碱性品红修饰磁性纳米粒子的制备及在分枝杆菌分离中的应用

痰或其它各种体液内结核分枝杆菌(MTB)阳性是诊断结核病(TB)的金标准.结核硬脂酸(TBSA)是鉴定分枝杆菌与其它非分枝杆菌的特征组分,可用于TB的诊断[1,2]。     

抗TB活性化合物的研究

结核病（tuberculosis,TB）是由结核分枝杆菌（mycobacterium tuberculosis,MTB）引起的一种缓慢性致死疾病。虽然目前结核病在发达国家发病率较低,但在发展中国家仍然是高发的重大传染性疾病。基于此种状况,寻找新的活性化合物或对现有药物分子进行改进,成为当下开发抗TB新药的热点。目前,在研的化合物包括喹啉类、喹诺酮类、咪唑类、苯并噻嗪酮类、唑烷酮类以及天然产物等,其中喹啉类化合物依然是重要研究对象。这些化合物大多数具有低微摩尔的体外抗结核活性,最有可能对体内药物敏感菌株或耐药菌株有效。本文详细介绍了2014~2017年间抗结核化合物的研究现状,就其化学结构特点、抗结核活性、构效关系和安全性等方面进行综述,并展望了该领域今后的发展方向。     

18F-FDG PET/CT显像联合肿瘤标志物检查对女性不明原因腹腔积液的诊断价值

本文探讨了18 F-脱氧葡萄糖(18 F-FDG)正电子发射计算机断层显像(PET/CT)联合肿瘤标志物检查对女性不明原因腹腔积液的鉴别诊断价值。选取95例不明原因腹腔积液女性患者的18 F-FDG PET/CT影像资料及肿瘤标志物资料进行回顾性分析,并与病理诊断结果进行对照。结果显示:95例患者中,经病理证实恶性腹腔积液74例,良性腹腔积液21例。PET/CT对良恶性腹腔积液的诊断灵敏度为98.65%,特异度为19.05%,准确度为81.05%。恶性腹腔积液的SUV max与良性腹腔积液比较,差异无统计学意义(P>0.05)。将患者按病因进一步细分后发现,卵巢癌组的SUV max明显高于其他良性原因组(P<0.05),但与结核组和其他恶性肿瘤组比较,差异无统计学意义(P>0.05)。肿瘤标志物中以CA125检测效率最高,其对卵巢癌及结核所致腹腔积液的诊断灵敏度为98.2%,特异度为7.7%,准确度为81.4%。PET/CT和CA125联合诊断对卵巢癌及结核所致腹腔积液的灵敏度、特异度及准确度与单一PET/CT或CA125诊断比较差异均无统计学意义(P>0.05)。本实验表明18 F-FDG PET/CT诊断女性不明原因腹腔积液的良恶性有较高的灵敏度和准确度,但特异性较差,联合肿瘤标志物检查并不能提高对卵巢癌及结核所致腹腔积液的诊断效能。     

ELISA法和化学发光法对血清中HIV-1HIV-2抗体、梅毒抗体和丙肝抗体的检测意义

目的探讨分析ELLSA法(酶联免疫吸附法)和化学发光法对血清中HIV-1/HIV-2抗体、梅毒抗体和丙抗体的临床检测意义。方法将382份脐血作为研究分析对象,分别采用酶联免疫吸附和化学发光法对所选标本进行检测,包含丙肝抗体、梅毒抗体、HIV-1/HIV-2抗体检测。结果采用ELLSA检测后HIV-1/HIV-2抗体、梅毒抗体、丙肝抗体阳性率分别为0.52%、0.79%、1.05%。采用化学发光法检测HIV-1/HIV-2抗体、梅毒抗体、丙肝抗体3种检测的阳性率分别为0.79%、1.05%、1.31%。标准抗体品梯度稀释后再进行检测,将此3种抗体稀释程度为10 pg/m L,三组抗体采用化学发光法进行检测,其结果均为阳性,采用酶联免疫吸附方式进行检测的只有梅毒抗体呈阳性,其余两项均为阴性。结论化学发光法作为临床进行血清中HIV-1/HIV-2抗体、梅毒抗体、丙肝抗体检测的首选方案,此检测方式具有更高的灵敏性。     

