Mechanism of uptake and retention of F-18 BMS-747 158-02 in cardiomyocytes: a novel PET myocardial imaging agent

Background BMS-747158-02 is a novel fluorine 18-labeled pyridazinone derivative designed for cardiac imaging. The uptake and retention mechanisms of F-18 BMS-747158-02 in cardiac myocytes were studied in vitro, and the biodistribution of F-18 BMS-747158-02 was studied in vivo in mice. Methods and Results Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC₅₀ of 16.6±3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC₅₀ of 18.2±6.7 nmol/L, 19.8±2.6 nmol/L, and 23.1±1.5 nmol/L, respectively). F-18 BMS-747158-02 had high uptake in monolayers of neonatal rat cardiomyocytes (10.3%±0.7% of incubated drug at 60 minutes) that was inhibited by 200 nmol/L of rotenone (91%±2%) and deguelin (89%±3%). In contrast, an inactive pyridaben analog, P-0 (IC₅₀ value>4 μmol/L in MC-1 assay), did not inhibit the binding of F-18 BMS-747158-02 in cardiomyocytes. Uptake and washout kinetics for F-18 BMS-747158-02 in rat cardiomyocytes indicated that the time to half-maximal (t_1/2) uptake was very rapid (approximately 35 seconds), and washout t_1/2 for efflux of F-18 BMS-747158-02 was greater than 120 minutes. In vivo biodistribution studies in mice showed that F-18 BMS-747158-02 had substatial myocardial uptake (9.5%±0.5% of injected dose per gram) at 60 minutes and heart-to-lung and heart-to-liver ratios of 14.1±2.5 and 8.3±0.5, respectively. Positron emission tomography imaging in the mouse allowed clear cardiac visualization and demonstrated sustained myocardial uptake through 55 minutes. Conclusions F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake and slow washout. These characteristics allow fast and sustained accumulation in the heart.     

微小切口胆囊切除术2260例效果观察

目的 总结微小切口胆囊切除术治疗胆道系统疾病的经验。方法 对2002-2004年连续收治的2260例胆囊、胆道系统疾病实施微小切口手术的临床观察资料进行回顾性分析。结果 本组2260例微小切口胆囊切除术的患者无一例因手术原因死亡；术后无残留小胆囊；无胆汁漏及腹腔脓肿，亦无伤口全层裂开及切口疝形成。结论 该术式损伤小、局部显露清楚、不易发生副损伤，可同时行胆总管探查术，特殊情况下可随时改变手术方式。     

Investigations into the C‐deuteriation of aryl alkyl ketones using urea as a pro‐base in the presence of a deuterium donor

Results are reported on the regioselective C‐deuteriation of a series of enolates derived from the deprotonation of aryl alkyl ketones using dilithiated urea as the pro‐base in the presence of a suitable deuterium donor. Copyright © 2006 John Wiley & Sons, Ltd.     

Distribution of the exfoliative toxin D gene in clinical Staphylococcus aureus isolates in France

Exfoliative toxin D (ETD) was identified recently as a new exfoliative toxin serotype. Like other exfoliative toxins, ETD induces intra-epidermal cleavage through the granular layer of the epidermis of neonatal mice. The distribution of ETD production was investigated in Staphylococcus aureus isolates from infected and colonised patients in France. The etd gene was found in 55 (10.5%) of 522 isolates tested. Isolates responsible for bullous impetigo and generalised staphylococcal scalded skin syndrome did not harbour etd, but etd was significantly more frequent in isolates causing cutaneous abscesses and furuncles. Most etd- and Panton-Valentine leukocidin-positive strains belonged to the clone of community-acquired methicillin-resistant S. aureus spreading currently throughout France.     

移情对建立新型医患关系伦理模式的利与弊

在现代社会这样一个转轨时期，医患矛盾越来越突出，如何缓和医患关系、建立新型医患关系伦理模式成为大家共同关心的课题。作者从移情的角度入手，阐述了新型医患关系伦理模式的内涵，分析了移情对于缓和医患关系有哪些有利之处与不利之处，并提出了如何适度利用移情的方法，使其发挥最大作用。     

64层螺旋CT诊断先天性冠状动脉起源异常的价值

目的：探讨64层螺旋CT冠状动脉造影诊断冠状动脉起源异常的临床价值。材料和方法：回顾性总结2005年12月至2006年12月间1800例64层螺旋CT冠脉造影的结果，统计冠状动脉起源异常的发生率。结果：1800例检查者中发现冠脉起源异常51例，发病率2．8％。包括右冠状动脉变异11例（21．6％）、左冠状动脉变异8例（15．7％）、左右冠均发生变异1例（2％）、单支冠状动脉1例（2％）、分支变异28例（54．9％）。结论：64层螺旋CT是诊断冠状动脉起源异常的安全有效方法，对临床治疗有重要的意义。     

