7－氯苄基四氢巴马汀的抗心律失常作用

７－氯苄基四氢巴马汀５ｍｇ·ｋｇ－１可明显拮抗乌头碱，哇巴因，氰仿所致的心律失常以及提高猫心电致颤阈，１０ｍｇ·ｋｇ－１时，还可抗ＣａＣｌ２所致的大鼠室颤，其提高猫心电致颤阈的作用比奎尼丁稍强。７－氟节基四氢巴马汀可浓度依赖性地降低蟾蜍坐骨神经动作电位的振幅和零相最大上升速率，延长传导延迟。在豚鼠心乳头状肌动作电住实验中，７－氯苄基四氨巴马汀亦能浓度依赖性地延长动作电位时程及有效不应期并能降低动作电位的振幅和零相最大上升速率。     

7－氯苄基四氢巴马汀对豚鼠乳头肌迟后去极，触发活动及猫心单相动作电位的影响

７一氯苄基四氢巴马汀对豚鼠乳头肌迟后去极，触发活动及猫心单相动作电位的影响夏国瑾，曾维忠，姚伟星，戴水平，江明性，黄文龙，黄忱亚，彭司勋（同济医科大学药理学教研室，武汉４３００３０；中国药科大学药物化学研究室，南京２１０００９）７－氯苄基四氢巴马汀（...     

7一氯苄基四氢巴马汀对大鼠α肾上腺素受体及心电图的影响

在大鼠肛尾肌标本，７－氯苄基四氢巴马汀（７－ｃｈｌｏｒ－ＢＴＨＰ）１０μｍｏｌ·Ｌ－１能竞争性地抑制苯福林致肛尾肌收缩的量效曲线，使量效曲线右移，最大效应不变，其ｐＡ２值为５．９，但对可乐定抑制电场刺激所致的大鼠输精管收缩的量效曲线无影。在毁脊髓大鼠，７－ｃｈｌｏｒ－ＢＴＨＰ５ｍｇ·ｋｇ－１在不同刺激频率下可使心率减慢，但对电刺激所致的血压升高无影响。７－ｃｈｌｏｒ－ＢＴＨＰ恒速灌注，能剂量依赖性地延长心电图Ｐ－Ｒ间期及减慢心率，直至动物死亡也未见过速性心律失常发生。     

The Effect of Benzyltetrahydropalmatine (BTHP) on Action Potentials and the Two Components of Delayed Rectifying Potassium Currents in Guinea Pig Ventricular Myocytes

苄基四氢巴马汀为四氢巴马汀的衍化物，本文采用标准膜片钳全细胞记录技术，研究了苄基四氢巴马汀对豚鼠心室肌单细胞动作电位及延迟整流钾通道（Ｉｋ）两种成分（Ｉｋｓ和Ｉｋｒ）的选择性作用。结果表明：（１）３０μｍｏｌ·Ｌ－１苄基四氢巴马汀可显著延长无钙细胞外液条件下动作电位的ＡＰＤ９０（从１４３±１６ｍｓ到１８４±２１ｍｓ，Ｐ＜００１，ｎ＝５），而对ＲＰ，ＡＰＡ无明显影响，其对ＡＰＤ９０的延长作用不依赖于胞外钙。（２）苄基四氢巴马汀对延迟整流钾通道两种成分均有不同程度的阻滞作用，其阻滞Ｉｋｒ的ＩＣ５０（半数抑制浓度）为７９μｍｏｌ·Ｌ－１，阻滞Ｉｋｓ的ＩＣ５０为２２４μｍｏｌ·Ｌ－１，可见苄基四氢巴马汀对Ｉｋ的阻滞作用无选择性     

7-氯苄基四氢巴马汀对离体大鼠心肌缺血再灌损伤的保护作用

目的：研究７－氯苄基四氢巴马汀对离体大鼠心肌缺血再灌损伤的影响。方法：利用Ｌａｎｇｅｎｄｏｒｆ大鼠心脏，结扎冠状动脉前降支（ＬＡＤ），缺血１０ｍｉｎ后，再灌注２０ｍｉｎ，造成缺血再灌损伤模型。结果：７－氯苄基四氢巴马汀（７－ｃｈｌｏｒＢＴＨＰ）可明显减慢心率，消除再灌注引起的心室纤颤，明显缩短心律失常持续时间，并能抑制离体大鼠心肌缺血、复灌时磷酸肌酸激酶（ＣＰＫ）及乳酸脱氢酶（ＬＤＨ）释放增加。结论：７－ｃｈｌｏｒＢＴＨＰ具有抗离体大鼠再灌注心律失常作用，对缺血再灌注损伤心肌有保护作用，其作用机制可能与其减慢心率，减少缺血复灌时心肌酶释放有关。     

