Differential metabolism of neonicotinoids by brown planthopper, Nilaparvata lugens, CYP6ER1 variants.

Imidacloprid is very effective in controlling Nilaparvata lugens Stål, which severely damages rice plants. Following heavy imidacloprid use, imidacloprid-resistant N. lugens, which showed cross-resistance to other neonicotinoids, appeared. We used the baculovirus/Sf9 expression system to express CYP6ER1 variants carrying A375del + A376G (del3) mutations, either with or without T318S mutation, which confer imidacloprid resistance in N. lugens. These CYP6ER1 variants metabolized imidacloprid but did not metabolize dinotefuran. Moreover, Drosophila expressing a CYP6ER1 variant carrying T318S + del3 mutations were resistant to imidacloprid, with a resistance ratio of 288.7, whereas the resistance ratio to dinotefuran was 3.6. These findings indicate that N. lugens has a low level of resistance to dinotefuran, and the increase of resistance is slow. We also studied the metabolism of other neonicotinoids, as well as sulfoxaflor and flupyradifurone, by CYP6ER1 variants carrying del3 mutations, either with or without the T318S mutation. Sulfoxaflor, was not metabolized by either CYP6ER1-del3 or CYP6ER1-T318Sdel3 variants. However, these variants did metabolize flupyradifurone. This study sheds light on the substrate selectivity of CYP6ER1 variants.

Differential metabolism of imidacloprid and dinotefuran by Bemisia tabaci CYP6CM1 variants.

Imidacloprid has been used to control one of most serious pests, Bemisia tabaci. However, B. tabaci has developed imidacloprid resistance mainly by over-expressing CYP6CM1. It was reported that imidacloprid-resistant B. tabaci showed no or low level of cross-resistance against dinotefuran. Here, we expressed CYP6CM1 variants using Sf9/baculovirus and/or Drosophila S2 cells and showed that CYP6CM1 variants metabolized imidacloprid but not dinotefuran. In addition, we demonstrated that imidacloprid and pymetrozine competed for a CYP6CM1 variant more efficiently than dinotefuran, using a luminescent substrate competition assay. These results suggest that lack of metabolic activity of CYP6CM1 variants against dinotefuran caused no or low level of cross-resistance.

[Assessment of health-related quality of life in cancer outpatients treated with chemotherapy].

PURPOSE: Few studies have been conducted to elucidate the health-related quality of life(HR-QOL)of cancer outpatients treated with chemotherapy. In this study, we attempted to determine the physical and psychological distress of cancer outpatients treated with chemotherapy. METHODS: Two-hundred and ninety-six outpatients with various malignancies, including malignant lymphoma, and esophageal, gastric, pancreatic, colon, lung, breast, ovarian, uterine and skin cancers, were investigated using the Japanese version of the M. D. Anderson symptom inventory from March through June 2010 in Tokyo Medical University Hospital. RESULTS: The results of the survey questionnaire indicated that 59 patients suffered from fatigue, 56 experienced numbness or tingling, 48 felt drowsy, 39 had low moods, 40 felt distressed, 38 had no appetite, 38 had dry mouth, 37 were in pain, 37 had disturbed sleep, 31 had shortness of breath, 24 had nausea, 17 suffered from vomiting, and 13 patients had memory problems. Furthermore, these symptoms interfered with work(65 patients), walking(56 patients), mood(52 patients), life enjoyment(49 patients), general activity(49 patients), and relationships with other people(42 patients). Medications prescribed for HR-QOL control were non-steroidal anti-inflammatory drugs(93 patients), morphine(32 patients), and adjuvant analgesics(47 patients). CONCLUSION: The present findings may help in the development of management strategies for physical and psychological distress, and improve HR-QOL of cancer outpatients treated with chemotherapy.

Synthesis and fungicidal activities of positional isomers of the N-thienylcarboxamide.

To investigate the effects of bioisosteric replacement of the phenyl group with the thienyl group, N-phenylcarboxamide and three regioisomers of N-(substituted-thienyl)carboxamide were synthesized. The inhibitory activity on the succinate dehydrogenase prepared from the gray mold Botrytis cinerea as well as the fungicidal activity against B. cinerea were evaluated. Two isomers, N-(2-substituted-3-thienyl)carboxamide and N-(4-substituted-3-thienyl)carboxamide exhibited the same level of activity as the phenyl derivative, whereas N-(3-substituted-2-thienyl)carboxamide exhibited lower activity than the phenyl derivative, suggesting that the 2-substituted-3-thienyl and 4-substituted-3-thienyl groups functioned as bioisosteres of the phenyl group in N-phenylcarboxamide, but the other did not.

Differential metabolism of neonicotinoids by Myzus persicae CYP6CY3 stably expressed in Drosophila S2 cells.

The peach-potato aphid, Myzus persicae, is a serious crop pest that has developed imidacloprid resistance, mainly through overexpression of CYP6CY3. Here, we established a metabolic assay using Drosophila S2 cells that stably expressed CYP6CY3. We found that CYP6CY3 showed metabolic activity against imidacloprid, as well as acetamiprid, clothianidin, and thiacloprid, but had no activity against dinotefuran. Our study suggested that stable gene expression in Drosophila S2 cells is useful for examining which insecticide is metabolized by P450 monooxygenases.