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  • 1. Berthelot, Claire C
    et al.
    Kamita, Shizuo George
    Sacchi, Romina
    Yang, Jun
    Nording, Malin L
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Department of Entomology, University of California Davis, Davis, CA, United States Of America.
    Georgi, Katrin
    Karbowski, Christine Hegedus
    German, J Bruce
    Weiss, Robert H
    Hogg, Ronald J
    Hammock, Bruce D
    Zivkovic, Angela M
    Changes in PTGS1 and ALOX12 Gene Expression in Peripheral Blood Mononuclear Cells Are Associated with Changes in Arachidonic Acid, Oxylipins, and Oxylipin/Fatty Acid Ratios in Response to Omega-3 Fatty Acid Supplementation2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 12, article id e0144996Article in journal (Refereed)
    Abstract [en]

    Introduction: There is a high degree of inter-individual variability among people in response to intervention with omega-3 fatty acids (FA), which may partly explain conflicting results on the effectiveness of omega-3 FA for the treatment and prevention of chronic inflammatory diseases. In this study we sought to evaluate whether part of this inter-individual variability in response is related to the regulation of key oxylipin metabolic genes in circulating peripheral blood mononuclear cells (PBMCs). Methods: Plasma FA and oxylipin profiles from 12 healthy individuals were compared to PBMC gene expression profiles following six weeks of supplementation with fish oil, which delivered 1.9 g/d eicosapentaenoic acid (EPA) and 1.5 g/d docosahexaenoic acid (DHA). Fold changes in gene expression were measured by a quantitative polymerase chain reaction (qPCR). Results: Healthy individuals supplemented with omega-3 FA had differential responses in prostaglandin-endoperoxide synthase 1 (PTGS1), prostaglandin-endoperoxide synthase 2 (PTGS2), arachidonate 12-lipoxygenase (ALOX12), and interleukin 8 (IL-8) gene expression in isolated PBMCs. In those individuals for whom plasma arachidonic acid (ARA) in the phosphatidylethanolamine (PE) lipid class decreased in response to omega-3 intervention, there was a corresponding decrease in gene expression for PTGS1 and ALOX12. Several oxylipin product/FA precursor ratios (e.g. prostaglandin E-2 (PGE(2))/ARA for PTGS1 and 12-hydroxyeicosatetraenoic acid (12-HETE)/ARA for ALOX12) were also associated with fold change in gene expression, suggesting an association between enzyme activity and gene expression. The fold-change in PTGS1 gene expression was highly positively correlated with ALOX12 gene expression but not with PTGS2, whereas IL-8 and PTGS2 were positively correlated. Conclusions: The regulation of important oxylipin metabolic genes in PBMCs varied with the extent of change in ARA concentrations in the case of PTGS1 and ALOX12 regulation. PBMC gene expression changes in response to omega-3 supplementation varied among healthy individuals, and were associated with changes in plasma FA and oxylipin composition to different degrees in different individuals.

  • 2. Bever, Candace S.
    et al.
    Rand, Amy A.
    Nording, Malin L.
    Department of Entomology and Nematology, and UCD Comprehensive Cancer Center, University of California Davis, Davis, CA, USA.
    Taft, Diana
    Kalanetra, Karen M.
    Mills, David A.
    Breck, Melissa A.
    Smilowitz, Jennifer T.
    German, J. Bruce
    Hammock, Bruce D.
    Effects of triclosan in breast milk on the infant fecal microbiome2018In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 203, p. 467-473Article in journal (Refereed)
    Abstract [en]

    Triclosan is frequently used for its antimicrobial properties and has been detected in human serum, urine, and breast milk. Animal and molecular studies have shown that triclosan exerts a wide range of adverse health effects at both high (ppm) and low (ppb) concentrations. Since triclosan is of growing concern to human and environmental health, there is a need to improve extraction procedures and to study additional effects from triclosan exposure. In this study, we have improved triclosan extraction from breast milk by using salt (MgSO4) to reduce emulsion formation and increase water polarity and water (similar to 80%) to enhance the overall extraction efficiency (similar to 3.5 fold). This extraction method was applied to breast milk samples collected from donors who i) recorded their use of triclosan-containing personal care products and ii) provided matching infant stool samples. Of the participants who had detectable amounts of triclosan in their breast milk, nine (75%) of them reported daily use of triclosan-containing personal care products. Levels of triclosan in breast milk were compared to the donor's infant's fecal microbiome. We found that the bacterial diversity in the fecal microbiome of the infants exposed to breast milk with detectable triclosan levels differed compared to their peers exposed to milk containing non-detectable amounts. This finding implies that exogenous chemicals are impacting microbiome diversity.

  • 3.
    Cipriano, Mariateresa
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Gouveia-Figueira, Sandra
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Persson, Emma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fowler, Christopher
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    The influence of monoacylglycerol lipase inhibition upon the expression of epidermal growth factor receptor in human PC-3 prostate cancer cells.2014In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 7, p. 441-447Article in journal (Refereed)
    Abstract [en]

    Background: It has been reported that direct activation of the cannabinoid CB1 receptor in epidermal growth factor (EGR)-stimulated PC-3 prostate cancer cells results in an anti-proliferative effect accompanied by a down-regulation of EGF receptors (EGFR). In the present study, we investigated whether similar effects are seen following inhibition of the endocannabinoid hydrolytic enzyme monoacylglycerol lipase (MGL).

    Results: CB1 receptor expression levels were found to differ greatly between two experimental series conducted using PC-3 cells. The monoacylglycerol lipase inhibitor JZL184 increased levels of 2-arachidonoylglycerol in the PC-3 cells without producing changes in the levels of anandamide and related N-acylethanolamines. In the first series of experiments, JZL184 produced a small mitogenic effect for cells that had not been treated with EGF, whereas an anti-proliferative effect was seen for EGF-treated cells. An anti-proliferative effect for the EGF-treated cells was also seen with the CB receptor agonist CP55,940. In the second batch of cells, there was an interaction between JZL184 and CB1 receptor expression densities in linear regression analyses with EGFR expression as the dependent variable.

    Conclusions: Inhibition of MGL by JZL184 can affect EGFR expression. However, the use in our hands of PC-3 cells as a model to investigate the therapeutic potential of MGL inhibitors and related compounds is compromised by their variability of CB1 receptor expression.

  • 4.
    Claeson, Anna-Sara
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Gouveia-Figueira, Sandra
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Perceived stress, sensory irritation and levels of prostaglandin F2 alpha in plasma after acrolein exposure: a pilot study2017In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 42, no 2, p. E28-E28Article in journal (Refereed)
  • 5.
    Claeson, Anna-Sara
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Gouveia-Figueira, Sandra
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Häggström, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Levels of oxylipins, endocannabinoids and related lipids in plasma before and after low-level exposure to acrolein in healthy individuals and individuals with chemical intolerance2017In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 121, p. 60-67Article in journal (Refereed)
    Abstract [en]

    Oxylipins and endocannabinoids play important biological roles, including effects upon inflammation. It is not known whether the circulating levels of these lipids are affected by inhalation of the environmental pollutant acrolein. In the present study, we have investigated the consequences of low-level exposure to acrolein on oxylipin, endocannabinoid and related lipid levels in the plasma of healthy individuals and individuals with chemical intolerance (CI), an affliction with a suggested inflammatory origin. Participants were exposed twice (60 min) to heptane and a mixture of heptane and acrolein. Blood samples were collected before exposure, after and 24 h post-exposure. There were no overt effects of acrolein exposure on the oxylipin lipidome or endocannibinoids detectable in the bloodstream at the time points investigated. No relationship between basal levels or levels after exposure to acrolein and CI could be identified. This implicates a minor role of inflammatory mediators on the systemic level in CI.

