平消胶囊联合左甲状腺素钠治疗结节性甲状腺肿的临床研究

目的 对狭叶薰衣草Lavandula angustifolia中的木脂素类化合物进行研究。方法 运用RP-HPLC、TLC、硅胶、凝胶、MCI-gel树脂等方法进行分离纯化,并根据理化性质和波谱数据鉴定化合物的结构。结果 从狭叶薰衣草中分离得到11个木脂素类化合物,分别鉴定为松脂醇（1）、丁香树脂醇（2）、fraxiresinol-4''-O-β-D-glucopyranoside（3）、syringaresinol-4''-O-β-D-glucopyranoside（4）、8-hydroxypinoresinol-4-O-β-D-glucopyranoside（5）、rel-（2α,3β）-7-O-methylcedrusin（6）、落叶松脂醇-4''-O-β-D-葡萄糖苷（7）、（2S,3R）-2,3-dihydro-2-（4-hydroxy-3-methoxyphenyl）-3-hydroxymethyl-7-methoxybenzofuran-5-（trans） propen-1-ol-3-O-β-glucoside（8）、（7S,8R）-dihydrodehydrodiconiferyl alcohol-9-β-D-glucopyranoside（9）、（7R,8R）-7,8-dihydro-9''-hydroxyl-3''-methoxyl-8-hydroxymethyl-7-（4-hydroxy-3-methoxyphenyl）-1''-benzofuranpropanol-9''-O-β-D-glucopyranoside（10）、（E）-3-（（2S,3S）-2-（4-hydroxy-3-methoxyphenyl）-3-hydroxymethyl-7-methoxy-2,3-dihydrobenzofuran-5-yl） allyl-2-hydroxyacetate（11）。结论 11个化合物均首次从狭叶薰衣草中分离得到。     

3,5-O-二咖啡酰基奎宁酸的稳定性和抗氧化活性研究

目的 考察影响化合物3,5-O-二咖啡酰基奎宁酸稳定性的因素并对3,5-O-二咖啡酰基奎宁酸的体外抗氧化活性进行初步研究。方法 采用HPLC考察3,5-O-二咖啡酰基奎宁酸在不同溶剂、pH、温度、光照条件下的稳定性;采用UV测定3,5-O-二咖啡酰基奎宁酸的体外抗氧化活性（清除DPPH自由基）。结果 溶剂的种类、pH值、温度、光照条件对3,5-O-二咖啡酰基奎宁酸稳定性具有一定影响。3,5-O-二咖啡酰基奎宁酸具有较强的体外清除DPPH自由基活性,其活性与Vc相当[3,5-O-二咖啡酰基奎宁酸和Vc的IC₅₀值分别为（372.56±1.04）μg·mL^-1和（294.54±1.03）μg·mL^-1]。结论 在该化合物的分离纯化及其分析检测时,不能采用纯有机溶剂为溶剂,应在中性或酸性条件下,低温、避光操作。3,5-O-二咖啡酰基奎宁酸作为抗氧化剂在制药、食品、化妆品以及精细化工行业具有广阔的应用前景。     

消乳散结胶囊联合他莫昔芬治疗乳腺增生症的疗效观察

目的 研究瑞香狼毒Stellera chamaejasme花中黄酮和木脂素类化学成分及其抗氧化活性,分析构效关系。方法 利用大孔吸附树脂、正反相硅胶、Sephadex LH-20等色谱分离材料,通过柱色谱和高效液相色谱等分离方法进行分离纯化,运用核磁共振（NMR）、质谱（MS）等波谱技术鉴定化合物结构,并采用FRAP法、DPPH法和ABTS法对分离得到的化合物进行体外抗氧化活性测试。结果 从瑞香狼毒花甲醇提取物中分离鉴定了12个化合物,分别鉴定为艾黄素（1）、槲皮素（2）、isoscutellarein-8-O-β-D-glucuronopyranoside（3）、槲皮素-3-O-β-D-葡萄糖苷（4）、紫云英苷（5）、hypolaetin-8-O-β-D-glucuronopyranoside（6）、kaempferol 3-O-β-D-glucopyranosyl-（1→2）-O-α-L-xylopyranoside（7）、rel-（3R,3''S,4R,4''S）-3,3'',4,4''-tetrahydro-6,6''-dimethoxy[3,3''-bi-2H-benzopyran]-4,4''-diol（8）、马台树脂醇（9）、乌拉尔醇（10）、环黄芪醇（11）、松脂醇（12）。抗氧化活性实验表明,黄酮和木脂素类化合物均显示了较强的抗氧化活性。结论 化合物1、3、5～7和10为首次从该植物中分离得到;化合物2、4、5和10表现出显著的抗氧化活性,其中黄酮类化合物C-3或C-8位连有糖链会降低其抗氧化活性。     

