Experimental Clostridium difficile enterocolitis in foals

Despite empirical clinical association of infection with Clostridium difficile with colitis in horses, a causal link has not been confirmed. The objective of this study was to develop a model of C. difficile-associated diarrhea in foals with normal transfer of passive immunity. Nine 1-day-old pony foals were inoculated intragastrically with spores or vegetative cells of C. difficile. Five foals were challenged with spores, with 2 receiving 10(5) colony-forming units (CFUs) and concurrently 3 receiving 10(7) CFUs once daily for 3 days. Clindamycin was administered orally to disrupt gastrointestinal flora. A further 4 foals were challenged by orogastric administration of 10(10) CFUs of vegetative cells once daily for 3 days or until diarrhea developed. This group did not receive clindamycin. Spore and vegetative cell preparations were negative for toxins of C. difficile and common enteropathogens. Clinical signs varied from mild abdominal discomfort and pasty feces to colic and watery diarrhea in 8 of 9 foals. Four of 5 foals challenged with spores developed mild diarrhea, whereas all foals challenged with vegetative cells developed moderate to severe diarrhea. C. difficile was isolated from feces of all foals between 24 and 72 hours after inoculation and toxins A or B or both were detected in the feces of all foals by an enzyme-linked immunosorbent assay. We concluded that spores and vegetative cells of C. difficile are capable of colonizing the gastrointestinal tract, producing toxins, and inducing clinical signs similar to those encountered in naturally occurring cases. This study fulfilled Koch's postulates for C. difficile-associated diarrhea in foals and provides a model for consistent reproduction of the disease for future studies.     

魔芋胶-甲硝唑骨架片的制备及体外释药特性研究

［目的］探讨骨架片体外药物释放的影响因素及其药物释放特性。[方法］以甲硝唑为模型药物,采用湿法制粒压片制备魔芋葡甘聚糖（KGM）-甲硝唑骨架片,以释放度为指标,研究了骨架材料含量、KGM粒度、释放介质pH值、离子强度以及不同转速对KGM-甲硝唑骨架片体外释药的影响。［结果］辅料片在蒸馏水中的溶胀度最大,在pH值为6.8的PBS中次之,在0.1 mol/L HCl中最小。KGM粒度对释药的影响不大。在10%-20%的范围内,骨架材料含量越高,缓释效果越好。骨架材料含量为20%时,12 h后药物的累积释放率为85%。在0.1 mol/L HCl中,2 h后KGM-甲硝唑骨架片中的药物几乎全部释放。药物释放速度随介质离子强度的增强而加快。转速大时,药物释放快,转速越小,药物控释越好。［结论］魔芋葡甘聚糖具有较好的缓、控释特性,是一种极有发展潜力的新型药物制剂辅料。     

HPLC法快速测定饲料中硝基咪唑类药物的研究

[目的]为建立一种检测饲料中硝基咪唑类药物的HPLC方法。[方法]提取饲料样品中的甲硝唑、二甲硝唑、罗硝唑和替硝唑,用Oasis MCX小柱进行净化后,以甲醇-水溶液为流动相,梯度洗脱,紫外检测波长为320 nm,进行HPLC测定。[结果]甲硝唑、罗硝唑、二甲硝唑和替硝唑的检测限分别为15.7、25.3、27.3和54.9μg/kg。在0.1～10.0μg/ml浓度范围内,4种硝基咪唑类药物色谱峰面积与浓度呈线性相关,相关系数为0.993～0.999,符合对饲料中抗生素分析的要求。4种硝基咪唑类药物平均回收率为82.5%～99.7%,符合对饲料中药物添加剂分析的准确度要求,变异系数为3.5%～14.0%,符合残留分析对精密度要求。[结论]该方法操作简单、结果准确,可用于测定饲料中硝基咪唑类药物的含量。     

结肠小袋纤毛虫体外药物急性毒杀试验

通过结肠小袋纤毛虫对甲硝唑、氟苯尼考和血虫净（三氮咪）的急性毒性试验,以机率单位法获得半数致死浓度（LC50）,结果显示：甲硝唑、氟苯尼考对结肠小袋纤毛虫2h的半数致死浓度（LC50,2h）分别是457．8mg／L,1705mg／L,12h的半数致死浓度（LC50,12h）分别是25．64mg／L、973．8mg／L。血虫净（三氮咪）12h和24h半数致死浓度（LC50）分别是331．8mg／L、295．4mg／L。甲硝唑是杀灭结肠小袋纤毛虫的理想药物。     

甲硝唑人工抗原的制备及其ELISA检测

采用碳二亚胺法将甲硝唑半抗原与牛血清白蛋白(BSA)连接制备人工免疫原,同样方法将其与卵清蛋白(OVA)连接制备人工包被原.经紫外扫描分析,两种方法合成的免疫原和包被原的结合比分别为8∶1、2∶1和6∶1、2∶1;动物免疫试验分析偶联物,小鼠抗体效价达1∶5 000,与3种硝基咪唑类药物的交叉反应率均小于10%.表明制备的抗体可以用于甲硝唑残留的检测,同时为检测试剂盒的研制奠定了基础.     

