速效咽喉灵冲剂毒性研究

本文报告了速效咽喉灵冲剂小鼠急性毒性和大鼠60天长期毒性试验。结果表明,速效咽喉灵冲剂对小鼠灌胃给药的LD_(50)>120g/kg/天;大鼠60天长期毒性试验对动物一般状况、体重增长、外周血象、肝肾功能及病理组织学检查等未见明显毒性     

速效咽喉灵冲剂的毒性研究

本文报告了速效咽喉灵冲剞小鼠急性毒性和大鼠60天长期毒性试验。结果表明,速效咽喉灵冲剂对小鼠灌胃给药的LD_(50)>120g/kg/d;大鼠60天长期毒性试验对动物一般状况,体重增长,外周血象、肝肾功能及病理组织学检查等未见明显毒性。     

心元胶囊的药理研究

心元胶囊由首乌、丹参、三七、西洋参等中药组成,临床对治疗和预防冠心病等心血管疾病有肯定疗效。动物试验证明,小鼠灌胃急性毒性试验LD_(50)。为每公斤体重262.95(251.7～274.7)克原生药(相当于临床用药的1143倍。三个剂量组大白鼠90天灌胃长期毒性试验,最高剂量64.3g/kg原生药灌胃给药以及恢复期观察,对动物的行为活动,体重,血象,血生化,脏器指数无影响,主要脏器无组织形态改变。药效学证明15g/kg原生药具有明显的改善结扎麻醉杂种狗冠状动脉心肌缺血后的血流     

痛立舒口服液动物毒理学研究

目的：研究痛立舒口服液小白鼠急性毒性和大白鼠60天长期毒性试验。方法：采用小白鼠最大耐受量测定法和长期毒性试验进行研究。结果：痛立舒口服液对小鼠灌胃给药的LD50＞189g(生药)kg。大鼠长期毒性试验对动物一般行为活动、体重增长、外周血象、肝肾功能及病理组织学检查等与对照组比较未见明显差异(P＞0.05)。     

地龙提取液药理与毒理实验研究

供本实验用地龙液,是按西南农业大学提供的技术工艺,取人工饲养的大平2号活地龙提得的溶液,收得率约60％左右。小鼠一次灌胃给药40ml/kg,观察7天,未见异常反应。亚慢性毒性试验,采用小鼠口服地龙液,连续90天,对两个剂量级及对照组动物的生长无影响,经病理学检查对心、肝、肾等组织,未引起实质性损害;又家兔灌胃     

人胚细胞素A、B两注射剂毒性试验和一般药理试验研究

人胚细胞素由人胚肝、胸腺等组织制备,临床应用肿瘤等疾病的预防和治疗有一定的疗效。动物试验证明,小鼠尾静脉和腹腔注射最大耐受量为每公斤体重分别为1.0和2.0克;2.5和5.0克,相当于临床拟用剂量的312和625倍,未见毒性反应。两注射剂杂种犬120天四肢肌肉注射和2周恢复期观察的长期毒性试验,对狗的行为活动、食量、体重、血象、血液生化、脏器指数,以及主要脏器     

次硝酸铋与葡萄糖酸锌对顺铂毒性防护的比较

本文以昆明种小鼠为实验对象,观察了次硝酸铋(BSN)和葡萄糖酸锌(ZG)对顺铂(CDDP)致死毒性及CDDP引起的外周血白细胞和肾功能变化,以比较两种药物对CDDP毒性的防护效果。 试验方法:1.致死毒性实验小鼠90只,雌雄各半,随机分成9组,每组10只,分别Po(口服)蒸馏水,BSN(50mg/kg)和ZG(140mg/kg),第六天开始ip(腹腔注射)CDDP(剂量为14.0,13.5,13.0mg/kg)以注射当日为0天,观察小鼠成活情况,共观察15天。2.白细     

