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  • 1.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Fatty acid oxidation and isoprostanes: oxidative strain and oxidative stress2010In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 82, no 4-6, p. 219-225Article in journal (Refereed)
    Abstract [en]

    Oxidative stress is implicated as one of the key causes underlying many diseases. Free radicals are important constituents of basal physiology. Assessment of free radicals or the end products of their action has proved to be difficult. Consequently, authentication of the contribution of free radicals to physiology and pathology has usually been equivocal. Isoprostanes are biosynthesized in vivo, predominantly through free radical attack on arachidonic acid and are now regarded as robust biomarkers of oxidative stress in vivo. Isoprostanes are associated with many human diseases, and their concentration is altered over the course of normal human pregnancy, but their (patho)physiological roles have not yet been clearly defined. Measurement of F-2-isoprostanes in body fluids could offer a unique analytical opportunity to study the role of free radicals in physiology and pathophysiology in order to comprehend both oxidative strain and oxidative stress.

     

  • 2.
    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)
  • 3.
    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.

  • 4.
    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.

  • 5.
    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.

  • 6.
    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.

  • 7.
    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.
    Miclescu, Adriana
    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.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Propofol mitigates systemic oxidative injury during experimental cardiopulmonary cerebral resuscitation2011In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 84, no 5-6, p. 123-130Article in journal (Refereed)
    Abstract [en]

    Effects of propofol, an intravenous anesthetic agent that exerts potent antioxidant properties, were investigated in an experimental model of cardiac arrest and cardiopulmonary resuscitation. An extended cardiac arrest with 15 randomized piglets was studied to assess the effect of propofol or its solvent intralipid as the control group. Oxidative stress (as measured by a major F(2)-isoprostane) and inflammation (a major metabolite of PGF(2α)) were evaluated in addition to the hemodynamic evaluation, protein S-100β and in situ tissue brain damage by immunochemistry at sacrifice after 3h of reperfusion following cardiac arrest and restoration of spontaneous circulation (ROSC). ROSC increased jugular bulb plasma levels of F(2)-isoprostane and PGF(2α) metabolite significantly more in controls than in the propofol-treated group. In situ tissue damage after ischemia-reperfusion was variable among the pigs at sacrifice, but tended to be greater in the control than the propofol-treated group. Propofol significantly reduced an ROSC-mediated oxidative stress in the brain.

  • 8.
    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.

  • 9.
    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.

  • 10. Bendsen, Nathalie T.
    et al.
    Stender, Steen
    Szecsi, Pal B.
    Pedersen, Steen B.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Hellgren, Lars I.
    Newman, John W.
    Larsen, Thomas M.
    Haugaard, Steen B.
    Astrup, Arne
    Effect of industrially produced trans fat on markers of systemic inflammation: evidence from a randomized trial in women2011In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 52, no 10, p. 1821-1828Article in journal (Refereed)
    Abstract [en]

    Consumption of industrially produced trans fatty acids (IP-TFA) has been positively associated with systemic markers of low-grade inflammation and endothelial dysfunction in cross-sectional studies, but results from intervention studies are inconclusive. Therefore, we conducted a 16 week double-blind parallel intervention study with the objective to examine the effect of IP-TFA intake on bio-markers of inflammation, oxidative stress, and endothelial dysfunction. Fifty-two healthy overweight postmenopausal women (49 completers) were randomly assigned to receive either partially hydrogenated soybean oil (15.7 g/day IP-TFA) or control oil without IP-TFA. After 16 weeks, IP-TFA intake increased baseline-adjusted serum tumor necrosis factor (TNF) alpha by 12% [95% confidence interval (CI): 5-20; P = 0.002] more in the IP-TFA group compared with controls. Plasma soluble TNF receptors 1 and 2 were also increased by IP-TFA [155 pg/ml (CI: 63-247); P < 0.001 and 480 pg/ml (CI: 72-887); P = 0.02, respectively]. Serum C-reactive protein, interleukin (IL) 6 and adiponectin and subcutaneous abdominal adipose tissue mRNA expression of IL6, IL8, TNF alpha, and adiponectin as well as ceramide content were not affected by IP-TFA, nor was urinary 8-iso-prostaglandin-F(2 alpha). In conclusion, this dietary trial indicates that the mechanisms linking dietary IP-TFA to cardiovascular disease may involve activation of the TNF alpha system.

  • 11. 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.

