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  • 1. Ambring, A
    et al.
    Friberg, P
    Axelsen, M
    Laffrenzen, M
    Taskinen, M-R
    Basu, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Johansson, M
    Effects of a Mediterranean-inspired diet on blood lipids, vascular function and oxidative stress in healthy subjects.2004In: Clin Sci (Lond), ISSN 0143-5221, Vol. 106, no 5, p. 519-25Article in journal (Refereed)
  • 2.
    Andersson, Agneta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Tengblad, Siv
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kamal-Eldin, Afaf
    Landberg, Rikard
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Åman, Per
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Whole-grain foods do not affect insulin sensitivity or markers of lipid peroxidation and inflammation in healthy, moderately overweight subjects2007In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 137, no 6, p. 1401-1407Article in journal (Refereed)
    Abstract [en]

    High intakes of whole grain foods are inversely related to the incidence of coronary heart diseases and type 2 diabetes, but the mechanisms remain unclear. Our study aimed to evaluate the effects of a diet rich in whole grains compared with a diet containing the same amount of refined grains on insulin sensitivity and markers of lipid peroxidation and inflammation. In a randomized crossover study, 22 women and 8 men (BMI 28 +/- 2) were given either whole-grain or refined-grain products (3 bread slices, 2 crisp bread slices, 1 portion muesli, and 1 portion pasta) to include in their habitual daily diet for two 6-wk periods. Peripheral insulin sensitivity was determined by euglycemic hyperinsulinemic clamp tests. 8-Iso-prostaglandin F(2alpha) (8-iso PGF(2alpha)), an F(2)-isoprostane, was measured in the urine as a marker of lipid peroxidation, and highly sensitive C-reactive protein and IL-6 were analyzed in plasma as markers of inflammation. Peripheral insulin sensitivity [mg glucose . kg body wt(-1) . min(-1) per unit plasma insulin (mU/L) x 100] did not improve when subjects consumed whole-grain products (6.8 +/- 3.0 at baseline and 6.5 +/- 2.7 after 6 wk) or refined products (6.4 +/- 2.9 and 6.9 +/- 3.2, respectively) and there were no differences between the 2 periods. Whole-grain consumption also did not affect 8-iso-PGF(2alpha) in urine, IL-6 and C-reactive protein in plasma, blood pressure, or serum lipid concentrations. In conclusion, substitution of whole grains (mainly based on milled wheat) for refined-grain products in the habitual daily diet of healthy moderately overweight adults for 6-wk did not affect insulin sensitivity or markers of lipid peroxidation and inflammation.

  • 3. Barregard, L
    et al.
    Sällsten, G
    Gustafson, P
    Andersson, L
    Johansson, L
    Basu, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Stigendal, L
    Experimental exposure to wood-smoke particles in healthy humans: effects on markers of inflammation, coagulation, and lipid peroxidation.2006In: Inhal Toxicol, ISSN 1091-7691, Vol. 18, no 11, p. 845-53Article in journal (Refereed)
  • 4.
    Basu, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Isoprostanes. Bioactive Lipids.2004In: The Oily Press, UK 2004 , 2004, p. 265-285Chapter in book (Other scientific)
  • 5.
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients.2003In: Toxicology, ISSN 0300-483X, Vol. 189, no 1-2, p. 113-27Article in journal (Refereed)
  • 6.
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    F2-isoprostane induced prostaglandin formation in the rabbit.2006In: Free Radic Res, ISSN 1071-5762, Vol. 40, no 3, p. 273-7Article in journal (Refereed)
  • 7.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    F2-isoprostane induced prostaglandin formation in the rabbit2006In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 40, no 3, p. 273-277Article in journal (Refereed)
    Abstract [en]

    F2-isoprostanes, non-enzymatic free radical mediated products of arachidonic acid, have shown to form during various oxidant stress status and have potent biological effects. This study investigates to what extent 8-iso-PGF (a major F2-isoprostane), a bioactive product of lipid peroxidation can modify endogenous prostaglandin F (PGF) formation since prostaglandins are inflammatory as well as potent vasoregulatory substances that modulate diverse important physiological functions, and also form during acute and chronic inflammation. An immediate appearance and disappearance of 8-iso-PGF was seen in both plasma and urine within a short interval after i.v. administration of 43 μg/kg of 8-iso-PGF to the rabbits. A successive but differential formation of PGF resulted in a rapid and pulsatile increase of plasma 15-keto-dihydro-PGF, a major metabolite of primary PGF. Later, this compound was excreted efficiently as intact compound into the urine during the 3 h of experiment. A 8-fold increase of PGF metabolite in plasma at 10 min and 12-fold increase in the urine at 30–60 after the i.v. administration of 8-iso-PGF was observed which continued throughout the 3 h of experiment. This observation suggests that pharmacologically administered or endogenously produced 8-iso-PGF during oxidant stress induces prostaglandin formation presumbly through the classical cyclooxygenase-catalysed arachidonic acid oxidation which might be inflammatory itself to the cells and exerts further vasoconstrictive effects.

  • 8.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    F2-isoprostanes in human health and diseases: from molecular mechanisms to clinical implications2008In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 10, no 8, p. 1405-1434Article, review/survey (Refereed)
    Abstract [en]

    Oxidative stress is implicated as one of the major underlying mechanisms behind many acute and chronic diseases, and involved in normal aging. However, the measurement of free radicals or their end products is complicated. Thus, proof of association of free radicals in pathologic conditions has been absent. Isoprostanes are prostaglandin-like bioactive compounds that are biosynthesized in vivo independent of cyclooxygenases, principally through free-radical catalyzation of arachidonic acid. Isoprostanes are now considered to be reliable biomarkers of oxidative stress, as evidenced by an autonomous study organized recently by the National Institutes of Health (NIH) in the United States. A number of these compounds have potent biologic activities such as vasoconstrictive and certain inflammatory properties. Isoprostanes are involved in many human diseases. Additionally, elevated levels of F2-isoprostanes have been seen in normal human pregnancy and after intake of some fatty acids, but their physiologic assignments have not yet been distinctive. This evidence indicates that measurement of bioactive F2-isoprostanes in body fluids offers a unique noninvasive analytic utensil to study the role of free radicals in physiology, oxidative stress–related diseases, experimental acute or chronic inflammatory conditions, and also in the assessment of various antioxidants, radical scavengers, and drugs.

  • 9.
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Isoprostanes: novel bioactive products of lipid peroxidation.2004In: Free Radic Res, ISSN 1071-5762, Vol. 38, no 2, p. 105-22Article in journal (Refereed)
  • 10.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Measurement of F2-isoprostanes in tissues and biological fluids as an in vivo index of oxidative stress2009In: Methods in Redox Signaling / [ed] Dipak K. Das, NY, USA: Mary Ann Liebert, Inc. , 2009, p. 38-45Chapter in book (Other academic)
  • 11.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Novel cyclooxygenase-catalyzed bioactive prostaglandin F-2 alpha from physiology to new principles in inflammation2007In: Medicinal research reviews (Print), ISSN 0198-6325, E-ISSN 1098-1128, Vol. 27, no 4, p. 435-468Article, review/survey (Refereed)
    Abstract [en]

    Prostaglandin F2 (PGF2), a foremost stable vasoactive cyclooxygenase (COX)-catalyzed prostaglandin, regulates a number of key physiological functions such as luteolysis, ovarian function, luteal maintenance of pregnancy, and parturition as a constitutive part of ongoing reproductive processes of the body. It has recently been implicated in the regulation of intricate pathophysiological processes, such as acute and chronic inflammation, cardiovascular and rheumatic diseases. Since the discovery of a second isoform of COXs, it has been shown that PGF2 can be formed in vivo from arachidonic acid through both isoforms of COXs, namely cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Being synthesized in various parts of the body, it metabolizes instantly to a number of rather inactive metabolites mainly in the lungs, liver, kidney, and efficiently excretes into the urine. 15-Keto-dihydro-PGF2, a major stable metabolite of PGF2 that reflects in vivo PGF2 biosynthesis, is found in larger quantities than its parent compound in the circulation and urine in basal physiological conditions, with short-lived pulses during luteolysis, induced termination of pregnancy and parturition, and is increased in tissues and various body fluids during acute, sub-chronic, and severe chronic inflammation. Further, the close relationship of PGF2 with a number of risk factors for atherosclerosis indicates its major role in inflammation pathology. This review addresses multiple aspects of PGF2 in addition to its emerging role in physiology to inflammation.

