环氧合酶-2抑制剂对大鼠胃黏膜损伤愈合的影响

目的　环氧合酶 (COX)是合成前列腺素 (PGs)的关键酶 ,传统的非甾体抗炎药 (NSAIDs)抑制COX 1和COX 2活性 ,引起严重的胃肠道不良反应。特异性COX 2抑制剂有望成为不引起胃损伤的新型NSAIDs。本研究探讨特异性和非特异性COX 2抑制剂对盐酸诱导大鼠胃黏膜损伤愈合的影响。方法　雄性SD大鼠胃内给予 0 .6mol/LHCl1ml,Westernblot和免疫组化法分析胃黏膜COX 1和COX 2表达。盐酸灌胃后 10min ,实验组胃内给予NS 3980 .4、4、4 0mg/kg和吲哚美辛 4 0mg/kg ,对照组胃内给予 1%阿拉伯树胶 (AG) 5ml/kg。盐酸灌胃前和灌胃后 1、3、6、12、2 4及 4 8h分别处死大鼠 ,剖腹取胃 ,观察各组动物损伤指数 (LI)及光镜下的胃黏膜病理学改变。结果　盐酸灌胃后COX 2在表层上皮细胞和颈黏液细胞表达显著增加 ,NS 398和吲哚美辛均延迟胃黏膜损伤的愈合。盐酸灌胃后 12h ,NS 398组 (4和 4 0mg/kg)及吲哚美辛组的LI分别为 (1.4 2± 0 .2 3) % ,(1.4 2± 0 .2 9) %和 (1.6 2± 0 .4 4 ) % ,明显高于对照组的 (0 .5 8± 0 .2 4 ) % (P <0 .0 5 )。结论　特异性和非特异性COX 2抑制剂延迟大鼠胃损伤后的愈合 ,提示COX 2表达在胃黏膜再生过程中起重要作用     

质子泵抑制剂对胃粘膜环氧化酶-2表达的影响

目的探讨质子泵抑制剂(PPI)对大鼠胃粘膜环氧化酶—2(COX-2)表达的影响。方法 1.大鼠经胃管给予Rabeprazole(雷巴拉唑),Lansoprazole(兰索拉唑),Pantoprazol(潘妥拉唑),50mg/kg,对照组给予0.5％碳氧甲基纤维素(carboxymethyllulose,CMC),5ml/kg每天一次,连续14天,应用免疫印渍检测胃粘膜COX-1和COX-2表达水平。2.连续14天给予0.5mg/kg,5mg/kg或50mg/kg的兰索拉唑,对照组给予0.5％CMC,应用酶免疫测定法(EIA)检测大鼠胃粘膜中前列腺素E_2(PGE_2)含量,并观察兰索拉唑对酒精所致急件胃粘膜损伤的保护作用.3.特异性COX-2抑制剂(NS-398)对大鼠胃粘膜PGE_2合成及胃粘膜保护作用的影响.结果 1.PPI显著地增加大鼠胃粘膜COX-2的表达水平而不影响COX-1的表达。2.胃粘膜中PGE_2含量,对照组为266±81pg/gwet tissue:0.5mg/kg,5mg/kg 50mg/kg的兰索拉唑组分別为427±32 pg/g,483±121 pg/g(p<0.05 vs.对照组),614±82pg/g(p<0.01 vs.对照组).3.酒精对大鼠胃粘膜的损伤指数.对照组为3.78±0.29％,0.5mg/kg～50mg/kg的兰索拉唑组分别为3.01±0.38％(p<0.05、vs.对照组).2.16±0.40％(p<0.005 vs.对照组)和0.96±0.20％(p<0.005 vs.对照组)。4.NS398有效地阻断了兰索拉唑诱导的PGE_2合成及胃粘膜保护作用。结论 PPI通过诱导胃粘膜COX-2表达,增加PGE_2合成而发挥胃粘膜保护作用。     

