电感耦合等离子体-质谱法测定注射用益气复脉(冻干)中的硫元素

目的 采用电感耦合等离子体-质谱（ICP-MS）法建立注射用益气复脉（冻干）中硫元素的含量测定方法。方法 以微波消解法处理样品,硝酸为消解试剂,样品经微波消解后,以锗（Ge）元素为内标元素,采用ICP-MS法测定药液中硫元素的量。结果 硫元素质量浓度在1～15 μg/mL内线性关系良好（r=0.999 0）;准确度试验（n=6）平均回收率为95.4%,RSD值为5.9%;结论 该方法简便、快速、准确,可用于测定注射用益气复脉（冻干）中硫元素的含量,为其质量控制、安全性评价提供一定参考。     

微波消解-ICP-MS测定洁白胶囊中重金属含量

目的 建立电感耦合等离子体质谱法（ICP-MS）测定洁白胶囊中Pb、Cd、As、Hg、Cu等重金属元素的方法,为洁白胶囊用药安全提供依据。方法 微波消解样品,以30.0 μg·L^-1的Sc 45、In 115作内标,采用ICP-MS同时测定上述5种元素的含量。结果 5种元素方法检出限为0.000 5~0.021 1 mg·kg^-1,线性关系良好（r>0.99）,加样回收率为98.2%~105.4%,RSD为2.3%~3.5%。本次测定的19批洁白胶囊中重金属含量为Pb：0.2~1.0 mg·kg^-1;Cd：0.012~0.027 mg·kg^-1;As：0.18~1.52 mg·kg^-1;Hg：0~0.151 mg·kg^-1;Cu：1.4~2.5 mg·kg^-1。参照药用植物及制剂外经贸绿色行业标准和新加坡进口中药材和中成药标准,结果符合规定。结论 该方法简便易行,准确度灵敏度高、重复性良好,适用于洁白胶囊中5种重金属的测定。     

复方氨基酸类注射液中铝元素3种测定方法的比较

目的 比较电感耦合等离子质谱法（ICP-MS）、电感耦合等离子原子发射光谱法（ICP-AES）和高效液相色谱法（HPLC）测定复方氨基酸类注射液中铝元素含量的差异。方法 通过方法学验证和样品测定，对比分析3种方法的线性、重复性、准确度、定量限、检测限和样品测定结果。结果 ICP-MS、ICP-AES和HPLC 3种方法在5~200μg·L^-1内相关系数均>0.999；重复性结果相对平均偏差RSD （n=6）分别为2.4%，5.5%和7.6%；加样回收率分别为103.2%，106.0%和105.7%；定量限分别为1.2，4.1，5.0μg·L^-1；ICP-MS法和ICP-AES法的检出限分别为0.4，1.2μg·L^-1；43批复方氨基酸类注射液样品的铝元素测定结果基本一致。结论 3种方法均可满足复方氨基酸类注射液中铝元素含量的测定要求，ICP-MS法简便、快速、准确。HPLC仪器成本较低，更易于实验室推广。     

电感耦合等离子体质谱法测定茯苓中17种金属元素

目的 建立ICP-MS法测定茯苓中砷（As）、铍（Be）、镉（Cd）、钴（Co）、铜（Cu）、锰（Mn）、钼（Mo）、镍（Ni）、铅（Pb）、锑（Sb）、硒（Se）、钛（Ti）、铊（TI）、钒（V）、铬（Cr）、锌（Zn）、汞（Hg）共17种金属元素的含量,并对不同产地的11批茯苓的金属元素含量进行评价。为中药材生产中的质量控制和临床上的安全用药提供了科学依据。方法 样品经微波消解处理后,以Se、Y、In、In-1、Bi为内标,采用ICP-MS法同时进行测定。结果 对于各测定元素,标准曲线的相关系数r>0.998,回收率在88.0%~107.3%,RSD值在0.1%~11.0%。结论 该方法简便、快速、准确,可用于茯苓中药材中17种元素的含量测定。     

ICP-MS检测紫花地丁中37种无机元素含量

目的 测定紫花地丁中37种无机元素的含量，并建立多元素的电感耦合等离子体质谱（inductively coupled plasma mass spectrometry，ICP-MS）测定方法，初步探索研究紫花地丁药材中重金属元素的污染情况。方法 以HNO₃和H₂O₂作为消解溶剂，采用微波消解法前处理样品，通过ICP-MS同时测定紫花地丁中37种无机元素的含量。结果 37种无机元素在0.5~500 ng·mL^-1内与峰面积呈良好的线性关系（r ≥ 0.99），在0.1，1和10 μg 3个添加水平下，大多数元素的平均回收率介于85.1%~120.6%，RSD（n=6）<6%，仪器精密度和重复性的RSD值均<3%；19批紫花地丁中5种中国药典2015年版明确需要控制的有害重金属元素（铜、铅、砷、汞、镉）的检出率分别为铜和铅100%，砷和汞89.5%和10.5%，镉在所有样品中均未检出；钼元素和锶元素在19批样品检出率均为100%，且含量远远高于其他元素，钼元素的最高含量为24.8 mg·kg^-1；锶元素的含量则可高达67.6 mg·kg^-1。结论 该方法具有简便、快速、准确的优点，可用于紫花地丁中37种无机元素的含量测定。     

