鼠得克Difenacoum对黑线姬鼠、高山姬鼠的毒力测定及适口性试验

鼠得克Difenacoum是第二代抗凝血杀鼠剂,其化学名称为3-(3-P二二苯基—1、2、3、4—四羟基萘基—4—羟基香豆素)。本药剂对有耐药性的鼠类效果更为显著。为确定其对黑线姬鼠、高山姬鼠的毒力(按抗凝血灭鼠剂常规测定法作一或三次灌胃测定)、适口性等毒杀效果,特作下述实验,现将实验情况简报于后:一、毒力测定:(一)药物:系军事医学科学院流行病学研究所1979年合成的纯品一克。(二)动物:野外捕获的黑线姬鼠、高山姬鼠在实验室饲养7～20天,分别选择20～35克健康成年鼠8—10只,雌雄各半备用。(三)给药:将鼠得克按所需浓度,精密称取后,用聚乙二…     

杀鼠灵防治动物饲养场褐家鼠的效果观察

动物饲养场的鼠害防治是鼠防领域中的难题。采用急性鼠药效果差,不安全。1981年6月,我们采用慢性灭鼠剂杀鼠灵(warfarin),在北京某实验动物场进行了灭鼠试验。现报道如下。 (一) 材料和方法杀鼠灵,化学名称为3-(α-丙酮基苄基)-4-羟基香豆素。先用淀粉将杀鼠灵稀释成含量0.1％的母粉,取1份母粉加19份玉米粉混合均匀,即成0.005％浓度的毒饵。试验现场是动物饲养场的豚鼠房。8个隔     

澳门地区褐家鼠对溴鼠灵的抗性检测及其Vkorc1基因多态性分析

第二代抗凝血灭鼠剂因比第一代抗凝血灭鼠剂有更好的灭杀效果和安全性而被广泛使用,但长期使用同样也存在引发鼠类抗性的隐患。近年,学者已发现了第二代抗凝血灭鼠剂溴敌隆 (bromadiolone) 和鼠得克 (difenacoum) 的抗性鼠。溴鼠灵 (brodifacoum) 是一种目前在国内广泛使用且毒性极强的第二代抗凝血灭鼠剂,能引发鼠类凝血功能障碍和细胞毒性,但对于溴鼠灵是否已驱动鼠类发生抗性进化尚不清楚。澳门地区从1995年开始持续使用溴鼠灵,为研究鼠类对溴鼠灵的抗药性进化提供了良好模型。本研究于2019年10—12月在澳门地区共捕获61只褐家鼠,对其中44只开展了LFP实验 (0.005%溴鼠灵),实验鼠的平均摄毒量为 (15.28 ± 1.40) mg/kg,在7天内全部死亡。此外,对全部61只褐家鼠的维生素K环氧化物还原酶复合体亚单位1 (vitamin K-epoxide reductas complex 1, Vkorc1) 的基因序列测定表明,在Vkorc1基因外显子的已知抗药关联位点处未检测到非同义核苷酸突变,但检测到2个同义核苷酸突变 [第68位氨基酸：H (CAC)-H (CAT),突变发生率为100%;第82位氨基酸：I (ATA)-I (ATT),突变发生率为32.72%]。该研究表明,使用溴鼠灵25年后,澳门地区褐家鼠虽没有产生群体抗药性,但仍需持续监测抗药性的发生和发展。     

杀鼠灵灭鼠试验

杀鼠灵(Warfarin)是香豆素类抗凝血灭鼠剂,我们于1984年3—5月对2.5/万的杀鼠灵毒饵的灭鼠效果作了初步试验观察,结果如下。 (一)小现场灭鼠效果 为开展大面积灭鼠工作积累经验,在本所实验动物房(约200平方米)作灭鼠效果观察,投药前用食饵消耗法测定鼠密度,然后投放毒饵65堆,每堆20克,每天补充消耗的毒饵,连续投放8天,过10天后再用食饵消耗法测定鼠密度,结果灭鼠率达87.5％,投放毒饵第3天拣到死鼠1只,第4天9只,第5天6只,第6天5     