环氧合酶-2选择性抑制剂对大肠腺瘤细胞的作用机制

目的 探索散发性大肠腺瘤细胞的原代培养；探讨环氧合酶（COX）－2选择怀抑制剂对大肠肿瘤防治的作用机制。方法 从人大肠腺瘤中分离培养上皮细胞；检测COX－2选择性抑制剂NSJ－398对细胞增殖的影响和大肠肿瘤中COX－2蛋白的表达。结果 取得大肠腺瘤30枚，培养成功23枚；NS－398对腺瘤细胞的抑制作用具有时间及剂量依存在；在大肠肿瘤中，COX－2蛋白表达显著增加，分别为83．1％和80．0％。结论 避免污染、恰当的消化时间、合适的细胞数和成纤维细胞的去除，是大肠遥瘤细胞原代培养成功的关键；NS－398对细胞生长具有明显抑制作用；COX－2蛋白在大肠肿瘤形成的早期阶段出现表达增强。     

环氧合酶-1和前列腺素E2在多潘立酮对大鼠胃黏膜保护中的作用

目的　研究多潘立酮对大鼠胃黏膜损伤是否具有保护作用 ,并探讨胃黏膜细胞中环氧合酶 1(COX 1)及前列腺素 (PG)E2是否参与其中。方法　研究分为对照组和实验组。后者分别用多潘立酮 0 .5mg/kg、1mg/kg和 2mg/kg灌胃 ,3次 /d ,连续 3d。各组大鼠灌入无水乙醇后 ,肉眼观察胃黏膜损伤指数 (LI) ,光镜下观察黏膜缺损深度 ,并计算黏膜缺损深度与胃壁全层厚度百分比。放射免疫法测定各组胃黏膜PGE2的水平。免疫组织化学方法检测COX 1和COX 2蛋白表达水平并以平均吸光度值表示其强度。RT PCR检测胃黏膜COX 1和COX 2mRNA表达变化。结果　多潘立酮 1mg/kg组的LI及黏膜缺损深度与胃壁全层厚度百分比显著低于对照组 (P <0 .0 5 ) ,0 .5mg/kg组和 2mg/kg的组LI亦显著低于对照组 (P <0 .0 5 )。多潘立酮 1mg/kg组大鼠胃黏膜COX 1蛋白表达水平及PGE2水平显著高于空白对照组 (P <0 .0 1)。各实验组和对照组在胃黏膜细胞内均无COX 2蛋白表达。三个实验组COX 1mRNA表达量与对照组比较差异均有显著性 (P <0 .0 1)。各组均未检测到COX 2mRNA表达。结论　多潘立酮对胃黏膜损伤具有保护作用 ,其机制之一可能与其增加胃黏膜COX 1mRNA和COX 1蛋白表达及促进胃黏膜PGE2分泌有关。     

胃康胶囊对消炎痛诱导大鼠胃粘膜损伤血液中相关细胞因子含量的影响

目的：观察胃康胶囊对消炎痛引起的大鼠急性胃粘膜损伤时血液中相关细胞因子[前列腺环素（PGI2）、血小板活化因子（PAG）、肿瘤坏死因子－α（TNF-α）、表皮生长因子（EGF）]含量的影响，探讨其在保护胃粘膜损伤过程中的分子机制。方法：Wistar大鼠30只灌胃给药1周后，用消炎痛复制成急性胃粘膜损伤模型，5h后处死大鼠进行以上血液相关细胞因子的检测。结果：胃康胶囊能降低急性胃粘膜损伤大鼠血液中PAF、TNF-α的含量，升高PGI2，EGF的含量，对抗胃酸分泌增加，结论：胃康胶囊对消炎痛引起的大鼠胃粘膜损伤有保护作用。对胃溃疡有预防作用。     