  • 12.
    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.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dahlman, Ingrid
    Karolinska Institutet, Department of Medicine.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Persson, Lena
    Karolinska Institutet, Department of Endocrinology, Metabolism and Diabetes.
    Berglund, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Pulkki, Kari
    University of Eastern Finland, Department of Clinical Chemistry and Eastern Finland Laboratory Centre.
    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
    University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Clinical Nutrition.
    Rudling, Mats
    Karolinska Institutet, Department of Endocrinology, Metabolism and Diabetes.
    Arner, Peter
    Karolinska Institutet, Department of Medicine.
    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.
    Dietary fat modification and liver fat content in abdominal obesityManuscript (preprint) (Other academic)
  • 13.
    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.

  • 14.
    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.

  • 15.
    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.

  • 16. Delgado-Lista, J.
    et al.
    Perez-Martinez, P.
    Garcia-Rios, A.
    Phillips, C. M.
    Williams, C. M.
    Gulseth, H. L.
    Helal, O.
    Blaak, E. E.
    Kiec-Wilk, B.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Drevon, C. A.
    Defoort, C.
    Saris, W. H.
    Wybranska, I.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lovegrove, J. A.
    Roche, H. M.
    Lopez-Miranda, J.
    Pleiotropic effects of TCF7L2 gene variants and its modulation in the metabolic syndrome: From the LIPGENE study2011In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 214, no 1, p. 110-116Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Variants of the TCF7L2 gene predict the development of type 2 diabetes mellitus (T2DM). We investigated the associations between gene variants of TCF7L2 and clinical features of the metabolic syndrome (MetS) (an entity often preceeding T2DM), and their interaction with non-genetic factors, including plasma saturated fatty acids (SFA) concentration and insulin resistance (IR). Methods: Fasting lipid profiles, insulin sensitivity, insulin secretion, anthropometrics, blood pressure and 10 gene variations of the TCF7L2 gene were determined in 450 subjects with MetS. Results: Several single nucleotide polymorphisms (SNP) showed phenotypic associations independent of SFA or IR. Carriers of the rare T allele of rs7903146, and of three other SNPs in linkage disequilibrium with rs7903146, had lower blood pressure and insulin secretion. High IR and the presence of the T-allele of rs7903146 acted synergistically to define those with reduced insulin secretion. Carriers of the minor allele of rs290481 exhibited an altered lipid profile, with increased plasma levels of apolipoprotein B, non-esterified fatty acids, cholesterol and apolipoprotein B in triglyceride rich lipoproteins, and LDL cholesterol. Carriers of the minor allele of rs11196224 that had higher plasma SFA levels showed elevated procoagulant/proinflammatory biomarkers, impaired insulin secretion and increased IR, whereas carriers of the minor allele of rs17685538 with high plasma SFA levels exhibited higher blood pressure. Conclusions/interpretation: SNP in the TCF7L2 gene are associated with differences in insulin secretion, blood pressure, blood lipids and coagulation in MetS patients, and may be modulated by SFA in plasma or IR.

  • 17.
    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.

  • 18. 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.

  • 19. 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.

  • 20. Garcia-Rodriguez, Cruz E.
    et al.
    Mesa, Maria D.
    Olza, Josune
    Vlachava, Maria
    Kremmyda, Lefkothea-Stella
    Diaper, Norma D.
    Noakes, Paul S.
    Miles, Elizabeth A.
    Ramirez-Tortosa, Maria Carmen
    Liaset, Bjorn
    Froyland, Livar
    Rossary, Adrien
    Farges, Marie-Chantal
    Vasson, Marie-Paule
    Aguilera, Concepcion M.
    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.
    Godfrey, Keith M.
    Calder, Philip C.
    Basu, Samar
    Gil, Angel
    Does Consumption of Two Portions of Salmon Per Week Enhance the Antioxidant Defense System in Pregnant Women?2012In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 16, no 12, p. 1401-1406Article in journal (Refereed)
    Abstract [en]

    Salmon is a rich source of marine n-3 fatty acids, which may increase oxidative stress and, in turn, could affect the antioxidant defense system in blood plasma and erythrocytes of pregnant women. 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. Higher selenium and retinol plasma concentrations were observed after dietary salmon supplementation. Besides, a concomitant increase in selenium and glutathione concentration as well as glutathione peroxidase and reductase activities were detected as pregnancy progressed. However, tocopherols, retinol, beta-carotene, and coenzyme Q(10) decreased in late pregnancy. Collectively, our findings lead to the hypothesis that increased farmed salmon intake may increase antioxidant defenses during pregnancy.

