粉防己碱对兔血小板聚集和血小板活化因子生成的影响(英文)

目的:探讨粉防己碱(Tet)对兔血小板聚集和PAF生成的影响.方法:卡西霉素(Cal)和PAF诱导血小板聚集的聚集率和Tet对血小板聚集的抑制率被测定;给予或未给予Tet处理之血小板用Cal刺激释放PAF的量也被测定.结果:在4—64 μmol·L~(-1)浓度范围,Tet明显抑制Cal和PAF诱导的血小板聚集.IC_(50)值分别为8.6μmol·L~(-1)和14.0μmol·L~(-1).Tet也浓度依赖性的抑制Cal诱导血小板释放PAF,IC_(50)值为21.0μmol·L~(-1).结论:Tet抑制血小板聚集作用与抑制内源性PAF生成有关.     

粉防己碱抑制豚鼠离体气道C神经纤维兴奋引起的收缩(英文)

目的:研究粉防己碱(Tet)对豚鼠离体气管/支气管的感觉神经C纤维兴奋的抑制作用.方法:记录电场刺激所致的C纤维兴奋所产生的标本收缩(phase Ⅱ)张力,了解Tet的作用.结果:Tet 0.3—30 μmol·L~(-1)抑制phase Ⅱ收缩,在气管/支气管上,Tet 1 μmol·L~(-1)的抑制率分别是:40±38％和75±22％;用氯苯那敏或阿托品作用后,Tet 1 μmol·L~(-1)的抑制率分别是70±16％和64±16％;Tet不抑制外源性P物质引起的标本收缩.结论:Tet 1μmol·L~(-1)抑制豚鼠离体气道收缩的机理与其抑制感觉神经C纤维兴奋释放神经肽的作用有关.     

粉防己碱对缺氧诱导的大鼠大脑皮层神经元NMDA受体通道变化的影响

目的:研究Tet对缺氧大鼠大脑皮层神经元NMDA受体通道变化的影响。方法:细胞贴附膜片箝法。用95％N_2 5％CO_2饱合无糖浴液产生细胞缺氧模型。结果:在缺氧状态下,35pS通道开放时间常数τ_2,35和100pS通道开放概率增加,Tet 7.5μmol·L~(-1)降低缺血所致35和100 pS通道开放概率,15和30μmol·L~(-1)完全抑制100pS通道,改变35pS的开放时间常数为单指数分布。结论:抑制缺氧所致NMDA受体通道开放是Tet对受缺氧损伤大脑保护作用的机制之一。     

三七超临界CO_2萃取物对谷氨酸损伤PC12细胞的保护作用

目的研究三七超临界CO_2萃取物(SFE)对谷氨酸损伤PC12细胞的保护作用,并探讨其可能作用机制。方法以谷氨酸损伤PC12细胞为模型,采用MTT法检测细胞存活率,LDH法检测乳酸脱氢酶的漏出率,Hoechst 33342染色法检测细胞凋亡,Fluo-3/AM荧光染色法检测细胞内钙离子浓度,Western blot法检测PICK1、GluR2蛋白的表达。结果谷氨酸对PC12细胞具有兴奋性毒性作用,其半数抑制浓度(IC50)为25 mmol·L~(-1)。不同浓度三七SFE(25、50、100 mg·L~(-1))、PICK1抑制剂FSC231(100μmol·L~(-1))、三七SFE(100 mg·L~(-1))+FSC231(100μmol·L~(-1))预处理可明显提高细胞存活率,减少LDH的释放,降低PC12细胞的凋亡率,减少钙离子内流,降低PICK1蛋白表达,增加GluR2蛋白表达。结论三七超临界CO_2萃取物对谷氨酸损伤后的PC12细胞具有保护作用,机制可能与抑制PICK1、增加GluR2蛋白表达有关。     

粉防己碱对吗啡在离体豚鼠回肠中依赖性的作用(英文)

