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。     

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen

Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.

Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.

Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available.     

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。     

Free flap monitoring with continuous tissue oxygen tension measurement

Intraoperative and postoperative free flap monitoring by means of oxygen tension measurement was carried out in 11 patients. We used an invasive flexible microcatheter that allowed for measurement of oxygen tension in all types of free flaps. Two cases of the measured flaps were buried free flaps which do not allow monitoring by clinical assessment. All flaps monitored in this study survived. One case of displacement of the microcatheter occurred. In one patient, the tissue pO₂ monitor successfully detected early vascular thrombosis with subsequent reoperation and salvage of the free flap.     

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。     

CS_2作业工人血清脂质过氧化水平与LDH同功酶谱研究

ＣＳ_２作业工人血清脂质过氧化水平与ＬＤＨ同功酶谱研究张文昌，连祥霖，张连娜，杨乃富（福建医学院劳动卫生学教研室，福州３５０００４）结果表明，高接触水平组（浓度为１０．４２～４６．５４ｍｇ／ｍ３或Σｍｇ·年≥５０）血清ＬＰＯ含量与对照比较，显著性增高?..     

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