ECT脑血流灌注显像、CT和MRI在难治性癫痫中的诊断价值分析

选择2013年10月~2018年12月于我院收治的53例经临床确诊的难治性癫痫患者临床资料，所有患者均于发作间期分别行常规CT、MRI、SPECT检查，观察3种方法对致痫病灶检出和定位准确率，探讨单光子发射计算机断层成像术（SPECT）、CT和MRI在难治性癫痫中的诊断价值。结果显示，SPECT检测患侧rCBF低于健侧[（46.05±7.62）vs（54.51±9.39），P<0.05]，MRI检测患侧NAA（cho+Cr）低于健侧[（0.47±0.05）vs（0.69±0.11），P<0.05]。SPECT对致痫灶检出率、定位准确率分别为81.13%、73.58%，均高于MRI和常规CT（P<0.05）。联合SPECT、CT、MRI对致痫灶检出率、定位准确率达94.34%、92.45%，高于单独诊断（P<0.05），联合rCBF+NAA（cho+Cr）预测致痫病灶位置的AUC达0.923，灵敏度和特异度达82.26%、98.91%，高于rCBF、NAA（cho+Cr）（P<0.05）。结论：PET-CT、MRI对难治性癫痫术前定位均有较高临床应用价值，PET-CT在致痫灶检率、定位定侧方面更有优势，联合诊断更有助于提高定位准确率。     

肿瘤标志物联合C反应蛋白在肺癌诊断中的价值

目的探讨肿瘤标志物与C反应蛋白联合检测在肺癌诊断中的价值。方法选取2012年1月—2014年12月佳木斯大学附属第一医院收治的50例肺癌患者为实验组,选取同期50例肺良性疾病患者为对照组,对比两组患者体内C反应蛋白和4项肿瘤标志物含量。结果 1实验组患者的4项肿瘤标志物检测结果明显高于对照组,C反应蛋白含量低于对照组,组间差异具统计学意义(P0.05);2 4项肿瘤标志物与C反应蛋白联合检测对肺癌的阳性检出率可达86.0%以上。结论肿瘤标志物与C反应蛋白在肺癌诊断中具有应用价值,两者联合应用可以提高肺癌的阳性检出率。     

基于甲基苯丙胺和吗啡的胶体金免疫层析试剂盒检测法的可靠性评价

通过固相萃取-液相色谱-多级质谱(SPE-LC-MS/MS)联用技术和毒品胶体金免疫层析试剂盒检测法对13种中药及调味品样品中甲基苯丙胺及吗啡分别进行定量分析,依据LC-MS/MS检测结果,对毒品胶体金免疫层析试剂盒检测法进行可靠性评价。实验结果表明:型号1试剂盒对甲基苯丙胺和吗啡的特异性均不高,检测准确率分别为57.7%与78.8%;型号2试剂盒对甲基苯丙胺的特异性不足,准确率为73.1%,但对吗啡的检测准确率达到100%。在利用毒品胶体金免疫层析试剂盒进行毒品快速筛查时,应注重排除干扰因素以提高免疫胶体金层析试剂盒的检测准确度。     

三种肿瘤标准物在食管癌早期诊断中的价值

目的:探讨血清肿瘤标记物癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、细胞角蛋白19片段抗原(CY-FRA21-1)联合检测在食管癌早期诊断中的应用价值,旨在为食管癌的诊治提供理论参考.方法:采用酶联免疫法(ELISA)测定67例食管癌患者、60例正常健康者的三种肿瘤标志物(CEA、NSE、CYFRA21-1)水平.结果:食管癌组3种血清标志物的水平显著高于对照组(P<0.05);CEA、NSE、CYFRA21-1在食管癌诊断中的均具有较高的特异性,但敏感性均较低.而3种肿瘤标志物联合检测在食管癌诊断中有较高的敏感性和特异性,分别为74.63%和85.07%.结论:血清3种项肿瘤标志物(CEA、NSE、CYFRA21-1)联合检测可以提高食管癌诊断的敏感性,对食管癌的早期诊断和鉴别具有重要的临床价值.     

发热病人病因判断中血细胞形态学检验的应用研究

目的探讨血细胞形态学检验在发热病人病因判断中的应用价值。方法随机抽取广东省汕头市龙湖人民医院2014年1月到2014年12月间收治的发热患者200例作为研究对象,并以200例健康受检者作为对照,分别对两组受检者的血液标本实施常规检验及血涂片染色显微镜检,在显微镜下观察各种细胞的细胞形态学变化,计算形态异常检出率,并分别比较其Hct、RDWSD、MCH、MCHC、MCV的检测水平。结果观察组外周血细胞异常变化检出率为60.0%,对照组仅为7.5%,其中,白细胞变化、大细胞性贫血、小细胞性贫血、异性淋巴细胞变化、异常细胞等的检出率均显著高于对照组,比较有统计学差异(P0.05)。而Hct、RDW-SD、MCHC、MCV等指标的检测结果也均显著高于对照组,比较有统计学差异(P0.05)。结论通过对血液标本的血细胞形态进行观察,能够对发热疾病的发生发展进行判断,一定程度上明确患病的原因,并为其临床治疗提供指导依据。     

