Absence of association between SERPINE2 genetic polymorphisms and chronic obstructive pulmonary disease in Han Chinese: a case-control cohort study

Background: Recent studies have proposed that the serine protease inhibitor E2 (SERPINE2) was a novel susceptibility gene for chronic obstructive pulmonary disease (COPD) in Caucasians. However, this issue still remained controversial. Additional evidence

Study of urinary 8-hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in diabetic nephropathy patients

Increased oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications. Urinary 8-hydroxydeoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. This article studied oxidative DNA damage in patients with diabetic nephropathy and in healthy control subjects by urinary 8-OHdG evaluations. Contents of 8-OHdG in urine were analyzed by capillary electrophoresis with end-column amperometric detection (CE-AD) after a single-step solid-phase extraction (SPE). Levels of urinary 8-OHdG in diabetic nephropathy patients with macroalbuminuria was significant higher than in control subjects (5.72 +/- 6.89 mumol/mol creatinine versus 2.33 +/- 2.83 mumol/mol creatinine, P = 0.018). A significant difference of 24 h urinary 8-OHdG excretions exists between the patients with macroalbuminuria and the patients with nonnoalbuminuria (19.2 +/- 16.8 mug/24 h versus 8.1 +/- 1.7 mug/24 h, P = 0.015). There was a positive correlation between urinary excretion of 8-OHdG and glycosylated hemoglobin (HbA(1)c) (r = 0.287, P = 0.022). A weak correlation exists between the levels of 8-OHdG and triglyceride (r = 0.230, P = 0.074). However, the urinary 8-OHdG contents are not correlated with blood pressure and total cholesterol. The increased excretion of urinary 8-OHdG is seen as indicating an increased systemic level of oxidative DNA damage in diabetic nephropathy patients. (C) 2004 Elsevier B.V. All rights reserved.

Relationship between COPD and polymorphisms of HOX-1 and mEPH in a Chinese population

Recent studies have proposed that susceptibility to chronic obstructive pulmonary disease (COPD) might be related with the polymorphisms of some genes encoding antioxidant enzymes, such as heme oxygenase-1 (HOX-1) and microsomal epoxide hydrolase (mEPH).

慢性阻塞性肺病中医五脏关系及其病变规律的研究

目的:用数据挖掘的方法分析慢性阻塞性肺病病变过程中中医五脏的传变规律及其相互影响关系。方法:建立慢性阻塞性肺病病例数据库,将数据库中的数据预处理转换,并导出到W eka的格式(.arff),然后利用W eka进行相关的数据挖掘分析。结果:在慢性阻塞性肺病的病变过程中,初起病位在肺,逐步转变为肺脾肾、肺脾心同病,后期肺脾心肝肾五脏俱损,且中焦脾土是其传变的关键。结论:应用数据挖掘的方法分析疾病病变过程中五脏的传变关系及其相互影响关系具有一定的应用前景。

