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- Nitter, M., et al.
(författare)
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Plasma methionine, choline, betaine, and dimethylglycine in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 25:8, s. 1609-1615
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disturbances in one carbon metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low. Patients and methods: We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1367 incident CRC cases (965 colon and 402 rectum) and 2323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CRC risk were estimated by conditional logistic regression, comparing the fifth to the first quintile of plasma concentrations. Results: Overall, methionine (OR: 0.79, 95% CI: 0.63-0.99, P-trend = 0.05), choline (OR: 0.77, 95% CI: 0.60-0.99, P-trend = 0.07), and betaine (OR: 0.85, 95% CI: 0.66-1.09, P-trend = 0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/l, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95% CI: 0.50-1.00, P-trend = 0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95% CI: 0.43-0.88, P-trend = 0.01). Plasma DMG was not associated with CRC risk. Conclusions: Individuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of CRC.
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- Nymo, S. H., et al.
(författare)
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The association between neutrophil gelatinase-associated lipocalin and clinical outcome in chronic heart failure: Results from CORONA
- 2012
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 271, s. 436-443
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To study the prognostic value of neutrophil gelatinase-associated lipocalin (NGAL) in chronic heart failure (HF) of ischaemic aetiology. Background. Neutrophil gelatinase-associated lipocalin is a marker of kidney injury as well as matrix degradation and inflammation and has previously been shown to be increased in HF. We investigated whether serum NGAL levels could provide prognostic information in chronic HF. Methods. We assessed NGAL as a predictor of primary outcomes (cardiovascular death, nonfatal stroke and nonfatal myocardial infarction, n=307) and all-cause mortality (n=321), cardiovascular mortality (n=259) and hospitalization (n=647) as well as the number of hospitalizations during follow-up for all (n=1934) and CV causes (n=1204) in 1415 patients with chronic HF (≥60years, New York Heart Association class II-IV, ischaemic systolic HF) in the CORONA population, randomly assigned to 10mg rosuvastatin or placebo. Results. Multivariate analysis revealed that NGAL added significant information when adjusting for clinical variables, but was no longer significant when further adjusting for apolipoprotein A-1 (ApoA-1), glomerular filtration rate (GFR), C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). However, belonging to the highest NGAL tertile was associated with more frequent hospitalization, even after adjusting for clinical variables, GFR and ApoA-1, but not after adjusting for CRP and NT-proBNP. There was no interaction between rosuvastatin treatment and NGAL. Conclusion. Neutrophil gelatinase-associated lipocalin added no significant information to NT-proBNP and GFR in a multivariate model for primary and secondary end-points. © 2012 The Association for the Publication of the Journal of Internal Medicine.
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- Gravning, J., et al.
(författare)
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Prognostic Effect of High-Sensitive Troponin T Assessment in Elderly Patients With Chronic Heart Failure Results From the CORONA Trial
- 2014
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Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 7:1, s. 96-103
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Tidskriftsartikel (refereegranskat)abstract
- Background The incremental prognostic value of high-sensitive troponin T (hs-cTnT) in heart failure (HF) beyond that of high-sensitivity C-reactive protein and amino-terminal probrain natriuretic peptide is debated. We examined the prognostic value of hs-cTnT in a subgroup of patients from the Controlled Rosuvastatin Multinational Trial in HF (CORONA) study. Methods and Results Hs-cTnT as a risk factor for the primary end point (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke; n=356), as well as all-cause mortality (n=366), cardiovascular mortality (n=299), and the composite of cardiovascular mortality and hospitalization from worsening of HF (n=465), was investigated in 1245 patients (60 years; New York Heart Association [NYHA] class II-IV, ischemic systolic HF) randomly assigned to 10 mg rosuvastatin or placebo. In multivariable analyses, adjusting for left ventricular ejection fraction, NYHA class, age, body mass index, diabetes mellitus, sex, intermittent claudication, heart rate, estimated glomerular filtration rate, apolipoprotein B/apolipoprotein A-1 ratio, amino-terminal probrain natriuretic peptide, high-sensitivity C-reactive protein, and hs-cTnT (both dichotomized according to the 99th percentile and as a continuous variable) was associated with all end points (primary end point: hazard ratio, 1.87 and 1.51, respectively, per SD change; P<0.001; all other end points: hazard ratio, 1.39-1.70). However, improved discrimination as assessed by C-statistics was only seen for the primary end point and all-cause mortality. Conclusions Elevated hs-cTnT levels provide strong and independent prognostic information in older patients with chronic ischemic HF. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.
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- Jansson, AM, et al.
