Purpose: To demonstrate the feasibility of PhotoPoint photodynamic therapy (PDT) with local drug delivery, optimize dosimetry in a rabbit jugular vein model, and investigate its ability to deplete potential neointimal precursor cells in the vessel wall in a canine arteriovenous graft (AVG) model.
Methods And Materials: Photosensitizer MV2101 was administered locally in rabbit veins, incubated for 0-40 min and activated with external laser light. In canine veins, MV2101 was incubated for 30 min and activated by light. Tissues were excised at acute and chronic timepoints.
Results: PhotoPoint PDT reduced cell populations in both models with maximum depletions occurring at 20 min (> or = 100 J/cm2) in rabbit veins (> 90% depletion) and 30 min (200 J/cm2) in canine veins (> 85% depletion). Chronic veins revealed no evidence of PhotoPoint PDT-related abnormalities.
Conclusions: PhotoPoint PDT with local MV2101 dramatically depleted potential neointimal precursor cells in the vessel wall. This suggests local drug delivery is feasible and that PhotoPoint PDT may be an efficacious treatment that could prolong AVG patency in the clinic.
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http://dx.doi.org/10.1016/s1522-1865(03)00080-5 | DOI Listing |
Alzheimers Dement
December 2024
Department of Bioengineering, University of California, Los Angeles, CA, USA, Los Angeles, CA, USA.
Background: The initiation of amyloid plaque deposition signifies a crucial stage in Alzheimer's disease (AD) progression, which often coincides with the disruption of neural circuits and cognitive decline. While the role of excitatory-inhibitory balance is increasingly recognized in AD pathophysiology, targeted therapies to modulate this balance remain underexplored. This study investigates the effect of perampanel, a selective non-competitive AMPA receptor antagonist, in modulating neurophysiological changes in hAPP-J20 transgenic Alzheimer's mice.
View Article and Find Full Text PDFBackground: Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer's disease (AD). SORL1 encodes the retromer-associated receptor SORLA that plays an essential role in recycling of AD-associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD.
View Article and Find Full Text PDFBackground: Although investment in biomedical and pharmaceutical research has increased significantly over the past two decades, there are no oral disease-modifying treatments for Alzheimer's disease (AD).
Method: We performed comprehensive human genetic and multi-omics data analyses to test likely causal relationship between EPHX2 (encoding soluble epoxide hydrolase [sEH]) and risk of AD. Next, we tested the effect of the oral administration of EC5026 (a first-in-class, picomolar sEH inhibitor) in a transgenic mouse model of AD-5xFAD and mechanistic pathways of EC5026 in patient induced Pluripotent Stem Cells (iPSC) derived neurons.
Background: Accumulating evidence highlights impairment of autophagy as a key pathological feature of neurodegenerative diseases including Alzheimer's disease (AD). Autophagy is a highly dynamic, lysosome-based degradation process that promotes the clearance of degenerative factors to maintain cellular functions, preserve metabolic integrity, and ensure survival. Impaired autophagic function leads to the abnormal accumulation of autophagic vesicles (i.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Focusing on novel AD treatments, the TREAT-AD centers offer an array of free research tools, shared via the AD Knowledge Portal in a Target Enablement Package (TEP). This abstract showcases the research conducted by the IUSM-Purdue TREAT-AD Center, specifically focusing on Targeting class-II PI3K's as a potential breakthrough in AD therapy. Endocytosis within the brain encompasses diverse pathways for internalizing extracellular cargoes and receptors into cells.
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