126 research outputs found

    Alpha-Linolenic Acid Intake and 10-Year Incidence of Coronary Heart Disease and Stroke in 20,000 Middle-Aged Men and Women in The Netherlands

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    Background - Whether intake of alpha-linolenic acid (ALA), the plant-derived n-3 polyunsaturated fatty acid (PUFA), could prevent cardiovascular diseases is not yet clear. We examined the associations of ALA intake with 10-year incidence of coronary heart disease (CHD) and stroke in the Netherlands. Methods - Data were collected from a general population of 20,069 generally healthy men and women, aged 20 to 65 years. Habitual diet was assessed at baseline (1993–1997) with a validated 178-item food frequency questionnaire. Incidences of CHD and stroke were assessed through linkage with mortality and morbidity registers. Hazard ratios (HR) were calculated with multivariable Cox proportional hazards models, adjusted for age, gender, lifestyle, and dietary factors. Results - During 8–13 years of follow-up, we observed 280 incident CHD events (19% fatal) and 221 strokes (4% fatal). Intakes of energy-adjusted ALA in quintiles ranged from less than 1.0 g/d in the bottom quintile (Q1) to more than 1.9 g/d in the top quintile (Q5). ALA intake was not associated with incident CHD, with HRs varying between 0.89 and 1.01 (all p>0.05) in Q2–Q5 compared with the bottom quintile of ALA intake. For incident stroke, however, participants in Q2–Q5 had a 35–50% lower risk compared with the reference group. HRs were 0.65 (0.43–0.97), 0.49 (0.31–0.76), 0.53 (0.34–0.83), and 0.65 (0.41–1.04) for Q2–Q5 respectively. Conclusion - In this general Dutch population, ALA intake was not associated with incident CHD. The data suggested that a low intake of ALA may be a risk factor for incident stroke. These results warrant confirmation in other population-based studies and in trial

    Fish consumption and its motives in households with versus without self-reported medical history of CVD: A consumer survey from five European countries

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    <p>Abstract</p> <p>Background</p> <p>The purpose of this study was to explore the cross-cultural differences in the frequency of fish intake and in motivations for fish consumption between people from households with (CVD+) or without (CVD-) medical history of cardiovascular disease, using data obtained in five European countries.</p> <p>Methods</p> <p>A cross-sectional consumer survey was carried out in November-December 2004 with representative household samples from Belgium, the Netherlands, Denmark, Poland and Spain. The sample consisted of 4,786 respondents, aged 18–84 and who were responsible for food purchasing and cooking in the household.</p> <p>Results</p> <p>Individuals from households in the CVD+ group consumed fish more frequently in Belgium and in Denmark as compared to those in the CVD- group. The consumption of fatty fish, which is the main sources of omega-3 PUFA associated with prevention of cardiovascular diseases, was on the same level for the two CVD groups in the majority of the countries, except in Belgium where CVD+ subjects reported to eat fatty fish significantly more frequently than CVD- subjects. All respondents perceived fish as a very healthy and nutritious food product. Only Danish consumers reported a higher subjective and objective knowledge related to nutrition issues about fish. In the other countries, objective knowledge about fish was on a low level, similar for CVD+ as for CVD- subjects, despite a higher claimed use of medical information sources about fish among CVD+ subjects.</p> <p>Conclusion</p> <p>Although a number of differences between CVD- and CVD+ subjects with respect to their frequency of fish intake are uncovered, the findings suggest that fish consumption traditions and habits – rather than a medical history of CVD – account for large differences between the countries, particularly in fatty fish consumption. This study exemplifies the need for nutrition education and more effective communication about fish, not only to the people facing chronic diseases, but also to the broader public. European consumers are convinced that eating fish is healthy, but particular emphasis should be made on communicating benefits especially from fatty fish consumption.</p

    Fabrication and in vitro deployment of a laser-activated shape memory polymer vascular stent

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    <p>Abstract</p> <p>Background</p> <p>Vascular stents are small tubular scaffolds used in the treatment of arterial stenosis (narrowing of the vessel). Most vascular stents are metallic and are deployed either by balloon expansion or by self-expansion. A shape memory polymer (SMP) stent may enhance flexibility, compliance, and drug elution compared to its current metallic counterparts. The purpose of this study was to describe the fabrication of a laser-activated SMP stent and demonstrate photothermal expansion of the stent in an <it>in vitro </it>artery model.</p> <p>Methods</p> <p>A novel SMP stent was fabricated from thermoplastic polyurethane. A solid SMP tube formed by dip coating a stainless steel pin was laser-etched to create the mesh pattern of the finished stent. The stent was crimped over a fiber-optic cylindrical light diffuser coupled to an infrared diode laser. Photothermal actuation of the stent was performed in a water-filled mock artery.</p> <p>Results</p> <p>At a physiological flow rate, the stent did not fully expand at the maximum laser power (8.6 W) due to convective cooling. However, under zero flow, simulating the technique of endovascular flow occlusion, complete laser actuation was achieved in the mock artery at a laser power of ~8 W.</p> <p>Conclusion</p> <p>We have shown the design and fabrication of an SMP stent and a means of light delivery for photothermal actuation. Though further studies are required to optimize the device and assess thermal tissue damage, photothermal actuation of the SMP stent was demonstrated.</p

    Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma

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    BACKGROUND: Germline mutations of the SDHD, SDHB and SDHC genes, encoding three of the four subunits of succinate dehydrogenase, are a major cause of hereditary paraganglioma and pheochromocytoma, and demonstrate that these genes are classic tumor suppressors. Succinate dehydrogenase is a heterotetrameric protein complex and a component of both the Krebs cycle and the mitochondrial respiratory chain (succinate:ubiquinone oxidoreductase or complex II). METHODS: Using conformation sensitive gel electrophoresis (CSGE) and direct DNA sequencing to analyse genomic DNA from peripheral blood lymphocytes, here we describe the mutation analysis of the SDHB and SDHC genes in 37 patients with sporadic (i.e. no known family history) head and neck paraganglioma and five pheochromocytoma and/or paraganglioma families. RESULTS: Two sporadic patients were found to have a SDHB splice site mutation in intron 4, c.423+1G>A, which produces a mis-spliced transcript with a 54 nucleotide deletion, resulting in an 18 amino acid in-frame deletion. A third patient was found to carry the c.214C>T (p.Arg72Cys) missense mutation in exon 4 of SDHC, which is situated in a highly conserved protein motif that constitutes the quinone-binding site of the succinate: ubiquinone oxidoreductase (SQR) complex in E. coli. Together with our previous results, we found 27 germline mutations of SDH genes in 95 cases (28%) of sporadic head and neck paraganglioma. In addition all index patients of five families showing hereditary pheochromocytoma-paraganglioma were found to carry germline mutations of SDHB: four of which were novel, c.343C>T (p.Arg115X), c.141G>A (p.Trp47X), c.281G>A (p.Arg94Lys), and c.653G>C (p.Trp218Ser), and one reported previously, c.136C>T, p.Arg46X. CONCLUSION: In conclusion, these data indicate that germline mutations of SDHB and SDHC play a minor role in sporadic head and neck paraganglioma and further underline the importance of germline SDHB mutations in cases of familial pheochromocytoma-paraganglioma

    A preliminary study of mercury exposure and blood pressure in the Brazilian Amazon

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    BACKGROUND: Fish is considered protective for coronary heart disease (CHD), but mercury (Hg) intake from fish may counterbalance beneficial effects. Although neurotoxic effects of methylmercury (MeHg) are well established, cardiovascular effects are still debated. The objective of the present study was to evaluate blood pressure in relation to Hg exposure and fish consumption among a non-indigenous fish-eating population in the Brazilian Amazon. METHODS: The study was conducted among 251 persons from six communities along the Tapajós River, a major tributary of the Amazon. Data was obtained for socio-demographic information, fish consumption, height and weight to determine body mass index (BMI), systolic and diastolic blood pressure, and Hg concentration in hair samples. RESULTS: Results showed that overall, systolic and diastolic blood pressure, were relatively low (mean: 113.9 mmHg ± 14.6 and 73.7 mmHg ± 11.0). Blood pressure was significantly associated with hair total Hg (H-Hg), age, BMI and gender. No association was observed between fish consumption and blood pressure, although there were significant inter-community differences. Logistic regression analyses showed that the Odds Ratio (OR) for elevated systolic blood pressure (≥ 130 mmHg) with H-Hg ≥ 10 μg/g was 2.91 [1.26–7.28], taking into account age, BMI, smoking, gender and community. CONCLUSION: The findings of this preliminary study add further support for Hg cardiovascular toxicity

    Translational models for vascular cognitive impairment: a review including larger species.

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    BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited. METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations). CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required

    The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia.

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    RATIONALE: The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. OBJECTIVES: This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. METHODS: The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. RESULTS: The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. CONCLUSION: This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.This work was supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). The authors thank Charlotte Oomen for valuable comments on the manuscript.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00213-015-4007-

    Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

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    Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

    Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation

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    Background and aims:Obesity is associated with a blunted beta-adrenoceptor-mediated lipolysis and fat oxidation. We investigated whether polymorphisms in codon 16, 27 and 164 of the beta (2)-adrenoceptor gene (ADRB2) and exon 10 of the G protein beta (3)-subunit gene (GNB3) are associated with alterations in in vivo lipolysis and fat oxidation.Design and methods:Sixty-five male and 43 female overweight and obese subjects (body mass index (BMI) range: 26.1-48.4 kg/m(2)) were included. Energy expenditure (EE), respiratory quotient (RQ), circulating free fatty acid (FFA) and glycerol levels were determined after stepwise infusion of increasing doses of the non-selective beta-agonist isoprenaline (ISO).Results:In women, the Arg16 allele of the ADRB2 gene was associated with a blunted increase in circulating FFA, glycerol and a decreased fat oxidation during ISO stimulation. In men, the Arg16 allele was significantly associated with a blunted increase in FFA but not in glycerol or fat oxidation.Conclusion:These results suggest that genetic variation in the ADRB2 gene is associated with disturbances in in vivo beta-adrenoceptor-mediated lipolysis and fat oxidation during beta-adrenergic stimulation in overweight and obese subjects; these effects are influenced by gene-gender interactions.International Journal of Obesity advance online publication, 28 November 2006; doi:10.1038/sj.ijo.0803499
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