百蕊草亲水性化学成分研究

目的 对百蕊草中亲水性化学成分进行研究。方法 采用硅胶柱色谱、SephadexLH-20凝胶柱色谱等分离手段,对百蕊草水提取物经AB-8大孔树脂吸附,50%乙醇洗脱的亲水性组分（TT50）进行分离纯化,应用核磁共振波谱分析、结合文献报道鉴定化合物结构。结果 从TT50中分离纯化得到6个化合物,分别鉴定为：山奈酚（1）,紫云英苷（2）,山奈酚-3,7-二-O-β-D-吡喃葡萄糖苷（3）,山奈酚-3-O-L-吡喃鼠李糖基（1→2）-β-D-吡喃葡萄糖苷（4）,山奈酚-3-O-L-吡喃鼠李糖基（1→2）-［6-O-乙酰基］-β-D-吡喃葡萄糖苷（5）,芸香苷（6）。结论 TT50中主要成分为以山奈酚为母核的黄酮苷类化合物,化合物4、5为首次从百蕊草中分离得到。     

以OATP1B1/OATP1B3转运体为作用靶点的何首乌肝毒性成分筛选

目的 建立以有机阴离子转运多肽1B1（OATP1B1）和OATP1B3为作用靶点的何首乌肝毒性成分快速筛选方法。方法 使用Discovery Studio 2.5软件将何首乌主要单体成分（48个）与OATP1B1/OATP1B3蛋白进行分子对接,以OATP1B1和OATP1B3主要转运底物胆红素作为阳性对照,对目标化合物进行虚拟筛选;采用CCK-8法考察芦荟大黄素-8-O-β-D-葡萄糖苷（AEG）、大黄素-8-O-β-D-葡萄糖苷（EG）、大黄素甲醚-8-O-β-D-葡萄糖苷（PG）、2,3,5,4''-四羟基二苯乙烯-2-O-β-D-葡萄糖苷（TSG）处理24 h后对人源肝永生化肝细胞HepaRG的毒性强弱,并采用实时荧光定量PCR （qRT-PCR）技术测定4种化合物对HepaRG细胞的OATP1B1和OATP1B3 mRNA表达量的影响。结果 与OATP1B1对接结果显示,polygonumnolide B3、cis-emodin-physcionbianthrones、polygonumnolide B2、大黄素甲醚-8-β-D-（6''-O-乙酰基）-葡萄糖苷、trans-emodin-physcionbianthrones、大黄素-3-甲醚-8-O-β-D-葡萄糖苷、polygonumnolide B4、大黄酚-8-O-葡萄糖苷、EG、大黄素-1-O-β-D-葡萄糖苷、AEG、大黄酚-8-O-β-D-葡萄糖苷、大黄酸-8-O-葡萄糖苷高于胆红素打分值的80%,可被初步认定为潜在毒性成分;与OATP1B3对接结果显示,trans-emodin-physcionbianthrones、PG、polygonumnolide A4及虎杖苷高于胆红素打分值的80%,可被初步认定为潜在毒性成分。CCK-8实验进一步证实AEG、EG及PG均具肝细胞毒性作用,半数抑制浓度分别为16.10、49.43、69.44 μg·mL^-1,与分子对接结果一致。与对照组比较,AEG、EG均可显著下调OATP1B1的mRNA表达水平（P<0.05）;PG可显著下调OATP1B3的mRNA表达水平（P<0.05）。结论 以OATP1B1/OATP1B3分子对接技术为切入点,可有效预测何首乌潜在肝毒性成分,实现快速高效的高通量筛选,为中药安全性评价提供新思路。     