0．025％杀鼠灵灭鼠效果观察

杀鼠灵是我国第二代抗凝血灭鼠剂。为了解其效果和使用方法,我们于1987年2-3月在湖北某宾馆进行了室内外灭鼠效果观察,结果报告如下。 试验药物 杀鼠灵原药系张家口市鼠药厂1983年产品,批号2-33,纯度为99.45％。     

诺丽发酵果汁化学成分及抗氧化活性研究

采用多种色谱技术从诺丽(Morinda citrifolia)发酵果汁中分离得到10个化合物,并应用波谱学方法进行结构鉴定,分别鉴定为6,7-二羟基香豆素(1)、7-羟基香豆素(2)、东莨菪亭(3)、6-羟基-7-甲氧基香豆素(4)、7-羟基-4-甲基香豆素(5)、1,2,3,4-四氢-β-咔啉-3-羧酸(6)、(1S,3S)-1-甲基-1,2,3,4-四氢-β-咔啉-3-羧酸(7)、(1R,3S)-1-甲基-1,2,3,4-四氢-β-咔啉-3-羧酸(8)、对羟基苯甲酸(9)、龙胆酸(10)。利用DPPH和ABTS+·自由基清除能力法进行抗氧化活性测定,其中化合物1、3、4、10抗氧化活性较强,化合物1和10清除DPPH和ABTS+·自由基能力的IC50值分别为160.87、8.32和6.17、9.71μmol/L。化合物2、5~8均系首次从该植物中分离,本研究得到诺丽发酵果汁中香豆素、有机酸和生物碱三类成分,并且化合物1、3、4、10抗氧化活性良好。     

四种常用抗凝血灭鼠剂对两种家栖鼠实验室药效比较

比较了几种抗凝血灭鼠剂对家栖鼠的毒效。以常规浓度（溴敌隆０．００５％,杀鼠迷、杀鼠灵和敌鼠钠０．０２５％）的毒饵,对靶标鼠进行单笼饲养无选择和有选择以及围栏群养有选择摄食试验,用毒杀率和摄食系数评价毒效和适口性。结果表明：⑴实验鼠单笼饲养试验：溴敌隆和杀鼠迷对大白鼠适口性好,毒杀率高,敌鼠钠适口性差;对小白鼠的毒效和适口性,溴敌隆最好,敌鼠钠最差;⑵三省四地区的褐家鼠单笼饲养无选择试验,溴敌隆、杀     

大隆灭鼠试验

大隆(TALON,brodifacoum)是一种香豆素类有机化合物。是70年代后期国外出现的第二代抗凝血灭鼠剂。大隆灭鼠剂与第一代抗凝血灭鼠剂比较有下述优点: 1.使用浓度低。采用单剂量投药就可有效     

氯敌鼠灭鼠研究

氯敌鼠,化学名称:2-(苯基对氯苯基)乙酰基1,3,茚满二酮。分子式C_(23)H_(15)O_3Cl分子量:374.5熔点:138—140℃结构式: 化学性质:是一种不溶于水,溶于丙酮、乙醇等有机溶剂的黄色粉末。氯敌鼠是一种较新的抗凝血灭鼠剂,国内还未见较详细的正式报道。仅见对长爪沙鼠进行过致死中量(毫克/公斤)的测定和部分灭鼠试验;一次投毒为0.05,3次投毒为0.012,它的毒力显著超过目前常用的敌鼠钠盐,尤其是一次毒力。为了寻找减少投     

滇南红厚壳的化学成分

从滇南红厚壳（Calophyllum polyanthum Wall.et Choisy)的果实乙醇提取物中分离得到2个新化合物－滇南红厚壳内酯A（calopolyanolide A,1),滇南红厚壳内酯B（calopolyanolide B,2)以及3个已知化合物calanolide E2(3),voleneol(4)和没食子酸（gallic acid,5)。经波谱学鉴定了2个新化合物的结构分别为：6,6－二甲基－12α-(2α,3α-H）-12α-（2－甲基－3－羟基丁酰基）－8b－羟基－4－苯基－吡喃并－二氢香豆素;6,6－二甲基－12a-(2α,3β-H）-12a-(2-甲基－3－羟基丁酰基）－8b－羟基－4－苯基－吡喃并－二氢香豆素。     

溴敌隆防治高原鼠兔和高原鼢鼠的研究

溴敌隆(Bromadiolone)是近年来新出现的第二代抗凝血杀鼠剂中的一个新品种,最近已在欧洲各国、加拿大、美国市场上出售。青海省化工科研设计所在国内首先合成。     

The effect of in vivo heat treatments on blowfly flight muscle mitochondrial function: Effects on partial reactions of the respiratory chain

1. 1. The development of thermotolerance has been shown to protect blowfly flight muscle mitochondrial function from damage resulting from an LD₅₀ in vivo heat dose.

