| 751. |
- Salihovic, Samira, Associate Senior Lecturer, 1985-, et al.
(författare)
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Non-targeted urine metabolomics and associations with prevalent and incident type 2 diabetes
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Better risk prediction and new molecular targets are key priorities in type 2 diabetes (T2D) research. Little is known about the role of the urine metabolome in predicting the risk of T2D. We aimed to use non-targeted urine metabolomics to discover biomarkers and improve risk prediction for T2D. Urine samples from two community cohorts of 1,424 adults were analyzed by ultra-performance liquid chromatography/mass spectrometry (UPLC-MS). In a discovery/replication design, three out of 62 annotated metabolites were associated with prevalent T2D, notably lower urine levels of 3-hydroxyundecanoyl-carnitine. In participants without diabetes at baseline, LASSO regression in the training set selected six metabolites that improved prediction of T2D beyond established risk factors risk over up to 12 years' follow-up in the test sample, from C-statistic 0.866 to 0.892. Our results in one of the largest non-targeted urinary metabolomics study to date demonstrate the role of the urine metabolome in identifying at-risk persons for T2D and suggest urine 3-hydroxyundecanoyl-carnitine as a biomarker candidate.
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| 752. |
- Salihovic, Samira, et al.
(författare)
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Perfluoroalkyl substances (PFAS) including structural PFOS isomers in plasma from elderly men and women from Sweden : Results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS)
- 2015
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 82, s. 21-27
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Tidskriftsartikel (refereegranskat)abstract
- Per- and polyfluoroalkyl substances (PFASs) are a class of compounds with unique chemical properties that have been shown useful in a wide variety of applications because they provide materials with reduced surface tension and exceptional non-stick properties. PFASs are commonly found in impregnation materials, coatings of papers and textiles, fire-fighting foams, pesticides, and cleaning agents. The potential for human exposure to PFASs is high because of their widespread distribution. The aim of this study was to investigate levels of PFASs in men and women from Sweden and to assess the influence of gender and parity among women. Levels of 13 PFASs were determined in plasma samples collected during 2001-2004 from 1016 (507 women) 70 year-old participants from the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS). The PFASs studied were nine perfluorinated carboxylic acids (PFCAs), four perfluorinated sulfonic acids (PFSAs) and perfluorooctane sulfonamide (PFOSA). In addition, structural isomers of perfluorooctane sulfonic acid (PFOS) were determined in a subset of 398 individuals. The detection rates were high and the majority of the studied compounds were detected in more than 75% of the participants. Levels of the selected analytes were found to be similar to other studies of non-occupationally exposed populations. Gender differences were observed in levels of PFHpA which was higher in men, while PFHxS was higher in women. Parity among women was shown to have a minor effect on PFAS concentrations and we found primi- and multiparous women to have slightly lower levels of PFUnDA when compared to nulliparous women.
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| 753. |
- Salihovic, Samira, Associate Senior Lecturer, 1985-, et al.