3,5-O-二咖啡酰基奎宁酸的制备及其对HeLa细胞的抗增殖活性研究

目的 制备高纯度3，5-O-二咖啡酰基奎宁酸，并评价其对人宫颈癌HeLa细胞的抗增殖活性。方法 采用柱色谱提取法和中压液相色谱法从奇蒿花中分离、纯化得到高纯度的3，5-O-二咖啡酰基奎宁酸。采用MTT法评价该化合物对人宫颈癌HeLa细胞的体外抗增殖活性。结果 柱色谱提取的提取率和中压液相色谱法的回收率分别为99.0%，61.2%，总回收率为54.0%。随着3，5-O-二咖啡酰基奎宁酸浓度升高，HeLa细胞存活率下降，细胞形态损伤增加，受试药物的IC₅₀值为26.5µg·mL^-1。结论 本研究提供了一种简单、高效、节能的3，5-O-二咖啡酰基奎宁酸制备方法。3，5-O-二咖啡酰基奎宁酸对HeLa细胞具有一定的体外抗增殖活性。     

HPLC测定安尔眠胶囊中2,3,5,4’-四羟基二苯乙烯-2-O-β-D-葡萄糖苷

目的 建立安尔眠胶囊中2,3,5,4’-四羟基二苯乙烯-2-O-β-D-葡萄糖苷（C₂₀H₂₂0₉）的含量测定方法。方法 采用高效液相色谱（HPLC）法,以Dionex Acclaim 120^® C₁₈色谱柱（150 mm×4.6 mm,5 μm）为分离柱,以乙腈-1%甲酸溶液（23：77）为流动相,体积流量1.0 mL/min,检测波长320 nm,柱温25 ℃。结果 2,3,5,4’-四羟基二苯乙烯-2-O-β-D-葡萄糖苷在0.010～0.200 μg呈现良好的线性关系（r=0.999 6）,平均回收率为97.35%,RSD为2.07%。结论 该方法<准确可靠,适用于安尔眠胶囊中2,3,5,4’-四羟基二苯乙烯-2-O-β-D-葡萄糖苷的含量测定。     

喙果黑面神化学成分研究

目的研究大戟科植物喙果黑面神(Breynia rostrata Merr.)的化学成分。方法利用硅胶、凝胶等色谱技术分离纯化化学成分,根据化合物的理化性质和光谱数据进行结构鉴定。结果从喙果黑面神的正丁醇萃取部分分离得到4个化合物,分别鉴定为6-O-甲基丙酰基-α-D-吡喃葡糖(6-O-methylpropanoyl-α-D-glucopyranose,1);4″-苯酚基-6-O-甲基丙酰基-β-D-吡喃葡糖苷(4″-phenolic-6-O-methylpropanoyl-β-D-glucopyranoside,2);1-O-没食子酰基-β-D-吡喃葡糖苷(1-O-galloyl-β-D-glucopyranoside,3);熊果苷(arbutin,4)。结论化合物1和2为新化合物,3和4均为首次从该种植物分离得到。     

藏药独一味中30种化学成分的UPLC-ESI-TOF MS分析鉴定

目的：建立快速高效的方法,对藏药独一味的化学成分进行有效的鉴定,为该药材质量监督提供技术支持。方法：采用超高效液相-电喷雾-飞行时间质谱（UPLC-ESI-TOF MS）联用技术,色谱分离用ACQUITY UPLC HSS T3（2.1 mm×100 mm,1.8 μm）,流动相组成比例分别为0.05%甲酸水和乙腈,梯度洗脱,流速0.3 mL·min^-1,进样量1 μL;质谱定性采用飞行时间质谱,正离子模式扫描。结果：在优化的液质联用条件下,通过电喷雾-飞行时间质谱鉴定出独一味30个成分,分别为（1） phlomiol;（2） lamalbid;（3） phlorigidoside C;（4）胡麻属苷;（5）山栀苷甲酯;（6）5-羟基马钱苷;（7） vanillyl-O-β-D-葡萄糖苷;（8）绿原酸;（9）6-O-乙酰山栀苷甲酯;（10） cistanosideE;（11）7,8-dehydropenstemoside;（12） chlorotuberoside;（13）7-epi-loganin;（14）7-dehydroxy-2-zaluzioside;（15）马钱苷;（16）连翘酯苷B;（17）8-O-乙酰山栀苷甲酯;（18）芦丁;（19）木犀草苷;（20）毛蕊花糖苷;（21）木犀草素-7-O-β-D-呋喃芹糖基（1→6）-O-β-D-吡喃葡萄糖苷;（22） salviifoside A;（23）8-epi-7-deoxyloganin;（24）异类叶升麻苷;（25）芹菜素-7-O-β-D-葡萄糖苷;（26）6β-n-butoxy-7,8-dehydropenstemonoside;（27）芹菜素;（28）6-O-syringyl-barlerin;（29）木犀草素;（30）槲皮素。结论：通过UPLC-ESI-TOF MS联用技术,阐明了独一味的化学成分,为独一味及其制剂的质量控制和监管提供了科学依据;同时,为其他藏药的化学成分快速分析提供参考。     