  • 12.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    The enigma of in vivo oxidative stress assessment: isoprostanes as an emerging target2007In: Scandinavian Journal of Food & Nutrition, ISSN 1748-2984 (electronic) 1748-2976 (paper), Vol. 51, no 2, p. 48-61Article in journal (Refereed)
    Abstract [en]

    Oxidative stress is believed to be one of the major factors behind several acute and chronic diseases, and may also be associated with ageing. Excess formation of free radicals in miscellaneous body environment may originate from endogenous response to cell injury, but also from exposure to a number of exogenous toxins. When the antioxidant defence system is overwhelmed, this leads to cell damage. However, the measurement of free radicals or their endproducts is tricky, since these compounds are reactive and short lived, and have diverse characteristics. Specific evidence for the involvement of free radicals in pathological situations has been difficult to obtain, partly owing to shortcomings in earlier described methods for the measurement of oxidative stress. Isoprostanes, which are prostaglandin-like bioactive compounds synthesized in vivo from oxidation of arachidonic acid, independently of cyclooxygenases, are involved in many human diseases, and their measurement therefore offers a way to assess oxidative stress. Elevated levels of F2-isoprostanes have also been seen in the normal human pregnancy, but their physiological role has not yet been defined. Large amounts of bioactive F2-isoprostanes are excreted in the urine in normal basal situations, with a wide interindividual variation. Their exact role in the regulation of normal physiological functions, however, needs to be explored further. Current understanding suggests that measurement of F2-isoprostanes in body fluids provides a reliable analytical tool to study oxidative stress-related diseases and experimental inflammatory conditions, and also in the evaluation of various dietary antioxidants, as well as drugs with radical-scavenging properties. However, assessment of isoprostanes in plasma or urine does not necessarily reflect any specific tissue damage, nor does it provide information on the oxidation of lipids other than arachidonic acid.

  • 13.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. Univ Auvergne, Univ Clermont Ferrand 2, UMR 1019, CRNH Auvergne,Unite Nutr Humaine, F-63000 Clermont Ferrand, France..
    Combe, Kristell
    Univ Auvergne, Univ Clermont Ferrand 2, UMR 1019, CRNH Auvergne,Unite Nutr Humaine, F-63000 Clermont Ferrand, France..
    Kwiatkowski, Fabrice
    Ctr Jean Perrin, F-63000 Clermont Ferrand, France..
    Caldefie-Chezet, Florence
    Univ Auvergne, Univ Clermont Ferrand 2, UMR 1019, CRNH Auvergne,Unite Nutr Humaine, F-63000 Clermont Ferrand, France..
    Penault-Llorca, Frederique
    Ctr Jean Perrin, F-63000 Clermont Ferrand, France..
    Bignon, Yves-Jean
    Ctr Jean Perrin, F-63000 Clermont Ferrand, France..
    Vasson, Marie-Paule
    Univ Auvergne, Univ Clermont Ferrand 2, UMR 1019, CRNH Auvergne,Unite Nutr Humaine, F-63000 Clermont Ferrand, France.;Ctr Jean Perrin, F-63000 Clermont Ferrand, France.;CHU Clermont Ferrand, Unite Explorat Nutr, F-63003 Clermont Ferrand, France..
    Cellular Expression of Cyclooxygenase, Aromatase, Adipokines, Inflammation and Cell Proliferation Markers in Breast Cancer Specimen2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, article id e0138443Article in journal (Refereed)
    Abstract [en]

    Current evidences suggest that expression of Ki67, cyclooxygenase (COX), aromatase, adipokines, prostaglandins, free radicals, beta-catenin and alpha-SMA might be involved in breast cancer pathogenesis. The main objective of this study was to compare expression/localization of these potential compounds in breast cancer tissues with tissues collected adjacent to the tumor using immunohistochemistry and correlated with clinical pathology. The breast cancer specimens were collected from 30 women aged between 49 and 89 years who underwent breast surgery following cancer diagnosis. Expression levels of molecules by different stainings were graded as a score on a scale based upon staining intensity and proportion of positive cells/area or individually. AdipoR1, adiponectin, Ob-R, leptin, COX-1, COX-2, aromatase, PGF(2a), F-2-isoprostanes and alpha-SMA were localised on higher levels in the breast tissues adjacent to the tumor compared to tumor specimens when considering either score or staining area whereas COX-2 and AdipoR2 were found to be higher considering staining intensity and Ki67 on score level in the tumor tissue. There was no significant difference observed on beta-catenin either on score nor on staining area and intensity between tissues adjacent to the tumor and tumor tissues. A positive correlation was found between COX-1 and COX-2 in the tumor tissues. In conclusion, these suggest that Ki67, COXs, aromatase, prostaglandin, free radicals, adipokines, beta-catenin and alpha-SMA are involved in breast cancer. These further focus the need of examination of tissues adjacent to tumor, tumor itself and compare them with normal or benign breast tissues for a better understanding of breast cancer pathology and future evaluation of therapeutic benefit.

  • 14.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Harris, Holly
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Vasson, Marie-Paule
    Wolk, Alicja
    Is There any Role for Serum Cathepsin S, CRP levels on Prognostic Information in Breast Cancer?: The Swedish Mammography Cohort2015In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 23, no 16, p. 1298-1302Article in journal (Refereed)
    Abstract [en]

    Breast cancer is the most common cancer among women, and both low-grade inflammation and cathepsins might have important roles in breast cancer. We questioned whether prediagnostic circulating levels of C-reactive protein (CRP), cathepsin B and cathepsin S were associated with breast cancer risk. Sixty-nine incident breast cancer cases diagnosed after blood collection and 719 controls from the Swedish Mammography Cohort were analysed for systemic CRP, cathepsin B and cathepsin S. Cathepsin S and inflammation (hsCRP) adjusted cathepsin S were inversely associated with breast cancer risk (cathepsin S: OR for top vs. bottom tertile = 0.46; 95% CI = 0.23-0.92; Ptrend = 0.02; hsCRP adjusted cathepsin S: OR of 0.44; 95% CI = 0.22-0.87; Ptrend = 0.02). hsCRP was significantly associated with increased breast cancer risk (OR for top vs. bottom tertile= 2.01; 95% CI = 1.02-3.95; Ptrend = 0.04). No significant association was observed between cathepsin B and breast cancer risk (OR for top vs. bottom tertile= 0.67; 95% CI = 0.32-1.40; Ptrend = 0.30). These observations lead to hypothesis that levels of cathepsin S and hsCRP observed in women who later developed breast cancer may provide prognostic information regarding tumor development and need to be evaluated in prospective studies.

  • 15.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Harris, Holly
    Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, .
    Wolk, Alicja
    Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, .
    Rossary, Adrien
    Chaire d'Excellence Program, Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, CRNH-Auvergne, INRA-UDA, Clermont-Ferrand, France;.
    Caldefie-Chézet, Florence
    Chaire d'Excellence Program, Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, CRNH-Auvergne, INRA-UDA, Clermont-Ferrand, France;.
    Vasson, Marie-Paule
    Chaire d'Excellence Program, Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, CRNH-Auvergne, INRA-UDA, Clermont-Ferrand, France;.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Inflammatory F2-isoprostane, prostaglandin F2α, pentraxin 3 levels and breast cancer risk: The Swedish Mammography Cohort2016In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 113, p. 28-32Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Breast cancer is a common cancer among women. Identifying cellular participation of F2-isoprostane, prostaglandin F2α (PGF2α) and pentraxin 3 (PTX3) in cancer we evaluated whether their prediagnostic systemic levels that originate from different inflammatory pathways were associated with breast cancer risk.

    METHODS: Seventy-eight breast cancer cases diagnosed after blood collection and 797 controls from the Swedish Mammography Cohort were analysed for urinary F2-isoprostane, PGF2α and plasma PTX3 levels.

    RESULTS: None of the biomarkers investigated were significantly associated with breast cancer risk. However, there was the suggestion of an inverse association with PTX3 with multivariable adjusted ORs (95% CI) of 0.56 (95% CI=0.29-1.06) and 0.67 (95% CI=0.35-1.28) for the second and third tertiles, respectively (ptrend=0.20). No associations were observed between F2-isoprostane (OR=0.87; 95% CI=0.48-1.57; ptrend=0.67) and PGF2α metabolite (OR=1.03; 95% CI=0.56-1.88; ptrend=0.91) comparing the top to bottom tertiles.