目的:研究粉防己碱(Tet)和尼莫地平(Nim)对吗啡在离体豚鼠回肠中戒断性反应的影响。方法:戒断性收缩由纳洛酮(1μmol·L~(-1))加入已在含吗啡(3μmol·L~(-1))的37.5℃ Krebs液中孵育4h的离体豚鼠回肠或加入从吗啡依赖豚鼠中取得的回肠引起。结果:离体豚鼠回肠在含吗啡的Krebs液中孵育4h,给Nim(0.01、0.05和0.1μmol·L~(-1))或Tet(1、10和50μmol·L~(-1))抑制其戒断性收缩。Nim和Tet体内或体外给药都能抑制吗啡依赖豚鼠离体回肠的戒断性收缩。结论:钙拮抗剂Nim和Tet抑制吗啡在离体豚鼠回肠的戒断性收缩。     

对乙酰氨基酚对肝细胞自噬行为的研究

目的研究对乙酰氨基酚对肝细胞自噬行为的影响。方法采用肝细胞模型,对乙酰氨基酚浓度1~8 mmol·L~(-1),检测肝细胞活力指标、肝细胞形态指标以及肝细胞自噬指标。结果对乙酰氨基酚在浓度1~8 mmol·L~(-1)范围内,浓度依赖的抑制肝细胞活力,改变肝细胞的形态结构;MDC观察自噬体结果提示在浓度0.5~8 mmol·L~(-1)范围内,能使肝细胞自噬明显升高,上调基因Beclin~(-1)的表达,自噬升高幅度呈现上升后下降的趋势,转折点为1 mmol·L~(-1)。结论本研究结果得出,对乙酰氨基酚能影响肝细胞的自噬行为,在0.5~1 mmol·L~(-1)浓度范围内,促进自噬;在2~8 mmol·L~(-1)浓度范围内,对自噬的促进作用逐渐减弱。     

粉防己碱和氯丙嗪对人胚肺成纤维细胞胶原和透明质酸合成的影响(英文)

目的：研究粉防己碱(Tet)和氯丙嗪(Chl)对人胚肺成纤维细胞胶原与透明质酸(HA)合成的影响,为应用钙拮抗剂防治器官纤维化提供依据.方法:采用[~3H]脯氨酸掺入和放射免疫法分别测定胶原与HA合成.结果:Tet 5—80 μmol L~(-1)和Chl 10—40 μmol L~(-1)均以浓度依赖方式抑制胶原与HA合成.Tet 5—20μmol L~(-1))对细胞无明显毒性却显著抑制胶原与HA合成(P<0.01).结论:Tet在低浓度(5—20μmol L~(-1))时对细胞无明显毒性作用而显著抑制成纤维细胞胶原与HA合成,可望成为治疗器官纤维化的有效药物.     

蛴螬多糖的急性毒性及对肝损伤的保护作用

目的评价蛴螬多糖的急性毒性并研究其对肝损伤的保护作用。方法用最大耐受量法测定蛴螬多糖小鼠腹腔注射的急性毒性。高剂量重复给药2周,观察肝功能及病理改变。采用四氯化碳(CCl_4)建立小鼠急性肝损伤模型,通过检测血清酶水平及肝组织病理改变来评价蛴螬多糖对急性肝损伤的影响。体外培养正常人肝细胞HL7702,MTT法测定蛴螬多糖对肝细胞活力的影响,丙二醛(MDA)和超氧化物歧化酶(SOD)含量测定分别检测蛴螬多糖对脂质过氧化的影响。结果蛴螬多糖对小鼠腹腔注射的最大耐受量为8 g·kg~(-1)。高剂量重复给药2周可明显降低正常大鼠肝脏中谷草转氨酶(AST)的含量,但对肝组织结构和凝血时间等无明显影响。蛴螬多糖25,50和100 mg·kg~(-1) 3个剂量组均可降低模型血清谷丙转氨酶(ALT)、AST和碱性磷酸酶(ALP)的水平,减轻肝损伤的组织病理变化程度;且呈剂量依赖性。体外实验发现,蛴螬多糖质量浓度在0.1～100 mg·L~(-1)范围内对肝细胞无毒,质量浓度为0.3～100 mg·L~(-1)时可抑制受损肝细胞,存活率下降;蛴螬多糖能明显抑制受损肝细胞MDA水平的升高和SOD活性的减弱。结论蛴螬多糖腹腔注射无明显毒性,大剂量注射未引起肝损伤;对CCl_4诱导的小鼠急性肝损伤具有明显的保护作用,其机制可能与抗氧化有关。     

