甲磺酸加替沙星对狗亚急性毒性试验研究

甲磺酸加替沙星 15、6 0和 12 0mg/kg给Beagle狗连续口服 12周毒性试验 ,结果表明 ,12 0和 6 0mg/kg组分别口服 3周和 4周有流涎和呕吐反应 ,停药后能恢复 ;12 0mg/Kg组在给药期体重增长受抑制 :12 0mg/kg组给药 8周和 12周碱性磷酸酶和血糖升高 :血液学、心电图、尿常规和病理解剖检查无明显病理改变 ;15mg/kg剂量组无任何毒性反应 ,属安全剂量。     

国产环丙沙星盐酸盐的临床前药理学研究——Ⅱ.大鼠亚慢性毒性及一般药理作用

大鼠口服国产环丙沙星盐酸盐毒理学研究表明,一般情况良好,食物水分消耗及造血机能正常。肝肾功能生化检查除500mg/kg组碱性磷酸酶活性偏高外,其他未见异常。提示本品对肝肾功能没有明显损害,主要脏器的病理学检查与对照组相似,未见明显病变。但给药组盲肠重量增加,且与剂量成线性关系。本品对神经系统和呼吸系统无明显作用,静注大剂量(10mg/kg)时可见短暂血压下降伴有心率加快,恢复迅速。表明国产环丙沙星具有相当大的安全范围。     

蜂胶亚急性毒性研究

目的 了解蜂胶的毒性.方法 根据30d喂养试验方法将大鼠分为3个剂量组及溶剂对照组.连续喂养30天后.摘眼球采血作血常规及生化指标测定,取出肝、肾、脾、睾丸称重.并对肝、肾、脾、胃肠、睾丸、卵巢作组织病理学检查.结果 各剂量组大鼠的体重及其增重、进食量、食物利用率与对照组比较差异均无统计学意义（P＞0.05）;个别剂量组血生化、血常规指标与对照组比较,差异有统计学意义（PP＜0.05）,但均在正常值范围内.故认为无生物学意义.其他各剂量组动物血常规（血红蛋白含量、红细胞计数、白细胞计数、白细胞分类）、各项生化指标（血清谷丙转氨酶、谷草转氨酶、尿素氮、肌酐、总胆固醇、甘油三酯、血糖、总蛋白、白蛋白）测定值均在正常值范围内.大鼠的脏体比与对照组比较.差异无统计学意义.对受检脏器作组织病理学检查,未见特异性病变.结论 大鼠连续服用蜂胶30 d,对机体未见不良影响.     

甲磺酸加替沙星对小鼠特异性免疫的调节作用研究

目的考察甲磺酸加替沙星(GFLX)对小鼠特异性免疫防御的调节作用。方法用溶血分光光度法测定GFLX对小鼠抗绵羊红细胞(SRBC)抗体产生的影响；用MTT法测定GFLX对小鼠脾淋巴细胞转化的影响；用结晶紫染色法测定GFLX对小鼠腹腔巨噬细胞产生TNF的影响；用足肿胀法测定GFLX对小鼠迟发型变态反应(DTH)的影响。结果GFLX能增加小鼠特异性抗SRBC抗体(溶血素)的产生；在0．05～40μg／ml范围内能协同刁豆蛋白(conA)或脂多糖(LPS)促进小鼠脾淋巴细胞转化；在0．01～10vg／ml范围内可抑制小鼠腹腔巨噬细胞产生TNF—α；促进小鼠DTH。结论GFLX有调节小鼠特异性免疫防御的作用。     

半夏的化学成分、药理作用及毒性研究进展

目的:综述半夏的化学成分、药理作用及毒性的研究进展,为其进一步研究及合理利用提供参考。方法:以"半夏""化学成分""药理作用""Pinellia ternate""Chemical composition""Pharmacological action"等为中英文关键词,在中国知网、万方数据、维普网、PubMed、ScienceDirect等数据库中组合检索1981年3月-2020年6月发表的相关文献,并结合查阅《中国药典》及相关中药典籍等,对半夏的化学成分、药理作用及毒性的研究进展进行归纳总结。结果与结论:半夏的化学成分包括生物碱类、有机酸类、挥发油类、黄酮类、甾体类和糖类等;其传统药理功效为燥湿化痰、降逆止呕、消痞散结。现代药理学研究发现,半夏亦具有抗肿瘤、抗炎、抗菌、抗癫痫等药理作用;其毒性主要表现为黏膜刺激性毒性、肝肾毒性、妊娠毒性等。半夏作为一种常用的有毒中药,其化学成分丰富、药理作用广泛。对半夏的有效成分及其作用机制进行深入研究,可为进一步研究半夏的药理作用和安全用药打下基础,为充分发挥半夏的药用价值及合理开发利用提供理论依据。     

补骨脂水提取物小鼠灌胃急性毒性及亚急性毒性试验研究

<正>补骨脂是中医、维吾尔医常用药材,均用其治疗白癜风~[1-3]。临床报道和基础研究均发现补骨脂及其复方具有肝毒性~[4-5],其安全性值得关注。本研究对补骨脂水提取物进行小鼠灌胃给药急性毒性及亚急性毒性试验,探讨其毒性作用特点,为其合理应用和药物开发提供科学依据。1材料与方法1.1药品与动物1.1.1动物100只昆明小鼠,♀、♂各半,体质量(20±2)     

