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    In vivo supplementation with coenzyme Q10 enhances the recovery of human lymphocytes from oxidative DNA damage.

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    We investigated the effect of in vitro and in vivo CoQ10 supplementation on the recovery of lymphocytes from oxidative DNA damage. Furthermore, we investigated whether CoQ10 supplementation modulates the activity of DNA repair enzymes by using cellular extracts from lymphocytes. Exposure of lymphocytes to oxidizing agents leads to an increase of DNA strand breaks, oxidized purines, and pyrimidines. Enrichment of cells with CoQ10 prevents DNA strandbreak formation and affects the kinetics of repair, which occurs faster in enriched than in native lymphocytes. In contrast, CoQ10 supplementation neither prevents endogenous formation of oxidized bases nor affects their repair. DNA repair enzyme activity is enhanced by in vivo CoQ10 supplementation. Changes in the redox state of several transcriptional factors have been proposed as mechanisms regulating cell proliferation and apoptosis. Because CoQ10 is mainly present as ubiquinol-10, both in plasma and lymphocytes, it can feasibly modulate the intracellular redox potential involved in the regulation of gene expression. The redox mechanism implicated in the enzyme transactivation could explain the property of CoQ10 to enhance the DNA repair activity and protect DNA from oxidative damage

    Coenzyme Q10 enrichment decreases oxidative DNA damage in human lymphocytes.

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    Ubiquinol-10, the reduced form of coenzyme Q10, is a powerful antioxidant in plasma and lipoproteins. It has been suggested that endogenous ubiquinol-10 also exerts a protective role even towards DNA oxidation mediated by lipid peroxidation. Even though the antioxidant activity of coenzyme Q10 is mainly ascribed to ubiquinol-10, a role for ubiquinone-10 (the oxidized form), has been suggested not only if appropriate reducing systems are present. To investigate whether the concentration of ubiquinol-10 or ubiquinone-10 affects the extent of DNA damage induced by H2O2, we supplemented in vitro human lymphocytes with both forms of coenzyme Q10 and evaluated the DNA strand breaks by Comet assay. The exposure of lymphocytes to 100 microM H2O2 resulted in rapid decrease of cellular ubiquinol-10 content both in ubiquinol-10-enriched and in control cells, whereas alpha-tocopherol and beta-carotene concentration were unchanged. After 30 min from H2O2 exposure, the amount of DNA strand breaks was lower and cells' viability was significantly higher in ubiquinol-10-enriched cells compared with control cells. A similar trend was observed in ubiquinone-10-enriched lymphocytes when compared with control cells. Our experiments suggest that coenzyme Q10 in vitro supplementation enhances DNA resistance towards H2O2-induced oxidation, but it doesn't inhibit directly DNA strand break formation

    Distribution of antioxidants among blood components and lipoproteins: significance of lipids/CoQ10 ratio as a possible marker of increased risk for atherosclerosis.

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    Total CoQ10 levels were evaluated in whole blood and in plasma obtained from a group of 83 healthy donors. Extraction with light petroleum ether/methanol was more efficient, for whole blood, than the extraction which is often used for plasma and serum, i.e., ethanol hexane. An excellent correlation was present between plasma CoQ10 and whole blood CoQ10. CoQ10 is mainly associated with plasma rather than with cellular components. Positive, significant correlations were found between the LDL-chol/CoQ10 ratio and the total-chol/HDL-chol ratio, which is usually considered a risk factor for atherosclerosis. The proportion of CoQ10 carried by LDL was 58 +/- 10\%, while the amount carried by HDL was 26 +/- 8\%. In VLDL + IDL CoQ10 was 16 +/- 8\%. The content of CoQ10 in single classes of lipoproteins is strictly correlated with CoQ10 plasma concentration. In a parallel study conducted on a population of diabetic patients (one IDDM group and one NIDDM) CoQ10 plasma levels were generally higher compared to the control group, also when normalised to total cholesterol. In particular the LDL fraction showed a CoQ10/chol ratio higher in NIDDM but not in IDDM patients, compared to controls. The CoQ10/triglycerides ratio was lower in NIDDM respect to controls and even lower in IDDM patients

    Oxidation of LDL and their subfractions: kinetic aspects and CoQ10 content.

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    Coenzyme Q10 in its reduced form, ubiquinol-10, although present in LDL at concentrations considerably lower than that of alpha-tocopherol, exerts a potent antioxidant action in this class of lipoproteins. Previous studies indicated that the content of CoQ10 is the lowest in the densest subfraction of LDL, i.e. LDL3, which is commonly regarded as the most peroxidizable and atherogenic one. These levels were associated with the highest levels of hydroperoxides detectable in the three subclasses. Enrichment of LDL with CoQ10, by means of exogenous supplementation, resulted in a significant increase of CoQ10 in LDL, mainly in LDL3, and in a lower extent of peroxidizability. Spontaneous oxidation of ubiquinol was monitored in plasma and in LDL of unsupplemented and of supplemented subjects and the time-course of oxidation was found considerably slower in CoQ10-enriched LDL. The lagphase of conjugated dienes formation upon induced oxidation was significantly correlated with the absolute content of ubiquinol-10. Distribution of CoQ10 among different classes of plasma lipoproteins was also studied: about 60\% of plasma CoQ10 was found associated with LDL

    Malignant mesothelioma: biology, diagnosis and therapeutic approaches.

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    Malignant mesothelioma (MM) is an aggressive neoplasm of serosal cavities, which is resistant to conventional therapy, with patient survival from presentation of <12 months. MM remains a universally fatal disease of increasing incidence worldwide. Although the main risk factor is asbestos exposure, other factors, Simian virus 40 infection and inheritance of susceptibility genes, likely play a role. Asbestos-related carcinogenic process is primarily based on the interaction between susceptibility (genetic and acquired) and exposure to carcinogenic environmental agents. Asbestos-induced carcinogenesis includes generation of reactive oxygen species, which induce DNA strand breaks and oxidant-induced base modifications to DNA. Persistent oxidative DNA damage can alter signaling cascades, gene expression, induce or arrest transcription, and increase replication errors and genomic instability. The long promotion phase observed in MM pathogenesis and the absence of early symptoms both contribute to late diagnosis of the disease. This results in delayed therapeutic intervention of patients, making the outcome of the disease very grim. There have been several developments in MM management, principally based on early detection, improved diagnosis, development of more effective therapies, and new insights into the pathobiology of the disease. Several programs have been used to screen asbestos-exposed individuals for lung and pleural disease. These programs involve annual pulmonary function tests, chest radiography and high resolution computer tomography. Blood tests make screening of target populations an attractive strategy. Many current gene and protein expression studies aim to identify clinically useful biomarkers and new therapeutic targets for improved management of MM

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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