In Alzheimer's disease (AD), different types of neurons and different brain areas show differential patterns of vulnerability towards neurofibrillary degeneration, which provides the basis for a ...highly predictive profile of disease progression throughout the brain that now is widely accepted for neuropathological staging. In previous studies we could demonstrate that in AD cortical and subcortical neurons are constantly less frequently affected by neurofibrillary degeneration if they are enwrapped by a specialized form of the hyaluronan-based extracellular matrix (ECM), the so called 'perineuronal net' (PN). PNs are basically composed of large aggregating chondroitin sulphate proteoglycans connected to a hyaluronan backbone, stabilized by link proteins and cross-linked via tenascin-R (TN-R). Under experimental conditions in mice, PN-ensheathed neurons are better protected against iron-induced neurodegeneration than neurons without PN. Still, it remains unclear whether these neuroprotective effects are directly mediated by the PNs or are associated with some other mechanism in these neurons unrelated to PNs. To identify molecular components that essentially mediate the neuroprotective aspect on PN-ensheathed neurons, we comparatively analysed neuronal degeneration induced by a single injection of FeCl3 on four different mice knockout strains, each being deficient for a different component of PNs. Aggrecan, link protein and TN-R were identified to be essential for the neuroprotective properties of PN, whereas the contribution of brevican was negligible. Our findings indicate that the protection of PN-ensheathed neurons is directly mediated by the net structure and that both the high negative charge and the correct interaction of net components are essential for their neuroprotective function.
•Optimization of a fully automated two-dimensional liquid chromatography system.•The optimized valve switching times are suitable to expand the scope of the method.•Very polar matrix components are ...separated by the first dimension.•Development of a model to estimate and explain the anayltes’ elution behaviour.•Citrate extraction leads to better detection rates and additional matrix separation.
In this study, a fully automated two-dimensional liquid chromatography system was evaluated for pesticide analysis. The first dimension was a hydrophilic interaction liquid chromatography column for matrix separation. The analytes were collected on a trap column and transferred to the second dimension with a reversed phase column. This separation system was coupled to a quadrupole time-of-flight mass spectrometer. Investigations were started to elucidate, whether this system is useful for screening purposes. Therefore, analytes with different masses, pKa and log Kow values were chosen. The aim was to test, if broadening the scope of this method, without a time-intensive adjustment of the valve switching times is possible. All in all, the limits of the system were determined. It is important that the analytes elute from the hydrophilic interaction liquid chromatography column within a small window. It could be deduced that the window within which the analytes elute expanded too far with the chosen analytes. Therefore, optimization with different buffers, columns, column temperatures, and flow rates was started to minimise the window. Furthermore, differences in the analytes’ elution behavior during hydrophilic interaction liquid chromatography separation were elucidated.
The intake of a natural carotenoid extract increases cutaneuos carotenoid concentration, radical scavenging capacity, light induced radical protection, and several skin lipids.
Nutrition rich in ...carotenoids is well known to prevent cell damage, premature skin aging, and skin cancer. Cutaneous carotenoids can be enriched in the skin by nutrition and topically applied antioxidants have shown an increase in radical protection after VIS/NIR irradiation. In this paper, it was investigated whether orally administered carotenoids increase the radical scavenging activity and the radical protection of the skin using in vivo electron paramagnetic resonance spectroscopy and the skin lipid profile was investigated applying HPTLC on skin lipid extracts. Furthermore, in vivo Raman resonance spectroscopy was used to measure the cutaneous carotenoid concentration. A double blind placebo controlled clinical study was performed with 24 healthy volunteers, who have shown a slow but significant and effective increase in cutaneous carotenoids in the verum group. The enhancement in carotenoids increases the radical scavenging activity of the skin and provides a significant protection against stress induced radical formation. Furthermore, the skin lipids in the verum group increased compared to the placebo group but only significantly for ceramide NS. These results indicate that a supplementation with dietary products containing carotenoids in physiological concentrations can protect the skin against reactive oxygen species and could avoid premature skin aging and other radical associated skin diseases.
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