南极海洋丝状真菌Lecanicillium kalimantanense HDN13-339 产生的胞外多糖结构表征及抗氧化活性研究D

目的 对来源于南极海洋丝状真菌Lecanicillium kalimantanense HDN13-339产生的胞外多糖的结构和抗氧化活性进行研究。方法 利用乙醇沉淀法、强阴离子交换色谱柱和凝胶渗透色谱柱对菌株所产胞外多糖进行分离纯化;通过PMP柱前衍生高效液相色谱法、红外光谱、气质联用色谱和核磁共振波谱对多糖的结构进行表征;通过测定DPPH自由基、超氧阴离子自由基、羟基自由基、ABTS自由基清除活性及Fe2+螯合能力研究胞外多糖的抗氧化活性。结果 从南极海洋丝状真菌Lecanicillium kalimantanense HDN13-339发酵产物中分离得到多糖HDN-51,其分子量为16.3 kDa,主要由甘露糖和半乳糖构成,糖链是由(1→)-Galf、(1→2)-Manp、(1→5)-Galf、(1→6)-Manp、(1→6)-Galf和(1→2,6)-Manp组成,HDN-51具有良好的抗氧化活性,特别是羟基自由基清除能力。结论　首次从南极海洋丝状真菌Lecanicillium kalimantanense HDN13-339中分离得到一种结构新颖的半乳甘露聚糖HDN-51,其具有一定的抗氧化活性。     

红树林根泥真菌Aspergillus versicolor sp.PJX-9胞外多糖结构特征及抗氧化活性研究

目的对来源于红树林根泥真菌Aspergillus versicolor sp.PJX-9胞外多糖进行结构和抗氧化活性的研究。方法利用乙醇沉淀法、强阴离子交换色谱和凝胶渗透色谱对菌株发酵液中的胞外多糖进行分离纯化;通过高效凝胶渗透色谱(HPGPC)、PMP柱前衍生高效液相色谱(HPLC)、红外光谱(IR)及气质联用色谱(GC-MS)等方法,研究胞外多糖的化学组成和结构特征;通过测定DPPH、超氧阴离子和羟基自由基清除率,研究胞外多糖的抗氧化活性。结果从发酵液中分离得到的多糖组分Pw1-1的分子量为12.3kDa,其主要由甘露糖组成,少量葡萄糖和半乳糖;Pw1-1糖链中主要为(1→2)-Manp,还有少量(1→6)-Manp、(1→6)-Glcp和(1→2,6)-Manp及末端Manp和Gal f;Pw1-1具有良好的体外抗氧化活性,随着浓度的增加清除能力亦增强,对DPPH、超氧阴离子和羟基自由基清除的EC50分别为3.39、1.50和1.72mg/mL。结论首次从红树林根泥真菌Aspergillus versicolor sp.PJX-9中分离得到胞外多糖Pw1-1,它是1种具有良好体外抗氧化活性的结构新颖的杂多糖。     

海洋真菌Cladosporium Sphaerospermum胞外多糖CS4-1结构特征和抗氧化活性

目的 对海洋真菌Cladosporium Sphaerospermum产生的胞外多糖CS4-1结构特征和抗氧化活性进行研究。方法 利用乙醇沉淀法、强阴离子交换色谱和凝胶渗透色谱对菌株所产胞外多糖进行分离纯化,运用PMP柱前衍生高效液相色谱法、高效凝胶渗透色谱法、气质联用色谱和化学方法分析多糖的结构特征,通过测定DPPH自由基、羟基自由基、ABTS自由基和超氧阴离子自由基清除活性以及还原能力评价多糖的抗氧化活性。结果 从海洋真菌Cladosporium Sphaerospermum发酵液中分离纯化得到胞外多糖CS4-1,其分子量为21.49 kDa;CS4-1含有甘露糖和半乳糖;糖链主要由Manp-(1→、→2)-Galp-(1→和→6)-Manp-(1→构成;CS4-1具有较好的抗氧化活性,在测定的5种活性指标中,清除超氧阴离子自由基的能力最强。结论 首次从海洋真菌Cladosporium Sphaerospermum分离得到抗氧化活性较好的多糖CS4-1,它是结构新颖的胞外多糖。     

