Therapeutic antibodies: their mechanisms of action and the pathological findings they induce in toxicity studies

Antibodies can swiftly provide therapeutics to target disease-related molecules discovered in genomic research. Antibody engineering techniques have been actively developed and these technological innovations have intensified the development of therapeutic antibodies. From the mid-1990’s, a series of therapeutic antibodies were launched that are now being used in clinic. The disease areas that therapeutic antibodies can target have subsequently expanded, and antibodies are currently utilized as pharmaceuticals for cancer, inflammatory disease, organ transplantation, cardiovascular disease, infection, respiratory disease, ophthalmologic disease, and so on. This paper briefly describes the modes of action of therapeutic antibodies. Several non-clinical study results of the pathological changes induced by therapeutic antibodies are also presented to aid the future assessment of the toxic potential of an antibody developed as a therapeutic.     

Secondary Stress Responses in Juvenile Brazilian Flounder,Paralichthys orbignyanus,throughout and after Exposure to Sublethal Levels of Ammonia and Nitrite

This study investigated the secondary stress responses of Paralichthys orbignyanus exposed to ammonia and nitrite and after recovery. Fish were exposed to 0.12, 0.28, and 0.57 mg NH₃‐N/L, or 5.72, 10.43, and 15.27 mg NO₂‐N/L for 10 d followed by the same time length for recovery. Ammonia‐ and nitrite‐free water was used as a control treatment. Blood samples were collected after 1, 5, and 10 d of exposure and after recovery. Fish exposed to ammonia presented lower and higher glucose levels after 10 d of exposure and recovery, respectively. Ammonia induced initial and transient ionic disturbances and metabolic alkalosis. Nitrite exposure caused hyperglycemia, increased plasma K⁺ levels, and respiratory alkalosis, whereas metabolic acidosis was observed after recovery. Increased proportion of monocytes and/or granulocytes and reduced number of lymphocytes were demonstrated in fish exposed to 0.28 mg NH₃‐N/L (Day 1) and 10.43 mg NO₂‐N/L (Day 5) and after recovery in the 0.28 and 0.57 mg NH₃‐N/L treatments. Exposure to ammonia decreased the proportion of granulocytes on Day 5. In conclusion, exposure to concentrations at 0.12 mg NH₃‐N/L and 5.72 mg NO₂‐N/L provoked physiological disorders in Brazilian flounder. Nonetheless, fish exposed to 5.72 mg NO₂‐N/L following a 10‐d recovery period showed complete resumption of homeostasis.     

甘蓝型油菜种子萌发期耐铝毒特性综合评价及其种质筛选

种子萌发是油菜植株形态建成的重要阶段,铝毒是酸性土壤中影响其种子萌发的主要因素之一,因此筛选出种子萌发过程中耐铝毒种质对油菜生产及研究具有重要意义。本研究利用5份甘蓝型油菜品种(系)筛选出油菜萌发期耐铝毒种质资源处理的适宜胁迫浓度为90μg mL~(-1)。并以该浓度处理148份甘蓝型油菜品种(系)种子,于萌发期测定其发芽势、发芽率、鲜重、干重、根长和芽长等指标,通过铝毒胁迫耐性综合评价值(A值)、平均隶属函数值(ASF值)、对铝毒加权耐性系数(WAC值)、相关性、频数、主成分、灰色关联度、聚类和逐步回归分析等鉴定萌发期耐铝性,建立萌发期对铝毒耐性综合评价模型并筛选出适宜的评价鉴定指标。结果表明, 148份甘蓝型油菜的萌发期各指标在品种(系)间存在显著差异;筛选出萌发期耐铝毒甘蓝型油菜品种(系) 01188、WH-20、A109、甲预31棚等。根据灰色关联度及回归分析结果认为,在油菜萌发期测定其根长、芽长、鲜重、发芽率和发芽势,通过回归方程估算其A值,可以初步判断甘蓝型油菜种质的耐铝毒特性。     

