In vitro effects and in vivo efficacy of a novel cyclooxygenase-2 inhibitor in dogs with experimentally induced synovitis

OBJECTIVE: To determine cyclooxygenase-2 (COX-2) selectivity, pharmacokinetic properties, and in vivo efficacy of ML-1,785,713 in dogs. ANIMALS: 21 healthy male and female mixed-breed dogs and 24 healthy male Beagles. PROCEDURE: Selectivity of ML-1,785,713 for inhibiting COX-2 was determined by comparing the potency for inhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood. Pharmacokinetic properties were determined after i.v. (2 mg/kg) and oral (8 mg/kg) administration in female mixed-breed dogs. In vivo efficacy was evaluated in male mixed-breed dogs with urate crystal-induced synovitis. Prophylactic efficacy was evaluated by administering ML-1,785,713 two hours before induction of synovitis whereas therapeutic efficacy was determined by administering ML-1,785,713 one hour after induction of synovitis. RESULTS: Blood concentrations that resulted in 50% inhibition of COX-1 and COX-2 activity in vitro were 119.1 microM and 0.31 microM, respectively, and selectivity ratio for inhibiting COX-2 relative to COX-1 was 384. ML-1,785,713 had high oral bioavailability (101%), low systemic clearance (77 mL/min/kg), and an elimination half-life of 5.9 hours. ML-1,785,713 was efficacious when administered prophylactically and therapeutically to dogs with urate crystal-induced synovitis. CONCLUSIONS AND CLINICAL RELEVANCE: ML-1,785,713 is a novel, potent COX-2 inhibitor that is the most selective COX-2 inhibitor described for use in dogs to date. ML-1,785,713 has oral bioavailability and low systemic clearance that is comparable to other non-steroidal anti-inflammatory drugs. It is effective after prophylactic and therapeutic administration in attenuating lameness in dogs with urate crystal-induced synovitis. Drugs that specifically inhibit COX-2 and not COX-1 at therapeutic doses may have an improved tolerability profile, compared with nonselective non-steroidal anti-inflammatory drugs.     

体外评定酸化剂作用效果的方法探讨

文章主要论述了体外法评定酸化剂作用效果的指标和评定方法。     

2007年第一季度饲料和原料中霉菌毒素调查报告

1样品概述 2007年1－3月,百奥明公司共收集来自全国各地的样本68份,其中：玉米28份,配合饲料样本34份,DDGS、豆粕、棉粕、菜粕、花生粕及玉米蛋白粉各1份。[第一段]     

CXCL8((3-73))K11R/G31P antagonizes the neutrophil chemoattractants present in pasteurellosis and mastitis lesions and abrogates neutrophil influx into intradermal endotoxin challenge sites in vivo

Toxic products such as reactive oxygen intermediates released by activated polymorphonuclear neutrophil (PMN) have an important role in the pathophysiology of diseases associated with the deposition of immune complexes (IC) in tissues. IC-induced activation of PMN requires adhesion mediated by integrin adhesion receptors. Of the integrins expressed on PMN, the beta(2) family has been found to be of particular importance for activation of PMN by IC. beta(2) Integrin ligand binding must be activated to enable adhesion to IC. Both activating and inhibitory signals regulate beta(2) integrin ligand avidity and adhesion. The second messenger cyclic adenosine monophosphate (cAMP) has been demonstrated to inhibit the activation of PMN in response to a variety of stimuli. The purpose of this study is to test the hypothesis that cAMP-dependent signals inhibit beta(2) integrin-dependent adhesion of equine PMN to immobilized IC and subsequent adhesion-dependent activation of respiratory burst activity. Treatment of equine PMN with beta(2) adrenergic agonists isoproterenol or clenbuterol, which trigger an increase in intracellular cAMP concentration, inhibited adhesion of equine PMN to IC in a dose dependent manner. Similarly, inhibition of cAMP hydrolysis by the non-specific phosphodiesterase (PDE) inhibitor pentoxifylline and the PDE 4-specific inhibitor rolipram inhibited adhesion of equine PMN to IC. Elevation of intracellular cAMP levels with pentoxifylline, clenbuterol and rolipram also inhibited IC-induced activation of respiratory burst activity in equine PMN. Importantly, co-treatment of equine PMN with rolipram and either beta(2) adrenergic agonist synergistically inhibited both the adhesion of equine PMN to IC as well as the subsequent respiratory burst activity.     