血浆及胃粘膜中β—内啡肽在大鼠应激性溃疡中的变化及作用

探讨冷束缚应激大鼠血浆及胃粘膜中β－内啡呐肽含量的变化及作用。方法：制作大鼠冷束缚应激模型,以放射免疫法测定应激０min（对照组）、１５min,2h及８h时大鼠血浆及胃粘膜中β－内啡肽的含量,同时测定胃液pH和胃粘膜溃疡指数（ＵＩ）,另设两组预处理组,分别于应激前１５min经颈静脉注射纳洛酮（１．６mg/kg）或等容量生理盐水（０．８mg/kg),测定其应激２h时的胃液pH及胃粘膜ＵＩ。结果：整个应激过程中,大鼠血浆及胃粘膜中β－内啡肽含量无显著变化（Ｐ＞０．０５）,应激各组大鼠的胃粘膜ＵＩ均显著高于对照组（Ｐ＜０．０１）,应激１５min组大鼠的胃液pH显著高于对照组（Ｐ＜０．０１）,临终前（应激８h组）大鼠的胃液pＨ亦显著高于对照组（Ｐ＜０．０５）;纳洛酮组大鼠液pＨ及胃粘膜ＵＩ较生理盐水对照组无显著差异（Ｐ＞０．０５）。结论：应激过程中大鼠血浆及胃粘膜中β－内啡肽含量稳定,阻断β－内啡肽受体不影响胃液pH及胃粘膜ＵＩ,β－内啡肽对应激所致的胃粘膜损伤可能不起重要作用。     

前列腺素缺乏条件下促胃动力药胃复安对大鼠胃粘膜的损伤作用与可能机制

目的探讨前列腺素(prostaglandin,PG)缺乏条件下促胃动力药胃复安对大鼠胃粘膜的损伤作用与可能机制。方法 PG缺乏状态由5mg/kg吲哚美辛诱导;雄性SD大鼠随机分组:对照组;胃复安两组(30mg/kg,60mg/kg);吲哚美辛两组(5mg/kg,25mg/kg);吲哚美辛5mg/kg合用胃复安三组(10mg/kg,30mg/kg,60mg/kg);阿托品组(阿托品-吲哚美辛5mg/kg+胃复安60mg/kg),禁食24h后,生理盐水或吲哚美辛灌胃,30min后皮下注射胃复安或生理盐水,阿托品灌胃前10min皮下注射,4h后取血,处死大鼠取胃行损伤测定:放免法测血浆内皮素(Endothelin ET-1);生化法测—氧化氮(nitric oxide NO)、丙二醛(Malondialdhyde MDA)、谷胱甘肽过氧化酶(Glutathioneperoxidase GSH-Px)含量。结果吲哚美辛合用胃复安三组胃粘膜均有明显损伤,ET-1、MDA升高(p<0.05.p<0.01),NO、GSH-Px下降(p<0.05,p<0.01);吲哚美辛25ng/kg组损伤严重,ET-1、MDA升高(p<0.01),NO、GSH-Px下降(p<0.01,P<0.05);胃复安60mg/kg胃有轻微损伤,各指标无显著变化;其余各组未见明显损伤及指标变化。结论(1)PG缺乏条件下促胃动力药胃复安可引起胃黏膜出血性损伤,可能与ET-1升高、NO下降致胃黏膜微循环紊乱有关.MDA升高,GSH-Px减少可能为损伤后的继发反应结果,加剧了黏膜损伤。(32)胃动力有潜在的引起胃黏膜损伤的能力,PG缺乏增加了胃黏膜对胃高动力的敏感性。提示临床上非甾体抗炎药(NSAIDs)服用者应慎用胃动力药,因为合用可能形成或加剧胃黏膜损伤。     

胃溃灵对胃粘膜损伤大鼠胃粘膜分泌的影响

目的 :研究胃溃灵对乙酸引起胃粘膜损伤大鼠胃粘膜分泌的影响。方法 :将 5 0只 SD大鼠制成乙酸胃粘膜损伤模型 ,并随机将大鼠等分为 5组 ,次日起给每组大鼠分别灌服等量生理盐水、大、中、小剂量 ( 12 g/ kg、6g/kg、3 g/ kg)胃溃灵、雷尼替丁 ,10 d后处死大鼠 ,观察大鼠胃粘膜损伤程度。采用阿尔新蓝与胃液中糖蛋白结合的方法 ,分别测定大鼠胃内游离粘液量、胃壁粘液量。结果 :胃溃灵能明显提高大鼠胃内游离粘液、胃壁粘液的分泌量 ,能明显抑制乙酸对大鼠胃粘膜的损伤。结论 :胃粘液分泌量增加可加强对粘膜的屏障作用 ,这是胃溃灵保护胃粘膜损伤的机制之一。     