  • 21.
    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.

  • 22. 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.

  • 23. 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.

  • 24. 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.

  • 25.
    Helmersson, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Axelsson, Tomas
    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, Oxidative Stress and Inflammation.
    A polymorphism in the cyclooxygenase 1 gene is associated with decreased inflammatory prostaglandin F2alpha formation and lower risk of cardiovascular disease2009In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 80, no 1, p. 51-56Article in journal (Refereed)
    Abstract [en]

    This study investigates the impact of genetic variation in the cyclooxygenase-1 (COX-1) gene on formation of the vasoconstrictive, pro-inflammatory prostaglandin F(2)(alpha) (PGF(2)(alpha)) and development of cardiovascular disease (CVD). We determined COX-1 genotypes, PGF(2)(alpha) formation and CVD prevalence in a Swedish cohort of 809 men at age 77 years. Of these, 237 had a history of CVD according to the registry data. Four of nine COX-1 single nucleotide polymorphisms were associated with altered formation of PGF(2)(alpha) (P<0.05). Two COX-1 gene variants (rs10306135 and rs883484) remained significantly associated with altered PGF(2)(alpha) formation after adjusted significance level for multiple testing (alpha-level=0.0059). Furthermore, individuals homozygote for the variant allele rs10306135 had lower prevalence of CVD, compared to the common allele (0% versus 30%, P=0.0047). In conclusion, subjects homozygote for the variant allele of a COX-1 gene polymorphism represent a subpopulation of men with decreased PGF(2)(alpha) formation and lower prevalence of CVD.

  • 26.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Björklund-Bodegard, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    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.
    24-Hour ambulatory blood pressure associates inversely with prostaglandin F-2 alpha, interleukin-6 and F-2-isoprostane formation in a Swedish population of older men2012In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 5, no 2, p. 145-153Article in journal (Refereed)
    Abstract [en]

    Vasoconstrictive prostaglandins (PGs), such as PGF(2 alpha), F-2-isoprostanes, and systemic inflammation may be involved in the physiological regulation of blood pressure (BP) and the pathophysiology leading to hypertension. However, studies evaluating these parameters and BP in human populations are sparse. We analysed the cross-sectional associations between 24-hour ambulatory BP and urinary 15-keto-dihydro-PGF(2 alpha) (indicator of PG-mediated vasoconstriction and inflammation), plasma interleukin-6 (IL-6), C-reactive protein (CRP), serum amyloid A (SAA) and urinary F-2-isoprostanes (indicator of vasoconstriction and oxidative stress) in 619 men in a Swedish older population (Uppsala Longitudinal Study of Adult Men, age 78 years). Both systolic and diastolic 24-hour BP correlated inversely with concentrations of 15-keto-dihydro-PGF(2 alpha) (P < 0.01) and F-2-isoprostanes (P< 0.01) independent on other cardiovascular risk factors. Additionally, diastolic 24-hour BP inversely correlated with plasma IL-6 (P< 0.05) and 24-hour pulse pressure showed a positive linear correlation with IL-6, CRP and SAA. In conclusion, high BP is associated with decreased formation of vasoconstrictive PGF(2 alpha) and F-2-isoprostanes in this population of older men. These findings, although unlike our original hypothesis, might have an important physiological function which needs to be further evaluated.

  • 27.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Miles, Elizabeth A
    Vlachava, Maria
    Kremmyda, Lefkothea-Stella
    Noakes, Paul S
    Diaper, Norma D
    Godfrey, Keith M
    Calder, Philip C
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Enhanced prostaglandin F(2α) formation in human pregnancy and the effect of increased oily fish intake: Results from the Salmon in Pregnancy Study2012In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 86, no 1-2, p. 35-38Article in journal (Refereed)
    Abstract [en]

    Oily fish intake during pregnancy may reduce the risk of allergic diseases in infancy possibly by shifts in the fatty acid balance and subsequent altered prostaglandin (PG) formation. This intervention is the first study to evaluate if increased oily fish intake affects in vivo PGF(2α) formation during pregnancy. British pregnant women were randomised to two portions of farmed salmon weekly (n=47), or maintenance of their normal diet low in fish (n=41), from pregnancy week 20 until parturition. The concentrations of eicosapentaenoic and docosahexaenoic acids in plasma phosphatidylcholine (PC) were higher and the concentration of arachidonic acid in plasma PC was lower in the salmon group than the control group at weeks 34 and 38 of pregnancy. PGF(2α) formation was evaluated by urinary measurement of 15-keto-dihydro-PGF(2α), a major PGF(2α) metabolite, at 20, 34 and 38 weeks. In both the salmon and control groups urinary 15-keto-dihydro-PGF(2α) concentrations increased significantly during pregnancy, which may be of physiological importance. Oily fish intervention altered fatty acid concentrations but did not affect urinary 15-keto-dihydro-PGF(2α) concentrations in pregnant women.

