紫杉醇与多烯紫杉醇

目的比较紫杉醇与多烯紫杉醇在药学特性及临床应用的差异,为临床合理应用两药提供依据。方法查阅分析相关文献资料,比较分析两药异同。结果紫杉醇与多烯紫杉醇在化学结构、药代动力学、药物相互作用、药物毒性及临床应用等方面有不同的特点。结论临床应用中应根据各自特点,注意合理使用。     

紫杉醇与多烯紫杉醇

目的比较紫杉醇与多烯紫杉醇在药学特性及临床应用的差异,为临床合理应用两药提供依据。方法查阅分析相关文献资料,比较分析两药异同。结果紫杉醇与多烯紫杉醇在化学结构、药代动力学、药物相互作用、药物毒性及临床应用等方面有不同的特点。结论临床应用中应根据各自特点,注意合理使用。     

紫杉醇概述

紫杉醇作为红豆杉植物次生代谢产物是近20年来世界范围内抗癌药物研究领域的重大发现，也一直是该领域的研究热点。红豆杉资源的短缺与紫杉醇需求量的增加形成了尖锐的矛盾，这成了国内外工作人员的研究重点（1）。     

紫杉醇、紫杉醇脂质体和白蛋白结合型紫杉醇在头颈肿瘤中的疗效比较

目的 探讨紫杉醇（paclitaxel,PTX）、PTX脂质体（paclitaxel liposome,L-PTX）和白蛋白结合型PTX（albumin bound paclitaxel,nab-PTX）在头颈肿瘤中的疗效。方法 采用回顾性研究,收集整理2017年1月-2018年6月69例宁波市医疗中心李惠利医院头颈恶性肿瘤患者的临床资料,其中31例PTX联合卡铂治疗为PTX组,26例L-PTX联合卡铂治疗为L-PTX组,12例nab-PTX联合卡铂治疗为nab-PTX组。比较3组患者近期临床疗效以及不良反应情况。结果 Nab-PTX组患者的近期疗效优于PTX组（66.67%vs 32.26%,χ²=4.209,P=0.040）。L-PTX组患者中性粒细胞减少发生率高于PTX组（χ²=4.079,P=0.043）,白细胞减少发生率高于PTX组（χ²=4.422,P=0.035）和nab-PTX组（χ²=5.640,P=0.018）;nab-PTX组患者脱发、恶心呕吐、腹泻等不良反应发生率低于PTX组（χ²=5.530,P=0.019;χ²=6.423,P=0.011;χ²=4.438,P=0.035）和L-PTX组（χ²=5.025,P=0.025;χ²=5.025,P=0.025;χ²=5.088,P=0.024）,周围神经炎发生率低于PTX组（χ²=4.711,P=0.030）。结论 Nab-PTX联合卡铂治疗头颈肿瘤的近期疗效显著,患者不良反应明显减少。     

紫杉醇的研究进展

在美国85岁以下的人群中,癌症是一种比心血管疾病更容易导致人类死亡的疾病。紫杉醇是目前用于对抗癌症最有效的药物之一,可以用来治疗转移性乳腺癌、晚期卵巢癌、非小细胞性肺癌、卡波济氏肉瘤等。紫杉醇是一种白色结晶体粉末,无臭、无味,不溶于水,易溶于有机溶剂氯仿、丙酮等。     

抗肿瘤新药紫杉醇

本实验继生脉散后报告炙甘草汤能提高心肌ＤＮＡ的合成率。证明了提高心肌ＤＮＡ合成并非偶然。同时报告了二参通脉汤增加肝脏细胞核蛋白的合成。     

紫杉醇脂质体与普通紫杉醇治疗胃癌疗效比较

目的 探讨采用周疗法紫杉醇脂质体联合方案和普通紫杉醇联合方案在治疗胃癌方面的临床疗效差异.方法 随机选取本院2009年2月~2012年11月期间收治的确诊为晚期胃癌的患者30例,随机平均分配为实验组和对照组,实验组采用紫杉醇脂质体进行联合治疗,对照组采用普通紫杉醇进行联合治疗,对比两组患者的临床疗效及毒副作用.结果 实验组患者治疗有效率为66.7%,对照组患者治疗有效率为60.0%,差异无显著性（P＞0.05）;两组患者的消化道及血液学毒性、脱发、呼吸困难及乏力等不良反应差异无显著性,但是对照组患者的面色潮红、肌肉及关节痛的发病率明显高于实验组患者（P＜0.05）.结论 采用紫杉醇脂质体较普通紫杉醇所取得的胃癌治疗效果无明显差异,但是前者能够明显降低患者毒副作用发病率,改善患者的治疗体验.     

紫杉醇国内外市场前景看好我国将成为紫杉醇产销大国

目前国际医药市场上抗癌药物品种多达七八十种,虽然种类不少,但没有一只抗癌药物能像紫杉醇那样在上市第二年即达2亿美元销售额。例如同为植物抗癌药,且开发上市已有半个世纪之久的长春新碱至今年销售额也不过在2亿美元左右。实际上国内外市场上的植物抗癌药至少有八九个品种,除紫杉醇和长春新碱外,还有鬼臼毒素衍生物（足叶乙甙）、喜树碱衍生物（如拓朴替康、伊立替康等）、莪术油提取物（榄香烯）、鸦胆子乳。     

紫杉醇产生菌发酵液树脂脱色和紫杉醇提取研究

目的:筛选能够对紫杉醇产生菌发酵液有效脱色同时制备高纯度紫杉醇的树脂及层析条件。方法:采用7种树脂对紫杉醇产生菌发酵液进行脱色和提取研究。结果:201×4型树脂处理样品的效果最好,80％的乙腈水溶液洗脱,紫杉醇的回收率为98．8％。结论:为提取紫杉醇提供一种操作简单、回收率高,污染较低的树脂层析方法。     

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.     

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.