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      Endothelial Function and Serum Concentration of Toxic Metals in Frequent Consumers of Fish

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          Abstract

          Background

          Endothelial dysfunction is involved in the pathogenesis of atherosclerosis. Consumption of fish is associated with reduced cardiovascular risk, but there is paucity of data concerning its effect on endothelial function. Furthermore, investigation of the effects of fish consumption on health must take into account the ingestion of contaminants, including transition metals and some metalloids, which may have unfavorable effects on health, including those on the cardiovascular system. We investigated the association between fish consumption, endothelial function (flow mediated dilation of the brachial artery), and serum concentration of some toxic metals in apparently healthy people.

          Methods

          Twenty-nine high fish consumers (at least 3 portions a week) were compared with 25 low fish consumers (less than 1 portion a week). All participants were free of diabetes, cardiovascular or other systemic diseases. Serum metal (antimonium, arsenic, mercury, lead, cobalt, copper, zinc, selenium, strontium) concentrations were measured in subgroups of 24 high fish consumers and 19 low fish consumers.

          Results

          Both groups exhibited similar habitual dietary patterns, age and anthropometric characteristics. The high fish consumers had higher flow mediated dilation (9.7±1.8 vs. 7.3±1.9%; P<0.001), but also higher serum concentrations of mercury (5.87±2.69 vs. 1.65±1.10 mcg/L; P<0.001) and arsenic (6.04±3.25 vs. 2.30±1.58 mcg/L; P<0.001). The fasting plasma glucose concentrations were significantly correlated with both mercury (r = 0.39; P = 0.01) and arsenic concentrations (r = 0.55; P<0.001).

          Conclusions

          Habitual consumption of high amounts of fish is associated with better endothelial function despite higher serum concentrations of mercury and arsenic.

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          Most cited references44

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          The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.

          Despite its very potent vasodilating action in vivo, acetylcholine (ACh) does not always produce relaxation of isolated preparations of blood vessels in vitro. For example, in the helical strip of the rabbit descending thoracic aorta, the only reported response to ACh has been graded contractions, occurring at concentrations above 0.1 muM and mediated by muscarinic receptors. Recently, we observed that in a ring preparation from the rabbit thoracic aorta, ACh produced marked relaxation at concentrations lower than those required to produce contraction (confirming an earlier report by Jelliffe). In investigating this apparent discrepancy, we discovered that the loss of relaxation of ACh in the case of the strip was the result of unintentional rubbing of its intimal surface against foreign surfaces during its preparation. If care was taken to avoid rubbing of the intimal surface during preparation, the tissue, whether ring, transverse strip or helical strip, always exhibited relaxation to ACh, and the possibility was considered that rubbing of the intimal surface had removed endothelial cells. We demonstrate here that relaxation of isolated preparations of rabbit thoracic aorta and other blood vessels by ACh requires the presence of endothelial cells, and that ACh, acting on muscarinic receptors of these cells, stimulates release of a substance(s) that causes relaxation of the vascular smooth muscle. We propose that this may be one of the principal mechanisms for ACh-induced vasodilation in vivo. Preliminary reports on some aspects of the work have been reported elsewhere.
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            Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study.

            The relationship between impaired brachial flow-mediated dilation (FMD) and subsequent clinical cardiovascular events is not well established, especially in older adults whose FMD is often diminished. We assessed the hypothesis that FMD predicts incident cardiovascular events in a population-based cohort of older adults. FMD was measured at the 1997 to 1998 Cardiovascular Health Study clinic visit in 2792 adults aged 72 to 98 years (82.7% white, 58.6% women) recruited at 4 clinic sites in the United States. Log-rank test and Cox proportional hazard models were used to examine the association between FMD and adjudicated cardiovascular events. A total of 674 subjects (24.1%) had an adjudicated event over the 5-year follow-up period. Event-free survival rates for cardiovascular events were significantly higher in subjects with FMD greater than the sex-specific medians than in subjects with FMD less than or equal to the sex-specific medians (78.3% versus 73.6%, log-rank P=0.006). FMD remained a significant predictor of cardiovascular events after adjustment for age, gender, diabetes mellitus, cigarette smoking, systolic and diastolic blood pressure, baseline cardiovascular disease status, and total cholesterol (hazard ratio, 0.91 [95% CI, 0.83 to 0.99], P=0.02 per unit SD of FMD) but added only approximately 1% to the prognostic accuracy of the best Cox model. Brachial artery diameter was also predictive of CV events in the adjusted Cox proportional hazard model (hazard ratio, 1.12 [95% CI, 1.02 to 1.28], P=0.025) and also added approximately 1% to the accuracy of our best Cox model. FMD is a predictor of future cardiovascular events but adds very little to the prognostic accuracy of traditional cardiovascular risk scores/factors in older adults. FMD and brachial artery diameter may have similar predictive values for cardiovascular events in older adults.
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              Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease.

