硝喹的抗疟机理探讨

硝喹(NQ)是一新的抗疟药。用于预防及治疗恶性疟,抗氯喹恶性疟及间日疟。氨苯砜对NQ有加强作用,临床合用喹哌或咯萘啶,只需各自60％的剂量其疗效即与正常剂量相当,NQ作用机理复杂,从电镜观察它影响原虫线粒体、粗面内质网和膜结构等;从生物化学研究发现它可抑制DNA合成,有期特异性,且较对宿主DNA强,PABA对其拮抗;对RNA的合成影响较小;对蛋白质合成抑制较对DNA敏感,前者为pmol水平,后者为μmol水平。     

疟疾治疗中的几个问题

一、根据药动学完善治疗方案:①奎宁:用二室模型分析最佳方案为静滴奎宁二盐酸负荷量7mg/kg(30min内滴完)然后10mg/kg(4h内滴完),以后每8h静滴10mg/kg(每次均在4h滴完)。②氯喹:根据二室模型计算机分析,其方案为初8h静滴氯喹(按基质计算)1.25mg/kg/h,随后0.62mg/kg/h,24h后可达到最理想的治疗浓度。     

Protective Effect of Folic Acid on Nitroquine Toxicity to Small Intestine in Mice

One hundred and ninety-five mice were used to study the mechanism of the protective ef-fects of folic acid on nitroqine toxicity to the small intestine.After oral administration of nitroquineacetate(570mg/kg×1),intramuscular injection of normal saline was given to one group of mice(NS group)and intramuscular injection of folic acid(8mg/kg×1)to another(NF group).Decrease incells in the crypts were observed in the animals of NS group,but the changes were much milder inthose of NF group even at 96 h after administration.The decrease of DNA content in the tissues ofthe small intestine was dose-and time-dependent.The value of cpm/mg of DNA after ~3H-TdRincorporation were much higher in NF group than in NS group.these rcsults suggest that DNA synthesis in the small intestine may be promoted by folic acid so thatthe renair of the damaged intestinal mucosa is acoelerated.     

药理学教学应当紧密结合临床

产生于诊断学占统治地位、药物品种少、治疗相对简单历史条件下的现有药理学教学模式已难以适应新形势下治疗学的迅速发展.改革药理学教学模式,加强与临床的联系,加强医、药有机融合,药理学专业人员参与查房已是当务之急.本文从教学时机的选择、人员配置、教材等方面就以上问题提出一些看法和设想,以供探讨.     

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．     

几类非甾体抗炎药物的研究进展(一)

白三烯(LT)抑制剂和受体拮抗剂、血小板活化因子(PAF)受体拮抗剂和合成酶抑制剂、磷脂酶A2(PLA2)抑制剂都是非甾体抗炎药,通过抑制炎症介质活性或拮抗其受体,阻断或减轻炎症过程.应用该类药物对治疗炎症疾病有良好前景.本文综述了它们近年来的研究进展.     

Studies on Toxicity of Nitroquine-Dapsone Compound and Therapeutic Effects of Folic or Folinic Acid on Toxicated Animals

The toxic effects of nitroquine-dapsone compound(NQD)in mice and dogs were studied.The therapeutic index of NQDin mice is 1911,the greatest among the 6 antimalarials tested.Thetoxic effects of NQD(50 mg/kg/day for 3 days per os)and nitro-quine in dogs were manifested by injuries on the adrenal cortexand intestinal epithelium.When folic acid(4 mg/kg/day for 4 days)or calcium leucovorinum(0.3 mg/kg/day for 4 days)were usedconcomitantly with NQD,the death rate and the incidence of dia-rrhea in the toxicated dogs were greatly reduced,the injury on theintestinal epithelium was much milder,and the goblet cells weremuch more numerous than those without treatment.The results suggestthat folic acid and calcium leucovorinum can protect the undifferen-tiated cells in the intestinal crypts from being injured by NQD.     

硝喹醋酸盐对体外培养鼠约氏疟原虫红内期蛋白合成的影响

在实验采用短时体外培养鼠约氏疟原虫红内期并与药物共同孵育的方法,以H~3-异亮氨酸掺入疟原虫蛋白质作指标,观察了抗疟新药硝喹对疟原虫蛋白质的影响,并用放线菌酮和氨基喋呤作对照。结果发现,硝喹和放线菌酮对~3H-异亮氨酸掺入疟原虫     

从祖国医学发展过程中体会到“百家争鸣”方针的作用

“百家争鸣”的方针,是伟大的中国共产党和英明的人民政府,指示我们向科学进军的新方向,这方向是正确的,我们一定要照这样的路线走去。我今日就是响应号召,把历史上“争鸣”