Blunted renal dopaminergic system activity in puromycin aminonucleoside-induced nephrotic syndrome.

BACKGROUND: A primary tubular sodium handling abnormality has been implicated in the edema formation of nephrotic syndrome. Dopamine synthesized by renal proximal tubules behaves as an endogenous natriuretic hormone by activating D(1)-like receptors as a paracrine/autocrine substance. METHODS: We examined the time courses of the urinary excretion of sodium, protein and dopamine in puromycin aminonucleoside (PAN)-treated and control rats. The rats were sacrificed during greatest sodium retention (day 7) as well as during negative sodium balance (day 14) for the evaluation of renal aromatic l-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine. Also, the influence of volume expansion (VE) and the effects of the D(1)-like agonist fenoldopam (10 microg/kg bw/min) on natriuresis and on proximal tubular Na(+),K(+)-ATPase activity were examined on day 7. RESULTS: The daily urinary excretion of dopamine was decreased in PAN-treated rats, from day 5 and beyond. This was accompanied by a marked decrease in the renal AADC activity, on days 7 and 14. During VE, the fenoldopam-induced decrease in proximal tubular Na(+),K(+)-ATPase activity was more pronounced in PAN-treated rats than in controls. However, the urinary sodium excretion during fenoldopam infusion was markedly increased in control rats but was not altered in PAN-treated animals. CONCLUSION: PAN nephrosis is associated with a blunted renal dopaminergic system activity which may contribute to enhance the proximal tubular Na(+),K(+)-ATPase activity. However, the lack of renal dopamine appears not to be related with the overall renal sodium retention in a state of proteinuria.     

腹茧症的外科诊治现状

笔者复习相关文献，对腹茧症的病因、病理、临床特点、诊断及治疗等方面的研究现状作一综述，旨在加深临床医生对该病的认识。     

五叶参抗血栓形成作用的研究

用人血进行体外实验研究证实,五叶参水煮制备液能明显抑制APD、复合诱聚剂诱导的血小板1min、5min、最大聚集率,并促进解聚发生(P均<0.05);该药还对体外血栓形成具有显著的抑制作用(P<0.05);五叶参水煮液与PPP混合后,尚能抑制多种凝血因子活性,使KPTT、PT、TT、AT、RVV-RT、RVV-CT等凝血试验时间延长(P均<0.05);此外,五叶参有加速红细胞电泳速度的作用。上述结果表明,五叶参是一种具有抑制血小板功能、凝血功能及红细胞聚集性等多个环节的抗血栓形成药物,值得进一步研究探讨。     

新辅助化疗对结直肠癌的作用

目的探讨短程5-FU/CF方案新辅助化疗对结直肠癌细胞凋亡、增殖和p53表达以及术后并发症和预后的影响。方法分别采用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法（TUNEL）和免疫组化SP法检测68例患者结直肠癌组织的细胞凋亡指数（AI）和ki-67增殖指数（PI）及凋亡相关基因p53的表达,并比较新辅助化疗组和对照组患者术后并发症的发生情况和预后情况。结果新辅助化疗组肿瘤细胞的AI均数为3.56%,明高于对照组的2.29%（P〈0.01）,PI均数为22.60%明显低于对照组的33.60%（P〈0.01）,p53阳性表达率为28.9%（11/38）明显低于对照组的56.7%（17/30）（P〈0.05）。两组中大肠癌细胞的AI与PI均呈负相关（r=-0.790,r=-0.663）（P〈0.01）。两组术后并发症的发生差异无显著性（P〈0.05）。两组的复发转移率和复发转移平均时间差异有显著性（P〈0.05）。结论短程5-FU/CF方案新辅助化疗可以显著诱导结直肠癌细胞凋亡,并抑制其增殖;降低结直肠癌组织p53的阳性表达率,而不增加术后并发症的发生,能延缓和减少结直肠癌术后的复发转移。     