  • 6.
    Figueira, João
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Gouveia-Figueira, Sandra
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Öhman, Carina
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nording, Malin L
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Öhman, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Metabolite quantification by NMR and LC-MS/MS reveals differences between unstimulated, stimulated, and pure parotid saliva2017In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 140, p. 295-300, article id S0731-7085(16)31308-5Article in journal (Refereed)
    Abstract [en]

    Saliva is a readily available biofluid that is sensitive to metabolic changes and can be collected through rapid and non-invasive collection procedures, and it shows great promise for clinical metabolomic studies. This work studied the metabolite composition of, and the differences between, saliva samples collected by unstimulated spitting/drooling, paraffin chewing-stimulated spitting, and parotid gland suction using targeted nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for metabolite quantification. As applied here, these two analytical techniques provide complementary metabolite information and together extend the metabolome coverage with robust NMR quantification of soluble metabolites and sensitive targeted LC-MS/MS analysis of bioactive lipids in specific metabolic pathways. The NMR analysis was performed on ultrafiltrated (3kDa cutoff) saliva samples and resulted in a total of 45 quantified metabolites. The LC-MS/MS analysis was performed on both filtered and unfiltered samples and resulted in the quantification of two endocannabinoids (AEA and PEA) and 22 oxylipins, which at present is the most comprehensive targeted analysis of bioactive lipids in human saliva. Important differences in the metabolite composition were observed between the three saliva sample collection methods, which should be taken into consideration when designing metabolomic studies of saliva. Furthermore, the combined use of the two metabolomics platforms (NMR and LC-MS/MS) proved to be viable for research and clinical studies of the salivary metabolome.

  • 7.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fowler, Christopher
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Relative and absolute reliability of measures of linoleic acid-derived oxylipins in human plasma2015In: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 121, no Part B, p. 227-233Article in journal (Refereed)
    Abstract [en]

    Modern analytical techniques allow for the measurement of oxylipins derived from linoleic acid in biological samples. Most validatory work has concerned extraction techniques, repeated analysis of aliquots from the same biological sample, and the influence of external factors such as diet and heparin treatment upon their levels, whereas less is known about the relative and absolute reliability of measurements undertaken on different days. A cohort of nineteen healthy males were used, where samples were taken at the same time of day on two occasions, at least 7 days apart. Relative reliability was assessed using Lin's concordance correlation coefficients (CCC) and intraclass correlation coefficients (ICC). Absolute reliability was assessed by Bland-Altman analyses. Nine linoleic acid oxylipins were investigated. ICC and CCC values ranged from acceptable (0.56 [13-HODE]) to poor (near zero [9(10)- and 12(13)-EpOME]). Bland-Altman limits of agreement were in general quite wide, ranging from ±0.5 (12,13-DiHOME) to ±2 (9(10)-EpOME; log10 scale). It is concluded that relative reliability of linoleic acid-derived oxylipins varies between lipids with compounds such as the HODEs showing better relative reliability than compounds such as the EpOMEs. These differences should be kept in mind when designing and interpreting experiments correlating plasma levels of these lipids with factors such as age, body mass index, rating scales etc.

  • 8.
    Gouveia-Figueira, Sandra C.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Karimpour, Masoumeh
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sehlstedt, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust2018In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 1018, p. 62-69Article in journal (Refereed)
    Abstract [en]

    Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF(2 alpha), 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p < 0.003). Hence, the majority of the responsive lipid metabolites were monohydroxy fatty acids. We conclude that it is possible to detect alterations in circulating bioactive lipid metabolites in response to biodiesel exhaust exposure using LC-MS/MS, with emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes.

  • 9.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Goldin, Kristina
    Hashemian, Sanaz A.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Lindberg, Agneta
    Persson, Monica
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Neurology, Östersund Hospital, SE-83183 Östersund, Sweden.
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Plasma levels of the endocannabinoid anandamide, related N-acylethanolamines and linoleic acid-derived oxylipins in patients with migraine2017In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 120, p. 15-24Article in journal (Refereed)
    Abstract [en]

    There is evidence that patients with migraine have deficient levels of the endogenous cannabinoid receptor ligand anandamide (AEA). It is not known, however, if this is a localised or generalised phenomenon. In the present study, levels of AEA, related N-acylethanolamines (NAEs) and linoleic acid-derived oxylipins have been measured in the blood of 26 healthy women and 38 women with migraine (26 with aura, 12 without aura) who were matched for age and body-mass index. Blood samples were taken on two occasions: the first sample near the start of the menstrual cycle (when present) and the second approximately fourteen days later. For a subset of migraine patients, two additional blood samples were taken, one during a migraine attack and one approximately 1 month later (to be at the same stage in the menstrual cycle, when present). NAEs and oxylipins were measured by liquid chromatography coupled to mass spectrometry. Twenty-nine lipids were quantified, of which 16 were found to have a high reproducibility of measurement. There were no significant differences in the levels of AEA, the related NAEs stearoylethanolamide and oleoylethanolamide or any of the nine linoleic acid derived oxylipins measured either between migraine patients with vs. without aura, or between controls and migraine patients (after stratification to take into account whether or not the individuals had regular menstruation cycles) in either of the first two samples. Levels of linoleoylethanolamide were lower in the patients with vs. without aura on the second sample but not in the first sample, but the biological importance of this fording is unclear. Due to time-dependent increases in their concentrations ex vivo prior to centrifugation, AEA and oleoylethanolamide levels in the samples collected during migraine attacks were not analysed, but for the other fourteen lipids, there were no significant differences in plasma concentrations during migraine vs. one month later. It is concluded that migraine is not associated with a generalised (as opposed to localised) deficiency in these lipids.

  • 10.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Centro de Química da Madeira, CCCEE, Universidade da Madeira, Campus Universitário da Penteada, piso 0, Funchal 9000-390, Portugal.
    Gouveia, Carla A.
    Carvalho, Maria J.
    Rodrigues, Ana I.
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Castilho, Paula C.
    Antioxidant Capacity, Cytotoxicity and Antimycobacterial Activity of Madeira Archipelago Endemic Helichrysum Dietary and Medicinal Plants2014In: Antioxidants, ISSN 2076-3921, Vol. 3, no 4, p. 713-729Article in journal (Refereed)
    Abstract [en]

    The potential bioactivity of dietary and medicinal endemic Helichrysum plants from Madeira Archipelago was explored, for the first time, in order to supply new information for the general consumer. In vitro antioxidant properties were investigated using DPPH, ABTS(+), FRAP and beta-Carotene assays, and the total phenolic content (TPC) and total flavonoid content (TFC) were also determined. Although the results generally showed a large variation among the three analyzed plants, the methanolic extracts showed the highest antioxidant capacity. Exception is made for H. devium n-hexane extract that showed good radical scavenger capacity associated to compounds with good reducing properties. In the Artemia salina toxicity assay and antimycobaterial activity, H. devium was the most potent plant with the lowest LD50 at 216.7 ± 10.4 and MIC ≤ 50mug·mL(-1). Chemometric evaluation (Principal Component Analysis-PCA) showed close interdependence between the ABTS, TPC and TFC methods and allowed to group H. devium samples.

  • 11.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Karimpour, Masoumeh
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure2017In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 409, no 11, p. 2967-2980Article in journal (Refereed)
    Abstract [en]

    The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 mu g/m(3)) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design. Bronchoscopy was performed 6 h post exposure and lung lavage fluids, i.e., bronchial wash (BW) and bronchoalveolar lavage (BAL), were sequentially collected. Mass spectrometry methods were used to detect a wide array of oxylipins (including eicosanoids), endocannabinoids, Nacylethanolamines, and related lipid metabolites in the collected BWand BAL samples. Six lipids in the human lung lavage samples were altered following biodiesel exhaust exposure, three from BAL samples and three from BW samples. Of these, elevated levels of PGE2, 12,13-DiHOME, and 13-HODE, all of which were found in BAL samples, reached Bonferroni-corrected significance. This is the first study in humans reporting responses of bioactive lipids following biodiesel exhaust exposure and the most pronounced responses were seen in the more peripheral and alveolar lung compartments, reflected by BAL collection. Since the responsiveness and diagnostic value of a subset of the studied lipid metabolites were established in lavage fluids, we conclude that our mass spectrometry profiling method is useful to assess effects of human exposure to vehicle exhaust.

