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.     

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.     

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.     

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．     

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.     

硝喹醋酸盐在体内对约氏鼠疟原虫红内期超微结构的影响

本文结果证明,硝喹能引起鼠疟原虫形态学的多种改变。在光镜下,早期出现大而不分裂的核,随后发现原虫胞浆中有散在的,大小不等的圆形红色颗粒,这些红色颗粒可能是胞浆中的变性物质,有可能是电镜中所观察到的自噬泡和膜性残体,但具体性质有待进一步研究。     

我国目前实验室内保有的食蟹猴疟原虫的生物学特征及对其株型的探讨

根据近十年来的实验研究资料,本虫株具有下列特征。外期:形态不规则,第7天胞质内可出现液泡,分叶,第8天成熟,同一天末即可在周围血流内找到原虫。复发率为60％左右。内期:喜入侵晚期网织红细胞(Ⅳ期);血传感染持续期较长,可长达6年以上。孢子增殖期:在巴拉巴按蚊、斯氏按蚊及雷氏按蚊体内都能完成孢子增殖,但巴拉巴按蚊为最适宜蚊种,在雷氏按蚊体内发育不良,黑孢子形成率可高达42.3％;巴拉巴按蚊体内,子孢子最早可于7.5天进腺。卵囊园形或椭园形,其最大径未超过60微米。根据上述特点,与本疟原虫的各虫株进行了比较。初步认为本虫株可能属于柬埔寨株。对虫株的复发特性及血传感染持续期之长进行了讨论分析。     

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