(författare)
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Multimarker Risk Assessment Including Osteoprotegerin and CXCL16 in Acute Coronary Syndromes.
- 2012
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1079-5642 .- 1524-4636. ; 32:12, s. 3041-3049
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Tidskriftsartikel (refereegranskat)abstract
- Objective-: CXCL16 and osteoprotegerin (OPG) both predict mortality in acute coronary syndromes. We hypothesized that a combination of CXCL16 and OPG concentrations would add prognostic information to the Global Registry of Acute Coronary Events (GRACE) score in patients hospitalized for acute coronary syndromes. Methods and Results-: We assessed the associations between circulating OPG and soluble CXCL16 levels, obtained within 24 hours of admission (day 1) and after 3 months, and mortality, heart failure and reinfarction in 1322 patients admitted with acute coronary syndromes. After adjustment for the GRACE score, medication, diabetes mellitus and sex, the combination of high values (fourth quartile) for OPG and CXCL16 at baseline was associated with increased short-term (3 months) cardiovascular mortality (hazard ratio, 3.28; 95% CI, 1.84-5.82; P<0.0001). The combined high values were also significantly associated with the long-term (median 91 months) prognosis after adjustment, with hazard ratios 2.18 for cardiovascular mortality (95% CI, 1.62-2.92; P<0.0001), and 2.22 for heart failure (95% CI, 1.67-2.96; P<0.0001). These long-term associations remained significant after further adjustment for left ventricular ejection fraction, C-reactive protein, and pro B-type natriuretic peptide. For 635 patients with blood samples within 24 hours and at 3 months, the combination of high CXCL16 and OPG values (fourth quartile) in the early or stable phase was of a similar order associated with mortality and morbidity beyond 3 months. Conclusion-: Circulating CXCL16 and OPG are independent predictors of long-term mortality and heart failure development in acute coronary syndromes patients, even after extensive adjustments. Their combination gives more information than either marker alone.
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- Jorgensen, A. P., et al.
(författare)
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Favorable long-term effects of growth hormone replacement therapy on quality of life, bone metabolism, body composition and lipid levels in patients with adult-onset growth hormone deficiency
- 2011
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; 21:2, s. 69-75
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The goal of growth hormone (GH) replacement is to improve quality of life (QoL) and prevent the long-term complications of GH deficiency (GHD). Thirty-nine patients with adult-onset GH deficiency (AOGHD) who had originally participated in a randomized placebo-controlled crossover study involving treatment with either GH or placebo for nine months were enrolled in an open, 33-month follow-up study of the effects on QoL as well as bone and metabolic parameters. Methods: GH replacement was dosed individually to obtain IGF-I concentrations that were within the upper part of the normal range for age (mean + 1SD). The variables were assessed on five occasions during the study. Results: QoL, as assessed by the sum scores of HSCL-58, AGHDA, physical activity (KIMS question 11) and the dimension vitality in SF-36, improved. Markers of bone formation and resorption remained increased throughout the study period. Bone mineral area (BMA), bone mineral content (BMC) and bone mineral density (BMD) increased in both the lumbar (L2-L4) spine and total body. BMC and BMD increased in the femur. Hypogonadal women however, showed reduced bone mass during the study period. The changes in body fat mass (BFM) and lean body mass (LBM) were sustained throughout the long-term treatment (BFM -2.18 (+/-4.87) kg LBM by 2.01( +/-3.25) kg). Low-density lipoprotein cholesterol (LDL-C) levels were reduced by 0.6 (+/-1.1) mmol/l, and high-density lipoprotein cholesterol (HDL-C) levels increased by 0.2 (+/-0.3) mmol/l. No changes were observed in body weight, fasting total cholesterol, triglycerides, HbA1c and plasma glucose. Mean fasting insulin levels increased significantly from 110 pmol/l to 159 pmol/l, p <0.02. Conclusion: Long-term replacement of growth hormone in patients with AOGHD induces favorable effects on QoL as well as bone and metabolic parameters. An increase in insulin levels is also noteworthy. (C) 2011 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.
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- Nymo, S. H., et al.