利福喷丁的毒性研究

(一)急性毒性:小鼠口服4g/kg,腹腔注射1g/kg;大鼠口服2g/kg,观察一周均未见动物死亡。 (二)长期毒性:大鼠、狗连续口服不同剂量的药物6～8月,饮食、活动等均未见异常,肝、肾功能,血象与对照组相比,无明显变化,病理组织检查,无药物性病变。 (三)三致毒性:致畸试验阳性,88 mg/kg与利福平相似出现胚胎毒性。     

一种新型聚酯醚降解材料生物相容性研究

作者主要叁照国际标准化组织（ＩＳＯ）对医用材料的评价标准，对新型聚酯醚降解（聚癸二酸－聚乙二醇共聚物ＰＳＢＥ）进行了１２项生物学检测指标的研究。包括小鼠腹腔注射ＬＤ５０的测定、急性全身毒性、热原、细胞毒性、过敏、溶血、皮肤和眼粘膜刺激、亚慢性毒性、体内短期和长期植入、小鼠骨髓多染红细胞微核和Ａｍｅ’ｓ试验。研究结果表明：新型聚酯醚降解材料ＰＳＢＥ具有优良的生物相容性。     

高催化活性Pt纳米颗粒的生物毒性研究

目的探究一种具有高催化活性的新型金属铂(Pt)纳米颗粒的生物毒性作用。方法选择C57BL/6雄性小鼠(SPF级)52只,鼠龄6~8周,体质量22~24 g。采用"一锅合成法"合成六面体状金属Pt纳米颗粒。将中国仓鼠卵巢(CHO)细胞与质量浓度0、0.4、1.2、3.7、11.0、33.0、100.0、300.0μg/mL Pt纳米颗粒溶液共培养,采用噻唑蓝(MTT)法测定细胞存活率、细胞毒性、细胞活性氧簇(ROS)变化。将小鼠分3批次(每批次为20、16、16只),按体质量随机分为正常对照组和实验组,测量小鼠30 d体质量变化、骨髓DNA和骨髓有核细胞(BMNC)数量、小鼠肝脏超氧化物歧化酶(SOD)和丙二醛(MDA)水平、Pt元素在小鼠体内的生物分布、血常规和生物化学指标及对主要脏器的病理分析,分析Pt纳米颗粒对小鼠的生物毒性作用。结果 Pt纳米颗粒尺寸为(8.58±1.23) nm,晶格间隙为0.227 nm,呈面心立方晶格。体外研究结果表明,质量浓度300.0μg/mL Pt纳米颗粒溶液作用24、48 h,CHO细胞存活率85%、90%。质量浓度50.0μg/mL Pt纳米颗粒溶液可抑制细胞内ROS的产生。动物研究结果表明,质量浓度5 mg/mL Pt纳米颗粒溶液可使正常C57BL/6小鼠出现短暂的体质量下降(给药后15 d左右可恢复正常);作用30 d后,大部分聚集于肝脏及脾脏,与正常小鼠相比,实验小鼠只在肝脏组织中发现轻微炎症。实验小鼠血常规、生物化学指标未发现明显差异性变化;DNA和BMNC数量均出现轻微减少;Pt纳米颗粒溶液体内作用7 d后,肝脏组织的MDA水平出现轻微降低现象,而SOD活性未出现明显改变。结论质量浓度300.0μg/mL以下的Pt纳米颗粒溶液对CHO细胞无明显细胞毒作用,而质量浓度5 mg/mL Pt纳米颗粒溶液对小鼠虽然具有急性氧化应激毒理作用,但其毒理效应可在30 d内由生物体自行调节而恢复。     

Acute toxicity studies of safer and more effective analogues of N,N-diethyl-2-phenylacetamide

The present work was designed to evaluate the toxicity of various synthesized aromatic amides that are analogs of N,N-diethyl-2-phenylacetamide, a well known insect repellent. The toxicity profile of these compounds was compared with N,N-diethyl-2-phenylacetamide as well as other registered insect repellents namely N,N-diethyl-3-methyl benzamide and N,N-diethylbenzamide. The primary skin irritation index values of the compounds, dermal toxicity of the chemicals and acute oral toxicity data to assess the safety of the synthesized aromatic amides are reported in this paper. Results of hematological and biochemical studies of these analogues are reported and discussed.     