Subacute and chronic toxicity studies of fluorocarbon propellants in mice, rats and dogs

Six subacute and chronic inhalation toxicity studies were conducted in rats, mice and dogs treated with fluorocarbon propellants. The studies varied in length from 2 weeks to 23 months and the dose of propellant varied from 164 mg/kg/day to 2240 mg/kg/day. The only signs of toxicity observed were sedation, ataxia and mild depression which occurred in the 2 studies in which the propellant doses were the highest. These effects, observed during and immediately after exposure, disappeared rapidly and were attributed to mild anesthetic properties of the fluorocarbon propellants. Abnormal values were not found in the hematologic, blood chemistry or urinalysis values in any of the 6 toxicity studies. Gross and microscopic examination of tissues of the respiratory tract, including lung, did not reveal any evidence of propellant toxicity, irritation or carcinogenicity. In the 3- and 12-month toxicity studies, EKG changes were not observed in dogs which had received large daily doses of the propellants.     

甲磺酸加替沙星与加替沙星的药物代谢动力学比较

目的甲磺酸加替沙星(GATM)和加替沙星(GAT)是喹诺酮类抗感染药物的新型制剂,对改变酸根的甲磺酸加替沙星在大鼠体内的药物代谢动力学规律和特点进行了考察并和加替沙星进行比较。方法以SD大鼠为研究对象,单剂量口服等克分子剂量(0.0497 mmol.kg-1)GATM和GAT后,采用高效液相色谱法(HPLC)检测血清中GAT的含量,采用3p97程序软件计算二者在大鼠体内的药代动力学参数。结果大鼠单次口服GATM(23.43 mg.kg-1)和GAT(20 mg.kg-1)后,二者的血药浓度经时变化符合一级消除动力学特征,药时曲线拟合为二房室模型,其中GATM的药代动力学参数为:血浆消除半衰期(T12β)9.13 h,药时曲线下面积(AUC)15.05 mg.L-1.h,血药峰浓度(Cm ax)4.41mg.L-1,达峰时间(Tm ax)0.5 h;而GAT的药代参数分别为:T12β10.70 h,AUC 13.84 mg.L-1.h,Cm ax4.25 mg.L-1,Tm ax0.5 h。结论在上述剂量条件下GATM与GAT的吸收(Tm ax、Cm ax、AUC)、分布(V/F)和消除(T12β、CL)参数差异未见显著性,二者的血药浓度经时变化相似,药代动力学规律基本一致。     

甲磺酸加替沙星对小鼠非特异性免疫防御的调节作用

目的考察甲磺酸加替沙星(GFLX)对小鼠非特异性免疫防御的调节作用.方法采用小鼠腹腔巨噬细胞体内、体外及半体内吞噬杀死金葡球菌来反映药物对非特异性免疫系统的影响.结果0.5MIC GFLX体外有促进小鼠腹腔巨噬细胞的杀菌作用;0.5MIC GFLX预处理腹腔巨噬细胞后,能显著提高腹腔巨噬细胞的吞噬及杀菌能力;静脉注射(20mg*kg-1)后巨噬细胞体外也有促进吞噬及杀菌作用;预防性口服给药(2,20mg*kg-1)3d后,小鼠抗感染作用增强,存活率提高.结论GFLX有促进小鼠非特异性免疫防御的作用.     

戴蒙开颗粒对比格犬和小鼠的一般药理学研究

目的 观察戴蒙开颗粒对麻醉犬心血管系统、呼吸系统,对小鼠神经系统的影响。方法 戊巴比妥钠麻醉犬,经十二指肠给予戴蒙开颗粒,记录给药前及给药后30、60、120、180、210、240 min舒张压（SBP）、收缩压（DBP）、平均动脉压（MBP）、心率（HR）、心电图（T波振幅,ST段偏移,PR间期,QRS时限和QT间期）、呼吸频率、呼吸深度的变化。采用灌胃给药,观察戴蒙开颗粒对小鼠阈下睡眠剂量戊巴比妥钠催眠作用、协调运动、一般行为和自发活动的影响。结果 戴蒙开颗粒低、中、高等不同剂量组的比格犬SBP、DBP、MBP、HR、PR间期,QRS时限、QT间期、T波、呼吸频率和呼吸深度等指标均未见明显变化,与对照组相比,P>0.05。戴蒙开颗粒高剂量组和阳性对照组的翻正反射消失率均极显著性的升高（P<0.01）;各剂量、各时间点小鼠协调运动障碍的评级与阴性组比较均无显著性差异（P>0.05）;戴蒙开颗粒低剂量组在给药后90 min自发活动数显著性地降低（P<0.05）,戴蒙开颗粒高剂量组在给药后30、60、90 min自发活动数均极显著性地降低（P<0.01）。结论 戴蒙开颗粒对比格犬心血管系统、呼吸系统未见明显影响;戴蒙开颗粒中、低剂量对小鼠神经系统未见明显影响。     