    CONCLUSIONS: The systemic levels of F2-isoprostane, PGF2α and PTX3 witnessed in women who later developed breast cancer may not provide prognostic information regarding tumor development in spite of their known involvement in situ cellular context. These observations may indicate that other mechanisms exist in controlling cellular formation of F2-isoprostane, PGF2α and PTX3 and their systemic availability in breast cancer patients.

  • 16.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Bioaktiva isoprostaner : nya markörer för oxidativ stress och inflammationsrelaterade sjukdomar2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 5, p. 274-278Article in journal (Refereed)
    Abstract [en]

    Oxidativ stress (fria radikaler) tros vara orsaken till åldrande och flera sjukdomar, däri bland arterioskleros, men det har saknats en pålitlig metodik för att påvisa aktiviteten av fria radikaler in vivo. Här presenteras isoprostaner som nya och tillförlitliga markörer för mätning av oxidativ stress in vivo genom indirekt mätning av radikalreaktioner. Isoprostaner kan ses i ökad mängd vid flera sjukdomstillstånd som är associerade med oxidativ stress och inflammation, till exempel kardiovaskulära sjukdomar, sjukdomar som är associerade med en ökad kardiovaskulär risk samt lungsjukdomar. Mätning av isoprostaner kan vidare ge ökad kunskap om fria radikalers fysiologiska roll och antioxidanternas roll vid sjukdomar samt vara ett verktyg vid utveckling av nya läkemedel mot oxidativ stress.

  • 17.
    Basu, Samar
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk näringsforskning.
    Helmersson, Johanna
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk näringsforskning.
    Factors regulating isoprostane formation in vivo.2005In: Antioxid Redox Signal, ISSN 1523-0864, Vol. 7, no 1-2, p. 221-35Article in journal (Other scientific)
  • 18.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Jarosinska, Dorota
    Sällsten, Gerd
    Mazzolai, Barbarra
    Barregård, Lars
    Regulatory factors of basal F2-isoprostane formation: population, age, gender and smoking habits in humans2009In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 43, no 1, p. 85-91Article in journal (Refereed)
    Abstract [en]

    Oxidative stress is assumed to be the key underlying factor in the pathogenesis of many common diseases. This study describes the basal levels of 8-iso-PGF(2alpha ), a major F(2)-isoprostane and an in vivo oxidative stress biomarker in healthy subjects from three countries, namely Italy, Poland and Sweden, in relation to their smoking habits, age and gender. It studied urinary 8-iso-PGF(2alpha ) in 588 subjects from Sweden (n=220), Italy (n=203) and Poland (n=165). Polish subjects had the highest levels of F(2)-isoprostanes followed by the Swedish and Italians when adjusted for smoking, age, sex and creatinine and the inter-country differences were statistically significant. Smokers had significantly higher levels of 8-iso-PGF(2alpha ) compared to non-smokers in all countries and there was a moderate decrease with age. Women had only slightly lower 8-iso-PGF(2alpha ) than men. There is a difference in F(2)-isoprostane levels in vivo between countries. Smoking, age and gender affect isoprostane formation and should be taken into consideration in clinical studies of oxidative stress.

  • 19.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Univ Clermont Auvergne, Fac Pharm, Dept Biochem Mol Biol & Nutr, BP 10448, F-63000 Clermont Ferrand, France..
    Kadiiska, Maria B.
    NIEHS, Immun Inflammat & Dis Lab, NIH, Res Triangle Pk, NC 27709 USA..
    Ozone exposure effect on systemic prostaglandin F-2 alpha in rat plasma and urine may not reveal pulmonary damage through inflammation2017In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 126, p. 79-83Article in journal (Refereed)
    Abstract [en]

    The acute ozone induced lung injury model has been widely used to explore injury and repair processes induced by oxidant overload. The current study evaluated acute ozone exposure effects on prostaglandin F-2 alpha (PGF(2 alpha)) in male Fischer rat plasma and urine with the hypothesis that ozone may induce an inflammatory response in the body that can be measured by the induction of PGF2 alpha. That might then lead to the identification of potential marker for acute lung injury through systemic inflammation. The time and dose-dependent effects of ozone exposure on the plasma and urinary levels of a major PGF(2 alpha) metabolite15-keto-dihydro-PGF(2 alpha) were determined using a radioimmunoassay. No statistically significant differences in the PGF(2 alpha) metabolite were found between the control and the experimental groups at either ozone exposure dose (2 ppm and 5 ppm) or any time point (2 h, 7 h and 16 h) post exposure for plasma and at 7 different post exposure time points (between 2 and 80 h) for urine. It is concluded that acute ozone exposure does not cause changes in plasma and urinary PGF(2 alpha), and therefore their measurement in plasma and urine may not be used to reveal pulmonary inflammation and damage by ozone.

  • 20.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vessby, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Type 1 diabetes is associated with increased cyclooxygenase- and cytokine-mediated inflammation2005In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, no 6, p. 1371-1375Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The extent of involvement of cyclooxygenase (COX)-mediated inflammation in type 1 diabetes is unknown, and the association between the COX- and cytokine-mediated inflammatory responses in type 1 diabetes is not fully understood.

    RESEARCH DESIGN AND METHODS: Plasma high-sensitivity C-reactive protein (CRP), 24-h urinary and plasma 15-keto-dihydro-prostaglandin F(2alpha) (a metabolite of prostaglandin F(2alpha) [PGF(2alpha)] and an indicator of COX-mediated inflammation), serum amyloid protein A (SAA), and interleukin (IL)-6 (indicators of inflammation) were measured in 38 subjects with type 1 diabetes and 41 healthy age- and sex-matched control subjects.

    RESULTS: The inflammatory indicators (urinary 15-keto-dihydro-PGF(2alpha), P < 0.01; IL-6, P < 0.04) were increased in men with diabetes. CRP and SAA did not show any significant difference between the diabetic and the control subjects. Urinary levels of 15-keto-dihydro-PGF(2alpha) correlated with the degree of glycemic control, HbA(1c) (r = 0.42, P < 0.0005). No correlation was found between the duration of diabetes and the inflammatory biomarkers or metabolic measurements.

    CONCLUSIONS: These results suggest that an early low-grade inflammatory process reflected by elevated levels of PGF(2alpha) and IL-6 is involved in type 1 diabetes. Thus, both COX- and cytokine-mediated inflammatory pathways are significantly related to type 1 diabetes.

  • 21.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Meisert, Isabelle
    Eggensperger, Elisabeth
    Krieger, Elisabeth
    Krenn, Claus G.
    Time course and attenuation of ischaemia-reperfusion induced oxidative injury by propofol in human renal transplantation2007In: Redox report, ISSN 1351-0002, E-ISSN 1743-2928, Vol. 12, no 4, p. 195-202Article in journal (Refereed)
    Abstract [en]

    Ischaemia-reperfusion injury resulting from interruption and restoration of blood flow might be related to free radical mediated oxidative stress and inflammation, and subsequently to post-surgery related complications. We studied the impact of renal transplantation on oxidative stress and inflammation by measuring F2-isoprostanes and prostaglandin F, respectively, during transplantation and post-surgery. Additionally, due to earlier observations, two dissimilar anaesthetic agents (thiopentone and propofol) were compared to determine their antioxidative capacity rather than their anaesthetic properties. Blood samples were collected before, post-intubation, immediately, 30, 60,120, 240 min, and 12 and 24 h after reperfusion. Oxidative stress and inflammatory response were detected by measuring 8-iso-PGF (a major F2-isoprostane and a biomarker of oxidative stress) and 15-keto-dihydro-PGF (a major metabolite of PGF and a biomarker of COX-mediated inflammatory response), respectively. Reperfusion of the transplanted graft significantly increased plasma levels of 8-iso-PGF. PGF metabolite levels, although elevated, did not reach statistical significance. In addition, significantly lower levels of 8-iso-PGF2a were observed in the propofol group compared to the thiopentone group. Together, these findings underline an augmented oxidative stress activity following an inflammatory response after human renal transplantation. Furthermore, propofol a well-known anaesthetic, counteracted oxidative stress by lowering the formation of a major F2-isoprostane.

