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  • 301.
    Oke, V.
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Brauner, S.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Gustafsson, J.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Zickert, A.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gunnarsson, I.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Svenungsson, E.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Increased Serum Levels of IFN-Λ Correlate with Th17 Axis Cytokines and Independently To IFN-α Identify Patient Group with Higher Organ Damage2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, p. 128-128Article in journal (Other academic)
  • 302.
    Oke, Vilija
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    Brauner, Susanna
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Gustafsson, Johanna
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    Zickert, Agneta
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    IFN-λ1 with Th17 axis cytokines and IFN-α define different subsets in systemic lupus erythematosus (SLE).2017In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, article id 139Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Interferon (IFN)-α is thought to have a pivotal role in systemic lupus erythematosus (SLE), and type III IFNs (IFN-λ) were recently also associated with SLE. In this study, we measured levels of IFN-α, IFN-λ1, and related cytokines, such as IL-17A, IL-23, and interferon-γ-induced protein 10 (IP-10), in a Karolinska University Hospital cohort of patients with SLE and control subjects. The objective of the study was to investigate if cytokine measurements could identify different subsets of patients with active SLE and higher disease damage.

    METHODS: We included 261 patients with SLE and 261 population control subjects. All participants underwent a standardized clinical examination. Medical files were reviewed. Patients with SLE were assessed for current organ manifestations, disease activity, and damage. Routine blood parameters, complement levels, and serology were analyzed at the time of inclusion. Levels of IFN-λ1, IFN-α, IL-17A, IL-23, and IP-10 were measured by enzyme-linked immunosorbent assay.

    RESULTS: IFN-λ1 and IFN-α were detected in 29% and 44% of patients, respectively, but their levels did not correlate. High serum levels of IFN-λ1 were positively associated with antinucleosome antibodies and lymphopenia but negatively with musculoskeletal damage. Positive correlations between levels of IFN-λ1, IL-17A, and IL-23 were observed. Patients with high levels of these three cytokines had more disease damage, especially renal impairment. High levels of IFN-α were associated with mucocutaneous disease; leukopenia; and low complement, Ro/SSA, and La/SSB. Vascular events and antiphospholipid antibodies were uncommon. We identified two subgroups with high disease activity: one with double-high IFN-λ1 and IFN-α and another with IP-10(high). The former had more neuropsychiatric manifestations, and the latter had more arthritis. Increased levels of both types I and III IFNs were found in a proportion of population control subjects. Therefore, high IFN levels do not seem to be SLE-specific biomarkers.

    CONCLUSIONS: Measurements of circulating IFN-λ1 and IFN-α define subsets of patients with SLE with different characteristics. Levels of IFN-λ1 correlate with T-helper type 17 cytokines and identify a subgroup with more damage. High disease activity is associated with either simultaneous upregulation of IFN-λ1 and IFN-α or independently with IP-10. Our findings could be of major importance when tailoring therapy for patients with SLE with agents targeting IFN pathways.

  • 303.
    Olausson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Peterson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Bergström, Mats
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Evaluation of the Meritas® BNP Test for Point-of-Care Testing2015In: Clinical Laboratory, ISSN 1433-6510, Vol. 61, no 7, p. 727-730Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: BNP and NT-proBNP are widely used as rule-out tests for heart failure (HF) and they are frequently requested by primary care doctors. A point-of-care (POC) test would reduce the time to diagnosis for patients with suspected HF. The aim of the study was to evaluate a POC BNP test.

    METHODS: Plasma BNP results obtained with the Meritas® POC instrument (n = 82) were compared with the corresponding plasma BNP results analyzed on an Advia Centaur analyzer (Siemens Healthcare, Erlangen, Germany).

    RESULTS: The two methods showed concordant results with a Passing-Bablok correlation between the two methods: BNP(Meritas) = 1.00 x BNP(Siemens) + 1.09; r = 0.9773.

    CONCLUSIONS: The study show that the Meritas® BNP assay could be used in primary care permitting rapid BNP testing to rule out heart failure.

  • 304.
    Olausson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Petterson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Bergström, Mats
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Evaluation of the Meritas® BNP Test for Point-of-Care Testing2015In: Clinical Laboratory, ISSN 1433-6510, Vol. 61, no 7, p. 727-730Article in journal (Refereed)
    Abstract [en]

    Background: BNP and NT-proBNP are widely used as rule-out tests for heart failure (HF) and they are frequently requested by primary care doctors. A point-of-care (POC) test would reduce the time to diagnosis for patients with suspected HF. The aim of the study was to evaluate a POC BNP test.

    Methods: Plasma BNP results obtained with the Meritas® POC instrument (n = 82) were compared with the corresponding plasma BNP results analyzed on an Advia Centaur analyzer (Siemens Healthcare, Erlangen, Germany).

    Results: The two methods showed concordant results with a Passing-Bablok correlation between the two methods: BNPMeritas = 1.00 x BNPSiemens + 1.09; r = 0.9773.

    Conclusions: The study show that the Meritas® BNP assay could be used in primary care permitting rapid BNP testing to rule out heart failure.

  • 305. Olofsson, P
    et al.
    Nordquist, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Vingsbo-Lundberg, C
    Larsson, Anders
    University Hospital, Uppsala, Sweden.
    Falkenberg, C
    Pettersson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Akerstrom, B
    Holmdahl, R
    Genetic links between the acute-phase response and arthritis developmentin rats2002In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 46, no 1, p. 259-268Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    The acute-phase inflammatory response is closely correlated with the development of rheumatoid arthritis, but the pathophysiologic role of its specific components is largely unknown. We investigated the genetic control of the acute-phase protein response in pristane-induced arthritis (PIA), which is a chronic erosive arthritis model in rats.

    METHODS:

    Plasma levels of the acute-phase proteins interleukin-6 (IL-6), alpha1-acid glycoprotein (orosomucoid), fibrinogen, and alpha1-inhibitor3 were quantified in 3 strains of rats during the development and progression of disease: DA and LEW.1F, which are susceptible to arthritis, and E3, which is resistant. Genetic linkage analysis was performed on an F2 intercross between E3 and DA to determine the genetic control of the acute-phase response in arthritis. Elevated levels of alpha1-acid glycoprotein were associated with acute inflammation, whereas levels of IL-6 were increased during the entire course of the disease.

    RESULTS:

    Using these acute-phase markers as quantitative traits in linkage analysis revealed a colocalization of loci controlling the acute-phase response and regions previously shown to control the development of arthritis in chromosomes 10, 12, and 14. In addition, 2 loci that were not associated with arthritis were found to regulate serum levels of the acute-phase protein Apr1 (acute-phase response 1) at the telomeric end of chromosome 12 and Apr2 on chromosome 5.

    CONCLUSION:

    The PIA model in rats is a useful tool for understanding some of the pathways leading to chronic erosive arthritis. The analysis of acute-phase proteins in PIA and its application as quantitative traits for studying the genetics of arthritis will promote the understanding of the genetic regulation of the acute-phase response.

  • 306.
    Olovsson, Matts
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Human Anatomy.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Biotin labelling of chicken antibodies and their subsequent use in ELISA and immunohistochemistry1993In: Comparative Immunology, Microbiology & Infectious Diseases, ISSN 0147-9571, E-ISSN 1878-1667, Vol. 16, no 2, p. 145-152Article in journal (Refereed)
    Abstract [en]

    Avian antibodies have many advantages to mammalian antibodies due to the phylogenetic differences between birds and mammals, resulting in an increased sensitivity and a decreased background in many immunological assays. Since the avidin-biotin system is an efficient detection system for antibodies with a high sensitivity, we wanted to investigate the activity and unspecific binding of optimally biotin labelled chicken antibodies in ELISA and immunohistochemistry. We report on the conditions for biotinylation of chicken antibodies and that optimally biotinylated antibodies show a high activity and a low background in both ELISA and immunohistochemistry.

  • 307.
    Olsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Norlund, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Pingel, Ronnie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Burell, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Gulliksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Svärdsudd, K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    The effect of group-based cognitive behavioral therapy on inflammatory biomarkers in patients with coronary disease: results from the SUPRIM-trial2018In: Upsala Journal of Medical Sciences, Supplement, ISSN 0300-9726, Vol. 123, no 3, p. 167-173Article in journal (Refereed)
    Abstract [en]

    Background: The Secondary Prevention in Uppsala Primary Healthcare Project (SUPRIM) is a prospective randomized controlled trial of a group-based cognitive behavioral therapy (CBT) stress management program for coronary heart disease (CHD) patients. The intervention reduced the risk of fatal or non-fatal first recurrent cardiovascular (CV) events. The aim of the present study was to analyze if the positive effects of the CBT program on clinical outcomes could have been mediated by changes in biomarkers for inflammation.

    Methods: Altogether 362 patients with CHD were randomly assigned to intervention or usual care. The inflammatory biomarkers (VCAM-1, TNF-R1, TNF-R2, PTX3, and hs-CRP) were serially assessed at five time points every six months from study start until 24 months later, and analyzed with linear mixed models.

    Results: Baseline levels of the inflammatory markers were near normal, indicating a stable phase. The group-based CBT stress management program did not significantly affect the levels of inflammatory biomarkers in patients with CHD. Three out of five (VCAM-1, TNF-R2, and PTX3) inflammatory biomarkers showed a slight increase over time in both study groups, and all were positively associated with age.