基于HGF/c-Met通路探究矢车菊素-3-O-葡萄糖苷改善高糖高脂诱导胰岛β细胞损伤的机制

目的 探究矢车菊素-3-O-葡萄糖苷对高糖高脂诱导的胰岛β细胞损伤的影响及机制。方法 使用不同浓度（10、20、30、40、50 μmol/L）矢车菊素-3-O-葡萄糖苷处理胰岛β细胞，CCK-8法检测细胞活力；将胰岛β细胞分为对照组、模型组及矢车菊素-3-O-葡萄糖苷10、50 μmol/L组，CCK-8法检测各组细胞活力，酶联免疫吸附法（ELISA）测定各组细胞胰岛素分泌量，DCFH-DA荧光探针法检测各处理组细胞活性氧（ROS）水平，比色法检测各处理组细胞超氧化物歧化酶（SOD）活性与丙二醛（MDA）含量，蛋白质免疫印迹（Western blotting）法检测各处理组细胞肝细胞生长因子（HGF）/间质表皮转化因子受体（c-Met）通路相关蛋白表达水平。使用c-Met抑制剂SU11274进行干预，实验将胰岛β细胞分为对照组、模型组、矢车菊素-3-O-葡萄糖苷组、矢车菊素-3-O-葡萄糖苷＋SU11274组，再通过CCK-8法检测各处理组细胞活力，ELISA法测定各组细胞胰岛素分泌量。结果 与对照组比较，不同浓度矢车菊素-3-O-葡萄糖苷作用均显著提高了胰岛β细胞活力（P＜0.05）。与模型组比较，矢车菊素-3-O-葡萄糖苷10、50 μmol/L组的细胞活力显著升高，胰岛素分泌水平显著增加，细胞内ROS水平和MDA含量显著降低，SOD活性显著升高，HGF、p-c-Met/c-Met蛋白水平显著上调（P＜0.05），且矢车菊素-3-O-葡萄糖苷50 μmol/L组改善更显著（P＜0.05）。使用c-Met抑制剂SU11274干预后，与矢车菊素-3-O-葡萄糖苷组比较，矢车菊素-3-O-葡萄糖苷＋SU11274组细胞活力则显著降低，胰岛素分泌水平显著减少（P＜0.05）。结论 矢车菊素-3-O-葡萄糖苷能够提高高糖高脂诱导下胰岛β细胞的活力，增加其胰岛素分泌量，并抑制氧化应激损伤，该作用与激活HGF/c-Met通路有关。     

Synthesis and evaluation of 2,6-piperidinedione derivatives as potentially novel compounds with analgesic and other CNS activities

New 2,6-piperidinediones 2_a–g and 4_a–d were prepared by initial condensation of aromatic aldehydes or cycloalkanones with cyanoacetamide to give α-cyanocinnamides l_a–g or cycloalkylidenes 3_a,b which underwent Michae1 addition with ethyl cyanoacetate or diethylmalonate. Compounds 4_a–d were alkylated by various alkyl halides to produce the N-alkylated 2,6-piperidinedione derivatives 5_a–m. Some new selected compounds 2_a–c,f, 4_a–d & 5_e,h,j were pharmacologically evaluated for potential anticonvulsant, sedative and analgesic activities. These compounds exhibited significant anticonvulsant and analgesic effects after a single I.P. administration 100 mg/kg b.wt. . On the other hand all the investigated compounds induced hypnotic activity and prolonged the phenobarbital sodium- induced sleep as compared with the control group and the most potent compound was found to be 2_f.     

