苯妥英锌的制备及初步药理学研究

当苯妥英与醋酸锌摩尔比为2∶1时,苯妥英锌成盐收率为92.8%。小鼠腹腔注射的 ED_(50)和 LD_(5)分别为9.74和138.1 mg/kg。与苯妥英钠相比,吸湿性和对眼的刺激性较小,在大鼠口服的亚急性毒性试验中,Hb、BP、WBC、SGPT 阳病理组织学检查表明两药的毒性无显著差异。     

苯妥英锌对家兔血清高密度脂蛋白胆固醇的影响

目的:研究家免口服苯妥英锌(PHTZ)对血清高密度脂蛋白胆固醇(HDL-C)的影响.方法:家兔分别口服PHTZ和苯妥英钠(PHTS)30d(剂量分别为:6,12,24mg·kg-1·d-1),用酶法测定血清中总胆固醇(TC)和三酰甘油(TG)的含量,HDL-C的测定采用磷钨酸镁盐沉淀后同TC测定法,低密度脂蛋白胆固醇(LDL-C)用费氏(Friedeuald)公式计算.用原子吸收分光光度法测定服药前后血清及服药后肝中Zn和Cu浓度.结果:PHTZ高、中剂量组分别使血清HDL-C升高76.0%(P＜0.01)和52.1%(P＜0.01),LDL-C分别降低19.7%(P＞0.05)和16.6%(P＞0.05),对TC和TG无显著影响.PHTZ使血清HDL-C升高的ED50为12.7mg·kg-1,PHTS使血清HDL-C提高的ED50为23.7mg·kg-1.PHTZ中剂量组使血清Zn浓度下降29.2%,与血清HDL-C上升的百分数呈负相关(r=-0.303 5,P＞0.05),使肝脏Zn浓度上升56.2%,与血清HDL-C上升的百分数呈正相关(r=0.726 3,P＜0.05),血清和肝脏中Cu无显著变化.结论:PHTZ使家兔血清HDL-C升高比PHTS更明显,ED50比PHTS低,可能与分子结构中的Zn有关.     

兔口服苯妥英锌的药物动力学

用紫外分光光度法测定了兔口服苯妥英锌或苯妥英钠后血清中苯妥英的浓度,用原子吸收分光光度法测定血清中锌及铜的含量。结果表明,两药 AUC、T_m、C_m 等主要药物动力学参数无显著差异。苯妥英锌组血锌浓度变化甚微,苯妥英钠组血锌浓度随血清中苯妥英浓度而变化。两药均不改变血清中铜含量。     

幼年家兔口服苯妥英锌7个月的小脑生长发育

苯妥英钠(phenytoin sodium,PS)虽是治疗除失神发作外各型癫痫病的首选药物之一,但长期服用后可引起小脑萎缩.苯妥英锌(phenytoin zinc,PZ)的抗癫痫作用及急性和亚急性毒性与PS相近,但大鼠长期口服后对脑重量的影响正好与PS相反,提示PZ长期服用后有可能减轻小脑萎缩.本研究选用1月龄家兔35只,随机分为对照组,PZ或PS10和30 mg·kg-1·d-1组.     

锌对大鼠消化道的毒性影响

锌对大鼠消化道的毒性影响盛锡联，刘力建，孔祥英由于儿童缺锌的发病率很高，近年来补锌已成潮流，有的人盲目大量长期补锌。已知缺锌可引起厌食、腹泻、消化吸收不良，导致生长发育落后，但如补锌过量又会如何？我们制作了大鼠锌过量模型，对锌的毒性对胃肠道的影响进行...     