    Conclusion: Group-based CBT stress management did not affect biomarkers for inflammation in patients with CHD. It is therefore unlikely that inflammatory processes including these biomarkers were mediating the effect the CBT program had on the reduction in CV events. The close to normal baseline levels of the biomarkers and the lack of elevated psychological distress symptoms indicate a possible floor effect which may have influenced the results.

    Keywords: Biomarkers, CBT, CHD, inflammation, stress management

  • 308.
    Olsson, Karl Wilhelm
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Jonzon, Anders
    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, Faculty of Medicine, Department of Neuroscience, Physiology.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22–27 weeks’ gestation2018In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447Article in journal (Refereed)
    Abstract [en]

    Background

    Early identification of infants at risk for complications from patent ductus arteriosus (PDA) may improve treatment outcomes. The aim of this study was to identify biochemical markers associated with persistence of PDA, and with failure of pharmacological treatment for PDA, in extremely preterm infants.

    Methods

    Infants born at 22–27 weeks’ gestation were included in this prospective study. Blood samples were collected on the second day of life. Fourteen biochemical markers associated with factors that may affect PDA closure were analyzed and related to persistent PDA and to the response of pharmacological treatment with ibuprofen.

    Results

    High levels of B-type natriuretic peptide, interleukin-6, -8, -10, and -12, growth differentiation factor 15 and monocyte chemotactic protein 1 were associated with persistent PDA, as were low levels of platelet-derived growth factor. High levels of erythropoietin were associated with both persistent PDA and failure to close PDA within 24 h of the last dose of ibuprofen.

    Conclusions

    High levels of inflammatory markers were associated with the persistence of PDA. High levels of erythropoietin were associated with both the persistence of PDA and failure to respond to pharmacological treatment.

  • 309. Ostlund, Eva
    et al.
    Al-Nashi, Maha
    Hamad, Rangeen Rafik
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Eriksson, Maria
    Bremme, Katarina
    Kahan, Thomas
    Normalized endothelial function but sustained cardiovascular risk profile 11 years following a pregnancy complicated by preeclampsia2013In: Hypertension Research, ISSN 0916-9636, E-ISSN 1348-4214, Vol. 36, no 12, p. 1081-1087Article in journal (Refereed)
    Abstract [en]

    Women with a history of preeclampsia are at increased risk of future cardiovascular disease. Preeclampsia is associated with elevated blood pressure, inflammation and endothelial dysfunction, and these findings remain 1 year after delivery. Whether these abnormalities persist long after delivery, and whether they may contribute to future cardiovascular disease, is not well studied. We studied 15 women with a history of preeclampsia and 16 matched controls with an uncomplicated pregnancy 11 years following the index pregnancy; all had also been previously examined at 1 year. We assessed arterial stiffness (pulse wave analysis), 24 h ambulatory blood pressure and endothelial function (forearm flow-mediated dilatation and pulse wave analysis following β receptor agonist provocation), and determined markers of glucose and lipid metabolism, inflammation and vascular function. The preeclampsia group had higher blood pressures and reduced night/day blood pressure ratios, increased body mass index and reduced glucose tolerance, and increased levels of tissue necrosis factor receptor 1 and intracellular adhesion molecule-1, suggesting inflammatory and vascular activation. However, the endothelial impairment observed in the preeclampsia group at 1 year was normalized at 11 years, whereas the control group remained unchanged during follow-up. Our findings of higher blood pressures, impaired glucose tolerance and normalization of endothelial function 11 years after preeclampsia suggest cardiovascular risk factors present already before pregnancy to be more important than permanent endothelial damage for the increased risk of future cardiovascular complications in women with a history of preeclampsia.

  • 310.
    Otterbeck, Alexander
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hanslin, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lantz, E. Lidberg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Stålberg, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Inhalation of specific anti-Pseudomonas aeruginosa IgY antibodies transiently decreases P. aeruginosa colonization of the airway in mechanically ventilated piglets2019In: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 7, article id 21Article in journal (Refereed)
    Abstract [en]

    Background: P. aeruginosa is a pathogen frequently resistant to antibiotics and a common cause of ventilator-associated pneumonia (VAP). Non-antibiotic strategies to prevent or treat VAP are therefore of major interest. Specific polyclonal avian IgY antibodies have previously been shown to be effective against pneumonia caused by P. aeruginosa in rodents and against P. aeruginosa airway colonization in patients. Objectives: To study the effect of specific polyclonal anti-P. aeruginosa IgY antibodies (Pa-IgY) on colonization of the airways in a porcine model. Method: The pigs were anesthetized, mechanically ventilated, and subject to invasive hemodynamic monitoring and allocated to either receive 10(9) CFU nebulized P. aeruginosa (control, n=6) or 10(9) CFU nebulized P. aeruginosa + 200 mg Pa-IgY antibodies (intervention, n=6). Physiological measurement, blood samples, and tracheal cultures were then secured regularly for 27 h, after which the pigs were sacrificed and lung biopsies were cultured. Results: After nebulization, tracheal growth of P. aeruginosa increased in both groups during the experiment, but with lower growth in the Pa-IgY-treated group during the experiment (p = 0.02). Tracheal growth was 4.6 x 10(3) (9.1 x 10(2)-3.1 x 10(4)) vs. 4.8 x 10(4) (7.5 x 10(3)-1.4 x 10(5)) CFU/mL in the intervention group vs. the control group at 1h and 5.0 x 10(0) (0.0 x 10(0)-3.8 x 10(2)) vs. 3.3 x 10(4) (8.0 x 10(3)-1.4 x 10(5)) CFU/mL at 12 h in the same groups. During this time, growth in the intervention vs. control group was one to two orders of ten lower. After 12 h, the treatment effect disappeared and bacterial growth increased in both groups. The intervention group had lower body temperature and cardiac index and higher static compliance compared to the control group. Conclusion: In this porcine model, Pa-IgY antibodies lessen bacterial colonization of the airways.

  • 311.
    Otterbeck, Alexander
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hanslin, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lidberg Lantz, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Stålberg, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Correction to: Inhalation of specific anti-Pseudomonas aeruginosa IgY antibodies transiently decreases P. aeruginosa colonization of the airway in mechanically ventilated piglets.2019In: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 7, article id 24Article in journal (Refereed)
    Abstract [en]

    Following publication of the original article, the authors flagged that an incorrect piece of data is given in the Materials and Methods section of the article.

  • 312.
    Palm, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Involvement of inflammation in normal pregnancy2013In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 5, p. 601-605Article in journal (Refereed)
    Abstract [en]

    Objective.

    To study the role of inflammatory biomarkers of cytokine and cyclooxygenase origin throughout normal pregnancy and postpartum.

    Design.

    Longitudinal prospective study.

    Setting.

    One outpatient antenatal clinic in Uppsala, Sweden.

    Population.

    Thirty-seven healthy women with normal pregnancies and normal neonatal outcome were included. 

    Methods.

    Blood and urine samples were collected from each woman at least 6 times during pregnancy and postpartum. Plasma levels of IL-6 and TNF-α were measured by using ELISA kits and urine levels of PGF2α metabolite were measured by using RIA.

    Main outcome measures.

    Median plasma and urine levels, the 25:th to the 75:th percentile and the average change per gestational week of IL-6, TNF-α and PGF2α metabolite .

    Results.

    IL-6 levels increased significantly throughout pregnancy and postpartum levels remained high. No change in TNF-α could be seen with advancing gestational age or postpartum period. The PGF2α metabolite levels increased significantly throughout pregnancy and decreased in postpartum period.

    Conclusion.

    These results suggest that mild but significant inflammatory activity is involved in development of normal pregnancy and might have important physiological effects.

  • 313.
    Panezai, Jeneen
    et al.
    Altamash Institute of Dental Medicine, Department of Periodontology, Karachi, Pakistan; Karolinska Institutet, Department of Dental Medicine, Division of Periodontology, Huddinge, Sweden.
    Ghaffar, Ambereen
    Habib Medical Centre, Rheumatology Clinic, Karachi, Pakistan.
    Altamash, Mohammad
    Habib Medical Centre, Rheumatology Clinic, Karachi, Pakistan.
    Engström, Per-Erik
    Karolinska Institutet, Department of Dental Medicine, Division of Periodontology, Huddinge, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Periodontal disease influences osteoclastogenic bone markers in subjects with and without rheumatoid arthritis2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 6, article id e0197235Article in journal (Refereed)
    Abstract [en]

    Background: Periodontal disease (PD) and rheumatoid arthritis (RA) are bone pathologies mediated through immuno-inflammatory mechanisms. The aim of this study was to investigate the serum markers osteopontin (OPN), tumor necrosis factor receptors 1 (TNFR1) and 2 (TNFR2) receptor activator of nuclear factor‐kappa B ligand (RANKL) and RANKL/ osteoprotegerin (OPG) ratio and compare them in PD and RA groups.

    Materials & methods: RA (with PD = 19 and without PD = 19), PD (n = 38) and 14 healthy subjects underwent bleeding on probing (BOP) and probing pocket depth (PPD) measurement. PD was defined as PPD measuring ≥5mm registered in ≥3 sites. Marginal bone loss (MBL) for premolars and molars was measured on digital panoramic radiographs. Serum samples were collected from all subjects. OPN, TNFR1, TNFR2 and RANKL were measured by enzyme-linked immunosorbent assays (ELISAs). OPG was measured as part of a multiplex proximity extension assay (PEA).