  • 22.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Nachat-Kappes, Rachida
    Caldefie-Chezet, Florence
    Vasson, Marie-Paule
    Eicosanoids and Adipokines in Breast Cancer: From Molecular Mechanisms to Clinical Considerations2013In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 18, no 3, p. 323-360Article, review/survey (Refereed)
    Abstract [en]

    Chronic inflammation is one of the foremost risk factors for different types of malignancies, including breast cancer. Additional risk factors of this pathology in postmenopausal women are weight gain, obesity, estrogen secretion, and an imbalance in the production of adipokines, such as leptin and adiponectin. Various signaling products of transcription factor, nuclear factor-kappaB, in particular inflammatory eicosanoids, reactive oxygen species (ROS), and cytokines, are thought to be involved in chronic inflammation-induced cancer. Together, these key components have an influence on inflammatory reactions in malignant tissue damage when their levels are deregulated endogenously. Prostaglandins (PGs) are well recognized in inflammation and cancer, and they are solely biosynthesized through cyclooxygenases (COXs) from arachidonic acid. Concurrently, ROS give rise to bioactive isoprostanes from arachidonic acid precursors that are also involved in acute and chronic inflammation, but their specific characteristics in breast cancer are less demonstrated. Higher aromatase activity, a cytochrome P-450 enzyme, is intimately connected to tumor growth in the breast through estrogen synthesis, and is interrelated to COXs that catalyze the formation of both inflammatory and anti-inflammatory PGs such as PGE(2), PGF(2 alpha), PGD(2), and PGJ(2) synchronously under the influence of specific mediators and downstream enzymes. Some of the latter compounds upsurge the intracellular cyclic adenosine monophosphate concentration and appear to be associated with estrogen synthesis. This review discusses the role of COX- and ROS-catalyzed eicosanoids and adipokines in breast cancer, and therefore ranges from their molecular mechanisms to clinical aspects to understand the impact of inflammation.

  • 23.
    Basu, Samar
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Smedman, Annika
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Risérus, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Vessby, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Conjugated linoleic acid (CLA) induces lipid perxidation in humans2000In: Proceedings if the OCC Meeting 2000, 2000Conference paper (Refereed)
  • 24.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cytokine-mediated inflammation is independently associated with insulin sensitivity measured by the euglycemic insulin clamp in a community-based cohort of elderly men2011In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 4, no 2, p. 164-168Article in journal (Refereed)
    Abstract [en]

    Both clinical and experimental studies suggest a close relation between an inflammatory state and insulin resistance. We investigated the association between cytokine-mediated inflammation (high sensitivity C reactive protein [hsCRP] and interleukin [IL] 6) and insulin sensitivity (insulin-mediated glucose disposal rate, assessed by the euglycemic insulin clamp) in a community-based cohort, with subgroup analyses of normal weight individuals without diabetes mellitus and metabolic syndrome (NCEP). hsCRP and IL-6 were inversely associated with insulin sensitivity (multivariable-adjusted regression coefficient for 1-SD increase of hsCRP -0.12 (-0.21-(-0.03), p=0.01) and of IL-6 -0.11 (-0.21-(-0.02), p=0.01) in models adjusting for age and components of the metabolic syndrome (systolic and diastolic blood pressure, antihypertensive drugs, HDL-cholesterol, triglycerides, fasting plasma glucose, waist circumference). The multivariable-adjusted association between hsCRP, IL-6 and insulin sensitivity were of a similar magnitude in normal weight individuals without diabetes and without the metabolic syndrome. Our data show that cytokine -mediated subclinical inflammation is independently associated with decreased insulin sensitivity also in apparently metabolically healthy normal weight individuals, indicating that the interplay between inflammatory processes and insulin resistance is present already in the early stages of the development of glucometabolic disease.

  • 25. Berg, K.
    et al.
    Haaverstad, R.
    Astudillo, R.
    Björngaard, M.
    Skarra, S.
    Wiseth, R.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Jynge, P.
    Oxidative stress during coronary artery bypass operations: Importance of surgical trauma and drug treatment2006In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 40, no 5, p. 291-297Article in journal (Refereed)
    Abstract [en]

    Objective. To investigate oxidative stress and myocardial injury at different stages of coronary artery bypass grafting (CABG). Design. Twenty patients underwent CABG with use of cardiopulmonary bypass (CPB) and with intermittent sampling of plasma and urine. Main markers were: 8-iso-PGF(2 alpha) (oxidative stress); troponin T (myocardial injury); and 15-keto-dihydro-PGF2 alpha and hsCRP (inflammation). Results. Plasma 8-iso-PGF2 alpha increased after start of surgery, but there was no further rise during CPB or after aortic cross-clamp release and no significant myocardial arterio-venous differences. An increase in troponin T was seen early after the operation, but no relationship was established between 8-iso-PGF2 alpha and troponin T. 8-iso-PGF2 alpha levels were elevated by preoperative withdrawal of acetylsalicylic acid (ASA) but reduced by intraoperative use of heparin. 15-keto-dihydro-PGF2 alpha was elevated during operation and hsCRP following operation. Conclusions. In the present study oxidative stress was multifactorial in origin with main impacts from surgical trauma, less from CPB and little if any from myocardial ischemia-reperfusion events. In addition, cardiovascular drugs in common use like ASA and heparin seemed to influence the pro- and antioxidant balance, a finding that has to be confirmed in future studies.

  • 26. Berg, K
    et al.
    Jynge, P
    Bjerve, K
    Skarra, S
    Basu, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Wiseth, R
    Oxidative stress and inflammatory response during and following coronary interventions for acute myocardial infarction.2005In: Free Radic Res, ISSN 1071-5762, Vol. 39, no 6, p. 629-36Article in journal (Refereed)
  • 27. Berg, Kirsti
    et al.
    Langaas, Mette
    Ericsson, Madelene
    Pleym, Hilde
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Nordrum, Ivar Skjak
    Vitale, Nicola
    Haaverstad, Rune
    Acetylsalicylic acid treatment until surgery reduces oxidative stress and inflammation in patients undergoing coronary artery bypass grafting2013In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 43, no 6, p. 1154-1163Article in journal (Refereed)
    Abstract [en]

    Acetylsalicylic acid (ASA) is a cornerstone in the treatment of coronary artery disease (CAD) due to its antiplatelet effect. Cessation of aspirin before coronary artery bypass grafting (CABG) is often recommended to avoid bleeding, but the practice is controversial because it is suggested to worsen the underlying CAD. The aims of the present prospective, randomized study were to assess if ASA administration until the day before CABG decreases the oxidative load through a reduction of inflammation and myocardial damage, compared with patients with preoperative discontinuation of ASA. Twenty patients scheduled for CABG were randomly assigned to either routine ASA-treatment (160 mg daily) until the time of surgery (ASA), or to ASA-withdrawal 7 days before surgery (No-ASA). Blood-samples were taken from a radial artery and coronary sinus, during and after surgery and analysed for 8-iso-prostaglandin (PG) F-2 alpha; a major F-2-isoprostane, high-sensitivity C-reactive protein (hs-CRP), cytokines and troponin T. Left ventricle Tru-Cut biopsies were taken from viable myocardium close to the left anterior descending artery just after connection to cardiopulmonary bypass, and before cardioplegia were established for gene analysis (Illumina HT-12) and immunohistochemistry (CD45). 8-Iso-PGF(2 alpha) at baseline (t(1)) were 111 (277) pmol/l and 221 (490) pmol/l for ASA and No-ASA, respectively (P = 0.065). Area under the curve showed a significantly lower level in plasma concentration of 8-iso-PGF(2 alpha) and hsCRP in the ASA group compared with the No-ASA group with (158 pM vs 297 pM, P = 0.035) and hsCRP (8.4 mg/l vs 10.1 mg/l, P = 0.013). All cytokines increased during surgery, but no significant differences between the two groups were observed. Nine genes (10 transcripts) were found with a false discovery rate (FDR) < 0.1 between the ASA and No-ASA groups. Continued ASA treatment until the time of CABG reduced oxidative and inflammatory responses. Also, a likely beneficial effect upon myocardial injury was noticed. Although none of the genes known to be involved in oxidative stress or inflammation took a different expression in myocardial tissue, the genetic analysis showed interesting differences in the mRNA level. Further research in this field is necessary to understand the role of the genes.

  • 28. Berg, Kirsti
    et al.
    Wiseth, Rune
    Bjerve, Kristian
    Brurok, Heidi
    Gunnes, Sigurd
    Skarra, Sissel
    Jynge, Per
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Oxidative stress and myocardial damage during elective percutaneous coronary interventions and coronary angiography. A comparison of blood-borne isoprostane and troponin release.2004In: Free Radic Res, ISSN 1071-5762, Vol. 38, no 5, p. 517-25Article in journal (Refereed)
  • 29.
    Bjermo, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dahlman, Ingrid
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Persson, Lena
    Berglund, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Pulkki, Kari
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Uusitupa, Matti
    Rudling, Mats
    Arner, Peter
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial2012In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 95, no 5, p. 1003-1012Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Replacing SFAs with vegetable PUFAs has cardiometabolic benefits, but the effects on liver fat are unknown. Increased dietary n-6 PUFAs have, however, also been proposed to promote inflammation-a yet unproven theory.

