How do xanthophylls protect lipid membranes from oxidative damage?

Here, we address the problem of the antioxidant activity of carotenoids in biomembranes. The activity of lutein and zeaxanthin in the quenching of singlet oxygen generated by photosensitization was monitored in lipid vesicles using a singlet oxygen-sensitive fluorescent probe and with the application of fluorescence lifetime imaging microscopy. The antioxidant activity of xanthophylls was interpreted on the basis of electron paramagnetic resonance oximetry results showing that xanthophylls constitute a barrier to the penetration of molecular oxygen into lipid membranes: to a greater extent in the 13-cis configuration than in all-trans. These results are discussed in relation to the trans-cis photoisomerization of xanthophylls observed in the human retina. It can be concluded that photoisomerization of xanthophylls is a regulatory mechanism that is important for both the modulation of light filtration through the macula and photoprotection by quenching singlet oxygen and creating a barrier to oxygen permeation to membranes

External quality monitoring facilitates improvement in already well-performing stroke units: insights from RES-Q Poland

Introduction. The Registry of Stroke Care Quality (RES-Q) is used in Poland for quality monitoring by numerous hospitals participating in the Angels Initiative. Our aim was to assess the degree of improvement in highly stroke-oriented centres that report cases to the RES-Q each year. Material and methods. This retrospective analysis included Polish stroke units that from January 2017 to December 2020 contributed to the RES-Q at least 25 patients annually. Results. Seventeen out of 180 Polish stroke units reported patients each year (2017, n = 1,691; 2018, n = 2,986; 2019, n = 3,750; 2020, n = 3,975). The percentage of ischaemic stroke patients treated with alteplase remained stable (26%, 29%, 30% and 28%, respectively). The door-to-needle time progressively decreased, from a median 49 minutes to 32 minutes. The percentage of patients treated ≤ 60 minutes and ≤ 45 minutes significantly increased (from 68% to 86% and from 43% to 70%, respectively), with no change observed between 2019 and 2020. Despite a general improvement in dysphagia screening (81%, 91%, 98% and 99%), screening performed within the first 24h from admission became less frequent (78%, 76%, 69% and 65%). In-hospital mortality significantly increased (11%, 11%, 13% and 15%), while the proportion of patients discharged home remained stable. Conclusions. Quality-oriented projects facilitate the improvement of stroke care, even in centres demonstrating good baseline performance. Polish stroke units that consistently reported cases to the RES-Q demonstrated improvement in terms of door-to- -needle time and dysphagia screening. However, there is still a need to shorten the time to dysphagia screening, and carefully monitor stroke unit mortality following the COVID-19 pandemic

Mechanical thrombectomy in acute stroke – Five years of experience in Poland

Objectives Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. Methods and results We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. Results Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250±99min. 90.3% of the studied patients had MT within 6h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% – emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b–TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization – in 30.7%, mRS of 0–2 – in 31.4% and mRS of 6 in 22% of cases. Conclusion Our results can help harmonize standards for MT in Poland according to international guidelines

How Do Phenolic Acids Change the Secondary and Tertiary Structure of Gliadin? Studies with an Application of Spectroscopic Techniques

The effect of the chemical structure of selected phenolic acids on the molecular organization of gliadins was investigated with the application of Fourier Transform Infrared (FTIR) technique, steady-state, and time-resolved fluorescence spectroscopy. Hydroxybenzoic (4-hydroxybenzoic, protocatechuic, vanillic, and syringic) and hydroxycinnamic (coumaric, caffeic, ferulic, sinapic) acids have been used as gliadins modifiers. The results indicated that hydroxybenzoic acids due to their smaller size incorporate into spaces between two polypeptide chains and form a hydrogen bond with them leading to aggregation. Additionally, syringic acids could incorporate into hydrophobic pockets of protein. Whereas hydroxycinnamic acids, due to their higher stiffness and larger size, separated polypeptide chains leading to gliadin disaggregation. These acids did not incorporate into hydrophobic pockets

Light-induced isomerization of the LHCII-bound xanthophyll neoxanthin : possible implications for photoprotection in plants

AbstractLight-harvesting pigment-protein complex of Photosystem II (LHCII) is the largest photosynthetic antenna complex of plants and the most abundant membrane protein in the biosphere. Plant fitness and productivity depend directly on a balance between excitations in the photosynthetic apparatus, generated by captured light quanta, and the rate of photochemical processes. Excess excitation energy leads to oxidative damage of the photosynthetic apparatus and entire organism and therefore the balance between the excitation density and photosynthesis requires precise and efficient regulation, operating also at the level of antenna complexes. We show that illumination of the isolated LHCII leads to isomerization of the protein-bound neoxanthin from conformation 9′-cis to 9′,13- and 9′,13′-dicis forms. At the same time light-driven excitation quenching is observed, manifested by a decrease in chlorophyll a fluorescence intensity and shortened fluorescence lifetimes. Both processes, the neoxanthin isomerization and the chlorophyll excitation quenching, are reversible in dim light. The results of the 77K florescence measurements of LHCII show that illumination is associated with appearance of the low-energy states, which can serve as energy traps in the pigment–protein complex subjected to excess excitation. Possible sequence of the molecular events is proposed, leading to a protective excess excitation energy quenching: neoxanthin photo-isomerization→formation of LHCII supramolecular structures which potentiate creation of energy traps→excitation quenching

Molecular organization of antifungal antibiotic amphotericin B in lipid monolayers studied by means of Fluorescence Lifetime Imaging Microscopy

International audienceAmphotericin B (AmB) is a life-saving polyene antibiotic used to treat deep-seated mycotic infections. Both the mode of therapeutic action as well as toxic side effects are directly dependent on molecular organization of the drug. Binding of AmB to lipid monolayers formed with dipalmitoylphosphatidylcholine, pure and containing 40 mol% cholesterol or ergosterol, the sterols of human and fungi respectively, has been examined by means of Fluorescence Lifetime Imaging Microscopy. AmB emits fluorescence with the characteristic lifetimes dependent on actual molecular organization: τ≤10 ps and τ=0.35 ns in the monomeric state, the emission from the S and the S states respectively and τ=14 ns and τ=3.5 ns in the form of a dimer and associated dimers respectively. Analysis of the Langmuir-Blodgett films reveals that AmB binds to the lipid membranes and to the cholesterol-containing lipid membranes preferentially in the form of associated dimers. The same form of AmB appears in the membranes containing ergosterol but additionally the monomers and dimers of the drug. can be observed, which can severely affect molecular organization of the lipid membrane. The results are discussed in terms of selectivity of AmB towards the ergosterol-containing biomembranes of fungi