Alzheimer’s disease and retinal neurodegeneration share a consistent stress response of the neurovascular unit

Background: The pathogenesis of Alzheimer’s disease (AD) is characterized by neuronal injury, activation of microglia and astrocytes, deposition of amyloid-beta and secondary vessel degeneration. In the polycystic kidney disease (PKD) rat model, we observed neuronal injury, microglial activation and vasoregression. We speculated that this neuroretinal degeneration shares important pathogenetic steps with AD. Therefore, we determined the activation of astrocytes and the accumulation of amyloid-beta in PKD retinae. Methods: Immunohistochemistry of PKD retinae for vimentin, carboxymethyllysin, beta-Amyloid 1-42, High-Mobility-Group-Protein B1 and amyloid protein precursor was performed. Results: Adjunct to astrocyte activation, accumulation of beta-Amyloid 1-42 and High-Mobility-Group-Protein B1 in astrocytes and around vessels of the superficial network was found in PKD retinae prior to the onset of vasoregression. Amyloid precursor protein was localized adjacent to the outer segment of photoreceptors in PKD and control rats. The parallel appearance of AD-related peptides indicates an alarmine based response to photoreceptor degeneration and secondary vasoregression. Conclusion: The model has broad overlap with AD and may be suitable to study beneficial pharmacological concepts. Copyright (c) 2012 S. Karger AG, Base

Two-Photon-Absorption Triggered Release of 5-Fluorouracil from Isomer-Pure Polymer Bound Syn-Head-to-Head Dimers for Novel Intraocular Lenses

Different stereoisomers of the cytotoxic 5-fluorouracil (5FU) homodimers were synthesized by photochemical [2+2]-cycloaddition and polymerized into MMA/HEMA to form a novel drug-loaded copolymer for intraocular lenses as irradiation-activated treatment for secondary cataract. Three isomers were obtained, and showed significant differences in cleavage efficiency on photo-cleavage via single-photon-absorption (SPA) and two-photon-absorption (TPA). The most efficient TPA cleavage rate was observed for the syn-head-to-head 5FU dimer, which was, consequently, used for drug loading of the polymeric material to obtain a drug-loaded material of higher efficiency compared to previous works. The light and thermal stability of the polymer were confirmed and multi-dose release of the drug in aqueous solution for possible repeated treatment of cataract was proven

Two-Photon-Absorption Triggered Release of 5-Fluorouracil from Isomer-Pure Polymer Bound Syn-Head-to-Head Dimers for Novel Intraocular Lenses

Different stereoisomers of the cytotoxic 5-fluorouracil (5FU) homodimers were synthesized by photochemical [2+2]-cycloaddition and polymerized into MMA/HEMA to form a novel drug-loaded copolymer for intraocular lenses as irradiation-activated treatment for secondary cataract. Three isomers were obtained, and showed significant differences in cleavage efficiency on photo-cleavage via single-photon-absorption (SPA) and two-photon-absorption (TPA). The most efficient TPA cleavage rate was observed for the syn-head-to-head 5FU dimer, which was, consequently, used for drug loading of the polymeric material to obtain a drug-loaded material of higher efficiency compared to previous works. The light and thermal stability of the polymer were confirmed and multi-dose release of the drug in aqueous solution for possible repeated treatment of cataract was proven

A note on comonotonicity and positivity of the control components of decoupled quadratic FBSDE

In this small note we are concerned with the solution of Forward-Backward Stochastic Differential Equations (FBSDE) with drivers that grow quadratically in the control component (quadratic growth FBSDE or qgFBSDE). The main theorem is a comparison result that allows comparing componentwise the signs of the control processes of two different qgFBSDE. As a byproduct one obtains conditions that allow establishing the positivity of the control process.Comment: accepted for publicatio

Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range

Quantitative analysis of time-resolved data in primary erythroid progenitor cells reveals that a dual negative transcriptional feedback mechanism underlies the ability of STAT5 to respond to the broad spectrum of physiologically relevant Epo concentrations