    OBJECTIVE:

    We investigated the effects of PUFAs on liver fat, systemic inflammation, and metabolic disorders.

    DESIGN:

    We randomly assigned 67 abdominally obese subjects (15% had type 2 diabetes) to a 10-wk isocaloric diet high in vegetable n-6 PUFA (PUFA diet) or SFA mainly from butter (SFA diet), without altering the macronutrient intake. Liver fat was assessed by MRI and magnetic resonance proton (1H) spectroscopy (MRS). Proprotein convertase subtilisin/kexin type-9 (PCSK9, a hepatic LDL-receptor regulator), inflammation, and adipose tissue expression of inflammatory and lipogenic genes were determined.

    RESULTS:

    A total of 61 subjects completed the study. Body weight modestly increased but was not different between groups. Liver fat was lower during the PUFA diet than during the SFA diet [between-group difference in relative change from baseline; 16% (MRI; P < 0.001), 34% (MRS; P = 0.02)]. PCSK9 (P = 0.001), TNF receptor-2 (P < 0.01), and IL-1 receptor antagonist (P = 0.02) concentrations were lower during the PUFA diet, whereas insulin (P = 0.06) tended to be higher during the SFA diet. In compliant subjects (defined as change in serum linoleic acid), insulin, total/HDL-cholesterol ratio, LDL cholesterol, and triglycerides were lower during the PUFA diet than during the SFA diet (P < 0.05). Adipose tissue gene expression was unchanged.

    CONCLUSIONS:

    Compared with SFA intake, n-6 PUFAs reduce liver fat and modestly improve metabolic status, without weight loss. A high n-6 PUFA intake does not cause any signs of inflammation or oxidative stress. Downregulation of PCSK9 could be a novel mechanism behind the cholesterol-lowering effects of PUFAs.

  • 30. Bräsen, Jan Hinrich
    et al.
    Leppänen, Olli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Inkala, Matias
    Heikura, Tommi
    Levin, Max
    Ahrens, Fabian
    Rutanen, Juha
    Pietsch, Hubertus
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Levonen, Anna-Liisa
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Zeller, Thomas
    Klöppel, Günter
    Laukkanen, Mikko O
    Ylä-Herttuala, Seppo
    Extracellular superoxide dismutase accelerates endothelial recovery and inhibits in-stent restenosis in stented atherosclerotic Watanabe heritable hyperlipidemic rabbit aorta2007In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 50, no 23, p. 2249-2253Article in journal (Refereed)
    Abstract [en]

    This study examined whether local gene therapy with extracellular superoxide dismutase (EC-SOD) could inhibit in-stent restenosis in atherosclerotic Watanabe heritable hyperlipidemic rabbits.

    Background

    Stenting causes an acute increase in superoxide anion production and oxidative stress; EC-SOD is a major component of antioxidative defense in blood vessels and has powerful cardioprotective effects in ischemic myocardium.

    Methods

    Endothelial denudation and stenting were done in 36 adult (15 to 18 months old) rabbits. Catheter-mediated intramural delivery of clinical good manufacturing practice-grade adenoviruses encoding rabbit EC-SOD were done simultaneously with stenting. Control animals received adenovirus-encoding nuclear-targeted β-galactosidase (AdLacZ). Circulating markers for oxidative stress (nonesterified 8-iso-prostaglandin F2 alpha) were measured. Analysis of 6-day, 28-day, and 90-day vessel histology, radical production, oxidation-specific epitopes, and expression studies were performed.

    Results

    The EC-SOD treatment reduced oxidant production in stented vessels compared with control vessels. Early systemic recovery of total SOD activity was observed in the treated rabbits. The EC-SOD significantly accelerated endothelial recovery (67.4% ± 10.8% vs. 24.2.1% ± 4.6% at 6 days, p < 0.05; 89.3% ± 3.7% vs. 45.1% ± 9.6% at 28 days, p < 0.05), and the beneficial effect involved increased proliferation of regenerating endothelium. The EC-SOD group showed a 61.3% lower (p < 0.05) neointimal formation at 28 days, with a similar, albeit nonsignificant trend at 90 days (1.20 ± 0.32 mm2 vs. 1.88 ± 0.24 mm2, p = 0.06).

    Conclusions

    The results suggest a central pathogenetic role of oxidation sensitive signaling processes in endothelial recovery and developing in-stent restenosis in atherosclerotic vessels. Local therapy against oxidative stress represents a promising therapeutic strategy in stent-induced vascular injury.

    Extracellular Superoxide Dismutase Accelerates Endothelial Recovery and Inhibits In-Stent Restenosis in Stented Atherosclerotic Watanabe Heritable Hyperlipidemic Rabbit Aorta

    Jan Hinrich Bräsen, Olli Leppänen, Matias Inkala, Tommi Heikura, Max Levin, Fabian Ahrens, Juha Rutanen, Hubertus Pietsch, David Bergqvist, Anna-Liisa Levonen, Samar Basu, Thomas Zeller, Günter Klöppel, Mikko O. Laukkanen, Seppo Ylä-Herttuala

    Percutaneous coronary interventions induce oxidative stress in vessels that already have compromised antioxidative defenses. Extracellular superoxide dismutase (EC-SOD) is a major antioxidant in healthy arteries, and exogenous EC-SOD confers powerful vasculoprotective and cardioprotective effects. However, the effects of EC-SOD therapy on stent-induced vascular injury have not been assessed. We present evidence showing that local therapy with EC-SOD, delivered using clinical-grade adenoviruses, attenuated tissue oxidant production, suppressed developing in-stent restenosis, and accelerated endothelial recovery.

  • 31. Bräuner, Elvira Vaclavik
    et al.
    Forchhammer, Lykke
    Møller, Peter
    Barregard, Lars
    Gunnarsen, Lars
    Afshari, Alireza
    Wåhlin, Peter
    Glasius, Marianne
    Dragsted, Lars Ove
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Raaschou-Nielsen, Ole
    Loft, Steffen
    Indoor particles affect vascular function in the aged: an air filtration-based intervention study.2008In: Am J Respir Crit Care Med, ISSN 1535-4970, Vol. 177, no 4, p. 419-25Article in journal (Refereed)
  • 32. Casadesus, Gemma
    et al.
    Smith, Mark A.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Hua, Jing
    Capobianco, Dae E.
    Siedlak, Sandra L.
    Zhu, Xiongwei
    Perry, George
    Increased isoprostane and prostaglandin are prominent in neurons in Alzheimer disease2007In: Molecular Neurodegeneration, ISSN 1750-1326, Vol. 2, no 1, p. 2-Article in journal (Refereed)
    Abstract [en]

    Background

    Inflammation and oxidative stress are both involved in the pathogenesis of Alzheimer disease and have been shown to be reciprocally linked. One group of molecules that have been directly associated with inflammation and the production of free radicals are the prostaglandin 13,14-dihydro 15-keto PGFand the isoprostane 8-iso-PGF.

    Results

    To further delineate the role of inflammatory and oxidative parameters in Alzheimer disease, in this study we evaluated the amount and localization of 13,14-dihydro 15-keto PGFand 8-iso-PGFin hippocampal post mortem tissue samples from age-matched Alzheimer disease and control patients. Our results demonstrate increased levels of 13,14-dihydro 15-keto PGFand 8-iso-PGFin the hippocampal pyramidal neurons of Alzheimer disease patients when compared to control patients.

    Conclusion

    These data not only support the shared mechanistic involvement of free radical damage and inflammation in Alzheimer disease, but also indicate that multiple pathogenic "hits" are likely necessary for both the development and propagation of Alzheimer disease.