    Results: OPN, TNFR1, TNFR2 and RANKL serum levels were the highest in the RA group with PD, while the RA group without PD were comparable to PD subjects only. The RANKL/OPG ratios were comparable between PD group and both RA groups with (p = 0.051) and without PD (p = 0.37). Serum RANKL levels were associated with MBL (p = 0.008) and PPD ≥ 5mm (p = 0.01).

    Conclusion: Peripheral osteoclastogenesis is a feature of periodontal disease with systemic levels of osteoclastogenic markers comparable to the effects observed in rheumatoid arthritis.

  • 314.
    Panezai, Jeneen
    et al.
    Altamash Institute of Dental Medicine, Department of Periodontology, Karachi, Pakistan, Karolinska Institutet, Department of Dental Medicine, Division of Periodontology, Huddinge, Sweden .
    Ghaffar, Ambereen
    Habib Medical Centre, Rheumatology Clinic, Karachi, Pakistan, Karachi, Pakistan .
    Altamash, Mohammad
    Altamash Institute of Dental Medicine, Department of Periodontology, Karachi, Pakistan .
    Sundqvist, Karl-Gösta
    Karolinska University Hospital, Department of Laboratory Medicine, Division of Clinical Immunology, Stockholm, Sweden .
    Engström, Per-Erik
    Karolinska Institutet, Department of Dental Medicine, Division of Periodontology, Huddinge, Sweden .
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Correlation of serum cytokines, chemokines, growth factors and enzymes with periodontal disease parameters.2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 11, article id e0188945Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Periodontal disease (PD) is characterized by inflammatory tissue destruction in tooth supporting apparatus. Many studies indicate that the underlying pathogenesis is in concordance with rheumatoid arthritis (RA) sharing immune-inflammatory events affect both diseases. The aim of this study was to investigate serum cytokines, chemokines, growth factors, enzymes and costimulatory proteins in association with periodontal conditions in PD and RA subjects.

    MATERIALS & METHODS: Periodontal examination was performed in RA (n = 38), PD (n = 38) and healthy subjects (n = 14). Bleeding on probing (BOP) and probing pocket depth (PPD) were measured. Marginal bone loss (MBL) for premolars and molars was measured on digital panoramic radiographs. PD was defined as present if the PPD was ≥5mm in ≥ 3 different sites. Serum samples were collected from all subjects. A multiplex proximity extension assay (PEA) was used to analyze the samples for simultaneous measurement of 92 cytokines. Cytokines with ≥ 60% quantitative results were included.

    RESULTS: A significant positive correlation was seen for ST1A1, FGF-19 and NT-3 whereas EN-RAGE, DNER, CX3CL1 and TWEAK associated inversely with BOP, PPD≥ 5mm and MBL but positively with number of teeth. Several CD markers (CD244, CD40, CDCP1, LIF-R, IL-10RA, CD5 and CD6) were found to be associated with BOP, shallow and deep pockets, MBL and number of teeth, either directly or inversely. Most chemokines (CCL8, CX3CL1, CXCL10, CXCL11, CCL11, CCL4, CCL20, CXCL5, CXCL6, and CCL23) were positively associated with number of teeth and some inversely related to MBL (CCL8, CXCL10). Proteins with enzymatic activity (ST1A1, HGF and CASP-8) were directly related to the severity of periodontal conditions and inversely related to number of teeth. Aside from FGF-19, other growth factors were also directly associated with MBL (HGF), number of teeth (VEGF-A, LAP TGF-beta-1) and, inversely to, shallow pockets (LAP TGF-beta-1, TGFA and Beta-NGF). Out of 33 cytokines, 32 associated inversely with shallow pockets, whereas only CD40 associated positively. Associations between cytokines and periodontal parameters in the RA group were comparatively less. Statistical analyses were adjusted for multivariate effects using the Benjamini-Hochberg false discovery rate method.

    CONCLUSION: Systemic inflammatory burden, via known and novel markers, is associated with periodontal conditions in PD and RA subjects. Shallow pockets are not associated with a higher inflammatory state.

  • 315.
    Parodis, I
    et al.
    Karolinska Inst, Sweden.
    Ding, H
    Univ Houston, USA.
    Zickert, A
    Karolinska Inst, Sweden.
    Arnaud, L
    Karolinska Inst, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Svenungsson, E
    Karolinska Inst, Sweden.
    Mohan, C
    Univ Houston, USA.
    Gunnarsson, I
    Karolinska Inst, Sweden.
    Serum soluble tumour necrosis factor receptor-2 (sTNFR2) as a biomarker of kidney tissue damage and long-term renal outcome in lupus nephritis2017In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 46, no 4, p. 263-272Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    We investigated the performance of soluble tumour necrosis factor receptor-2 (sTNFR2) as a biomarker of renal activity, damage, treatment response, and long-term outcome in lupus nephritis (LN).

    METHOD:

    Serum sTNFR2 levels were assessed in 64 LN patients (52 proliferative, 12 membranous) before and after induction treatment, and in 314 non-lupus controls. In LN patients, renal biopsies were performed at baseline and post-treatment. Patients with ≥ 50% reduced proteinuria, normal or improved estimated glomerular filtration rate (eGFR) by ≥ 25%, and inactive urinary sediment were considered clinical responders (CRs). Patients with ≥ 50% improved renal activity index were considered histopathological responders (HRs). Long-term renal outcome was determined using the chronic kidney disease (CKD) stage after a median follow-up of 11.3 years.

    RESULTS:

    sTNFR2 levels were elevated in LN patients versus controls both at baseline (p < 0.001) and post-treatment (p < 0.001), and decreased following treatment (p < 0.001). Baseline sTNFR2 correlated with Chronicity Index scores in both baseline (r = 0.34, p = 0.006) and post-treatment (r = 0.43, p < 0.001) biopsies. In membranous LN, baseline sTNFR2 levels were higher in CRs (p = 0.048) and HRs (p = 0.03) than in non-responders, and decreased only in CRs (p = 0.03). Both baseline (p = 0.02) and post-treatment (p = 0.03) sTNFR2 levels were associated with decreasing eGFR throughout long-term follow-up, and post-treatment levels were higher in patients with long-term follow-up CKD stage ≥ 3 versus 1-2 (p = 0.008).

    CONCLUSIONS:

    Our data suggest serum sTNFR2 as a marker of kidney tissue damage and a predictor of long-term prognosis in LN, and merit further evaluation of sTNFR2 as a predictor of clinical and histopathological treatment outcomes in membranous LN.

  • 316.
    Parodis, Ioannis
    et al.
    Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden;Karolinska Univ Hosp, Rheumatol, Stockholm, Sweden.
    Gokaraju, Sirisha
    Univ Houston, Dept Biomed Engn, Houston, TX USA.
    Zickert, Agneta
    Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden;Karolinska Univ Hosp, Rheumatol, Stockholm, Sweden.
    Zhang, Ting
    Univ Houston, Dept Biomed Engn, Houston, TX USA.
    Habazi, Deena
    Univ Houston, Dept Biomed Engn, Houston, TX USA.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Svenungsson, Elisabet
    Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden;Karolinska Univ Hosp, Rheumatol, Stockholm, Sweden.
    Mohan, Chandra
    Univ Houston, Dept Biomed Engn, Houston, TX USA.
    Gunnarsson, Iva
    Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden;Karolinska Univ Hosp, Rheumatol, Stockholm, Sweden.
    A Role of Vascular Cell Adhesion Molecule 1 and Activated Leukocyte Cell Adhesion Molecule in Lupus Nephritis2018In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70Article in journal (Other academic)
  • 317.
    Pelander, Lena
    et al.
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Häggström, Jens
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Syme, Harriet
    Department of Clinical Science and Services, The Royal Veterinary College, Hertfordshire, United Kingdom.
    Elliott, Jonathan
    Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, United Kingdom..
    Heiene, Reidun
    ABC Dyreklinikk Lillehammer AS, Hamarvegen 68A, 26 13 Lillehammer, Norway..
    Ljungvall, Ingrid
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Comparison of the diagnostic value of symmetric dimethylarginine, cystatin C, and creatinine for detection of decreased glomerular filtration rate in dogs2019In: Journal of Veterinary Internal Medicine, ISSN 0891-6640, E-ISSN 1939-1676, Vol. 33, no 2, p. 630-639Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Early detection of decreased glomerular filtration rate (GFR) in dogs is challenging. Current methods are insensitive and new biomarkers are required.

    OBJECTIVE: To compare overall diagnostic performance of serum symmetric dimethylarginine (SDMA) and serum cystatin C to serum creatinine, for detection of decreased GFR in clinically stable dogs, with or without chronic kidney disease (CKD).

    ANIMALS: Ninety-seven client-owned dogs: 67 dogs with a diagnosis or suspicion of CKD and 30 healthy dogs were prospectively included.

    METHODS: Prospective diagnostic accuracy study. All dogs underwent physical examination, systemic arterial blood pressure measurement, urinalysis, hematology and blood biochemistry analysis, cardiac and urinary ultrasound examinations, and scintigraphy for estimation of glomerular filtration rate (mGFR). Frozen serum was used for batch analysis of SDMA and cystatin C.