2. 2. The principal sites of the damage have been studied using specific inhibitors of the respiratory chain, rotenone and antimycin A, together with substrates that stimulate respiration through the different complexes.

3. 3. Complex I was identified as the primary site for heat damage. State III respiration was inhibited following the LD₅₀ in vivo heat dose, and uncoupling with FCCP did not restore respiration to control levels, indicating that the respiratory enzymes were inactivated. The development of thermotolerance protected this site from heat damage.

4. 4. In contrast, G3-P stimulated respiration was the same in control, LD₅₀ in vivo treated controls and LD₅₀, in vivo treated thermotolerant mitochondria, and significantly higher than state III respiration of LD₅₀ in vivo treated controls. This suggested that respiration through G3-P dehydrogenase, Co enzyme Q and Complex III is not damaged. However, as G3-P stimulated respiration of coupled mitochondria from LD₅₀ in-vivo treated flies was markedly reduced (El-Wadawi and Bowler, 1995. J. exp. Biol. 198: 2413–2421), phosphorylation at complex III may be inhibited also.

5. 5. Ferrocyanide stimulated respiration through cytochrome c-Complex IV was also inhibited in LD₅₀ in vivo treated flies, as compared with unheated control mitochondria. However, thermotolerance protected this site also from heat damage.

     

士的宁杀灭高原鼢鼠的试验研究

士的宁(strychnine)是从番木鳖(Shrychox nuxvomica)种子提得的一种生物碱。作为兴奋剂用于医疗方面和作为生化试剂使用,但作为杀鼠剂用来防治害鼠,国内尚未见有报道。在国外,士的宁被用于防治危害森林草地、作物地内的地下鼠和其它有害哺乳动物(Marsh,1978;Barnes,1980;Crouch,1980;Anthony,1984)。作者于1983-1984年期间针对草原主要害鼠之一--高原鼢鼠(Myospalax baileyi)进行了灭杀试验研究。     

