995 resultados para pre-oxidation
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BACKGROUND: The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin(®) to determine tumor response. in vivo. Lasers Surg. Med. 47:323-330, 2015. © 2015 Wiley Periodicals, Inc. METHODS: Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne(®) -mediated photodynamic therapy with 100 mW/cm(2) fluence rate and a variable fluence (5, 10, 30, and 50 J/cm(2) ). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin(®) and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group). RESULTS: Tumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm(2) but not in the 5, 30, and 50 J/cm(2) groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm(2) and 50 J/cm(2) groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm(2) group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin(®) compared to controls. CONCLUSIONS: Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics. Lasers Surg. Med. 47:323-330, 2015.
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The AMPK/Snf1 kinase has a central role in carbon metabolism homeostasis in Saccharomyces cerevisiae. In this study, we show that Snf1 activity, which requires phosphorylation of the Thr210 residue, is needed for protection against selenite toxicity. Such protection involves the Elm1 kinase, which acts upstream of Snf1 to activate it. Basal Snf1 activity is sufficient for the defense against selenite, although Snf1 Thr210 phosphorylation levels become increased at advanced treatment times, probably by inhibition of the Snf1 dephosphorylation function of the Reg1 phosphatase. Contrary to glucose deprivation, Snf1 remains cytosolic during selenite treatment, and the protective function of the kinase does not require its known nuclear effectors. Upon selenite treatment, a null snf1 mutant displays higher levels of oxidized versus reduced glutathione compared to wild type cells, and its hypersensitivity to the agent is rescued by overexpression of the glutathione reductase gene GLR1. In the presence of agents such as diethyl maleate or diamide, which cause alterations in glutathione redox homeostasis by increasing the levels of oxidized glutathione, yeast cells also require Snf1 in an Elm1-dependent manner for growth. These observations demonstrate a role of Snf1 to protect yeast cells in situations where glutathione-dependent redox homeostasis is altered to a more oxidant intracellular environment and associates AMPK to responses against oxidative stress.
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Se realiza una revisión bibliográfica con el objetivo de conocer los protocolos actuales de rehabilitación tras la reconstrucción quirúrgica del ligamento cruzado anterior de la rodilla. Se efectúa una búsqueda de los estudios clínicos experimentales actuales que evalúan los procedimientos y protocolos de fisioterapia utilizados durante la rehabilitación del LCA. La búsqueda se realiza en las bases de datos: Medline, PEDro y Science Direct, entre diciembre de 2013 y enero de 2014. Se incluyen los publicados a partir del 2010, desarrollados en humanos con ruptura parcial o total del ligamento y redactados en español o inglés. Se analizan los 21 estudios que cumplen con los criterios de inclusión y exclusión estipulados y se valora el proceso metodológico empleado, la presencia de sesgos y limitaciones, la aplicabilidad de los resultados y la descripción precisa de los protocolos. Se concluye afirmando que no existe unanimidad en los protocolos y procedimientos de fisioterapia y que éstos no ofrecen diferencias destacables si se comparan con los diseñados 20 años atrás. Por lo que se propone y elaborar un protocolo de rehabilitación propio teniendo en cuenta la información obtenida y usando como referencia las guías clínicas más empleadas en la práctica clínica.
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Various studies suggest that oxidative modifications of low density lipoprotein (LDL), and also other lipoproteins, have an important role in the development of atherosclerosis. In addition to the oxidation products formed endogenously, oxidised triacylglycerols (TAG) and oxysterols in the diet contribute to the oxidised lipoproteins found in circulation. However, studies on both the effect of oxidised dietary lipids on lipoprotein lipid oxidation and the reactions that modify oxidised fat after ingestion have been scarce. Studies on the effects of dietary antioxidants on the lipid oxidation in vivo and the risk of atherosclerosis have been inconclusive. More clinical trials are needed to test the importance of lipoprotein oxidation as a cardiovascular risk factor in humans. In the recent years, various methods have been optimised and applied to the analysis of lipid oxidation products in vivo, and information on the molecular structures of oxidised lipids in plasma, lipoproteins and atherosclerotic plaques has started to accumulate. However, specific structures of oxidised TAG molecules present in these tissues and lipoprotein fractions have not been investigated earlier. In the orginal research in this thesis, an approach based on highperformance liquid chromatographyelectrospray ionisationmass spectrometry (HPLCESIMS) and baseline diene conjugation (BDC) methods was used in order to investigate lipid oxidation level and oxidised TAG molecular structures in pig and human lipoproteins after dietary interventions. The approach was optimised with human LDL samples, which contained various oxidation products of TAG. LDL particles of hyperlipidaemic subjects contained an elevated amount of conjugated dienes. In the pig studies, several oxidised TAG structures with hydroxy, keto, epoxy or aldehydic groups were found in chylomicrons and VLDL after diets rich in sunflower seed oil. Also, the results showed that oxidised sunflower seed oil increased the oxidation of lipoprotein lipids and their TAG molecules. TAG hydroperoxides could be detected neither in the small intestinal mucosa of the pigs fed on the oxidised oil nor in their chylomicrons or VLDL.6 In the clinical studies, dietary flavonol aglycones extracted from sea buckthorn berries did not have an effect on lipoprotein lipid oxidation and other potential risk factors of atherosclerosis, but their absorption was demonstrated. Oil supplementation seemed to increase the bioavailability of the flavonols. Oxidised TAG molecules were detected in LDL particles of the subjects after both flavonol and control diets.
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Epicatechin conjugates obtained from grape have shown antioxidant activity in various systems. However, how these conjugates exert their antioxidant benefits has not been widely studied. We assessed the activity of epicatechin and epicatechin conjugates on the erythrocyte membrane in the presence and absence of a peroxyl radical initiator, to increase our understanding of their mechanisms. Thus, we studied cell membrane fluidity by fluorescence anisotropy measurements, morphology of erythrocytes by scanning electron microscopy, and finally, red cell membrane proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Our data showed that incubation of red cells in the presence of epicatechin derivatives altered membrane fluidity and erythrocyte morphology but not the membrane protein pattern. The presence in the medium of the peroxyl radical initiator 2,2′-azobis(amidinopropane) dihydrochloride (AAPH) resulted in membrane disruptions at all levels analyzed, causing changes in membrane fluidity, cell morphology, and protein degradation. The presence of antioxidants avoided protein oxidation, indicating that the interaction of epicatechin conjugates with the lipid bilayer might reduce the accessibility of AAPH to membranes, which could explain in part the inhibitory ability of these compounds against hemolysis induced by peroxidative insult.
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BACKGROUND: Frailty is detected by weight loss, weakness, slow walking velocity, reduced physical activity or poor endurance/exhaustion. Handwriting has not been examined in the context of frailty, despite its functional importance. OBJECTIVE: Our goal was to examine quantitative handwriting measures in people meeting 0, 1, and 2 or more (2+) frailty criteria. We also examined if handwriting parameters were associated with gait performance, weakness, poor endurance/exhaustion and cognitive impairment. METHODS: From the population-based Lc65+, 72 subjects meeting 2+ frailty criteria with complete handwriting samples were identified. Gender-matched controls meeting 1 criterion or no criteria were identified. Cognitive impairment was defined by a Mini-Mental State Examination score of 25 or less or the lowest 20th percentile of Trail Making Test Part B. Handwriting was recorded using a writing tablet and measures of velocity, pauses, and pressure were extracted. RESULTS: Subjects with 2+ criteria were older, had more health problems and need for assistance but had higher education. No handwriting parameter differed between frailty groups (age and education adjusted). Writing velocity was not significantly slower among participants from the slowest 20th percentile of gait velocity but writing pressure was significantly lower among those from the lowest 20th percentile of grip strength. Poor endurance/exhaustion was not associated with handwriting measures. Low cognitive performance was related to longer pauses. CONCLUSIONS: Handwriting parameters might be associated with specific aspects of the frailty phenotype, but not reliably with global definitions of frailty at its earliest stages among subjects able to perform handwriting tests.