依据药物敏感试验根除幽门螺杆菌的临床疗效随访

目的:在幽门螺杆菌(Helicobacter pylori,H.pylori)感染的患者中,根据药物敏感试验选择治疗方案与常规一线治疗方案进行临床疗效优劣的随访.方法:在浙江省嘉兴市第一医院内镜室行胃镜检查的患者中,胃镜检查时取材标本2块,分别送检常规组织病理学检查及组织切片染色检测及H.pylori的分离、培养、鉴定:其中H.pylori培养结果阳性的纳入治疗组,仅组织切片染色检测H.pylori阳性纳入对照组.治疗组根据药敏试验结果治疗10 d,对照组根据标准一线治疗方案治疗10d.治疗结束4 wk后的患者进行复查,任选一种复查方式(H.pylori培养或组织切片染色或14C呼气试验),三项之一阴性者可判断H.pylori根除.结果:H.pylori培养结果阳性的纳入治疗组(n=4680),仅组织切片染色检测H.pylori阳性纳入对照组(n=3505).治疗组根据药敏试验结果选用2种敏感度最高值抗生素参与的四联疗法治疗,对照组选用常规四联疗法,治疗结束4 wk后复查评估根除率.最终,治疗组的根除率为91.18%,比对照组根除率73.07%高,且差异有统计学意义(P0.05).结论:依据H.pylori的药物敏感试验选择的治疗方案明显优于标准一线治疗方案.     

Surface-Bound Proteins with Preserved Functionality

Biocompatibility of materials strongly depends on their surface properties. Therefore, surface derivatization in a controllable manner provides means for achieving interfaces essential for a broad range of chemical, biological, and medical applications. Bioactive interfaces, while manifesting the activity for which they are designed, should suppress all nonspecific interaction between the supporting substrates and the surrounding media. This article describes a procedure for chemical derivatization of glass and silicon surfaces with polyethylene glycol (PEG) layers covalently functionalized with proteins. While the proteins introduce the functionality to the surfaces, the PEGs provide resistance against nonspecific interactions. For formation of aldehyde-functionalized surfaces, we coated the substrates with acetals (i.e., protected aldehydes). To avoid deterioration of the surfaces, we did not use strong mineral acids for the deprotection of the aldehydes. Instead, we used a relatively weak Lewis acid for conversion of the acetals into aldehydes. Introduction of α,ω-bifunctional polymers into the PEG layers, bound to the aldehydes, allowed us to covalently attach green fluorescent protein and bovine carbonic anhydrase to the surfaces. Spectroscopic studies indicated that the surface-bound proteins preserve their functionalities. The surface concentrations of the proteins, however, did not manifest linear proportionality to the molar fractions of the bifunctional PEGs used for the coatings. This finding suggests that surface-loading ratios cannot be directly predicted from the compositions of the solutions of competing reagents used for chemical derivatization.     

Guidewire cannulation increases the success rate of needle‐knife fistulotomy for difficult bile duct access

Background and Aim: Selective bile duct cannulation is a prerequisite for performing therapeutic endoscopic biliary intervention. This study aimed to evaluate if using a soft‐tipped guidewire to cannulate the bile duct would increase the success rate of needle‐knife fistulotomy for difficult bile duct access. Methods: We reviewed sixty 60 patients with difficult bile duct access who underwent conventional cannulation with radiocontrast dye (29) or guidewire cannulation (31) after needle‐knife fistulotomy. Results: There were no significant differences in the demographic data between the two groups. The initial success rate of selective bile duct cannulation was significantly higher in the guidewire cannulation group compared with the conventional cannulation group: 100% versus 79.3%, P = 0.009. The success rate of selective biliary cannulation in the patients with non‐dilated common bile duct (< 8 mm) was significantly higher in the guidewire cannulation group compared with the conventional cannulation group: 100% versus 68.4%, P = 0.003. The incidence of post‐endoscopic retrograde cholangiopancreatography pancreatitis was not significantly different between the two groups. No serious complications occurred in either group. Conclusions: In this retrospective and small case series, guidewire cannulation after needle‐knife fistulotomy increased the success rate of selective bile duct cannulation in patients with difficult bile duct access.     

Areca nut‐induced micronuclei and cytokinesis failure in Chinese hamster ovary cells is related to reactive oxygen species production and actin filament deregulation

Epidemiological studies have shown a strong association between environmental exposure to betel quid (BQ) and oral cancer. Areca nut (AN), an ingredient of BQ, contains genotoxic and mutagenic compounds. In this study, we found that AN extract (ANE) inhibited the growth of Chinese hamster ovary cells (CHO‐K1) in a dose‐ and time‐dependent manner. Intracellular reactive oxygen species (ROS) levels and micronuclei (MN) frequency were significantly increased following ANE treatment in CHO‐K1 cells. Addition of catalase markedly inhibited ANE‐induced MN formation, indicating that ANE‐induced genotoxicity was correlated with intracellular H₂O₂. Incubation of CHO‐K1 cells with ANE (400–800 μg/ml) for 24 hr caused G2/M arrest, and prolonged exposure to ANE (800 μg/ml) significantly induced cell death. Surprisingly, ANE itself caused cytokinesis failure and subsequent increase in binucleated cell formation. Coexposure to catalase (2,000 U/ml) and ANE (800 μg/ml) reduced the generation of binucleated cells, indicating that ANE‐induced cytokinesis failure was associated with oxidative stress. Following prolonged exposure to ANE, an accumulation of hyperploid/aneuploid cells concomitant with bi‐, micro‐ or multinucleated cells was found. In summary, our results demonstrate that ANE exposure to CHO‐K1 cells caused increased MN frequency, G2/M arrest, cytokinesis failure, and an accumulation of hyperploid/aneuploid cells. These events are associated with an increase in intracellular H₂O₂ level and actin filament disorganization. Environ. Mol. Mutagen., 2009. © 2009 Wiley‐Liss, Inc.     