西沙比利通过一氧化氮影响大鼠胃HCO3^—分泌的实验研究

本文研究了西沙比利对大鼠胃粘膜损伤的影响和对胃粘膜－氧化氮含量分泌的影响，结果表明加入无水乙醇后，西沙比利1mg/kg组胃粘膜溃疡面积及溃疡深度显著低于空白对照组(10.2±6.9mm     

西沙必利对大鼠失血性休克复苏后胃损害的作用

目的：观察西沙利对大鼠失血性休克复苏后胃损害的作用。方法：108例只Wistar大鼠随机分为假休克（SS）组、失血性休克复苏（HS）组和失血性休克复苏后西沙必利治疗（HSC）组，同位素标记生物微球法测量胃血流量，同时测定胃粘膜内pH(pHi)、胃排空、胃MDA含量和Na^ -K^ -ATPase活性，以及门静脉血乳酸水平。结果：HSC组与HS相比，大鼠胃内色素相对残留低率显降低，胃血流量显下降，胃pHi有显回升，4h胃粘膜MDA含量降低、Na^ -K^ -ATPase活性增加，门静脉血乳酸水平显下降。结论：失血性休克复苏后西沙必利促胃动力治疗，通过增加胃血流量，有助于改善复苏后持续存在的胃缺血缺氧状况。     

Usefulness of procalcitonin for diagnosis of infective endocarditis

The aim of this study was to evaluate the accuracy of procalcitonin (PCT) in predicting infective endocarditis (IE). 23 adult patients with IE, 30 patients with sepsis and 30 with tick-borne encephalitis were included in this prospective study. The PCT serum level, C-reactive protein (CRP), total leukocyte, and immature polymorphonuclear (PMN) cell counts were determined on admission, prior to the institution of antibiotic therapy, and compared according to the diagnosis. The median PCT level in patients with IE endocarditis was 0.81 ng/ml, in patients with sepsis it was 43.74 ng/ml, and in the group with viral infection it was 0.25 ng/ml (P < 0.001). The highest PCT level was found in patients with Staphylococcus aureus endocarditis. The area under the receiver operating characteristic curve that used PCT to predict IE was 0.722 (95% CI 0.572–0.873), compared with 0.909 (95% CI 0.829–0.989) for CRP, 0.699 (95% CI 0.551–0.846) for immature PMN cell count, and 0.619 (95% CI 0.468–0.770) for leukocyte count. Our study fails to demonstrate superiority of PCT as a diagnostic laboratorial parameter in predicting IE compared to CRP.     

慢型、潜在型克山病患者的血管内皮功能观察

目的观察山东省慢型、潜在型克山病患者的临床特点和血管内皮功能,探讨机体内皮功能失调与克山病发生发展的关系。方法选择慢型、潜在型克山病患者57人、病区健康人34人,分别采集清晨空腹血检测ET、NO、NOS、iNOS及cNOS含量及活性。结果(1)克山病患者ET水平明显高于病区健康人(P<0.01);心功能越差,ET升高越明显(P<0.01);(2)NO和NOS含量,潜在型、慢型克山病均明显高于病区健康人(P<0.01);慢型高于潜在型(P<0.01);iN-OS含量克山病患者也高于病区健康人(P<0.05);慢型克山病高于潜在型克山病(P<0.05)。结论ET、NO水平的变化可能作为一种中间环节参与了克山病的发病机制;心功能不同,血浆ET、NO升高的程度也不同;ET、NO可作为克山病病情严重程度的预测指标。     

Papillomavirus Infectious Pathways: A Comparison of Systems

The HPV viral lifecycle is tightly linked to the host cell differentiation, causing difficulty in growing virions in culture. A system that bypasses the need for differentiating epithelium has allowed for generation of recombinant particles, such as virus-like particles (VLPs), pseudovirions (PsV), and quasivirions (QV). Much of the research looking at the HPV life cycle, infectivity, and structure has been generated utilizing recombinant particles. While recombinant particles have proven to be invaluable, allowing for a rapid progression of the HPV field, there are some significant differences between recombinant particles and native virions and very few comparative studies using native virions to confirm results are done. This review serves to address the conflicting data in the HPV field regarding native virions and recombinant particles.     