核素131I胆道腔内辐照支架的制作和动物实验及临床应用研究

恶性梗阻性黄疸(malignant obstructive jaundice,MOJ)发现时多为晚期,如不治疗生存期仅3个月。由于肿瘤位置特殊、患者一般情况较差,仅5%～20%的患者可行外科切除和分流手术,并且手术死亡率相当高,分流术病死率高达10%～43%。1974年Molnar和Stocknm首先采用PTCD术（经皮肝胆管内外引流术，Percutaneous Transhepatic Cholangic Drainage,PTCD）,使MOJ患者的临床症状得到缓解, 获得进一步治疗的机会。1989年金属支架开始应用于胆道系统,恢复了胆汁的生理性引流,并使大多数患者拔除引流管,提高了生活质量,成为非手术治疗MOJ的首选方法。但肿瘤生长是造成支架堵塞、黄疸复发的主要原因。文献报道MOJ患者放置金属支架后,支架堵塞的概率达20%～86%,其中大多数由肿瘤生长通过支架网眼或超过支架边缘引起。因此,在支架置放的同时如何积极控制肿瘤生长成为提高疗效的关键问题。MOJ的局部治疗方法有多种,但都存在不足之处。国内学者采用动脉化疗栓塞结合PTCD或支架置放的方法治疗MOJ,使患者的生存期得到延长。但引起MOJ的胆管癌、淋巴结转移癌、胰腺癌、壶腹癌多为少血供肿瘤,而且由于血供特殊,大部分病例碘油沉积欠佳,因此动脉化疗栓塞对这类肿瘤的作用是有限的。外辐照治疗对胆管癌、淋巴结转移癌、胰腺癌、壶腹癌等引起MOJ的肿瘤有一定疗效,并与胆道引流术结合应用于上述肿瘤引起的MOJ。由于瘤体周围有肝脏、胰腺、胃肠道、肾脏等对射线敏感的器官, 限制了外辐照剂量,影响了疗效的提高。近几年,一种斩新的治疗手段正在应用于临床，就是通过PTCD手术时建立的通道再行腔内辐照治疗(核素内辐照治疗),可以较好的控制肿瘤继续生长，抑制支架再狭窄的发生,可使MOJ的治疗取得更好的效果。本研究的目的就是探索胆道内辐照支架制作的可行性，并设计特别的施源器，其具体方法可以简述为：以球囊扩张器扩张重度狭窄胆管+置入特制的二腔单囊管+腔内低剂量率放疗+腔内热频热疗+胆管引流等联合方法治疗。同时，就该二腔单囊管内辐照支架的安全性进行动物实验，从分子生物学、核医学的角度阐述了实验研究的机理和病理改变，同时进行了临床的应用研究，探讨胆道支架发生再阻塞的相关因素及对策，进一步提高（MOJ）患者的生存期。本工作结果总结如下： 1 对放射源和施源器均进行了改进，放射源为液态放射性核素131I，施源器为可调节的长柱形球囊，是专门设计的硅橡胶二腔单囊管，其功能为：中腔通接胆管腔（蓝色），具有引流胆汁作用；另一腔管连接球囊（绿色），是长柱状形可调节长短的球囊，囊内装填放射性液态核素131I；囊内还设置射频加热电极，能加热升温。另外，还可以根据肿瘤的大小和长度，来调节施源器的长度（长柱形球囊），一般照射长度超出支架两端1-2cm。二腔单囊管内辐照支架的特点：剂量分布合理，低剂量率效应，射线能量适中，放疗、热疗同步实施，引流、扩张和局部用药作用。与其他治疗方法比较，这一核医学治疗技术的最大优点是：大直径柱状液态源，近似面源，液囊适形病变胆管腔，均匀贴紧病灶壁，剂量分布合理，γ射线能量适中，低剂量率持续照射，同时联合射频温热治疗及胆道引流、局部用药对症处理等。 2 动物实验研究结果指出，囊装液态131I支架对胆管壁的放射性损伤随131I放射性活度的增加而逐渐加重,呈现明显的放射性活度效应关系。而普通支架组胆管壁无放射性损伤,但是胆管壁粘膜层和肌层增生较131I支架组重,胆管出现再狭窄倾向。本研究为临床合理应用131I支架治疗胆管癌及胆管良性狭窄选择合适的131I放射性活度,提供了必要的剂量学和基础研究依据。 3 动物实验研究结果表明,131I支架组犬胆管组织Fas表达较普通支架组明显,且其表达水平的变化与犬胆管壁平滑肌细胞凋亡的检测结果相同。131I支架组胆管腔面积比普通支架组明显增加,胆管狭窄程度比普通支架组轻。这主要是由于131I辐射促进Fas 基因表达,诱导增殖性平滑肌细胞凋亡,从而减轻胆管损伤后愈合过程中的管腔狭窄。 4． 胆道恶性梗阻胆道腔内囊装液态131I辐照治疗施源的直径为8mm时是胆管充分扩张的最低限度,根据近距离放疗的剂量学特点,它能保证胆管癌腔内辐照治疗时将施源管因素导致的放疗反应和局部肿瘤复发减至最低。并具有创伤小,操作简单,疗效明显,易被患者接受的特点。 5．囊装液态131I治疗恶性梗阻性黄疸（肝门部胆管癌18例），临床疗效满意，随访7～21个月,3个月生存率83.33 %(15/ 18)；6个月生存率72.22%(13/18)；9个月生存率56.25%(12/16)；12个月生存率46.15%(6/13),15个月生存率36.33%(4/11)；18个月生存率22.22%(2/9),21个月生存率28.57%(2/7)。4例发生并发症,其中2例为放射性胆管炎胆道出血,1例为胆汁性腹膜炎,另1例是胰瘘胰腺炎

Characterization of prolidase activity using capillary electrophoresis with tris(2,2'-bipyridyl)ruthenium(II) electrochemiluminescence detection and application to evaluate collagen degradation in diabetes mellitus