              The National Kidney Foundation has advocated the use of the abbreviated Modification of Diet in Renal Disease (MDRD) equation to estimate glomerular filtration rate (GFR) from serum creatinine measurements in clinical laboratories. However, healthy persons were not included in the development of the MDRD equation. To assess the accuracy of the MDRD equation in patients with chronic kidney disease compared with healthy persons and to develop a new equation that uses both patients with chronic kidney disease and healthy persons. Cross-sectional study. The Mayo Clinic, a tertiary-care medical center. Consecutive patients (n = 320) who had an iothalamate clearance test specifically for chronic kidney disease evaluation and consecutive healthy persons (n = 580) who had an iothalamate clearance test specifically for kidney donor evaluation. Serum creatinine levels, GFR, demographic characteristics, and clinical characteristics were abstracted from the medical record. The MDRD equation underestimated GFR by 6.2% in patients with chronic kidney disease and by 29% in healthy persons. Re-estimated coefficients for serum creatinine and sex were similar to the original MDRD equation in the chronic kidney disease series but not in the healthy series. At the same serum creatinine level, age, and sex, GFR was on average 26% higher in healthy persons than in patients with chronic kidney disease (P < 0.001). A quadratic GFR equation was developed to estimate logarithmic GFR from the following covariates: 1/SCr, 1/SCr2, age, and sex (where SCr = serum creatinine). The new equation was not developed in a general population sample. Elderly and African-American persons were underrepresented. The MDRD equation systematically underestimates GFR in healthy persons. A new equation developed with patients who have chronic kidney disease and healthy persons may be a step toward accurately estimating GFR when the diagnosis of chronic kidney disease is unknown.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                17 November 2014
                : 9
                : 11
                : e112478
                Affiliations
                [1 ]Dipartimento Biomedico di Medicina Interna e Specialistica Laboratorio di Nutrizione Clinica, University of Palermo, Palermo, Italy
                [2 ]Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo, Palermo, Italy
                [3 ]Dipartimento di Scienze per la Promozione della Salute e Materno Infantile, University of Palermo, Palermo, Italy
                [4 ]Dipartimento di Scienze del Farmaco, University of Catania, Catania, Italy
                [5 ]Scientific Institute for Research, Hospitalization and Health Care, Policlinico San Donato, San Donato, Milan, Italy
                University of Pecs Medical School, Hungary
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: S. Buscemi S. Vasto FD GG S. Berganti FG S. Verga. Performed the experiments: S. Buscemi S. Vasto FD FMM EA GR. Analyzed the data: S. Buscemi GG S. Berganti FG FMM GR S. Verga. Contributed reagents/materials/analysis tools: S. Buscemi S. Vasto FD FMM EA. Contributed to the writing of the manuscript: S. Buscemi S. Vasto GG S. Berganti FG EA GR S. Verga.

                Article
                PONE-D-14-37161
                10.1371/journal.pone.0112478
                4234466
                25401695
                e18b993d-ad82-4e4b-aa39-a130ca6c2239
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 August 2014
                : 16 September 2014
                Page count
                Pages: 7
                Funding
                This work was supported by the Regione Sicilia, Assessorato Regionale delle Risorse Agricole e Alimentari - Dipartimento Regionale degli Interventi per la Pesca decreto n° 134 del 28.05.2010 (project code: P09/5/120). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Nutrition
                Diet
                Toxicology
                Toxic Agents
                Toxins
                Heavy Metals
                Medicine and Health Sciences
                Vascular Medicine
                Atherosclerosis
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. Data are available from the Dipartimento Biomedico di medicina Interna e Specialistica of the University of Palermo (Italy)- Institutional Data Access - for researchers who meet the criteria for access to confidential data. Requests can be sent to the corresponding author.

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