珠三角地区人群血浆中邻苯二甲酸酯的暴露水平研究

采用高效液相色谱-串联质谱(HPLC-MS/MS)法对珠三角地区人群血浆中16种邻苯二甲酸酯(PAEs)的暴露情况进行分析。样品预处理采用乙腈沉淀蛋白,正己烷液液萃取。结果表明,血浆中检出邻苯二甲酸二甲酯(DMP)、邻苯二甲酸二异丁酯(DiBP)、邻苯二甲酸二正丁酯(DnBP)、邻苯二甲酸丁基苄基酯(BBP)、邻苯二甲酸二环己基酯(DCHP)与邻苯二甲酸二(2-乙基己基)酯(DEHP)。其中DEHP的检出率为100%;其次为DiBP、DnBP与DMP,检出率分别为98.0%、62.0%和49.0%;DCHP与BBP的检出率最低,均为5.00%。∑PAEs的含量为12.4～1 399 ng/g,中值与平均值分别为39.8、57.7 ng/g。6种PAEs中DEHP占比最高,为90.01%～99.96%。对不同性别与年龄人群的PAEs暴露水平进行研究,发现女性与低年龄组(≤40岁)人群血浆中的PAEs浓度较高,但仅DMP存在显著性差异。     

几种抗结核药的应用

论述了四类抗结核药物的应用，着重讨论了利福平、氧氟沙星、力排肺疾等的应用。     

Photoelectrochemical Sensor for Isoniazid: Application in Drugs Used in the Treatment of Tuberculosis

The present work describes the development of a photoelectrochemical sensor based on titanium dioxide, cadmium telluride quantum dots and the tris (2,2′-bipyridyl) ruthenium(II) chloride complex for detection of Isoniazid (INH). The Ru(bpy)₃²⁺/CdTe-QDs/TiO₂/FTO photoelectrochemical platform was characterized by scanning electrochemical microscopy, electrochemical impedance spectroscopy and amperometry. The photoelectrochemical sensor presented two linear ranges for INH concentrations ranging from 0.5 to 150 μmol L⁻¹ and 150 to 1270 μmol L⁻¹, with a theoretical detection limit of 0.02 μmol L⁻¹. The sensor was successfully applied for the determination of INH in drugs samples used in the treatment of tuberculosis.     

Therapeutic Monitoring of Isoniazid, Pyrazinamide and Rifampicin in Tuberculosis Patients Using LC

The objective of this study was to measure plasma concentration of isoniazide (INH), pyrazinamide (PZA) and rifampisin (RIF) in tuberculosis patients by using HPLC. 100 μL of plasma was deproteinized by adding trichloroacetic acid and acetonitrile to yield INH, PZA and RIF respectively. They were analysed by HPLC using a reversed phase C₁₈ pre-column linked to a 4 μm C₁₈ analytical column with a gradient solvent programme, which delivered 3% to 40% (v/v) acetonitrile in phosphate buffer in 20 min at rate of 0.8 mL min^?1. Signals were monitored by diode-array detector. Acetanilide was used as internal standard. The method is reproducible and accurate with lower limits of quantification of 0.6 mg L^?1 for INH, 1.5 mg L^?1 for PZA and 0.7 mg L^?1 for RIF. The plasma of 25 patients receiving daily standard therapy were assayed for INH, PZA and RIF 3 h after administration. Plasma concentration were found between 0.98 and 6.27 mg L^?1 for INH, 11.05 and 47.26 mg L^?1 for PZA, 5.09 and 33.20 mg L^?1 for RIF respectively. Many of the plasma levels were found to be sub therapeutic. This practical method may be used for monitoring drug plasma levels of patients who fail to respond to treatment.     

Spontaneous Formation of the Bioactive Form of the Tuberculosis Drug Isoniazid

It works even without the enzyme : The formation of the bioactive form 1 of isoniazid inside Mycobacterium tuberculosis does not depend on specific interactions within the active site of the inhibited enzyme, but rather relies on the fast addition of acyl radicals to electron-deficient heterocycles such as NAD⁺.     

Synthesis of Terminal Oligosaccharides from Type Specific Lipooligosaccharide of Mycobacterium Tuberculosis

Abstract

The coupling reaction between 1,3-di-O-acetyl-4-O-benzyl-2-O-methyl-α-L-rhamnopyranose (9) and methyl 4-O-benzyl-2-O-methyl-α-L-rhamno-pyranoside (4) was carried out in the presence of boron trifluoride-etherate followed by deacetylation to give the disaccharide (11) containing a free 3′ position. The second glycosylation reaction with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide in the presence of mercuric salts followed by removal of benzyl and acetyl groups provided the trisaccharide 2. The boron trifluoride catalysed condensation of 1,3,4-tri-O-acetyl-2-O-methyl-L-fucopyranose (14) and methyl 2,4,6-tri-O-benzyl-α-d-glucopyranoside (15) gave the disaccharide (16) from which the protecting groups were removed to form the disaccharide (3).     