苯妥英锌对大鼠血脂的影响

考察了大鼠口服苯妥英锌或苯妥英钠１５ｍｇ／（ｋｇ·ｄ）４５ｄ对血脂的影响。服药前后比较，苯妥英锌使大鼠血清ＨＤＬ－Ｃ和ＨＤＬ－Ｃ／ＴＣ分别上升８％和１７％（ｐ＜０．０５），（ＬＤＬ＋ＶＬＤＬ）－Ｃ下降３４％（ｐ＜０．０１）；苯妥英钠则使大鼠血清ＨＤＬ－Ｃ和ＨＤＬ－Ｃ／ＴＣ分别下降３７％（ｐ＜０．０１）和２１％（ｐ＜０．０５），（ＬＤＬ＋ＶＬＤＬ）－Ｃ上升３０％（ｐ＜０．０５）。     

幼年家兔口服苯妥英锌7个月小脑生长发育的研究

目的:考察长期口服苯妥英锌(phenytoinzinc,PZ)对幼年家兔小脑生长发育的影响。方法:1月龄新西兰家兔分别给予PZ或苯妥英钠(phenytoinsodium,PS)7个月(剂量分别为:30、10mg·kg-1·d-1),药前、药中(4个月)和药后进行三次CT扫描,测量小脑最大横径和蚓部最大横径。服药结束后处死动物,Bouin氏液灌注固定脑组织,测定全脑的长、宽和高以及重量。结果:CT扫描显示PS组服药4个月和7个月后,小脑最大横径分别缩短14.0%(P<0.05)和32.2%(P<0.01);蚓部最大横径分别缩短16.4%(P<0.05)和30.8%(P<0.01)。PZ组仅在服药7个月后,小脑和蚓部的最大横径比对照组分别缩短16.1%(P<0.05)和19.7%(P<0.05)。固定后的小脑和蚓部的长度和宽度,PS组均比对照组明显缩短;全脑湿重和乙醇脱水后重量以及小脑重量与对照组比较均显著减轻,其中全脑脱水后重量减轻15.4%(P<0.05),小脑重量减轻18.4%(P<0.05)。而PZ组的上述测定值与对照组均无显著性差异。结论:幼兔长期口服高剂量PS后导致小脑萎缩,而口服PZ后对小脑的形态影响比PS轻,有可能降低本类抗癫痫药物长期服用后引起的小脑萎缩。     

苯妥英锌对烧伤的临床治疗作用

目的 :观察苯妥英锌治疗烧伤的作用。方法 :选择烧伤部位的面积和深度相近的 19例Ⅱ度烧伤患者 ,分为两组 ,分别用苯妥英锌和磺胺嘧啶银的软膏 (2 5 % )外用治疗 ,观察创面肿胀程度、发炎、创面结痂、局部疼痛以及创面愈合时间 ,并进行烧伤后创面组织学检查。结果 :苯妥英锌组创面的渗出比对照组少 ,疼痛明显减轻 (P <0 .0 5 ) ,创面细菌的转阴率 1wk后为 30 % (对照组为 33.3% ) ,创面愈合时间为 16.1± 2 .8d(对照组为 16.8± 2 .7d) ,创面毛细血管胚芽与成纤维细胞数量明显多于对照组。结论 :苯妥英锌对Ⅱ度烧伤的治疗优于磺胺嘧啶银     

苯妥英对缺氧小鼠的保护作用

苯妥英 (ｐｈｅｎｙｔｏｉｎ ,ＰＨＴ)临床多用于癫痫及强心甙中毒的治疗。国外研究发现 ,苯妥英对置于低压缺氧容器的小鼠有明显的保护作用[1] ,而其它缺氧模型的研究未见报道。为进一步探讨苯妥英提高缺氧小鼠耐受性的作用 ,本文采用常压及化学性缺氧的方法 ,研究了苯妥英的抗缺氧作用。1　材料和方法1.1　药物　苯妥英 :上海新亚药业公司产品 ,批号95 0 5 10 1;亚硝酸钠 :天津市化学试剂一厂出品 ,批号810 718;氰化钾 :上海试剂一厂出品 ,批号 790 90 1,实验前均用生理盐水配成所需浓度。1.2　动物　昆明种小鼠 ,♀♂兼用 ,体重 (2 0± 2…     

