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      Oxidative Modifications in Crystallin Proteins and Lens Epithelial Cells Associated with Photosensitized Reactions Mediated by the Major Chromophore Arising from Glucose Degradation

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          Abstract

          Deleterious effect mediated by glucose degradation, as a parallel pathway to Maillard reaction, was analyzed in terms of the feasibility of inducing photo-crosslinking in isolated bovine crystalline proteins when exposed to ultraviolet A (UVA)-visible light. These experiments showed evidence supporting the generation of a glucose-derived chromophore (GDC). The ability of this chromophore to induce oxidative damage in lens protein and bovine lens epithelial cells (BLEC) was further assessed. The analysis of dityrosine and carbonyl levels in lens proteins irradiated at 5 and 20% O2 indicates the occurrence of mixed type I/type II photosensitizing mechanisms. When BLEC were exposed to photosensitized reactions induced by GDC a decrease in cellular viability and intracellular reduced (GSH) and oxidized (GSSG) glutathione ratio was observed, as well as an increase in the amount of intracellular reactive oxygen species. Our data suggest a major effect of type I photosensitizing mechanism in both lens proteins photo-oxidation and oxidative stress induced in BLEC.

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          Long Term Outcomes Following Hospital Admission for Sepsis Using Relative Survival Analysis: A Prospective Cohort Study of 1,092 Patients with 5 Year Follow Up

          Background Sepsis is a leading cause of death in intensive care units and is increasing in incidence. Current trials of novel therapeutic approaches for sepsis focus on 28-day mortality as the primary outcome measure, but excess mortality may extend well beyond this time period. Methods We used relative survival analysis to examine excess mortality in a cohort of 1,028 patients admitted to a tertiary referral hospital with sepsis during 2007–2008, over the first 5 years of follow up. Expected survival was estimated using the Ederer II method, using Australian life tables as the reference population. Cumulative and interval specific relative survival were estimated by age group, sex, sepsis severity and Indigenous status. Results Patients were followed for a median of 4.5 years (range 0–5.2). Of the 1028 patients, the mean age was 46.9 years, 52% were male, 228 (22.2%) had severe sepsis and 218 (21%) died during the follow up period. Mortality based on cumulative relative survival exceeded that of the reference population for the first 2 years post admission in the whole cohort and for the first 3 years in the subgroup with severe sepsis. Independent predictors of mortality over the whole follow up period were male sex, Indigenous Australian ethnicity, older age, higher Charlson Comorbidity Index, and sepsis-related organ dysfunction at presentation. Conclusions The mortality rate of patients hospitalised with sepsis exceeds that of the general population until 2 years post admission. Efforts to improve outcomes from sepsis should examine longer term outcomes than the traditional primary endpoints of 28-day and 90-day mortality.
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            Preparation of Artificial Plasma Membrane Mimicking Vesicles with Lipid Asymmetry

            Lipid asymmetry, the difference in lipid distribution across the lipid bilayer, is one of the most important features of eukaryotic cellular membranes. However, commonly used model membrane vesicles cannot provide control of lipid distribution between inner and outer leaflets. We recently developed methods to prepare asymmetric model membrane vesicles, but facile incorporation of a highly controlled level of cholesterol was not possible. In this study, using hydroxypropyl-α-cyclodextrin based lipid exchange, a simple method was devised to prepare large unilamellar model membrane vesicles that closely resemble mammalian plasma membranes in terms of their lipid composition and asymmetry (sphingomyelin (SM) and/or phosphatidylcholine (PC) outside/phosphatidylethanolamine (PE) and phosphatidylserine (PS) inside), and in which cholesterol content can be readily varied between 0 and 50 mol%. We call these model membranes “artificial plasma membrane mimicking” (“PMm”) vesicles. Asymmetry was confirmed by both chemical labeling and measurement of the amount of externally-exposed anionic lipid. These vesicles should be superior and more realistic model membranes for studies of lipid-lipid and lipid-protein interaction in a lipid environment that resembles that of mammalian plasma membranes.
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              Efficacy and Safety of Endovascular Treatment versus Intravenous Thrombolysis for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

              Background and Purpose Although endovascular therapy (ET) is increasingly used in patients with moderate to severe acute ischemic stroke, its efficacy and safety remains controversial. We performed a meta-analysis aiming to compare the benefits and safety of endovascular treatment and intravenous thrombolysis in the treatment of acute ischemic stroke. Methods We systematically searched PubMed, Embase, Science direct and Springer unitil July, 2013. The primary outcomes included good outcome (mRS ≤ 2) and excellent outcome (mRS ≤ 1) at 90 days or at trial end point. Secondary outcomes were occurrence of symptomatic hemorrhage and all-cause mortality. Results Using a prespecified search strategy, 5 RCTs with 1106 patients comparing ET and intravenous thrombolysis (IVT) were included in the meta-analysis. ET and IVT were associated with similar good (43.06% vs 41.78%; OR=1.14; 95% CI, 0.77 to 1.69; P=0.52;) and excellent (30.43% vs 30.42%; OR=1.05; 95% CI, 0.80 to 1.38; P=0.72;) outcome. For additional end points, ET was not associated with increased occurrence of symptomatic hemorrhage (6.25% vs. 6.22%; OR=1.03; 95% CI, 0.62 to 1.69; P=0.91;), or all-cause mortality (18.45% vs. 17.35%; OR=1.00; 95% CI, 0.73 to 1.39; P=0.99;). Conclusions Formal meta-analysis indicates that there are similar safety outcomes and functional independence with endovascular therapy and intravenous thrombolysis for acute ischemic stroke.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                jbchs
                Journal of the Brazilian Chemical Society
                J. Braz. Chem. Soc.
                Sociedade Brasileira de Química
                1678-4790
                February 2016
                : 27
                : 2
                : 411-422
                Affiliations
                [1 ] Pontificia Universidad Católica de Chile Chile
                [2 ] Fundación Ciencia y Tecnología para el Desarrollo Chile
                [3 ] Université Pierre et Marie Curie France
                [4 ] Universidad de Talca Chile
                [5 ] Universidad de Talca Chile
                Article
                S0103-50532016000200411
                10.5935/0103-5053.20150315
                642137de-7cca-4ed8-b408-b6842fd0d1c2

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0103-5053&lng=en
                Categories
                CHEMISTRY, MULTIDISCIPLINARY

                General chemistry
                cataract disease,photosensitizing reactions,oxidative stress,bovine crystalline proteins,bovine lens cell model

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