  • 12.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Karimpour, Masoumeh
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bosson, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mass spectrometry profiling of oxylipins, endocannabinoids and N-acylethanolamines in human lung lavage fluids reveal responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposureManuscript (preprint) (Other academic)
  • 13.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Karimpour, Masoumeh
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bosson, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Effect of controlled exposure to biodiesel exhaust on human plasma bioactive lipid profilesManuscript (preprint) (Other academic)
  • 14.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Development and Validation of a Sensitive UPLC-ESI-MS/MS Method for the Simultaneous Quantification of 15 Endocannabinoids and Related Compounds in Milk and Other Biofluids2014In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 86, no 2, p. 1186-1195Article in journal (Refereed)
    Abstract [en]

    The endocannabinoid (eCB) system has gained an increasing interest over the past decades since the discovery of anandamide and 2-arachidonoyl glycerol (2-AG). These, and structurally related compounds, are associated with a wide variety of physiological processes. For instance, eCB levels in milk have been associated with infants' feeding and sleeping behavior. A method based on ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) was developed and validated for the simultaneous quantification of 15 eCBs and related compounds, including both fatty acid amides and glycerols. Linearity (0.9845 < R-2 < 1), limit of detection and quantification (0.52-293 pg on column), inter- and intraday accuracy (>70%) and precision (CV < 15%), stability, and recovery (in milk and plasma) were established in accordance to the U.S. Food and Drug Administration guidelines. The method was successfully applied to bovine and elk milk revealing species-specific eCB profiles, with significant different levels of 2-AG, 2-linoleoyl glycerol, docosahexaenoyl ethanolamide, palmitoyl ethanolamide, and oleoyl ethanolamide. Furthermore, stearoyl ethanolamide and docosatetraenoyl ethanolamide were only detected in elk milk. In summary, our UPLC-ESI-MS/MS method may be used for quantification of eCBs and related compounds in different biofluids and applied to investigations of the role of these emerging compounds in various physiological processes.

  • 15.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Validation of a tandem mass spectrometry method using combined extraction of 37 oxylipins and 14 endocannabinoid-related compounds including prostamides from biological matrices2015In: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 121, no Part A, p. 110-121Article in journal (Refereed)
    Abstract [en]

    There is a clinical need for more relevant coverage of bioactive lipids using smaller sample volumes. Therefore, we have validated a tandem mass spectrometry method for combined solid phase extraction of 37 compounds in the oxylipin (OxL) and 14 in the endocannabinoid (eCB) metabolome, as well as prostamides. The limits of quantification (LOQ) for compounds in the eCB metabolome were in the range 0.5-1000fg on column, intraday accuracy and precision ranges (%) were 83-125 and 0.3-17, respectively, and interday accuracy and precision ranges (%) were 80-119 and 1.2-20, respectively, dependent upon the compound and the concentration studied. Corresponding values for OxL were 0.5fg-4.2pg on column (LOQ), 85-115% (inter- and intraday accuracy) and <5% (precision). The combined extraction method was successfully applied to tissues, cell extracts, human plasma and milk samples. A deeper study of levels in elk, pig and cow brain, as well as cow heart and liver revealed tissue and species-specific elevation of eicosanoids: arachidonate diols, 20-HETE and 12(S)-HEPE (cow liver), LTB4 (cow brain), and monohydroxy metabolites (HETEs), epoxides and 5-oxo-ETE in elk brain, which might be caused by factors of stress and/or post-mortem reactions in the tissues.

  • 16.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology. Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gaida, Jamie E.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Alfredson, Hakan
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Serum Levels of Oxylipins in Achilles Tendinopathy: An Exploratory Study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0123114Article in journal (Refereed)
    Abstract [en]

    Background: Linoleic acid-derived oxidation products are found in experimental pain models. However, little is known about the levels of such oxylipins in human pain. In consequence, in the present study, we have undertaken a lipidomic profiling of oxylipins in blood serum from patients with Achilles tendinopathy and controls.

    Methodology/Principal findings: A total of 34 oxylipins were analysed in the serum samples. At a significance level of P<0.00147 (<0.05/34), two linoleic acid-derived oxylipins, 13-hydroxy-10E,12Z-octadecadienoic (13-HODE) and 12(13)-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME) were present at significantly higher levels in the Achilles tendinopathy samples. This difference remained significant when the dataset was controlled for age, gender and body-mass index. In contrast, 0/21 of the arachidonic acid- and 0/4 of the dihomo-γ-linolenic acid, eicosapentaenoic acid or docosahenaenoic acid-derived oxylipins were higher in the patient samples at this level of significance. The area under the Receiver-Operator Characteristic (ROC) curve for 12,13-DiHOME was 0.91 (P<0.0001). Levels of four N-acylethanolamines were also analysed and found not to be significantly different between the controls and the patients at the level of P<0.0125 (<0.05/4).

    Conclusions/Significance: It is concluded from this exploratory study that abnormal levels of linoleic acid-derived oxylipins are seen in blood serum from patients with Achilles tendinopathy. Given the ability of two of these, 9- and 13-HODE to activate transient receptor potential vanilloid 1, it is possible that these changes may contribute to the symptoms seen in Achilles tendinopathy.

  • 17.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Späth, Jana
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Zivkovic, Angela M.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Profiling the Oxylipin and Endocannabinoid Metabolome by UPLC-ESI-MS/MS in Human Plasma to Monitor Postprandial Inflammation2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 7, article id e0132042Article in journal (Refereed)
    Abstract [en]

    Bioactive lipids, including oxylipins, endocannabinoids, and related compounds may function as specific biochemical markers of certain aspects of inflammation. However, the postprandial responsiveness of these compounds is largely unknown; therefore, changes in the circulating oxylipin and endocannabinoid metabolome in response to a challenge meal were investigated at six occasions in a subject who freely modified her usual diet. The dietary change, and especially the challenge meal itself, represented a modification of precursor fatty acid status, with expectedly subtle effects on bioactive lipid levels. To detect even the slightest alteration, highly sensitive ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization (ESI) tandem mass spectrometry (MS/MS) methods for bioactive lipid profiling was employed. A previously validated UPLC-ESI-MS/MS method for profiling the endocannabinoid metabolome was used, while validation of an UPLC-ESI-MS/MS method for oxylipin analysis was performed with acceptable outcomes for a majority of the parameters according to the US Food and Drug Administration guidelines for linearity (0.9938 < R-2 < 0.9996), limit of detection (0.0005-2.1 pg on column), limit of quantification (0.0005-4.2 pg on column), inter-and intraday accuracy (85-115%) and precision (<5%), recovery (40-109%) and stability (40-105%). Forty-seven of fifty-two bioactive lipids were detected in plasma samples at fasting and in the postprandial state (0.5, 1, and 3 hours after the meal). Multivariate analysis showed a significant shift of bioactive lipid profiles in the postprandial state due to inclusion of dairy products in the diet, which was in line with univariate analysis revealing seven compounds (NAGly, 9-HODE, 13-oxo-ODE, 9(10)-EpOME, 12(13)-EpOME, 20-HETE, and 11,12-DHET) that were significantly different between background diets in the postprandial state (but not at fasting). The only change in baseline levels at fasting was displayed by TXB2. Furthermore, postprandial responsiveness was detected for seven compounds (POEA, SEA, 9(10)-DiHOME, 12(13)-DiHOME, 13-oxo-ODE, 9-HODE, and 13-HODE). Hence, the data confirm that the UPLC-ESI-MS/MS method performance was sufficient to detect i) a shift, in the current case most notably in the postprandial bioactive lipid metabolome, caused by changes in diet and ii) responsiveness to a challenge meal for a subset of the oxylipin and endocannabinoid metabolome. To summarize, we have shown proof-of-concept of our UPLC-ESI-MS/MS bioactive lipid protocols for the purpose of monitoring subtle shifts, and thereby useful to address lipid-mediated postprandial inflammation.

