苦豆子生物碱衍生物施普睿达对小鼠肝癌H22的抑制作用

目的 观察苦豆子生物碱衍生物施普睿达体内对小鼠肝癌H22的抑制作用及量效关系. 方法 将75只昆明种小鼠移植肝癌H22细胞后,随机分为5组,每组15只. 空白对照组给予纯化水10 mL•kg^-1•d^-1,低、中、高剂量给药组分别给予施普睿达150,300,600 mg•kg^-1•d^-1,阳性对照组每2 d给予顺铂（4 mg•kg^-1）,各组均连续给予相应药物10 d. 观察施普睿达对实体瘤的抑瘤率,通过体重变化,肝重,脾、胸腺指数等多项指标综合考察施普睿达对荷瘤动物免疫机能的影响. 结果 低、中和高剂量药物组对小鼠肝癌H22抑瘤率分别为33.44%,41.90%,48.25%,各组对小鼠的肝、脾指数和胸腺指数几乎无影响;而阳性对照组小鼠的肝、脾指数和胸腺指数明显下降. 结论 施普睿达对小鼠肝癌H22有较好的治疗作用,而且不影响荷瘤动物免疫功能,属于低毒的抗肿瘤新药.     

大鼠烯丙基半胱氨酸浓度的测定及组织分布

目的 建立高效液相色谱法测定血清和组织烯丙基半胱氨酸（SAC）浓度的 方法 , 并进行组织分布研究. 方法 采用Hypersil ODS2 色谱柱, 以50 mmol•L^-1 醋酸盐缓冲液 （pH 5.8 ）：甲醇：乙腈（50：22：28）为流动相; 柱温为35 ℃ , 荧光检测激发波长为350 nm , 发射波长为455 nm.样品的预处理后邻苯二甲醛（OPA）-2-巯基乙醇柱前衍生; 进样10 μL. 结果 血清样品在2～120 mg•L^-1浓度范围内, 线性关系良好; 组织样品在2～120 mg•g^-1浓度范围内, 线性关系良好.低、中、高3种浓度的萃取回收率为70.9%～83.5%; 相对回收率为90.2%～110.0%; 日内、日间RSD为4.1%～7.7%.肾脏达峰浓度Cmax为65.7 mg•kg^-1, 肝脏为58.1 mg•kg^-1, 脾脏为51.3 mg•kg^-1, 心脏为43.3 mg•kg^-1, 肺为35.1 mg•kg^-1, 脑组织为26.7 mg•kg^-1 ; 各组织AUC _0~8肾脏为171.9 mg•h•kg^-1, 心脏为113.9 mg•h•kg^-1, 肝脏为107.2 mg•h•kg^-1, 脾脏为90.4 mg•h•kg^-1, 肺为93.6 mg•h•kg^-1,脑组织为79.8 mg•h•kg^-1. 结论 该法简便、快速、准确、灵敏、选择性强, SAC在大鼠体内分布广泛, 其中肾脏分布较多, 而在脑组织中分布较少.     

槲皮素对去卵巢大鼠股骨OPG与RANKL表达的影响

目的观察槲皮素对去卵巢大鼠股骨骨保护素（osteoprotegerin, OPG）及核因子κB受体活化子配体（ligand of receptor activator of NF κB,RANKL）表达的影响。方法健康雌性SD大鼠48只,按体质量随机分为6组：假手术组（SHAM组）、单纯去卵巢组（OVX组）、17β-雌二醇组（ERT组,0.1 mg•kg^-1•d^-1）、高剂量槲皮素组（QH组,300 mg•kg^-1•d^-1）、中剂量槲皮素组（QM组,150 mg•kg^-1•d^-1）、低剂量槲皮素组（QL组,75 mg•kg^-1•d^-1）。除假手术组外其余各组均切除双侧卵巢,术后1周开始给药,给药 16周后处死所有大鼠,测定腰椎及股骨骨生物力学性能：弹性模量（ELASTIC） 、刚度（STIFFNESS）、最大应力（M STRESS）及最大承载力（M LORD）,用免疫组织化学染色方法观察股骨OPG、RANKL表达情况。结果 槲皮素高、中剂量均能上调股骨OPG、下调RANKL表达,部分改善股骨、腰椎生物力学性能。结论 槲皮素可通过调节骨组织中OPG、RANKL的相对含量而抑制骨吸收,防止骨质疏松。     

丙种球蛋白佐治支原体肺炎60例

目的 观察丙种球蛋白佐治支原体肺炎的疗效. 方法 将116例患儿随机分为治疗组（60例）和对照组（56例）. 两组均给予止咳、退热处理,对照组应用阿奇霉素10 mg•kg^-1•d^-1,静脉滴注,qd,3～5 d. 治疗组在对照组基础上静脉滴注人血丙种球蛋白400 mg•kg^-1•d^-1,连用3 d. 1周后观察疗效. 结果 治疗组退热、止咳、平喘、肺部音吸收时间及住院天数比对照组均明显缩短. 结论 丙种球蛋白佐治支原体肺炎疗效明显,值得临床推广.     

