Toxic organic cations can damage nigrostriatal dopaminergic pathways as seen in most parkinsonian syndromes and in some cases of illicit drug exposure. Here, we show that the organic cation transporter 3 (Oct3) is expressed in nondopaminergic cells adjacent to both the soma and terminals of midbrain dopaminergic neurons. We hypothesized that Oct3 contributes to the dopaminergic damage by bidirectionally regulating the local bioavailability of toxic species. Consistent with this view, Oct3 deletion and pharmacological inhibition hampers the release of the toxic organic cation 1-methyl-4-phenylpyridinium from astrocytes and protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration in mice. Furthermore, Oct3 deletion impairs the removal of the excess extracellular dopamine induced by methamphetamine and enhances striatal dopaminergic terminal damage caused by this psychostimulant. These results may have far-reaching implications for our understanding of the mechanism of cell death in a wide range of neurodegenerative diseases and may open new avenues for neuroprotective intervention.astrocytes ͉ Parkinson's disease ͉ extraneuronal monoamine transporter ͉ dopamine ͉ methamphetamine
The aim of this study is to evaluate compliance and outcomes with implementation of an enhanced recovery surgical protocol in older women undergoing pelvic reconstructive surgery. This is a retrospective cohort study of women undergoing pelvic reconstructive surgery after implementation of the pathway over a 12-month period. Overall compliance was defined as a categorial variable requiring adherence to all of the selected bundle components in patients <65 years old compared to those ≥65. Intraoperative and 30-day postoperative complications were also compared and were reviewed by organ system, these were categorized using the Clavien-Dindo Classification system. There was no significant difference in overall compliance in patients <65 compared to ≥65. Factors that increased compliance in patients ≥65 include laparotomy, hysterectomy, hyperlipidaemia, time after implementation of the protocol and primary surgeon. There was an increase in compliance from 19% to 77% over the 12-month study period. Intra and postoperative complications were similar between the two groups. Enhanced recovery in older patients undergoing pelvic reconstructive surgery is feasible with similar rates of compliance and complications compared to younger patients. Compliance with the protocol increases as time after implementation of the protocol increases in all patients.
This report is being published concurrently in Urogynecology and in International Urogynecology Journal. The report is identical except for minor stylistic and spelling differences in keeping with each journal’s style. Citations from any of the two journals can be used when citing this article.
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