Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis.

BACKGROUND: The ubiquitin-proteasome system (UPS) is thought to be functionally active in atherosclerosis (AS) lesions. Aspirin was found to be a potent inhibitor of the UPS in some tumour studies; however, its effect on AS remains to be demonstrated in vivo. METHODS: New Zealand rabbits were placed on a normal diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without (H) or with aspirin (HI) for 12 weeks. Proteasome activity, concentrations of plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin-conjugates (Ub), IkappaBalpha, phosphorylated IkappaB (pIkappaBalpha) and p65 were investigated by Western blotting or immunochemistry. RESULTS: Concentrations of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI. Histological analysis showed that atheroma was increased in H. Ub and IkappaBalpha were mainly localised in subendothelium and media vascular smooth muscle cells. Western blots revealed that Ub, IkappaBalpha, and pIkappaBalpha were increased, whereas p65 was lower in HI vs. H. The activity of the 20S proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome was not affected in any of the groups. CONCLUSIONS: Aspirin can attenuate the pathogenesis of atheroma formation, the degradation of IkappaBalpha and pIkappaBalpha, and lower the expression of p65, indicating that its therapeutic effects on AS may be via inhibition of the UPS.     

The galea fascia flap in orbital reconstruction: innovative harvest technique.

AIM: To report the treatment of a recurrent adenoid-cystic carcinoma of the lacrimal gland required orbital exenteration with an en bloc resection of the lateral orbital rim and wall and an anterior portion of the temporal muscle. Reconstruction was planned with both the objectives of a shortened healing time for faster epithetic reconstruction and no visible scars. METHOD: After a cranially extended temporal approach, the dissection of the superficial galea layer was connected with the subcutaneous dissection of the upper and lower eyelid after subciliary incisions. RESULTS: Ample exposure of the temporal, frontal and orbital region was obtained, facilitating the orbital exenteration with en bloc resection of the lateral orbital rim and wall and the anterior portion of the temporal muscle. The epithelialization of the eye socket covered with the galea fascia flap was accelerated, providing faster epithetic reconstruction, without visible scars. CONCLUSIONS: Healing time is accelerated, providing faster epithetic rehabilitation without visible scars, which is important in the postoperative rehabilitation ladder after eye exenteration for both patient and surgeon. Further more ablative surgery within this region gets safer and easier due to the ample exposure of this innovative surgical technique. Further evaluation of the effectiveness and safety of this new approach is advisable.     

Taming regulatory T cells by autologous T cell immunization: A potential new strategy for cancer immune therapy

Regulatory T cells (Tregs) play important roles in the maintenance of immune homeostasis, and is also involved in tumor immune tolerance. Dampening or elimination of Treg functions has been shown to lead to enhanced immune responses against tumors, and thus inhibition of tumor growth. Recently, we have developed a new immunization scheme, referred to as irradiated mitogen-activated autologous T cell vaccination (ATCV), and shown that such immunization could significantly enhance anti-tumor immunity in vivo. Mechanistically, the enhanced anti-tumor response appears to be due to reduced Treg functions and inhibition of activation-induced cell death (AICD) in effector T cells. Thus, ATCV may constitute a novel strategy in cancer immune therapy.     

Trade Herbal Products and Induction of CYP2C19 and CYP2E1 in Cultured Human Hepatocytes

Abstract: The aim of this study was to evaluate in vitro the dose‐dependent induction potential of six commonly used trade herbal products on CYP2C19 and CYP2E1 metabolic activities in cultured human hepatocytes. S‐mephenytoin and chlorzoxazone were used as specific CYP substrates, respectively, and rifampicin was used as a positive induction control for both enzymes. The hepatocytes were exposed to herbal extracts in increasing and biological relevant concentrations for 72 hrs and CYP substrate metabolites were quantified by validated HPLC methodologies. The major findings were that St John's wort was the most potent CYP‐modulating herb, showing a dose‐dependent induction/inhibition of both CYP2C19 and CYP2E1, with induction at low dosages and inhibition at higher. Ginkgo biloba showed an induction/inhibition profile towards CYP2C19 which was similar but weaker than that observed for St John's wort. If cooperative mechanisms are involved is still an open question. Common sage induced CYP2C19 in a log‐linear dose‐dependent manner with increasing concentrations. Common valerian was a weak inducer of CYP2C19, while horse chestnut and cone flower were characterized as non‐inducers of CYP2C19. Only St John's wort showed an inductive effect towards CYP2E1. In addition to St John's wort, Gingko biloba and common sage should be considered as possible candidates for clinically relevant drug‐herb interactions with selected CYP2C19 substrates.     

急诊抗菌药物的使用调查与分析

目的考察了解急诊抗菌药物的使用情况。方法随机抽取2008年7—12月的急诊处方2700张，对其中抗菌药物的应用情况进行统计分析。结果急诊抗菌药物使用率49．1％，药物应用形式以单用为主（占66．3％）；给药途径以口服和静脉注射为主。不合理用药处方占抗菌药物处方的10．8％，分别在选药方案、给药方案、溶媒使用、联合应用等方面存在问题。结论我院急诊抗菌药物的应用基本合理，但仍存在一定问题，需进一步加强管理。     

健肝愈胃汤合西药治疗门脉高压性胃病临床观察

目的探讨中药健肝愈胃汤（自拟）、西药心得安、奥美拉唑、胶态果胶铋胶囊联合治疗门脉高性胃病（PHG）的疗法。方法将136例PHG患者随机分成两组,对照组52例常规口服心得安、奥美拉唑、果胶铋;治疗组84例在常规服用以上西药的同时服用中药健肝愈胃汤。两组疗程均为2个月。结果治疗组临床治疗总有效率89.3%。显效率46.4%;对照组临床治疗总有效率80.7%,显效率13.5%。两组比较有显著性差异（P〈0.05）。结论中药健肝愈胃汤、西药心得安、奥美拉唑、果胶铋联合治疗PHG疗效显著。     

一种适用于聚合酶链反应的常见念珠菌基因组DNA提取方法的研究

目的介绍一种简单、快速的真菌DNA提取方法,提高真菌DNA提取效率,减少毒性和污染性,以适应临床研究需要。方法同时用溶细胞酶结合Biospin真菌基因组DNA提取试剂盒和十六烷基三甲基溴化铵(CTAB)法,提取白色念珠菌、热带念珠菌、克柔念珠菌和净平滑念珠菌基因组DNA,用A260/A280的比值检测DNA的纯度并计算质量浓度,同时行聚合酶链反应(PCR)以评价其可靠性。结果溶细胞酶结合Biospin真菌基因组DNA提取试剂成功提取所用真菌基因组DNA,其纯度及质量浓度能满足PCR反应的要求。结论用溶细胞酶结合Biospin真菌基因组DNA提取试剂提取DNA,简单、快速、高效,可用于PCR反应。