牛磺酸对豚鼠乳头状肌慢反应动作电位的影响(英文)

目的:研究牛磺酸对豚鼠乳头状肌慢反应动作电位的影响.方法:高钾(24 mmol·L~(-1))或河豚毒素(40 μmol·L~(-1))诱发慢反应动作电位.哇巴因诱发振荡后电位.结果:牛磺酸(20mmol·L~(-1))减少V_(max),延长APD_(50)并拮抗氯化钙(3 mmol·L~(-1))增加APA和V_(max)及缩短APD的作用,增加哇巴因诱发OAP所需浓度并延长其发生时间.结论:牛磺酸有钙拮抗剂的性质     

胍丁胺对异丙肾上腺素诱发豚鼠乳头状肌后除极的影响(英文)

目的:研究胍丁胺(Agm)对异丙肾上腺素(Iso)诱发豚鼠乳头状肌早发和晚发后除极(EAD和DAD)的影响及其作用机制。方法:细胞内玻璃微电极技术。结果:(1)Agm明显抑制Iso诱发的EAD和DAD;(2)预先应用NOS抑制剂L-NAME0.5mmol·L~(-1),不能影响Agm1.0mmol·L~(-1)对Iso 20nmol·L~(-1)诱发EAD和DAD的抑制作用;(3)预先应用咪唑啉受体(IR)和肾上腺素能α_2受体(α_2-AR)拮抗剂idazoxan 0.1mmol·L~(-1)则可阻断这种作用。结论:Agm对Iso诱发EAD和DAD的抑制作用由α_2-AR和/或IR介导,并与钙内流减少有关。     

环戊腺苷对异丙肾上腺素诱发的豚鼠乳头状肌后除极和触发活动的影响(英文)

目的:观察选择性A_1受体激动剂环戊腺苷(CPA)对异丙肾上腺素(Iso)诱发的豚鼠乳头状肌后除极和触发活动的影响.方法:应用Iso 50 nmoi·L~(-1)诱发稳定而可重复的早发和迟发后除极(EAD和DAD).用玻璃微电极技术记录EAD和DAD诸参数.结果:CPA能明显地缓解Iso诱发的豚鼠乳状肌早发后除极、迟发后除极和触发活动.8-苯茶碱和格列苯脲能拮抗CPA对Iso诱发早发和迟发后除极的抑制作用.结论:ATP敏感性钾通道参与了Iso诱发的早发和迟发后除极以及CPA对Iso诱发的两种后除极的抑制作用.     

雌二醇抑制豚鼠心室肌细胞内向整流和延迟整流钾通道电流

目的:研究雌二醇(Estradiol,Est)对心室肌细胞动作电位(AP)、内向整流钾通道电流(I_(K1))及延迟整流钾通道电流(I_K)的影响。方法:全细胞膜片箝技术。结果:EST 10μmol·L~(-1)使豚鼠心室肌细胞AP时程明显缩短,APD_(50)由给药前(474±71)ms缩短至(330±75)ms(P<0.05),Est 100μmol·L~(-1)使APD_(50)缩短至(229±67)ms(P<0.01),使APD_(90)由(587±60)ms缩短至(418±79)ms(P<0.05)。Est浓度依赖性地抑制I_K尾电流(I_K·tail),10μmol·L~(-1)浓度下,I_K·tail减少53％(P<0.05),100μmol·L~(-1)浓度下,I_K·tail减少80％(P<0.05)。10μmol·L~(-1)以上浓度Est明显抑制I_(K1),在-100mV刺激电压下,内向电流最大抑制为49％(P<0.01);在-40mV刺激电压下,外向电流最大抑制为72％(P<0.01)。同时,Est使I_(K1)翻转电位向负电位方向移位(由-70mV变为-76mV)。结论:Est对豚鼠心室肌细胞I_(K1)和I_K通道具有明显的抑制作用。     

未成年人心房肌细胞瞬间外向钾电流和内向整流钾电流的特性(英文)

目的:研究未成年人心房肌细胞瞬间外向钾电流(I_(to))和内向整流钾电流(I_(Kl))的特性。方法:膜片箝全细胞技术。结果:I_(to)是电压依赖性电流,快速激活,快速失活,被I_(to)的选择性阻断剂4-AP阻断。IC_(50)=0.64mmol·L~(-1)。4-AP1mmol·L~(-1)使I_(to)的半数激活电位增加;4-AP0.3mmol·L~(-1)使I_(to)的半数失活电位减少,对激活曲线没有明显影响并使I_(to)的恢复时间延长。I_(Kl)也表现出电压依赖的特性,其反转电位在-40mV。结论:在未成年人心房肌细胞上,I_(to)和I_(Kl)是两种重要的K~ 通道电流。4-AP0.3mmol·L~(-1)时对I_(to)的失活和失活后的恢复有明显影响,1mmol·L~(-1)时影响I_(to)的激活。     

粉防己碱抗氯化铯诱发家兔在体心脏早期后除极化及心律失常的作用

目的　研究粉防己碱 (Tet)抗氯化铯 (CsCl)诱发触发活动及触发性心律失常作用。方法　 14只家兔分对照组和Tet组 ,Tet组给予Tet 0 5mg·kg-1·min-1共 10min ,对照组给予生理盐水 ,然后给予CsCl1 5mmol/kg静脉注射 ,给药前后记录心电图和右室心内膜单向动作电位 (MAP)。结果　Tet组和对照组均诱发早期后除极 (EAD) ,但Tet组EAD幅度小于对照组 ,室性心律失常发生率低于对照组。结论　Tet有抗CsCl诱发EAD及室性心律失常作用。其机制可能是Tet抑制慢钙通道 ,减少内向电流     

