氟吗啉对非洲爪蟾的急性毒性

本研究以非洲爪蟾(Xenopus laevis)处于不同发育期的幼体(蝌蚪)为对象进行了杀菌剂氟吗啉急性毒性的研究。试验以受试蝌蚪48、72、96h死亡数，半数致死浓度及蝌蚪的中毒形态观察为评价终点。试验结果表明。处在同一发育期的蝌蚪，96h LC50值比48h LC50值低。处于不同发育阶段的蝌蚪，随着发育阶段的改变，发育后期的蝌蚪(46／47期和48／50期)要比发育前期的蝌蚪对化学物质氟吗啉表现更敏感：形态观察发现，在不同发育期，中高剂量蝌蚪表现出不同程度的黏液分泌过多、脊柱弯曲、弯尾及体色变淡等症状。     

杀菌剂氟吗啉对两栖动物非洲爪蟾生长发育的影响

使用杀菌剂氟吗啉对发育期在46/47阶段到65/66阶段的非洲爪蟾幼体进行长达20周的生长发育影响研究,通过对生长发育指标成活率、体重、体长和尾长、变态率、畸形数和性别的测定和统计,结果表明:非洲爪蟾变态期(56/58阶段)幼体的生长发育对外界干扰因素非常敏感,导致成活率降低;氟吗啉对非洲爪蟾生长发育的影响虽与对照没有显著差异,但随着处理质量浓度的增大(0.1519～0.9116 mg/L),氟吗啉可降低非洲爪蟾的变态成功率,在同样条件下,氟吗啉有延缓蝌蚪变态发育的影响,处理组变态高潮期所需的时间延长,清水对照蝌蚪的变态高潮期为(14.86±2.79)d.丙酮(13.56±2.7)d,雌二醇组(18.75±4.58)d,氟吗啉从低到高剂量分别为(16.00±2.31)(16.33±2.66)、(17.20±4.82)、(17.50±4.24)d,并且实验中幼体发育还表现出体重减轻,个体较小,出现中毒症状甚至导致死亡;氟吗啉对幼体的性别分化未产生影响.     

应用胚胎检测技术评价氟吗啉对斑马鱼胚胎-幼体发育的影响

采用斑马鱼胚胎发育技术，通过对斑马鱼急性毒性及胚胎时期的鱼卵进行染毒来观测孵化率、畸形率及死亡率，由此评价氟吗啉对斑马鱼胚胎-幼体发育的影响。试验结果表明，氟吗啉对斑马鱼胚胎及成鱼这一段时期的影响较小，根据国家环保局对水生生物的毒性划分标准，氟吗啉的毒性为“低级毒”。     

氟吗啉原药对Wintar大鼠致畸性毒性研究

以Ｗｉｓｔａｒ大鼠为实验动物,进行了氟吗啉（ＳＹＰ－Ｌ１９０）原药对该品系大鼠的致畸性毒性研究,设计剂量为３０ｍｇ／ｋｇ、１３２ｍｇ／ｋｇ、３００ｍｇ／ｋｇ３个剂量组和１个有性对照组（食用油）及１个阳性对照组（敌枯双）,对妊娠大鼠于第６～１５天染毒,在动物怀孕第２０天将妊娠大鼠脱颈椎处死,取出胎鼠进行检查,结果表明：在本试验条件下,以３００ｍｇ／ｋｇ剂量经口投与Ｗｉｓｔａｒ妊娠大鼠,可产生较明显的     

氟吗啉原药对Wistar大鼠致畸性毒性研究

以Wistar大鼠为实验动物,进行了氟吗啉(SYP-L190)原药对该品系大鼠的致畸性毒性研究.设计剂量为30mg/kg、132mg/kg、300mg/kg3个剂量组和1个阴性对照组(食用油)及1个阳性对照组(敌枯双),对妊娠大鼠于第6～15天染毒.在动物怀孕第20天将妊娠大鼠脱颈椎处死,取出胎鼠进行检查.结果表明:在本试验条件下,以300mg/kg剂量经口投与wistar妊娠大鼠,可产生较明显的胚胎毒性作用,但没有出现致畸作用.     

杀菌剂氟吗啉和多菌灵对蚯蚓的急性毒性

采用自然土和OECD标准人工土研究了氟吗啉和多菌灵对蚯蚓的急性毒性，并对试验过程中蚯蚓的中毒症状和形态、行为变化进行了观察。结果表明，氟吗啉在自然土壤中对蚯蚓的LC50为592．73mg／kg，95％置信区间为562．41～623．80mg／kg；氟吗啉在人工土壤中对蚯蚓的LC50为318．79mg／kg，95％置信区间为181．63-543．79mg／kg。多菌灵在自然土壤中对蚯蚓的LC50为26．53mg／kg，95％置信区间为15．98-42．93mg／kg；多菌灵在人工土壤中对蚯蚓的LC50为5．57mg／kg，95％置信区间为2．48～11．83mg／kg。依据农药对蚯蚓的毒性等级划分标准，氟吗啉在自然土壤和人工土壤中对蚯蚓的毒性均为低毒级；多菌灵在自然土壤中对蚯蚓的毒性为低毒级，而在人工土壤中对蚯蚓的毒性为中毒级。     