Reassessment of the toxin profile of Cylindrospermopsis raciborskii T3 and function of putative sulfotransferases in synthesis of sulfated and sulfonated PSP toxins

The toxigenic freshwater cyanobacterium Cylindrospermopsis raciborskii T3 has been used as a model to study and elucidate the biosynthetic pathway of tetrahydropurine neurotoxins associated with paralytic shellfish poisoning (PSP). There are nevertheless several inconsistencies and contradictions in the toxin profile of this strain as published by different research groups, and claimed to include carbamoyl (STX, NEO, GTX2/3), decarbamoyl (dcSTX), and N-sulfocarbamoyl (C1/2, B1) derivatives. Our analysis of the complete genome of another PSP toxin-producing cyanobacterium, Raphidiopsis brookii D9, which is closely related to C. raciborskii T3, resolved many issues regarding the correlation between biosynthetic pathways, corresponding genes and the T3 toxin profile. The putative sxt gene cluster in R. brookii D9 has a high synteny with the T3 sxt cluster, with 100% nucleotide identity among the shared genes. We also compared the PSP toxin profile of the strains by liquid chromatography coupled to mass spectrometry (LC-MS/MS). In contrast to published reports, our reassessment of the PSP toxin profile of T3 confirmed production of only STX, NEO and dcNEO. We gained significant insights via correlation between specific sxt genes and their role in PSP toxin synthesis in both D9 and T3 strains. In particular, analysis of sulfotransferase functions for SxtN (N-sulfotransferase) and SxtSUL (O-sulfotransferase) enzymes allowed us to propose an extension of the PSP toxin biosynthetic pathway from STX to the production of the derivatives GTX2/3, C1/2 and B1. This is a significantly revised view of the genetic mechanisms underlying synthesis of sulfated and sulfonated STX analogues in toxigenic cyanobacteria.     

基于整合用药及靶点网络探讨中药治疗2型糖尿病合并高脂血症的核心处方及作用机制

目的 基于整合用药网络及靶点网络,筛选中医药治疗2型糖尿病合并高脂血症的核心处方及药对,并探讨潜在的分子作用机制。方法 以中国学术期刊全文数据库（CNKI）、万方数据库（Wanfang Data）、维普生物医学数据库（VIP）及Web of Science、PubMed中英文数据库为数据来源,结合古今医案云平台、R Studio Apriori关联规则函数进行数据挖掘,得到治疗2型糖尿病合并高脂血症的核心处方。通过TCMSP、UniProt、Swiss Target Prediction等数据库得到核心处方药物有效成分及潜在靶点,利用Cytoscape 3.8.1构建中药复方的药物-成分-靶点网络;与OMIM、Therapeutic Target Database、DrugBank等数据库得到的疾病靶点取交集,构建2型糖尿病合并高脂血症核心靶点蛋白质相互作用（PPI）网络。将核心靶点导入Metascape数据库进行基因本体（GO）注释及京都基因与基因组百科全书（KEGG）通路富集分析;并将处方的核心成分及2型糖尿病合并高脂血症的关键靶点逐一进行分子对接以初步验证其有效性。结果 由文献检索共得到中医药治疗糖尿病合并高脂血症经验方256首,涉及组成中药236味。综合数据挖掘结果得到核心处方,包括丹参、黄芪、茯苓、泽泻、山药、山楂、白术、葛根;高频药对有“山楂-丹参”“葛根-黄芪”等。经过数据库综合筛选,得到核心处方中有效活性成分132个。其中芹黄素、木犀草素、异鼠李素、丹参新醌甲、熊竹素为核心活性成分,核心处方治疗的核心靶点为类视黄醇X受体、细胞肿瘤抗原p53、RELA原癌基因、丝氨酸蛋白激酶磷酸、热休克蛋白α等。主要通路包括脂质与动脉粥样硬化通路、化学致癌-受体激活、胰岛素抵抗、PPAR信号通路及胆汁分泌。经分子对接论证,预测的核心靶点与关键成分之间有较强的结合活性。结论 中药治疗2型糖尿病合并高脂血症的核心处方组合可通过多活性成分,于多靶点、多通路调控,可为临床应用及药物开发提供参考思路。     

