48 research outputs found
Transport of small anionic and neutral solutes through chitosan membranes: Dependence on cross-linking and chelation of divalent cations
Chitosan membranes were prepared by solvent casting and cross-linked with glutaraldehyde at several ratios
under homogeneous conditions. The cross-linking degree, varying from 0 to 20%, is defined as the ratio between
the total aldehyde groups and the amine groups of chitosan. Permeability experiments were conducted using a
side-by-side diffusion cell to determine the flux of small molecules of similar size but with different chemical
moieties, either ionized (benzoic acid, salicylic acid, and phthalic acid) or neutral (2-phenylethanol) at physiological
pH. The permeability of the different model molecules revealed to be dependent on the affinity of those structurally
similar molecules to chitosan. The permeability of the salicylate anion was significantly enhanced by the presence
of metal cations commonly present in biological fluids, such as calcium and magnesium, but remained unchanged
for the neutral 2-phenylethanol. This effect could be explained by the chelation of metal cations on the amine
groups of chitosan, which increased the partition coefficient. The cross-linking degree was also correlated with
the permeability and partition coefficient. The change in the permeation properties of chitosan to anionic solutes
in the presence of these metallic cations is an important result and should be taken into consideration when trying
to make in vitro predictions of the drug release from chitosan-based controlled release systems
Systemic proteasome inhibition triggers neurodegeneration in a transgenic mouse model expressing human α-synuclein under oligodendrocyte promoter: implications for multiple system atrophy
Multiple system atrophy (MSA) is a progressive late onset neurodegenerative α-synucleinopathy with unclear pathogenesis. Recent genetic and pathological studies support a central role of α-synuclein (αSYN) in MSA pathogenesis. Oligodendroglial cytoplasmic inclusions of fibrillar αSYN and dysfunction of the ubiquitin–proteasome system are suggestive of proteolytic stress in this disorder. To address the possible pathogenic role of oligodendroglial αSYN accumulation and proteolytic failure in MSA we applied systemic proteasome inhibition (PSI) in transgenic mice with oligodendroglial human αSYN expression and determined the presence of MSA-like neurodegeneration in this model as compared to wild-type mice. PSI induced open field motor disability in transgenic αSYN mice but not in wild-type mice. The motor phenotype corresponded to progressive and selective neuronal loss in the striatonigral and olivopontocerebellar systems of PSI-treated transgenic αSYN mice. In contrast no neurodegeneration was detected in PSI-treated wild-type controls. PSI treatment of transgenic αSYN mice was associated with significant ultrastructural alterations including accumulation of fibrillar human αSYN in the cytoplasm of oligodendroglia, which resulted in myelin disruption and demyelination characterized by increased g-ratio. The oligodendroglial and myelin pathology was accompanied by axonal degeneration evidenced by signs of mitochondrial stress and dysfunctional axonal transport in the affected neurites. In summary, we provide new evidence supporting a primary role of proteolytic failure and suggesting a neurodegenerative pathomechanism related to disturbed oligodendroglial/myelin trophic support in the pathogenesis of MSA
Mesenchymal Stem Cells in a Transgenic Mouse Model of Multiple System Atrophy: Immunomodulation and Neuroprotection
Mesenchymal stem cells (MSC) are currently strong candidates for cell-based therapies. They are well known for their differentiation potential and immunoregulatory properties and have been proven to be potentially effective in the treatment of a large variety of diseases, including neurodegenerative disorders. Currently there is no treatment that provides consistent long-term benefits for patients with multiple system atrophy (MSA), a fatal late onset α-synucleinopathy. Principally neuroprotective or regenerative strategies, including cell-based therapies, represent a powerful approach for treating MSA. In this study we investigated the efficacy of intravenously applied MSCs in terms of behavioural improvement, neuroprotection and modulation of neuroinflammation in the (PLP)-αsynuclein (αSYN) MSA model.MSCs were intravenously applied in aged (PLP)-αSYN transgenic mice. Behavioural analyses, defining fine motor coordination and balance capabilities as well as stride length analysis, were performed to measure behavioural outcome. Neuroprotection was assessed by quantifying TH neurons in the substantia nigra pars compacta (SNc). MSC treatment on neuroinflammation was analysed by cytokine measurements (IL-1α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, GM-CSF, INFγ, MCP-1, TGF-β1, TNF-α) in brain lysates together with immunohistochemistry for T-cells and microglia. Four weeks post MSC treatment we observed neuroprotection in the SNc, as well as downregulation of cytokines involved in neuroinflammation. However, there was no behavioural improvement after MSC application.To our knowledge this is the first experimental approach of MSC treatment in a transgenic MSA mouse model. Our data suggest that intravenously infused MSCs have a potent effect on immunomodulation and neuroprotection. Our data warrant further studies to elucidate the efficacy of systemically administered MSCs in transgenic MSA models