前列腺干细胞抗原在人前列腺癌组织中的表达及意义

目的 探讨前列腺干细胞抗原（PSCA）在人前列腺癌（PCa）和正常前列腺（NP）、良性前列腺增生（BPH）组织中的表达及其与临床分期、病理分级的关系。方法 采用免疫组织化学（IHC）链霉菌过氧化物酶法（SP法）检测26例人PCa石蜡包埋标本、10例BPH患者的前列腺切除标本及3例NP标本中PSCA的表达。结果 PSCA在PCa组织中表达阳性率为96．2％，其中强阳性率为88．5％。NP组织阳性率为66．7％（均为弱阳性）。BPH组织阳性率为70．0％（均为弱阳性）。PCa与NP、BPH组织表达水平差异有显著性意义（P〈0．01），BPH与NP组织表达水平无统计学意义（P〉0．05）。PSCA在PCa组织主要表达于癌细胞，细胞间质和肌肉组织均无表达；NP及BPH组织表达则定位于前列腺上皮的基底细胞层。PSCA表达水平与PCa临床分期、病理分级均无相关性（P〉0.05）。结论 PSCA是一个新的细胞表面抗原，可能在PCa的诊断、免疫治疗等方面具有广阔的应用前景。     

三七有效组分Rx对兔动脉粥样硬化的实验研究

目的：探讨三七有效组分R。对兔动脉粥样硬化的影响。方法：40只雄性新西兰大白兔随机分成正常对照组、高脂模型组、三七总皂甙组三七有效组分Rx高荆量组、三七总皂甙组三七有效组分Rx低刺量组，喂饲12周后同时处死．分别测定血一氧化氮(NO)、内皮素(ET)、PAI、t—PA、血浆脂质过氧化物、红细胞内超氧化物歧化酶(SOD)，并行主动脉壁形态学、主动脉壁光镜、透射电镜观察。结果：三七有效组分Rx高、低剂量组明显升高血NO、t—PA，降低血清ET、PAI水平，抗脂质过氧化，提高红细胞内SOD活性。大体形态、光镜、电镜显示，三七有效组分Rx高、低剂量组能减轻动脉粥样硬化病变程度，减少泡沫细胞层数。结论：三七有效组分Rx有干预动脉粥样硬化的作用。     

Relevance of Endocavitary Structures in Ablation Procedures for Ventricular Tachycardia

Endocavitary Structures and Ventricular Tachycardia Ablation. Background: Radiofrequency (RF) ablation for ventricular tachycardia (VT) has high failure rates. Whether endocavitary structures (ECS) such as the papillary muscles (PMs), moderator bands (MBs), or false tendons (FTs) impact VT ablation is unknown. Methods and Results: We retrospectively reviewed records of 190 consecutive patients presenting for VT ablation and identified 46 (24%) where ECS affected ablation. In 31 of 46 patients (67%), the ECS created difficulty with catheter manipulation (n = 20), interpretation of pace map data (n = 7), or with accurately defining a scar (n = 4). In 15 of 46 (33%), specific mapping and RF energy delivery targeting the ECS itself was necessary to eliminate the arrhythmia. Detailed electroanatomic mapping was performed in 11 of 15 (73%), noncontact mapping in 3 of 15 (20%), multielectrode catheter mapping in 1 of 15 (7%), and intracardiac ultrasound in 14 of 15 (93%) patients. The ablated ECS was a PM in 5 of 15, the MB in 7 of 15, and an FT in 3 of 15. The arrhythmogenic substrate on the ECS was a focus of automatic tachycardia in 9 of 15 and the slow zone responsible for reentrant arrhythmia in the remaining 6 of 15. Successful elimination of tachycardia without recurrence was obtained in all 15 cases. There was no evidence of valvular damage or disruption of the valvular apparatus. Conclusion: During VT ablation procedures, ECS should be considered for specific mapping and targeted ablation. Once recognized, these structures can be successfully targeted for ablation without valve damage. (J Cardiovasc Electrophysiol, Vol. 21, pp. 245–254, March 2010)     