(författare)
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Plasma perfluoroalkyls are associated with decreased levels of proteomic inflammatory markers in a cross-sectional study of an elderly population
- 2020
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 145
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl substances (PFAS) have been linked to immunotoxicity in experimental studies. Although PFAS exposure is associated with altered immune response in epidemiological studies of children, it is less known whether this is observed also in elderly adults. Eight PFAS and 86 proteins were measured in plasma from 965 elderly individuals from Sweden (all aged 70, 50% women). PFAS were measured using isotope-dilution ultra-pressure liquid chromatography coupled to tandem mass spectrometry. Proteins were measured using a multiplex proximity extension assay (PEA) and covered among others inflammatory marker proteins such as monocyte chemoattractant proteins, tumor necrosis factors, and interleukins. We examined cross-sectional associations using multivariable linear regression at two levels of adjustment. We observed significant decreases in levels of 24 proteins in relation to a ln-unit increase in PFAS concentrations following adjustment for sex, sample storage time in freezer, and correction for multiple testing. Associations of PFAS and hepatocyte growth factor (HGF) and macrophage colony-stimulating factor 1 (CSF-1) remained significant (p-value < 0.05) following full covariate adjustment for smoking, exercise habits, education, energy, and alcohol intake, body mass index (BMI), glomular filtration rate (GFR) as well as corticoid- and COX-inhibitor treatment. CSF-1 was inversely associated with perfluorohexane sulfonic acid (PFHxS) beta: -0.08: 95% confidence interval (CI); -0.13, -0.02), perfluorooctanoic acid (PFOA) beta: -0.04: 95% CI; -0.07, -0.006, perfluorononanoic acid (PFNA) beta: -0.04: 95% CI; -0.08, -0.003, perfluorodecanoic acid (PFDA) beta: -0.03: 95% CI; -0.06, -0.003, and perfluoroundecanoic acid (PFUnDA) beta: -0.05: 95% CI; -0.08, -0.02. The magnitude and direction of PFAS vs protein relationships were similar also for HGF. Our findings implicate PFAS exposure with decreased levels of proteomic markers of inflammation in elderly humans.
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| 754. |
- Salihovic, Samira, 1985-, et al.
(författare)
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The metabolic fingerprint of p,p'-DDE and HCB exposure in humans
- 2016
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Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 88, s. 60-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) are organochlorine pesticides with well-known endocrine disrupting properties. Exposure to p,p'-DDE and HCB concerns human populations worldwide and has been linked to metabolic disorders such as obesity and type 2 diabetes, but details about these associations in humans from the general population are largely unknown.Objectives: We investigated the associations between p,p'-DDE and HCB exposure and global metabolomic profiles in serum samples from 1016 participants from the Swedish population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.Methods: HCB and p,p'-DDE levels were determined using gas chromatography coupled to high-resolution mass spectrometry (GC-HRMS). Metabolite levels were determined by using a non-targeted metabolomics approach with ultra-performance liquid chromatography coupled to time-of- flight mass spectrometry (UPLC-TOFMS). Association analyses were performed using multivariate linear regression.Results: We found circulating levels of p,p-DDE and HCB to be significantly associated with circulating levels of 16 metabolites following adjustment for age, sex, education level, exercise habits, smoking, energy intake, and alcohol intake. The majority of the 16 metabolites belong to lipid metabolism pathways and include fatty acids, glycerophospholipids, sphingolipids, and glycerolipids. Overall, p,p'-DDE and HCB levels were found to be correlated to different metabolites, which suggests that different metabolic fingerprints may be related to circulating levels of these two pesticides.Conclusions: Our findings establish a link between human exposure to organochlorine pesticides and metabolites of key metabolic processes mainly related to human lipid metabolism.
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| 755. |
- Sandhagen, Bo, et al.
(författare)
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Whole blood viscosity and erythrocyte deformability are related to endothelium-dependent vasodilation and coronary risk in the elderly : The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study
- 2012
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Ingår i: Clinical hemorheology and microcirculation. - 1386-0291 .- 1875-8622. ; 50:4, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- It has previously been shown that a high hemoglobin value, a major determinant of whole blood viscosity (WBV), predicts cardiovascular events. One putative mechanism might be an impaired endothelial function. Erythrocyte deformability is another rheologic feature of the erythrocyte being of importance for the flow properties of the blood, especially in the capillaries. The present study evaluates the relationships between blood viscosity, erythrocyte deformability assessed as erythrocyte fluidity (EF), coronary risk and endothelial vasodilatory function. In the population-based PIVUS study (1016 subjects aged 70); endothelium-dependent vasodilation (EDV) was evaluated by the invasive forearm technique with acetylcholine given in the brachial artery and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD). WBV, plasma viscosity (PV) and EF were measured in a random sample of 573 subjects. WBV and PV were positively and EF negatively related to Framingham risk score. EDV was inversely related to both whole blood and plasma viscosity. FMD was not related to any rheologic variable. In multiple regression analyses WBV and EF were significantly related to EDV independently of gender, hypertension, smoking, hypercholesterolemia, obesity and diabetes. Acetylcholine-induced vasodilation in the forearm, but not FMD, was negatively related to whole blood viscosity and positively related to EF independently of traditional risk factors in elderly subjects, indicating a pathophysiological link between impaired hemorheology and coronary risk.