  • 33.
    Cederberg, Jonas
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Basu, Samar
    Department of Public Health and Caring Sciences.
    Eriksson, Ulf J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Increased rate of lipid peroxidation and protein carbonylation inexperimental diabetic pregnancy.2001In: Diabetologia, Vol. 44, p. 766-774Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Diabetic pregnancy displays increased incidence of congenital malformations and elevated levels of lipid peroxides in the offspring. The aim of the present work was to study if exogenous administration of one lipid peroxide, the isoprostane 8-iso-PGF(2alpha), is teratogenic per se in rat embryos in vitro, and if such teratological effects may be diminished by supplementation of an antioxidative agent, i.e., N-acetylcysteine or superoxide dismutase, to the culture medium. METHODS: Day-9 embryos were cultured in vitro for 48 hr and subjected to 8-iso-PGF(2alpha) with and without N-acetylcysteine or superoxide dismutase. RESULTS: Addition of 2 micromol/l of the isoprostane 8-iso-PGF(2alpha) to the culture medium caused high malformation rate, decreased protein and DNA contents, decreased somite number and crown-rump-length as well as marked accumulation of the isoprostane in the embryonic tissues. Adding N-acetylcysteine or superoxide dismutase to the culture medium with isoprostane normalized almost all morphological and biochemical parameters, including the elevated tissue concentration of 8-iso-PGF(2alpha). CONCLUSIONS: Results indicate that the isoprostane (8-iso-PGF(2alpha)) serves both as an oxidative stress indicator and a teratogenic agent. The findings support earlier studies of enhanced oxidative stress and increased malformation rate in embryos exposed to a diabetes-like environment, and suggest prevention of dysmorphogenesis by administration of antioxidative agents.

  • 34.
    Clausen, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Interstitial F2-Isoprostane 8-Iso-PGF As a Biomarker of Oxidative Stress after Severe Human Traumatic Brain Injury2012In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, no 5, p. 766-775Article in journal (Refereed)
    Abstract [en]

    Oxidative stress is a major contributor to the secondary injury process after experimental traumatic brain injury (TBI). The importance of oxidative stress in the pathobiology of human TBI is largely unknown. The F(2)-isoprostane 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)), synthesized in vivo through non-enzymatic free radical catalyzed peroxidation of arachidonic acid, is a widely used biomarker of oxidative stress in multiple disease states, including TBI and cerebral ischemia/reperfusion. Our hypothesis is that harvesting of biomarkers directly in the injured brain by cerebral microdialysis (MD) is advantageous because of its high spatial and temporal resolution compared to blood or cerebrospinal fluid sampling. The aim of this study was to test the feasibility of measuring 8-iso-PGF(2α) in MD, ventricular cerebrospinal fluid (vCSF), and plasma samples collected from patients with severe TBI, and to compare the MD signals with MD-glycerol, implicated as a biomarker of oxidative stress, as well as MD-glutamate, a biomarker of excitotoxicity. Six patients (4 men, 2 women) were included in the study, three of whom had a focal/mixed TBI, and three a diffuse axonal injury (DAI). Following the bedside analysis of routine MD biomarkers (glucose, lactate:pyruvate ratio, glycerol, and glutamate), two 12-h MD samples per day were used to analyze 8-iso-PGF(2α) from 24 h up to 8 days post-injury. The interstitial levels of 8-iso-PGF(2α) were markedly higher than the levels obtained from plasma and vCSF (p<0.05), supporting our hypothesis. The MD-8-iso-PGF(2α) levels correlated strongly (p<0.05) with MD-glycerol and MD-glutamate, which are widely used biomarkers of membrane phospholipid degradation/oxidative stress and excitotoxicity, respectively. This study demonstrates the feasibility of analyzing 8-iso-PGF(2α) in MD samples from the human brain. Our results support a close relationship between oxidative stress and excitotoxicity following human TBI. MD-8-iso-PGF(2α) in combination with MD-glycerol may be useful biomarkers of oxidative stress in the neurointensive care setting.

  • 35. De Jong, A
    et al.
    Plat, J
    Bast, A
    Godschalk, R W L
    Basu, S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Mensink, R P
    Effects of plant sterol and stanol ester consumption on lipid metabolism, antioxidant status and markers of oxidative stress, endothelial function and low-grade inflammation in patients on current statin treatment2008In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 62, no 2, p. 263-73Article in journal (Refereed)
    Abstract [en]

    Objective: The present study was designed to examine for the first time, side-by-side, the effects of plant sterol and stanol consumption on lipid metabolism and markers of antioxidant status, oxidative stress, endothelial dysfunction and low-grade inflammation in subjects on stable statin-treatment. Design: Double-blind, randomized, placebo-controlled, intervention trial. Setting: University. Subjects: Forty-five patients on current statin treatment were recruited via newspaper advertisements. Data of 41 patients were used in statistical analysis. Intervention: Subjects consumed margarine with no added plant sterols or stanols for 4 weeks and were then divided into three groups of 15 subjects. For the next 16 weeks, one group continued with the control margarine and the other two groups with either a plant sterol- or stanol (2.5 g/day)-enriched margarine. Blood was sampled at the end of the run-in and intervention periods. Results: Plant sterol and stanol consumption significantly (P = 0.026) reduced low-density lipoprotein (LDL) cholesterol by 0.34 mmol/l (95% confidence interval (CI), -0.67 to -0.04 mmol/l). No effects were shown on enzymatic and non-enzymatic antioxidants and markers of oxidative modification of lipids and DNA. In addition, no effect was found on soluble adhesion molecules, C-reactive protein and monocyte chemotactic protein-1 concentrations. Conclusions: We conclude that 16 weeks of plant sterol or stanol consumption did not affect markers of antioxidant status, oxidative stress, endothelial dysfunction and low-grade inflammation in patients on stable statin treatment, despite a significant reduction of LDL cholesterol.

  • 36.
    Degerman Gunnarsson, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lindau, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Blennow, K
    Darreh-Shori, T
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Nordberg, A
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Basun, H
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Pittsburgh compound-B and Alzheimer's disease biomarkers in CSF, plasma and urine: An exploratory study2010In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 29, no 3, p. 204-212Article in journal (Refereed)
    Abstract [en]

    Background:

    The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PIB) is an in vivo ligand for measuring β-amyloid (Aβ) load. Associations between PET PIB and cerebrospinal fluid (CSF) Aβ1–42 and apolipoprotein E ε4 (APOE ε4) have been observed in several studies, but the relations between PIB uptake and other biomarkers of Alzheimer’s disease (AD) are less investigated.

    Method:

    PET PIB, PET 18Fluoro-2-deoxy-D-glucose and different AD biomarkers were measured twice in CSF, plasma and urine 12 months apart in 10 patients with a clinical diagnosis of mild to moderate AD.

    Results:

    PIB retention was constant over 1 year, inversely related to low CSF Aβ1–42 (p = 0.01) and correlated positively to the numbers of the APOE ε4 allele (0, 1 or 2) (p = 0.02). There was a relation between mean PIB retention and CSF ApoE protein (r = –0.59, p = 0.07), and plasma cystatin C (r = –0.56, p = 0.09).

    Conclusion:

    PIB retention is strongly related to CSF Aβ1–42, and to the numbers of the APOE ε4 allele.

  • 37. Dragsted, Lars O
    et al.
    Pedersen, Anette
    Hermetter, Albin
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Hansen, Max
    Haren, Gitte R
    Kall, Morten
    Breinholt, Vibeke
    Castenmiller, Jacqueline J M
    Stagsted, Jan
    Jakobsen, Jette
    Skibsted, Leif
    Rasmussen, Salka E
    Loft, Steffen
    Sandström, Brittmarie
    The 6-a-day study: effects of fruit and vegetables on markers of oxidative stress and antioxidative defense in healthy nonsmokers.2004In: Am J Clin Nutr, ISSN 0002-9165, Vol. 79, no 6, p. 1060-72Article in journal (Refereed)
  • 38. Eichhorn, Judith C P
    et al.
    Lee, Rosalind
    Dunster, Christina
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kelly, Frank J
    Alpha- and gamma-tocopherol plasma and urinary biokinetics following alpha-tocopherol supplementation.2004In: Ann N Y Acad Sci, ISSN 0077-8923, Vol. 1031, p. 339-40Article in journal (Refereed)
  • 39.
    Ekström, Eva-Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Lindström, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Raqib, Rubhana
    El Arifeen, Shams
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Brismar, Kerstin
    Selling, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Persson, Lars-Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Effects of prenatal micronutrient and early food supplementation on metabolic status of the offspring at 4.5 years of age. The MINIMat randomized trial in rural Bangladesh.2016In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 45, no 5, p. 1656-1667Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Fetal nutritional insults may alter the later metabolic phenotype. We hypothesized that early timing of prenatal food supplementation and multiple micronutrient supplementation (MMS) would favourably influence childhood metabolic phenotype.