Expression of a peroxisome proliferator-activated receptor gamma 1 splice variant that was identified in human lung cancers suppresses cell death induced by cisplatin and oxidative stress.

PURPOSE: The activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) has been implicated in the inhibition of tumor progression in lung cancers through the induction of differentiation and apoptosis. Recently, we identified a novel splice variant of human PPAR gamma1 (hPPAR gamma1) that exhibits dominant-negative activity in human tumor-derived cell lines. This study aimed to examine the expression and pathophysiologic roles of a truncated splice variant of hPPAR gamma1 (hPPAR gamma1(tr)) in primary human lung cancer tissues. EXPERIMENTAL DESIGN: The expression and localization of hPPAR gamma1(tr) was surveyed in human primary lung cancer tissues using immunohistochemistry and Western blot analysis. Using transfectants stably expressing wild-type hPPAR gamma1 (hPPAR gamma1(wt)) and hPPAR gamma1(tr), we also analyzed the pathophysiologic roles of hPPAR gamma1(tr). RESULTS: We showed that PPAR gamma is expressed predominantly in the nucleus of nontumorous tissues, whereas it is present in both the nucleus and the cytoplasm of tumorous tissues in squamous cell carcinoma (SCC) of the lung. Western blot analysis confirmed the presence of PPAR gamma1(tr) in primary lung SCC tissue but not in nontumorous tissue. Expression of PPAR gamma1(tr) in Chinese hamster ovary cells attenuated their susceptibility to cell death induced by oxidative stress or cisplatin, whereas their susceptibility was completely recovered by down-regulation of PPAR gamma1(tr) with small interfering RNA. CONCLUSIONS: hPPAR gamma1(tr) is expressed strongly in tumorous tissues of primary human lung SCC and its overexpression renders transfected cells more resistant to chemotherapeutic drug- and chemical-induced cell death. These data suggest that the decreased drug sensitivity of PPAR gamma1(tr)-expressing cells may be associated with increased tumor aggressiveness and poor clinical prognosis of patients.     

大环内酯类药物治疗铜绿假单胞茵慢性感染机制的研究进展

近年来大量研究表明长期应用大环内酯类药物或大环内酯类药物与其它抗生素联用均能有效控制铜绿假单胞菌所致的慢性感染.大环内酯类在治疗铜绿假单胞菌慢性感染方面主要具有①抑制铜绿假单胞菌藻酸盐和表多糖的产生;②影响铜绿假单胞菌Ⅲ型分泌系统,减少毒力因子的产生;③破坏铜绿假单胞菌表面结构,抑制细菌对宿主的黏附;④抑制细菌QS系统.减少自身信号诱导分子的合成;⑤增加炎症细胞聚集.减少炎性细胞凋亡,对抗机体的炎症反应;⑥增加呼吸道痰液的清除,降低痰液粘稠度;⑦对铜绿假单胞菌具有暴露时间依从性杀菌活性等方面的功能,能最终达到对铜绿假单胞菌慢性感染的有效控制.     

Dopamine transporters and cognitive function in methamphetamine abuser after a short abstinence: A SPECT study.

The purpose of this study was to examine the change of dopamine transporters (DAT) binding in methamphetamine (METH) abusers in a two-week period of abstinence and its association with cognitive function. Seven healthy subjects and seven METH abusers were recruited. At baseline conditions, the values of specific uptake ratio (SUR) of DAT binding measured by single photon emission computed tomography were lower in METH abusers than in controls. After a two-week period of abstinence, DAT binding was partially recovered and there were no statistic differences in SUR between METH abusers and controls. There was a borderline correlation between the changes of DAT binding in the right, but not the left, striatum and the %Error of Wisconsin Card Sorting Test. These findings indicate that DAT binding in METH abusers can be reversed in a short period of abstinence. The recovery of DAT binding was asymmetric and possibly parallel with the improvement of cognitive function.     

Investigation of the metabolism and reductive activation of carcinogenic aristolochic acids in rats.

The metabolic activation of aristolochic acids (AAs) that have been demonstrated to be mutagenic and carcinogenic was investigated. In vitro metabolism study indicated that AAs were metabolized to N-hydroxyaristolactam, which could be either reduced to aristolactams or rearranged to 7-hydroxyaristolactams via the Bamberger rearrangement. In vivo metabolism study is important because the intermediates (aristolactam-nitriumion) of the nitroreduction process are thought to be responsible for the carcinogenicity of AAs. Liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry (MS/MS) were applied to the analyses of a series of positional isomers of hydroxyaristolactams in rat urine samples after the in vivo study of AAs. Three hydroxylated metabolites of aristolactam II and two hydroxylated metabolites of aristolactam I were identified. The structures of the positional isomers were elucidated from the interpretation of MS/MS spectra and theoretical calculations. In addition, several new metabolites were detected in the rat urine by high-resolution mass spectrometry and MS/MS, including those from the decarboxylation of AAs and the conjugations of acetylation, glucuronidation, and sulfation of aristolochic acid Ia.