A new method for prolidase (PLD, EC 3.4.13.9) activity assay was developed based on the determination of proline produced from enzymatic reaction through capillary electrophoresis (CE) with tris(2,2'-bipyridyl)ruthenium(11) [Ru(bpy)(3)(2+)] electrochemiluminescence detection (ECL). A detection limit of 12.2 fmol (S/N = 3) for proline, corresponding to 1.22 x 10(-8) units of prolidase catalyzing for 1 min was achieved. PLD activity determined by CE-ECL method was in agreement with that obtained from the classical Chinard's one. CE-ECL showed its powerful resolving ability and selectivity as no sample pretreatmentwas needed and no interference existed. The clinical utility of this method was successfully demonstrated by its application to assay PLD activity in the serum of diabetic patients in order to evaluate collagen degradation in diabetes mellitus (DM). The results indicated that enhanced collagen degradation occurred in DM.

Analysis of nephroloxic and carcinogenic aristolochic acids in Aristolochia plants by capillary electrophoresis with electrochemical detection at a carbon fiber microdisk electrode

Aristolochic acids (AAs) are the main bioactive ingredients in the most of Aristolochia plants, which are used to make dietary supplements, slimming pills and Traditional Chinese Medicines (TCMs). Excessive ingestion of AAs can lead to serious nephropathy. Therefore, quantitative analysis and quality control for the plants containing AAs is of great importance. In this paper, capillary electrophoresis (CE) with electrochemical detection (ED) at a 33 mu m carbon fiber microdisk electrode (CFE) has been applied to detect AA-I and AA-II in Aristolochia plants. Under the optimum conditions: detection potential at 1.20 V, 2.0 x 10(-2) mol L-1 phosphate buffer solution (PBS) (pH 10.0), injection time 25 s at a height of 17 cm and separation voltage at 12.5 kV, the AA-I and AA-II were baseline separated within 5 min. Low detection limits for AA-I and AA-II were 4.0 x 10(-8) mol L-1 and 1.0 x 10(-7) mol L-1, respectively. Wide linear ranges were from 4.0 x 10(-8) mol L-1 to 1.9 x 10(-5) mol L-1 and 1.0 X 10(-7) mol L-1 to 5.0 x 10(-5) mol L-1 for AA-I and AA-II, respectively. The proposed method has been successfully applied to analyze AAs contents in plant extracts. The results indicated that the contents of AAs in each part of Aristolochia debilis Sieb. Et Zucc.

NMR-based metabonomic study on the subacute toxicity of aristolochic acid in rats

The subacute toxicity of aristolochic acid (AA) was investigated by H-1 NMR spectroscopic and pattern recognition (PR)-based metabonomic methods. Model toxins were used to enable comparisons of the urinary profiles from rats treated with known toxicants and AA at various time intervals. Urinary H-1 NMR spectra were data-processed and analyzed by pattern recognition method. The result of visual comparison of the spectra showed that AA caused a renal proximal tubular and papillary lesion and a slight hepatic impair. Pattern recognition analysis indicated that the renal proximal tubule lesion was the main damage induced by AA, and the renal toxicity induced by AA was a progressive course with the accumulation of dosage by monitoring the toxicological processes from onset, development and part-recovery. These results were also supported by the conventional clinical biochemical parameters.

Purification of human tissue prokallikrein excreted from insect cells by liquid chromatography

Tissue kallikrein, generally existing in living bodies as prokallikrein, is a serine proteinase that has proven of great significance to treat hypertension, cardiopathy and nephropathy. Although the extraction of tissue kallikrein from human urine is the most commonly used method to obtain such a protein, not only the yield is very little, but also the procedure is rather complex. Furthermore, the biological safety is uncertain. Therefore, the preparation of such a protein by genetic engineering method, including gene expression, cell culture, separation and purification, is very important. In this paper, a new method to obtain purified tissue prokallikrein excreted from insect cells by liquid chromatography has been proposed. In contrast to the previously published papers, the purification procedure is simplified to only three steps with the final yield of 57% and the purity of 95%, which is not only convenient, but also low-cost and suitable for the large-scale preparation of such a protein. The purified protein is further validated as prokallikrein by high performance liquid chromatography-mass spectrometry and amino acid sequencing. (c) 2005 Elsevier B.V. All rights reserved.