomechanisms, and subtypes in chronic rhinosinusitis. This review summarizes the state of the art on chronic rhinosinusitis and nasal polyposis in different aspects of the disease. It defines potential gaps in the current research, and points to future research perspectives and targets.     

GA2LEN skin test study I: GA²LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe

Background:  Skin prick testing is the standard for diagnosing IgE-mediated allergies. However, different allergen extracts and different testing procedures have been applied by European allergy centres. Thus, it has been difficult to compare results from different centres or studies across Europe. It was, therefore, crucial to standardize and harmonize procedures in allergy diagnosis and treatment within Europe.
Aims:  The Global Asthma and Allergy European Network (GA²LEN), with partners and collaborating centres across Europe, was in a unique position to take on this task. The current study is the first approach to implement a standardized procedure for skin prick testing in allergies against inhalant allergens with a standardized pan-European allergen panel.
Methods:  The study population consisted of patients who were referred to one of the 17 participating centres in 14 European countries ( n  = 3034, median age = 33 years). Skin prick testing and evaluation was performed with the same 18 allergens in a standardized procedure across all centres.
Results:  The study clearly shows that many allergens previously regarded as untypical for some regions in Europe have been underestimated. This could partly be related to changes in mobility of patients, vegetation or climate in Europe.
Conclusion:  The results of this large pan-European study demonstrate for the first time sensitization patterns for different inhalant allergens in patients across Europe. The standardized skin prick test with the standardized allergen battery should be recommended for clinical use and research. Further EU-wide monitoring of sensitization patterns is urgently needed.     

融合蛋白 NrCAM-Fc的重组体的构建

目的：构建神经原相关的细胞粘附分子（NrCAM）和免疫球蛋白Fc片段融合基因的重组质粒并通过Baculovirus载体转染到昆虫细胞。方法：利用RT－PCR方法从神经母细胞瘤细胞系SK－N－SN获得NrCAM的信号肽区和跨膜区片段并直接克隆到pGEMT载体，经多次酶切、连接、转化、筛选获得NrCAM-Fc的重组副合基因，测序后将此基因通过Baculovirus载体转染至昆虫细胞。结果：多种酶切和测序结果表明NrCAM-Fc的序列与原序列符合率达98％以上，NrCAM与Fc连接处序列保证了Fc的读码框架（ORF）。结论：Baculovirus载体转染效率高，检测方法简便易行。     

MGA5 Health Utilities Index: Further Evidence of Responsiveness

Quality adjusted life years (QALYs) are well recognized as a valid measure for outcomes in cost-effectiveness analyses. However, it is difficult to obtain a summary utility score from health status measure such as the SF-36.
OBJECTIVE: To predict a summary utility score (represented by HUI) from the scores on the SF-36.
METHODS: A structural equation framework was applied to data collected from 1992 to 1995 on the Southern California Kaiser Permanente population (n = 5,794). An instrumental variable (IV) method mitigated the endogeneity in estimating the HUI(MarkII). Socioeconomic and disease variables were used as covariates. A split-sample analysis provided cross-validation.
RESULT: This model predicted 33.68% of the observed variance in HUI index scores with an adjusted R²of 0.3335. Observed HUI index scores were distributed with a mean of 0.7963 and std. deviation of 0.1796. Parameter estimates of most of the SF-36 components (except General Health & Social Functioning) showed statistical significance at α= 0.05 level. People with high chronic disease scores were found to have low SF-36 scores, and parameter estimates of this covariate were also found statistically significant at α= 0.05 level in all structural equations. However, all the socioeconomic variables showed statistical insignificance. Comparison of "Forecasting" and "Estimation" sub-samples showed satisfactory results during cross-validation.
CONCLUSION: Result of this study provides a quantitative link between two important measures of health status. The present model can be used to estimate overall health utility summary scores from previous studies using the SF-36.     

γ-去氢骆驼蓬碱等咔啉类生物碱的辐射防护作用

γ- Harmine(Ⅰ),’harmine(Ⅱ )and harmaline(Ⅲ )were isolated from PeganumHarmala L.( Zygophylaceae).Tests were conducted with mice to detect whether γ- harmine( a newcompound), harmine,harmof(Ⅳ)and harmalol(Ⅴ) are effective radioprotective compounds againstγ-ray irradiation, Intraperitoneal injection of the hydrochlorides of the four alkaloids 50～80mg·kg^-1×1 in NIH male mice 30～45 minutes before 8.6～9. 7 Gy whole body ⁶⁰Co irradiationsignificantly increased the survival effects(1. 33～2. 61)and 30-day survivai rate in comparison withcontrol mice.The results indicatethat γ- harmine exhibited relatively good radioprotective effect.γ-harmine is the first alkaloid isolated from a plant having ptotective effects against whole-body lethal irradiation in mice.     

南蛇藤素抑制豚鼠体外精子的受精能力

南蛇藤素(Cel)对豚鼠精子前向运动(FM)、获能(Cap)、顶体反应(AR)和穿透去透明带仓鼠卵(SPA)均有明显的抑制作用,其作用强度随剂量而增加;对Cel的敏感性依次为精子Cap>FM>SPA>AR。Cel对豚鼠精子AR,FM和Cap的抑制作用比乙酸棉酚(GA)明显为强。