去壁灵芝孢子粉片的含量测定与免疫调节及心脏保护功能研究

目的 研究并评价“仙芝3号”去壁灵芝孢子粉片的免疫调节和心脏保护作用。方法 首先运用UPLC-Q-TOFMS和比色法分析“仙芝3号”去壁灵芝孢子粉片的主要化学成分,考察其对斑马鱼巨噬细胞减少症模型、斑马鱼心衰模型、H2O2诱导的心肌及内皮细胞氧化应激模型、脂多糖诱导的小胶质细胞炎症模型的影响,通过巨噬细胞形成能力、巨噬细胞吞噬能力、抗神经炎症能力、心脏收缩舒张改善能力、抗心肌及内皮细胞氧化应激损伤能力等多个指标评估其免疫调节及心脏保护作用。结果 “仙芝3号”去壁灵芝孢子粉片可以提高巨噬细胞形成及吞噬能力,改善心脏收缩舒张功能,减少神经炎症并缓解心肌及内皮细胞因氧化应激而造成的损伤,从而起到免疫调节和心脏保护作用。结论 “仙芝3号”去壁灵芝孢子粉片有望用于免疫功能调节及心脏功能保护。     

Investigation of the prevalence of tetQ, tetX and tetX1 genes in Bacteroides strains with elevated tigecycline minimum inhibitory concentrations

In this study, the antibiotic susceptibilities to tigecycline and tetracycline of 35 selected Bacteroides fragilis group strains were determined by Etest, and the presence of tetQ, tetX, tetX1 and ermF genes was investigated by polymerase chain reaction (PCR). tetQ was detected in all 12 B. fragilis group isolates (100%) exhibiting elevated tigecycline minimum inhibitory concentrations (MICs) (≥8 μg/mL) as well as the 8 strains (100%) with a tigecycline MIC of 4 μg/mL, whilst tetX and tetX1 were present in 15% and 75% of these strains, respectively. All of these strains were fully resistant to tetracycline (MIC ≥ 16 μg/mL). On the other hand, amongst the group of strains with tigecycline MICs < 4 μg/mL (15 isolates), tetQ, tetX and tetX1 were found less frequently (73.3%, 13.3% and 46.7%, respectively). All but two strains harbouring the tetQ gene in this group were non-susceptible to tetracycline, with a MIC > 4 μg/mL. These data suggest that in most cases tigecycline overcomes the tetracycline resistance mechanisms frequently observed in Bacteroides strains. However, the presence of tetX and tetX1 genes in some of the strains exhibiting elevated MICs for tigecycline draws attention to the possible development and spread of resistance to this antibiotic agent amongst Bacteroides strains. The common occurrence of ermF, tetX, tetX1 and tetQ genes together predicted the presence of the CTnDOT-like Bacteroides conjugative transposon in this collection of Bacteroides strains.     

Metabolism and hepatotoxicity of N,N-dimethylformamide,N-hydroxymethyl-N-methylformamide,and N-methylformamide in the rat

The metabolism and hepatotoxicity ofN,N-dimethylformamide (DMF) and two of its metabolites,N-hydroxymethyl-N-methylformamide (HMMF) andN-methylformamide (NMF) were evaluated over a 4-day period in rats. DMF toxicity was dose dependent and delayed toxicity after the administration of a high DMF dose (13.7 mmol/kg) in comparison to a lower dose (4.1 mmol/kg) was observed. Treatment of rats with 13.7 mmol/kg DMF, HMMF, or NMF showed i) that DMF is more toxic than HMMF or NMR, and ii) that hepatotoxicity occurs later for DMF than for HMMF or NMF. Analysis of serum and urine samples demonstrated that DMF is first metabolized to HMMF, which is then partially converted to NMF. After HMMF administration, NMF was found both in serum and in urine. The time course of DMF and HMMF toxicity in relation to NMF formation fitted the hypothesis that the hepatotoxicity of DMF and HMMF is mediated via NMF. The degree of hepatotoxicity after HMMF and NMF treatment is similar. However, the degree of DMF hepatotoxicity is much higher than in the case of NMF or HMMF. The role of NMF as an obligatory intermediate in DMF and HMMF hepatotoxicity is discussed.     