姜黄素与吡喹酮对小鼠日本血吸虫肝纤维化组织血管内皮生长因子表达的影响

目的 探讨杀虫治疗后血吸虫肝纤维化的进展以及姜黄素抗血吸虫肝纤维化的作用及其机制. 方法 100只小鼠随机分为5组. A、B、C、D 4组小鼠感染日本血吸虫尾蚴, E组小鼠作为正常组. A、B、C、D 4组小鼠感染尾蚴6周后, A组小鼠以吡喹酮治疗; B组小鼠予吡喹酮治疗后以高剂量姜黄素（300 mg•kg^-1•d^-1）治疗8周, C组小鼠予吡喹酮治疗后以低剂量姜黄素（150 mg•kg^-1•d^-1）治疗8周, D组小鼠不作任何治疗（实验对照组）. E组小鼠正常饲养. 第14周末处死小鼠, 留取肝脏组织, 观察各组小鼠肝组织病理改变, 测定其肝脏丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性及血管内皮生长因子（VEGF）、Ⅰ、Ⅲ型胶原的表达变化. 结果 A、B、C组治疗后小鼠肝纤维化程度明显减轻, 肝组织中SOD活性升高而MDA含量以及VEGF、Ⅰ、Ⅲ型胶原表达均明显低于D组, 但未恢复正常. 与A组比较, B、C组进一步减轻肝纤维化程度, 显著升高肝组织中SOD活性、降低MDA含量以及VEGF、Ⅰ、Ⅲ型胶原表达水平, 且高剂量姜黄素治疗效果明显高于低剂量组. 结论 杀虫治疗后行抗肝纤维化治疗仍属必要. 姜黄素可呈剂量依赖性地通过抑制肝组织VEGF表达, 降低肝组织氧化应激水平而发挥抗肝纤维化作用.     

奥卡西平单药和添加治疗儿童癫痫的疗效与安全性

目的 观察奥卡西平治疗儿童部分性发作（PS）和全面性强直-阵挛发作（ GTCS）癫痫患者的疗效、耐受性和副作用. 方法 73例癫痫患儿, 其中56例新诊断者进入单治组, 17例应用过其他抗癫痫药物治疗者进入加治组. 奥卡西平起始剂量5～10 mg•kg^-1•d^-1, 最大剂量30～40 mg•kg^-1•d^-1, 维持剂量中位值20 mg•kg^-1•d^-1, bid. 加治组其他抗癫痫药物的使用不变. 通过自身对比开放性观察, 分析单治组与加治组52周的疗效、不良反应、耐受性和安全性. 结果 全部患者总有效率84.9%、控制率54.8%、累积退出率11.0%, 其中3例（4.1%）失访, 不良反应或其他原因退出者5例（6.8%）, 其中因皮疹退出2例（2.7% ）. 常见不良反应：乏力8例、烦躁7例, 困倦和皮疹各2例. 单治组临床控制率（62.5%）显著高于加治组（29.4%）. 结论 奥卡西平是治疗儿童部分性发作和全面性强直-阵挛发作癫痫相对理想的药物选择.     

人参皂苷Rg3对环磷酰胺的增效作用

目的 观察人参皂苷Rg3与环磷酰胺（CTX） 联用对S180小鼠抑瘤率、血清白细胞介素（IL）- 2水平及脾淋巴细胞转化能力的影响,探讨人参皂苷Rg3对CTX增效作用的机制. 方法 小鼠右腋皮下接种含S180荷瘤细胞1.0×10⁷个&#8226;mL^-1的溶液0.2 mL制备肿瘤模型, 随机分为5组：对照组, 阴性对照组, 低、中、高剂量药物组; 对照组每天灌胃给予0.9%氯化钠溶液, 阴性对照组每天给予CTX腹腔注射, 低、中、高剂量药物组腹腔注射CTX 20 mg&#8226;kg^-1&#8226;d^-1, 同时分别灌胃给予人参皂苷Rg3 2.5, 5.0, 10.0 mg&#8226;kg^-1&#8226;d^-1, 连续10 d.实验结束后测定人参皂苷Rg3对CTX的增效作用. 结果 人参皂苷Rg3与CTX伍用可发挥协同作用, 可提高抑瘤率（P< 0.05）; 人参皂苷Rg3与CTX伍用能提高S180荷瘤小鼠血清IL-2的含量, 促进T淋巴细胞转化, 从而提高荷瘤小鼠的免疫功能而达到抗肿瘤作用.结论 人参皂苷Rg3与CTX合用可提高机体的免疫力, 增强CTX的抑瘤作用.     