苄基四氢巴马汀对缺血—复灌与单相动作电位的影响

苄基四氢巴马汀(benzyltetrahydropalmatin,BTHP)是四氢巴马汀的衍生物,剂量1～10mg/kg有抗多种实验性心律失常的作用,对大鼠心缺血—复灌所致心律失常也有效。本文观察BTHP对在位猫心缺血—复灌时单相动作电位(MAP)变化的影响。     

dl-四氢巴马汀对家兔窦房结和豚鼠心室肌慢反应电活动的影响

用细胞内固定微电极技术观察到dl-四氢巴马汀(THP)30～100μM使家兔窦房结细胞动作电位的振幅(APA)、零相去极化速率(SP_0)和舒张期4相去极化速率(SP_4)逐渐降低,小剂量使动作电位复极90％的时程(APD_(90))延长,大剂量使其缩短,并使心率(HR)减慢。THP 30～300μM使高K~+除极和河豚毒素(TTX)所致的豚鼠乳头状肌细胞慢反应动作电位的APA、零相最大上升速率(V_(max))逐渐降低,复极50％的时程(APD_(50))缩短。实验结果提示THP可能有钙拮抗作用。     

四丙酰关附醇胺的抗心律失常作用及其与关附甲素的比较

在几种动物模型上观察了四丙酰关附醇胺（ＴＰＧＦＡ）的抗心律失常作用．ＴＰＧＦＡ使引发室性早搏，室性心动过速和心室纤颤所需乌头碱用量增加５０％的剂量分别为１．６，１．４ＦＫ和１．８ｍｇ·ｋｇ－１；ＴＰＧＦＡ２ｍｇ·ｋｇ－１可提高豚鼠心脏毒毛花苷Ｇ中毒的耐受量和家兔心脏电致室颤阈；ＴＰＧＦＡ还降低Ｃａ－Ｃｌ２诱发的大鼠室颤发生率和死亡率，以及麻醉大鼠心脏冠脉结扎—再灌性室性心动过速和室颤的发生率．ＴＰＧＦＡ的上述抗心律失常作用较关附甲素强．ＴＰＧ－ＦＡ显著延长大鼠心电图的ＱＴｃ间期，而对Ｐ－Ｒ间期和ＱＲＳ时程影响不明显．小鼠ｉｖＴＰＧＦＡ的ＬＤ５０为４２ｍｇ·ｋｇ－１．     

蛇床子素对麻醉开胸犬心电图和血流动力学的影响

麻醉开胸犬，ｉｖ７．５－１５ｍｇ·ｋｇ￣（－１）蛇床子素后，收缩期血压，舒张期血压，平均血压，左室收缩压，室内压最大上升速率及心输出量，总外周阻力均降低，在１０ｍｉｎ时为作用高峰；ｉｖ７．５ｍｇ·ｋｇ￣（－１），心电困无影响，但ｉｖ１５ｍｇ·ｋｇ￣（－１），心电图的Ｐ－Ｒ间期略延长。且室内压最大下降速率也降低。提示蛇床子素有抑制心脏作用，且外周阻力降低，血压下降，故在临床应用时应引起注意。     

7-氯苄基四氢帕马丁及奎尼丁对豚鼠离体心房及大鼠血管环的作用比较

７－氯苄基四氢帕马丁（７－Ｃｌ－ＢＴＨＰ）及奎尼丁（Ｑｕｉ）均能明显延长豚鼠离体左心房的功能性不应期,显著抑制肾上腺素诱发的自律性,但７－Ｃｌ－ＢＴＨＰ能明显增强豚鼠离体左心房的收缩力,而Ｑｕｉ则对其无影响．在心脏肥厚大鼠及正常大鼠的离体主动脉环,７－Ｃｌ－ＢＴＨＰ及Ｑｕｉ对去甲肾上腺素所致的收缩均有抑制作用．７－Ｃｌ－ＢＴＨＰ的ＩＣ５０分别为７６及３９μｍｏｌ·Ｌ－１,而Ｑｕｉ的ＩＣ５０则分别为４．６及８μｍｏｌ·Ｌ－１．Ｑｕｉ对氯化钾所致心脏肥厚及正常大鼠主动脉环的收缩有明显的抑制作用,其ｐＤ２′分别为４．３及４．０,而７－Ｃｌ－ＢＴＨＰ则对其无影响．结果提示７－Ｃｌ－ＢＴＨＰ的抗心律失常作用可能与延长不应期,降低自律性和抗α受体作用有关．     

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.

     

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.     

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.     

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.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.