In vitro and in vivo inhibition of chicken brain neurotoxic esterase by leptophos analogs

Inhibition of chicken brain neurotoxic esterase (NTE) by a series of O-halogenated-phenyl-O-alkyl phenylphosphonates was studied in vitro. The “apparent” activity was found to consist of “true” NTE (sensitive to mipafox) plus a minor mipafox-resistant component. The pI₅₀ of O-(2,6-dichlorophenyl) O-methyl phenylphosphonate for “true” NTE was 6.65, whereas it was about 3 for mipafox-resistant hydrolysis of phenyl valerate. This compound is suitable as an alternative to mipafox in the assay of “true” NTE, whereas the use of leptophos oxon gives a less accurate measure. The ethoxy analogs are about as potent in vitro as the corresponding methoxy compounds. Leptophosoxon and ethoxyleptophosoxon are more potent in vitro inhibitors than desbromoleptophosoxon. Within a like group of chlorinated phenylphosphonates, a reasonable correlation between in vitro neurotoxic esterase inhibition of the oxon and in vivo delayed neurotoxic potential by the corresponding phosphonothionate exists. In vivo inhibition of “apparent” NTE from chicken brain, studied 24 hr after an oral dose, is dose dependent for leptophos, ethoxyleptophos, and desbromoleptophos, the latter one being a very potent in vivo inhibitor. Ethoxyleptophos and leptophos have about equal in vivo esterase inhibitory properties. For desbromoleptophos and leptophos there is good agreement between the minimum dose causing delayed neurotoxicity and the dose leading to substantial inhibition of “apparent” NTE; ethoxyleptophos, on the other hand, inhibits the esterase at a dose much lower than the one which is neurotoxic. Several possible explanations for this discrepancy are considered.     

The process of antagonism of Sclerotium cepivorum in white rot affected onion roots by Trichoderma koningii

Trichoderma koningii (strain Tr5) grew in the epidermal mucilage of onion roots without entering healthy epidermal tissue. When placed on the epidermis of Sclerotium cepivorum -infected roots, T. koningii colonized epidermal passage cells, with little colonization of other epidermal tissues, then branched and spread throughout the root cortical tissues damaged by enzymes and toxins which diffused ahead of S. cepivorum hyphae, and impeded the path of the infection. When T. koningii colonized infected tissue, many S. cepivorum hyphae became detached at septa, cell walls dissolved and many hyphal apices burst. Contact between hyphae was not necessary for lysis to occur. T. koningii produced two endochitinases ( R _f 0·15 and 0·24) and two exo-acting chitinolytic enzymes ( R _f 0·46 and 0·62) during degradation of crabshell chitin and S. cepivorum cell walls. The R f 0·24 and 0·46 proteins were detected when T. koningii colonized S. cepivorum -infected roots and are likely to be a component of the antagonism process.     

Steric,electronic, and polar parameters that affect the toxic actions of O-alkyl,O-phenyl phosphonothionate insecticides

The toxic action of a series of O-alkyl, O-substituted-phenyl alkyl- and aryl-phosphonates and phosphonothionates have been evaluated by correlating the linear free energy parameters for steric (E_s), electronic (σ), and polar ($\text{σ}{}^1$) effects with topical LD₅₀ to the house fly and oral LD₅₀ to the white mouse. In molecules free from major steric interactions with the reactive P atom, variations in these linear free energy parameters account for >90% of the variations in the LD₅₀ values, and the degree of correlation with LD₅₀ is at least as precise as that with the biomolecular rate constants for inhibition of the target-site enzyme acetylcholinesterase. The value of correlations of linear free energy parameters with LD₅₀ in understanding quantitative structure-activity relationships is illustrated.     

Investigations into carbamate insecticide selectivity: I: Evaluation of potential selectophores

In an effort to improve the generally unfavorable mouse/housefly toxicity ratio of most carbamate insecticides, potential selectophores (nitrile, carbamoyl oxime, carboxylic ester, or amide) were incorporated into a series of phenyl N-methylcarbamates. In addition to the insect and mouse toxicity determinations, the anticholinesterase activity of these compounds was determined for purified housefly head acetylcholinesterase and bovine erythrocyte acetylcholinesterase. The presence of these functional groups, in general, did not give enhanced selectivity ratios and, in one case, (o-N-methylcarbamoyloxyiminomethylphenyl N-methylcarbamate), a very unfavorable selectivity ratio of <0.03 was obtained. A mechanism implicating a Beckmann rearrangement is advanced to rationalize the high rodenticidal activity of this molecule. In general, the carbamates showed poor insecticidal activity when applied alone to the housefly, but, when the flies were pretreated with piperonyl butoxide, the compounds were quite toxic. Finally, an explanation is derived which seeks to justify the inability of these potential selectophores to improve the mouse/housefly toxidity ratio.     

The effect of piperonyl butoxide and triorthocresyl phosphate on the activity and metabolism of altosid (isopropyl 11-methoxy, 3,7,11-trimethyldodeca-2,4-dienoate) in Tenebrio molitor L. and Oncopeltus fasciatus (dallas)

Altosid (I) was found to have an ED₅₀ of 0.026 μg/g in T. molitor and 5.0 μg/g in O. fasciatus. The juvenilizing activity of I in T. molitor was increased by co-treatment with piperonyl butoxide (PB) and triorthocresyl phosphate (TOCP). The activity of I in O. fasciatus, was considerably decreased by PB and TOCP indicating the blocking of an activation reaction. The presumptive metabolities of I, isopropyl 11-hydroxy-3,7,11-trimethyldodeca-2,4-dienoate, (II), 11-methoxy-3,7,11-trimethyldodeca-2,4-dienoic acid (III), and 11-hydroxy-3,7,11-trimethyldodeca-2,4-dienoic acid (IV) were tested for juvenilizing activity in O. fasciatus and II was found to be four times more active than I. IV was more active than III but less active than I. Co-treatment of II with PB or TOCP did not decrease activity, indicating that II is a true activation product. Uptake studies with ¹⁴C-I showed that the difference in activity between the two insects was not due to differences in uptake. Forty-eight hours after treatment 30% of I was lost from the cuticle by evaporation. Metabolic studies showed that PB inhibited the formation of II and TOCP inhibited the formation of III in T. molitor while in O. fasciatus both synergists inhibited the formation of II.     

天然饲料补充正辛酸减少商品肉鸡空肠弯曲菌的寄居

空肠弯曲菌能引起人类的食物性传染疾病,且流行病学研究也表明家禽及其产品是人类感染该疾病的重要来源。减少家禽肠道中的空肠弯曲菌会减少其对家禽产品的污染。正辛酸是中链脂肪酸,据报道其可有效杀死包括空肠弯曲菌在内的各种细菌性病原体,但对于已经寄居在商品肉鸡肠道中空肠弯曲菌的治疗效果还未见报道。试验旨在研究正辛酸对42日龄鸡盲肠中空肠弯曲菌的治疗效果。试验共设4个试验组。前两个试验组,