  • 28.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Prostaglandin F2α formation is associated with mortality in a Swedish community-based cohort of older males2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 4Article in journal (Refereed)
    Abstract [en]

    Aims

    An increasing number of clinical studies highlight the importance of the inflammatory mediator prostaglandin F2α (PGF). Prostaglandin F2α activity has been suggested to play pivotal roles in the development of cardiovascular diseases and cancer. However, whether systemic PGF concentrations may signal mortality is unknown. The aim was to evaluate in vivo PGF formation, by measuring urinary 15-keto-dihydro-PGF, and mortality risk in a community setting.                     

    Methods and results

    Urinary 15-keto-dihydro-PGF was measured in a Swedish population of 670 men (aged 77–78 years) and the participants were followed up for a median of 9.7 years (383 died, among them 156 of cardiovascular causes and 102 of cancer). In Cox regression models, urinary 15-keto-dihydro-PGF was significantly associated with cardiovascular mortality [multivariate hazard ratio (HR) for 1 SD increase of urinary 15-keto-dihydro-PGF: 1.18; 95% CI:1.04–1.34; P = 0.01) independent of established cardiovascular risk factors including C-reactive protein. Urinary 15-keto-dihydro-PGF was also independently associated with total mortality (multivariate HR for 1 SD increase of urinary 15-keto-dihydro-PGF: 1.11; 95% CI: 1.01–1.21; P = 0.03). The combination of 15-keto-dihydro-PGF concentrations above the median and high serum high-sensitive C-reactive protein (>3 mg/L) was independently associated with a two-fold increased risk of cancer and total mortality (P = 0.02 and P < 0.001, respectively).                     

    Conclusion

    This is the first study to show that the inflammatory mediator PGF was independently associated with mortality and specifically cardiovascular mortality 10 years later. The results are in line with the emerging evidence of the importance of the inflammatory mediator PGF in fatal cardiovascular disease.

  • 29.
    Jobs, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Nerpin, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Jobs, Magnus
    Sundström, Johan
    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, Oxidative Stress and Inflammation.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    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.
    Association Between Serum Cathepsin S and Mortality in Older Adults2011In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 306, no 10, p. 1113-1121Article in journal (Refereed)
    Abstract [en]

    Context: Experimental data suggest that cathepsin S, a cysteine protease, is involved in the complex pathways leading to cardiovascular disease and cancer. However, prospective data concerning a potential association between circulating cathepsin S levels and mortality are lacking.

    Objective: To investigate associations between circulating cathepsin S levels and mortality in 2 independent cohorts of elderly men and women.

    Design, Setting, and Participants: Prospective study using 2 community-based cohorts, the Uppsala Longitudinal Study of Adult Men (ULSAM; n=1009; mean age: 71 years; baseline period: 1991-1995; median follow-up: 12.6 years; end of follow-up: 2006) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n=987; 50% women; mean age: 70 years; baseline period: 2001-2004; median follow-up: 7.9 years; end of follow-up: 2010). Serum samples were used to measure cathepsin S.

    Main Outcome Measure: Total mortality.

    Results: During follow-up, 413 participants died in the ULSAM cohort (incidence rate: 3.59/100 person-years at risk) and 100 participants died in the PIVUS cohort (incidence rate: 1.32/100 person-years at risk). In multivariable Cox regression models adjusted for age, systolic blood pressure, diabetes, smoking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease, higher serum cathepsin S was associated with an increased risk for mortality (ULSAM cohort: hazard ratio [HR] for 1-unit increase of cathepsin S, 1.04 [95% CI, 1.01-1.06], P=.009; PIVUS cohort: HR for 1-unit increase of cathepsin S, 1.03 [95% CI, 1.00-1.07], P=.04). In the ULSAM cohort, serum cathepsin S also was associated with cardiovascular mortality (131 deaths; HR for quintile 5 vs quintiles 1-4, 1.62 [95% CI, 1.11-2.37]; P=.01) and cancer mortality (148 deaths; HR for 1-unit increase of cathepsin S, 1.05 [95% CI, 1.01-1.10]; P=.01).

