兽用喹诺酮类药物发展动态

综述了兽用喹诺酮类药物—包括国内外已上市的、尚在开发中的以及人用药可转化为兽用药三个部分的品种,并对在我国尚未上市的兽用喹诺酮类药物的药理作用及用途作了简介。     

卡死克对草地天敌昆虫通缘步甲的影响

试验研究了卡死克对通缘步甲成虫的急性致死毒性及田间撒施卡死克毒饵后对其种群数量消长的影响。室内口腔灌喂250ppm浓度的卡死克药液2μl／头后的第1～15天，灌药组与灌清水组的存活率均在70～90％，统计结果无显著差异，说明药剂对该步甲元急性致死毒性。在毒饵撒施后的7～17天，采用陷阱诱捕法调查对通缘步甲田间种群数量的影响，结果表明：处理区与对照区的日均诱捕数量为28．3和28．5头，两区间的差异并不显著。卡死克既不杀伤草地上游猎捕食的通缘步甲又能有效控制蝗虫种群数量的增长，使其能够发挥控制害虫的作用。通缘步甲发生数量大，与蝗虫种群消长有跟随现象，是一种值得研究保护利用的优势天敌种类。     

苏丹红和饲料着色剂的区别

本文主要从苏丹红和饲料着色剂的化学结构、作用机理及毒性等方面说明饲料着色剂与苏丹红的天壤之别。     

国产头孢噻呋钠的毒性试验

为了解国产头孢噻呋钠的毒性,进行了小鼠的急性毒性及对鸡的亚慢性毒性试验。结果表明,小鼠肌肉注射头孢噻呋钠,LD50为1 673.02 mg/kg;鸡注射头孢噻呋钠21 d,未发现与药物相关的体征变化,各组间的体重变化无显著性差异;采食量、饮水量随鸡龄增加而增加,平行比较无显著性差异;各阶段鸡的RBC、WBC分类记数(中性粒细胞/N、碱性粒细胞/B、酸性粒细胞/E、大单核细胞/M、淋巴细胞/L)均在正常值范围内,各组间无显著性差异;各组间血清生化值BUN、GPT、ALB也无显著性差异;各组脏器无显著性差异,说明该药毒性较低。     

Evaluation of Joint Toxicity of Enrofloxacin and Three Antimicrobials on MRC-5 Cells

The aim of this study was to evaluate the combined toxicity of enrofloxacin with each of three antimicrobials (ciprofloxacin,florfenicol and sulfamethazine).MRC-5 cells were used as a cell model to simulate the damage of lung cells caused by mixed contamination of antimicrobials.Multiple concentration gradients and mixing ratios were set.CCK-8 method was used to determine the inhibition rate of cell growth caused by four antimicrobials and the inhibition rate of cell growth caused by enofloxacin mixed with three antimicrobials,respectively.Then Chou-Talalay method was used to fit the median effect plot and to calculate the combination index (CI) value.The results showed that the growth inhibition rates of MCR-5 cells caused by four single drugs went up in a step-like manner with the increase of drug concentration in the tested concentration range,among them,the growth inhibitory rate of MCR-5 cells by florfenicol was low (<4.5%).The combined toxicity of the three binary combinations showed a concentration-dependent and mixing-ratio dependence.Mixing enrofloxacin and ciprofloxacin showed synergistic toxicity (CI<1) on MRC-5 cells at high and middle concentration groups,and antagonistic toxicity (CI>1) at the very-low-concentration groups.Mixing ciprofloxacin and florfenicol mainly showed an inhibited toxicity (CI>1).Binary combination enrofloxacin and sulfamethazine might present either a synergistic joint toxicity (CI<1) or an antagonistic joint toxicity (CI>1) as the concentration and mixing ratio changing.This study showed that it was necessary to assess the combined toxicity of antimicrobials in the toxicity evaluation of antimicrobials.Using Chou-Talalay method,the joint toxicity of multiple antimicrobials could be quickly and efficiently determined at cellular level.     

Retrospective evaluation of toceranib phosphate (Palladia®) toxicity in cats

The purpose of this study was to describe the toxicity profile of toceranib phosphate in tumour bearing cats. Medical records were reviewed from seven institutions. Patients with incomplete medical records and those receiving concurrent chemotherapy or NSAIDs (non‐steroidal anti‐inflammatory) were excluded. Fifty‐five cats met the inclusion criteria. Carcinoma was diagnosed in 55% of cases. Median oral toceranib dose was 2.7 mg kg^?1 and was most commonly administered on Monday, Wednesday and Friday. Thrombocytopenia (16.3%) and neutropenia (9.1%) were the most common haematologic toxicities. Azotemia (14.5%) and alanine aminotransferase (ALT) elevations (7.2%) were the most frequently encountered biochemical alterations. Gastrointestinal (GI) toxicity was seen in 21.8% of cats, and was lower than previously reported in dogs. The results of this study showed that treatment of cats with toceranib is well‐tolerated and toxicity is uncommon. Additional studies to define a more structured dosing schedule and to evaluate the efficacy of toceranib in the treatment of feline cancers are needed.     

