糖皮质激素受体基因转染对肺泡巨噬细胞表达炎性因子的影响

目的:分析过量表达的外源性糖皮质激素受体在调控肺泡巨噬细胞表达炎性细胞因子中的作用。方法:实验于2005-10/2006-03在解放军南京军区南京总医院呼吸病实验室完成。①选用成年健康Wistar大鼠10只,雌雄不拘。采用大鼠糖皮质激素受体真核表达质粒pCMV-rGR转染体外培养肺泡巨噬细胞,将肺泡巨噬细胞分为转染组与非转染组,其中转染组细胞在质粒转染24h后用于实验,各组对以下时相点进行观察:正常对照(加等量生理盐水)、脂多糖 地塞米松作用4,8和12h,脂多糖与地塞米松作用浓度分别为100μg/L,1×10-5mol/L,于不同时相点收集细胞。②转染24h后WesternBlotting检测细胞总蛋白和核蛋白中糖皮质激素受体蛋白表达变化。同时收集细胞培养上清,采用酶联免疫吸附法浊定细胞培养上清中肿瘤坏死因子α、白细胞介素1β水平。③多组间比较用方差分析,两两比较用SNK检验。结果:①质粒转染肺泡巨噬细胞后糖皮质激素受体表达变化:转染组细胞总蛋白中糖皮质激素受体表达明显高于非转染组(3.75±0.25,1.21±0.16,P<0.01),转染组细胞核蛋白中糖皮质激素受体表达量与非转染组相近(1.15±0.12,1.09±0.11,P>0.05)。②脂多糖和地塞米松作用后核蛋白中糖皮质激素受体表达变化:脂多糖和地塞米松作用后4,8,12h转染组细胞核蛋白中糖皮质激素受体表达量分别为4.02±0.09,2.13±0.08,1.22±0.15,非转染组细胞核蛋白中糖皮质激素受体表达量分别为4.08±0.13,2.09±0.11,1.19±0.17,两组细胞核蛋白中糖皮质激素受体表达变化趋势一致,均于4h达到峰值,8h显著降低,12h达到最低,两组同时相点比较,差异不明显(P>0.05)。③脂多糖和地塞米松作用后细胞培养上清中细胞因子表达变化:转染组脂多糖和地塞米松作用后4,8,12h肿瘤坏死因子α表达分别为(32.16±3.99),(56.82±8.43),(73.34±9.97)ng/L,非转染细胞分别为(34.28±4.25),(59.82±9.65),(71.41±8.35)ng/L;转染组脂多糖和地塞米松作用后4,8,12h细胞上清中白细胞介素1β质量浓度分别为(67.57±18.37),(83.17±8.55),(97.55±8.27)ng/L,非转染分别为(62.23±15.64),(85.72±9.37),(99.07±9.25)ng/L。两组细胞上清中肿瘤坏死因子α、白细胞介素1β表达随时间逐渐增加,均于12h均达到峰值,同时相点两组比较均无明显差异(P>0.05)。结论:①通过体外糖皮质激素受体基因转染可以有效地在肺泡巨噬细胞中过量表达外源性糖皮质激素受体,并且定位于胞质内。②地塞米松作用后,肺泡巨噬细胞核内糖皮质激素受体表达明显增加,但随后又出现表达下调现象。③体外基因转染后胞质中过量表达的外源性糖皮质激素受体不能发生核移位,所检测的均为内源性糖皮质激素受体。④通过基因转染而过量表达的外源性糖皮质激素受体,不能发挥正常的抑炎生物学活性。     

Angiotensin-converting-enzyme inhibitors in the management of cardiac failure: are we ignoring the evidence?

The benefits of angiotensin-converting enzyme (ACE) inhibition in the management of cardiac failure have been extensively documented. However, little is known about its impact upon the investigation and management of this condition. We assessed how patients diagnosed as having cardiac failure were investigated, which patients were treated with ACE inhibitors and with what dosages. We reviewed the case notes of all 343 patients discharged from Aberdeen Royal Infirmary 1 July-31 December 1992 with a diagnosis of cardiac failure. In addition, a questionnaire was sent to the general practitioners of the 166 patients still alive in October 1994. Only 40% of patients were discharged from hospital on ACE inhibitors. In 58.8%, the diagnosis of cardiac failure was based purely on clinical or radiological grounds. At discharge, 76.1% of patients were on lower doses of ACE inhibitors than those used in the major survival studies; with 68.9% receiving similar doses two years later. The majority of patients with heart failure are under- investigated and under-treated.      

Providing web-based feedback and social norms information to reduce student alcohol intake: a multisite investigation

Background

Unhealthy alcohol use among university students is cause for concern, yet the level of help seeking behavior for alcohol use is low within the student population. Electronic brief interventions delivered via the Internet present an alternative to traditional treatments and could enable the delivery of interventions on a population basis. Further evidence is needed of the effectiveness of Internet-delivered interventions and of their generalizability across educational institutions.

Objective

Our objective was to evaluate the effectiveness across 4 UK universities of a Web-based intervention for student alcohol use.

Methods

In total, 1112 participants took part. Participants were stratified by educational institution, gender, age group, year of study, and self-reported weekly consumption of alcohol and randomly assigned to either the control arm or to the immediate or delayed intervention arms. Intervention participants gained access to the intervention between weeks 1 to 7 or weeks 8 to 15, respectively. The intervention provided electronic personalized feedback and social norms information on drinking behavior accessed by logging on to a website. Participants registered interest by completing a brief screening questionnaire and were then asked to complete 4 further assessments across the 24 weeks of the study. Assessments included a retrospective weekly drinking diary, the Alcohol Use Disorders Identification Test (AUDIT), and a readiness-to-change algorithm. The outcome variable was the number of units of alcohol consumed in the last week. The effect of treatment arm and time on units consumed last week and average units consumed per drinking occasion were investigated using repeated measures multivariate analysis of covariance (MANCOVA). In addition, the data were modeled using a longitudinal regression with time points clustered within students.

Results

MANCOVA revealed a main effect of time on units of alcohol consumed over the last week. A longitudinal regression model showed an effect of assessment across time predicting that participants who completed at least 2 assessments reduced their drinking. The model predicted an additional effect of being assigned to an intervention arm, an effect that increased across time. Regression analysis predicted that being male or being assigned to an intervention arm increased the odds of not completing all assessments. The number of units of alcohol consumed over the last week at registration, age, university educational institution, and readiness to change were not predictive of completion.

Conclusions

Delivering an electronic personalized feedback intervention to students via the Internet can be effective in reducing weekly alcohol consumption. The effect does not appear to differ by educational institution. Our model suggested that monitoring alone is likely to reduce weekly consumption over 24 weeks but that consumption could be further reduced by providing access to a Web-based intervention. Further research is needed to understand the apparent therapeutic effect of monitoring and how this can be utilized to enhance the effectiveness of brief Web-based interventions.     

The Allergic Rhinitis and its Impact on Asthma (ARIA) score of allergic rhinitis using mobile technology correlates with quality of life: The MASK study

Mobile technology has been used to appraise allergic rhinitis control, but more data are needed. To better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ‐5D (EuroQuol) and WPAI‐AS (Work Productivity and Activity Impairment in allergy) in 1288 users in 18 countries. This study showed that quality‐of‐life data (EQ‐5D visual analogue scale and WPA‐IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0‐2). Users with a score of 3 or 4 had a significant impairment in quality‐of‐life questionnaires.