Subacute toxicity of Basalin in rats

Basalin, a herbicide, was administered orally to male rats at doses ranging from 60 mg to 1.92 g/kg for 13 weeks. Oral LD50 of the compound was 1.65 g/kg. Toxic effects included hyperexcitability and tremors. The cumulative lethal dose (CLD50) at the end of week 13 was 135 mg/kg with a cumulative toxicity factor (CTF) of 12.22. At 1.92 g/kg, no animals survived to 13 weeks. At 60 and 120 mg/kg, there were no significant changes in body weight gain compared with the controls and a significant decrease in total leukocyte count (TLC), erythrocyte sedimentation rate (ESR) and Hb was observed. There was a decrease in spermatogenesis and infiltration of mononucleated cells in the liver.     

青蒿酯钠静脉注射对犬的亚急性毒性

给犬iv青蒿酯钠每天一次,连续14d,90mg/kg使全部动物中毒死亡,45mg/kg中毒表现明显,2/6犬死亡,22.5mg/kg出现轻度中毒,11.25mg/kg未见明显毒副作用,可视为基本安全剂量。毒性作用的主要症状表现为呕吐、摄食量减少,重者出现粘液血便等;心电图Q-T间期延长,Q-T比值增大;化验及病理检查显示骨髓造血抑制,首先是红系成熟障碍,胆汁淤滞,内脏淤血,45mg/kg以上剂量还出现粒系成熟障碍及心、肝、肾、胃肠道、视网膜等组织实质性损伤及相应的血液学和血液生化变化。血液网织红细胞减少或消失仍是最敏感的指标。停药后28d各种变化基本恢复正常。     

Subacute toxicity of alpha-ergocryptine in Sprague-Dawley rats. 1: general toxicological effects.

The dietary subacute toxicity of the ergot alkaloid alpha-ergocryptine was studied in Sprague-Dawley rats. Rats were fed 0, 4, 20, 100 or 500 mg ergocryptine/kg diet for 28-32 days (equal to 0, 0.36, 1.7, 8.9 and 60 mg ergocryptine/kg body weight/day for females and 0, 0.34, 1.4, 6.6 and 44 mg ergocryptine/kg body weight/day for males). The present study describes the general toxicological effects; the effects on metabolic and hormonal parameters will be reported separately. Body weight, body weight gain, food intake and food efficiency were all decreased with a U-shaped dose-response curve, as in both sexes the ranking severity of effects was in the order 100-20-500 and 4 mg/kg diet. Other changes with a U-shaped dose-response relationship included: hematological parameters (decreased MCV and MCH), serum enzyme activities (slightly increased/decreased ALAT, ASAT, GGT), increased serum urea concentrations, decreased glomular filtration (creatinine and urea clearances), decreased absolute organ weights, increased and decreased relative organ weights, atrophy of thymus and in females atrophy of ovary and uterus with in the mid-dose groups no detectable morphological features of an oestric cycle in the uterus. Other parameters, including increased relative liver, heart and ovarian weights and necrosis of the tail, were influenced in a dose-related manner or only in the high dose group. The U-shaped changes for the parameters mentioned above might be caused by the U-shaped dose-response relationship for food intake, which may be explained by the dopaminergic properties of alpha-ergocryptine. It is concluded that in rats fed ergocryptine for 28 days the dose-effect curve is rather steep and that the NOAEL is 4 mg/kg diet.     

Comparison of inhalation toxicity studies of gentamicin in rats and dogs

Abstract

Nebulized gentamicin solution was administered to rats (nose-only) and dogs (face mask) for 14 days with a 14-day recovery period. Control groups of each were exposed to saline aerosols. Mean estimated inhaled lung doses of gentamicin were 39, 123 and 245?mg/kg for rats (deposited doses 6, 17 and 34?mg/kg) over 30, 90 and 180?min, respectively. Since dogs do not tolerate exposures as long as rats, inhaled lung doses were limited to 7, 14 and 41?mg/kg (deposited doses of 1, 3 and 8?mg/kg) over 15, 30 and 60?min. Comparable doses were achieved at the low dose for rats and high dose for dogs. Serum AUCs (14?±?2?µg/mL*h (mean?±?SD) at 6?mg/kg in rats and 11?±?7?µg/mL*h at 8?mg/kg in dogs) showed comparable exposure between the two, implying similar absorbed doses and confirming similar deposited lung doses. Rat exposures resulted in dose-related lung pathology (including low dose) manifested as upper respiratory tract irritant reactions with alveolar histiocytosis, inflammation, airway epithelial metaplasia and lymphomegaly in lung tissue. This was associated with high lung tissue gentamicin levels 24?h post-dose on Day 14 (375?±?33?µg/g at deposited dose of 6?mg/kg). Dose-related kidney tubular necrosis (a well-known toxicity of parenteral gentamicin) was observed, but no test-article related effects on lung histopathology in dogs (even at highest deposited dose of 8?mg/kg) and low levels of lung tissue gentamicin (42?±?11?µg/g) 24?h post-dose on Day 14.