1—（2，6—二甲基苯氧基）—2—（3，4—二甲氧基苯乙氨基）丙烷盐酸盐抑制豚鼠心室肌细胞内向整流和延迟整流钾电流

目的:研究1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙氨基)丙烷盐酸盐(DDPH)对心室肌细胞动作电位(AP)、内向整流钾通道电流(I_(K1))及延迟整流钾通道电流(I_K)的影响。方法:全细胞膜片箝技术。结果:DDPH 10,100μmol·L~(-1)使豚鼠心室肌细胞AP时程APD_(50)明显缩短;但DDPH(>1μmol·L~(-1))延长APD_(90)。DDPH浓度依赖性地抑制I_K尾电流(I_(K·tail)),EC_(50)为13.3(11.6.6-16.7)μmol·L~(-1)。DDPH(>1.0μmol·L~(-1))明显抑制I_(Kl);同时,DDPH使I_(Kl)翻转电位向正电位方向移动。结论:DDPH对豚鼠心室肌细胞I_(Kl)和I_K具有明显的抑制作用。     

多柔比星对大鼠离体胸主动脉和颈总动脉血管环的舒张作用及其机制

目的研究多柔比星(DOX)对大鼠离体胸主动脉和颈总动脉血管环的作用及其机制。方法采用离体血管环恒温灌流系统,通过累积加药法每10 min加入DOX依次使其终浓度递增为1,3,10,30和100μmol·L~(-1),观察其对基础状态、去氧肾上腺素(PE,1μmol·L~(-1))和氯化钾(KCl,60 mmol·L~(-1))预收缩的胸主动脉及颈总动脉血管环的作用,并采用左旋硝基精氨酸甲酯(L-NAME)、4-氨基吡啶(4-AP)、溴化四乙铵(TEA)、氯化钡(BaCl_2)、格列苯脲(Gli)、吲哚美辛(Indo)和普萘洛尔预处理探讨其对血管作用的可能机制。结果 DOX对基础状态下及KCl预收缩的胸主动脉和颈总动脉血管环张力无明显影响;DOX可浓度依赖性地舒张PE预收缩的内皮完整胸主动脉和颈总动脉环(P<0.05),且其对去内皮胸主动脉血管环也有舒张作用,但舒张程度弱于内皮完整组(P<0.05);一氧化氮合酶抑制剂L-NAME 0.1 mmol·L~(-1)、电压依赖性钾通道(K_V)抑制剂4-AP 1 mmol·L~(-1)、钙敏感性钾通道(K_(Ca))抑制剂TEA 1 mmol·L~(-1)和内向整流型钾通道(K_(IR))抑制剂BaCl_21 mmol·L~(-1)均可明显抑制DOX的舒血管作用(P<0.05),环氧化酶抑制剂Indo 0.01 mmol·L~(-1)、ATP敏感性钾通道抑制剂Gli 0.01 mmol·L~(-1)和β肾上腺素能受体阻滞剂普萘洛尔0.01 mmol·L~(-1)对DOX舒血管作用无明显影响;DOX 1,10和100μmol·L~(-1)可浓度依赖性减弱无钙液中PE诱发的血管收缩,并可使氯化钙量效曲线右移。结论 DOX对大鼠离体胸主动脉和颈总动脉血管环有浓度依赖性舒张作用,其舒血管机制可能与血管内皮细胞一氧化氮/cGMP途径、K_V、K_(Ca)、K_(IR)、血管平滑肌细胞内钙释放和外钙内流有关。     

东亚钳蝎蝎毒二、三级提取物对快反应心肌细胞动作电位的影响

目的:从东亚钳蝎蝎毒(BMK)中筛选有钠通道阻滞作用的活性成分.方法:培养小鼠心肌细胞,记录快反应动作电位,观察22种BMK蝎毒提取物3 mg·L~(-1)对动作电位的影响,并与河豚毒2.5 mg·L~(-1)、尼莫地平3 mg·L~(-1)、氯化钡24.4 mg·L~(-1)进行对照.结果:BMK-1及其它19种组分使除级化参数V_(max),APA,OS和MDP减小.其作用与河豚毒相似,而与尼莫地平和氯化钡不同.结论:快反应心肌细胞动作电位的改变表明,BMK蝎毒中的20种组分有钠通道阻滞作用.     

金丝桃甙对钙离子内流的影响

研究表明,金丝桃甙(HyP)对兔乳头肌模型,与维拉帕米(Ver)一样,呈剂量依赖性抑制CaCl₂诱发的正性肌力作用,使CaCl₂的量-效曲线显著右下移动,但不平行,可能系非竞争性拮抗;对豚鼠心室肌动作电位模型,Hyp可显著缩短动作电位二相平台期,而对膜静息电位、动作电位零相上升幅度和速率及动作电位时程无明显影响;在小鼠心房组织标本上,Hyp和Ver一样,可抑制高钾诱发的45Ca内流。上述结果提示Hyp对钙内流有一定阻滞作用。     

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.

---

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.     

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.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

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.