多发性硬化患者血清尿酸水平变化的研究

目的　探讨多发性硬化 (MS)患者血清尿酸 (UA)水平的变化及其临床意义。方法　采用酶定量分析法对 4 3例MS患者和 4 5名正常对照者的血清UA水平进行检测。结果　MS组血清UA水平明显低于对照组 (P <0 0 1)。MS组中病程越长 (P <0 0 1)、神经伤残程度越重 (DSS评分越高 ) (P <0 0 5 ) ,血清UA水平越低 ;女性患者UA水平明显低于男性患者 (P <0 0 0 1) ;经过糖皮质激素治疗后血清UA水平明显回升 (P <0 0 0 1) ,但治疗前血清UA水平越低则疗效越差 (P <0 0 1、P <0 0 5 )。结论　MS患者血清UA水平降低 ,且与MS的病程、伤残程度、疗效及性别密切相关。UA水平升高可能为激素治疗MS的一个作用机制     

胸腰椎骨折术后内固定松动、断裂的原因及预防

目的 探讨椎弓根螺钉系统用于胸腰椎骨折术后出现松动、断裂的原因，并提出相应的预防对策。方法 12例胸腰椎骨折术后内固定失效病例，采用RF系统3例，AF系统9例。均未行植骨融合，AF系统中未按要求安装横连结3例，术后伤椎前缘高度平均恢复至正常的85．2％。结果 术后8—21个月出现棒断裂4例，螺钉断裂3例，钉帽松动5例。结论 内固定物的自身问题、术者的经验欠缺及操作不规范是胸腰椎骨折术后椎弓根螺钉系统松动、断裂的原因，但伤椎骨结构未能得到良好重建及术后椎间盘退变可能是其更重要的因素。因此重视内固定物的选择、加强规范操作，强调对损伤椎体及椎间盘的全面处理是预防内固定失效的有效措施。     

APTT测定值和APTT测定值比率的临床应用价值探讨

目的;探讨APIT测定值(秒)和APIT测定值比率中哪一种是更稳定、更可靠的临床应用指标。方法:将同一标本采用法国STA-Compat全自动血凝仪以及两种手工法同时测定,比较同组标本不同方法的APTT测定值(秒)和APTT测定值比率。结果:手工法(一)与法国STA-Compact全自动血凝仅比较,如APTT值以秒表示,对照组、口服抗凝剂组及肝病组病人同组标本不同方法之间存在显著性差异(P<0.01,P0.10,P>0.50,P>0.05);手工法(二)与法国STA-Compact全自动血凝仪在对照组、口服抗凝剂组及白血病组的比较中,也获得类似的结果。结论:将APTT测定值(秒)转化为病人与对照APTT测定值比率报告,使不同方法结果间更具可比性。在APTT报告的标准化方面,建议将APTT和APTT测定值比率同时报告。     

Modeling of relationships between pharmacokinetics and blockade of agonist-induced elevation of intraurethral pressure and mean arterial pressure in conscious dogs treated with alpha(1)-adrenoceptor antagonists.

Fiduxosin is a new alpha(1)-adrenoceptor antagonist targeted for the treatment of symptomatic benign prostatic hyperplasia. The purpose of this study was to determine and compare the potencies of the alpha(1)-adrenoceptor antagonists terazosin, doxazosin, tamsulosin, and fiduxosin, based on relationships between plasma drug concentrations and blockade of phenylephrine (PE)-induced intraurethral (IUP) and mean arterial pressure (MAP) responses after single oral dosing in conscious male beagle dogs. Magnitude of blockade and plasma concentrations were evaluated at selected time points over 24 h. All drugs produced dose-dependent antagonism of PE-induced IUP and MAP responses. When IUP and MAP blockade effects were plotted against drug plasma concentrations, direct relationships were observed that were well described by the sigmoidal maximal effect model. IUP IC(50) values for terazosin, doxazosin, tamsulosin, and fiduxosin were 48.6, 48.7, 0.42, and 261 ng/ml, respectively. MAP IC(50) values were 12.2, 13.8, 1.07, and 1904 ng/ml, respectively. Uroselectivity index values, defined as MAP IC(50)/IUP IC(50), were 0.25, 0.28, 2.6, and 7.3, respectively. These results extend previous observations with terazosin in this model, showing that doxazosin exhibits a uroselectivity index comparable to terazosin, consistent with the lack of alpha(1)-adrenoceptor subtype selectivity or uroselectivity of these drugs. Tamsulosin, an alpha(1a)-/alpha(1d)-subtype selective agent, had an index value approximately 10-fold greater than the nonselective drugs. Based on its pharmacokinetic profile and a relative uroselectivity 29-fold greater than the nonselective drugs, fiduxosin is expected to exhibit greater selectivity for urethral compared with vascular alpha(1)-adrenoceptors in human and should be a novel, long-acting, uroselective alpha(1)-adrenoceptor antagonist.     

RNA干扰技术在以VEGF/VEGFR为靶点的膀胱癌治疗研究中的应用前景

RNA干扰（RNAi）是正常生物体内抑制特定基因表达的一种现象，它是指当细胞中导入与内源性mRNA编码区同源的双链RNA（dsRNA），该mRNA发生降解而导致基因沉默的现象。利用RNAi技术干涉VEGF表达，达到抑制肿瘤发展和转移的研究已较为广泛。膀胱癌生长、转移不仅有VEGF表达增多，同时发现VEGFR表达亦增高，成为RNAi的新靶点。现主要综述以VEGF/VEGFR为靶点的RNAi技术在膀胱癌治疗研究中的优势、发展前景以及存在问题与对策。     

Buccal mucosal graft for urethral reconstruction.

Urethral reconstruction with graft substances, such as skin and bladder mucosa, has been previously used when primary anastomosis cannot be achieved. However, stricture and meatal prolapse are associated with these grafts. We report the use of buccal mucosa for the reconstruction of urethral defects in 3 patients. One patient with failed operation for hypospadias received tube buccal mucosal graft for urethral replacement. Two patients with urethral necrosis and stricture received onlay buccal mucosal graft. All patients were disease-free during follow-up (range, 12 to 49 months; mean, 36 months). One patient had a pinhole fistula that was successfully managed with simple repair. This technique appears to be useful for urethral reconstruction when a local graft is not available, even in patients with complicated conditions.     

全雄激素阻断前后前列腺癌细胞中Bcl-2和Bcl-XL基因表达改变

全雄激素阻断是前列腺癌(PCa)治疗的重要手段。虽然已发现一些蛋白分子涉及雄激素的调节[1] ,但其分子机理尚不清楚。我们采用分子生物学方法检测人PCa全雄激素阻断前后Bcl 2和Bcl XL 蛋白的表达,探讨PCa发生发展的分子机理。材料与方法　4 2例局限性PCa患者。全雄激素阻断治疗采用抑那通或诺雷德皮下注射加口服Flutamide 3个月,然后患者接受PCa根治术。PCa标本分别经穿刺活检和根治术标本取得,10 %福尔马林固定后石蜡包埋,病理证实。Bcl 2和Bcl XL 蛋白单克隆抗体(1/ 2 0 0 )和试剂盒购于SantaCruzInc。显微镜下,细胞着色棕黄…     

甲壳素涂层PGLA神经导管修复兔面神经缺损的实验研究

目的:探讨甲壳素涂层PGLA神经导管修复兔面神经缺损的效果。方法:成年雄性新西兰兔24只,无菌条件下切断双侧面神经下颊支,制成15mm的兔面神经下颊支缺损模型。左侧用甲壳素涂层聚丙交脂-乙交脂共聚物[poly(L-lactide-co-glycolide),PGLA]神经导管修复;右侧用翻转自体神经修复作为对照。术后5周、10周和14周行大体观察、电生理检查、组织学、电镜观察评价修复效果。结果:术后5周观察到神经导管中有新生轴索通过,再生神经发育不成熟;右侧自体神经修复近段有髓神经纤维均匀疏散分布,远段未见明显再生神经束形成。术后14周左侧再生神经已通过神经导管长入远端,电生理检查结果表明自体神经修复侧再生神经质量优于神经导管修复侧,差异有统计学意义(P<0.01)。自体神经修复再生纤维密度优于神经导管修复侧,差异有统计学意义(P<0.01),但自体神经修复侧近段神经髓鞘部分空泡样变性及脱髓鞘改变,远段再生神经纤维束形成少,面肌联带运动程度较导管修复侧严重。结论:甲壳素涂层PGLA神经导管能有效修复周围神经缺损,有望替代自体神经移植。     

蛇毒Ⅱ类磷脂酶A2功能分化的分析研究

目的：研究蛇毒Ⅱ类磷脂酶A2(PLA2)中D49 PLA2和K49 PLA2的功能分化及其功能分化决定位点的鉴定。方法：运用序列比较分析，进化树构建和DIVERGE v1．04软件计算研究D49 PLA2和K49 PLA2的功能分化情况及其分化位点。结果：序列比较分析，进化树构建和DIVERGE v1．04软件计算结果表明蛇毒Ⅱ类PLA2中D49 PLA2和K49 PLA2的确发生了功能分化，对于K49 PLA2来说，1S，7K，11Q，E12，R34，T56，N88，L92，E108，K116，K128可能为功能分化决定位点。对于D49 PLA2，L2，G33，G35，F46和Y118可能为功能分化决定位点。结论：我们首次通过序列比较分析，进化树构建和DIVERGE v1．04软件计算鉴定出蛇毒Ⅱ类PLA2中D49 PLA2和K49 PLA2可能的功能分化位点，为今后通过基因重组和定点突变方法研究蛇毒Ⅱ类PLA2结构功能关系提供了线索。