    RESULTS: The area under the curve of creatinine, SDMA, and cystatin C for detection of an mGFR <30.8 mL/min/L was 0.98 (95% confidence interval [CI], 0.93-1.0), 0.96 (95% CI, 0.91-0.99), and 0.87 (95% CI, 0.79-0.93), respectively. The sensitivity of both creatinine and SDMA at their prespecified cutoffs (115 μmol/L [1.3 mg/dL] and 14 μg/dL) for detection of an abnormal mGFR was 90%. The specificity was 90% for creatinine and 87% for SDMA. When adjusting the cutoff for cystatin C to correspond to a diagnostic sensitivity of 90% (0.49 mg/L), specificity was lower (72%) than that of creatinine and SDMA.

    CONCLUSIONS AND CLINICAL IMPORTANCE: Overall diagnostic performance of creatinine and SDMA for detection of decreased mGFR was similar. Overall diagnostic performance of cystatin C was inferior to both creatinine and SDMA.

  • 318.
    Peura, Sari
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, Sci Life Labs, Almas Alle 5, S-75007 Uppsala, Sweden.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden; Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Unit Paediat Allergy & Pulmonol, Stockholm, Sweden.
    Andolf, Ellika
    Karolinska Inst, Danderyd Hosp, Div Obstet & Gynaecol, Dept Clin Sci, Stockholm, Sweden.
    Hedman, Anna
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Pershagen, Göran
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Normal values for calprotectin in stool samples of infants from the population-based longitudinal born into life study2018In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 78, no 1-2, p. 120-124Article in journal (Refereed)
    Abstract [en]

    Faecal calprotectin is a protein used as a diagnostic marker for inflammatory bowel diseases. We determined upper limits for normal calprotectin values for neonatal, 6, 12 and 24 months old children using a turbidimetric immunoassay in a cohort of Swedish children. The advantage of the method is that opposite to previously used enzyme-linked immunosorbent assay (ELISA) method, it enables measuring single samples, and thus, shortens the analysis time significantly. There were 72 samples (41.7% female) collected neonatally, 63 samples (34.9% female) at 6 months, 60 samples (40.0% female) at 12 months and 51 samples (43.1% female) at 24 months. The upper limits for normal values were 233, 615, 136 and 57 µg mg-1 for infants aged 0, 6, 12 and 24 months, respectively.

  • 319.
    Ribom, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pietras, Kristian
    Ludwiginstitutet för Cancerforskning.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Growth factor analysis of low-grade glioma CSF: PDGF and VEGF are not detectable2003In: Neurological Sciences, ISSN 1590-1874, E-ISSN 1590-3478, Vol. 24, no 2, p. 70-73Article in journal (Refereed)
    Abstract [en]

    Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) are involved in the development of grade 2 gliomas. The aim of the present study was to determine the presence of these growth factors in the cerebrospinal fluid (CSF) and to assess their usefulness as biological markers. CSF was collected from 7 adult patients with newly diagnosed supratentorial low-grade gliomas by lumbar puncture and was analysed together with matched serum samples using radioreceptor and enzyme-linked immunosorbant assays. Neither PDGF nor VEGF were detected in the CSF, and FGF-2 was measurable at extremely low concentrations in only 2 of 7 patients. Serum levels were within normal limits. We conclude that these growth factors are not released into the CSF in any significant amounts and are therefore not suitable as biological markers in grade 2 gliomas.

  • 320.
    Ridefelt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Axelsson, John
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Diurnal variability of total calcium during normal sleep and after an acute shift of sleep2012In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 50, no 1, p. 147-151Article in journal (Refereed)
    Abstract [en]

    Background: Serum total calcium is becoming a widely used test when screening for hyperparathyroidism (HPT) and other causes of hypercalcemia, even if serum calcium is tightly regulated in the body it is unclear whether the reference values are correct for tests taken at different times of the day or for individuals with altered sleep patterns. Thus, the aim was to investigate how timing of testing and sleep affects serum calcium.

    Methods: The diurnal variation of total calcium in serum during night-time and day-time conditions was studied in seven healthy volunteers. Serum samples for calcium measurements were collected every hour (48 samples per individual) to evaluate the effect of sampling times, sleep and food intake on the test results.

    Results: The median intra-individual coefficients of variations for calcium were 3.3% during night-time sleep and 2.8% during day-time sleep conditions. There was a clear diurnal variation in serum calcium, with a trough at 08.00 h in the morning after night-time sleep and a difference of approximately 0.07 mmol/L between trough and peak. Calcium was lower around the end of the sleep periods, for both night-time and day-time sleep. Food intake did not affect calcium concentrations.

    Conclusions: Evaluation of serum calcium results should take diurnal variation into account and allow slightly higher calcium values in the afternoon in comparison with samples collected in the morning.

  • 321.
    Ridefelt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Age- and sex-specific reference values for non-HDL cholesterol and remnant cholesterol derived from the Nordic Reference Interval Project (NORIP).2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Non-HDL-cholesterol (non-HDL-C) has been reported to be a better marker of cardiovascular risk than LDL-cholesterol (LDL-C) especially in individuals with high triglyceride values. Further, levels of remnant cholesterol have been suggested to in part explain residual risk not captured with LDL-C. The aim of the present study was to define reference values for non-HDL-C and remnant cholesterol based on data from the Nordic Reference Interval Project (NORIP).

    METHODS: We analyzed the test results for total cholesterol, HDL-cholesterol and triglycerides from 1392 healthy females and 1236 healthy males. Non-HDL-C was calculated as measured total cholesterol minus measured HDL-cholesterol. Remnant cholesterol was calculated using the Friedewald equation for LDL-C: measured total cholesterol minus measured HDL-cholesterol and minus calculated LDL-cholesterol. The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values.

    RESULTS: Age (18-<30, 30-49 and ≥50 years) and sex-specific reference intervals were calculated for non-HDL-cholesterol and remnant-cholesterol. Levels of non-HDL-C and remnant cholesterol differed between sex and age strata.

    CONCLUSIONS: Age- and sex-specific reference intervals should be used for the triglyceride rich lipid variables non-HDL-C and remnant cholesterol. Since these markers may add information on risk burden beyond LDL-C, our hope is that these reference intervals will aid the introduction of automatic reporting of non-HDL-C by hospital laboratories.

  • 322.
    Risberg, Anitha
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Larsson, Anders
    Department of Medical Sciences.
    Olsson, Kerstin
    Lyrenäs, Sven
    Department of Women's and Children's Health.
    Sjöquist, Mats
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Relationship between urinary albumin and albumin/creatinine ratio during normal pregnancy and pre-eclampsia.2004In: Scand J Clin Lab Invest, ISSN 0036-5513, Vol. 64, no 1, p. 17-23Article in journal (Other scientific)
    Abstract [en]

    Risberg A, Larsson A, Olsson K, Lyrenäs S, Sjöquist M.

    Department of Nursing and Health Sciences, Mid Sweden University, Ornsköldsvik, Sweden. anitha.risberg@mh.se

    Pre-eclampsia is a serious complication of pregnancy and it is important to detect the condition as early as possible. Albuminuria is an important symptom of pre-eclampsia and repeated urine analyses to screen for the condition are part of the standard antenatal care. The purpose of this study was to investigate whether measurement of the urine albumin/creatinine ratio in spot samples could be a complement to the dipstick method and could reduce the need for 24-h urine collections. Urine samples were collected for 24 h in weeks 12, 24 and 36 of pregnancy from both normotensive women and women who developed hypertension or who had pregnancy-induced hypertension (PIH) when they entered the study. The 24-h albumin excretion was significantly correlated to the albumin/creatinine ratio in all measurements (Pearson correlation coefficient). In week 12, the values were: n = 44, r = 0.964, p < 0.001 (normotensive group) and in the PIH group: n = 8, r = 0.789, p < 0.05. In week 24, the correlation values were r = 1.0 and p < 0.001 in both the normotensive group (n = 41) and in the PIH group (n = 11). In week 36 the correlation values were r = 0.791 and p < 0.001 in the normotensive group (n = 39) and r = 1.0 and p < 0.001 in the PIH group (n = 16). Microalbuminuria was defined as urine albumin excretion higher than 30 mg/24 h and this corresponded to an albumin/creatinine ratio of 2.9. Microalbuminuria was found in three persons in the PIH group and in two persons in the normotensive group. Overt albuminuria (> 300 mg/24 h) was found in one of the 46 normotensive women (2%) and in 3 of the 19 PIH women (16%). In all these women the high albumin values had been detected by using the albumin/creatinine ratio method. In conclusion, it has been found that the albumin excretion in urine correlates significantly to the albumin/creatinine ratio during pregnancy. The urinary albumin/creatinine ratio appears to be a good alternative to the dipstick method and to 24-h urine collections.

    PMID: 15025425 [PubMed - indexed for MEDLINE]

  • 323.
    Risberg, Anitha
    et al.
    Department of Health Sciences, Section of Health and Rehab, Luleå University of Technology, Luleå, Sweden..
    Sjöquist, Mats
    Swedish Centre for Animal Welfare, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Wedenberg, Kai
    Västerås Sjukus.
    Olsson, Ulf
    Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Water balance during parturition and early puerperium: A prospective open trial2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 13-14, p. 837-842Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate how water balance is regulated during labor and 27h postpartum.

    DESIGN AND METHODS: A prospective open trial with 49 women giving birth vaginally. Ringer-acetate was infused intravenously and combined with epidural analgesia in seven women (fluid group). Intravenous infusions of oxytocin in 5% glucose were given to 12 women (oxytocin group). Thirty women delivered their babies without infusion (nofluid group). Blood and urine samples were collected at arrival, at early stage 1, at early stage 2, and at aftercare, and 9, 15, and 27h postpartum. Plasma osmolality, sodium, cystatin C, vasopressin, oxytocin, urine flow, urine osmolality, and urine sodium were measued.