  • 18.
    Haglund, Peter
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wiberg, Karin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Danielsson, Conny
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Björklund, Erland
    Lunds universitet.
    Sporring, Sune
    Lunds universitet.
    Hyphenated techniques for dioxin analysis: LC-LC-GC-ECD, GCxGC-ECD, and selective PLE with GC-HRMS or bioanalytical detection2004In: Organohalogen Compounds, Vol. 66, p. 376-382Article in journal (Refereed)
  • 19. Hellström, Fredrik
    et al.
    Gouveia-Figueira, Sandra
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Nording, Malin L.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Björklund, Martin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation. Department of Occupational and Public Health Sciences, Centre for Musculoskeletal Research, University of Gävle, Sweden.
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Association between plasma concentrations of linoleic acid-derived oxylipins and the perceived pain scores in an exploratory study in women with chronic neck pain2016In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, article id 103Article in journal (Refereed)
    Abstract [en]

    Background: Chronic musculoskeletal pain may be associated with changes in the balance of algogenic and anti-nociceptive compounds, and such changes may be visible in plasma samples. We have undertaken an exploratory study to measure the levels of endocannabinoids, related N-acylethanolamines and oxylipins (primarily those derived from linoleic acid) in plasma samples from women with chronic neck pain (NP) and chronic widespread pain (CWP), and to investigate whether the observed levels are associated with the pain experienced by these women.

    Methods: Blood samples from 35 women with NP, 15 with CWP and 27 age-matched controls were analysed for the lipids using ultra performance liquid chromatography coupled to tandem mass spectrometry. Current pain (“NRSday”) and the average pain during the last week (“NRSweek”) were rated by the participants using a numerical rating scale.

    Results: There were no significant differences in the plasma concentrations of the fifteen lipids investigated between the women with pain and the controls. However, significant correlations were seen for the NP group between the NRSday scores and the plasma concentrations of the linoleic acid derivatives 9- and 13-hydroxy-octadecadienoic acid (Spearman’s rho values 0.51 [P = 0.0016]) and 0.53 [P = 0.0011], respectively).

    Conclusions: The data obtained in this exploratory study indicate that although no group differences are seen in plasma lipid concentrations, there is an association between the NRSday scores and the 9- and 13-hydroxy-octadecadienoic acid levels. Whether or not the association reflects a causality (i.e. that the circulating lipids contribute to the perceived pain of the pain participants), requires further investigation.

  • 20. Håkansson, Irene
    et al.
    Gouveia-Figueira, Sandra C.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ernerudh, Jan
    Vrethem, Magnus
    Ghafouri, Nazdar
    Ghafouri, Bijar
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Department of Entomology and Nematology, University of California, Davis, USA.
    Oxylipins in cerebrospinal fluid in clinically isolated syndrome and relapsing remitting multiple sclerosis2018In: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 138, p. 41-47Article in journal (Refereed)
    Abstract [en]

    Although oxylipins are involved in inflammation, data on these lipid mediators in multiple sclerosis are sparse. In this study, a panel of oxylipins were analysed swith liquid chromatography tandem mass spectrometry in cerebrospinal fluid (CSF) from 41 treatment naive patients with clinically isolated syndrome (CIS) or relapsing remitting MS (RRMS) and 22 healthy controls. CSF levels of 9-hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE) were significantly higher in patients than in healthy controls (9-HODE median 380 nM (interquartile range 330-450 nM) in patients and 290 nM (interquartile range 250-340 nM) in controls, 13-HODE median 930 nM (interquartile range 810-1080 nM) in patients and 690 nM (interquartile range 570-760 nM) in controls, p < 0.001 in Mann-Whitney U tests). 9-HODE and 13-HODE performed well for separation of patients and healthy controls (AUC 0.85 and 0.88, respectively, in ROC curve analysis). However, baseline CSF levels of the oxylipins did not differ between patients with signs of disease activity during one, two and four years of follow-up and patients without. In conclusion, this study indicates that 9-HODE and 13-HODE levels are increased in CSF from CIS and RRMS patients compared with healthy controls, but does not support 9-HODE or 13-HODE as prognostic biomarkers of disease activity in patients during follow-up.

  • 21.
    Jansson, Stina
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Söderström, Hanna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Implementation of Problem-Based Learning in Environmental Chemistry2015In: Journal of Chemical Education, ISSN 0021-9584, E-ISSN 1938-1328, Vol. 92, no 12, p. 2080-2086Article in journal (Refereed)
    Abstract [en]

    Environmental Chemistry covers a range of topics within the discipline of chemistry, from toxicology to legislation, which warrants interdisciplinary study. Consequently, problem-based learning (PBL), a style of student-centered learning which facilitates the integration of multiple subjects, was investigated to determine if it would be a more appropriate instructional method for teaching Environmental Chemistry than the traditional teacher-centered education model. This article describes the practical aspects of course development and implementation of PBL in a master’s level course in Environmental Chemistry. Overall, the results, which were collected from the initial two years of the course, indicated that the students were pleased and found PBL to be an efficient methodology for not only learning, but also acquiring an in-depth understanding of Environmental Chemistry. This is intended as a case-study with the target audience consisting primarily of high school and undergraduate chemistry teachers, but may also be useful for teachers in other subject areas with an interest in student-centered education.

  • 22.
    Karimpour, Masoumeh
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Surowiec, Izabella
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wu, Junfang
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gouveia-Figueira, Sandra
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Pinto, Rui
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Bioinformatics Infrastructure for Life Sciences, Sweden.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Zivkovic, Angela M.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Postprandial metabolomics: A pilot mass spectrometry and NMR study of the human plasma metabolome in response to a challenge meal2016In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 908, p. 121-131Article in journal (Refereed)
    Abstract [en]

    The study of postprandial metabolism is relevant for understanding metabolic diseases and characterizing personal responses to diet. We combined three analytical platforms – gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) – to validate a multi-platform approach for characterizing individual variation in the postprandial state. We analyzed the postprandial plasma metabolome by introducing, at three occasions, meal challenges on a usual diet, and 1.5 years later, on a modified background diet. The postprandial response was stable over time and largely independent of the background diet as revealed by all three analytical platforms. Coverage of the metabolome between NMR and GC-MS included more polar metabolites detectable only by NMR and more hydrophobic compounds detected by GC-MS. The variability across three separate testing occasions among the identified metabolites was in the range of 1.1–86% for GC-MS and 0.9–42% for NMR in the fasting state at baseline. For the LC-MS analysis, the coefficients of variation of the detected compounds in the fasting state at baseline were in the range of 2–97% for the positive and 4–69% for the negative mode. Multivariate analysis (MVA) of metabolites detected with GC-MS revealed that for both background diets, levels of postprandial amino acids and sugars increased whereas those of fatty acids decreased at 0.5 h after the meal was consumed, reflecting the expected response to the challenge meal. MVA of NMR data revealed increasing postprandial levels of amino acids and other organic acids together with decreasing levels of acetoacetate and 3-hydroxybutanoic acid, also independent of the background diet. Together these data show that the postprandial response to the same challenge meal was stable even though it was tested 1.5 years apart, and that it was largely independent of background diet. This work demonstrates the efficacy of a multi-platform metabolomics approach followed by multivariate and univariate data analysis for a broad-scale screen of the individual metabolome, particularly for studies using repeated measures to determine dietary response phenotype.