Toxicity in animals: target species

The macrocyclic lactone endectocides typified by ivermectin are safe and effective drugs when used according to label directions. However, off-label use, misuse and overdosing can result in toxicity in animal patients as revealed by pharmacovigilance activities. Preclinical toxicity studies demonstrates that the major clinical signs of toxicity are those associated with neurotoxic effects and these are the most common adverse drug reactions noted in overdosed treated animals. Subpopulations of some strains or breeds of some species appear to be uniquely sensitive to the neurotoxic effects of the macrocyclic lactones due to enhanced brain penetration by these drugs as a result of a deficiency in P-glycoprotein arising as a result of a mutation in the MDR1 gene.     

Toxicity in animals. Trends in evolution?

Animals acquire toxicity either by metabolic synthesis of toxins (secondary metabolites), by expression of toxin genes or by the uptake, storage and sequestration of toxins produced by other organisms, i.e., microbes, plants or other animals. Variability of toxin structure and function is high. Peptide toxins in particular, although relying on a limited number of structural frameworks, often exhibit considerable structural hypervariability. An accelerated rate of evolution in the toxin gene structure (conserved introns, but high substitution rates in the exons) leads to the functional diversity of these peptides or proteins. The selective forces which may drive toxin evolution are unknown. Venomousness or the possession of toxins can be essential for survival, but the advantage of toxin biosynthesis may also be of minor importance or has been lost during evolution.     

Toxicity of zinc in three microbial test systems

A feasibility study on the potential use of three bacterial test systems on the toxicity screening of zinc is presented. In this investigation, the toxicity screening procedures included, were the Microtox test using a luminescent halophyte bacterial strain, Photobacterium phosphoreum, a motility test employing Spirillum volutans, and a growth zone inhibition test using Bacillus cereus as the test organism. The EC₅₀ value of zinc has been found to be 1.35 mg/L with the Microtox test under optimum test conditions (T₁₅o_ct_15min). However, the toxic response of zinc was significantly dependent upon the test temperature and incubation time. It decreased at higher temperatures and increased with longer incubation periods. In the case of the motility test, the minimum effective concentration (90%) value of zinc was 3.00 mg/L at optimum assay conditions (T₂₈o_ct_60min) while the toxicity of zinc in the growth zone inhibition procedure was found to be 2.25 mg/L at 30°C after 18 h incubation. Overall, the study showed that the Microtox test was the most sensitive screening procedure followed by the growth zone inhibition test, and the motility test was least sensitive among the three test systems. The growth zone inhibition procedure was the simplest of all the systems. © 1996 by John Wiley & Sons, Inc.     

Toxicity of Diplodia maydis in farm and laboratory animals

The acute toxicity of maize culture material of eight strains of Diplodia maydis in ducklings, as well as the ability of five of these strains to induce typical diplodiosis (a neuromuscular disease) in cattle and sheep was shown. Typical diplodiosis was induced in 17 sheep and 11 cattle. Two of the five toxic strains were isolated from maize involved in diploidiosis outbreaks, the others from commercial maize. Strains inducing diplodiosis could be isolated from commercial maize from the USA, Argentina and South Africa. There was no correlation between the toxicity of D. maydis strains in ducklings and their ability to induce diplodiosis in cattle and sheep. Some isolates were acutely toxic to ducklings and rats but were unable to induce diplodiosis in either cattle or sheep. Others, equally toxic to ducklings and rats, induced diplodiosis in cattle and sheep at low dose levels. Two doses, each of 5 g/kg, of maize culture material of isolates from the USA, Argentina and South Africa induced diplodiosis in sheep. Culture material incubated for less than 8 wk could not induce diplodiosis in cattle. Acute toxicity in ducklings and rats also increased with longer incubation periods. Cultures of non-sporulating and profusely sporulating strains were equally toxic to ducklings. Heat treatment of culture material for 48 days at 45 degrees C failed to reduce toxicity in ducklings.