Shiga toxin (Stx) binds to globotriaosyl ceramide (Gb3) receptors on the surface of vascular endothelial cells, which is followed by Gb3-dependent endocytosis, and initiates a cascade leading to cell damage. The Gb3 receptor is localized in lipid rafts, in which cholesterol is tightly packed primarily with sphingolipids in a liquid-ordered state. Recent studies have indicated that phosphodiesterase (PDE) type 4 inhibitors enhance the expression of ATP-binding cassette 1 (ABCA1) which promotes cholesterol efflux from non-rafts at the plasma membrane. Here we report that rolipram, a PDE4 inhibitor, reduced the sensitivity to Stx2 of human umbilical vascular endothelial cells in association with increased apolipoproteinA-I (apoA-I)-mediated cholesterol efflux, and shift of some Gb3 molecules from lipid rafts into non-rafts. Although rolipram treatment did not reduce Gb3 content at the plasma membrane and Stx binding to whole cells of HUVECs, it reduced Stx2 endocytosis. Knockdown of ABCA1 by transfection with siRNA ABCA1 in vascular endothelial cells abrogated the protective effect of rolipram on Stx2-exposed cells. Our present results suggest that the expression level of ABCA1 protein is one of critical determinants of Stx sensitivity levels in vascular endothelial cells.

Clinical chart review of 49 cases with spinal cord injured pain was performed. Retrospective data about the characteristics of patients, the level of injury, the completeness of injury and the etiology was collected. Of pathogenesis of spinal cord injury, degenerative disease was 25 subjects (51%), 12 was traumatic (24%), 4 was vascular (8%) and 4 was neoplastic disease (8%). Thirty two subjects have injured at the cervical level (65%), 13 at the thoracic level (27%) and 4 at the lumbosacral level (8%). At-level neuropathic pain was present in 19 subjects (39%), below-level neuropathic pain was present in 42 subjects (85%). Gabapentin was effective in 24 patients (41%), clonazepam was effective in 17 (30%) and tricyclic antidepressants was effective in 21 patients (38%). We analized relationship between the characteristics of SCI pain and the result of various evaluation; Visual Analogue Scale (VAS), Hospital Anxiety Depression Scale (HAD), Pain Disability Assessment Scale (PDAS) and McGill Pain Questionnaire (MPQ).