    METHODS: Pregnant women recruited 1 January to 31 December 2002 in Matlab, Bangladesh, were randomized into supplementation with capsules of either 30 mg of iron and 400 μg of folic acid, 60 mg of iron and 400 μg of folic acid, or MMS containing a daily allowance of 15 micronutrients, and randomized to food supplementation (608 kcal) either with early invitation (9 weeks' gestation) or usual invitation (at 20 weeks). Their children (n = 1667) were followed up at 4.5 years with assessment of biomarkers of lipid and glucose metabolism, inflammation and oxidative stress.

    RESULTS: Children in the group with early timing of food supplementation had lower cholesterol (difference -0.079 mmol/l, 95% confidence interval (CI) -0.156; -0.003), low-density lipoprotein (LDL) (difference -0.068 mmol/l, 95% CI -0.126; -0.011) and ApoB levels (difference -0.017 g/l, 95% CL -0.033; -0.001). MMS supplementation resulted in lower high-density lipoprotein (HDL) (difference -0.028 mmol/l, 95% CL -0.053; -0.002), lower glucose (difference -0.099 mmol/l, 95% CL -0.179; -0.019) and lower insulin-like growth factor 1 (IGF-1) (difference on log scale -0.141 µg/l, 95% CL -0.254; -0.028) than 60 mg iron and 400 μg folic acid. There were no effects on markers of inflammation or oxidative stress.

    CONCLUSIONS: Findings suggest that in a population where malnutrition is prevalent, nutrition interventions during pregnancy may modify the metabolic phenotype in the young child that could have consequences for later chronic disease risks.

  • 40. Fischer, C P
    et al.
    Hiscock, N J
    Penkowa, M
    Basu, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kallner, A
    Sjöberg, L-B
    Pedersen, B K
    Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle2004In: J Physiol, no 558, p. 633-645Article in journal (Refereed)
  • 41. Fischer, C.P
    et al.
    Hiscock, N.J
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kallner, Anders
    Sjöberg, Lars-Börje
    Febbraio, M.A
    Pedersen, B.K
    Vitamin E isoform-specific inhibition of the exercise-induced heat shock protein 72 expression in humans2006In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 100, no 5, p. 1679-1687Article in journal (Refereed)
    Abstract [en]

    Increased levels of reactive oxygen and nitrogen species, as seen in response to exercise, challenge the cellular integrity. Important protective adaptive changes include induction of heat shock proteins (HSPs). We hypothesized that supplementation with antioxidant vitamins C (ascorbic acid) and E (tocopherol) would attenuate the exercise-induced increase of HSP72 in the skeletal muscle and in the circulation. Using randomization, we allocated 21 young men into three groups receiving one of the following oral supplementations: RRR-α-tocopherol 400 IU/ day + ascorbic acid (AA) 500 mg/day (CEα), RRR-α-tocopherol 290 IU/day + RRR-γ-tocopherol 130 IU/day + AA 500 mg/day (CEαγ), or placebo (Control). After 28 days of supplementation, the subjects performed 3 h of knee extensor exercise at 50% of the maximal power output. HSP72 mRNA and protein content was determined in muscle biopsies obtained from vastus lateralis at rest (0 h), postexercise (3 h), and after a 3-h recovery (6 h). In addition, blood was sampled for measurements of HSP72, α-tocopherol, γ-tocopherol, AA, and 8-isoprostaglandin-F (8-PGF). Postsupplementation, the groups differed with respect to plasma vitamin levels. The marker of lipid peroxidation, 8-iso-PGF, increased from 0 h to 3 h in all groups, however, markedly less (P < 0.05) in CEα. In Control, skeletal muscle HSP72 mRNA content increased 2.5-fold (P < 0.05) and serum HSP72 protein increased 4-fold (P < 0.05) in response to exercise, whereas a significant increase of skeletal muscle HSP72 protein content was not observed (P = 0.07). In CEα, skeletal muscle HSP72 mRNA, HSP72 protein, and serum HSP72 were not different from Control in response to exercise. In contrast, the effect of exercise on skeletal muscle HSP72 mRNA and protein, as well as circulating HSP72, was completely blunted in CEαγ. The results indicate that γ-tocopherol comprises a potent inhibitor of the exercise-induced increase of HSP72 in skeletal muscle as well as in the circulation.

  • 42.
    Florvall, Gösta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hemocue urine albumin point-of-care test shows strong agreement with the results obtained with a large nephelometer2006In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 29, no 2, p. 422-423Article in journal (Refereed)
  • 43.
    Florvall, Gösta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Apolipoprotein A1 Is a Stronger Prognostic Marker Than Are HDL and LDL Cholesterol for Cardiovascular Disease and Mortality in Elderly Men2006In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 61, no 12, p. 1262-1266Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare apolipoprotein A1 (ApoA1) and B (ApoB) with high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) as markers for cardiovascular mortality and morbidity in elderly men. We analyzed serum ApoA1, ApoB, total cholesterol, HDL-C, and LDL-C in a group of 77-year-old men (n = 785). The results were correlated with data from the Swedish cause of death registry. Receiver-operating characteristic curves showed that, of the studied serum markers, ApoA1 was the best predictor for ischemic heart disease mortality (area under the curve = 0.724, 95% confidence interval, 0.691-0.755). There were also significant correlations between the apolipoproteins and other known risk markers for cardiovascular disease such as triglycerides, high-sensitivity C-reactive protein (hsCRP), and cystatin C. Serum ApoA1 is a better risk marker than are ApoB, ApoB/ApoA1 ratio, HDL-C, and LDL-C for cardiovascular disease and mortality in elderly men.

  • 44. Freund-Levi, Yvonne
    et al.
    Vedin, Inger
    Hjorth, Erik
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Irving, Gerd Faxen
    Schultzberg, Marianne
    Eriksdotter, Maria
    Palmblad, Jan
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Wahlund, Lars-Olof
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Effects of Supplementation with Omega-3 Fatty Acids on Oxidative Stress and Inflammation in Patients with Alzheimer's Disease: The OmegAD Study2014In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 42, no 3, p. 823-831Article in journal (Refereed)
    Abstract [en]

    Background: Oxidative stress and inflammation are two key mechanisms suggested to be involved in the pathogenesis of Alzheimer's disease (AD). Omega-3 fatty acids (omega-3 FAs) found in fish and fish oil have several biological properties that may be beneficial in AD. However, they may also auto-oxidize and induce in vivo lipid peroxidation. Objective: The objective of this study was to evaluate systemic oxidative stress and inflammatory biomarkers following oral supplementation of dietary omega-3 FA. Methods: Forty patients with moderate AD were randomized to receive 1.7 g DHA (22:6) and 0.6 g EPA (20:5) or placebo for 6 months. Urinary samples were collected before and after supplementation. The levels of the major F-2-isoprostane, 8-iso-PGF(2 alpha) a consistent in vivo biomarker of oxidative stress, and 15-keto-dihydro-PGF(2 alpha), a major metabolite of PGF(2 alpha) and biomarker of inflammatory response, were measured. Results: F-2-isoprostane in urine increased in the placebo group after 6 months, but therewas no clear difference in treatment effect between supplemented and non-supplemented patients on the urinary levels of F-2-isoprostanes and 15-keto-dihydro-PGF(2 alpha). At baseline, the levels of 15-keto-dihydro-PGF(2 alpha) showed negative correlative relationships to omega-3 FAs, and a positive correlation to linoleic acid. 8-iso-PGF(2 alpha) correlated negatively to the omega-6 FA arachidonic acid. Conclusion: The findings indicate that supplementation of omega-3 FAs to patients with AD for 6 months does not have a clear effect on free radical-mediated formation of F-2-isoprostane or cyclooxygenase-mediated formation of prostaglandin F-2 alpha. The correlative relationships to FAs indicate a potential role of FAs in immunoregulation.

  • 45. Garcia-Rodriguez, Cruz E.
    et al.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Dolores Mesa, Maria
    Miles, Elizabeth A.
    Noakes, Paul S.
    Vlachava, Maria
    Kremmyda, Lefkothea-Stella
    Diaper, Norma D.
    Godfrey, Keith M.
    Calder, Philip C.
    Gil, Angel
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Does Increased Intake of Salmon Increase Markers of Oxidative Stress in Pregnant Women?: The Salmon in Pregnancy Study2011In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 15, no 11, p. 2819-2823Article in journal (Refereed)
    Abstract [en]

    The Salmon in Pregnancy Study provided two meals of salmon per week to pregnant women from week 20 of gestation; the control group maintained their habitual diet low in oily fish. Salmon is a rich source of marine n-3 fatty acids. Since marine n-3 fatty acids may increase oxidative stress, we investigated whether increased salmon consumption could affect markers of oxidative stress in mid and late pregnancy. Urinary 8-iso-prostaglandin F(2 alpha), urinary 8-hydroxy-2'-deoxyguanosine, and plasma lipid peroxide concentrations did not change from week 20 to 38 of pregnancy and were not altered by increased consumption of salmon. Thus, increased intake of salmon during pregnancy does not increase oxidative stress, as judged by the markers of oxidative damage to lipids and DNA measured herein.