Promising Lead Compounds in the Development of Potential Clinical Drug Candidate for Drug-Resistant Tuberculosis

According to WHO report, globally about 10 million active tuberculosis cases, resulting in about 1.6 million deaths, further aggravated by drug-resistant tuberculosis and/or comorbidities with HIV and diabetes are present. Incomplete therapeutic regimen, meager dosing, and the capability of the latent and/or active state tubercular bacilli to abide and do survive against contemporary first-line and second line antitubercular drugs escalate the prevalence of drug-resistant tuberculosis. As a better understanding of tuberculosis, microanatomy has discovered an extended range of new promising antitubercular targets and diagnostic biomarkers. However, there are still no new approved antitubercular drugs of routine therapy for several decades, except for bedaquiline, delamanid, and pretomanid approved tentatively. Despite this, innovative methods are also urgently needed to find potential new antitubercular drug candidates, which potentially decimate both latent state and active state mycobacterium tuberculosis. To explore and identify the most potential antitubercular drug candidate among various reported compounds, we focused to highlight the promising lead derivatives of isoniazid, coumarin, griselimycin, and the antimicrobial peptides. The aim of the present review is to fascinate significant lead compounds in the development of potential clinical drug candidates that might be more precise and effective against drug-resistant tuberculosis, the world research looking for a long time.     

肺结核与肺癌病人全血微量元素观察

选取肇庆市第一人民医院传染病区和肿瘤病区的住院病人全血微量元素观察．结核组72例，肺癌组65例．从14种微量元素观察结果中作统计学处理，发现肺癌病人的3种有害元素N1，Cd。Pb对的含量高于肺结核．而Sr与常量元素Ca的含量亦明显高于肺结核．本文认为在肺结核与肺癌的鉴别诊断上能利用微量元素结果的差异提供一早期鉴别诊断途径．同时提示肺结核病人在治疗时应注意补充钙．     

A Novel Approach in Treatment of Tuberculosis by Targeting Drugs to Infected Macrophages Using Biodegradable Nanoparticles

Mycobacterium tuberculosis, the causative agent of tuberculosis is now causing death of more than 10 million people. Because of the development of drug-resistant TB, drug delivery to the infected site through nanoparticle had been studied for long time. Nanoparticles indicate different sorts of association with the natural particles of the body. Nanoparticles can be used as controlled or specific drug delivery system. It can be through temporal controlled or can be distribution controlled. Glucose polymer-based nanoparticles might play an important role as drug delivery system in case of targeted drug delivery in the infected site of the body or in infected macrophages, as they are biodegradable so there should not be any side effects of these particles in the body and also they show very slow immune response. CD4, Beta 1, TGFb-1, IL-2, IL-13 SEC14L1, GUSB, BPI, and CCR7 are major biomarkers secreted after infection of this bacterium by the macrophages which can be used for targeted drug delivery in infected macrophages. As these markers can be used for delivery of drugs at destined position, they can be very beneficial in reducing toxicities of antituberculer drugs to the other uninfected sites and in operating only the infected macrophages.     

Quinoline Derivatives with Potential Activity Against Multidrug‐resistant Tuberculosis

Tuberculosis (TB), which affects primarily the lungs (pulmonary TB) apart from other vital organs, is a life‐threatening chronic deadliest infectious disease caused by members of Mycobacterium tuberculosis (MTB) complex and mainly by MTB itself. The emergence of MTB new virulent forms that are resistant to some or all first‐line and second‐line anti‐TB agents, including multidrug‐resistant (MDR), extensively drug‐resistant, and totally drug‐resistant strains has further aggravated the spread of this disease and was increased up to an alarming level in the recent decades. More than ever, it is imperative to develop novel, high effective, and fast acting anti‐TB drugs to prevent the spread of TB, particularly in its hard‐to‐kill MDR‐TB, extensively drug‐resistant‐TB, and totally drug‐resistant‐TB strains. In recent years, numerous compounds have been synthesized for this purpose, but only a handful of compounds have entered human trials after the discovery of rifampicin, reflecting the inherent difficulties of developing new anti‐TB agents. Despite of bedaquiline and delamanid have received approval from many countries for treatment of MDR‐TB infected patients, both drugs are associated with serious side effects and are only recommended for those MDR‐TB patients without other treatment options. All these aforementioned facts make it an urgent need to develop novel drugs. Quinoline‐based derivatives including quinolones ex biological activities, and some of them displayed excellent in vitro and in vivo activities against MDR‐TB. This review outlines the recent developments of quinoline‐based derivatives with potential activity against MDR‐TB as well as the structure–activity relationship.