The structure and mode of action of different botulinum toxins

The seven serotypes (A–G) of botulinum neurotoxin (BoNT) are proteins produced by Clostridium botulinum and have multifunctional abilities: (i) they target cholinergic nerve endings via binding to ecto‐acceptors (ii) they undergo endocytosis/translocation and (iii) their light chains act intraneuronally to block acetylcholine release. The fundamental process of quantal transmitter release occurs by Ca²⁺‐regulated exocytosis involving sensitive factor attachment protein‐25 (SNAP‐25), syntaxin and synaptobrevin. Proteolytic cleavage by BoNT‐A of nine amino acids from the C‐terminal of SNAP‐25 disables its function, causing prolonged muscle weakness. This unique combination of activities underlies the effectiveness of BoNT‐A haemagglutinin complex in treating human conditions resulting from hyperactivity at peripheral cholinergic nerve endings. In vivo imaging and immunomicroscopy of murine muscles injected with type A toxin revealed that the extended duration of action results from the longevity of its protease, persistence of the cleaved SNAP‐25 and a protracted time course for the remodelling of treated nerve–muscle synapses. In addition, an application in pain management has been indicated by the ability of BoNT to inhibit neuropeptide release from nociceptors, thereby blocking central and peripheral pain sensitization processes. The widespread cellular distribution of SNAP‐25 and the diversity of the toxin's neuronal acceptors are being exploited for other therapeutic applications.     

螺旋CT多功能重建在骨关节外伤中的应用

目的 探讨螺旋cT功能重建在骨与关节外伤中的应用，提高重建技术的使用能力和诊断水平。方法 对使用双层螺旋CT，SSD，MPR，MIP等多种方式重建检查的49例复杂的骨与关节外伤病例进行回顾性分析。结果 49例骨关节外伤重建成像，其中，颅底3例，颌面部7例，颈、胸、腰、骶椎共17例，肩胛骨3例，髋关节8例，膝关节11例。SSD在显示碎骨片明显移位的空间关系方面较MIP，MPR为佳，它可以直观地、立体地、清晰地、多角度显示骨关节损伤，而MIP在显示骨折细节方面较优，尤其在外伤中颅窝观察有关神经孔方面。结论 螺旋CT的SSD，MPR和MIP技术的综合应用，对复杂的骨折、关节损伤的显示效果良好，具有较高的临床应用价值。     

血小板激活因子拮抗剂SRI63-441对缺血再灌注损伤大鼠心肌的保护作用

目的 研究血小板激活因子拮抗剂SRI63-441对大鼠缺血再灌注损伤心肌的保护作用。方法 将实验大鼠分成3组,对照组未行缺血及药物治疗,再灌注组及SRI63—441治疗组结扎大鼠左冠状动脉前降支(LAD)缺血30分钟后,行再灌注10小时,其中治疗组结扎前1分钟给予SRI63—441(1mg/kg),观察大鼠再灌注心律失常,再灌注区心肌组织中丙二醛浓度、超氧化物歧化酶活性的变化。结果 SRI63—441能明显降低再灌注时室性心律失常的严重程度,使缺血30分钟再灌注10小时大鼠的心肌梗塞面积从21.6±3.1％降至12.7±2.5％,心肌组织中脂质过氧化最终产物丙二醛(MDA)含量下降,超氧化物歧化酶(SOD)活性升高。结论SRI63—441用于大鼠心肌缺血再灌注可减少心肌损伤,提示PAF为心肌再灌注损伤的重要介质,而PAF拮抗剂有可能用于心肌缺血再灌注损伤的治疗。     

干细胞动员对骨创伤大鼠免疫功能的保护作用

目的：观察自体干细胞动员对骨创伤大鼠的免疫功能的保护作用，为战创伤后的免疫抑制及继发性感染、系统性炎症反应等治疗提供依据。方法：挤压折断法复制大鼠双后肢股骨骨折模型，于致伤后0、24、48h连续给模型动物肌肉注射GM—CSF20μg／kg，致伤后72h细胞增殖法检测T、B淋巴细胞活性，ELISA法检测血清IL-1、IL-2、IFN-7、TNF—α浓度，自动系列化分析法检测C3、CA、IgM、IgG浓度，称重法观察脾重与体重的比例变化。结果：股骨骨折模型大鼠致伤后72h，GM—CSF动员骨髓干细胞组大鼠的T、B淋巴细胞活性和血清IFN-γ、IL-2浓度高于对照组（P〈0．01），IL-1、TNF—α浓度低于对照组（P〈0．01），血清C3、CA、IgM、IgG浓度及脾／体重比值高于对照组（P〈0．01）。结论：GM—CSF动员自体干细胞动员对大鼠骨创伤诱导的免疫功能抑制具有保护作用。