    RESULTS: The oxytocin group had significantly lower plasma osmolality than the nofluid group before parturition, and they had lower plasma sodium concentration at early stage 1 and 2. Plasma vasopressin concentration was low and did not differ between groups or before and after parturition. Water diuresis developed postpartum in all groups. The cystatin C concentration decreased significantly after parturition in the oxytocin and nofluid groups.

    CONCLUSIONS: The vasopressin levels were suppressed during parturition irrespective of the P-osmolality and the nongravid regulation of water balance had not returned within 27h postpartum.

  • 324.
    Rollborn, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Nordin, Gunnar
    Equalis, Uppsala, Sweden.
    Xu, Xiao Yan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Mandic-Havelka, Aleksandra
    Karolinska Univ Hosp, Karolinska Inst, Clin Chem, Dept Mol Med & Surg, Stockholm, Sweden.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Analysis of HbA1c on an automated multicapillary zone electrophoresis system.2017In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, no 1, p. 15-18Article in journal (Refereed)
    Abstract [en]

    Hemoglobin A1c (HbA1c) is a frequently requested laboratory test and there is thus a need for high throughput instruments for this assay. We evaluated a new automated multicapillary zone electrophoresis instrument (Capillarys 3 Tera, Sebia, Lisses, France) for analysis of HbA1c in venous samples. Routine requested HbA1c samples were analyzed immunologically on a Roche c6000 instrument (n = 142) and then with the Capillarys 3 Tera instrument. The Capillarys 3 Tera instrument performed approximately 70 HbA1c tests/hour. There was a strong linear correlation between Capillarys 3 Tera and Roche Tina-Quant HbA1c Gen 3 assay (y = 1.003x - 0.3246 R(2 )= .996). The total CV for the 12 capillaries varied between 0.8 and 2.2% and there was a good agreement between duplicate samples (R(2 )= .997). In conclusion, the Capillarys 3 Tera instrument has a high assay capacity for HbA1c. It has a good precision and agreement with the Roche Tina-Quant HbA1c method and is well suited for high volume testing of HbA1c.

  • 325.
    Ronquist, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Nilsson, Sten
    Karolinska University Hospital, Department of Oncology and Pathology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Prostasome-derived proteins capable of eliciting an immune response in prostate cancer patients2006In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 119, no 4, p. 847-853Article in journal (Refereed)
    Abstract [en]

    Prostate cancer consistently remains a difficult clinical enigma. Therefore, the development of novel strategies for diagnosis and treatment (e.g. immunotherapy) of prostate cancer is essential. We tried to identify the prostasome-derived proteins that were immunogenic in prostate cancer patients. Prostate cancer patients’ sera (n 5 44) with high enzyme-linked immunosorbent assay (ELISA) titers against prostasomes were selected for immunoblotting against purified seminal prostasomes. The SDS-PAGE and immunoblotting experiments were performed with Bio-Rad systems. Twenty-five of the recognized proteins were isolated and analyzed by means of mass spectrometry. Out of 44 patients’ sera, 31 (70%) demonstrated in immunoblotting experiments reactivity against several prostasomal protein bands in the molecular weight range of 10– 200 kDa. Some of the bands (55, 70 and 170 kDa) were more frequently recognized by the patients’ sera. Concomitantly run control sera generated only very weak or no bands at all. The most frequently occurring prostasomal proteins were identified as heat shock proteins (HSP 70, 71) and clusterin. This study identified the most important molecular targets of autoantibodies against prostasomes generated in connection with the development of prostate cancer in man. These immunogenic prostasomal proteins could be appropriate target molecules for specific immunotherapy of prostate cancer patients.

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

  • 326.
    Ronquist, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Semjonow, Axel
    Department of Urology-Prostate Centre, University Clinic, Mu¨nster,.
    Wülfing, Christian
    Department of Urology-Prostate Centre, University Clinic, Mu¨nster,.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Serum antibodies against prostasomal clusterin in prostate cancer patients2008In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 3, p. 219-227Article in journal (Refereed)
    Abstract [en]

    Objective. Clusterin is a ubiquitous secretory sulphated glycoprotein present in prostasomes. It is an antiapoptotic mediator in prostate cancer and is among the most frequently occurring prostasomal proteins immunogenic in prostate cancer patients. The aim of the present study was to investigate the occurrence of anticlusterin antibodies in the serum of patients with prostate cancer and whether there is a relationship between anticlusterin antibody titres and other clinico-pathological variables. Material and methods. Serum samples were collected from 391 consecutive patients with suspected prostate cancer (150 benign prostate and 241 prostate cancer). The patients’ serum samples were used in an ELISA where microtitre wells were coated with purified clusterin from serum of a healthy volunteer. Flow cytometric studies of clusterin and prostasomes were performed. Results. Flow cytometric analyses revealed the presence of clusterin on the surface of seminal prostasomes. Anti-clusterin ELISA titres in sera of patients did not differ significantly from those of a control group. A significant ‘‘inverse’’ correlation existed between anti-clusterin ELISA titres and lymph node metastases (p50.047), but only 11 out of 161 patients had metastases. These titres correlated significantly with total prostate (p50.021) and transitional zone (p50.015) volumes of the patients. Conclusions. The correlation between serum anti-clusterin antibody titres and other clinico-pathological variables was generally weak in prostate cancer patients, although clusterin has been assigned an important role in tumourigenesis and progression of prostate cancer. However, the anti-clusterin antibody titre appeared to be related to prostate volume, correlating to both transitional zone volume and total volume of the prostate.

  • 327.
    Ronquist, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ek, Bo
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Human Prostasomes Express Glycolytic Enzymes with Capacity for ATP Production2013In: Andrology, ISSN 2047-2919, Vol. 1, no S2, p. 76-76Article in journal (Other academic)
  • 328.
    Ronquist, Göran K
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ek, Bo
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Morrell, Jane
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Biochemical characterization of stallion prostasomes and comparison to their human counterparts2013In: Systems biology in reproductive medicine, ISSN 1939-6376, Vol. 59, no 6, p. 297-303Article in journal (Refereed)
    Abstract [en]

    Release of nanometer-sized prostasomes into human and equine semen suggests essential functions in their relationships with sperm cells and the fertilization process. The two types of prostasomes displayed ultrastructural similarities, albeit the human prostasomes were somewhat larger than the stallion prostasomes. A high ratio of saturated fatty acids was characteristic for the two prostasome types. Electrophoretic separation systems revealed an equine prostasomal pattern different from that of human. The 21 distinctive low molecular weight protein spots in the 2D-gel (with no counterparts in human prostasomes) were identified via peptide mass fingerprinting, several of which may be different isoforms. Out of the three high molecular weight bands characteristic for human prostasomes (CD10, CD13, and CD26), CD10 and CD13 were retrieved in equine prostasomes. We present some new proteins of horse prostasomes not found in their human counterparts. Further studies are warranted to reveal the function of these proteins.

  • 329.
    Ronquist, Göran K
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Prostasomes are heterogeneous regarding size and appearance but affiliated to one DNA-containing exosome family2012In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 72, no 16, p. 1736-1745Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Prostate acinar epithelial cells release microvesicles (prostasomes) that possess pleiotropic biological effects relevant for successful fertilization. Prostasomes are formed in a similar way as exosomes but are heterogeneous as regards size and appearance. Like exosomes they are thought to be mediators of intercellular communication.

    METHODS:

    We prepared seminal prostasomes in accordance with the prevailing protocol for exosome preparation including passage through a 0.2 µm filter and centrifugation in a sucrose gradient.

    RESULTS:

    We compared the "filterable prostasomes" with those trapped on the filter ("nonfilterable prostasomes") and, qualitatively, no conspicuous differences were apparent regarding ultrastructure and SDS-PAGE banding pattern. Moreover, both types of prostasomes contained DNA fragments and Western blot revealed presence of prostate specific membrane antigen (PSMA), CD38, and annexin A1.

    CONCLUSIONS:

    Reasonably, prostasomes could be included in the exosome family and be regarded as one entity containing chromosomal DNA.

  • 330.
    Ronquist, K Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ek, Bo
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Morrell, Jane
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Ström Holst, Bodil
    Humblot, Patrice
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Prostasomes from four different species are able to produce extracellular adenosine triphosphate (ATP)2013In: Biochimica et Biophysica Acta - General Subjects, ISSN 0304-4165, E-ISSN 1872-8006, Vol. 1830, no 10, p. 4604-4610Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Prostasomes are extracellular vesicles. Intracellularly they are enclosed by another larger vesicle, a so called "storage vesicle" equivalent to a multivesicular body of late endosomal origin. Prostasomes in their extracellular context are thought to play a crucial role in fertilization.

    METHODS:

    Prostasomes were purified according to a well worked-out schedule from seminal plasmas obtained from human, canine, equine and bovine species. The various prostasomes were subjected to SDS-PAGE separation and protein banding patterns were compared. To gain knowledge of the prostasomal protein systems pertaining to prostasomes of four different species proteins were analyzed using a proteomic approach. An in vitro assay was employed to demonstrate ATP formation by prostasomes of different species.

