Aging pathways for organophosphate-inhibited human butyrylcholinesterase, including novel pathways for isomalathion, resolved by mass spectrometry.

Some organophosphorus compounds are toxic because they inhibit acetylcholinesterase (AChE) by phosphylation of the active site serine, forming a stable conjugate: Ser-O-P(O)-(Y)-(XR) (where X can be O, N, or S and Y can be methyl, OR, or SR). The inhibited enzyme can undergo an aging process, during which the X-R moiety is dealkylated by breaking either the P-X or the X-R bond depending on the specific compound, leading to a nonreactivatable enzyme. Aging mechanisms have been studied primarily using AChE. However, some recent studies have indicated that organophosphate-inhibited butyrylcholinesterase (BChE) may age through an alternative pathway. Our work utilized matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry to study the aging mechanism of human BChE inhibited by dichlorvos, echothiophate, diisopropylfluorophosphate (DFP), isomalathion, soman, sarin, cyclohexyl sarin, VX, and VR. Inhibited BChE was aged in the presence of H2O18 to allow incorporation of (18)O, if cleavage was at the P-X bond. Tryptic-peptide organophosphate conjugates were identified through peptide mass mapping. Our results showed no aging of VX- and VR-treated BChE at 25 degrees C, pH 7.0. However, BChE inhibited by dichlorvos, echothiophate, DFP, soman, sarin, and cyclohexyl sarin aged exclusively through O-C bond cleavage, i.e., the classical X-R scission pathway. In contrast, isomalathion aged through both X-R and P-X pathways; the main aged product resulted from P-S bond cleavage and a minor product resulted from O-C and/or S-C bond cleavage.     

Comparison of 180° and 360° acquisition for myocardial perfusion SPECT with compensation for attenuation, detector response, and scatter: Monte Carlo and mathematical observer results

BACKGROUND: The optimal projection data acquisition strategy for myocardial perfusion (MP) single photon emission computed tomography (SPECT) remains controversial. METHODS: We compared MP SPECT using 180 degrees and 360 degrees projection data obtained with the same acquisition time, reconstructed either with filtered back projection (FBP) or the iterative ordered-subsets expectation maximization (OS-EM) algorithm with various combinations of attenuation, detector response, and scatter compensation using mathematical observers and a myocardial defect detection task. We used Monte Carlo-simulated projection data from a population of 3-dimensional nurbs-based cardiac-torso (NCAT) phantoms with ranges of variability in patient anatomy, organ uptake, defect location, defect size, and noise level based on clinical data. Projection data from 180 degrees and 360 degrees acquisitions were generated by assuming the same acquisition time. After iterative or FBP reconstruction, standard postprocessing methods were applied. For each acquisition and reconstruction method, we optimized the number of iterations and cut-off frequency of the Butterworth filter using the Channelized Hotelling Observer methodology. The optimum set of parameters was that which gave the maximum area under the curve. RESULTS: For both acquisition protocols, OS-EM with compensations provided better performance than FBP or OS-EM without compensation. For FBP, the optimized 180 degrees acquisition provided a statistically significant increase in AUC as compared with optimized 360 degrees acquisition. For OS-EM, the AUCs for 180 degrees were slightly larger than for 360 degrees acquisitions when comparing images reconstructed with the same compensations. However, the differences were smaller and not statistically significant. CONCLUSION: With optimized reconstruction and filtering parameters, 180 degrees acquisition provided a statistically significant improvement over 360 degrees acquisition for FBP reconstruction. However, for OS-EM the differences were small and not statistically significant.     

蛙皮素对PC-3细胞骨架及细胞内游离Ca~(2+)的影响

目的:观察蛙皮素(BBS)对前列腺癌PC-3细胞骨架形态及细胞内游离Ca2+([Ca2+]i)浓度的影响。方法:①利用免疫荧光法(IH),结合激光扫描共聚焦显微镜(LSCM)检测10-5mol/L浓度BBS处理的PC-3细胞角蛋白(CK)的表达,以反映其对细胞骨架形态的影响;②应用Fluo-3/AM荧光标记技术和LSCM检测不同浓度BBS(10-9、10-7、10-5mol/L)处理的PC-3细胞[Ca2+]i浓度。结果:①10-5mol/L浓度的BBS可促进PC-3细胞CK表达及伪足形成;②BBS可提高PC-3细胞[Ca2+]i浓度,并具有浓度依赖性。结论:实验证明一定浓度的BBS可明显提高PC-3细胞[Ca2+]i浓度及CK表达,进而影响PC-3细胞骨架形态。本研究为探索BBS应用于肿瘤研究以及BBS作用后细胞内信息传递途径提供了基础。     

Feasibility of treating hyperfibrinogenemia with intermittently administered batroxobin in patients with ischemic stroke/transient ischemic attack for secondary prevention.

This study evaluated the safety and efficacy of batroxobin in treating hyperfibrinogenemia for secondary stroke prevention. Patients with ischemic stroke or transient ischemic attack (TIA) were measured for plasma fibrinogen levels. Selected participants had concomitant hyperfibrinogenemia (plasma fibrinogen > or = 3.0 g/l). Patients enrolled between 1 July 2003 and 31 December 2004 were treated with batroxobin; patients enrolled between 1 January 2002 and 30 June 2003 were treated without batroxobin. Batroxobin was administered intermittently via intravenous injection at 3-monthly intervals. Patients in both groups were followed for 1 year. Any cerebrovascular events and suspected adverse events were recorded. In total, 112 ischemic stroke/TIA patients with concomitant hyperfibrinogenemia were enrolled, 52 being treated with batroxobin and 60 without batroxobin. Six patients (11.5%) with batroxobin and 16 patients (26.7%) without batroxobin had recurrent cerebral ischemic events during follow-up. Stroke/TIA recurrence in patients without batroxobin was higher than that in patients with batroxobin (P < 0.05). Two patients with batroxobin and two patients without batroxobin developed hemorrhagic stroke during follow-up. There were five deaths (9.6%) in the batroxobin group, and seven deaths (11.7%) in the nonbatroxobin group during follow-up (P > 0.05). Intermittent intravenous injection of batroxobin can efficiently reduce the risk for stroke/TIA recurrence in patients with concomitant hyperfibrinogenemia.     

