甲壳素的乙酰化制备及生物相容性评价

目的 制备乙酰化甲壳素（Acetylated Chitin,AC）并评价其生物相容性。方法 通过乙酸酐和乙酸混合体系制备AC。通过红外光谱和元素分析对AC进行表征,以L929细胞和Wistar大鼠为模型评价AC的细胞相容性和组织相容性。进行溶血实验检测AC的血液相容性。结果 红外光谱和元素分析结果显示,甲壳素的乙酰化反应发生在C3和C6位点,AC产物的酰化度为1.92。生物相容性评价结果显示,AC膜片的细胞毒性评级为0级;在肌肉组织植入初期有轻度炎症反应,降解速度缓慢;溶血率<5%,有良好的血液相容性。结论 成功制备了AC,并且其总体上具有良好的生物相容性。     

甲壳素疝补片修复大鼠腹壁部分缺损模型的研究

目的 评价制备的甲壳素疝补片的基本力学性能、细胞相容性及其对腹壁部分缺损大鼠模型的修复作用。方法 AGS-X拉力机测试甲壳素疝补片基本力学性能,评价甲壳素疝补片对L929细胞相容性,制作SD大鼠腹壁部分缺损模型,评价甲壳素疝补片对腹壁缺损的修复作用。结果 甲壳素疝补片无明显细胞毒性,较聚丙烯补片炎症反应轻,不引起腹壁组织生理结构的非正常变化,其力学强度还需要进一步提高。     

甲壳素衍生物神经导管的制备及其性质研究

目的 制备通透性良好的甲壳素衍生物神经导管,并研究其基本理化性质和生物相容性。方法 以碱化甲壳素为原料,涂层法制备不同醋酸钾含量的甲壳素衍生物神经导管;测定导管的吸水性、机械强度、通透性、降解性等;以 SD大鼠和RSC96细胞,评价神经导管的生物相容性。结果 神经导管的吸收性、机械强度、通透性因醋酸钾含量不同而变化。神经导管具备良好的组织相容性,降解炎症反应轻,对RSC96细胞具有较好的细胞相容性。     

壳聚糖基去甲斑蝥素膜片体内抗H22肿瘤生长的研究

目的 评价壳聚糖基水凝胶载去甲斑蝥素的抗肿瘤活性。方法 以叠氮化羟乙基壳聚糖(AZ-HE-CTS)为原料,制备了AZ-HE-CTS膜片,以小鼠成纤维细胞L929和SD大鼠模型评价细胞相容性和体内降解性;并制备了AZ-HE-CTS载去甲斑蝥素(NCTD)膜片,将载药膜片植入H22荷瘤小鼠体内给药,测定小鼠瘤重、胸腺指数、脾脏指数、血清中肿瘤坏死因子α(TNF-α)的浓度,评价载药膜片体内对H22肝肿瘤生长的抑制效果。结果 AZ-HE-CTS膜片具有良好的细胞相容性,体内降解缓慢,组织炎症反应轻;载药膜片原位植入对小鼠H22肿瘤具有抑制作用,能调动小鼠免疫系统,促进血清中TNF-α的表达。结论 壳聚糖基去甲斑蝥素膜片具有显著的抗肿瘤活性。     

肝素缓释膜材料的制备与评价*

目的 为建立一种长效的肝素给药途径,制备肝素缓释膜材料,并评价其性质。方法 利用明胶与肝素交联成膜,测定其肝素缓释性质、细胞相容性及动物组织相容性。结果 该材料具有良好的肝素缓释效果, L929成纤维细胞在材料表面的生长受到一定抑制作用,载药膜片皮下植入和肌肉植入能逐步降解,但在降解过程中有一定的炎症反应,组织相容性还需要进一步完善。结论 该材料肝素缓释能力持久,为肝素缓释给药提供了实验依据。     