电感耦合等离子体-质谱法测定不同时期秀丽隐杆线虫中26种无机元素

目的 通过电感耦合等离子体-质谱（ICP-MS）法建立同时测定秀丽隐杆线虫体内26种元素含量的方法,同时分析线虫生长发育不同阶段体内元素的含量变化。方法 以65%~68% HNO₃作为消解液,采用湿法消解处理线虫,利用ICP-MS同时测定线虫中26种元素Al、As、B、Ba、Bi、Ca、Cd、Co、Cr、Cu、Fe、Ga、In、K、Mg、Mn、Mo、Na、Ni、Pb、Sc、Se、Te、V、Zn、Zr。将线虫同步化后获得的卵均匀分成5组,分别培养至L1期、L2期、L3期、L4期以及Adult期,应用建立的ICP-MS法测定26种元素含量。结果 26种元素在0~500 μg·L^-1线性关系良好,R² ≥ 0.999 3;仪器检出限为0.000 1~0.090 3 μg·L^-1;仪器精密度（RSD）为0.4%~1.8%;重复性（RSD）为0.0%~2.5%;稳定性（RSD）为0.8%~4.6%;平均加标回收率为80.8%~118.5%,RSD为0.2%~1.5%。L4期线虫中总体元素含量最高,其次是L2期,L1期线虫中总体元素含量最低。结论 通过ICP-MS测定了线虫生长发育过程中体内元素的含量,该方法快捷灵敏、简便高效,适用于对线虫中元素的分布情况进行分析,为进一步研究单一元素或多种元素对秀丽隐杆线虫的潜在影响提供参考。     

电感耦合等离子体质谱（ICP-MS）法测定人凝血因子Ⅷ/血管性血友病因子复合物冻干注射剂中的21中元素

目的 建立电感耦合等离子体质谱（ICP-MS）同时测定人凝血因子Ⅷ/血管性血友病因子复合物冻干注射剂中硼（B）、镁（Mg）、铝（Al）、硅（Si）、钒（V）、镉（Cr）、锰（Mn）、铁（Fe）、钴（Co）、镍（Ni）、铜（Cu）、锌（Zn）、锶（Sr）、锆（Zr）、钼（Mo）、铑（Rh）、钯（Pd）、锡（Sn）、钡（Ba）、铈（Ce）、铅（Pb）元素含量的方法。方法 样品经微波消解后,以钪（Sc）、锗（Ge）、铟（In）、铋（Bi）为内标,采用电感耦合等离子体质谱（ICP-MS）法同时测定上述元素的含量。ICP-MS 功率为1550 W,采样深度为10.0 mm,等离子气、雾化气、辅助气流量分别为15.0、0.99、0.9 L·min^-1,泵速为0.10 r·s^-1,雾化室温度为2℃,硼（B）元素采用No Gas调谐模式,其它元素采用He调谐模式,数据采集3次。结果 21种元素在测定的浓度范围内,线性关系良好,相关系数r＞0.9990;检出限为0.001～2.04 µg·L^-1;各元素回收率为87.78%～102.72%,RSD为1.31%～7.91%。结论 该方法快速简便、灵敏度高、准确性好,可用于人凝血因子Ⅷ/血管性血友病因子复合物冻干注射剂中金属元素的检测。     

氯化丁基胶塞中11种无机元素含量的电感耦合等离子体发射光谱-质谱法测定

目的 测定氯化丁基胶塞在5种不同提取条件下可提取无机元素成分，评估其迁移量对药品安全的影响，以降低干粉针的包材风险。方法 氯化丁基胶塞分别在5种溶剂（水、15%乙醇、0.9%氯化钠、pH 3.5磷酸缓冲液、pH 8.0磷酸缓冲液）中提取后，采用电感耦合等离子体发射光谱-质谱法（ICP-MS）分别测定5种提取溶液中镁（Mg）、铝（Al）、硅（Si）、硫（S）、钙（Ca）、钛（Ti）、铁（Fe）、锌（Zn）、砷（As）、镉（Cd）、锑（Sb）11种元素的量。结果 建立了11种元素的标准曲线，各元素的线性关系均良好（R>0.99），检测了5种提取溶液的各元素检出限和定量限，均满足检测要求，5种提取溶液中11种元素测定结果均低于限度值。结论 用于天津天士力之骄药业有限公司冻干产品包装用的氯化丁基胶塞，Fe、Zn、As、Cd、Sb 5种元素迁移量均低于每日允许暴露量（PDE），另外6种无PDE报道的元素，评估结果显示迁移量不会给药品带来安全风险。     

微波消解-ICP-MS法同时测定天麻中15种稀土元素

目的 建立ICP-MS法同时测定天麻中15种稀土元素的含量。方法 采用微波消解法处理样品,电感耦合等离子体质谱法测定。结果 15种元素中在0~100 μg·L^-1范围内,线性相关系数在0.999 6~0.999 9。平均加标回收率在89.3%~108.8%之间,精密度RSD在1.01%~2.51%,重复性RSD在1.44%~6.05%。结论 本方法简便快速准确,可用于天麻中15种稀土元素的测定,为天麻的质量研究和控制工作提供技术支持。     

ICP-MS同时测定氢化可的松注射液中21种元素杂质的迁移量

目的 建立同时测定氢化可的松注射液中21种元素杂质(Hg、As、Cd、Pb、Co、V、Ni、Li、Sb、Cu、Ba、Cr、Fe、Zn、Mn、Al、B、Ca、Mg、Si、Ti)含量的电感耦合等离子体质谱法(inductively coupled plasma mass spectrometry，ICP-MS)。方法 采用标准加入法，样品经稀释直接进样，以Ge、In、Bi元素为内标，采用ICP-MS测定67批样品和加速试验样品中的21种元素杂质的含量。结果 各元素在相应的浓度范围内均具有良好的线性关系(r≥0.999 8)，加样回收率为96.10%~101.94%，RSD均<4.34%(n=9)。随着时间的推移，Al元素发生了迁移，各元素的每日摄入量均低于相应的每日允许暴露量。结论 该方法简便快速，具有良好的灵敏度和准确度，可用于氢化可的松注射液中21种元素杂质迁移量的检测。     

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.