牛磺酸对半乳糖胺及硫酸亚铁-抗坏血酸所致大鼠肝细胞损伤的保护作用

以半乳糖胺(Galn)和硫酸亚铁-抗坏血酸(Fe-Vit C)与原代肝细胞共同培养,制成不同的肝细胞损伤模型,用不同浓度的牛磺酸预处理,以观察其对肝细胞的保护作用,结果表明:Fe—Vit C作用60min即可引发肝细胞的脂质过氧化(LPO),使培养液中的丙二醛含量明显升高,但不造成肝细胞破坏,0.6～3mmol·L~(-1)牛磺酸可明显减轻LPO程度,而浓度为30～60mmol·L~(-1)时非但不能减少LPO,反而使乳酸脱氢酶(LDH)的释放明显升高,Galn则可造成明显的肝细胞损伤,使LDH释放,0.6～3 mmol·L~(-1)牛磺酸对于这种肝细胞损伤有一定的保护作用,而30～60 mmol·L~(-1)的牛磺酸本身则可造成正常及中毒肝细胞的损伤。     

五味子酚对大鼠嗜中性白细胞功能与形态的作用(英文)

目的:探讨五味子酚(Sal)对大鼠嗜中性白细胞(Neu)功能的调节作用.结果:Sal 1,10,100μmol·L~(-1)剂量依赖性抑制Neu功能,Sal 100μmol·L~(-1)使Neu表面伪足和皱褶消失,并可降低细胞内钙离子浓度、升高细胞内cAMP水平.结论:Sal可通过影响细胞内钙离子浓度、cAMP水平及细胞表面形态抑制Neu的功能.     

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.     

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.     

Emerging drugs for epilepsy

Epilepsy affects ≤ 1% of the world's population. Antiepileptic drugs (AEDs) are the mainstay of treatment, although more than a third of patients are not rendered seizure free with existing medications. Uncontrolled epilepsy is associated with increased mortality and physical injuries, and a range of psychosocial morbidities, posing a substantial economic burden on individuals and society. Limitations of the present AEDs include suboptimal efficacy and their association with a host of adverse reactions. Continued efforts are being made in drug development to overcome these shortcomings employing a range of strategies, including modification of the structure of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening of compounds in traditional and newer animal models. This article reviews the need for new treatments and discusses some of the emerging compounds that have entered clinical development. The ultimate goal is to develop novel agents that can prevent the occurrence of seizures and the progression of epilepsy in at risk individuals.     

盐酸达泊西汀中甲磺酸甲酯、甲磺酸乙酯及甲磺酸异丙酯的顶空毛细管GC-ECD法测定

建立了衍生化顶空毛细管气相色谱-电子捕获检测器(ECD)法测定盐酸达泊西汀中的甲磺酸甲酯(MMS)、甲磺酸乙酯(EMS)和甲磺酸异丙酯(IMS).应用碘化钠衍生技术,使用PW-5毛细管柱,载气为氮气,ECD检测,程序升温.MMS、EMS和IMS分别在0.03～0.30、0.05～0.50和0.05～0.50 μg/ml浓度范围内线性关系良好,平均回收率分别为63.5％、100.3％和96.2％,最低检测限分别为0.30、0.50和0.50 ng/ml.     

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.