不同形态硼对油菜幼苗铝毒的缓解效应及其FTIR特征分析

采用水培法,以油菜品种Cao 221167为试验材料,设置无机态硼酸(BA)和有机态山梨醇硼(SB)及不同Al~(3+)(0、100、200和500μmol L~(–1))处理,研究不同形态硼(B)对油菜幼苗铝(Al)毒的缓解作用及不同形态B之间的缓解效应差异,以及利用FTIR(傅里叶红外光谱)技术分析叶片各物质含量的变化。结果表明,Al毒胁迫下,不同形态B(BA和SB)处理,显著提高植株生物量和根系长度(0、100、200和500μmol L~(–1) Al毒胁迫下BA处理根长分别增加了52.15%、101.45%、366.70%和18.73%;SB处理分别增加了46.80%、133.98%、261.36%和10.77%),提高色素含量和SOD活性,而降低了Al含量、MDA含量和POD活性。不同形态B处理下,油菜幼苗在200μmol L~(–1) Al~(3+)处理下长势、生物量及色素含量最高。在500μmol L~(–1) Al~(3+)处理下,油菜幼苗株高、根长、总干鲜重及色素含量显著低于无Al处理;FTIR分析表明,Al毒胁迫下油菜叶片中蛋白质和低聚糖等含量明显上升,加硼明显降低了蛋白质和低聚糖的含量,且BA处理降低幅度明显高于SB处理。说明不同形态B(BA和SB)的添加均明显缓解Al毒,且BA对Al毒缓解效果优于SB,这为农业生产中施用何种硼肥来缓解Al毒起到一定的指导作用。     

玉米赤霉烯酮对动物繁殖性能的毒性作用及其机制

玉米赤霉烯酮（ZEA）一种由镰刀菌属产生的次级代谢物，化学结构与内源性雌激素相似，因此，ZEA可通过与雌激素竞争性结合雌激素受体，导致动物机体生殖激素代谢紊乱，诱发生殖器官形变及功能障碍，严重危害动物繁殖系统，解决ZEA污染问题己经成为当务之急。本文对ZEA的理化特性、毒性作用等进行综述，以期为有效缓解ZEA毒性及提高动物繁殖性能、促进畜牧业健康发展提供理论依据。     

结石通片对小鼠的急性毒性试验及其对乙二酰胺致大鼠肾结石的作用研究

[目的] 研究结石通片对小鼠的急性毒性作用,对健康大鼠的利尿作用,以及对乙二酰胺致大鼠肾结石的调节作用。[方法] 取ICR小鼠40只,雌、雄各半,随机分为对照组与给药组,每组20只,观察结石通片给药前后小鼠的体重变化和死亡情况;另取SD大鼠36只,雌、雄各半,分为对照组、低剂量组（给予5%结石通片溶液）和高剂量组（给予10%结石通片溶液）,统计各组大鼠24 h排尿量;并采用42只雄性SD大鼠,考查结石通片对给予乙二酰胺（2%掺喂）后大鼠体重、肾重和肾重比的影响。[结果] 给予结石通片溶液后,连续观察7 d,小鼠的各项生理活动未见明显异常,给药组与对照组相比体重差异不显著（P>0.05）;与对照组比较,给予结石通片溶液后大鼠24 h内排尿量明显增加（P<0.01）;与对照组比较,给药组随着给药剂量的增加,结晶和结石的数量极显著（P<0.01或P<0.001）减少,形成结石的动物数量极显著（P<0.01或P<0.001）减少。[结论] 结石通片对小鼠无明显急性毒性作用,对大鼠利尿作用明显,并对乙二酰胺致大鼠肾结石具有明显抑制作用。     

Toxicity of cadmium and its competition with mineral nutrients for uptake by plants:A review