Serum Mucin Antigen (CASA) as a Marker of Amiodarone-Induced Pulmonary Toxicity

Amiodarone is used to treat life-threatening cardiac arrhythmias. Amiodarone-induced pulmonary toxicity (APT) can be difficult to diagnose. APT may result in increased mucus production and mucin expression. Thus, serum mucin-1 was evaluated as a marker for amiodarone-induced pulmonary toxicity. Concentrations of mucin-1 in peripheral blood were determined using cancer-associated serum antigen (CASA) assay in patients taking amiodarone. Eight of ten patients who developed major amiodarone toxicity had high serum CASA levels. Patients with toxicity had a significantly higher mean rank CASA concentration compared with those without major toxicity. CASA shows potential as a marker for amiodarone-induced toxicity, particularly pulmonary toxicity.     

Is azathioprine a better immunosuppressive than 6-mercaptopurine?

The toxicities and immunosuppressive potencies of single doses of 6-mercaptopurine and azathioprine have been compared in mice, using the 30-day mortality as a measure of toxicity, and reduction in spleen plaque-forming cells in response to sheep erythrocytes as a measure of immunosuppression. When compared on the basis of equivalent toxicity, 6-mercaptopurine was consistently the more effective agent by the intraperitoneal route. By the subcutaneous route, 6-mercaptopurine was more effective at doses above the LD-30; at lower doses, azathioprine was marginally better, but the difference was probably not significant. For the same cost in toxicity, azathioprine was six to seven times more effective as an immunosuppressive by the subcutaneous as by the intraperitoneal route.     

磁导向阿霉素-羧甲基葡聚糖磁性毫微粒的毒性的研究

以阿霉素(ADR)为药物模型，制备了阿霉素—羧甲基葡聚糖磁性毫微粒(ADR—CMD MNPs)，对比研究了静脉给药后其与阿霉素普通制剂对小鼠的急性毒性作用、累积毒性作用以及药物在动物心肌组织的分布情况，结果表明：相对于普通制剂，阿霉素的磁性毫微粒制剂的急性毒性明显降低，LD50值达到阿霉素普通制剂的5.06倍，连续给药情况下小鼠的死亡率、体重和白细胞损失都有明显下降；药物分布实验表明阿霉素磁性毫微粒制剂静脉给药后在小鼠心肌组织中的浓度和积累作用明显低于普通制剂，这对降低阿霉素固有的对心肌组织毒副作用非常有利。     

Tropism and toxicity of adeno-associated viral vector serotypes 1, 2, 5, 6, 7, 8, and 9 in rat neurons and glia in vitro

Recombinant adeno-associated viral (rAAV) vectors are frequently used for gene delivery to the central nervous system and are capable of transducing neurons and glia in vitro. In this study, seven serotypes of a rAAV vector expressing green fluorescent protein (GFP) were characterized for tropism and toxicity in primary cortical cells derived from embryonic rat brain. At 2 days after transduction, serotypes 1 and 5 through 8 expressed GFP predominately in glia, but by 6 days post-transduction expression was neuronal except for AAV5. AAV2 and 9 produced minimal GFP expression. Using cell viability assays, toxicity was observed at higher multiplicities of infection (MOI) for all serotypes except AAV2 and 9. The toxicity of AAV1 and 5-8 affected mostly glia as indicated by a loss of glial-marker immunoreactivity. A frameshift mutation in the GFP gene reduced overall toxicity for serotypes 1, 5 and 6, but not 7 and 8 suggesting that the toxicity was not solely due to the overexpression of GFP. Collectively, a differential tropism and toxicity was observed among the AAV serotypes on primary cortical cultures with an overall preferential glial transduction and toxicity.     