红树林放线菌Streptomyces sp.CHQ-61产生的胞外多糖结构及自由基清除活性

目的 探究红树林放线菌Streptomyces sp.CHQ-61产生的胞外多糖的结构及自由基清除活性。方法 利用乙醇沉淀法、阴离子交换层析柱和凝胶层析柱对菌株发酵产物中的胞外多糖进行分离纯化,运用核磁共振、气质联用色谱、红外光谱、高效凝胶渗透色谱和柱前衍生高效液相色谱分析鉴定多糖的结构特征,采用DPPH、超氧阴离子和羟基自由基清除率评价胞外多糖的抗氧化活性。结果 从红树林放线菌Streptomyces sp.CHQ-61发酵产物中分离得到多糖XH-1,其分子量为8.9 kDa,丙酮酸含量为4.0 %,主要由半乳糖和氨基葡萄糖组成,糖链主要含有(1→6)Galp,还有少量的(1→3)GlcNp、(1→4,6)Galp、(1→3,6)GlcNp、末端Galp和GlcNp,XH-1具有一定的体外自由基清除活性,其清除DPPH、超氧阴离子和羟基自由基的EC50分别为0.5、0.8和3.0 mg/mL。结论 本文首次报道了红树林根泥放线菌Streptomyces sp.CHQ-61产生的胞外多糖XH-1为1种含有丙酮酸的半乳糖和氨基葡萄糖组成的结构新颖的胞外多糖,其具有较强的体外自由基清除活性。     

北极海洋真菌Aspergillus jensenii胞外多糖的结构及抗氧化活性研究

目的 对北极海洋真菌Aspergillus jensenii胞外多糖的结构及抗氧化活性进行研究。方法 采用醇沉法提取、强阴离子交换色谱和凝胶渗透色谱对胞外多糖进行分离纯化;运用PMP柱前衍生高效液相色谱、高效凝胶渗透色谱、气相色谱-质谱和核磁共振波谱对多糖结构进行分析;通过测定ABTS自由基、DPPH自由基、羟基自由基和超氧阴离子自由基的清除能力评价多糖抗氧化活性。结果 分离得到1种多糖AJ1-1,其主要由甘露糖和少量半乳糖组成,糖链是以→2)-α-D-Manp-(1→和→6)-α-D-Manp-(1→为主,分支位于→2)-α-D-Manp-(1→的C-6位和→6)-α-D-Manp-(1→的C-2位,支链由Galf和Manp组成;AJ1-1具有较强的清除自由基能力（特别是对ABTS自由基、DPPH自由基和羟基自由基）。结论 首次从北极海洋真菌Aspergillus jensenii发酵液中分离得到含有呋喃型半乳糖分支的新颖半乳甘露聚糖,其是1种潜在的抗氧化多糖。     

红树林根泥放线菌Saccharopolyspora sp.胞外多糖的结构研究

目的 对源自红树林根泥放线菌Saccharopolyspora sp.的胞外多糖进行分离和结构研究。方法 通过乙醇沉淀、Q Sepharose Fast Flow阴离子交换层析柱和Sephacryl S-100凝胶层析柱对菌株发酵液中的胞外多糖进行分离纯化;采用HPGPC和PMP柱前衍生HPLC对多糖的纯度、分子量和单糖组成进行测定;通过IR、甲基化分析和NMR波谱对多糖的结构进行表征。结果 从放线菌Saccharopolyspora sp. 发酵液中分离得到两种多糖SSW1-1和SSW2-1,在HPGPC上均呈单一对称峰,分子量分别为17.0 kDa和12.7 kDa;SSW1-1和SSW2-1具有相似的单糖组成,主要由甘露糖组成;胞外多糖SSW1-1是以(1→2)-Manp和(1→6-Manp为主链的甘露聚糖,在(1→2)-Manp的C6位存在末端Manp、(1→3)-Manp和(1→2)-Manp的分支。结论 首次从红树林根泥放线菌Saccharopolyspora sp.发酵液中分离得到胞外多糖SSW1-1和SSW2-1,它们具有不同化学特征,SSW1-1是一种结构新颖的高分支的甘露聚糖。     