(författare)
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Inflammatory cytokines in chronic heart failure: interleukin-8 is associated with adverse outcome. Results from CORONA
- 2014
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 16:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Aim We investigated the ability of prototypical inflammatory cytokines to predict clinical outcomes in a large population of patients with chronic systolic heart failure (HF). Methods and results Serum levels of tumour necrosis factor-alpha (TNF-alpha), soluble TNF receptors type I and II (sTNF-RI and sTNF-RII), and the chemokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) were analysed in 1464 patients with chronic ischaemic systolic HF in the CORONA study, aged >= 60 years, in NYHA class II-IV, and related to the primary endpoint (n = 320), as well as any coronary event (n = 255), all-cause mortality (n = 329), cardiovascular (CV) mortality (n = 268), and the composite endpoint hospitalization from worsening heart failure (WHF) or CV mortality (n = 547). TNF-alpha, sTNF-RI, sTNF-RII, and IL-8, but not MCP-1, were independent predictors of all endpoints except the coronary endpoint in multivariable models including conventional clinical variables. After further adjustment for estimated glomerular filtration rate, the ApoB/ApoA-1 ratio, NT-proBNP, and high-sensitivity C-reactive protein, only IL-8 remained a significant predictor of all endpoints (except the coronary endpoint), while sTNF-RI remained independently associated with CV mortality. Adding IL-8 to the full model led to a significant improvement in net reclassification for all-cause mortality and CV hospitalization, but only a borderline significant improvement for the primary endpoint, CV mortality, and the composite endpoint WHF hospitalization or CV mortality. Conclusion Our study supports a relationship between IL-8 and outcomes in patients with chronic HF. However, the clinical usefulness of IL-8 as a biomarker in an unselected HF population is at present unclear.
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- Arora, Satish, et al.
(författare)
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Virtual Histology Assessment of Cardiac Allograft Vasculopathy Following Introduction of Everolimus—Results of a Multicenter Trial
- 2012
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Ingår i: American Journal of Transplantation. - : Wiley-Blackwell. - 1600-6135 .- 1600-6143. ; 12:10, s. 2700-2709
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Tidskriftsartikel (refereegranskat)abstract
- In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 +/- 3.8% and 1.6 +/- 3.9%, respectively; p = 0.65). However, VH analysis revealed a significant increase in calcified (2.4 +/- 4.0 vs. 0.3 +/- 3.1%; p = 0.02) and necrotic component (6.5 +/- 8.5 vs. 1.1 +/- 8.6%; p = 0.01) among everolimus patients compared to controls. The increase in necrotic and calcified components was most prominent in everolimus patients with time since HTx andgt;5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal components and is more prominent in patients with a longer time since HTx. A significant increase in vWF and VCAM accompanied these qualitative changes and the prognostic implication of these findings requires further investigation.
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- Caidahl, K, et al.
(författare)
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Osteoprotegerin: a biomarker with many faces
- 2010
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 30:9, s. 1684-1686
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Gullestad, L., et al.
(författare)
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Galectin-3 predicts response to statin therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)
- 2012
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 33:18, s. 2290-2296
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether plasma galectin-3, a mediator of fibrogenesis, can identify patients with chronic heart failure (HF) for whom statins are effective. Patients with ischaemic systolic HF enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) were randomly assigned to 10 mg/day of rosuvastatin or placebo. Galectin-3 was measured in plasma. The primary outcome was cardiovascular death, myocardial infarction, or stroke. Of 1492 patients, 411 had a primary event during a median follow-up of 32.8 months. There was an interaction between baseline galectin-3 and rosuvastatin on the primary endpoint (P-value for interaction 0.036). Among patients with below the median plasma concentrations of galectin-3 (19.0 ng/mL), those assigned to rosuvastatin had a lower primary event rate [hazard ratio (HR) 0.65; 95 confidence interval (CI), 0.460.92; P 0.014], lower total mortality (HR 0.70; 95 CI, 0.500.98; P 0.038), and lower event rate of all-cause mortality and HF hospitalizations (HR 0.72; 95 CI, 0.540.98; P 0.017) compared with placebo, but no benefit was observed in patients with higher levels of galectin-3. The combination of concurrently low concentrations of galectin-3 and N-terminal pro-B-type natriuretic peptide (102.7 pmol/L) identified patients with a large benefit with rosuvastatin (HR 0.33; 95 CI, 0.160.67; P 0.002). Patients with systolic HF of ischaemic aetiology who have galectin-3 values 19.0 ng/mL may benefit from rosuvastatin treatment. However, the data from this post hoc analysis should be interpreted with caution since the overall results of the CORONA study did not show a significant effect on the primary endpoint.
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- Gullestad, L., et al.
