苦参碱-美法仑复合物MAT-MEL的合成及其体内外抗肿瘤活性的研究

目的 制备苦参碱-美法仑复合物(MAT-MEL),测定其抗肿瘤活性.方法 以槐果碱和美法仑为原料,利用拼合原理制备MAT-MEL;采用MTT法在体外测定复合物对人乳腺癌MCF-7细胞、人肝癌SMMC-7721细胞及小鼠骨肉瘤S180细胞的生长抑制作用;采用S180小鼠移植肿瘤模型评价复合物的体内抗肿瘤活性.结果 MAT-MEL的收率为61％,其结构通过核磁、质谱和元素分析得到确证;对3种细胞株的IC50分别为116.7±27.8、56.3±19.5、1.9±1.0 nmol· mL-1;3、6、9 μmol·kg-1的复合物对小鼠S180的抑瘤率分别为49.56％、54.58％、77.18％.结论 MAT-MEL具有显著的抗肿瘤活性.     

利奈唑胺与万古霉素对耐甲氧西林金黄色葡萄球菌体外抗菌活性

目的 评价利奈唑胺(嗯唑烷酮类抗菌药)、万古霉素(胺基糖苷类抗生素)2种抗菌药物对耐甲氧西林金黄色葡萄球菌(MRSA)的体外抗菌活性.方法 用琼脂二倍稀释法,测定抗菌药物的最低抑菌浓度(MIC);用肉汤稀释法,测定抗菌药物的最低杀菌浓度(MBC),绘制杀菌曲线(KCs).结果 利奈唑胺对临床分离的98株MRSA的MIC50为1 μg·mL-1,MIC90为2 μg·mL-1,MBC50为8 μg·mL-1,MBC90为32 μg·mL-1,敏感率为100%;万古霉素对临床分离的98株MRSA的MIC50为1 μg·mL-1,MIC90为1 μg·mL-1,MBC50为8 μg·mL-1,MBC90为32 μg·mL-1,敏感率为100%.随着抗菌药物浓度的升高,其杀菌时间缩短不甚明显,呈现非浓度依赖性的特点.结论 利奈唑胺对MRSA的体外抗菌活性与万古霉素相当,均显示非浓度依赖性的杀菌曲线.     

Investigation on anti-tumor Effects of Cinnabar and Gypsum in vitro

目的 观察朱砂与石膏的体外抗肿瘤作用.方法 采用MTT法检测朱砂、石膏对BGC-823胃癌细胞、A549肺腺癌细胞增殖的影响;通过Hoechst 33258荧光染色研究其对BGC-823胃癌细胞凋亡的影响.结果 朱砂对BGC-823胃癌细胞生长的半数抑制浓度(IC50)为3.44μg·mL-1,抑制肺腺癌A549细胞的IC50为7.69μg·mL-1;石膏仅在1.5mg· mL-1浓度时对BGC-823胃癌细胞、A549肺腺癌细胞生长有显著的抑制作用.朱砂及石膏作用48h后BGC-823细胞贴壁细胞数量明显减少,细胞中未检测到明显的凋亡小体.结论 朱砂体外有明显的抗肿瘤作用.     

5-Fu与TRAIL联用抗结肠癌细胞株HT-29效应的实验研究

目的 观察肿瘤坏死因子相关凋亡诱导配体(TRAIL)与5-氟尿嘧啶(5-Fu)联用对结肠癌细胞株HT-29体外生长增殖、凋亡的影响,评价其联用效果.方法 体外培养HT-29细胞,采用磺基罗丹明B(SRB)法测定细胞的存活率,Webb系数法判断联用是否具协同作用,流式细胞FITC-Annexin V/PI双染法检测细胞的凋亡.结果 结肠癌细胞株HT-29对TRAIL不敏感(IC50＞10 μg·mL-1),对5-Fu敏感(IC50＜10 μg·mL-1);0.1、1、10 μg·mL-1 TRAIL分别与0.05、0.1、0.5 μg·mL-1 5-Fu联用48 h,除0.1 μg·mL-1 TRAIL与0.5 μg·mL-1 5-Fu联用组外,其余联用组细胞存活率均明显低于TRAIL单用组或5-Fu单用组水平;0.1 μ·mL-1 TRAIL及0.5 μg·mL-1 5-Fu单用或联用时,HT-29细胞凋亡率分别为8.6%、18.1%和30.8%.结论 5-Fu 与TRAIL联用具有协同的细胞毒和细胞凋亡作用.     

草豆蔻中总黄酮体外抗肿瘤活性研究

目的 评价草豆蔻中总黄酮的体外抗肿瘤活性.方法 采用四甲基偶氮唑蓝(MTT)法体外检测草豆蔻中总黄酮对多种肿瘤细胞株的生长抑制作用.结果 草豆蔻中总黄酮对人胃癌细胞株SGC-7901有较强抑制作用,IC50为3.48μg·mL-1;对人肝癌细胞株HepG2、人慢性粒细胞白血病细胞株K562和人肝癌细胞株SMMC-7721也有一定的抑制作用,IC50分别为32.30μg·mL-1、29.21μg·mL-1和16.38μg·mL-1.结论 草豆蔻中总黄酮具有抗肿瘤活性.     