饲用黄丝藻粉的急性毒性和亚慢性毒性试验

试验旨在通过研究黄丝藻粉对大鼠的急性毒性和亚慢性毒性试验,初步评价其饲用安全性。5 000 mg/kg体重黄丝藻粉灌胃给予Wistar大鼠进行急性毒性试验;黄丝藻粉按0、1 250、2 500、5 000 mg/kg 添加于饲料中饲喂大鼠,进行90 d亚慢性毒性试验。每周称量大鼠体重与饲料消耗,分别于喂养 45、90 d 时剖检,进行血常规和血液生化指标检测,计算脏器系数,并对主要脏器进行组织病理学检查。结果表明,5 000 mg/kg体重黄丝藻粉给予大鼠均未出现死亡,LD₅₀>5 000 mg/kg体重,根据WHO对化学物质的毒性评级,黄丝藻粉属于实际无毒物质。亚慢性毒性试验中,高、中、低剂量黄丝藻粉饲喂大鼠90 d后平均饲料消耗、体增重、脏器系数与对照组相比均无显著差异（P>0.05）。各处理组血常规指标、低剂量组血液生化指标与正常对照组相比均无显著差异（P>0.05）;高、中剂量组除血液总胆固醇（CHO）、甘油三酯（TG）显著低于对照组（P<0.05）外,其他血液生化指标均无显著差异（P>0.05）;高、中剂量组总胆固醇和甘油三酯均在大鼠正常生化指标范围内;解剖及主要脏器HE染色检查均未发现明显变化。试验结果表明,黄丝藻粉属于实际无毒物质;5 000 mg/kg添加剂量喂养大鼠90 d,未观察到明显的有害作用,有望在动物饲料中添加应用。     

Exogenous testosterone modulates tumor necrosis factor-alpha and acute phase protein responses to repeated endotoxin challenge in steers

Clinical responses to some disease agents differ between sexes and this dimorphism has been attributed to the immunomodulating effects of steroid hormones. Our objective was to determine in steers the effect of testosterone on circulating concentrations of immune response mediators (tumor necrosis factor-alpha, TNF-alpha; serum amyloid-A, SAA; haptoglobin, HG; xanthine oxidase, XO; nitric oxide, NO) after two consecutive endotoxin challenges (LPS1 and LPS2, 5 days apart; 0.25 microg/kg BW). Sixteen crossbred steers (328+/-6 kg) were assigned to control (CON, n=8) or testosterone cypionate treatment (TES, n=8; 100 mg/m2 body surface; i.m. injection 12 and 2 days before LPS1). The response to LPS was calculated as area under the timexconcentration curve (AUC) for the parameter measured. After LPS1, TNF-alpha AUC was greater in TES than CON (P<0.05). Plasma HG and SAA concentrations increased (P<0.01) after LPS1 and LPS2. In all steers SAA AUC was greater after LPS1 than LPS2 (P<0.01) but the response was augmented over CON with testosterone treatment (P<0.05). HG response to LPS1 within 24 h was not affected by testosterone. However, 5 days after LPS1 mean plasma HG concentration remained higher in TES than CON (P<0.01). HG response to LPS2 was greater in TES than CON (P<0.01). Plasma nitrate+nitrite concentration (NO production marker) and XO activity increased after each LPS challenge but responses were not affected by testosterone treatment. Results indicate that the presence of circulating testosterone increases the magnitude of the TNF-alpha response to LPS challenge as well as the subsequent increases in acute phase proteins (APP). Effects of testosterone on increases in TNF-alpha and APP may underlie a differential presentation of disease symptoms between sexes or between steers and bulls. The data also suggest a role for testosterone in the development of tolerance to repeated immune challenge through its effect on the increased magnitude and duration of HG response.     

胆翘注射液急性和亚慢性毒性试验

旨在评价胆翘注射液的毒性,为临床安全用药提供理论依据。以昆明小鼠为研究对象,进行急性和亚慢性毒性试验。在急性毒性试验中,给予小鼠不同浓度的胆翘注射液来测定胆翘注射液的半数致死量和最大耐受量;在亚慢性毒性试验中,小鼠以(10、5、2.5g/kg)不同剂量连续腹腔注射给药28d,在给药第28天观察小鼠的临床体征、体重及饲料利用率、血常规、血液生化指标和病理组织学变化。结果显示,急性毒性试验各剂量组小鼠均无死亡,无法测出LD_(50),最大耐受量为20g/kg。亚慢性毒性试验中用药组小鼠的临床体征、体重及饲料利用率、血常规、血液生化指标与空白组小鼠相比,无显著差异(P0.05),组织病理学观察,实质器官无异常病变。表明胆翘注射液实际无毒,安全性好。