  • 46. Guron, Gregor S
    et al.
    Grimberg, Elisabeth S
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Herlitz, Hans
    Acute effects of the superoxide dismutase mimetic tempol on split kidney function in two-kidney one-clip hypertensive rats.2006In: J Hypertens, ISSN 0263-6352, Vol. 24, no 2, p. 387-94Article in journal (Refereed)
  • 47.
    Halvorsen, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Neural injury after use of vasopressin and adrenaline during porcine cardiopulmonary resuscitation2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 1, p. 11-19Article in journal (Refereed)
    Abstract [en]

    Background. Our aim was to investigate cerebral and cardiac tissue injury subsequent to use of vasopressin and adrenaline in combination compared with vasopressin alone during cardiopulmonary resuscitation (CPR). Methods. In a randomized, prospective, laboratory animal study 28 anesthetized piglets were subject to a 12-min untreated cardiac arrest and subsequent CPR. After 1 min of CPR, 10 of the piglets received 0.4 U/kg of arg(8)-vasopressin (V group), and 10 piglets received 0.4 U/kg of arg(8)-vasopressin, 1 min later followed by 20 mu g/kg body weight of adrenaline, and another 1 min later continuous administration (10 mu g/kg/min) of adrenaline (VA group). After 8 min of CPR, the piglets were defibrillated and monitored for another 3 h. Then they were killed and the brain immediately removed pending histological analysis. Results. During CPR, the VA group had higher mean blood pressure and cerebral cortical blood flow (CCBF) but similar coronary perfusion pressure. After restoration of spontaneous circulation there was no difference in the pressure variables, but CCBF tended to be (36% +/- 16%) higher in the V group. Neuronal injury and signs of a disrupted blood-brain barrier (BBB) were greater, 20% +/- 4% and 21% +/- 4%, respectively, in the VA group. In a background study of repeated single doses of adrenaline every third minute after 5 min arrest but otherwise the same protocol, histological measurements showed even worse neural injury and disruption of the BBB. Conclusion. Combined use of vasopressin and adrenaline caused greater signs of cerebral and cardiac injury than use of vasopressin alone during experimental cardiopulmonary resuscitation.

  • 48. Hansson, Patrik
    et al.
    Barregard, Lars
    Halltorp, Melina
    Sibthorpe, Sara
    Svelander, Cecilia
    Sandberg, Ann-Sofie
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Hoppe, Michael R.
    Hulthen, Lena
    Habitual high intake of fatty fish is related to lower levels of F-2-isoprostane in healthy women2015In: Nutrition (Burbank, Los Angeles County, Calif.), ISSN 0899-9007, E-ISSN 1873-1244, Vol. 31, no 6, p. 847-852Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to determine whether habitual dietary intake of fatty fish, whole grains, fruits and vegetables, or a combination of them all, is associated with oxidative stress levels, measured as urine concentration of 8-iso-prostaglandin F-2 alpha (8-iso-PGF(2 alpha)) in healthy women. Methods: Eighty-one participants were included in this cross-sectional study. Mean age of the women was 26.1 +/- 6.2 (mean SD) years and mean body mass index (BMI) was 22.4 +/- 3.0 kg/m(2). The concentration of 8-iso-PGF(2 alpha) was determined in urine, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels were determined in blood. Participants' habitual fish, whole grain, fruit, and vegetable intake was estimated from a food frequency questionnaire. Results: In the multivariate analysis, there was a significant inverse association between 8-iso-PGF(2 alpha) and high fatty fish intake (P < 0.001). Fatty fish intake was positively correlated to serum phospholipid concentrations of EPA (P = 0.001) and DHA (P = 0.002). A borderline effect of DHA was seen on 8-iso-PGF(2 alpha), but higher serum phospholipid concentrations of fatty acids were generally not related to lower F-2-isoprostane levels. No overall effect from whole grains or fruits and vegetables Was seen. Conclusions: The results indicate that high intake of fatty fish is related to lower levels of oxidative stress, but high levels of omega-3 fatty acids in intake may not alone explain the effect High habitual intake of whole grains or fruits and vegetables did not seem to affect the Fa-isoprostane level.

  • 49. Harris, Holly
    et al.
    Wolk, Alicja
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Vasson, Marie-Paule
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Soluble vascular endothelial growth factor receptors 2 (sVEGFR-2) and 3 (sVEGFR-3) and breast cancer risk in the Swedish Mammography Cohort2016In: International Journal of Molecular Epidemiology and Genetics, ISSN 1948-1756, E-ISSN 1948-1756, Vol. 7, no 1, p. 81-86Article in journal (Refereed)
    Abstract [en]

    Vascular endothelial growth factor (VEGF) is a signalling protein that has been established as a contributor to tumor angiogenesis, and expression of VEGF and its soluble receptors (sVEGFR2 and sVEGFR3) have been demonstrated in breast cancer cells. However, no prospective studies have examined the association between prediagnostic sVEGFR levels and breast cancer risk. We conducted a prospective case-control study nested within the Swedish Mammography Cohort examining the association between sVEGFR2 and 3 levels and breast cancer risk. The analysis included 69 incident breast cancer cases diagnosed after blood collection and 719 controls. Logistic regression models were used to calculate odds ratios and 95% confidence intervals. After adjustment for breast cancer risk factors, sVEGFR2 levels were associated with breast cancer risk (OR=1.28; 95% CI=1.06-1.56 per 1000 ng/L increase in concentration) while sVEGFR3 levels were not related to such risk (OR=1.00; 95% CI=0.93-1.07). Our results suggest that sVEGFR2 levels may be positively associated with breast cancer risk, however future studies with larger case groups are necessary to confirm this association.

  • 50. Helal, O.
    et al.
    Defoort, C.
    Robert, S.
    Marin, C.
    Lesavre, N.
    Lopez-Miranda, J.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Basu, Samur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Lovegrove, J.
    McMonagle, J.
    Roche, H. M.
    Dignat-George, F.
    Lairon, D.
    Increased levels of microparticles originating from endothelial cells, platelets and erythrocytes in subjects with metabolic syndrome: Relationship with oxidative stress2011In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 21, no 9, p. 665-671Article in journal (Refereed)
    Abstract [en]

    Background and aims: The Metabolic Syndrome (MetS) is associated with increased cardiovascular risk. Circulating microparticles (MP) are involved in the pathogenesis of atherothrombotic disorders and are raised in individual with CVD. We measured their level and cellular origin in subjects with MetS and analyzed their associations with 1/anthropometric and biological parameters of MetS, 2/inflammation and oxidative stress markers.

    Methods and results: Eighty-eight subjects with the MetS according to the NCEP-ATPIII definition were enrolled in a bicentric study and compared to 27 healthy controls. AnnexinV-positive MP (TMP), MP derived from platelets (PMP), erythrocytes (ErMP), endothelial cells (EMP), leukocytes (LMP) and granulocytes (PNMP) were determined by flow cytometry. MetS subjects had significantly higher counts/mu l of TMP (730.6 +/- 49.7 vs 352.8 +/- 35.6), PMP (416.0 +/- 43.8 vs 250.5 +/- 23.5), ErMP (243.8 +/- 22.1 vs 73.6 +/- 19.6) and EMP (7.8 +/- 0.8 vs 4.0 +/- 1.0) compared with controls. LMP and PNMP were not statistically different between groups. Multivariate analysis demonstrated that each criterion for the MetS influenced the number of TMP. Waist girth was a significant determinant of PMP and EMP level and blood pressure was correlated with EMP level. Glycemia positively correlated with PMP level whereas dyslipidemia influenced EMP and ErMP levels. Interestingly, the oxidative stress markers, plasma glutathione peroxy-dase and urinary 8-iso-prostaglandin F(2) alpha, independently influenced TMP and PMP levels whereas inflammatory markers did not, irrespective of MP type.

    Conclusion: Increased levels of TMP, PMP, ErMP and EMP are associated with individual metabolic abnormalities of MetS and oxidative stress. Whether MP assessment may represent a marker for risk stratification or a target for pharmacological intervention deserves further investigation.

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