我国血吸虫对吡喹酮抗药性研究之概要

血吸虫病是一种严重危害人类健康、影响社会经济发展的重大传染病,为全球公共卫生负担和危害最严重的被忽视的热带病之一。吡喹酮是20世纪70年代研制出的一种高效、低毒、价廉的广谱抗蠕虫口服药,为世界卫生组织（WHO）推荐的抗血吸虫的首选药物。吡喹酮在血吸虫病流行区现场大规模反复使用已超过40年,血吸虫是否会对吡喹酮产生抗药性引起国际社会极大担忧,为学术界关注的热点科学问题。针对血吸虫病防治中这一重大需求,自1996年起, 在国家科技支撑计划、国家自然科学基金、江苏省自然科学基金等项目基金资助下,我们在血吸虫病流行区现场和实验室,对血吸虫在吡喹酮药物的压力是否会产生抗药性、抗性虫株的生物学特性、抗性的检测、吡喹酮抗性的交叉抗药性及抗药性的预防和控制等科学问题进行较为系统的研究,本文就其研究及其意义作一概述。     

Non alcoholic fatty liver disease and risk of incident diabetes in subjects who are not obese

Background and aims

It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.

神经外科重症监护病房常见病原菌的分布与耐药性研究

目的调查珠江医院神经外科重症监护病房(ICU)病原菌的分布与耐药情况,分析ICU院内感染的发生原因,探讨防治对策。方法应用法国VITEKⅡ全自动细菌鉴定仪鉴定病原菌,用纸片扩散法检测药敏结果。结果神经外科ICU菌群主要以革兰阴性杆菌(71.6%)为主,鲍曼不动杆菌占16.7%,大肠埃希菌占15.7%,铜绿假单胞菌占13.7%,肺炎克雷伯菌占13.7%等。但葡萄球菌、粪肠球菌等阳性球菌(28.4%)也有增加的趋势。亚胺培南和头孢哌酮/舒巴坦仍保持最高抗菌活性,细菌的耐药率分别为15.3%和30.6%。结论我院神经外科ICU感染主要病原菌是革兰阴性杆菌,对常用抗菌药物耐药性较高,但革兰阳性球菌所占比例呈增高趋势。控制第二、三代头孢菌素以及制酸剂(质子泵抑制剂)的预防性用药,减少耐药菌株的产生,有针对性地使用抗生素是控制危重病人感染的有效措施。     

928株革兰阴性杆菌耐药性监测

目的：了解青岛地区临床分离的重要革兰阴性杆菌的耐药情况以指导合理用药。方法：2001年青岛3家医院临床分离的5种革兰阴性杆菌用Kirby-Bauer法进行药敏试验。结果：5种病原菌均占3家医院革兰阴性杆菌分离率的前5位，大肠埃希菌对氟喹诺酮类药物的耐药率达60％－87％，细菌对亚胺培南均呈高度敏感，但铜绿假单胞菌耐亚胺培南株占25．8％，头孢他啶的抗菌活性是三代头孢菌素中最高的；复方酶抑制剂表现出良好的抗菌活性。结论：细菌耐药问题仍是目前临床的严重问题，地域性的耐药性监测是必要的。     

Studies on Propafenone-type Modulators of Multidrug-Resistance IV: Synthesis and Pharmacological Activity of 5-Hydroxy and 5-Benzyloxy Derivatives

A series of 5-hydroxy and 5-benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR-modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3 . Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a–d . Subsequent cleavage of the benzyl group gave the 5-hydroxy analogs 6a–d . Structure activity relationship studies showed, that the 5-hydroxy derivates 6a–d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5-benzyloxy analogs 5a–d showed almost identical EC₅₀ values, independent of their log P value.     

改善胰岛素敏感性对血压影响的相关研究

目的 :观察胰岛素增敏剂二甲双胍改善 2型糖尿病胰岛素敏感性后对血压的影响。方法 :71例 2型糖尿病人口服二甲双胍 (格华止 ) 85 0 mg,qd-bid。治疗前后测定 BMI、血压、FBG、PBG、FINS、PINS,并按 HOMA模型计算胰岛素抵抗指数和胰岛素分泌指数。结果 :( 1)二甲双胍治疗 8周后 ,BMI治疗前后无显著性差异 ;血压治疗后明显下降 ,降压幅度达 ( 13.1± 4.97) /( 4 .2 2± 9.93) mm Hg,血压治疗前后有显著性差异。 ( 2 )治疗后 F BG、 PBG、 FINS均明显下降 ,治疗前后有显著性差异。 ( 3)治疗后 HOMA-IR下降 ,IAI升高 ,治疗前后有显著性差异 ,但 HOMA-IS、 FINS/FBG无显著性差异。结论 :二甲双胍治疗 2型糖尿病 ,在降低血糖、改善 IR的同时 ,伴有血压的明显下降     

Prior diabetes mellitus is associated with increased morbidity in cystic fibrosis patients undergoing bilateral lung transplantation: an ‘orphan’ area? A retrospective case–control study

Background: The aim of this study was to determine whether pre-existing diabetes mellitus increases the risk of rejection, infection and/or death in cystic fibrosis patients undergoing bilateral sequential single-lung transplantation.
Methods: A retrospective audit of 25 consecutive patients with cystic fibrosis who underwent bilateral sequential single-lung transplantation between 1 January 2003 and 31 December 2005 at a tertiary referral hospital was carried out.
Results: Although 32% patients had diabetes diagnosed before lung transplantation, 92% had random blood glucose levels ≥11.1 mmol/L requiring insulin during admission. Patients with pre-existing diabetes had increased infection-related (3.9 vs 1.2, P = 0.01) and putative rejection-related (1.4 vs 0.5, P = 0.04) hospital admissions post-transplantation compared with those without diabetes pre-transplant. During the period of observation, four of eight patients with a prior diagnosis of diabetes died compared with none of 17 patients without prior diabetes ( P = 0.0055).
Conclusion: Almost all cystic fibrosis patients develop hyperglycaemia after lung transplantation, but patients with prior diabetes have more complication-related admissions to hospital and a higher mortality rate.     

肝癌多药耐药产生与低糖环境的关系

目的探讨局部微环境低糖与肝细胞癌多药耐药性(MDR)产生的关系及影响机制。方法低糖培养HepG2细胞,应用流式细胞术Annexin V/PI法检测低糖培养的细胞在化疗药物5-氟脲嘧啶(5-Fu)作用后的凋亡情况,分别应用荧光定量聚合酶链反应(PCR)技术和Western blot技术检测低糖培养后HepG2细胞内多药耐药相关基因mdr1、MRP1、LRP的mRNA和蛋白水平的表达。结果在低糖环境下生长时间越长的HepG2细胞对5-Fu的抵抗越强,而且随着低糖培养时间的增加,5-Fu诱导的HepG2细胞的凋亡高峰延迟。低糖培养的HepG2细胞内多药耐药相关基因mdr1、MRP1、LRP在mRNA和蛋白水平的表达随低糖培养时间的延长而升高,以LRP的改变最为显著。结论肝癌生长微环境葡萄糖耐量不足也是肝癌产生MDR的原因之一。低糖可通过上调一组多药耐药相关基因的表达而诱导肝癌的多药耐药性。     

Bacterial ghosts (BGs)—Advanced antigen and drug delivery system

Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy.