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。     

产超广谱β-内酰胺酶菌的检测方法及耐药性的比较

【目的】比较3种方法检测产超广谱β-内酰胺酶(ESBLs)菌株的检出率，了解近期广东省人民医院大肠埃希菌和肺炎克雷伯菌产ESBLs菌株的感染率及其耐药情况。【方法】walkaway-40机鉴定菌种，MIC初筛，双纸片协同试验，确证试验、药敏纸片扩散法。【结果】大肠埃希菌72株和肺炎克雷伯菌78株，确证试验检出率分别为46％和33％。上述产ESBLs菌株对三代头孢菌素和氨曲南大多耐药，对氨苄西林，环丙沙星多呈耐药，亚胺培南100％敏感，对5种复方制剂耐药率为18．2％～100％。【结论】双纸片协同法和NCCLs确证试验均是检测ESBLs的好方法，各实验室应重视ESBLs菌株的检测和药敏试验。     

眼睛葡萄膜恶性黑色素瘤肝转移的外科治疗

眼睛葡萄膜恶性黑色素瘤由葡萄膜黑色素细胞发育来,最常见的转移部位为肝脏,葡萄膜恶性黑色素瘤40%～80 9/6的病人有肝脏转移[1,2].过去认为恶性黑色素瘤病人肝转移为Ⅳ期病人,不适合手术切除.     

不同种属脱细胞真皮与自体皮复合移植的比较性研究

目的　观察不同种属脱细胞真皮基质 (acellulardermalmatrix,ADM)与自体皮复合移植的效果 ,为异种ADM的临床应用提供理论依据。　方法　本地产白色小猪 6头 ,分为异种 (人 )ADM +自体刃厚皮组 (A组 )、同种异体 (猪 )ADM +自体刃厚皮组 (B组 )、单纯自体刃厚皮组 (C组 )及单纯自体中厚皮组 (D组 )。观察术后 2、4、8、12、2 4周内移植物存活率 ,以及移植皮片收缩程度、移植区组织学变化等情况。　结果　A、B组移植后皮片外观光滑、有弹性 ;两组均获得了满意的皮片成活率 ,并可迅速诱导成纤维细胞、血管内皮细胞等宿主修复细胞的长入 ;两组移植皮片收缩面积有大于C、D组的趋势 (P <0.0 5);术后 2 4周移植区组织与单纯中厚皮移植组织结构一致。　结论　在观察期内(复合移植后 2 4周 ) ,与自体皮复合移植时 ,同、异种ADM具有相近的生物学作用 ,异种来源的ADM可能具有更广阔的应用前景     

预移植在胚胎移植中的意义

目的 :评价预移植在胚胎移植中的作用。　方法 :在超声波引导下胚胎移植 114个周期 ,其中 10 1个周期进行预移植。比较预移植与未预移植周期临床妊娠率和胚胎种植率 ;按预移植与实际胚胎放置深度差值分组 ,并比较两组妊娠率和胚胎种植率。　结果 :预移植周期与未预移植周期临床妊娠率和种植率统计学差异无显著性(5 9.4 1%和 6 1.5 4 % ,35 .81%和 31.4 3% ,P均 >0 .0 5 ) ;按预移植与实际胚胎放置深度差值分组后 ,两组妊娠率和种植率统计学差异也无显著性 (6 1.5 4 %和 5 8.6 7% ,4 0 .79%和 34.0 9% ,P均 >0 .0 5 )。　结论 :在胚胎移植技术中 ,预移植不能准确指引胚胎移植深度