艾司西酞普兰与文拉法辛治疗难治性抑郁症的对照研究

目的 探讨艾司西酞普兰对难治性抑郁症患者的疗效和安全性. 方法 68例难治性抑郁症的住院患者随机分为治疗组和对照组各34例, 治疗组给予艾司西酞普兰,起始剂量10 mg&#8226;d^-1,早餐后服,根据病情调整10～20 mg&#8226;d^-1,平均剂量（16.62±3.65） mg&#8226;d^-1. 对照组给予文拉法辛缓释剂,起始剂量75 mg&#8226;d^-1,早餐后服用,7～10 d加至治疗量150～225 mg&#8226;d^-1,平均剂量（175.54±20.50） mg&#8226;d^-1. 两组疗程均6周. 采用汉密尔顿抑郁量表（HAMD）评定疗效,不良反应和安全性采用不良反应量表（TESS）及实验室检查评定. 结果 有效率和痊愈率治疗组分别为58.8%,20.6%;对照组分别为61.8%,23.5%;两组比较差异无显著性（P＞0.05）. TESS评定显示,两组不良反应发生率差异无显著性（P＞0.05）. 结论 艾司西酞普兰治疗难治性抑郁症的疗效与文拉法辛相似,起效快,不良反应较轻.     

喹硫平治疗精神分裂症30例

目的 考察喹硫平治疗精神分裂症的有效性及安全性. 方法 将60例精神分裂症患者分为治疗组和对照组, 每组30例.治疗组给予喹硫平, 初始剂量100 mg&#8226;d^-1, 2周内加至400~800 mg&#8226;d^-1, 以后3周内视病情及不良反应调整剂量, 最大剂量1 200 mg&#8226;d^-1, 平均（728.3±199.9） mg&#8226;d^-1.对照组给予利培酮, 起始剂量1 mg&#8226;d^-1, 2周后加至治疗量3~6 mg&#8226;d^-1, 平均（4.9±0.9） mg&#8226;d^-1.疗程均为8周.两组根据情况给予苯海索、氮类药或普萘洛尔等对症处理, 以阴性和阳性症状量表（PANSS）、不良反应量表（TESS）分别评定疗效、病情严重程度和不良反应. 结果 治疗组与对照组的显效率均为70.0%, 有效率分别为90.0%和86.7%.两组在治疗前PANSS评分差异无显著性, 在治疗8周末, 两组PANSS评分较治疗前显著下降, 均差异有极显著性（均P< 0.01）.两组比较差异无显著性（P＞0.05）.治疗组的不良反应较对照组少而轻.结论 喹硫平可显著改善精神分裂症症状, 且不良反应发生率低, 是一种安全有效的抗精神病药物.     

依托咪酯与丙泊酚联合用于高龄患者胆囊切除胆总管探查手术的麻醉

目的 研究依托咪酯与丙泊酚联合用于高龄患者胆囊切除胆总管探查手术麻醉的应用价值. 方法 30例择期行开腹胆囊切除、胆道探查术患者,随机分为依托咪酯＋丙泊酚组（A组）和依托咪酯组（B组）. A组经静脉给予咪达唑仑0.03 mg&#8226;kg^-1,依托咪酯0.2 mg&#8226;kg^-1,丙泊酚0.5 mg&#8226;kg-1,芬太尼3～4 μg&#8226;kg^-1复合维库溴铵0.15 mg&#8226;kg-1诱导. B组经静脉给予咪达唑仑0.03 mg&#8226;kg^-1,依托咪酯0.3 mg&#8226;kg^-1,芬太尼3～4 μg&#8226;kg^-1复合维库溴铵0.15 mg&#8226;kg^-1诱导. 采用惠普多功能监护仪记录患者麻醉前、麻醉诱导后、插管即刻、插管后1 min及手术全程血压、心率,并记录患者肌震颤及术后24 h恶心呕吐等不良反应发生率. 结果 A组3例、B组2例于麻醉诱导后出现血压轻度下降,A组1例、B组2例于气管插管后血压上升、心率增快,但两组间比较差异无显著性（P＞0.05）. A组有1例术后第1天出现恶心,B组有6例术后第1天出现恶心、5例呕吐,与A组比较,差异有显著性（P＜0.05）. 结论 依托咪酯与丙泊酚联合用于高龄患者胆囊切除胆总管探查手术麻醉中,对血流动力学影响轻微,同时降低术后恶心呕吐的发生率.     

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.