    Conclusions: Among elderly individuals in 2 independent cohorts, higher serum cathepsin S levels were associated with increased mortality risk. Additional research is needed to delineate the role of cathepsin S and whether its measurement might have clinical utility.

  • 30.
    Jobs, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ingelsson, Erik
    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.
    Nerpin, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Jobs, M
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    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.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Serum cathepsin S is associated with serum C-reactive protein and interleukin-6 independently of obesity in elderly men2010In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, no 9, p. 4460-4464Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Cathepsin S has been suggested provide a mechanistic link between obesity and atherosclerosis, possibly mediated via adipose tissue-derived inflammation. Previous data have shown an association between circulating cathepsin S and inflammatory markers in the obese, but to date, community-based reports are lacking. Accordingly, we aimed to investigate the association between serum levels of cathepsin S and markers of cytokine-mediated inflammation in a community-based sample, with prespecified subgroup analyses in nonobese participants. METHODS: Serum cathepsin S, C-reactive protein (CRP), and IL-6 were measured in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men; mean age 71 years, n = 991). CRP and IL-6 were also measured at a reexamination after 7 yr. RESULTS: After adjustment for age, body mass index, fasting plasma glucose, diabetes treatment, systolic blood pressure, diastolic blood pressure, hypertension treatment, serum cholesterol, serum high-density lipoprotein cholesterol, prior cardiovascular disease, smoking, and leisure time physical activity, higher cathepsin S was associated with higher CRP (regression coefficient for 1 sd increase, 0.13; 95% confidence interval 0.07-0.19; P < 0.001) and higher serum IL-6 (regression coefficient for 1 sd increase, 0.08; 95% confidence interval 0.01-0.14; P = 0.02). These associations remained similar in normal-weight participants (body mass index <25 kg/m(2), n = 375). In longitudinal analyses, higher cathepsin S at baseline was associated with higher serum CRP and IL-6 after 7 yr. CONCLUSIONS: These results provide additional evidence for the interplay between cathepsin S and inflammatory activity and suggest that this association is present also in normal-weight individuals in the community.

  • 31.
    Jobs, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jobs, Magnus
    University of Dalarna.
    Nerpin, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Iggman, David
    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.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lars, Lind
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 1, p. 163-165Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.

    RESEARCH DESIGN AND METHODS:

    Serum cathepsin S, insulin sensitivity (euglycemic-hyperinsulinemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.

    RESULTS:

    After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01).

    CONCLUSIONS:

    Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.

  • 32.
    Jonasson, Sofia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hjoberg, Josephine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Allergen-induced formation of F2-isoprostanes in a murine asthma model identifies oxidative stress in acute airway inflammation in vivo2009In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 80, no 1, p. 1-7Article in journal (Refereed)
    Abstract [en]

    F2-isoprostanes have been associated with various forms of oxidant stress. The levels of F2-isoprostanes in a murine asthma model were studied both in situ and in vivo and further investigated whether the formation of F2-isoprostanes was associated with increased ovalbumin (OVA)-induced airway inflammation after a 17-day (OVA-17) or a 24-day (OVA-24) protocol. Bronchial reactivity was assessed by using a ventilator (FlexiVent). OVA-treated animals had higher lung resistance and lung compliance compared to control groups (P<0.001). 8-Iso-PGF2α levels in bronchoalveolar lavage (BAL) and 8-iso-PGF2α immunoreactivity in lung tissue were analyzed. OVA-17 mice showed a 2.5-fold increased level of 8-iso-PGF2α in BAL compared to PBS-17 mice (P=0.023). Lung tissue from OVA-24 mice had more intense 8-iso-PGF2α staining compared to OVA-17 mice. This study showed an accumulation of F2-isoprostanes in acute airway inflammation and a markedly increased tissue damage caused by oxidative stress in an ongoing inflammation.