  • 23.
    Larsson, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Gouveia-Figueira, Sandra
    Umeå University.
    Claesson, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lehtipalo, Stefan
    Umeå University.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tyden, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Pinto, Rui
    Umeå University.
    Nording, M. L.
    Umeå University.
    Oxylipin Profiling In The Acute Respiratory Distress Syndrome2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 193, article id A4419Article in journal (Refereed)
  • 24.
    Larsson, Nirina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lundström, Susanna
    Pinto, Rui
    Rankin, Greg
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Karimpour, Masoumeh
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Behndig, Annelie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wheelock, Craig
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lipid mediator profiles differ between lung compartments in asthmatic and healthy humans2014In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 43, no 2, p. 453-463Article in journal (Refereed)
    Abstract [en]

    Oxylipins are oxidised fatty acids that can exert lipid mediator functions in inflammation, and several oxylipins derived from arachidonic acid are linked to asthma. This study quantified oxylipin profiles in different regions of the lung to obtain a broad-scale characterisation of the allergic asthmatic inflammation in relation to healthy individuals. Bronchoalveolar lavage fluid (BALF), bronchial wash fluid and endobronchial mucosal biopsies were collected from 16 healthy and 16 mildly allergic asthmatic individuals. Inflammatory cell counts, immunohistochemical staining and oxylipin profiling were performed. Univariate and multivariate statistics were employed to evaluate compartment-dependent and diagnosis-dependent oxylipin profiles in relation to other measured parameters. Multivariate modelling showed significantly different bronchial wash fluid and BALF oxylipin profiles in both groups ((RY)-Y-2[cum]=0.822 and Q(2)[cum]=0.759). Total oxylipin concentrations and five individual oxylipins, primarily from the lipoxygenase (LOX) pathway of arachidonic and linoleic acid, were elevated in bronchial wash fluid from asthmatics compared to that from healthy controls, supported by immunohistochemical staining of 15-LOX-1 in the bronchial epithelium. No difference between the groups was found among BALF oxylipins. In conclusion, bronchial wash fluid and BALF contain distinct oxylipin profiles, which may have ramifications for the study of respiratory diseases. Specific protocols for sampling proximal and distal airways separately should be employed for lipid mediator studies.

  • 25.
    Lindgren, Lenita
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Gouveia-Figueira, Sandra
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fowler, Christopher
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Endocannabinoids and related lipids in blood plasma following touch massage: a randomised, crossover study2015In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 8, article id 504Article in journal (Refereed)
    Abstract [en]

    Background: The endocannabinoid system is involved in the regulation of stress and anxiety. In a recent study, it was reported that short-term changes in mood produced by a pleasant ambience were correlated with changes in the levels of plasma endocannabinoids and related N-acylethanolamines (Schrieks et al. PLoS One 10: e0126421, 2015). In the present study, we investigated whether stress reduction by touch massage (TM) affects blood plasma levels of endocannabinoids and relatedN-acylethanolamines.

    Results: A randomized two-session crossover design for 20 healthy participants was utilised, with one condition that consisted of TM and a rest condition as control. TM increased the perceived pleasantness rating of the participants, and both TM and rest reduced the basal anxiety level as assessed by the State scale of the STAI-Y inventory. However, there were no significant effects of either time (pre- vs. post-treatment measures) as main effect or the interaction time x treatment for the plasma levels of the endocannabinoids anandamide and 2-arachidonoylglycerol or for eight other related lipids. Four lipids showed acceptable relative reliabilities, and for two of these (linoleoyl ethanolamide and palmitoleoyl ethanolamide) a significant correlation was seen between the TM-related change in levels, calculated as (post-TM value minus pre-TM value) − (post-rest value minus pre-rest value), and the corresponding TM-related change in perceived pleasantness.

    Conclusions: It is concluded that in the participants studied here, there are no overt effects of TM upon plasma endocannabinoid levels. Possible associations of related N-acylethanolamines with the perceived pleasantness should be investigated further.

  • 26.
    Lundström, Susanna L.
    et al.
    Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
    Levanen, Bettina
    Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Nording, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Klepczynska-Nystrom, Anna
    Division of Occupational and Environmental Medicine, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Sköld, Magnus
    Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Haeggström, Jesper Z.
    Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
    Grunewald, Johan
    Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Svartengren, Magnus
    Division of Occupational and Environmental Medicine, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Hammock, Bruce D.
    Department of Entomology and Cancer Research Center, University of California Davis, Davis, California, United States of America.
    Larsson, Britt-Marie
    Division of Occupational and Environmental Medicine, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Eklund, Anders
    Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wheelock, Åsa M.
    Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wheelock, Craig E.
    Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
    Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 8, p. e23864-Article in journal (Refereed)
    Abstract [en]

    Background: Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM) and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications.

    Objectives: This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air.

    Methods: Sixty-four oxylipins representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPAR gamma). Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information.

    Results: Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and alpha-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E(2) (PGE(2)). Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change.

    Conclusions: Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas.

  • 27.
    Nording, Malin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Denison, Michael S
    Baston, David
    Persson, Ylva
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Spinnel, Erik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Analysis of dioxins in contaminated soils with the calux and caflux bioassays, an immunoassay, and gas chromatography/high-resolution mass spectrometry2007In: Environmental Toxicology & Chemistry, Vol. 26, no 6, p. 1122-9Article in journal (Refereed)
    Abstract [en]

    The chemically activated luciferase expression assay, the chemically activated fluorescence expression assay, and the enzyme-linked immunosorbent assay (ELISA) are all bioanalytical methods that have been used for the detection and quantification of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs). However, no comparisons of the results obtained by these three methods have been published analyzing identical replicates of purified sample extracts. Therefore, we have evaluated the performance of each of these methods for analyzing PCDD/Fs in aliquots of extracts from aged-contaminated soil samples and compared the results with those obtained by gas chromatography/high-resolution mass spectrometry (GC/HRMS). The quantitative performance was assessed and the effects of sample purification and data interpretation on the quality of the bioassay results were investigated. Results from the bioanalytical techniques were, in principle, not significantly different from each other or from the GC/HRMS data (p = 0.05). Furthermore, properly used, all of the bioanalytical techniques examined were found to be sufficiently sensitive, selective, and accurate to be used in connection with soil remediation activities when aiming at the remediation goal recommended by the U.S. Environmental Protection Agency (i.e., <1000 pg toxic equivalency/g). However, a site-specific correction factor should be applied with the use of the ELISA to account for differences between the toxic equivalency factors and the ELISA cross-reactivities of the various PCDD/F congeners, which otherwise might significantly underestimate the PCDD/F content.

  • 28.
    Nording, Malin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Frech, Kristina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Analysis of Polycyclic Aromatic Hydrocarbons in Soil with an Enzyme-Linked Immunosorbent Assay Kit and with Gas Chromatography Coupled to Mass Spectroscopy2003In: Organohalogen Compounds, Vol. 60, p. 327-330Article in journal (Refereed)
  • 29.
    Nording, Malin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Frech, Kristina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Persson, Ylva
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Forsman, Mats
    Swedish Defence Research Agency, Umeå, Sweden.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    On the semi-quantification of polycyclic aromatic hydrocarbons in contaminated soil by an enzyme-linked immunosorbent assay kit2006In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 555, no 1, p. 107-113Article in journal (Refereed)
    Abstract [en]

    Polycyclic aromatic hydrocarbons (PAHs) are of environmental concern, for instance when found in contaminated soils at sites where industrial activities have occurred. For efficient screening of such soils, the commercially available enzyme-linked immunosorbent assay (ELISA) kit, the PAH RISc® soil test, can be used. However, the site-specific performance may vary due to differences in soil properties and contamination profiles. Hence, in this study we have examined various contributing factors to the total ELISA measurements uncertainties. These factors include contributions from co-extracted (non-target) compounds, the extraction efficiency and differences in cross-reactivity among the target analytes. Reference values were obtained through pressurized liquid extraction (PLE) and gas chromatography coupled to mass spectrometry (GC–MS) analysis. The results showed that the ELISA does not seem to respond to non-target compounds in the soil extracts to any large extent. Furthermore, high molecular weight PAHs were found to be more efficiently extracted with PLE than with methanol agitation, which is used for ELISA. If this, and the cross-reactivity of the individual PAHs, were taken into consideration, the ELISA and GC–MS results were in good agreement.