氟吗啉对家蚕的毒性和安全性评价

研究了氟吗啉对家蚕的胃毒、触杀、熏蒸毒性,并进行安全性评价。试验结果表明：氟吗啉对家蚕2龄起蚕胃毒毒性的LC50为10548．4mg／L;对家蚕触杀毒性的结果为10000．0mg/L浓度以下对2龄起蚕没有毒性作用;对家蚕熏蒸毒性的结果为10000．0mg／L浓度以下对2龄起蚕没有毒性作用。与氟吗啉的推荐使用剂量100-200mg/kg相比,氟吗啉对家蚕安全,对家蚕毒性为“低毒”。     

95%氟吗啉原药亚慢性经口毒性研究

９５％氟吗啉原药对Ｗｉｓｔａｒ大鼠１３周经口喂饲毒性研究结果表明：３０００ｍｇ／ｋｇ及５０００ｍｇ／ｋｇ浓度组雄鼠体重增长受以不同程度的抑制,肝脏也出现不同程度的肿大,肝功能异常,全部雄鼠肝小叶中心部的细胞肿大;５０００ｍｇ／ｋｇ浓度组雄鼠还表现为平均摄食量减少,食物利用率下降,肾功能异常,并有１只雄鼠记异常、双后肢及爪部红肿。３０００ｍｇ／ｋｇ及５０００ｍｇ／ｋｇ浓度组雌鼠体重增长受到抑制,摄食     

新型高效杀菌剂氟吗啉

氟吗啉（flumorph,SYP-L190)是由沈阳化工研究院刘长令等人于1994年创制的新型内吸性杀菌剂。通过7年多的实验室、温室、大田试验，结果表明氟吗啉在100－200mg/L（相当于100－200ga.i./hm^2）剂量下对卵菌纲病原菌引起的黄瓜霜霉病、白菜霜霉病、番茄晚疫病、辣椒疫病、葡萄霜霉病等具有优异的活性。毒理（性）结果表明，其对哺乳动物低毒，氟吗啉对酰胺类菌剂如甲霜灵抗性或敏感的菌株均有活性，具有优异的保护活性、治疗活性和抑制孢子萌发活性，持效期长，无药害、对作物安全，增产效果明显（通常增产20％－50％）；其生物活性尤其是治疗活性、抑制孢子萌发活性以及持效期等明显优于同类品种烯酰吗啉。氟吗啉已获中国和美国发明专利（中国专利号：ZL96115551．5，美国专利号：US6020332），并于1999年商品化，氟吗啉是我国第一个真正实现工业化的、具有自主知识产权的农药品种，也是我国有史以来第一个创制的农用含氟杀菌剂，第一个获得中国发明专利的农用杀菌剂、第一个获得美国发明专利的新农药品种。     

氟吗啉对辣椒疫病的防治效果

室内离体试验结果表明:氟吗啉对沈阳、丹东、彰武3地采集的不同菌株辣椒疫病病原菌(PhytophthoracapsiciLeonian)的EC50值分别为0.171、0.137、0.097ìg/ml,与对照药剂烯酰吗啉的抑菌活性基本一致;温室试验结果表明:供试药剂20%氟吗啉可湿性粉剂对辣椒疫病的EC90值为39.51ìg/ml,活性略优于对照药剂50%烯酰吗啉可湿性粉剂(43.38ìg/ml);多点田间小区试验结果表明:氟吗啉及其混剂对辣椒疫病有优异的防治效果,生产上使用50%氟吗·锰锌可湿性粉剂在推荐使用剂量为600～800ga.i./hm2,施药3～4次,间隔8～10d的条件下,对辣椒疫病有良好的防治效果,优于相同剂量72%杜邦克露可湿性粉剂和25%甲霜灵可湿性粉剂的防治效果。     