Dicyclohexylmethane as a Liquid Organic Hydrogen Carrier: A Model Study on the Dehydrogenation Mechanism over Pd(111)
We have studied the dehydrogenation of the liquid organic hydrogen carrier (LOHC) dicyclohexylmethane (DCHM) to diphenylmethane (DPM) and its side reactions on a Pd(111) single crystal surface. The adsorption and thermal evolution of both DPM and DCHM was measured in situ in ultrahigh vacuum (UHV) using synchrotron radiation-based high-resolution X-ray photoelectron spectroscopy (HR-XPS). We found that after deposition at 170 K, the hydrogen-lean DPM undergoes C-H bond scission at the methylene bridge at 200 K and, starting at 360 K, complete dehydrogenation of the phenyl rings occurs. Above 600 K, atomic carbon incorporates into the Pd bulk. For the hydrogen-rich DCHM, the first stable dehydrogenation intermediate, a double π-allylic species, forms already at 190 K. Until 340 K, further dehydrogenation of the phenyl rings and of the methylene bridge occurs, yielding the same intermediate that is formed upon heating of DPM to this temperature, that is, DPM dehydrogenated at the methylene bridge. The onset for the complete dehydrogenation of this intermediate occurs at a much higher temperature than after adsorption of DPM. This behavior is mainly attributed to coadsorbed hydrogen from DCHM dehydrogenation. The results are discussed in comparison to our previous study of DPM and DCHM on Pt(111) revealing strong material dependencies
Dicyclohexylmethane as a liquid organic hydrogen carrier A model study on the dehydrogenation mechanism over palladium surfaces
We have studied the dehydrogenation of the liquid organic hydrogen carrier (LOHC) dicyclohexylmethane (DCHM) to diphenylmethane (DPM) and its side reactions on a Pd(111) single crystal surface. The adsorption and thermal evolution of both DPM and DCHM was measured in situ in ultrahigh vacuum (UHV) using synchrotron radiation-based high-resolution X-ray photoelectron spectroscopy (HR-XPS). We found that after deposition at 170 K, the hydrogen-lean DPM undergoes C-H bond scission at the methylene bridge at 200 K and, starting at 360 K, complete dehydrogenation of the phenyl rings occurs. Above 600 K, atomic carbon incorporates into the Pd bulk. For the hydrogen-rich DCHM, the first stable dehydrogenation intermediate, a double π-allylic species, forms already at 190 K. Until 340 K, further dehydrogenation of the phenyl rings and of the methylene bridge occurs, yielding the same intermediate that is formed upon heating of DPM to this temperature, that is, DPM dehydrogenated at the methylene bridge. The onset for the complete dehydrogenation of this intermediate occurs at a much higher temperature than after adsorption of DPM. This behavior is mainly attributed to coadsorbed hydrogen from DCHM dehydrogenation. The results are discussed in comparison to our previous study of DPM and DCHM on Pt(111) revealing strong material dependencies
Surface Reactions of Dicyclohexylmethane on Pt 111
We
investigated the surface reaction of the liquid organic hydrogen
carrier dicyclohexylmethane (DCHM) on Pt(111) in ultrahigh vacuum
by high-resolution X-ray photoelectron spectroscopy, temperature-programmed
desorption, near-edge X-ray absorption fine structure, and infrared
reflection–absorption spectroscopy. Additionally, the hydrogen-lean
molecule diphenylmethane and the relevant molecular fragments of DCHM,
methylcyclohexane, and toluene were studied to elucidate the reaction
steps of DCHM. We find dehydrogenation of DCHM in the range of 200–260
K, to form a double-sided π-allylic species coadsorbed with
hydrogen. Subsequently, ∼30% of the molecules desorb, and for
∼70%, one of the π-allyls reacts to a phenyl group between
260 and 330 K, accompanied by associative hydrogen desorption. Above
360 K, the second π-allylic species is dehydrogenated to a phenyl
ring. This is accompanied by C–H bond scission at the methylene
group, which is an unwanted decomposition step in the hydrogen storage
cycle, as it alters the original hydrogen carrier DCHM. Above 450
K, we find further decomposition steps which we assign to C–H
abstraction at the phenyl rings