甲硝唑对鸡回忆性体液免疫应答反应的作用

本试验系统观察了甲硝唑对鸡回忆性体液免疫应答反应的作用,并与咪唑类化合物左旋咪唑进行了比较。28日龄鸡,免疫注射绵羊红细胞 牛血清白蛋白(SRBC BSA)悬液,或稀释的布氏杆菌(BA)抗原。56日龄时,以10.0、100.0mg/kg甲硝唑或10.0mg/kg 左旋咪唑饮水给药,连用3d,给药第二天同时进行第二次免疫注射。结果表明甲硝唑(10.0~100.0mg/kg)可使鸡体内对颗粒性胸腺依赖性抗原SRBC和非胸腺依赖性抗原BA抗体滴度回忆性免疫应答反应明显升高;但使鸡对可溶性胸腺依赖性抗原BSA抗体滴度回忆性免疫应答反应明显降低。与甲硝唑比较,左旋咪唑(10.0mg/kg)也存在着非常类似的作用。     

甲硝唑和替硝唑对幼犬肝功能的影响研究

[目的]为小动物临床用药提供参考。[方法]分别向刚断奶的幼犬腹腔注射1倍剂量、2倍剂量、5倍剂量的甲硝唑和替硝唑5d,并分别在用药前、停药后第1天、第7天测定试验犬的肝功能指标,探讨甲硝唑和替硝唑对犬肝功能的影响。[结果]2倍剂量的甲硝唑和替硝唑对幼犬肝功能的影响更为明显;大剂量的2种药物均可引起幼犬TRP增加、排黄色尿液等临床表现、肝静脉及肝窦充血、脂肪变性等病理学变化。[结论]替硝唑对幼犬的毒副作用低于甲硝唑。     

盐酸米诺环素软膏联合甲硝唑缓释药膜治疗慢性牙周炎的疗效观察

目的探讨盐酸米诺环素软膏联合甲硝唑缓释药膜治疗慢性牙周炎的疗效．方法根据治疗方案将138例慢性牙周炎患者分为两组,69例患者使用盐酸米诺环素软膏治疗为对照组,69例患者使用盐酸米诺环素软膏和甲硝唑缓释药膜治疗为观察组,疗程4周,随访1a,比较两组患者的牙周改善情况、治疗效果、不良反应情况、复发情况．结果治疗后,两组患者牙龈指数、菌斑指数、牙齿松动指数、牙周袋深度均显著下降;观察组患者牙龈指数、菌斑指数、牙齿松动指数、牙周袋深度、复发率均明显低于对照组;观察组患者治疗总有效率明显高于对照组,差异均具有统计学意义（P〈0．05）;观察组患者不良反应发生率高于对照组,差异无统计学意义（P〉0．05）．结论盐酸米诺环素软膏联合甲硝唑缓释药膜是治疗慢性牙周炎的有效药物,可明显改善患者的牙周状况,提高药物的治疗效果,不良反应少,且复发率低,值得临床推广使用．     

Determination of the in vitro susceptibility of feline tritrichomonas foetus to 5 antimicrobial agents

BACKGROUND: The nitroimidazole, ronidazole, has been demonstrated to have in vitro and in vivo activity against the protozoan Tritrichomonas foetus in cats. The purpose of this study was to evaluate the in vitro susceptibility of feline T. foetus isolates obtained from naturally infected cats to 5 antimicrobial agents and to compare the in vitro time kill of ronidazole and metronidazole. HYPOTHESIS: We hypothesized that nitroimidazoles have in vitro activity against T. foetus, whereas furazolidone, omeprazole, and paromomycin do not. ANIMALS: Fecal specimens were cultured from 4 naturally infected Bengal cats with a history of T. foetus-associated diarrhea. METHODS: A 24-hour susceptibility assay was performed on all 4 isolates for the 5 antimicrobial agents. A time-kill microdilution method was performed on 2 isolates for metronidazole and ronidazole. RESULTS: Paromomycin and omeprazole showed no in vitro effect at concentrations < or = 80 microg/mL. There was no significant difference in 24-hour susceptibilities among metronidazole, ronidazole, and furazolidone. In addition, only the results of the highest concentration tested (80 microg/mL) and concentrations of 1.25 and 2.5 microg/mL revealed significant differences in the rate of trophozoite killing, with ronidazole having a faster reduction in trophozoite survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Time-kill assays demonstrated ronidazole had a higher lethal activity compared with metronidazole. These findings contrast with a previously published report and may reflect strain variation, different methodologies, or both. The lack of clinical response seen with metronidazole administration to treat feline trichomoniasis may not reflect inherent resistance but rather in vivo events involving drug distribution and pharmacokinetics.     

高效液相色谱法同时测定兽药复方酮康唑软膏中的酮康唑和甲硝唑含量

建立了同时提取、测定兽药复方酮康唑软膏中酮康唑、甲硝唑含量的高效液相色谱(HPLC)法。采用C18色谱柱,甲醇-水为流动相,梯度洗脱,检测波长239nm。结果表明,酮康唑和甲硝唑2种成分线性关系良好(r > 0.999)。在3个不同浓度水平下酮康唑和甲硝唑平均加样回收率分别为 97.8% 和100.0%,溶液稳定性和方法重复性的RSD均小于1%。应用该方法测定3个不同厂家样品中2种组分的含量,结果符合要求。本方法简便,可靠,专属性强,重现性好,为该制剂的质量标准提高提供了研究基础。