    RESULTS:

    The SDS-PAGE banding pattern of prostasomes from the four species revealed a richly faceted picture with most protein bands within the molecular weight range of 10-150kDa. Some protein bands seemed to be concordant among species although differently expressed and the number of protein bands of dog prostasomes seemed to be distinctly fewer. Special emphasis was put on proteins involved in energy metabolic turnover. Prostasomes from all four species were able to form extracellular adenosine triphosphate (ATP). ATP formation was balanced by ATPase activity linked to the four types of prostasomes.

    CONCLUSION:

    These potencies of a possession of functional ATP-forming enzymes by different prostasome types should be regarded against the knowledge of ATP having a profound effect on cell responses and now explicitly on the success of the sperm cell to fertilize the ovum.

    GENERAL SIGNIFICANCE:

    This study unravels energy metabolic relationships of prostasomes from four different species.

  • 331.
    Ronquist, K Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ek, Bo
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Human prostasomes express glycolytic enzymes with capacity for ATP production2013In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 304, no 6, p. E576-E582Article in journal (Refereed)
    Abstract [en]

    Prostasomes are prostate-derived, exosome-like microvesicles that transmit signaling complexes between the acinar epithelial cells of the prostate and sperm cells. A vast majority of prostasomes has a diameter of 30 - 200 nm and they are generally surrounded by a classical membrane bilayer. Using a selected proteomic approach, it became increasingly clear that prostasomes harbor distinct subsets of proteins that may be linked to adenosine triphosphate (ATP) metabolic turnover that in turn might be of importance in the role of prostasomes as auxiliary instruments in the fertilization process. Among the 21 proteins identified most of the enzymes of anaerobic glycolysis were represented and three of the glycolytic enzymes present are among the ten top proteins found in most exosomes, once again linking prostasomes to the exosome family. Other prostasomal enzymes involved in ATP turnover were adenylate kinase, ATPase, 5'-nucleotidase and hexose transporters. The identified enzymes in their prostasomal context were operational for ATP formation when supplied with substrates. The net ATP production was low due to a high prostasomal ATPase activity that could be partially inhibited by vanadate that was utilized in order to profile the ATP forming ability of prostasomes. Glucose and fructose were equivalent as glycolytic substrates for prostasomal ATP formation and the enzymes involved were apparently surface-located on prostasomes, since an alternative substrate not being membrane-permeable (glyceraldehyde 3-phosphate) was operative, too. There is no clear cut function linked to this subset of prostasomal proteins but some possible roles are discussed.

  • 332.
    Ronquist, Karl Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sanchez, Claire
    Department of Oncology-Pathology, Karolinska Institutet and University Hospital, Stockholm, Sweden..
    Dubois, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Chioureas, Dimitris
    Department of Oncology-Pathology, Karolinska Institutet and University Hospital, Stockholm, Sweden..
    Fonseca, Pedro
    Department of Oncology-Pathology, Karolinska Institutet and University Hospital, Stockholm, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ullén, Anders
    Department of Oncology-Pathology, Karolinska Institutet and University Hospital, Stockholm, Sweden..
    Yachnin, Jeffrey
    Department of Oncology-Pathology, Karolinska Institutet and University Hospital, Stockholm, Sweden..
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Panaretakis, Theocharis
    Department of Oncology-Pathology, Karolinska Institutet and University Hospital, Stockholm, Sweden..
    Energy-requiring uptake of prostasomes and PC3 cell-derived exosomes into non-malignant and malignant cells2016In: Journal of Extracellular Vesicles, ISSN 2001-3078, E-ISSN 2001-3078, Vol. 5, article id 29877Article in journal (Refereed)
    Abstract [en]

    Epithelial cells lining the prostate acini release, in a regulated manner (exocytosis), nanosized vesicles called prostasomes that belong to the exosome family. Prostate cancer cells have preserved this ability to generate and export exosomes to the extracellular space. We previously demonstrated that human prostasomes have an ATP-forming capacity. In this study, we compared the capacity of extracellular vesicles (EVs) to generate ATP between normal seminal prostasomes and exosomes secreted by PC3 cells (PC3 exosomes), a prostate cancer cell line. Proteomic analyses identified enzymes of the glycolytic chain in both prostasomes and PC3 exosomes, and we found that both of them were capable of generating ATP when supplied with substrates. Notably, the net production of extracellular ATP was low for prostasomes due to a high ATPase activity contrary to an elevated net ATP level for PC3 exosomes because of their low ATPase activity. The uptake of the 2 types of EVs by normal prostate epithelial cells (CRL2221) and prostate cancer cells (PC3) was visualized and measured, demonstrating differential kinetics. Interestingly, this uptake was dependent upon an ongoing glycolytic flux involving extracellular ATP formation by EVs and/or intracellular ATP produced from the recipient cells. We conclude that the internalization of EVs into recipient cells is an energy-requiring process also demanding an active V-ATPase and the capacity of EVs to generate extracellular ATP may play a role in this process.

  • 333.
    Rosqvist, Fredrik
    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.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Johansson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Arner, Peter
    Dahlman, Ingrid
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Overfeeding Polyunsaturated and Saturated Fat Causes Distinct Effects on Liver and Visceral Fat Accumulation in Humans2014In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 7, p. 2356-2368Article in journal (Refereed)
    Abstract [en]

    Excess ectopic fat storage is linked to type 2 diabetes. The importance of dietary fat composition for ectopic fat storage in humans is unknown. We investigated liver fat accumulation and body composition during overfeeding saturated (SFA) or polyunsaturated (PUFA) fat. LIPOGAIN was a double-blind, parallel-group, randomized trial. Thirty-nine young and normal-weight individuals were overfed muffins high in SFA (palm oil) or n-6 PUFA (sunflower oil) for 7 weeks. Liver fat, visceral (VAT), subcutaneous abdominal (SAT), and total adipose tissue (TAT), pancreatic fat, and lean tissue was assessed by MRI. Transcriptomics were performed in SAT. Both groups gained similar weight. SFA however markedly increased liver fat compared with PUFA and caused 2-fold larger increase in VAT than PUFA. Conversely, PUFA caused a nearly 3-fold larger increase in lean tissue than SFA. Increase in liver fat directly correlated with changes in plasma SFA and inversely with PUFA. Genes involved in regulating energy dissipation, insulin resistance, body composition and fat cell differentiation in SAT were differentially regulated between diets, and associated with increased PUFA in SAT. In conclusion, overeating SFA promotes hepatic and visceral fat storage whereas excess energy from PUFA may instead promote lean tissue in healthy humans.

  • 334. Roth, Gregory A
    et al.
    Johnson, Catherine
    Abajobir, Amanuel
    Abd-Allah, Foad
    Abera, Semaw Ferede
    Abyu, Gebre
    Ahmed, Muktar
    Aksut, Baran
    Alam, Tahiya
    Alam, Khurshid
    Alla, François
    Alvis-Guzman, Nelson
    Amrock, Stephen
    Ansari, Hossein
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Asayesh, Hamid
    Atey, Tesfay Mehari
    Avila-Burgos, Leticia
    Awasthi, Ashish
    Banerjee, Amitava
    Barac, Aleksandra
    Bärnighausen, Till
    Barregard, Lars
    Bedi, Neeraj
    Belay Ketema, Ezra
    Bennett, Derrick
    Berhe, Gebremedhin
    Bhutta, Zulfiqar
    Bitew, Shimelash
    Carapetis, Jonathan
    Carrero, Juan Jesus
    Malta, Deborah Carvalho
    Castañeda-Orjuela, Carlos Andres
    Castillo-Rivas, Jacqueline
    Catalá-López, Ferrán
    Choi, Jee-Young
    Christensen, Hanne
    Cirillo, Massimo
    Cooper, Leslie
    Criqui, Michael
    Cundiff, David
    Damasceno, Albertino
    Dandona, Lalit
    Dandona, Rakhi
    Davletov, Kairat
    Dharmaratne, Samath
    Dorairaj, Prabhakaran
    Dubey, Manisha
    Ehrenkranz, Rebecca
    El Sayed Zaki, Maysaa
    Faraon, Emerito Jose A
    Esteghamati, Alireza
    Farid, Talha
    Farvid, Maryam
    Feigin, Valery
    Ding, Eric L
    Fowkes, Gerry
    Gebrehiwot, Tsegaye
    Gillum, Richard
    Gold, Audra
    Gona, Philimon
    Gupta, Rajeev
    Habtewold, Tesfa Dejenie
    Hafezi-Nejad, Nima
    Hailu, Tesfaye
    Hailu, Gessessew Bugssa
    Hankey, Graeme
    Hassen, Hamid Yimam
    Abate, Kalkidan Hassen
    Havmoeller, Rasmus
    Hay, Simon I
    Horino, Masako
    Hotez, Peter J
    Jacobsen, Kathryn
    James, Spencer
    Javanbakht, Mehdi
    Jeemon, Panniyammakal
    John, Denny
    Jonas, Jost
    Kalkonde, Yogeshwar
    Karimkhani, Chante
    Kasaeian, Amir
    Khader, Yousef
    Khan, Abdur
    Khang, Young-Ho
    Khera, Sahil
    Khoja, Abdullah T
    Khubchandani, Jagdish
    Kim, Daniel
    Kolte, Dhaval
    Kosen, Soewarta
    Krohn, Kristopher J
    Kumar, G Anil
    Kwan, Gene
    Lal, Dharmesh Kumar
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Linn, Shai
    Lopez, Alan
    Lotufo, Paulo A
    El Razek, Hassan Magdy Abd
    Malekzadeh, Reza
    Mazidi, Mohsen
    Meier, Toni
    Meles, Kidanu Gebremariam
    Mensah, George
    Meretoja, Atte
    Mezgebe, Haftay
    Miller, Ted
    Mirrakhimov, Erkin
    Mohammed, Shafiu
    Moran, Andrew E
    Musa, Kamarul Imran
    Narula, Jagat
    Neal, Bruce
    Ngalesoni, Frida
    Nguyen, Grant
    Obermeyer, Carla Makhlouf
    Owolabi, Mayowa
    Patton, George
    Pedro, João
    Qato, Dima
    Qorbani, Mostafa
    Rahimi, Kazem
    Rai, Rajesh Kumar
    Rawaf, Salman
    Ribeiro, Antônio
    Safiri, Saeid
    Salomon, Joshua A
    Santos, Itamar
    Santric Milicevic, Milena
    Sartorius, Benn
    Schutte, Aletta
    Sepanlou, Sadaf
    Shaikh, Masood Ali
    Shin, Min-Jeong
    Shishehbor, Mehdi
    Shore, Hirbo
    Silva, Diego Augusto Santos
    Sobngwi, Eugene
    Stranges, Saverio
    Swaminathan, Soumya
    Tabarés-Seisdedos, Rafael
    Tadele Atnafu, Niguse
    Tesfay, Fisaha
    Thakur, J S
    Thrift, Amanda
    Topor-Madry, Roman
    Truelsen, Thomas
    Tyrovolas, Stefanos
    Ukwaja, Kingsley Nnanna
    Uthman, Olalekan
    Vasankari, Tommi
    Vlassov, Vasiliy
    Vollset, Stein Emil
    Wakayo, Tolassa
    Watkins, David
    Weintraub, Robert
    Werdecker, Andrea
    Westerman, Ronny
    Wiysonge, Charles Shey
    Wolfe, Charles
    Workicho, Abdulhalik
    Xu, Gelin
    Yano, Yuichiro
    Yip, Paul
    Yonemoto, Naohiro
    Younis, Mustafa
    Yu, Chuanhua
    Vos, Theo
    Naghavi, Mohsen
    Murray, Christopher
    Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015.2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 70, no 1, p. 1-25Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world.

