Phenotypic plasticity in vascular smooth muscle cells (VSMC) is necessary for vessel maintenance, repair and adaptation to vascular changes associated with aging. De-differentiated VSMC contribute to pathologies including atherosclerosis and intimal hyperplasia. As resveratrol has been reported to have cardio- protective effects, we investigated its role in VSMC phenotypic modulation. We demonstrated the novel finding that resveratrol promoted VSMC differentiation as measured by contractile protein expression, contractile morphology and contraction in collagen gels. Resveratrol induced VSMC differentiation through stimulation of SirT1 and AMPK. We made the novel finding that low or high dose resveratrol had an initially different mechanism on induction of differentiation. We found that low dose resveratrol stimulated differentiation through SirT1-mediated activation of AKT, whereas high dose resveratrol stimulated differentiation through AMPK-mediated inhibition of the mTORC1 pathway, allowing activation of AKT. The health effects of resveratrol in cardiovascular diseases, cancer and longevity are an area of active research. We have demonstrated a supplemental avenue where-by resveratrol may promote health by maintaining and enhancing plasticity of the vasculature.

Thompson AM, Wagner R, Rzucidlo EM. Age-related loss of SirT1 expression results in dysregulated human vascular smooth muscle cell function.

Recombinant human acid sphingomyelinase (rhASM) is being developed as an enzyme replacement therapy for patients with acid sphingomyelinase deficiency (Niemann-Pick disease types A and B), which causes sphingomyelin to accumulate in lysosomes. In the acid sphingomyelinase knock-out (ASMKO) mouse, intravenously administered rhASM reduced tissue sphingomyelin levels in a dose-dependent manner. When rhASM was administered to normal rats, mice, and dogs, no toxicity was observed up to a dose of 30mg/kg. However, high doses of rhASM≥10mg/kg administered to ASMKO mice resulted in unexpected toxicity characterized by cardiovascular shock, hepatic inflammation, adrenal hemorrhage, elevations in ceramide and cytokines (especially IL-6, G-CSF, and keratinocyte chemoattractant [KC]), and death. The toxicity could be completely prevented by the administration of several low doses (3mg/kg) of rhASM prior to single or repeated high doses (≥20mg/kg). These results suggest that the observed toxicity involves the rapid breakdown of large amounts of sphingomyelin into ceramide and/or other toxic downstream metabolites, which are known signaling molecules with cardiovascular and pro-inflammatory effects. Our results suggest that the nonclinical safety assessment of novel therapeutics should include the use of specific animal models of disease whenever feasible.

Reports in a segmentation study conducted to determine whether consumer‐based variables such as activities, interests and opinions could be used to segment markets based on service quality expectations. Identifies those consumer‐based variables found to be significantly related to service quality dimensions and discusses their managerial significance to the healthcare market.

Susan Howe's recent collage poems—an intricate, sui generis form—are the flowering of her editorial theory, which I describe as “intimate editing.” I challenge scholarly assumptions that sideline Howe's engagement with the field of textual criticism from accounts of her poetry by showing how her unique approach to texts puts avant-garde poetry and textual editing into conversation, introducing reciprocal possibilities for both. Poems can model new forms of editing, and editorial debates can expand the reach and resonance of innovative poetry. Drawing on The Birth-mark, Howe's collection of creative-critical essays that probe the motivations and ethos of textual criticism, I show how intimate editing expands the typical, often rigid, values of traditional editing and contributes to growing discussions about what a feminist textual criticism might look like. Then I discuss the collage poems, particularly those in Concordance, as whimsical manifestations of Howe's textual approach.