乙基多杀菌素和联苯肼酯对地熊蜂的毒性及风险评估

【目的】明确乙基多杀菌素和联苯肼酯对地熊蜂Bombus terrestris的毒性, 探讨这两种农药亚致死浓度对地熊蜂体内乙酰胆碱酯酶(AchE)、谷胱甘肽-S-转移酶(GST)和羧酸酯酶(CarE) 3种解毒酶活性的影响。【方法】采用饲喂法测定60 g a.i./L乙基多杀菌素和43%联苯肼酯对地熊蜂采集蜂的急性经口毒性,依据农药对蜜蜂生态风险的危害熵(hazard quotient, HQ)值评估这两种农药对地熊蜂的风险。同时测定了这两种农药亚致死剂量(LD₅₀和LD₈₀)处理后地熊蜂AchE, GST和CarE的活性变化。【结果】60 g a.i./L乙基多杀菌素和43%联苯肼酯对地熊蜂采集蜂的急性经口毒性测定48 h时LD₅₀值分别为3.590和1 447 μg a.i./蜂,其中60 g a.i./L乙基多杀菌素表现为中毒,43%联苯肼酯表现为低毒。两种农药对地熊蜂采集蜂的HQ值均低于50,表现为低风险。LD₅₀和LD₈₀剂量的乙基多杀菌素处理组与对照组相比,3 h时地熊蜂AchE活性被激活,显著高于对照组(P＜0.05),分别为对照组的1.45和1.23倍,24 h后活性受到抑制,两个剂量处理组AchE活性均显著低于对照组(P＜0.05);CarE活性3 h时同样被激活,显著高于对照组(P＜0.05),LD₅₀和LD₈₀剂量处理组CarE活性分别为对照组的1.24和1.53倍, 24 h后活性受到抑制,其中LD₅₀剂量处理组CarE活性显著低于对照组(P＜0.05),LD₈₀剂量处理组CarE活性与对照组差异不显著(P＞0.05);LD₅₀和LD₈₀剂量处理组GST活性3 h被激活,显著高于对照组(P＜0.05),分别为对照组的2.24和2.58倍,24 h后活性降低,但两个剂量处理组GST活性仍显著高于对照组(P＜0.05)。43%联苯肼酯处理后,与对照组相比3 h时LD₅₀和LD₈₀剂量处理组AchE活性与对照组差异不显著(P＞0.05),24 h后AchE活性降低,显著低于对照组(P＜0.05),分别是对照组的75%和80%;CarE活性3 h时被抑制,LD₅₀剂量处理组CarE活性显著低于对照组(P＜0.05),LD₈₀剂量处理组CarE活性低于对照组,但差异不显著(P＞0.05),24 h后CarE活性被激活,其中LD₅₀剂量处理组CarE活性高于对照组,但差异不显著(P＞0.05),LD₈₀剂量处理组CarE活性显著高于对照组(P＜0.05);LD₅₀剂量处理组GST活性3 h时被激活,显著高于对照组(P＜0.05),24 h后活性降低,但仍显著高于对照组(P＜0.05),3 h和24 h的活性分别为对照组的2.04和1.72倍,LD₈₀剂量处理组3 h的GST活性与对照组无显著差异(P＞0.05),24 h后活性降低,显著低于对照组(P＜0.05)。【结论】乙基多杀菌素和联苯肼酯对地熊蜂的HQ 评估均表现为低风险,其中联苯肼酯对地熊蜂的安全性较高,在熊蜂授粉过程中可以按照推荐剂量应用,但过量施用或者长期施用可能会造成熊蜂体内药剂积累引起生理或者行为的变化,乙基多杀菌素在温室及大田授粉期的使用剂量和方法有待进一步研究。     

Relation between Intensity of Biocide Practice and Residues of Anticoagulant Rodenticides in Red Foxes (Vulpes vulpes)

Anticoagulant rodenticides (ARs) are commonly used to control rodent infestations for biocidal and plant protection purposes. This can lead to AR exposure of non-target small mammals and their predators, which is known from several regions of the world. However, drivers of exposure variation are usually not known. To identify environmental drivers of AR exposure in non-targets we analyzed 331 liver samples of red foxes (Vulpes vulpes) for residues of eight ARs and used local parameters (percentage of urban area and livestock density) to test for associations to residue occurrence. 59.8% of samples collected across Germany contained at least one rodenticide, in 20.2% of cases at levels at which biological effects are suspected. Second generation anticoagulants (mainly brodifacoum and bromadiolone) occurred more often than first generation anticoagulants. Local livestock density and the percentage of urban area were good indicators for AR residue occurrence. There was a positive association between pooled ARs and brodifacoum occurrence with livestock density as well as of pooled ARs, brodifacoum and difenacoum occurrence with the percentage of urban area on administrative district level. Pig holding drove associations of livestock density to AR residue occurrence in foxes. Therefore, risk mitigation strategies should focus on areas of high pig density and on highly urbanized areas to minimize non-target risk.     

Purification and characterization of insecticidal toxins from venom glands of the parasitic wasp, Bracon hebetor

The potency of venom from Bracon hebetor against lepidopterous larvae has been known for over 40 years, but previous attempts to purify and characterize individual protein toxins have been largely unsuccessful. Three protein toxins were purified from venom of this small parasitic wasp and the amino acid sequences of 22–31 consecutive residues at the amino-terminus were determined. These relatively large toxins (apparent molecular mass 73 kDa) were labile under many isolation techniques, but anion-exchange chromatography allowed purification with retention of biological activity. Two purified toxins were quite insecticidal (LD₅₀ < 0.3μg/g) when injected into six species of lepidopterous larvae. On a molar basis, one toxin (Brh-I) has the highest known biocidal activity against Heliothis virescens (LD₅₀ = 2 pmol/g).     

