海带褐藻多糖硫酸酯对小鼠急性肝损伤的保护作用

目的研究海带褐藻多糖硫酸酯(fucoidan from Laminaria japonica,FL)对四氯化碳所致小鼠急性肝损伤的保护作用。方法小鼠50只,随机分为正常组、模型组、阳性药对照组以及高、低剂量给药组,阳性药对照组灌胃联苯双酯100mg·kg~(-1),给药组分别按200,100mg·kg~(-1)剂量灌胃褐藻多糖硫酸酯,每天1次,连续给药10d。末次给药后1h,除正常对照组外其余各组均腹腔注射10%四氯化碳溶液0.1mL·(10g)~(-1)。24h后,取血测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)和总胆红素(BIL)水平,取肝脏称重,计算肝脏指数,同时观察肝脏病理学变化。结果高剂量的褐藻多糖硫酸酯能显著降低肝损伤小鼠血清ALT、AST和BIL水平,肝脏指数明显下降,病理观察结果也显示能减轻小鼠的肝损伤程度。结论褐藻多糖硫酸酯对四氯化碳所致小鼠急性肝损伤有保护作用。     

乙酰化海带褐藻多糖硫酸酯的制备及其抗氧化活性研究

目的 优选乙酰化海带褐藻多糖硫酸酯的制备方法,并测定不同条件下制备得到的乙酰化衍生物的体外抗氧化活性.方法 以甲酰胺为溶剂;乙酸酐为酰化试荆,N-溴代琥珀酰亚胺(NBS)为催化剂,采用正交设计法,考察反应时间、反应温度及酰化剂用量对海带褐藻多糖硫酸酯酰化反应的影响,测定不同条件下乙酰化衍生物的清除超氧阴离子、羟自由基和有机自由基DPPH的能力,及还原能力.结果 酰化荆用量和反应温度对海带褐藻多糖硫酸酯乙酰化有显著影响(P＜0.05).不同条件下制备的乙酰化衍生物的清除超氧阴离子、羟自由基和有机自由基DPPH的能力,及还原能力不同.结论 NBS作为催化荆对海带褐藻多糖硫酸酯进行乙酰化是可行的,可以代替传统毒性较强的吡啶对海带褐藻多糖硫酸酯的羟基进行乙酰化.乙酰化后多糖的抗氧化活性明显增强,对其进行深入研究有重要意义.     

褐藻多糖硫酸酯的药理学研究进展

目的 介绍褐藻多糖硫酸酯在药理学上的研究进展.方法 查阅国内外有关文献进行分析和综述.结果 褐藻多糖硫酸酯具有抗凝血作用、抑制平滑肌增殖、抗血管成形术后的再狭窄、对血管形成的影响、抗炎症反应、抗缺血、对肾脏胃黏膜的保护作用等.结论 褐藻多糖硫酸酯可能成为治疗人类许多疾病的重要药物.     

褐藻多糖硫酸酯抗PAF作用研究

目的：对从褐藻多糖硫酸酯分离的各组分进行抗PAF作用测定和化学分析，探讨其构效关系。方法：用碱提醇沉法获取褐藻中褐藻多糖硫酸酯的不同组分。用兔血小板聚集试验检测其抗PAF作用。用硫酸-咔唑法测定其葡萄糖醛酸含量，用氯化钡沉淀法测定其硫酸根含量，用硫酸-半胱氨酸法测定其岩藻糖含量。结果：研究结果表明，各组分均呈现出一定的抗PAF活性；各组分中岩藻糖含量变化不大，而SO4^2-和葡萄糖醛酸含量变化较大。葡萄糖醛酸含量愈低、硫酸根含量愈高，其抗PAF作用愈强。结论：褐藻多糖硫酸酯各组分均有一定的抗PAF活性，其作用随葡萄糖醛酸含量降低、硫酸根含量升高而增强。     