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| 756. |
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| 757. |
- Sarabi, Mahziar, et al.
(författare)
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An ordinary mixed meal transiently impairs endothelium-dependent vasodilation in healthy subjects
- 2001
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772 .- 1365-201X. ; 172:2, s. 107-113
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Tidskriftsartikel (refereegranskat)abstract
- This study was designed to evaluate the effects of an ordinary mixed meal on endothelium-dependent vasodilation. Ten young healthy volunteers were given a mixed meal (minced meat sauce with rice, 900 kcal, 34% of the energy content was fat). In the fasting state, at 60 and 120 min after the start of the meal, endothelium-dependent vasodilation and endothelium-independent vasodilation were evaluated by local infusion of metacholine (4 microg min (-1)) and sodium nitroprusside (10 microg min (-1)) in the brachial artery. Blood flow in the forearm was measured using venous occlusion plethysmography. Endothelium-dependent vasodilation decreased from 15.4 +/- 3.3 (mean +/- SD) at fasting to 13.7 +/- 3.5 mL min (-1) (100 mL tissue)-1 (P < 0.01) 60 min after feeding, but had returned to the fasting level at 120 min. At 60 min, but not in the fasting state, the serum level of free fatty acids was inversely related to endothelium-dependent vasodilation (r=-0.74, P < 0.05), although no significant net changes in FFA levels were seen. Endothelium-independent vasodilation was not affected by the mixed meal. No similar attenuations in endothelium-dependent vasodilation were seen during control meals. In conclusion, an ordinary mixed meal transiently attenuated endothelium-dependent vasodilation. Free fatty acids may be involved in this effect on endothelial function.
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| 758. |
- Sarabi, Mahziar, et al.
(författare)
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Effects of age, gender and metabolic factors on endothelium-dependent vasodilation : a population-based study
- 1999
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 246:3, s. 265-274
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: A progressive decline in endothelium-dependent vasodilation (EDV) in the human forearm with age has previously been reported. The aim of this study was to evaluate the interplay between age, gender and metabolic factors on EDV in healthy subjects in a population-based study. SETTING: Tertiary university hospital. SUBJECTS AND DESIGN: Thirty-six healthy men and 30 women, aged 20-69 years, underwent measurements of forearm blood flow (FBF) at rest and during local infusions of 2 and 4 microg min-1 of metacholine (evaluating EDV) and 5 and 10 microg min-1 of sodium nitroprusside (evaluating endothelium-independent vasodilation, EIDV) and during reactive hyperaemia by venous occlusion plethysmography. RESULTS: Age was inversely related to EDV (r = - 0.41, P < 0.05 in men; r = - 0.61, P < 0.01 in women) and maximal FBF during reactive hyperaemia in both men and women. EIDV was significantly related to age in an inverse way in women only. EDV was more pronounced in females than in males before menopause (48 +/- 3 SD years, 635 +/- 186 vs. 502 +/- 269% in males, P < 0.05), but similar in women and men thereafter (374 +/- 141 vs. 370 +/- 185% in men). The slope of the regression line for the relationship between age and EDV was flatter in premenopausal than in postmenopausal women (- 2.3 vs. - 6.4), whilst this slope was similar in younger and older men (- 5.5 vs. - 5.3). In multiple regression analysis, fasting blood glucose levels and the waist/hip ratio remained the only significant predictors of EDV in men (P < 0.01 for both), whilst age was the only significant independent predictor of EDV in women (P < 0.01). CONCLUSION: The interplay between age and metabolic factors as determinants of endothelial function is different in healthy men and women.