  • 33. Kadiiska, Maria B.
    et al.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Brot, Nathan
    Cooper, Christopher
    Csallany, A. Saari
    Davies, Michael J.
    George, Magdalene M.
    Murray, Dennis M.
    Roberts, L. Jackson, II
    Shigenaga, Mark K.
    Sohal, Rajindar S.
    Stocker, Roland
    Van Thiel, David H.
    Wiswedel, Ingrid
    Hatch, Gary E.
    Mason, Ronald P.
    Biomarkers of oxidative stress study V: Ozone exposure of rats and its effect on lipids, proteins, and DNA in plasma and urine2013In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 61, p. 408-415Article in journal (Refereed)
    Abstract [en]

    Ozone exposure effect on free radical-catalyzed oxidation products of lipids, proteins, and DNA in the plasma and urine of rats was studied as a continuation of the international Biomarker of Oxidative Stress Study (BOSS) sponsored by NIEHS/NIH. The goal was to identify a biomarker for ozone-induced oxidative stress and to assess whether inconsistent results often reported in the literature might be due to the limitations of the available methods for measuring the various types of oxidative products. The time- and dose-dependent effects of ozone exposure on rat plasma lipid hydroperoxides, malondialdehyde, F-2-isoprostanes, protein carbonyls, methionine oxidation, and tyrosine- and phenylalanine oxidation products, as well as urinary malondialdehyde and F-2-isoprostanes were investigated with various techniques. The criterion used to recognize a marker in the model of ozone exposure was that a significant effect could be identified and measured in a biological fluid seen at both doses at more than one time point. No statistically significant differences between the experimental and the control groups at either ozone dose and time point studied could be identified in this study. Tissue samples were not included. Despite all the work accomplished in the BOSS study of ozone, no available product of oxidation in biological fluid has yet met the required criteria of being a biomarker. The current negative findings as a consequence of ozone exposure are of great importance, because they document that in complex systems, as the present in vivo experiment, the assays used may not provide meaningful data of ozone oxidation, especially in human studies. 

  • 34. Kadiiska, Maria B.
    et al.
    Peddada, Shyamal
    Herbert, Ronald A.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Hensley, Kenneth
    Jones, Dean P.
    Hatch, Gary E.
    Mason, Ronald P.
    Biomarkers of oxidative stress study VI. Endogenous plasma antioxidants fail as useful biomarkers of endotoxin-induced oxidative stress2015In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 81, p. 100-106Article in journal (Refereed)
    Abstract [en]

    This is the newest report in a series of publications aiming to identify a blood-based antioxidant biomarker that could serve as an in vivo indicator of oxidative stress. The goal of the study was to test whether acutely exposing Gottingen mini pigs to the endotoxin lipopolysaccharide (LPS) results in a loss of antioxidants from plasma. We set as a criterion that a significant effect should be measured in plasma and seen at both doses and at more than one time point Animals were injected with two doses of LPS at 2.5 and 514/kg iv. Control plasma was collected from each animal before the LPS injection. After the LPS injection, plasma samples were collected at 2, 16, 48, and 72 h. Compared with the controls at the same time point, statistically significant losses were not found for either dose at multiple time points in any of the following potential markers: ascorbic acid, tocopherols (alpha, delta, gamma), ratios of GSH/GSSG and cysteine/cystine, mixed disulfides, and total antioxidant capacity. However, uric acid, total GSH, and total Cys were significantly increased, probably because LPS had a harmful effect on the liver. The leakage of substances from damaged cells into the plasma may have increased plasma antioxidant concentrations, making changes difficult to interpret Although this study used a mini-pig animal model of LPS-induced oxidative stress, it confirmed our previous findings in different rat models that measurement of antioxidants in plasma is not useful for the assessment of oxidative damage in vivo.

  • 35. Kirkhus, Bente
    et al.
    Lamglait, Amandine
    Eilertsen, Karl-Erik
    Falch, Eva
    Haider, Trond
    Vik, Hogne
    Hoem, Nils
    Hagve, Tor-Arne
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Olsen, Elisabeth
    Seljeflot, Ingebjorg
    Nyberg, Lena
    Elind, Elisabeth
    Ulven, Stine M.
    Effects of similar intakes of marine n-3 fatty acids from enriched food products and fish oil on cardiovascular risk markers in healthy human subjects2012In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 107, no 9, p. 1339-1349Article in journal (Refereed)
    Abstract [en]

