An adjuvanted pandemic influenza H1N1 vaccine provides early and long term protection in health care workers

Mass vaccination was the most effective prophylaxis for protecting the population during the influenza H1N1 pandemic. We have evaluated the tolerability, immunogenicity and kinetics of the antibody response to a monovalent oil-in-water (AS03) adjuvanted human pandemic split influenza A/California/7/2009 H1N1 (3.75 μg haemagglutinin) vaccine in health care workers. Vaccination elicited a rapid and early protective level of haemagglutination inhibition antibody from 6 to 7 days post vaccination, and by 14 to 21 days post vaccination, up to 98% of vaccinees had protective antibody titres which persisted for at least 3 months in 84-92% of subjects. A rapid induction of protective antibody is important in reducing community spread of pandemic influenza and in helping maintain the integrity of the health care system during the pandemic.     

Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine

The nucleocapsid （N） protein of SARS-coronavirus （SARS CoV） is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membraneglycoprotein, In this study, the N protein of SARS-CoV was expressed in Escherichia coli DH5alpha and identified with pooled sera from patients in the convalescence phase of SARS.     

Small interfering RNA inhibits SARS-CoV nucleocapsid gene expression in cultured cells and mouse muscles

SARS-CoV is a newly identified coronavirus that causes severe acute respiratory syndrome （SARS）. Currently, there is no effective method available for prophylaxis and treatment of SARS-CoV infections. In the present study, the influence of small interfering RNA （siRNA） on SARS-CoV nucleocapsid （N） protein expression was detected in cultured cells and mouse muscles. Four siRNA expression cassettes driven by mouse U6 promoter targeting SARS-CoV N gene were prepared, and their inhibitory effects on expression of N and enhanced green fluorescence protein （EGFP） fusion protein were observed. A candidate siRNA was proved to down-regulate N and EGFP expression actively in a sequence-specific manner. The expression vector of this siRNA was constructed and confirmed to reduce N and EGFP expression efficiently in both cultured cells and adult mouse muscles. Our findings suggest that the siRNA should provide the basis for prophylaxis and therapy of SARS-CoV infection in human.     

An epoxygenase metabolite of arachidonic acid mediates angiotensin II-induced rises in cytosolic calcium in rabbit proximal tubule epithelial cells.

Previous studies from this and other laboratories have shown that angiotensin II (AII) induces [Ca2+]i transients in proximal tubular epithelium independent of phospholipase C. AII also stimulates formation of 5,6-epoxyeicosatrienoic acid (5,6-EET) from arachidonic acid by a cytochrome P450 epoxygenase and decreases Na+ transport in the same concentration range. Because 5,6-EET mimics AII with regard to Na+ transport, it effects on calcium mobilization were evaluated. [Ca2+]i was measured by video microscopy with the fluorescent indicator fura-2 employing cultured rabbit proximal tubule. AII-induced [Ca2+]i transients were enhanced by arachidonic acid and attenuated by ketoconazole, an inhibitor of cytochrome P450 epoxygenases. Arachidonic acid also elicited a [Ca2+]i transient that was attenuated by ketoconazole. 5,6-EET augmented [Ca2+]i similar to that seen with AII, but was unaffected by ketoconazole. By contrast, the other regioisomers (8,9-, 11,12-, and 14,15-EET) were much less potent. [Ca2+]i transients resulted from influx through verapamil- and nifedipine-sensitive channels. These results suggest a novel mechanism for AII-induced Ca mobilization in proximal tubule involving cytochrome P450-dependent arachidonic acid metabolism and Ca influx through voltage-sensitive channels.     

颅骨缺损修补术中的组织重建技术

目的:颅骨缺损修补术中细节问题如不加以注意,可能会引发一些并发症。通过分组对比观察,探讨颅骨缺损修补手术中的组织构建技巧,以期提高此类患者的疗效,改善生活质量。方法:①对象:选择2000-01/2007-01颅盖骨缺损患者86例。②分组:将86例患者随机分两组,普通术式修复法组26例,其中男19例,女7例;年龄5～56岁;颞肌组织重建组60例,男51例,女9例;年龄8～69岁。颅盖骨缺损修补手术时间为缺损后1个月～6年。③干预:颞肌组织重建组:将钛网塑型,固定,将颞肌筋膜和肌肉呈扇形贴紧钛网表面,间断缝合颞肌筋膜和肌肉缘于钛网表面;普通术式修复法:采用翻转皮瓣,即颞肌筋膜外的皮瓣,显露出骨缺损区,覆盖钛网,直接把颞部肌肉全部盖在钛网下。④评估:对两组患者术后一般情况、咀嚼、疼痛、颞部肌肉萎缩、外观皮肤凹陷进行比较,并观察不良事件及副反应。结果:86例患者随访时间为1个月～6年。①颞肌组织构建患者术后咀嚼有力、头面部疼痛轻、颞部肌肉萎缩不明显、外观无或较轻皮肤凹陷。普通术式修复的患者出现临床症状,可能因为局部钛网压迫颞肌层,致咀嚼时疼痛、无力。②普通术式修复法出现钛网松动3例,经局部加压包扎固定1个月后好转;两组2例硬膜外血肿自行吸收;3例术后癫痫,治疗后得到良好控制。结论:颅骨缺损重建术中,组织重建尤为重要,特别要注意重建生理的组织结构。采用间断缝合颞肌筋膜和肌肉缘于钛网外面的方法处理,可防止术后患者咀嚼无力、疼痛和外观变形等并发症,并有利于术后尽快的生理修复,使患者尽早正常生活。     