紫贻贝粗多糖的提取及其体外抗氧化的研究

目的研究紫贻贝粗多糖的提取及其抗氧化活性。方法通过乙醇沉淀、Sevage法除蛋白后得到贻贝粗多糖。对其DPPH自由基清除能力、还原力、羟自由基清除能力进行测定,考察其抗氧化能力。结果在10～60μg·mL^-1浓度范围内,紫贻贝粗多糖显示良好的DPPH自由基清除能力、还原力及羟自由基清除能力,并且随着紫贻贝多糖浓度的升高而增加,同时,在此浓度范围内紫贻贝粗多糖的浓度与抗氧化活性呈较好的量效关系。结论紫贻贝粗多糖具有良好的抗氧化活性。     

锡兰海木耳多糖的提取、理化性质及抗氧化活性研究

目的 从红藻锡兰海木耳（Sarcodia ceylonensis）中提取多糖,对其化学组成和理化性质进行分析,并进行体外抗氧化活性评价。方法 依次通过冷水、热水（85 ℃）和4% NaOH溶液提取海木耳多糖;通过化学方法测定其总糖和硫酸根含量;利用PMP柱前衍生高效液相色谱法、高效凝胶渗透色谱法、红外光谱等方法对其单糖组成、相对分子质量和结构特征进行分析;通过测定其对超氧阴离子自由基（O2-）、羟自由基（?OH）和DPPH自由基的清除作用、对Fe2+的螯合能力和还原能力评价其体外抗氧化活性。结果 3种多糖SCW（冷水提取多糖）、SCH（热水提取多糖）和SCA（碱液提取多糖）的相对分子质量分别为6.65 × 105、2.55 × 105和1.35 × 105;单糖组成相似,均含有半乳糖、岩藻糖、甘露糖和葡萄糖醛酸,其中3,6-内醚-半乳糖和半乳糖含量均达到20%以上;硫酸根含量较高,分别为12.74%、13.46%和19.76%;3种多糖对O2-、?OH和DPPH自由基均有显著的清除作用,对Fe2+均表现出显著的螯合能力,其中SCA抗氧化活性最强。结论 从锡兰海木耳中提取得到3种硫酸多糖,均具有显著的体外抗氧化活性,为其将来作为食品和化妆品添加剂提供了有用参考。     

象拔蚌多糖体外抗氧化活性研究

目的研究象拔蚌多糖的体外抗氧化活性。方法检测象拔蚌多糖对1,1-二苯基-2-三硝基苯(DPPH)自由基清除活性及对大鼠肝脏匀浆一氧化氮合酶(NOS)、过氧化氢(H2O2)和丙二醛(MDA)含量的影响。结果象拔蚌多糖具有较强清除DPPH自由基活性,浓度达4 mg.mL-1时,抑制率为94.50%。象拔蚌多糖能降低大鼠肝脏匀浆H2O2和MDA含量,抑制NOS活性。结论象拔蚌多糖具有较强的体外抗氧化活性。     

3种海藻多糖抗氧化及其抗衰老活性的初步研究

为探讨海藻多糖抗氧化活性及抗衰老作用,体外测定昆布多糖,羊栖菜多糖,海蒿子多糖对羟基自由基,超氧自由基及其DPPH自由基的清除作用;采用秀丽隐杆线虫为研究模型,在培养基中添加不同浓度的海藻多糖,每日定时观察并记录线虫存活数,计算平均存活率。结果表明海藻多糖具有抗氧化能力,其中1.2mg/mL的昆布多糖羟基自由基清除能力最强,达到92.10%;海蒿子多糖DPPH自由基的清除能力最强,当浓度达到1.2mg/mL时,清除率为59.55%;1mg/mL海蒿子多糖超氧自由基的清除率达15.66%。秀丽隐杆线虫寿命实验表明,不同的海藻多糖均能延长线虫的寿命,且在实验浓度下,多糖浓度越高寿命延长越明显。研究结果表明所选海藻多糖具有显著的体外抗氧化活性,动物实验表明海藻多糖具有抗衰老作用,能显著延长线虫寿命。该结果为海藻多糖应用于医药、保健品领域的开发提供了一定的实验基础。     

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.     

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.     

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.