降钙素原在医院获得性肺炎和呼吸机相关性肺炎的诊断和抗感染管理中的应用价值

医院获得性肺炎(HAP)和呼吸机相关性肺炎(VAP)是我国现患率居第一位的医院感染性疾病。国内外相关指南相继进行了更新,旨在提高HAP/VAP诊断和治疗水平,改善患者的结局,但我们仍然面临诸多挑战。降钙素原(PCT)是较C反应蛋白(CRP)更特异的感染相关生物学标志物,对重症细菌感染和脓毒症具有反应快速、特异性高的优点,动态监测PCT可指导HAP/VAP的诊断及抗菌药物治疗的疗程。     

Palliative management of refractory dyspnea in COPD

COPD is a progressive illness with worldwide impact. Patients invariably reach a point at which they require palliative interventions. Dyspnea is the most distressing symptom experienced by these patients; when not relieved by traditional COPD management strategies it is termed “refractory dyspnea” and palliative approaches are required. The focus of care shifts from prolonging survival to reducing symptoms, increasing function, and improving quality of life. Numerous pharmacological and non-pharmacological interventions can achieve these goals, though evidence supporting their use is variable. This review provides a summary of the options for the management of refractory dyspnea in COPD, outlining currently available evidence and highlighting areas for further investigation. Topics include oxygen, opioids, psychotropic drugs, inhaled furosemide, Heliox, rehabilitation, nutrition, psychosocial support, breathing techniques, and breathlessness clinics.     

Expression of membrane-type matrix metalloproteinases in synovial tissue from patients with rheumatoid arthritis or osteoarthritis

We investigated the expression of membrane-type matrix metalloproteinase (MT-MMP) and matrix metalloproteinase (MMP) mRNAs in synovial tissue from patients with rheumatoid arthritis (RA, n = 5) or osteoarthritis (OA, n = 5) by Northern blot analysis. Northern analysis demonstrated strong expression of MT1-MMP, MT3-MMP, MMP-1, and MMP-3 and weak expression of MT2-MMP and MMP-8 in synovial tissue from patients with RA or OA. MT4-MMP was not detected. No significant difference was shown in the expression of MT-MMP mRNAs between RA and OA. Synovial tissue of RA or OA patients expressed MT-MMPs as well as MMPs. These results indicate that, in addition to MMPs, MT1-MMP, MT3-MMP, and probably MT2-MMP may play a role in the degradation of bone and cartilage matrix in RA and OA. Such information may provide a clue to the development of a novel therapeutic approach targeted on the prevention of joint destruction. Received: April 30, 2000 / Accepted: September 19, 2000     

Methemoglobin Forming Effect of Dimethyl Trisulfide in Mice

Abstract

Dimethyl trisulfide (DMTS) is a natural organic trisulfide that has been patented as a promising antidotal candidate against cyanide (CN). The primary mode of action of DMTS is as a sulfur donor that enables the conversion of CN to thiocyanate. Recently, it was discovered that DMTS is capable of oxidizing hemoglobin (Hb) to methemoglobin (MetHb) in vitro. The goal of these experiments was to measure the extent of DMTS-induced MetHb formation in vivo. In these experiments, intramuscular (IM) injections of formulated DMTS were administered to mice. Following the IM injection, blood was drawn and analyzed for MetHb using a rapid spectrophotometric method. Methemoglobin levels peaked in a dose-dependent manner between 20 and 30?min., and then began dropping. The highest MetHb levels measured for the 50, 100, 200 and 250?mg/kg doses of DMTS were respectively 3.28, 6.12, 9.69, and 10.76% MetHb. These experiments provide the first experimental evidence that IM administered DMTS generates MetHb in vivo and provide additional evidence for the presence of a secondary therapeutic pathway for DMTS - CN scavenging by DMTS-generated MetHb.