利用风险分析原理完善动物源性食品安全标准体系

近年来，一些危害人类生命健康的重大动物源性食品安全事件不断发生，如发生在比利时的二恶英事件，英国的疯牛病事件，日本的大肠杆菌0157污染事件以及禽流感疫情等。食品安全已成为一个日益引起关注的全球性热点问题。建立以风险分析为基础的标准体系，推行动物源性食品安全科学的管理模式。     

河南省5个地点中华蜜蜂的初步调查

为了摸清河南省的中华蜜蜂资源,了解其生物学特性,进一步为地方良种的选育和养蜂生产提供科学依据,我们于2004年7～9月先后在遂平、南湾、汝阳、孟津、商城等地区不同海拔的5个点采集了中蜂标本,主要从自然巢房及半人工饲养的巢房(如墙洞蜂巢和活框蜂箱)内采集。由于河南省内的中华蜜蜂很少转地饲养,所以采集的蜜蜂基本上是长期生活在当地环境的中华蜜蜂。每群采50只工蜂放入75%乙醇杀死,第二天更换一次乙醇浸泡保存。现将调查的初步结果分述如下:1 自然环境河南省地处中原,位于北纬31°23'～36°22',东经110°21'～116°39'[1];属于大陆型…     

干扰素在动物疫病预防及兽医临床治疗中的应用

本文介绍了兽药市场常见干扰素的种类和主要成分,以及作者在临床治疗和预防控制动物疫病中使用干扰素的一些体会和注意事项。     

氮硅添加对高寒草甸生物量和多样性的影响——以青藏高原为例

草地施肥多集中于添加氮肥与磷肥,很少涉及硅肥。硅作为对植物有益的一种元素,能提高植物对环境的抗性,促进植物的生长。本研究以青藏高原高寒草甸为研究对象,通过添加不同组合的氮肥和硅肥,研究群落地上生物量和生物多样性的变化。结果表明,氮肥和硅肥的添加均能提高群落的地上生物量,然而硅肥提高群落地上生物量的幅度远低于氮肥;在添加氮肥导致群落物种多样性下降的同时,添加硅肥可以缓解群落多样性下降的趋势;硅肥的生物学功能在群落水平上存在着最佳浓度效应。同时,我们推测硅肥在维持群落中杂草的存活率上发挥着积极的作用,并通过比较不同硅肥处理时,杂草生物量所占群落生物量比重的变化,支持了上述推测。     

利用质量控制图监控不同实验条件对布鲁氏菌试管凝集实验结果的影响

运用建立的质量控制图,监控不同实验条件对布鲁氏菌试管凝集实验结果可能造成的影响。在每次日常检测时对标准阳性血清进行试管凝集实验并使用浊度仪测量其上清液的光密度(OD值),在收集足够有效数据后,绘制当前条件下的质量控制图。通过模拟日常实验条件下孵育温度、时间等容易产生偏离的条件,记录不同实验条件下标准阳性血清试管凝集实验后上清液的OD值,绘制控制用控制图。运用绘制的质量控制图对不同实验条件进行监控,发现孵育温度和孵育时间均对实验结果产生较大影响,从而导致失控。采用质量控制图对布鲁氏菌试管凝集实验进行监控,可提高质量监控的有效性、科学性。严格控制实验条件是保证实验结果的重要前提。     

创新思路扎实工作推进现代畜牧业又好又快发展——在全国畜牧站长工作会议上的讲话

新年伊始,我们在江西南昌召开全国畜牧站长工作会议.这次会议是在全国农业系统认真学习党的十七大精神,深入贯彻落实科学发展观,探索中国特色农业现代化道路,扎实推进新农村建设的形势下召开的.这次会议非常重要.