磁性附着体中软磁合金引起小鼠成纤维细胞L929凋亡的研究

目的研究磁性附着体中软磁合金对小鼠成纤维细胞L929凋亡的影响,进而评价其生物相容性。方法提取含钛合金、软磁合金、钴铬合金的浸提液,分别以25%、50%、100%浓度处理L929细胞24 h,并测量细胞凋亡率(AP)。结果随着金属浸提液浓度的增加,L929细胞凋亡率亦增加,软磁合金与含钛合金及钴铬合金之间AP值的差异均无统计学意义(P>0.05)。结论本实验为磁性附着体的临床应用提供一定的生物学依据。磁性附着体中软磁合金的生物相容性要求合临床应用材料的要求,可以在临床推广。     

两种壳聚糖修饰材料细胞相容性及蛋白吸附行为的评价

目的对甘油明胶/壳聚糖(CGG)和玉米醇溶蛋白/壳聚糖(ZC)两种壳聚糖修饰生物材料的细胞相容性和蛋白吸附作用进行初步评价。方法应用M TT比色法,评价两种材料对L 929小鼠细胞的细胞毒性,测定他们对大鼠原代表皮细胞的细胞粘附率和细胞增殖率;同时应用考马斯亮兰G-250染色法测定材料对牛血清蛋白的吸附作用。结果本实验结果显示,两种壳聚糖修饰材料对L 929细胞生长抑制反应级别为1级或0级,属于无明显毒性作用。大鼠皮肤成纤维细胞在CGG上的粘附率和增殖率分别达到88.8%和96.0%;在ZC上的粘附率和增殖率分别达到80.7%和94.7%。两种材料不同时间对蛋白的吸附量存在有差异。结论两种修饰材料具有良好的细胞相容性,其中CGG在细胞体外增殖作用和蛋白吸附作用方面要优于单纯壳聚糖和ZC。     

美法仑-甘草次酸复合物的合成及其体外抗肿瘤活性研究

目的设计合成美法仑–甘草次酸复合物,并对其体内外抗肿瘤活性进行研究。方法以美法仑和18α-甘草次酸为原料,通过酯化、氧化、酰化和缩合反应制备目标化合物3a和3b,结构经元素分析、MS、1H-NMR确证,并采用MTT法对其体外抗肿瘤活性进行研究,同时考察了其对正常大鼠肝细胞BRL和小鼠成纤维细胞L929的细胞毒性。结果目标化合物3a、3b的体外抗肿瘤活性明显优于母体药物18α-甘草次酸和美法仑,且对正常细胞的毒性小于氮芥类药物美法仑。结论美法仑–甘草次酸复合物3a和3b抗肿瘤活性良好,具有开发成抗肿瘤候选药物的前景。     

复合海绵的细胞毒性及生物相容性研究

目的评价复合海绵的细胞毒性及生物相容性。方法采用MTT实验考察复合海绵浸提液对L929细胞增殖的抑制作用;扫描电镜观察L929细胞在海绵表面的生长情况;利用分光光度法测定其对鼠抗凝血的溶血作用;在鼠肝脏造成活性出血创面,用复合海绵或明胶海绵止血后,光镜观察海绵与肝脏组织的相容性。结果复合海绵浸提液对L929细胞增殖无抑制作用,该细胞可在海绵表面正常生长;无溶血作用,组织相容性较好。结论复合海绵无细胞毒性,且具有良好的生物相容性。     

银杏内酯纳米粒细胞毒性研究

目的研究制备的银杏内酯纳米粒的细胞毒性作用。方法小鼠成纤维细胞L929在含银杏内酯纳米粒的培养液中培养7d,并与同浓度的银杏内酯药物和空白纳米粒(PBCA)比较,MTT法观测细胞形态变化,测量吸光度,计算细胞相对增值率。结果银杏内酯组、银杏内酯纳米粒组与空白纳米粒组对L929细胞的生长抑制作用无统计学差异(P>0.05),而且细胞毒性均为Ⅰ级。结论银杏内酯纳米粒对L929细胞无明显的细胞毒性。     

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.