粉防己碱，Fura 2－AM和Bay k 8644对脂多糖刺激大鼠腹腔巨噬细胞释放血小板活化因子的影响

目的：研究钙与脂多糖（ＬＰＳ）刺激大鼠腹腔巨噬细胞（ＰＭ）释放血小板活化因子（ＰＡＦ）的关系．方法：通过ＰＡＦ的生物测定法，观察了粉防己碱（Ｔｅｔ）、Ｆｕｒａ２ＡＭ和Ｂａｙｋ８６４４对ＬＰＳ刺激ＰＭ释放ＰＡＦ的影响．结果：ＬＰＳ刺激ＰＭ释放ＰＡＦ，但并不使其细胞内钙增高，Ｔｅｔ在０１，１０，１０，１００μｍｏｌ·Ｌ－１和Ｆｕｒａ２ＡＭ在００１，０１，１０，１０μｍｏｌ·Ｌ－１时降低ＬＰＳ刺激的ＰＭ释放ＰＡＦ（分别为９８±１１，６５±１６，４７±０８，３４±０４，９２±１７，５２±１３，３７±０４，３．２±０３μｇ·Ｌ－１，无药物时１１８±１２μｇ·Ｌ－１），Ｂａｙｋ８６４４在１０，５０，１０μｍｏｌ·Ｌ－１时能增加ＬＰＳ刺激的ＰＡＦ释放能增加ＬＰＳ刺激的ＰＡＦ释放（分别为１３２±１７，１６２±１４，１７６±１５μｇ·Ｌ－１），并且Ｂａｙｋ８６４４在５０μｍｏｌ·Ｌ－１时能全部或部分逆转Ｔｅｔ和Ｆｕｒａ２ＡＭ对ＰＡＦ释放的抑制作用．结论：尽管ＬＰＳ并不明显增加巨噬细胞内钙，但细胞内钙对ＬＰＳ刺激的ＰＡＦ释放是必要的．     

彗星试验检测7种化合物对外周血淋巴细胞DNA的损伤

目的：检测过氧化氢（Ｈ２Ｏ２）、甲磺酸乙酯（ＥＭＳ）、丝裂霉素Ｃ（ＭＭＣ）、二甲基亚硝胺（ＤＭＮＡ）、苯并（ａ）芘（ＢａＰ）、２－氨基Ｗｕ（２－ＡＦ）和环磷酰胺（ＣＰ）诱发小鼠、大鼠及人外周血淋巴细胞ＤＮＡ单链断裂。方法：体外单细胞微量凝胶碱性电泳试验（慧星试验）。结果：除ＥＭＳ０．９７ｍｍｏｌ·Ｌ＾－１在小鼠淋巴细胞，ＭＭＣ３０μｍｏｌ·Ｌ＾－１在小鼠、人淋巴细胞中呈阴性外，其余均为阳性。最低可     

Efectsofmoxonidineinjectedintorostralventrolateralmedulaonbloodpressure,heartrate,andrenalsympatheticnerveactivityinrats

目的：观察延髓腹外侧头端（ＲＶＬＭ）注射莫索尼定（Ｍｏｘ）对麻醉大鼠血压（ＢＰ）、心率（ＨＲ）及肾交感神经放电（ＲＳＮＡ）的影响．方法：麻醉大鼠ＲＶＬＭ注射１μＬＭｏｘ１，１０，１００μｍｏｌ·Ｌ－１，同步记录ＢＰ，ＨＲ及ＲＳＮＡ．结果：Ｍｏｘ１，１０，１００μｍｏｌ·Ｌ－１分别使ＢＰ从１３９±１０ｋＰａ降至１３０±１７ｋＰａ（Ｐ＜００５），１３８±１８ｋＰａ至１１４±１５ｋＰａ（Ｐ＜００１），ａｎｄ１３９±１９ｋＰａ至９４±１７ｋＰａ（Ｐ＜００１）．Ｍｏｘ不影响ＨＲ．Ｍｏｘ１μｍｏｌ·Ｌ－１增加ＲＳＮＡ５０％（Ｐ＜００５），１０μｍｏｌ·Ｌ－１对ＲＳＮＡ无影响（Ｐ＞００５），１００μｍｏｌ·Ｌ－１则降低ＲＳＮＡ２３％（Ｐ＜００５）．在缓冲神经切断大鼠，Ｍｏｘ１０μｍｏｌ·Ｌ－１抑制ＲＳＮＡ５０％（Ｐ＜００５），明显不同于缓冲神经完整的动物（Ｐ＜００１）．结论：麻醉大鼠ＲＶＬＭ注射Ｍｏｘ可降低ＢＰ，但不影响ＨＲ，且ＲＳＮＡ变化与其降压作用并不平行     

Regulatory role of protein tyrosine phosphorylation in platelet activating factor induced signal transduction in platelets 1