Combined toxicity of ethanol with chlorpromazine,diazepam, chlormethiazole or pentobarbital in mice

The intravenous toxicity of chlorpromazine, diazepam, chlormethiazole and pentobarbital was estimated at various intervals after intraperitoneal ethanol administration as well as after 6-day treatment in mice. The effects of these drugs on the acute toxicity of ethanol were also estimated. The most toxic combination seemed to be chlormethiazole or pentobarbital with ethanol.     

Circadian variations in the nephrotoxicity of the vancomycin-gentamicin combination in rats]

Male Wistar rats were used to evaluate the influence of time of administration of a single high dose of vancomycin (V), gentamicin (G) or vancomycin-gentamicin combination (V/G) on excretion of a brush border enzyme, alanine aminopeptidase (AAP) and of a lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG). Increased urinary excretion is considered as an early manifestation of renal toxicity. The rats were placed in temperature-controlled quarters with intermittent lighting (12 hours light/12 hours dark). V was given intraperitoneally in a dose of 200 mg/kg, G was given intramuscularly in a dose of 100 mg/kg, and the V/G combination was given in the same doses and by the same routes as each drug alone. A control batch of rats received an intraperitoneal injection of saline. In the four batches, the injection was given at 8 am, 2 pm, 8 pm and 2 am. Substantial brush border toxicity was found. Toxicity of G was greatest at 2 pm and lowest at 2 am, whereas for V, toxicity was greatest at 2 am and lowest at 2 pm. With the V/G combination, brush border toxicity was greatest at 2 am and lowest at 8 am. Lysosomal toxicity was no significant after administration of V or G. In contrast, the V/G combination induced very significant lysosomal toxicity which was greatest at 2 pm and smallest at 8 am. These results show that circadian variations in renal toxicity occur not only with V and G alone but also with the V/G combination.     

Predisposing factors for nevirapine toxicity among AIDS patients with low baseline CD4 count

The objective of the study was to determine the predisposing factors and incidence of toxicity among AIDS patients treated with a nevirapine (NVP)-based regimen in clinical practice. A retrospective cohort study of representative samples of AIDS patients treated with a NVP-based regimen was performed. A total of 206 adult HIV/AIDS cases with median age (IQR) 33 years (range, 29-38 years), 51% male, treated between January 2004-December 2005, were included. Most (92.2%) of the patients were na?ve to antiretroviral drug. The incidence of NVP toxicity was 1.09/100 person-months. The median onset time was 4 weeks post NVP initiation (2.57 weeks for skin toxicity and 12.43 weeks for hepatic toxicity). History of drug allergy and NVP toxicity were significantly associated (p = 0.006), as were sulfamethoxazole allergy and toxicity (p = 0.015). Regarding concomitant medication, concurrent anti-tuberculosis drugs significantly increased the risk of NVP associated liver toxicity (p = 0.001). Therefore, it is important to monitor adverse events from NVP, including liver function tests among HIV/AIDS patients with history of drug allergy, especially against sulfamethoxazole, and those concurrently treated with antituberculosis drugs.     

The serum digitalis concentration--does it diagnose digitalis toxicity?

We propose that an investigation of the serum digitalis concentration as a test for digitalis toxicity should (1) study patients with similar toxic manifestations, (2) obtain control concentrations from nontoxic patients with symptoms suggesting toxicity, (3) define criteria for toxicity and nontoxicity, (4) select representative patients, (5) describe the study population and (6) analyze how much diagnostic information the serum digitalis concentration provides that cannot be inferred from other observations. To determine if available evidence validates the digitalis concentration as a test for toxicity 27 reports were reviewed. No investigation employed symptomatic controls. Of five studies most consistent with points 1-5 only three demonstrated higher mean serum digitalis concentrations in toxic patients. Whether knowledge of the digitalis concentrations was diagnostically more useful than knowledge of the digitalis dosage, renal function, serum potassium concentration and cardiac status was not determined in any study. The usefulness of the serum digitalis concentration as a test for digitalis toxicity is therefore not established.