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| 759. |
- Sarabi, Mahziar, et al.
(författare)
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Endothelin plays an important role in the endothelium-dependent vasodilatation in the human forearm
- 1999
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 59:1, s. 17-22
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Tidskriftsartikel (refereegranskat)abstract
- Endothelium-dependent vasodilatation (EDV) in humans has been evaluated mainly by local infusion of a muscarinic-receptor agonists in the forearm. It has been postulated that the function of the vasodilator nitric oxide (NO) can be evaluated with this technique. However, the role of the vasoconstrictor endothelin in this model has not been investigated. METHODS: Ten male hypertensive and seven male normotensive subjects were subjected to measurements of forearm blood flow (FBF) by venous occlusion plethysmography during local intra-arterial infusion of metacholine (4 microg/min) or nitroprusside (10 microg/min). In parallel, forearm venous plasma endothelin (ir-ET) was determined. RESULTS: Metacholine and nitroprusside increased FBF 2.3 and 2.2 times the baseline level (6.6+/-2.8 SD ml/min/100 ml tissue) in hypertensive subjects and 5.1 times the baseline level (2.7+/-3.0 ml/min/100 ml tissue) for both drugs in the normotensive subjects. None of the drugs induced any significant changes in ir-ET levels in any of the groups (baseline 1.5+/-0.4 pmol/l in hypertensive and 1.1+/-1.2 pmol/l in normotensive subjects). However, in the hypertensive subjects, the individual change in venous ir-ET levels during infusion with metacholine, but not with nitroprusside, was inversely related to the degree of vasodilatation induced by this agent (r = -0.71, p < 0.02). A similar correlation coefficient (r=-0.69) was found in healthy subjects. CONCLUSION: Muscarinic-receptor-agonist-stimulated vasodilatation in the human forearm, thought mainly to reflect NO synthesis, was inversely related to the change in endothelin levels, suggesting an important role for this endothelium-derived vasoconstrictor in this model of EDV.
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| 760. |
- Sarabi, Mahziar, et al.
(författare)
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Endothelium-dependent vasodilation is related to the fatty acid composition of serum lipids in healthy subjects
- 2001
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Ingår i: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 156:2, s. 349-355
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The fatty acid (FA) composition of the serum lipids has been associated with cardiovascular disease (CVD). As an attenuated endothelium-dependent vasodilation (EDV) has been suggested as an early marker of atherosclerosis, we investigated the relationships between the proportion of FA in serum lipids (cholesterol esters and phospholipids) together with the levels of serum LDL- and HDL-cholesterol and triglycerides and EDV, as well as endothelium-independent vasodilation (EIDV). Fifty-six healthy subjects (31 men and 25 women), aged between 20 and 69 years, underwent measurements of forearm blood flow (FBF) at rest and during local infusion of 2 and 4 microg/min of metacholine (Mch, evaluating EDV), 5 and 10 microg/min of sodium nitroprusside (SNP, evaluating endothelium-independent vasodilation, EIDV) using venous occlusion plethysmography. An index of endothelial function was calculated as the ratio between EDV and EIDV. The proportion of palmitic (16:0) and palmitoleic (16:1) acids were inversely related (r=-0.35 and -0.35, P<0.01 for both), while linoleic acid (18:2 n6) and the HDL-cholesterol concentration were positively related (r=0.35 and 0.36, P<0.01 for both) to the endothelial function index. In multiple regression analysis also including age and gender, palmitoleic acid and HDL-cholesterol were significant independent predictors of endothelial function. Alfa-linolenic acid (18:3 n3) was positively correlated to both EDV and EIDV (r=0.40 and 0.43, P<0.01 for both), indicating a protective effect of this essential FA on vasodilation in general. It is concluded that the FA composition of serum lipids, partly reflecting the composition of dietary fat and previously associated with the development of CVD, was associated with endothelial function in apparently healthy subjects.
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