Prevalence and characterization of the mechanisms of macrolide, lincosamide and streptogramin resistance in viridans group streptococci

The presence of erm genes conferring constitutive and inducible resistance, as well as that of the mefA gene conferring only constitutive resistance, was investigated using PCR in 70 erythromycin resistant (MIC≥1 mg/l) strains of viridans group streptococci (VGS) (18 Streptococcus mitis biotype 1, 16 S. mitis biotype 2, 15 S. oralis, 12 S. salivarius and nine S. sanguis) isolated from the oropharynx of healthy Greek children. All of the 56 isolates belonging to resistance phenotype M harbored the mefA gene. All of the 14 isolates constitutively resistant to macrolides and lincosamides (phenotype CR) harbored the ermB gene. Co-presence of both genes was not observed, whereas class A erm gene (previously known as ermTR) was not detected. Our results are consistent with a possible role of VGS as a reservoir of resistance genes now prevalent in pathogenic species of streptococci.     

银杏叶提取物与刺梨配伍抗实验性肝损伤作用

目的：比较复方银杏叶胶囊（CGB）与单方银杏叶提取物（GBE）的保肝作用。方法：用CGB、GBE给小鼠灌胃30d后,腹腔注射CCl4诱发肝损伤,测定小鼠血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）及肝匀浆超氧化物歧化酶（SOD）、丙二醛（MDA）含量;用H2O2诱导人肝L-02细胞氧化损伤,观察细胞增殖及总抗氧化能力。结果：CGB2．4、0．8和0．4g／kg3个剂量组与模型组比较,小鼠血清ALT、AST明显降低（P〈0．01,P〈0．05）,同时肝匀浆中SOD显著升高、MDA下降（P〈0．01,P〈0．05）;CGB组细胞增殖率和总抗氧化能力分别较模型组和单方组显著提高（P〈0．05、P〈0．01）。结论：CGB的抗肝损伤作用优于单方银杏叶提取物。     

Metabolic activation of aromatic and heterocyclicN-hydroxyarylamines by wild-type and mutant recombinant human NAT1 and NAT2 acetyltransferases

Recombinant human NAT1 and polymorphic NAT2 wild-type and mutantN-acetyltransferases (encoded byNAT2 alleles with mutations at 282/857, 191, 282/590, 341/803, 341/481/803, and 341/481) were expressed inEscherichia coli strains XA90 and/or JM105, and tested for their capacity to catalyze the metabolic activation (viaO-acetylation) of theN-hydroxy (N-OH) derivatives of 2-aminofluorene (AF), and the heterocyclic arylamine mutagens 2-amino-3-methylimidazo [4,5-f]quinoline (IQ), 2-amino-3,4-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Both NAT1 and NAT2 (including all mutant human NAT2s tested) catalyzed the metabolic activation of each of theN-hydroxyarylamines to products that bound to DNA. Metabolic activation of N-OH-AF was greater than that of the heterocyclicN-hydroxyarylamines. The relative capacity of NAT1 versus NAT2 to catalyze activation varied withN-hydroxyarylamine substrate. N-OH-MeIQx and N-OH-PhIP exhibited a relative specificity for NAT2. These results provide mechanistic support for a role of the genetic acetylation polymorphism in the metabolic activation of heterocyclic amine mutagens and carcinogens.     

Photodegradation and phototoxicity of thioridazine and chlorpromazine evaluated with chemical analysis and aquatic organisms

The photochemical behaviour of chlorpromazine (CPZ) and thioridazine (THR) incubated under VIS light and a UV-A lamp was investigated with a high-performance liquid chromatography photodiode array detector (HPLC-PAD) and two bioassays. VIS light caused the decrease of CPZ and THR to 25% and 34% of the initial level, respectively, while UV-A degraded the drugs almost totally. CPZ and THR were very toxic to the protozoan Spirostomum ambiguum (Spirotox) and anostracan crustacean Thamnocephalus platyurus (Thamnotoxkit F^TM) with 24-h LC50 values of around 0.5 mg l⁻¹. In spite of the drastic decrease of the concentration of the drugs, the irradiated samples were toxic to the protozoan, especially when a sublethal end-point was taken into consideration. Contrary to the protozoan the crustacean was not sensitive to the products of photodegradation. Mass spectrometry analysis showed the presence of dimers and trimers of the CPZ and mono-, di-, and tri-oxygenated derivatives of THR. The presented data give a strong indication of the importance of the investigation of the environmental fate of drugs, especially those known to be phototoxic.