乳腺癌患者外周血EMA和EGP-2mRNA的表达及其临床意义

目的 探讨上皮膜抗原(EMA)和表皮糖蛋白基因(EGP-2)在乳腺癌患者外周血中的表达及其与肿瘤微转移的关系. 方法采用RT-PCR方法检测53例乳腺癌患者(乳癌组)和24例乳腺良性疾病患者(良性病组)EMA和EGP-2mRNA在外周血中的表达,并分析其与临床指标之间的关系. 结果乳癌组外周血EMA和EGP-2mRNA的表达率分别为33.96%和28.30%,而在良性病组外周血表达率分别为0和4.17%,差异均有统计学意义(P＜0.05).EMA和EGP-2mRNA的检出率与腋窝淋巴结转移、TNM分期等临床参数呈正相关;EMA和EGP-2mRNA联合检测敏感度和准确性在乳腺癌组分别为52.83%和66.23%,相对于EPG-2 mRNA单项检测敏感度及准确性有明显升高,但与EMA mRNA无统计学差异.结论 EMA和EGP-2联合检测时准确性明显升高,故两者可作为标志物检测乳腺癌患者外周血微转移,有可能对乳腺癌的疗效和预后判断有意义.     

多聚酶链反应检测细菌DNA对大鼠空、回肠吻合口瘘的早期诊断价值

目的:探讨PCR检测大鼠外周血及腹水中细菌DNA对空肠-空肠、回肠-回肠吻合口瘘的早期诊断价值。方法:健康Wistar雌性大鼠50只，随机分成5组，每组10只：A组为假手术组;B组为空肠-空肠吻合组;C组为空肠吻合口瘘组;D组为回肠-回肠吻合组;E组为回肠吻合口瘘组。采集手术前后外周血及术后腹水，抽提DNA, 比较lacZ基因和16SrRNA基因的PCR阳性率，并观察各组的病理学情况。结果:（1）C，E组术后外周血lacZ基因PCR阳性率与B，D组无显著性差异（P>0.05）;C，E组术后外周血16SrRNA基因PCR阳性率显著高于B，D组（P<0.05）。（2）C，E组腹水lacZ基因和16SrRNA基因PCR阳性率均显著高于B，D组（P<0.05）。（3）C，E组腹水lacZ基因阳性率显著高于外周血（P<0.05）;C，E组腹水16SrRNA基因阳性率与外周血无显著性差异（P>0.05）。结论:（1）PCR检测术后外周血16SrRNA基因对空、回肠吻合口瘘的早期诊断有一定意义;（2）检测术后腹水lacZ基因和16SrRNA基因对空肠-空肠、回肠-回肠吻合口瘘的早期诊断也有一定意义。     

短发卡RNA对人胃癌细胞STAT3基因的沉默作用

目的:探讨STAT3基因小发夹RNA（shRNA）表达质粒对胃癌MKN-45细胞STAT3基因的干扰作用。方法:根据STAT3 mRNA 编码序列，设计RNA干扰靶点，构建STAT3基因的特异性小RNA干扰质粒（psiRNA-H1/STAT3），使用脂质体转染人胃癌细胞系（MKN-45细胞）。实验分为对照（A）组，psiRNA-H1转染（B）组和psiRNA-H1/STAT3转染（C）组。通过RT-PCR和Western Blot检测STAT3特异性小RNA干扰基因对胃癌细胞STAT3基因mRNA和蛋白表达的影响。结果:psiRNA-H1/STAT3经限制性酶切及部分序列分析证明基因插入正确，并经测序证实。将其成功转染MKN-45细胞后，该细胞的STAT3 mRNA和蛋白表达均明显下降(P<0.05)。 结论:将成功构建的针对STAT3基因的shRNA表达载体转染MKN-45细胞，能有效抑制该细胞的STAT3 mRNA和蛋白表达，为STAT3基因靶向治疗提供一定的实验依据。     