褐藻多糖硫酸酯的药理活性及作用机制研究进展

目的介绍关于褐藻多糖硫酸酯的最新药理活性的研究状况及可能的机制,为进一步研究其各种生物学功能提供参考。方法对近几年来有代表性的中英文文献进行分析、归纳。结果褐藻多糖硫酸酯拥有许多有前景的药理活性。结论加强对褐藻多糖硫酸酯的药理活性和作用机制的进一步研究,对于有目的的进行应用开发方面的研究有重要指导意义。     

褐藻多糖硫酸酯的抗炎与抗氧化活性研究进展

褐藻多糖硫酸酯是一种天然来源的海藻多糖，具有多种生物活性，尤其是抗炎和抗氧化应激活性近年来受到了研究者的广泛关注。研究表明，褐藻多糖硫酸酯可通过与细胞膜上的选择素结合而参与炎症的病理过程，也可作为清道夫受体的配体发挥抗炎症作用，它亦参与调节多种炎症相关因子的生成。褐藻多糖硫酸酯还可以抑制活性氧自由基的生成并促进其清除，从而表现出抗氧化活性。     

岩藻聚糖硫酸酯药理学活性研究进展

岩藻聚糖硫酸酯是一类来源于褐藻且结构复杂的海洋硫酸多糖,主要由硫酸化岩藻糖、半乳糖、甘露糖、葡萄糖醛酸及少量葡萄糖和木糖组成。研究表明,岩藻聚糖硫酸酯具有抗凝血与促凝血、抗炎、抗肿瘤、抗氧化、抗病毒、抗菌、免疫调节、降血脂、降血糖、抗补体及促进肠道益生菌生长等多种药理学活性。本文对岩藻聚糖硫酸酯的上述活性进行了综述,并对其应用前景进行展望,为其深度开发利用提供有用参考。     

褐藻多糖硫酸酯化学研究的进展

褐藻多糖硫酸酯是一类硫酸化多糖,存在于褐藻中,首先由Kylin在1913年用稀酸从掌状海带中提取出来。Kylin将提取物水解后分离出L-岩藻糖,他将这种多糖命名为fucoidin,现根据多糖的命名原则一般定名为fucoidan。中文名称以前一直称为墨角藻多糖、岩藻多糖或褐藻糖胶,但这一名称并不规范,本文称之为褐藻多糖硫酸酯。以后随着海藻化学和海藻工业的发展,陆续在褐藻多糖硫酸酯的分离纯化、组分、结构、理化性质、应用等方面进行了大量的工作。     

褐藻中岩藻聚糖硫酸酯抗凝血活性研究

目的对褐藻中岩藻聚糖硫酸酯的抗凝血活性进行研究。方法将20只新西兰白兔随机分为2组：岩藻聚糖硫酸酯组和空白对照组，分别测定其APTT、PT和TT。结果岩藻聚糖硫酸酯组和空白对照组APTT测定分别为62．7±11．3（s）、35．6±9．7（s），P〈0．05，差别有显著性意义；PT测定分别为19．5±4．8（s）、13．4±4．7（s），P〈0．05，差别有显著意义；TT测定分别为39．3±9．8（s）、21．5±7．3（s），P〈0．05，差别有显著性意义。结论褐藻中岩藻聚糖硫酸酯具有显著的抗凝血活性。     

桂郁金多糖抗凝血及纤溶活性研究

目的研究桂郁金多糖体内抗凝血作用和含药血清体外纤溶活性。方法小鼠连续3 d灌胃给予高、中、低剂量桂郁金多糖,分别检测全凝血时间(CT)、凝血因子Ⅱ(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)和凝血因子Ⅰ(Fbg),并将含药血清用纤维蛋白平板法进行体外纤溶试验。结果桂郁金多糖能明显延长CT、APTT和TT(P<0.05),对PT和Fbg无明显影响;含药血清体外无纤溶活性。结论桂郁金多糖具有显著的体内抗凝血活性,该药通过内源性凝血途径和共同凝血途径发挥抗凝血作用。     

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.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

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.     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

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.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.