    There is convincing evidence that consumption of fish and fish oil rich in long-chain (LC) n-3 PUFA (n-3 LCPUFA), EPA (20 : 5n-3) and DHA (22 : 6n-3) reduce the risk of CHD. The aim of the present study was to investigate whether n-3 LCPUFA-enriched food products provide similar beneficial effects as fish oil with regard to incorporation into plasma lipids and effects on cardiovascular risk markers. A parallel 7-week intervention trial was performed where 159 healthy men and women were randomised to consume either 34 g fish pate (n 44), 500 ml fruit juice (n 38) or three capsules of concentrated fish oil (n 40), all contributing to a daily intake of approximately 1 g EPA and DHA. A fourth group did not receive any supplementation or food product and served as controls (n 37). Plasma fatty acid composition, serum lipids, and markers of inflammation and oxidative stress were measured. Compared with the control group, plasma n-3 LCPUFA and EPA: arachidonic acid ratio increased equally in all intervention groups. However, no significant changes in blood lipids and markers of inflammation and oxidative stress were observed. In conclusion, enriched fish pate and fruit juice represent suitable delivery systems for n-3 LCPUFA. However, although the dose given is known to reduce the risk of CVD, no significant changes were observed on cardiovascular risk markers in this healthy population.

  • 36.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Palm, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Insulin-like growth factor binding protein-1 (IGFBP-1) during normal pregnancy2013In: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 29, no 2, p. 129-132Article in journal (Refereed)
    Abstract [en]

    Background:

    Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is the main binder of IGFs in secretory endometrium and decidualized stromal endometrial cells and IGFBP-1 has been shown to modulate IGF bioactivities and influence fetal growth. To be able to evaluate IGFBP-1 values during pregnancy it is important to establish normal values in pregnant women.

    Materials & Methods:

    We have studied IGFBP-1 concentrations in maternal plasma from 52 healthy women with normal singleton pregnancies. Several plasma samples were collected from each woman and the samples were grouped according to gestational age into the following periods: week 7-17; week 17-24; week 24-28; week 28-31; week 31-34; week 34-38; -2 to 0 weeks prior to delivery and postpartum (>6 weeks after delivery).

    Results:

    The 2.5 and 97.5 percentiles for IGFBP-1 were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values.

    Conclusions:

    IGFBP-1 is increased during pregnancy compared to postpartum. Two peaks, at week 17-24 and just before delivery, were observed.

  • 37.
    Lindström, Emma
    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).
    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).
    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.
    Ekström, Eva-Charlotte
    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).
    Associations between oxidative parameters in pregnancy and birth anthropometry in a cohort of women and children in rural Bangladesh: The MINIMat-cohort2012In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 46, no 3, p. 253-264Article in journal (Refereed)
    Abstract [en]

    Oxidative stress is suggested as a potential mechanism in impaired foetal growth, smaller birth size and thus subsequently adult chronic diseases. We have investigated associations between oxidative stress in pregnancy and birth anthropometry (weight, height, head and chest circumferences). In the MINIMat-trial (Maternal and Infant Nutrition Interventions, Matlab) in rural Bangladesh, free 8-iso-prostaglandin P-2 alpha (lipid peroxidation) was analysed in pregnancy week 14 and 30 and 8-Hydroxy-2 '-Deoxyguanosine (DNA oxidation) in week 19. We found that higher levels of lipid peroxidation in early pregnancy were associated with larger infant size (birth length and chest circumference). In late pregnancy, no clear pattern of associations was found. Increasing level of DNA oxidation was associated with lower birth length in girls but no other associations were found. In conclusion, a higher level of lipid peroxidation in early (but not late) pregnancy was associated with a favourable larger birth size suggesting that timing of lipid peroxidation is of importance.

  • 38.
    Lindström, Emma
    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).
    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).
    Raqib, Rubhana
    International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
    El Arifeen, Shams
    International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
    Brismar, Kerstin
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital.
    Ekström, Eva-Charlotte
    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).
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Associations between oxidative parameters in pregnancy and metabolic, oxidative and inflammatory markers in offspring in early childhood: The MINIMat trial in rural Bangladesh2012Article in journal (Other academic)
  • 39.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Samar, Basu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Oxidative stress in animal models with special reference to esperimental porcine endotoxemia2011In: Studies on experimental models / [ed] Samar Basu & Lars Wiklund, Totowa, NJ: Springer Science+Business Media B.V., 2011, p. 497-510Chapter in book (Refereed)
  • 40.
    Michaëlsson, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, Alicja
    Langenskiöld, Sophie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Economics.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Warensjö Lemming, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Milk intake and risk of mortality and fractures in women and men: cohort studies2014In: British Medical Journal, ISSN 1756-1833, Vol. 349, p. g6015-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine whether high milk consumption is associated with mortality and fractures in women and men.

    DESIGN: Cohort studies.

    SETTING: Three counties in central Sweden.

    PARTICIPANTS: Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997.

    MAIN OUTCOME MEASURE: Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture.

    RESULTS: During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker).