目的：研究蛋白酪氨酸磷酸化（ＰＴＰ）在血小板激活因子（ＰＡＦ）诱导血小板信号传导中的作用．方法：用水洗兔血小板考查Ｇｅｎ抑制聚集及５羟色胺释放,Ｆｕｒａ２和ＢＣＥＣＦ负载测胞内钙及ｐＨ,特异性抗酪氨酸单抗及免疫印迹法检测ＰＴＰ．结果：Ｇｅｎ１００和２００μｍｏｌ·Ｌ－１分别抑制ＰＡＦ诱导的５羟色胺释放为２３７％±２０％及４１％±８％,对胞内钙增加和Ｎａ＋／Ｈ＋交换也有抑制作用．ＰＡＦ增加Ｍｒ为７００００,６００００,５００００,４２０００／４００００,３４０００的ＰＴＰ．Ｇｅｎ２００,４００μｍｏｌ·Ｌ－１明显抑制该效应．用Ｓｔａ２０ｎｍｏｌ·Ｌ－１,ＢＡＰＴＡ２００μｍｏｌ·Ｌ－１,依他酸２ｍｍｏｌ·Ｌ－１,分别阻断ＰＫＣ及胞内钙增加和内流,也减少ＰＴＰ形成．结论：ＰＴＰ参与ＰＡＦ诱导血小板信号传导途径,ＰＫＣ活化和胞内钙动员对ＰＴＰ有调节作用．     

钙拮抗剂TMB-8抑制BHQ,NE和KCl引起的培养乳牛基底动脉单个平滑肌细胞内游离钙的升高

用ＡＲＣＭＭＩＣ阳离子测定系统，测量单个细胞内游离钙浓度（［Ｃａ２＋］ｉ），研究８（Ｎ，Ｎ二乙胺）ｎ辛基３，４，５三甲氧基苯甲酸酯（ＴＭＢ８）对培养乳牛基底动脉平滑肌［Ｃａ２＋］ｉ的作用。在细胞外钙浓度为１３ｍｍｏｌ·Ｌ－１时，ＴＭＢ８（３０μｍｏｌ·Ｌ－１）可明显抑制ＢＨＱ，ＮＥ及ＫＣｌ引起［Ｃａ２＋］ｉ的升高。在细胞外钙为零＋ＥＧＴＡ０１ｍｍｏｌ·Ｌ－１时，ＴＭＢ８（１０，３０及１００μｍｏｌ·Ｌ－１）可浓度依赖性地降低静息［Ｃａ２＋］ｉ，ＴＭＢ８（３０μｍｏｌ·Ｌ－１）可几乎完全阻断ＢＨＱ及ＮＥ引起［Ｃａ２＋］ｉ的增加。研究表明ＴＭＢ８降低培养乳牛基底动脉平滑肌［Ｃａ２＋］ｉ的机制，主要是抑制肌浆网Ｃａ２＋的释放，或增加肌浆网对Ｃａ２＋的摄入，并由此间接地抑制细胞外钙的内流。     

Effects of heparin on growth factor-induced mitogenic and proliferative responses of rat pulmonary a

目的：探讨肝素是否能抑制生长因子诱导的大鼠肺动脉平滑肌细胞（ＰＡＳＭＣ）分裂和增殖．方法：应用含１０％ＦＢＳ的Ｍ１９９培养液培养大鼠ＰＡＳＭＣ．细胞分裂及细胞增殖分别用［ｍｅｔｈｙｌ３Ｈ］ＴｄＲ和细胞计数监测．结果：ＦＢＳ（１０％），以及ＦＢＳ（１％）与ＰＤＧＦ（５０μｇ·Ｌ－１），ＦＧＦ（５０μｇ·Ｌ－１），或ＩＬ１α（１００ｎｇ·Ｌ－１）联合应用均能增加大鼠ＰＡＳＭＣ分裂．肝素（１００ｍｇ·Ｌ－１）抑制１０％ＦＢＳ诱导的大鼠ＰＡＳＭＣ增殖（２８％±６％）和胸腺嘧啶摄取反应（２７％±７％），抑制ＦＢＳ（１％）与ＰＤＧＦ（５０μｇ·Ｌ－１），ＦＧＦ（５０μｇ·Ｌ－１），或ＩＬ１α（１００ｎｇ·Ｌ－１）联用诱导的大鼠ＰＡＳＭＣ增殖（２５％±６％，２７％±７％，２０％±４％），以及胸腺嘧啶摄取反应（２３％±７％，２６％±６％，２０％±６％）．结论：肝素抑制生长因子诱导的大鼠ＰＡＳＭＣ的分裂与增殖．     