  • 30.
    Nording, Malin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Swedish Defence Research Agency, Umeå, Sweden.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Evaluation of the structure/cross-reactivity relationship of polycyclic aromatic compounds using an enzyme-linked immunosorbent assay kit2003In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 487, no 1, p. 43-50Article in journal (Refereed)
    Abstract [en]

    A commercially available enzyme-linked immunosorbent assay (ELISA) kit, the PAH soil test, was evaluated with regard to cross-reactivity. Phenanthrene in methanol was used as reference substance. Anthracene, naphthalene and fluorene were chosen as representatives of the 16 US-EPA priority-pollutant polycyclic aromatic hydrocarbons (PAHs). In addition, a number of polycyclic aromatic compounds (PACs), including methyl-, phenyl-, and carbonyl-PAHs, as well as NSO-heterocyclic PACs, found at former industrial sites, were chosen for elucidation of structure/cross-reactivity relationships. The study emphasizes the importance of a priori knowledge of sample composition for accurate interpretation of test results.

  • 31.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Figuring out how I belong2018In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 359, no 6383, p. 1558-1558Article in journal (Other academic)
  • 32.
    Nording, Malin L
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Jun, Yang
    Hoang, Laura
    Zamora, Vanessa
    Uyeminami, Dale
    Espiritu, Imelda
    Pinkerton, Kent E
    Hammock, Bruce D
    Luria, Ayala
    Bioactive lipid profiling reveals drug target engagement of a soluble epoxide hydrolase inhibitor in a murine model of tobacco smoke exposure2015In: Journal of metabolomics, ISSN 2059-0008, Vol. 1, no 1, article id 1Article in journal (Refereed)
    Abstract [en]

    The inflammatory process underlying chronic obstructive pulmonary disease (COPD) may be caused by tobacco smoke (TS) exposure. Previous studies show that epoxyeicosatrienoic acids (EETs) possess promising anti-inflammatory properties, therefore stabilization of EETs and other fatty acid epoxides through inhibition of soluble epoxide hydrolase (sEH) was investigated in mouse models of acute and subchronic inflammation caused by TS exposure. During the entire TS exposure, the potent sEH inhibitor 1-(1-methylsulfonyl-piperidin-4-yl)-3-(4-trifluoromethoxy-phenyl)-urea (TUPS) was given via drinking water. To assess drug target engagement of TUPS, a tandem mass spectrometry method was used for bioactive lipid profiling of a broad range of fatty acid metabolites, including EETs, and their corresponding diols (DHETs) derived from arachidonic acid, as well as epoxides and diols derived from other fatty acids. Several, but not all, plasma epoxide/diol ratios increased in mice treated with sEH inhibitor, compared to non-treated mice, suggesting a wider role for sEH involving more fatty acid precursors besides arachidonic acid. This study supports qualitative use of epoxide/diol ratios explored by bioactive lipid profiling to indicate drug target engagement in mouse models of TS exposure relevant to COPD, which may have ramifications for future therapeutic interventions of sEH.

  • 33.
    Nording, Malin Linder
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Yang, Jun
    Georgi, Katrin
    Karbowski, Christine Hegedus
    German, J. Bruce
    Weiss, Robert H.
    Hogg, Ronald J.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Hammock, Bruce D.
    Zivkovic, Angela M.
    Individual Variation in Lipidomic Profiles of Healthy Subjects in Response to Omega-3 Fatty Acids2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 10, p. e76575-Article in journal (Refereed)
    Abstract [en]

    Introduction: Conflicting findings in both interventional and observational studies have resulted in a lack of consensus on the benefits of omega 3 fatty acids in reducing disease risk. This may be due to individual variability in response. We used a multi-platform lipidomic approach to investigate both the consistent and inconsistent responses of individuals comprehensively to a defined omega 3 intervention. Methods: The lipidomic profile including fatty acids, lipid classes, lipoprotein distribution, and oxylipins was examined multi- and uni-variately in 12 healthy subjects pre vs. post six weeks of omega 3 fatty acids (1.9 g/d eicosapentaenoic acid [EPA] and 1.5 g/d docosahexaenoic acid [DHA]). Results: Total lipidomic and oxylipin profiles were significantly different pre vs. post treatment across all subjects (p=0.00007 and p=0.00002 respectively). There was a strong correlation between oxylipin profiles and EPA and DHA incorporated into different lipid classes (r(2)=0.93). However, strikingly divergent responses among individuals were also observed. Both omega 3 and omega 6 fatty acid metabolites displayed a large degree of variation among the subjects. For example, in half of the subjects, two arachidonic acid cyclooxygenase products, prostaglandin E-2 (PGE(2)) and thromboxane B2 (TXB2), and a lipoxygenase product, 12-hydroxyeicosatetraenoic acid (12-HETE) significantly decreased post intervention, whereas in the other half they either did not change or increased. The EPA lipoxygenase metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) varied among subjects from an 82% decrease to a 5,000% increase. Conclusions: Our results show that certain defined responses to omega 3 fatty acid intervention were consistent across all subjects. However, there was also a high degree of inter-individual variability in certain aspects of lipid metabolism. This lipidomic based phenotyping approach demonstrated that individual responsiveness to omega 3 fatty acids is highly variable and measurable, and could be used as a means to assess the effectiveness of omega 3 interventions in modifying disease risk and determining metabolic phenotype.

  • 34.
    Nording, Malin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nichkova, Mikaela
    Brena, Beatriz
    Gee, Shirley J
    Hammock, Bruce D
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Immunochemical determination of dioxins in soil samples2005In: Organohalogen Compounds, Vol. 67, p. 35-38Article in journal (Refereed)
  • 35.
    Nording, Malin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nichkova, Mikaela
    Department of Entomology and Cancer Research Center, University of California, USA.
    Spinnel, Erik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Persson, Ylva
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gee, Shirley J.
    Department of Entomology and Cancer Research Center, University of California, USA.
    Hammock, Bruce D.
    Department of Entomology and Cancer Research Center, University of California, USA.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Rapid screening of dioxin-contaminated soil by accelerated solvent extraction/purification followed by immunochemical detection2006In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 385, no 2, p. 357-366Article in journal (Refereed)
    Abstract [en]

    Since soils at industrial sites might be heavily contaminated with polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), there is a need for large-scale soil pollution surveys and, thus, for cost-efficient, high-throughput dioxin analyses. However, trace analysis of dioxins in complex matrices requires exhaustive extraction, extensive cleanup, and very sensitive detection methods. Traditionally, this has involved the use of Soxhlet extraction and multistep column cleanup, followed by gas chromatography-high-resolution mass spectrometry (GC/HRMS), but bioanalytical techniques may allow much more rapid, cost-effective screening. The study presented here explores the possibility of replacing the conventional method with a novel approach based on simultaneous accelerated solvent extraction (ASE) and purification, followed by an enzyme-linked immunosorbent assay (ELISA). Both the traditional and the novel cleanup and detection approaches were applied to contaminated soil samples, and the results were compared. ELISA and GC/HRMS results for Soxhlet-extracted samples were linearly correlated, although the ELISA method slightly underestimated the dioxin levels. To avoid an unacceptable rate of false-negative results, the use of a safety factor is recommended. It was also noted that the relative abundance of the PCDDs/PCDFs, evaluated by principal component analysis, had an impact on the ELISA performance. To minimize this effect, the results may be corrected for differences between the ELISA cross-reactivities and the corresponding toxic equivalency factor values. Finally, the GC/HRMS and ELISA results obtained following the two sample preparation methods agreed well; and the ELISA and GC/HRMS results for ASE extracts were strongly correlated (correlation coefficient, 0.90). Hence, the ASE procedure combined with ELISA analysis appears to be an efficient approach for high-throughput screening of PCDD-/PCDF-contaminated soil samples.