阿魏酸-磷脂复合物的制备及其物理特性

目的制备阿魏酸-磷脂复合物,提高阿魏酸的脂溶性,以期进行进一步的制剂研究。方法采用溶剂挥发法制备阿魏酸-磷脂复合物,并以单因素法优化制备工艺,对复合物进行红外及X-衍射分析,考察阿魏酸表观油水分配系数的变化。结果阿魏酸磷脂复合物的制备工艺为:以无水乙醇为溶剂,药物-磷脂投料摩尔比为1∶1,室温下磁力搅拌4 h,真空干燥;红外及X-衍射图谱验证了复合物的形成;阿魏酸-磷脂复合物在0.1 mol.L-1HCl中的表观油水分配系数显著提高。结论阿魏酸磷脂复合物提高了阿魏酸的脂溶性。     

海洋放线菌N331生物碱活性组分的研究

目的 对海洋放线菌N331发酵液中的抗菌活性成分进行研究.方法 采用大孔树脂吸附、硅胶柱层析分离纯化抗菌活性成分,并对其理化性质和生物活性进行初步研究.结果 从海洋放线菌N331的发酵液中分离到一种结晶状活性组分,鉴定为生物碱类物质,由几种极性相近的化合物组成;其对金黄色葡萄球菌敏感茼及其耐药菌的最小押菌浓度均为4μg·mL-1,对口腔上皮癌KB细胞和肺癌A549细胞的半数抑制浓度(IC50)分别为2.0,3.0μg·mL-1,与顺铂的抗肿瘤效价相当.结论 海洋放线菌N331能产生抗茸及细胞毒性较强的生物碱类活性物质.     

十味板蓝根颗粒剂抗病毒作用的实验研究

目的:探讨十味板蓝根颗粒剂体外抗柯萨奇病毒B3株(CVB3)、单纯疱疹病毒II型(HSV II)的作用.方法:采用组织细胞培养法,观察药物毒性和细胞病变效应,评价十味板蓝根颗粒剂的细胞毒性及抗病毒效果.结果:十味板蓝根颗粒剂对Hep-2和Hela细胞毒性均较低(TD0为1 mg·mL-1),浓度在125μg·mL-1以上时,可以明显抑制HSV-II病毒对Hela细胞感染;浓度达250 μg·mL-1以上时,明显抑制CVB3病毒对Hep-2细胞的致病变作用,对Hep-2和Hela细胞有保护作用,并且随着药物浓度的增加,CPE特征逐渐减弱,病毒抑制率(细胞存活率)明显升高.结论:十味板蓝根颗粒剂在体外能明显抑制CVB3和HSV-II病毒的致细胞病变作用.     

重组L-门冬酰胺酶前体脂质体对HL-60细胞生长的影响

目的:研究L-门冬酰胺酶(L-ASNase)脂质体对体外培养的人早幼粒细胞白血病(HL-60)细胞活性的影响.方法:实验分3组:对照1组加入新鲜RPMI1640培养液倍比稀释的空白脂质体;对照2组加入L-ASNase(终浓度分别为2.5,5,10,20和40 μg·mL-1);实验组加入L-ASNase脂质体(前体脂质体水合而得,终浓度分别为2.5,5,10,20和40 μg·mL-1).MTT法测定细胞存活率,电镜观察细胞形态学,流式细胞仪检测肿瘤细胞周期的改变.结果:L-门冬酰胺酶脂质体(经前体脂质体水合而得)组HL-60细胞的G0/G1期细胞量明显增加,S期的细胞明显减少;增殖指数(PI)显著下降;HL-60细胞凋亡比例显著增多.结论:L-门冬酰胺酶脂质体抑制HL-60细胞的繁殖,可能与抑制细胞的S期有关.     

银杏磷脂胶囊的制备与质量控制

目的制备银杏磷脂胶囊,并建立其质量控制方法.方法在银杏叶提取物中加入大豆卵磷脂,控制萃取压力10MPa、温度50℃,用二氧化碳进行萃取1 h,制备成银杏磷脂胶囊.采用薄层色谱法进行定性鉴别、高效液相色谱法测定总黄酮醇苷的含量.结果薄层色谱法在与对照品溶液相应的位置上,显相同颜色的荧光斑点.总黄酮醇苷(槲皮素、山奈素和异鼠李素)的线性范围分别为7.53～120.51 μg·mL-1(r=0.9998)、7.46～119.36 μg·mL-1(r=0.999 5)、5.05～80.77 μg·mL-1(r=0.9996).平均回收率分别为101.5%,RSD为1.4%.结论制备工艺简洁、收得率高,同时减少了环境污染;质量控制方法快速、准确、重复性好,可作为银杏磷脂胶囊的质量控制方法.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.