经峡部径路行甲状腺手术的术式改进

目的探讨经峡部径路行甲状腺手术的临床价值。方法回顾性分析10年间575l例行甲状腺手术患者的临床资料。按手术方式分为两组：经峡部径路甲状腺切除术的3288例为改良组；同期施行传统切除术式的2463例为常规组。比较两种手术方式对手术时间、术中出血、术后引流及并发症的影响。结果改良组手术时间较常规组明显缩短（P〈0．01），术中出血量、喉返神经神经损伤率、术后气管局部不适及低钙血症的发生率明显减少（P〈0．01），术后引流量减少（P〈0．05），患者对手术耐受性好，术后出血发生率两组无统计学差异。结论经峡部径路行甲状腺手术可明显缩短手术时间；减少术中出血量，以及降低喉返神经损伤、术后出血、低钙血症等并发症的发生。     

BRMS1在不同转移性乳腺癌细胞中的表达及其与HDAC活性的关系

目的:探讨肿瘤转移抑制基因（BRMS1）在不同转移性乳腺癌细胞中的表达及其与组蛋白去乙酰化酶（HDAC）活性的关系和意义。方法:采用 RT-PCR技术检测3种细胞株〔非转移性MCF-7(A株)，低转移性MDA-MB-453（B株），高转移性MDA-MB-231（C株）〕中BRMS1基因的表达。用Western blot检测在上述3种细胞株中BRMS1蛋白的表达。ELISA检测3种细胞株中HDAC的活性。结果:(1) 在A，B，C 3种细胞株中BRMS1 基因表达依次比例为3.1∶2.0∶1.0。C细胞株比A细胞株BRMS1基因表达降低2.1倍，BRMS1 基因表达随转移程度的增高而明显降低（P＜0. 001)。(2)在A，B，C 3种细胞株中BRMS1蛋白表达依次比例为3.2∶1.9∶1.0。C细胞株比A细胞株BRMS1蛋白表达降低2.2倍，BRMS1随转移程度的增高而明显降低（P＜0. 001)。(3)A，B，C 3种细胞株中HDAC活性依次比例为1.0∶1. 8∶2.6。C细胞株比A细胞株HDAC活性增高1.6倍，随转移程度的增高HDAC活性升高（P＜0. 001)。结论:（1）BRMS1基因和蛋白的表达在3种细胞株中随转移程度的增高而呈递减趋势。（2）HDAC活性在3种细胞株中随转移潜能的增高而呈递增趋势;提示BRMS1可能通过参与调节HDAC活性调控乳腺癌的转移。     

Handling of asymmetrical dimethylarginine and symmetrical dimethylarginine by the rat kidney under basal conditions and during endotoxaemia.

BACKGROUND: Asymmetrical dimethylarginine (ADMA) is capable of inhibiting nitric oxide synthase enzymes, whereas symmetrical dimethylarginine (SDMA) competes with arginine transport. The potential role of inflammation in the metabolism of ADMA has been elucidated in an in vitro model using tumour necrosis factor-alpha, resulting in a decreased activity of the ADMA-degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH). The kidney probably plays a crucial role in the metabolism of ADMA by both urinary excretion and degradation by DDAH. We aimed to further elucidate the role of the kidney in a rat model under basal conditions and during endotoxaemia. METHODS: Twenty-five male Wistar rats weighing 275-300 g were used for this study. The combination of arteriovenous concentration differences and kidney blood flow allowed calculation of net organ fluxes. Blood flow was measured using radiolabelled microspheres according to the reference sample method. Concentrations of ADMA, SDMA and arginine were measured by high-performance liquid chromatography. RESULTS: The kidney showed net uptake of both ADMA and SDMA and fractional extraction rates were 35% and 31%, respectively. Endotoxaemia resulted in a lower systemic ADMA concentration (P = 0.01), which was not explained by an increased net renal uptake. Systemic SDMA concentrations increased during endotoxaemia (P = 0.007), which was accompanied by increased creatinine concentrations. CONCLUSIONS: The rat kidney plays a crucial role in the regulation of concentrations of dimethylarginines, as both ADMA and SDMA were eliminated from the systemic circulation in substantial amounts. Furthermore, evidence for the role of endotoxaemia in the metabolism of dimethylarginines was obtained as plasma levels of ADMA were significantly lower in endotoxaemic rats.