    OBJECTIVES: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden.

    METHODS: CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility.

    RESULTS: In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75.

    CONCLUSIONS: CVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD.

  • 335.
    Roth, Gregory A
    et al.
    Institute for Health Metrics and Evaluation, University of Washington, Seattle.
    Johnson, Catherine O
    Abate, Kalkidan Hassen
    Jimma University, Jimma, Ethiopia..
    Abd-Allah, Foad
    Ahmed, Muktar
    Alam, Khurshid
    Alam, Tahiya
    Alvis-Guzman, Nelson
    Ansari, Hossein
    Ärnlöv, Johan
    Atey, Tesfay Mehari
    Awasthi, Ashish
    Awoke, Tadesse
    Barac, Aleksandra
    Bärnighausen, Till
    Bedi, Neeraj
    Bennett, Derrick
    Bensenor, Isabela
    Biadgilign, Sibhatu
    Castañeda-Orjuela, Carlos
    Catalá-López, Ferrán
    Davletov, Kairat
    Dharmaratne, Samath
    Ding, Eric L
    Dubey, Manisha
    Faraon, Emerito Jose Aquino
    Farid, Talha
    Farvid, Maryam S
    Feigin, Valery
    Fernandes, João
    Frostad, Joseph
    Gebru, Alemseged
    Geleijnse, Johanna M
    Gona, Philimon Nyakauru
    Griswold, Max
    Hailu, Gessessew Bugssa
    Hankey, Graeme J
    Hassen, Hamid Yimam
    Havmoeller, Rasmus
    Hay, Simon
    Heckbert, Susan R
    Irvine, Caleb Mackay Salpeter
    James, Spencer Lewis
    Jara, Dube
    Kasaeian, Amir
    Khan, Abdur Rahman
    Khera, Sahil
    Khoja, Abdullah T
    Khubchandani, Jagdish
    Kim, Daniel
    Kolte, Dhaval
    Lal, Dharmesh
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Linn, Shai
    Lotufo, Paulo A
    Magdy Abd El Razek, Hassan
    Mazidi, Mohsen
    Meier, Toni
    Mendoza, Walter
    Mensah, George A
    Meretoja, Atte
    Mezgebe, Haftay Berhane
    Mirrakhimov, Erkin
    Mohammed, Shafiu
    Moran, Andrew Edward
    Nguyen, Grant
    Nguyen, Minh
    Ong, Kanyin Liane
    Owolabi, Mayowa
    Pletcher, Martin
    Pourmalek, Farshad
    Purcell, Caroline A
    Qorbani, Mostafa
    Rahman, Mahfuzar
    Rai, Rajesh Kumar
    Ram, Usha
    Reitsma, Marissa Bettay
    Renzaho, Andre M N
    Rios-Blancas, Maria Jesus
    Safiri, Saeid
    Salomon, Joshua A
    Sartorius, Benn
    Sepanlou, Sadaf Ghajarieh
    Shaikh, Masood Ali
    Silva, Diego
    Stranges, Saverio
    Tabarés-Seisdedos, Rafael
    Tadele Atnafu, Niguse
    Thakur, J S
    Topor-Madry, Roman
    Truelsen, Thomas
    Tuzcu, E Murat
    Tyrovolas, Stefanos
    Ukwaja, Kingsley Nnanna
    Vasankari, Tommi
    Vlassov, Vasiliy
    Vollset, Stein Emil
    Wakayo, Tolassa
    Weintraub, Robert
    Wolfe, Charles
    Workicho, Abdulhalik
    Xu, Gelin
    Yadgir, Simon
    Yano, Yuichiro
    Yip, Paul
    Yonemoto, Naohiro
    Younis, Mustafa
    Yu, Chuanhua
    Zaidi, Zoubida
    Zaki, Maysaa El Sayed
    Zipkin, Ben
    Afshin, Ashkan
    Gakidou, Emmanuela
    Lim, Stephen S
    Mokdad, Ali H
    Naghavi, Mohsen
    Vos, Theo
    Murray, Christopher J L
    The Burden of Cardiovascular Diseases Among US States, 1990-20162018In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 3, no 5, p. 375-389Article in journal (Refereed)
    Abstract [en]

    Importance: Cardiovascular disease (CVD) is the leading cause of death in the United States, but regional variation within the United States is large. Comparable and consistent state-level measures of total CVD burden and risk factors have not been produced previously.

    Objective: To quantify and describe levels and trends of lost health due to CVD within the United States from 1990 to 2016 as well as risk factors driving these changes.

    Design, Setting, and Participants: Using the Global Burden of Disease methodology, cardiovascular disease mortality, nonfatal health outcomes, and associated risk factors were analyzed by age group, sex, and year from 1990 to 2016 for all residents in the United States using standardized approaches for data processing and statistical modeling. Burden of disease was estimated for 10 groupings of CVD, and comparative risk analysis was performed. Data were analyzed from August 2016 to July 2017.

    Exposures: Residing in the United States.

    Main Outcomes and Measures: Cardiovascular disease disability-adjusted life-years (DALYs).

    Results: Between 1990 and 2016, age-standardized CVD DALYs for all states decreased. Several states had large rises in their relative rank ordering for total CVD DALYs among states, including Arkansas, Oklahoma, Alabama, Kentucky, Missouri, Indiana, Kansas, Alaska, and Iowa. The rate of decline varied widely across states, and CVD burden increased for a small number of states in the most recent years. Cardiovascular disease DALYs remained twice as large among men compared with women. Ischemic heart disease was the leading cause of CVD DALYs in all states, but the second most common varied by state. Trends were driven by 12 groups of risk factors, with the largest attributable CVD burden due to dietary risk exposures followed by high systolic blood pressure, high body mass index, high total cholesterol level, high fasting plasma glucose level, tobacco smoking, and low levels of physical activity. Increases in risk-deleted CVD DALY rates between 2006 and 2016 in 16 states suggest additional unmeasured risks beyond these traditional factors.

    Conclusions and Relevance: Large disparities in total burden of CVD persist between US states despite marked improvements in CVD burden. Differences in CVD burden are largely attributable to modifiable risk exposures.

  • 336. Ruge, T
    et al.
    Södergren, A
    Wållberg-Jonsson, S
    Larsson, Anders
    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.
    Circulating plasma levels of cathepsin S and L are not associated with disease severity in patients with rheumatoid arthritis2014In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, no 5, p. 371-373Article in journal (Refereed)
    Abstract [en]

    Background:

    Rheumatoid arthritis (RA) is characterized by chronic synovitis and articular cartilage destruction. Increased activities of cathepsin S and cathepsin L, two potent cysteine proteases, are thought to play a role in the pathogenesis of the irreversible articular cartilage destruction. Nevertheless, data regarding the potential importance of the cathepsins as circulating biomarkers in RA patients are limited.

    Method:

    Subjects enrolled in this study are part of a larger study where patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study. In total, 71 patients were included, along with 44 age- and sex-matched control subjects. Plasma levels of cathepsin S and L were analysed. Disease severity was assessed using the 28-joint count Disease Activity Score (DAS28).