Cadmium(Cd)is a toxic heavy metal occurring in the environment naturally and is also generated through various anthropogenic sources and acts as a pollutant.Human health is affected by Cd pollution in farmland soils because food is the main source of Cd intake in the non-smoking population.For crops,Cd toxicity may result from a disturbance in uptake and translocation of mineral nutrients and disturbance in plant metabolism,inhibiting plant growth and development.However,plants have Cd tolerance mechanisms,including restricted Cd uptake,decreased Cd root-to-shoot translocation,enhanced antioxidant enzyme activities,and increased production of phytochelatins.Furthermore,optimal supply of mineral nutrients is one of the strategies to alleviate the damaging effects of Cd on plants and to avoid its entry into the food chain.The emerging molecular knowledge contributes to understanding Cd uptake,translocation,and remobilization in plants.In this review,Cd toxicity and tolerance mechanisms,agricultural practices to minimize Cd accumulation,Cd competition with essential elements(calcium,copper,iron,zinc,and manganese),and genes associated with Cd uptake are discussed in detail,especially regarding how these mineral nutrients and genes play a role in decreasing Cd uptake and accumulation in crop plants.     

Sublethal effect of avermectin and acetamiprid on the mortality of different life stages of Brontispa longissima (Gestro) (Coleoptera: Hispidae) and its larvae parasitoid Asecodes hispinarum Bouček (Hymenoptera: Eulophidae)

The beneficial parasitoid Asecodes hispinarum Bouček plays an important role in integrated pest management (IPM) of the coconut leaf beetle, Brontispa longissima (Gestro), in China. A. hispinarum females parasitize 3rd to 4th instars B. longissima larvae. Hatched parasitoid larvae develop within the host, and parasitoid adults emerge through holes that they chew through the cuticle of the host. Although chemicals serve as the main short term control agents, the compatibility of biological and chemical control has never been investigated for this system. This study examined the responses of immature and adult B. longissima and its larval parasitoid A. hispinarum to avermectin and acetamiprid. Avermectin caused complete mortality of 2nd to 4th instar larvae, and of adults of B. longissima at 10, 15 and 2 d after treatment, respectively. However, 26.7% of the 2nd instar larvae, 55.3% of the 4th instar larvae, and 74%, of adult B. longissima were still alive 40 d after acetamiprid application. Following avermectin exposure, 17.5%, 9.2% and 23% of mummified B. longissima larvae contained viable adult parasitoids for the parasitoid egg, larva and pupa treatments, respectively, and the numbers of dead parasitoids per mummy were 3.3, 7.2 and 13.3 for the egg, larva and adult treatments, respectively. However, for acetamiprid treatment, 70–75.9% of mummified B. longissima larvae contained viable adult parasitoids in all three stage treatments, and the number of dead parasitoids per mummy was 2.8, 2 and 3.4 in egg, larva and adult treatments, respectively. This study showed that a sublethal dose of avermectin is more toxic than acetamiprid to B. longissima and A. hispinarum. Therefore, direct contact of the parasitoid with avermectin should be avoided when this insecticide is used to control B. longissima.     

5种杀虫剂对青菜黄曲条跳甲的毒力测定及田间药效

为了筛选有效防治青菜黄曲条跳甲的药剂,在室内测定了5种杀虫剂对黄曲条跳甲成虫的毒力,并开展了这5种药剂对黄曲条跳甲的田间药效试验。毒力测定结果表明,10%啶虫脒WP对黄曲条跳甲的毒力最高,28%杀虫·啶虫脒WP毒力最低,LC50分别为7.20 mg/L和18.63 mg/L,5种药剂的毒力大小依次为:10%啶虫脒WP>42%啶虫·哒螨灵WP>5%鱼藤酮SL>15%哒螨灵EC>28%杀虫·啶虫脒WP。田间药效试验结果表明,42%啶虫·哒螨灵WP和15%哒螨灵EC的防效最优,10%啶虫脒WP、28%杀虫·啶虫脒WP和5%鱼藤酮SL 3种药剂总体防效相当,但低于42%啶虫·哒螨灵WP和15%哒螨灵EC。综合来看,建议使用42%啶虫·哒螨灵WP 126~189 g/hm2、15%哒螨灵EC 90~135 g/hm2、28%杀虫·啶虫脒WP 294~420 g/hm2、10%啶虫脒WP 60~90 g/hm2、5%鱼藤酮SL 150~225 g/hm2对青菜黄曲条跳甲进行防治。