腹腔镜联合手术728例临床分析

目的探讨腹腔镜联合手术的优越性。方法回顾分析1992年7月～2006年3月开展腹腔镜联合手术728例临床资料，其中腹腔镜胆囊切除术（laparoscopic choleeysteetomy，LC）联合肝囊肿开窗引流术586例，LC联合阑尾切除术80例，Lc联合卵巢囊肿切除术46例，LC联合肾囊肿去顶引流术16例。结果726例在腹腔镜下完成手术，2例因腹腔粘连中转开腹，无胆道损伤、出血、感染、死亡等并发症发生。512例随访2～60个月，平均16个月，无胆道结石及肝、肾、卵巢囊肿复发。结论腹腔镜联合手术一次性处理两种或两种以上腹部病变是安全有效的，具有创伤小、痛苦轻、恢复快等优点。     

结核分枝杆菌稳定L型变异的聚合酶链反应研究

目的：探讨结核分枝杆菌稳定L型变异的分子机制。方法：采用结核分枝杆菌聚合酶链反应(PCR)诊断试剂扩增结核分枝杆菌稳定L型纯培养物的染色体DNA，琼脂糖凝胶电泳、聚丙烯酰胺凝胶电泳(polyscrylamid gel electrophoresis，PAGE)薄层凝胶扫描分析。结果：结核分枝杆菌稳定L型比细菌型多一DNA条带。结论：结核分枝杆菌稳定L型的形成可能与基因突变有关，在特异性PCR反应中可形成与其亲代细菌型有差异的产物。     

早期脑室置管行颅内压监护对中型颅脑损伤患者的预后影响

目的　探讨早期脑室置管行颅内压 (ICP)和脑灌注压 (CPP)监护在中型颅脑损伤中的临床应用价值。方法　将 12 5例伤后 2 4h入院无手术指征的中型颅脑损伤 (GCS 9～ 12分 )患者 ,随机分为ICP监护组 :入院后即经恻脑室内穿刺置管行ICP与CPP连续监测 ,根据颅内压变化调整治疗方案 ;对照组 :入院后不做ICP监测 ,依据临床观察的意识及生命体征变化 ,进行治疗。结果　颅内压监护组脱水剂剂量、应用时间均低于对照组 ,疗效优于对照组 ,两组差异有显著意义 (P <0 0 5 )。结论　中型颅脑损伤病情极不稳定 ,早期行ICP监护能及早发现病情变化 ,对及时采取有效治疗措施 ,降低死残率 ,改善预后有重要意义。     

奥沙利铂为主的静脉化疗联合腹腔温热灌注和体外高频透热治疗晚期大肠癌的临床观察

目的 探讨奥沙利铂为主的化疗联合腹腔温热灌注治疗晚期肠癌的临床效果.方法 对42例晚期大肠癌患者,予腹腔温热灌洗化疗及体外高频透热治疗,联合以奥沙利铂为主的静脉化疗,至少2个周期,观察疗效及不良反应.结果 全组患者完成169个周期治疗,CR 5例,PR 22例,SD 8例,PD 7例,总有效率66.3%.完全缓解率11.9%.不良反应以白细胞下降及消化道反应多见,少数患者出现周围性神经毒性,以I-Ⅱ 度为主.结论 以奥沙利铂为主的静脉化疗联合腹腔温热灌注和体外高频透热治疗,对晚期大肠癌具有一定的疗效,毒副作用小;腹腔局部化疗是一种值得关注的治疗途径.     

Analysis of the Surface Ozone During Summer and Autumn at a Coastal Site in East China

The levels and temporal variations of surface ozone at a coastal site in East China during summer and autumn were analyzed and the influences of meteorological parameters on ozone were investigated. An inland city was chosen as a comparison site. The main results and conclusions of this study are: (1) ozone pollution, with a maximum 1 h concentration of 150.98 ppbv, was severe during summer and autumn at the coastal site; (2) the ozone level was obviously higher at the coastal site than that at the inland site in September; (3) besides temperature and solar radiation, sea-land breeze circulation is an important factor influencing the ozone level at the coastal site, and sea breeze often induce high ozone levels (the average ozone concentration for sea breeze was about 13 ppbv higher than that for land breeze).     

改良低压回肠代膀胱术的疗效评价

目的 总结改良原位低压回肠代膀胱术的疗效及患者生活质量。方法 膀胱癌患者53例，平均年龄61岁，均施行根治性膀胱全切术。截取末端35—45cm回肠，“U”形缝合形成代“膀胱”，并与输尿管形成抗返流的“乳头”缝合。结果 术后所有患者血生化及电解质均正常，随访3—6个月，51例患者白天完全可控排尿，完全夜间可控制排尿25例。47例无残余尿，5例有残余尿20-35mL。结论 改良低压回肠代膀胱术，膀胱容量大、压力低、无返流、效果好、无吸收性酸中毒，患者白天均能够控制尿液，夜间需定时排尿，生活质量高，多数患者满意。