基因载体、基因选择、基因转移与类风湿关节炎

目的:综合分析类风湿关节炎的基因治疗现状及应用前景。资料来源:应用计算机检索Pubmed及highwire1997-01/2006-06有关类风湿关节炎基因治疗的文献,检索词“gene therapy,rheumatoid arthritis,interleukin-1 receptor antagonist,soluble tumor necrosis factoreceptor”,并限定文章语言种类为English。资料选择:对检索到的类风湿关节炎基因治疗方面的相关信息进行整理,选取针对性强的文章。同一领域的文献则选择近期发表或权威杂志的文章。资料提炼:共检索到67篇相关文献,其中30篇文章符合要求。排除37篇,其中21篇系重复同一研究,16篇为Meta分析。资料综合:类风湿关节炎的基因疗法作为生物治疗的一种新趋势,在很短时间内从理论和实验室取得成功,为临床类风湿关节炎的治疗提供了新的思路。文章主要针对类风湿关节炎基因治疗的目的基因、转移载体、转移途径选择、基因表达调控以及临床应用前景等进行分析。结论:类风湿关节炎的基因治疗已在动物实验中取得了可喜的成就,许多研究已经证明其临床应用的价值,但临床应用安全性及有效性尚有待进一步观察。     

IgA肾病的治疗进展

IgA 肾病是最常见的原发性肾小球疾病,由于其发病机制尚未明确,目前仍无特异性治疗药物.临床上的治疗目标是有效降低蛋白尿,控制血压和(或) 高尿酸并减少肾组织进一步损伤,维持肾功能稳定.对反复发作的镜下血尿患者,扁桃体切除术作为治疗的一种手段;对单纯性血尿和病理改变较轻者,主要加强随访观察;对于有尿蛋白和(或)高血压的缓慢进展的IgA肾病,血管紧张素转化酶抑制剂和血管紧张素受体拮抗剂可用于大部分病例,必要时可使用糖皮质激素,也可应用细胞毒性药物或吗替麦考酚酯等免疫抑制剂进行治疗;病情进展较快的高危患者,可用糖皮质激素冲击治疗,或使用细胞毒药物或免疫抑制剂等强化治疗.     

美通宁片中褪黑素的含量测定

目的：制定美通宁片中褪黑素质量控制指标。方法：采用薄层扫描法测定美通宁片中褪黑素的含量。以苯;氯仿：甲醇（4：9：1）为展开剂。结果;通过方法学考察,平均回收率98．5％。变异系数RSD＝4．12％。结论：方法可靠、准确,操作简便可行。     

Hypercholesterolemia promotes early renal dysfunction in apolipoprotein E-deficient mice

Background

Aging and dyslipidemia are processes which can lead to deleterious consequences to renal function. Therefore, the aim of this study was to determine the effects of both hypercholesterolemia and aging on renal function in mice.

Methods

Male hypercholesterolemic apolipoprotein E-deficient mice (ApoE, n = 13) and age-matched C57BL/6 control mice (C57, n = 15) were studied at 2 (young) and 8 (adult) month-old. At each time point, animals were placed in metabolic cages for 24 hours to urine volume and urinary creatinine quantification. Blood samples were collected for serum cholesterol, urea and creatinine measurements. Glomerular filtration rate (GFR) was estimated through creatinine clearance determination. Mesangial expansion was evaluated by Periodic Acid Schiff staining, renal fibrosis was determined through Masson's trichrome staining and neuronal nitric oxide synthase (nNOS) expression in the kidney was performed by Western Blotting. To statistical analysis two-way ANOVA followed by Fisher's post hoc test was used.

Results

Total plasma cholesterol was increased about 5-fold in ApoE mice at both time points compared to C57 animals. At 2-month-old, GFR was already markedly reduced in ApoE compared to C57 mice (187 ± 28 vs 358 ± 92 μL/min, p < 0.05). Adult C57 (-77%) and ApoE (-50%) mice also presented a significant reduction of GFR. In addition, serum urea was significantly increased in young ApoE animals compared to C57 mice (11 ± 1.3 vs 7 ± 0.9 mmol/L, p < 0.01). A significant mesangial expansion was observed at 2-month old ApoE mice compared to C57 mice (35 ± 0.6 vs 30 ± 0.9%, respectively, p < 0.05), which was aggravated at 8-month old animals (40 ± 3 and 35 ± 3%, respectively). Tubulointersticial fibrosis was augmented at both young (17 ± 2%, p < 0.05) and adult (20 ± 1%, p < 0.05) ApoE mice compared to respective C57 age controls (8 ± 1 and 12 ± 2%, respectively). The expression of nNOS was markedly reduced in a time-dependent manner in both strains.

Conclusions

These data show that both hypercholesterolemia and aging contribute to the loss of renal function in mice.