Synuclein Analysis in Adult Xenopus laevis

The α-, β- and γ-synucleins are small soluble proteins expressed in the nervous system of mammals and evolutionary conserved in vertebrates. After being discovered in the cartilaginous fish Torpedo californica, synucleins have been sequenced in all vertebrates, showing differences in the number of genes and splicing isoforms in different taxa. Although α-, β- and γ-synucleins share high homology in the N-terminal sequence, suggesting their evolution from a common ancestor, the three isoforms also differ in molecular characteristics, expression levels and tissue distribution. Moreover, their functions have yet to be fully understood. Great scientific interest on synucleins mainly derives from the involvement of α-synuclein in human neurodegenerative diseases, collectively named synucleinopathies, which involve the accumulation of amyloidogenic α-synuclein inclusions in neurons and glia cells. Studies on synucleinopathies can take advantage of the development of new vertebrate models other than mammals. Moreover, synuclein expression in non-mammalian vertebrates contribute to clarify the physiological role of these proteins in the evolutionary perspective. In this paper, gene expression levels of α-, β- and γ-synucleins have been analysed in the main organs of adult Xenopus laevis by qRT-PCR. Moreover, recombinant α-, β- and γ-synucleins were produced to test the specificity of commercial antibodies against α-synuclein used in Western blot and immunohistochemistry. Finally, the secondary structure of Xenopus synucleins was evaluated by circular dichroism analysis. Results indicate Xenopus as a good model for studying synucleinopathies, and provide a useful background for future studies on synuclein functions and their evolution in vertebrates.     

Expanding the Genetic Code in Xenopus laevis Oocytes

Heterologous expression of ligand‐gated ion channels (LGICs) in Xenopus laevis oocytes combined with site‐directed mutagenesis has been demonstrated to be a powerful approach to study structure–function relationships. In particular, introducing unnatural amino acids (UAAs) has enabled modifications that are not found in natural proteins. However, the current strategy relies on the technically demanding in vitro synthesis of aminoacylated suppressor tRNA. We report here a general method that circumvents this limitation by utilizing orthogonal aminoacyl‐tRNA synthetase (aaRS)/suppressor tRNA_CUA pairs to genetically encode UAAs in Xenopus oocytes. We show that UAAs inserted in the N‐terminal domain of N‐methyl‐D ‐aspartate receptors (NMDARs) serve as photo‐crosslinkers that lock the receptor in a discrete conformational state in response to UV photo treatment. Our method should be generally applicable to studies of other LGICs in Xenopus oocytes.     

Developmental Toxicity and Biotransformation of Two Anti-Epileptics in Zebrafish Embryos and Early Larvae

The zebrafish (Danio rerio) embryo is gaining interest as a bridging tool between in-vitro and in-vivo developmental toxicity studies. However, cytochrome P450 (CYP)-mediated drug metabolism in this model is still under debate. Therefore, we investigated the potential of zebrafish embryos and larvae to bioactivate two known anti-epileptics, carbamazepine (CBZ) and phenytoin (PHE), to carbamazepine-10,11-epoxide (E-CBZ) and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), respectively. First, zebrafish were exposed to CBZ, PHE, E-CBZ and HPPH from 5¼- to 120-h post fertilization (hpf) and morphologically evaluated. Second, the formations of E-CBZ and HPPH were assessed in culture medium and in whole-embryo extracts at different time points by targeted LC-MS. Finally, E-CBZ and HPPH formation was also assessed in adult zebrafish liver microsomes and compared with those of human, rat, and rabbit. The present study showed teratogenic effects for CBZ and PHE, but not for E-CBZ and HPPH. No HPPH was detected during organogenesis and E-CBZ was only formed at the end of organogenesis. E-CBZ and HPPH formation was also very low-to-negligible in adult zebrafish compared with the mammalian species. As such, other metabolic pathways than those of mammals are involved in the bioactivation of CBZ and PHE, or, these anti-epileptics are teratogens and do not require bioactivation in the zebrafish.     

持久性有机污染物（POPs）生殖发育毒性的研究进展

持久性有机污染物（persistent organic pollutants,POPs）具有长期残留性、生物蓄积性、半挥发性及高毒性等特征,随着科学技术的发展,POPs的替代物质不断生产出,同时由于检测技术的发展,目前检测出某些POPs替代物质也拥有POPs类似的特性。它们对于人类的健康都存在很大的威胁。研究发现它们几乎对人类的各个系统存在危害。对于孕期暴露于POPs的子代也有毒性作用。本文主要综述了持久性有机污染物的生殖发育毒性及其相关机制的研究进展,希望为POPs的生殖发育毒性研究提供一些理论基础。     

黄瓜霜霉病菌对氟吗啉的抗性风险研究初报

以黄瓜霜霉病菌为材料,通过室内抗性诱导以及大棚抗性诱导等方法,对其抗性情况进行研究。结果表明：经过室内连续15代的抗性诱导,黄瓜霜霉病菌对氟吗啉的抗性略有上升,抗性倍数从初始的1．8l倍上升到3．58倍。在大棚条件下,黄瓜霜霉病菌对氟吗啉的抗性并没有上升,抗性倍数均维持在1．03-1.69之间。另外,抗性菌株的竞争能力明显低于敏感菌株。在不加药的条件下,抗性菌株的频率逐渐下降,从初始的50％下降到0．79％;在间隔用药的情况下,抗性菌株的频率从初始的50％逐渐上升到62.82％,上升速率也非常缓慢。这些结果初步表明,黄瓜霜霉病对氟吗啉的抗性风险可能较低。