(författare)
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The predictive value of galectin-3 for mortality and cardiovascular events in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)
- 2012
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 164:6, s. 878-883
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Tidskriftsartikel (refereegranskat)abstract
- Background Galectin-3 is a new biomarker involved in inflammation and fibrogenesis and could therefore contribute to myocardial remodeling. We examined the prognostic value of baseline galectin-3 in a substudy involving approximately 30% of participants in the CORONA study. Methods Patients (n = 1462) aged >60 years with systolic, ischemic heart failure (HF) were randomized to 10 mg/d rosuvastatin or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, or stroke (n = 408). Results In the unadjusted analysis, galectin-3 was associated with all end points considered, except hospitalization for worsening of HF. In multivariable analyses, adjusting for other clinical and biochemical predictor variables, galectin-3 was significantly associated with the primary end point (hazard ratio [HR] 1.53 [1.10-2.12], P = .011) as well as all-cause (HR 1.61 [1.20-2.29], P = .002) and cardiovascular mortality (HR 1.70 [1.19-2.42], P = .003), sudden death (HR 1.83 [1.14-2.94], P = .012), and the coronary end point (HR 1.48 [1.03-2.12], P = .035). However, when N-terminal pro-brain natriuretic peptide was added to the model, galectin-3 association with the end points was markedly attenuated and no longer significant. Conclusions Galectin-3 is not associated with outcome in older patients with advanced chronic systolic HF of ischemic etiology when adjusting for N-terminal pro-brain natriuretic peptide and may therefore have limited use in the prognostication of elderly patients with systolic HF in clinical practice. (Am Heart J 2012;164:878-83.)
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- Latini, R., et al.
(författare)
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Pentraxin-3 in chronic heart failure: the CORONA and GISSI-HF trials
- 2012
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 14:9, s. 992-999
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Tidskriftsartikel (refereegranskat)abstract
- Pentraxin-3 (PTX3) is a component of the humoral arm of innate immunity which can regulate inflammatory processes. Since the role of inflammation in the progression of chronic heart failure (HF) is debated, we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF. Plasma levels of PTX3 were measured at randomization and after 3 months in 1457 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and 1233 patients enrolled in the GISSI-Heart Failure trial (GISSI-HF). The relationships between baseline PTX3 levels or their changes over time and mortality were evaluated with multivariable Cox proportional hazard models including clinical factors, high sensitivity C-reactive protein (hsCRP), and N-terminal pro brain natriuretic peptide (NT-proBNP). PTX3 concentration [median (Q1Q3) 5.34 (3.557.64) ng/mL, n 2690] was higher in females, in older patients, and those with lower body mass index. Baseline elevated PTX3 was associated with a higher risk of all-cause mortality [759 events, hazard ratio (HR) for 1 SD increase 1.20, 95 confidence interval (CI) 1.121.30, P 0.0001], cardiovascular mortality (587 events, HR 1.27, 95 CI 1.171.38, P 0.0001), or hospitalization for worsening HF (720 events, HR 1.21, 95 CI 1.121.30, P 0.0001), and marginally improved discrimination. Three-month changes in PTX3 were associated with fatal events after adjustment for hsCRP or NT-proBNP. Rosuvastatin lowered hsCRP levels but significantly raised PTX3. In two independent clinical trials that enrolled patients with chronic HF, PTX3 was consistently associated with outcomes. The opposite effects of a statin on hsCRP and PTX3 call for further investigation. NCT00336336 (GISSI-HF), NCT00206310 (CORONA).
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- Paulsen, Morten T., et al.
(författare)
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Sensory perception of salmon and culinary sauces : An interdisciplinary approach
- 2012
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Ingår i: Food Quality and Preference. - : Elsevier. - 0950-3293 .- 1873-6343. ; 23:2, s. 99-109
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Tidskriftsartikel (refereegranskat)abstract
- Sauces play an important role in the sensory perception of meals. The combination of sauce and other foods in a meal might cause sensory interactions which change sensory attributes and the overall impression of the meal. The main aim of this study was to investigate the effects of culinary sauces, with different levels and combinations of the basic tastes, on the sensory attributes of salmon using mixed tasting technique. Seventeen different combinations of salmon and culinary sauces were evaluated by a trained panel at Nofima using descriptive analysis. The samples were analyzed in this sequence; first the salmon, then the sauce and finally the combination of salmon and sauce. Significant changes were found in salmon for all combinations, most importantly; bitter, acid and salty sauces significantly reduced salmon flavor, while salty sauce also reduced fish-oil flavor. Bitter, acid and salty sauces significantly increased the attribute complexity and bitter sauce reduced the attribute harmony. This study can be seen as a model for product development combining experimental design and sensory analysis with culinary knowledge. Results may be applied for tailoring fish meals for specific consumer segments. (C) 2011 Elsevier Ltd. All rights reserved.
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