八种新烟碱类杀虫剂对地熊蜂工蜂的毒性及风险评估

【目的】评价新烟碱类杀虫剂对地熊蜂Bombus terrestris工蜂的毒性和生态风险性,为温室施用新烟碱类杀虫剂提供科学依据。【方法】分别采用饲喂法和接触法测定了噻虫嗪、噻虫胺、啶虫脒、吡虫啉、烯啶虫胺、呋虫胺、噻虫啉和氟吡呋喃酮8种新烟碱类杀虫剂对地熊蜂成年工蜂的急性经口和急性接触毒性。同时评估了8种新烟碱类杀虫剂对地熊蜂工蜂的生态风险性。【结果】8种杀虫剂经饲喂法测定,噻虫胺对地熊蜂成年工蜂的毒性最高,24 h和48 h的LD 50值分别为0.0433和0.0330μg a.i./蜂;氟吡呋喃酮毒性最低,24 h和48 h的LD 50值分别为72.4119和67.9079μg a.i./蜂。接触法测定的毒性与饲喂法测得的结果一致,噻虫胺的毒性最高,24 h和48 h的LD 50值分别为0.0220和0.0192μg a.i./蜂;氟吡呋喃酮的毒性最低,24 h和48 h的LD 50值分别为141.7641和130.3062μg a.i./蜂。生态风险评估表明,啶虫脒、噻虫啉和氟吡呋喃酮对地熊蜂成年工蜂的经口毒性和接触毒性均表现为低风险,吡虫啉、烯啶虫胺和呋虫胺的毒性表现为中等风险。噻虫嗪和噻虫胺对地熊蜂成年工蜂的经口毒性表现为中等风险,而接触毒性则表现为高风险。【结论】检测的8种新烟碱类杀虫剂中啶虫脒、噻虫啉与氟吡呋喃酮对地熊蜂成年工蜂的毒性为低毒,而噻虫嗪、噻虫胺、吡虫啉、烯啶虫胺、呋虫胺这5种杀虫剂均为高毒。在设施蔬菜花期使用地熊蜂授粉时,建议禁用这5种中、高风险的新烟碱类杀虫剂,以避免对熊蜂授粉的危害,而另3种低风险药剂可根据田间试验情况合理施用。     

ORG 33201: A new highly selective orally active aromatase inhibitor

Org 33201 has been selected as a very potent aromatase inhibitor. The compound is an enantiomer of a SC₂H₅ substituted imidazoylethylphenalene. Org 33201 inhibited human aromatase activity for 50% at a concentration of 2.2 × 10⁹ mol/l. More than 200-fold higher concentrations were needed for the inhibition of other cytochrome P-450 enzymes. In vivo the compound was active in rats (ED₅₀ = 0.035 mg/kg) and dogs (1 mg/kg gave 70% inhibition) after oral administration. It can be concluded that Org 33201 is a potent and highly selective orally active aromatase inhibitor.     

Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor

CGS 20267 is a new non-steroidal compound which potently inhibits aromatase in vitro (IC₅₀ of 11.5 nM) and in vivo (ED₅₀ of 1–3 μg/kg p.o.). CGS 20267 maximally inhibits estradiol production in vitro in LH-stimulated hamster ovarian tissue at 0.1 μM with an IC₅₀ of 0.02 μM and does not significantly affect progesterone production up to 350 μM. In ACTH-stimulated rat adrenal tissue in vitro, aldosterone production was inhibited with an IC₅₀ of 210 μM (10,000 times higher than the IC₅₀ for estradiol production); no significant effect on corticosterone production was seen at 350 μM. In vivo, in ACTH-treated rats, CGS 20267 does not affect plasma levels of corticosterone or aldosterone at a dose of 4 mg/kg p.o. (1000 times higher than the ED₅₀ for aromatase inhibition in vivo). In adult female rats, a 14-day treatment with 1 mg/kg p.o. daily, completely interrupts ovarian cyclicity and suppresses uterine weight to that seen 14 days after ovariectomy. In adult female rats bearing estrogen-dependent DMBA-induced mammary tumors, 0.1 mg/kg p.o. given daily for 42 days caused almost complete regression of tumors present at the start of treatment. Thus compared to each other, CGS 16949A and CGS 20267 are both highly potent in inhibiting estrogen biosynthesis in vitro and in vivo. The striking difference between them is that unlike CGS 16949A, CGS 20267 does not affect adrenal steroidogenesis in vitro or in vivo, at concentrations and doses several orders of magnitude higher than those required to inhibit estrogen biosynthesis.