  • 36.
    Nording, Malin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sporring, Sune
    Björklund, Erland
    Wiberg, Karin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Efficient Screeing of Dioxins in Food and Feed Using Shape-Selective Pressurized Liquid Extraction and Cell Based Bioassay Analysis2004In: Organohalogen Compounds, Vol. 66, p. 617-622Article in journal (Refereed)
  • 37.
    Nording, Malin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sporring, Sune
    Department of Analytical Chemistry, Lund University, Lund, Sweden .
    Wiberg, Karin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Björklund, Erland
    Department of Analytical Chemistry, Lund University, Lund, Sweden .
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Monitoring dioxins in food and feedstuffs using accelerated solvent extraction with a novel integrated carbon fractionation cell in combination with a CAFLUX bioassay2005In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 381, no 7, p. 1472-1475Article in journal (Refereed)
    Abstract [en]

    The concentrations of dioxins in fish oil and fish meal were determined with accelerated solvent extraction, using a novel integrated carbon fractionation extraction cell followed by a miniturized multilayer silica column and bioanalysis on a recently-developed chemically-activated fluorescent gene expression cell bioassay. The developed method allows for simultaneous gravimetric lipid weight determination, which was shown for both matrices under study (about 100% lipid recovery of each sample). Initial results practically meet the quality criteria on screening methods for control of dioxins in food and feedstuffs laid down in the EU Commission Directives 2002/69/EC (food) and 2002/70/EC (feed). This demonstrates that the developed method can be used as a screening tool for monitoring dioxins in food and feed after some additional improvements and testing on a greater number of matrices.

  • 38. Smilowitz, Jennifer T.
    et al.
    Zivkovic, Angela M.
    Wan, Yu-Jui Yvonne
    Watkins, Steve M.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Hammock, Bruce D.
    German, J. Bruce
    Nutritional lipidomics: Molecular metabolism, analytics, and diagnostics2013In: Molecular Nutrition & Food Research, ISSN 1613-4125, E-ISSN 1613-4133, Vol. 57, no 8, p. 1319-1335Article, review/survey (Refereed)
    Abstract [en]

    MS with new bioinformatics toolsets to characterize the structures and abundances of complex lipids. Yet, translating lipidomics to practice via nutritional interventions is still in its infancy. No single instrumentation platform is able to solve the varying analytical challenges of the different molecular lipid species. Biochemical pathways of lipid metabolism remain incomplete and the tools to map lipid compositional data to pathways are still being assembled. Biology itself is dauntingly complex and simply separating biological structures remains a key challenge to lipidomics. Nonetheless, the strategy of combining tandem analytical methods to perform the sensitive, high-throughput, quantitative, and comprehensive analysis of lipid metabolites of very large numbers of molecules is poised to drive the field forward rapidly. Among the next steps for nutrition to understand the changes in structures, compositions, and function of lipid biomolecules in response to diet is to describe their distribution within discrete functional compartments lipoproteins. Additionally, lipidomics must tackle the task of assigning the functions of lipids as signaling molecules, nutrient sensors, and intermediates of metabolic pathways.

  • 39.
    Spinnel, Erik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lundin, Lisa
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Comparison of cell based bioassay and GC/MS dioxin analysis in fly ash2005In: Organohalogen Compounds, Vol. 67, p. 359-62Article in journal (Refereed)
  • 40.
    Spinnel, Erik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nichkova, M
    Persson, Ylva
    Gee, S.J.
    Hammock, B D
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ase with Carbon Trap Combined with an Immunoassay as a Fast and Reliable Screening Method to Detect Polychlorinated-P-Dioxins and Furans from Soil Samöles2006In: Organohalogen Compounds, ISSN 1026-4892, Vol. 68, p. 936-939Article in journal (Refereed)
  • 41.
    Surowiec, Izabella
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Karimpour, Masoumeh
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gouveia-Figueira, Sandra
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wu, Junfang
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Multi-platform metabolomics assays for human lung lavage fluids in an air pollution exposure study2016In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 408, no 17, p. 4751-4764Article in journal (Refereed)
    Abstract [en]

    Metabolomics protocols are used to comprehensively characterize the metabolite content of biological samples by exploiting cutting-edge analytical platforms, such as gas chromatography (GC) or liquid chromatography (LC) coupled to mass spectrometry (MS) assays, as well as nuclear magnetic resonance (NMR) assays. We have developed novel sample preparation procedures combined with GC-MS, LC-MS, and NMR metabolomics profiling for analyzing bronchial wash (BW) and bronchoalveolar lavage (BAL) fluid from 15 healthy volunteers following exposure to biodiesel exhaust and filtered air. Our aim was to investigate the responsiveness of metabolite profiles in the human lung to air pollution exposure derived from combustion of biofuels, such as rapeseed methyl ester biodiesel, which are increasingly being promoted as alternatives to conventional fossil fuels. Our multi-platform approach enabled us to detect the greatest number of unique metabolites yet reported in BW and BAL fluid (82 in total). All of the metabolomics assays indicated that the metabolite profiles of the BW and BAL fluids differed appreciably, with 46 metabolites showing significantly different levels in the corresponding lung compartments. Furthermore, the GC-MS assay revealed an effect of biodiesel exhaust exposure on the levels of 1-monostearylglycerol, sucrose, inosine, nonanoic acid, and ethanolamine (in BAL) and pentadecanoic acid (in BW), whereas the LC-MS assay indicated a shift in the levels of niacinamide (in BAL). The NMR assay only identified lactic acid (in BW) as being responsive to biodiesel exhaust exposure. Our findings demonstrate that the proposed multi-platform approach is useful for wide metabolomics screening of BW and BAL fluids and can facilitate elucidation of metabolites responsive to biodiesel exhaust exposure.

  • 42.
    Trindade, Mirta
    et al.
    Catedra de Bioquímica, Faculty of Chemistry, University de la República, Montevideo, Uruguay.
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Department of Entomology and Cancer Research Center, University of California, Davis, California 95616, USA.
    Nichkova, Mikaela Ivanova
    Department of Entomology and Cancer Research Center, University of California, Davis, California 95616, USA.
    Spinnel, Erik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Last, Michael S
    Department of Pulmonary and Critical Care Medicine, University of California, Davis, California 95616, USA.
    Gee, Shirley
    Department of Entomology and Cancer Research Center, University of California, Davis, California 95616, USA.
    Hammock, Bruce
    Department of Entomology and Cancer Research Center, University of California, Davis, California 95616, USA.
    Last, Jerold A
    Department of Pulmonary and Critical Care Medicine, University of California, Davis, California 95616, USA.
    González-Sapienza, Gualberto
    Catedra de Inmunología, Department of Biosciences, Faculty of Chemistry, University de la República, Montevideo, Uruguay.
    Brena, Beatriz M
    Catedra de Bioquímica, Faculty of Chemistry, University de la República, Montevideo, Uruguay and Laboratory of Environmental Quality, Intendencia Municipal de Montevideo, Montevideo, Uruguay.
    Enzyme-Linked Immunosorbent Assay for Screening Dioxin Soil Contamination by Uncontrolled Combustion During Informal Recycling in Slums2008In: Environmental Toxicology and Chemistry, ISSN 0730-7268, Vol. 27, no 11, p. 2224-2232Article in journal (Refereed)
    Abstract [en]

    Uncontrolled combustion due to garbage recycling is a widespread activity among slum dwellers in distressed economy countries, and has been indicated as a major source of dioxin contamination. However, due to the high cost and complexity of gas chromatography-high resolution mass spectrometry (GC-HRMS) analysis, the magnitude of the problem remains largely unknown. This work describes a first approach towards the use of a dioxin antibody-based enzyme-linked immunosorbent assay (ELISA) as the basis for a sustainable, simple, and low cost monitoring program to assess the toxicological impact of uncontrolled combustion in slums. A panel of sixteen samples was analyzed by GC-HRMS and ELISA on split extracts. Close to 20 % of the analyzed samples showed dioxin concentrations up to almost twice the guidance level for residential soil in several countries, pointing out the need for performing a large-scale monitoring program. Despite the potential for variations in dioxin congener distribution due to the mixed nature of the incinerated material, there was a good correlation between the toxic equivalents as determined by GC-HRMS and ELISA. Furthermore, an inter-laboratory ELISA validation showed that the capacity to perform the dioxin ELISA was successfully transferred between laboratories. It was concluded that the ELISA method performed very well as a screening tool to prioritize samples for instrumental analysis, which allows cutting down costs significantly.

