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      Impact of Oxidative Stress in Premature Aging and Iron Overload in Hemodialysis Patients

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          Abstract

          Background. Increased oxidative stress is a well described feature of patients in hemodialysis. Their need for multiple blood transfusions and supplemental iron causes a significant iron overload that has recently been associated with increased oxidation of polyunsaturated lipids and accelerated aging due to DNA damage caused by telomere shortening. Methods. A total of 70 patients were evaluated concomitantly, 35 volunteers with ferritin levels below 500 ng/mL (Group A) and 35 volunteers with ferritin levels higher than 500 ng/mL (Group B). A sample of venous blood was taken to extract DNA from leukocytes and to measure relative telomere length by real-time PCR. Results. Patients in Group B had significantly higher plasma TBARS ( p = 0.008), carbonyls ( p = 0.0004), and urea ( p = 0.02) compared with those in Group A. Telomeres were significantly shorter in Group B, 0.66 (SD, 0.051), compared with 0.75 (SD, 0.155) in Group A ( p = 0.0017). We observed a statistically significant association between relative telomere length and ferritin levels ( r = −0.37, p = 0.001). Relative telomere length was inversely related to time on hemodialysis ( r = −0.27, p = 0.02). Conclusions. Our findings demonstrate that iron overload was associated with increased levels of oxidative stress and shorter relative telomere length.

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          Most cited references45

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          Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings.

          To determine the accuracy of echocardiographic left ventricular (LV) dimension and mass measurements for detection and quantification of LV hypertrophy, results of blindly read antemortem echocardiograms were compared with LV mass measurements made at necropsy in 55 patients. LV mass was calculated using M-mode LV measurements by Penn and American Society of Echocardiography (ASE) conventions and cube function and volume correction formulas in 52 patients. Penn-cube LV mass correlated closely with necropsy LV mass (r = 0.92, p less than 0.001) and overestimated it by only 6%; sensitivity in 18 patients with LV hypertrophy (necropsy LV mass more than 215 g) was 100% (18 of 18 patients) and specificity was 86% (29 of 34 patients). ASE-cube LV mass correlated similarly to necropsy LV mass (r = 0.90, p less than 0.001), but systematically overestimated it (by a mean of 25%); the overestimation could be corrected by the equation: LV mass = 0.80 (ASE-cube LV mass) + 0.6 g. Use of ASE measurements in the volume correction formula systematically underestimated necropsy LV mass (by a mean of 30%). In a subset of 9 patients, 3 of whom had technically inadequate M-mode echocardiograms, 2-dimensional echocardiographic (echo) LV mass by 2 methods was also significantly related to necropsy LV mass (r = 0.68, p less than 0.05 and r = 0.82, p less than 0.01). Among other indexes of LV anatomy, only measurement of myocardial cross-sectional area was acceptably accurate for quantitation of LV mass (r = 0.80, p less than 0.001) or diagnosis of LV hypertrophy (sensitivity = 72%, specificity = 94%).(ABSTRACT TRUNCATED AT 250 WORDS)
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            Oxidative stress shortens telomeres.

            Telomeres in most human cells shorten with each round of DNA replication, because they lack the enzyme telomerase. This is not, however, the only determinant of the rate of loss of telomeric DNA. Oxidative damage is repaired less well in telomeric DNA than elsewhere in the chromosome, and oxidative stress accelerates telomere loss, whereas antioxidants decelerate it. I suggest here that oxidative stress is an important modulator of telomere loss and that telomere-driven replicative senescence is primarily a stress response. This might have evolved to block the growth of cells that have been exposed to a high risk of mutation.
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              Telomere shortening in atherosclerosis.

              Eukaryotic chromosomes end with telomeres, which shorten with cellular ageing. We investigated whether atherosclerosis is associated with systemic evidence of accelerated cellular ageing. We compared mean length of terminal restriction fragments (TRF), a measure of average telomere size, in leucocyte DNA of ten patients with severe coronary artery disease (CAD) with that of 20 controls without CAD. Adjusting for age and sex, cases had mean TRF lengths of 303 (SD 90) base pairs shorter than those of controls (p=0.002)-ie, equivalent in size to individuals with no CAD who are 8.6 years older. Although this is a pilot study, the findings could be relevant to the pathogenesis of atherosclerosis.
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                Author and article information

                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi Publishing Corporation
                1942-0900
                1942-0994
                2016
                5 October 2016
                : 2016
                : 1578235
                Affiliations
                1Unidad de Investigación en Epidemiología Clínica, Servicio de Hemodiálisis, Unidad Médica de Alta Especialidad (UMAE) No. 1 Bajío, Instituto Mexicano del Seguro Social (IMSS), León, GTO, Mexico
                2Departamento de Investigaciones Médicas, Universidad de Guanajuato, León, GTO, Mexico
                3Unidad de Investigación Médica en Enfermedades Oncológicas, CMN, SXXI, IMSS, 06720 Ciudad de México, Mexico
                Author notes
                *Blanca Murillo-Ortiz: bomo907@ 123456hotmail.com

                Academic Editor: Claudio Cabello-Verrugio

                Author information
                http://orcid.org/0000-0003-4775-2755
                http://orcid.org/0000-0001-9813-9120
                http://orcid.org/0000-0002-2153-6619
                Article
                10.1155/2016/1578235
                5069386
                dd38eed8-cc09-48f3-b7f6-0ae9e44013a9
                Copyright © 2016 Blanca Murillo-Ortiz et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 April 2016
                : 15 July 2016
                : 23 August 2016
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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