钙拮抗剂TMB-8对培养牛大脑中动脉内皮细胞[Ca2+]i和一氧化氮释放的影响

目的旨在观察ＴＭＢ８对血管内皮细胞［Ｃａ２＋］ｉ水平和ＮＯ释放的影响，探讨扩张脑血管的机制。用ＡＲＣＭＭＩＣ阳离子测定系统，测量单个细胞内游离钙浓度（［Ｃａ２＋］ｉ），用血红蛋白法测量一氧化氮（ＮＯ）的释放。结果表明，在细胞外钙浓度为１３ｍｍｏｌ·Ｌ－１时，ＴＭＢ８１２５及２５０μｍｏｌ·Ｌ－１对静息［Ｃａ２＋］ｉ和甲基血红蛋白ΔＥ无明显影响，而５０及１００μｍｏｌ·Ｌ－１时可升高静息［Ｃａ２＋］ｉ和甲基血红蛋白ΔＥ。表明ＴＭＢ８５０及１００μｍｏｌ·Ｌ－１升高脑血管内皮［Ｃａ２＋］ｉ，激活ＮＯ合酶，促进ＮＯ合成和释放，这可能是其扩张脑血管的重要机制之一。     

Effects of platelet activating factor and ginkgolid B on the cAMP levels in washed rabbit platelets

研究了血小板激活因子（ＰＡＦ）和ＰＡＦ拮抗剂银杏内酯Ｂ对洗涤兔血小板中ｃＡＭＰ含量的作用．结果表明ＰＡＦ（０．１－１．０μｍｏｌ·Ｌ－１）对血小板的基础ｃＡＭＰ水平无影响，但对前列腺素Ｅ１（ＰＧＥ１）２μｍｏｌ·Ｌ－１及４，５－二氢－６－［４－（１Ｈ－咪唑－１－）苯基］－５－甲基－３－（２Ｈ）－哒嗪酮（ＣＩ－９３０）２０μｍｏｌ·Ｌ－１引起的ｃＡＭＰ升高有显著的抑制作用．银杏内酯Ｂ能完全拮抗ＰＡＦ抑制ＰＧＥ１和ＣＩ－９３０升高ｃＡＭＰ的作用，ＩＣ５０分别为４．７和１２．５μｍｏｌ·Ｌ－１．合用磷酸肌酸／磷酸肌酸激酶和阿司匹林对ＰＡＦ和银杏内酯Ｂ的作用均无影响．提示ＰＡＦ对磷酸二酯酶的激活作用及腺苷酸环化酶的抑制作用是ＰＡＦ的直接作用，与其同ＰＡＦ受体结合有关．     

8-(N,N-Diethylamino)-n-octyl-3,4,5-trimethoxybenzoate reduced (Ca~(2 ))_i elevation induced by histamine,serotonin,and glutamate in cultured calf basilar artery smooth muscle cells

目的：研究８（Ｎ，Ｎ二乙胺）ｎ辛基３，４，５三甲氧基苯甲酸酯对培养乳牛基底动脉平滑肌［Ｃａ２＋］ｉ的作用．方法：采用ＡＲＣＭＭＩＣ阳离子测定系统，测量细胞内游离钙浓度（［Ｃａ２＋］ｉ）．结果：在细胞外钙浓度为１３ｍｍｏｌ·Ｌ－１时，ＴＭＢ８３０μｍｏｌ·Ｌ－１可明显抑制组胺，５羟色胺和谷氨酸引起的［Ｃａ２＋］ｉ的升高．在外钙为零＋依他酸０１ｍｍｏｌ·Ｌ－１时，ＴＭＢ８３０μｍｏｌ·Ｌ－１可明显降低静息［Ｃａ２＋］ｉ，ＴＭＢ８３０μｍｏｌ·Ｌ－１可几乎完全阻断组胺和５羟色胺增加［Ｃａ２＋］ｉ的作用．结论：ＴＭＢ８降低培养乳牛基底动脉平滑肌静息［Ｃａ２＋］ｉ，抑制Ｈｉｓ，５ＨＴ和Ｇｌｕ引起的［Ｃａ２＋］ｉ的增加．     

No functional β_3-adrenergic receptors expressed in rat skeletal muscle cells

目的：研究原代培养的大鼠骨骼肌细胞中是否存在功能性β３肾上腺素受体（β３ＡＲ）．方法：利用柱层析方法测定异丙肾上腺素（Ｉｓｏ），β３ＡＲ激动剂ＣＧＰ１２１７７Ａ和β３ＡＲ拮抗剂ＳＲ５９２３０Ａ对培养骨骼肌细胞环磷腺苷（ｃＡＭＰ）生成作用．结果：Ｉｓｏ剂量依赖性刺激骨骼肌细胞ｃＡＭＰ的生成，ＥＣ５０为１５１ｎｍｏｌ·Ｌ－１．普萘洛尔０．１μｍｏｌ·Ｌ－１抑制Ｉｓｏ刺激的ｃＡＭＰ的生成，ＫＢ值为３４７ｎｍｏｌ·Ｌ－１．ＣＧＰ１２１７７Ａ无刺激ｃＡＭＰ生成作用，但可抑制Ｉｓｏ的作用．ＳＲ５９２３０Ａ１０ｎｍｏｌ·Ｌ－１不能抑制Ｉｓｏ刺激ｃＡＭＰ的产生．结论：大鼠骨骼肌细胞中不存在功能性β３ＡＲ或至少不与腺苷酸环化酶耦联     

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.