  • 43.
    Weidemann, Eva
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bidleman, Terry
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Carlin, Danielle J.
    Collina, Elena
    Cormier, Stephania A.
    Gouveia-Figueira, Sandra C.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gullett, Brian K.
    Johansson, Christer
    Lucas, Donald
    Lundin, Lisa
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lundstedt, Staffan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Marklund, Stellan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ortuno, Nuria
    Sallam, Asmaa A.
    Schmidt, Florian M.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Jansson, Stina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    14th congress of combustion by-products and their health effects-origin, fate, and health effects of combustion-related air pollutants in the coming era of bio-based energy sources2016In: Environmental science and pollution research international, ISSN 0944-1344, E-ISSN 1614-7499, Vol. 23, no 8, p. 8141-8159Article in journal (Refereed)
    Abstract [en]

    The 14th International Congress on Combustion By-Products and Their Health Effects was held in UmeAyen, Sweden from June 14th to 17th, 2015. The Congress, mainly sponsored by the National Institute of Environmental Health Sciences Superfund Research Program and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, focused on the "Origin, fate and health effects of combustion-related air pollutants in the coming era of bio-based energy sources". The international delegates included academic and government researchers, engineers, scientists, policymakers and representatives of industrial partners. The Congress provided a unique forum for the discussion of scientific advances in this research area since it addressed in combination the health-related issues and the environmental implications of combustion by-products. The scientific outcomes of the Congress included the consensus opinions that: (a) there is a correlation between human exposure to particulate matter and increased cardiac and respiratory morbidity and mortality; (b) because currently available data does not support the assessment of differences in health outcomes between biomass smoke and other particulates in outdoor air, the potential human health and environmental impacts of emerging air-pollution sources must be addressed. Assessment will require the development of new approaches to characterize combustion emissions through advanced sampling and analytical methods. The Congress also concluded the need for better and more sustainable e-waste management and improved policies, usage and disposal methods for materials containing flame retardants.

  • 44.
    Wu, Junfang
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Zivkovic, Angela M.
    Larsson, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Öhman, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    NMR-based metabolite profiling of human milk: A pilot study of methods for investigating compositional changes during lactation2016In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 469, no 3, p. 626-632Article in journal (Refereed)
    Abstract [en]

    Low-molecular-weight metabolites in human milk are gaining increasing interest in studies of infant nutrition. In the present study, the milk metabolome from a single mother was explored at different stages of lactation. Metabolites were extracted from sample aliquots using either methanol water (MeOH/H2O) extraction or ultrafiltration. Nuclear magnetic resonance (NMR) spectroscopy was used for metabolite identification and quantification, and multi- and univariate statistical data analyses were used to detect changes over time of lactation. Compared to MeOH/H2O extraction, ultrafiltration more efficiently reduced the interference from lipid and protein resonances, thereby enabling the identification and quantification of 36 metabolites. The human milk metabolomes at the early (9-24 days after delivery) and late (31-87 days after delivery) stages of lactation were distinctly different according to multi- and univariate statistics. The late lactation stage was characterized by significantly elevated concentrations of lactose, choline, alanine, glutamate, and glutamine, as well as by reduced levels of citrate, phosphocholine, glycerophosphocholine, and N-acetylglucosamine. Our results indicate that there are significant compositional changes of the human milk metabolome also in different phases of the matured lactation stage. These findings complement temporal studies on the colostrum and transitional metabolome in providing a better understanding of the nutritional variations received by an infant.

  • 45.
    Wu, Jungfang
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gouveia-Figueira, Sandra
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Zivkovic, Angela M
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Oxylipins, endocannabinoids, and related compounds in human milk: levels and effects of storage conditions2016In: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 122, p. 28-36Article in journal (Refereed)
    Abstract [en]

    The presence of fatty acid derived oxylipins, endocannabinoids and related compounds in human milk may be of importance to the infant. Presently, clinically relevant protocols for storing and handling human milk that minimize error and variability in oxylipin and endocannabinoid concentrations are lacking. In this study, we compared the individual and combined effects of the following storage conditions on the stability of these fatty acid metabolites in human milk: state (fresh or frozen), storage temperature (4 °C, -20 °C or -80 °C), and duration (1 day, 1 week or 3 months). Thirteen endocannabinoids and related compounds, as well as 37 oxylipins were analyzed simultaneously by liquid chromatography coupled to tandem mass spectrometry. Twelve endocannabinoids and related compounds (2–111 nM) and 31 oxylipins (1.2 pM–1242 nM) were detected, with highest levels being found for 2-arachidonoylglycerol and 17(R)-hydroxydocosahexaenoic acid, respectively. The concentrations of most endocannabinoid-related compounds and oxylipins were dependent on storage condition, and especially storage at 4 °C introduced significant variability. Our findings suggest that human milk samples should be analyzed immediately after, or within one day of collection (if stored at 4 °C). Storage at -80 °C is required for long-term preservation, and storage at -20 °C is acceptable for no more than one week. These findings provide a protocol for investigating the oxylipin and endocannabinoid metabolome in human milk, useful for future milk-related clinical studies.

  • 46. Zivkovic, AM
    et al.
    Yang, J
    Hegedus, C
    Nording, Malin
    Department of Entomology, University of California, Davis, CA, USA.
    O´Sullivan, A
    Hogg, RJ
    Weiss, RH
    Bay, C
    Hammock, BD
    Serum oxylipin profiles in IgA nephropathy patients reflect kidney functional alterations2012In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 8, no 6, p. 1102-1113Article in journal (Refereed)
    Abstract [en]

    Immunoglobulin A nephropathy (IgAN) is a leading cause of chronic kidney disease, frequently associated with hypertension and renal inflammation. ω-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fish oil (FO) improve kidney function in animal models, but have inconsistent metabolic effects in humans. Oxylipin profiles in serum from IgAN patients supplemented with either FO or corn oil (CO) placebo were analyzed by liquid chromatography coupled to tandem mass spectrometry. EPA cyclooxygenase and lipoxygenase metabolites, and EPA and DHA epoxides and diols were increased in response to FO supplementation, as were total epoxides and epoxide/diol ratios. Several of these metabolites were drivers of separation as assessed by multivariate analysis of FO patients pre- vs. post-supplementation, including 17,18-dihydroxyeicosatrienoic acid, prostaglandin D3, prostagalandin E3, Resolvin E1, 12-hydroxyeicosapentaenoic acid, and 10(11)-epoxydocosapentaenoic acid. In patients whose proteinuria improved, plasma total oxylipins as well as several hydroxyoctadecadienoic acids, hydroxyeicosatetraenoic acids, and leukotriene B4 metabolites were among the metabolites that were significantly lower than in patients whose proteinuria either did not improve or worsened. These data support the involvement of oxylipins in the inflammatory component of IgAN as well as the potential use of oxylipin profiles as biomarkers and for assessing responsiveness to ω-3 fatty acid supplementation in IgAN patients.

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  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf