[Survey of Prophylactic Administration of Naldemedine for Opioid-induced Constipation].

Opioid-induced constipation (OIC), an adverse event that occurs due to opioid analgesics, reportedly causes poor quality of life and adherence to opioid analgesics in patients. Therefore, this issue must be addressed appropriately. Naldemedine (NAL), a peripherally-acting µ-opioid receptor antagonist, is currently recommended for treating OIC when other laxatives are ineffective, but there have been no clinical reports of NAL being used prophylactically for OIC. Therefore, we conducted a retrospective survey of hospitalized patients who received NAL as prophylaxis for OIC with strong opioid analgesics to clarify the reality of this situation and to consider points to be taken into account in its clinical implementation. In this study, 61.7% of the subjects had an Eastern Cooperative Oncology Group performance status score of 3 or higher. The rate of addition of new laxatives and increased laxatives during seven days of NAL prophylaxis was 46.8%, and the rate of diarrhea was 6.1%. This study suggests that patients initiated with strong opioid analgesics during hospitalization often presented with poor performance status, and it is important to pay attention to constipation even under NAL prophylaxis. However, the incidence of diarrhea was low, and the safety of NAL prophylaxis was considered to be good.

Furin-mediated cleavage of LRP1 and increase in ICD of LRP1 after cerebral ischemia and after exposure of cultured neurons to NMDA.

The N-methyl-D-aspartate (NMDA) receptor has been implicated in several neurodegenerative diseases, including stroke. Low-density lipoprotein receptor-related protein 1 (LRP1) plays pivotal roles in endocytosis and signaling in the cell. Immature LRP1 is processed by furin in the trans-Golgi network (TGN) and transported to the cell surface as its mature form. Activation of mature LRP1 exerts a protective effect against glutamate-induced degeneration of the rat retinal ganglion cells, as was shown in our previous study. However, the roles of LRP1 in the pathogenesis of excitotoxic neuronal injuries remain to be determined. The aim of this present study was to achieve further insight into the pathophysiologic roles of LRP1 after excitotoxic neuronal injuries. Our findings are the first to demonstrate that LRP1 was significantly cleaved by furin after cerebral ischemia in rats as well as after exposure of cultured cortical neurons to NMDA. It was noteworthy that the intracellular domain (ICD) of LRP1 was co-localized with TGN and furin. Furthermore, a furin inhibitor inhibited the cleavage of LRP1 and co-localization of LRP1-ICD with TGN or furin. Our findings suggest that furin-mediated cleavage of LRP1 and changes in the localization of LRP1-ICD were involved in the excitotoxic neuronal injury.