A case of glyphosate encephalopathy presented with retrograde amnesia and an increase of blood flow in the medial temporal lobes on the arterial spin labeling images.

Background: Suicide attempts with glyphosatebased herbicides are not rare in rural areas in Japan. There are some reports on glyphosate encephalopathy, however, the detailed features of the clinical course are still unclear. Case: A female case in her early 70s was hospitalized after ingesting a glyphosate-based herbicide. On the fifth day after admission, she developed confusion and cognitive impairment including retrograde amnesia, even though her general condition was improved. An increase of blood flow in the bilateral medial temporal lobes was observed on the arterial spin labeling (ASL) of magnetic resonance image (MRI). The electroencephalogram (EEG) showed paroxysmal activities centered on the right temporal electrodes, suggesting pathological lesions with abnormal neuronal activity or glial activity in the medial temporal lobes. After sodium valproate and olanzapine were administered, her psychiatric symptoms and cognitive impairment were improved and the findings on the MRI and the EEG were rectified, although retrograde amnesia remained. Conclusions: Patients who ingested glyphosate would need careful management considering the subsequent glyphosate encephalopathy with pathological lesions in the medial temporal lobes. The findings of ASL study and EEG were salient and may be useful for the early detection and management of encephalopathy.departmental bulletin pape

Inhibition of ABCG2 enhances chemo-sensitivity of murine glioma stem cell-like cells to temozolomide and reduces spheroid-forming capability

[Abstract] Current evidence indicates that glioma stem cell-like cells (GSC_S) in humans play critical roles in the pathogenesis of carcinogenesis ofglioblastoma (GBM ). The GSC_S are known to overexpress members of the adenosine triphosphate-binding cassette (ABC) family transporters to exhibit multidrug resistance. Eradication of the GSC compartment is therefore essential to achieve a stable and long-lasting remission of GBM. To elucidate the characteristics of GSC_S in detail, we generated murine GSC lines from Sleeping Beauty transposon-mediated spontaneous GBM . Using these several cell lines, we evaluated the significance of ABC transporters in the GSC kinetics by cell morphology assays, flow cytometry, and quantitativeRT-PCR for mRNA expressions. As a consequence, we show that siRNA-mediated ABCG2 inhibition enhances the sensitivity of GSC_S to temozolomide (TMZ) and in turn reduces their spheroid-forming capability. Furthermore, we show that GSC_S treated with Abcg2-specific siRNA become sensitive to TMZ and reduce their spheroid-forming capability. In conclusion, our data suggest that targeting of drug transporters in GSC_S is a promising strategy to enhance their chemo-sensitivity for achieving a longlasting remission of GBM