    CONCLUSIONS: High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.

  • 41.
    Miclescu, Adriana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nordquist, Lena
    Uppsala University.
    Hysing, Eva-Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Butler, Stephen
    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.
    Lind, Anne-Li
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Targeting oxidative injury and citokines activity in the treatment with anti-TNF alpha antibodies against CRPS 12013In: Pain Practice, ISSN 1530-7085, E-ISSN 1533-2500, Vol. 13, no 8, p. 641-648Article in journal (Refereed)
    Abstract [en]

    Cytokines and oxygen free radicals have been implicated in the potential pathogenic development of complex regional pain syndrome (CRPS). We aimed to analyze the relationship between clinical status, circulating levels of cytokines, and markers of oxidative damage during the treatment with anti-TNFα antibodies. The patient chosen for treatment had not had improvement through a number of conventional therapies and fulfilled the current diagnostic criteria for CRPS-1. We investigated the clinical variables before and after systemic administration of 1.4 mg/kg anti-TNFα antibody (infliximab), repeated after 1 month in a dose of 3 mg/kg. Blood samples were collected before and after anti-TNFα antibodies administration, and plasma was analyzed for 8-isoprostane-prostaglandin F2α (8-iso-PGF2α, a marker of oxidative injury) and cytokines (TNF-α, IL-4, IL-6, IL-7, IL-8, IL-10, IL-17A). Plasma concentrations of 8-iso-PGF2α were measured with radioimmunoassay (RIA), and the kinetics of cytokines were detected in plasma by antibody-based proximity ligation (PLA). Pathologically high levels of 8-iso-PGF2α were found in the patient. Immediately after each administration of infliximab, the levels of 8-iso-PGF2α decreased. Although the patient showed an improvement of the cutaneous dystrophic symptoms and diminished pain associated with these lesions, the levels of circulating TNFα increased after the administration of anti-TNFα antibodies. In a patient with CRPS-1 treated with anti-TNFα antibodies, we report increased levels of circulating TNFα and a temporary mitigation of oxidative stress as measured by plasma F2-isoprostane. This case report provides evidence 2 supporting the indication of monitoring the oxidative stress biomarkers during treatment with anti-TNFα antibodies in CRPS 1.

  • 42. Miles, Elizabeth A
    et al.
    Noakes, Paul S
    Kremmyda, Lefkothea-Stella
    Vlachava, Maria
    Diaper, Norma D
    Rosenlund, Grethe
    Urwin, Heidi
    Yaqoob, Parveen
    Rossary, Adrien
    Farges, Marie-Chantal
    Vasson, Marie-Paule
    Liaset, Bjørn
    Frøyland, Livar
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Garcia, Erika
    Olza, Josune
    Mesa, Maria D
    Aguilera, Concepcion M
    Gil, Angel
    Robinson, Sian M
    Inskip, Hazel M
    Godfrey, Keith M
    Calder, Philip C
    The Salmon in Pregnancy Study: study design, subject characteristics, maternal fish and marine n-3 fatty acid intake, and marine n-3 fatty acid status in maternal and umbilical cord blood2011In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 94, no 6, p. 1986S-1992SArticle in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Oily fish provides marine n-3 (omega-3) fatty acids that are considered to be important in the growth, development, and health of the fetus and newborn infant.

    OBJECTIVES:

    The objectives were to increase salmon consumption among pregnant women and to determine the effect on maternal and umbilical cord plasma marine n-3 fatty acid content.

    DESIGN:

    Women (n = 123) with low habitual consumption of oily fish were randomly assigned to continue their habitual diet or were provided with 2 portions of farmed salmon/wk to include in their diet from week 20 of pregnancy until delivery.

    RESULTS:

    Median weekly consumption frequency of study salmon in the salmon group was 1.94 portions, and total fish consumption frequency was 2.11 portions/wk in the salmon group and 0.47 portions/wk in the control group (P < 0.001). Intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from the diet, from seafood, and from oily fish were higher in the salmon group (all P < 0.001). Percentages of EPA and DHA in plasma phosphatidylcholine decreased during pregnancy in the control group (P for trend = 0.029 and 0.008, respectively), whereas they increased in the salmon group (P for trend for both < 0.001). EPA and DHA percentages were higher in maternal plasma phosphatidylcholine at weeks 34 and 38 of pregnancy and in umbilical cord plasma phosphatidylcholine in the salmon group (P < 0.001 for all).

    CONCLUSION:

    If pregnant women, who do not re