    Results:

    Plasma levels of cathepsin S and L were significantly increased in patients with RA compared to healthy controls (p < 0.05 for both). However, in the patients with RA, no association between the cathepsins and the severity of the disease, as characterized by DAS28, was observed (p > 0.51).

    Conclusions:

    Although circulating levels of cathepsin S and L were significantly increased in patients with recently diagnosed RA, our data do not support the notion that circulating levels of cathepsins are relevant biomarkers for disease severity.

  • 337.
    Ruge, Toralph
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden; Karolinska Inst, Dept Med, Stockholm, Sweden.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA USA.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Circulating endostatin and the incidence of heart failure.2018In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, no 5, p. 244-249Article in journal (Refereed)
    Abstract [en]

    Objective: Circulating levels of endostatin are elevated in many underlying conditions leading to heart failure such as hypertension, diabetes, chronic kidney disease and ischemic heart disease. Yet, the association between endostatin and the incidence of heart failure has not been reported previously in the community.

    Design: We investigated the longitudinal association between serum endostatin levels and incident heart failure in two community-based cohorts of elderly: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 966; mean age 70 years, 51% women, 81 events, mean follow-up 10 years) and Uppsala Longitudinal Study of Adult Men (ULSAM, n = 747 men; mean age 78 years, 98 heart failure events, mean follow-up 8 years). We also investigated the cross-sectional association between endostatin and echocardiographic left ventricular systolic function and diastolic function (ejection fraction and E/A-ratio, respectively).

    Results: Higher serum endostatin was associated with an increased risk for heart failure in both cohorts after adjustment for established heart failure risk factors, glomerular filtration rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) (PIVUS: multivariable hazard ratio (HR) per 1-standard deviation (SD) increase, HR 1.46 (95%CI, 1.17-1.82, p < .001); ULSAM: HR 1.29 (95%CI, 1.00-1.68, p < .05). In cross-sectional analyses at baseline, higher endostatin was significantly associated with both worsened left ventricular systolic and diastolic function in both cohorts.

    Conclusion: Higher serum endostatin was associated with left ventricular dysfunction and an increased heart failure risk in two community-based cohorts of elderly. Our findings encourage further experimental studies that investigate the role of endostatin in the development of heart failure.

  • 338. Ruge, Toralph
    et al.
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska institutet, Stockholm, Sweden.
    Jansson, Jan-Håkan
    Söderberg, Stefan
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    The association between circulating endostatin levels and incident myocardial infarction2018In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, no 6, p. 315-319Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Increased levels of circulating endostatin have been observed in patients with prevalent ischemic heart disease. However, the association between circulating endostatin, and incident myocardial infarction (MI) is less studied. Our main aim was to study the association between circulating endostatin and incident MI in the community adjusted for established cardiovascular risk factors in men and women.

    DESIGN: Circulating endostatin was measured in a nested case control study based on three large community-based Swedish cohorts, including 533 MI cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with adjustments for established cardiovascular risk factors.

    RESULTS: Higher endostatin was associated with a higher incidence of MI independently of established cardiovascular risk factors (OR 1.19, 95 % CI 1.03-1.37, p = 0.02), but this association was abolished after additional adjustment for C-reactive protein. Sex-stratified analyses suggest that the association was substantially stronger in women as compared to men Conclusions: In our community based sample, higher endostatin predicted incident myocardial infarction predominantly in women but not independently of CRP. Thus, our findings do not support a broad utility of endostatin measurements for the prediction of incident myocardial infarction in clinical practice.

  • 339.
    Ruge, Toralph
    et al.
    Department of Emergency Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden..
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Kjøller, Erik
    Department of Cardiology, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark..
    Hilden, Jørgen
    Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark..
    Kolmos, Hans Jørn
    Department of Clinical Microbiology, Odense University Hospital, Denmark..
    Sajadieh, Ahmad
    Copenhagen University Hospital of Bispebjerg & Frederiksberg, Denmark..
    Kastrup, Jens
    Rigshospitalet of Copenhagen University, Denmark..
    Jensen, Gorm Boje
    Copenhagen University Hospital Hvidovre, Denmark..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Nowak, Christoph
    Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden..
    Jakobsen, Janus Christian
    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Cardiology, Holbæk Hospital, Holbæk, Denmark..
    Winkel, Per
    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark..
    Gluud, Christian
    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark..
    Ärnlöv, Johan
    Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
    Circulating endostatin as a risk factor for cardiovascular events in patients with stable coronary heart disease: A CLARICOR trial sub-study2019In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 284, p. 202-208Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Raised levels of serum endostatin, a biologically active fragment of collagen XVIII, have been observed in patients with ischemic heart disease but association with incident cardiovascular events in patients with stable coronary heart disease is uncertain.

    METHODS: The CLARICOR-trial is a randomized, placebo-controlled trial of stable coronary heart disease patients evaluating 14-day treatment with clarithromycin. The primary outcome was a composite of acute myocardial infarction, unstable angina pectoris, cerebrovascular disease or all-cause mortality. In the present sub-study using 10-year follow-up data, we investigated associations between serum endostatin at entry (randomization) and the composite outcome and its components during follow-up. The placebo group was used as discovery sample (1204 events, n = 1998) and the clarithromycin-treated group as replication sample (1220 events, n = 1979).

    RESULTS: In Cox regression models adjusting for cardiovascular risk factors, glomerular filtration rate, and current pharmacological treatment, higher serum endostatin was associated with an increased risk of the composite outcome in the discovery sample (hazard ratio per standard deviation increase 1.11, 95% CI 1.03-1.19, p = 0.004), but slightly weaker and not statistically significant in the replication sample (hazard ratio 1.06, 95% CI 1.00-1.14, p = 0.06). In contrast, strong and consistent associations were found between endostatin and cardiovascular and all-cause mortality in all multivariable models and sub-samples. Addition of endostatin to a model with established cardiovascular risk factors provided no substantial improvement of risk prediction (<1%).

    CONCLUSIONS: Raised levels of serum endostatin might be associated with cardiovascular events in patients with stable coronary heart disease. The clinical utility of endostatin measurements remains to be established.

  • 340. Ruge, Toralph
    et al.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Endostatin: a promising biomarker in the cardiovascular continuum?2017In: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 11, no 10, p. 905-916Article, review/survey (Refereed)
    Abstract [en]

    The current review article aims to provide an up-to-date summary of previous studies in humans that have reported the association between circulating endostatin levels and different cardiovascular phenotypes. We also aim to provide suggestions for future directions of future research evaluating endostatin as a clinically relevant cardiovascular biomarker. With a few exceptions, higher circulating levels of endostatin seem to reflect vascular and myocardial damage, and a worsened prognosis for cardiovascular events or mortality in individuals with hypertension, diabetes, kidney disease, cardiovascular disease, as well as in the general population. Circulating endostatin seems to be a promising biomarker for cardiovascular pathology, but there is not enough evidence to date to support the use of endostatin measurements in clinical practice.

  • 341. Ruge, Toralph
    et al.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Tobias E
    Carrero, Juan-Jesús
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    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 Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Endostatin Level is Associated with Kidney Injury in the Elderly: Findings from Two Community-Based Cohorts2014In: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 40, no 5, p. 417-424Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to investigate the associations between circulating endostatin and the different aspects of renal dysfunction, namely, estimated (cystatin C) glomerular filtration rate (GFR) and urine albumin-creatinine ratio (ACR).

    Methods: Two independent longitudinal community-based cohorts of elderly. ULSAM, n = 786 men; age 78 years; median GFR 74 ml/min/1.73 m(2); median ACR 0.80 mg/mmol); and PIVUS, n = 815; age 75 years; 51% women; median GFR; 67 ml/min/1.73 m(2); median ACR 1.39 mg/mmol. Cross-sectional associations between the endostatin levels and GFR as well as ACR, and longitudinal association between endostatin at baseline and incident CKD (defined as GFR <60 ml/min/1.73 m(2)) were assessed.

    Results: In cross-sectional regression analyses adjusting for age, gender, inflammation, and cardiovascular risk factors, serum endostatin was negatively associated with GFR (ULSAM: B-coefficient per SD increase -0.51, 95% CI (-0.57, -0.45), p < 0.001; PIVUS -0.47, 95% CI (-0.54, -0.41), p < 0.001) and positively associated with ACR (ULSAM: B-coefficient per SD increase 0.24, 95% CI (0.15, 0.32), p < 0.001; PIVUS 0.13, 95% CI (0.06-0.20), p < 0.001) in both cohorts. Moreover, in longitudinal multivariable analyses, higher endostatin levels were associated with increased risk for incident CKD defined as GFR <60 ml/min/1.73 m(2) at re-investigations in both ULSAM (odds ratio per SD increase of endostatin 1.39 (95% CI 1.01-1.90) and PIVUS 1.68 (95% CI 1.36-2.07)).

    Conclusions: Higher circulating endostatin is associated with lower GFR and higher albuminuria and independently predicts incident CKD in elderly subjects. Further studies are warranted to investigate the underlying mechanisms linking endostatin to kidney pathology, and to evaluate the clinical relevance of our findings.

  • 342.
    Rönn, Monika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Söderberg, Stefan
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden; Umea Univ, Ctr Heart, Umea, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Bisphenol A is related to circulating levels of adiponectin, leptin and ghrelin, but not to fat mass or fat distribution in humans2014In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 112, p. 42-48Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Since bisphenol A (BPA) has been shown to induce obesity in experimental studies, we explored the associations between BPA and fat mass, fat distribution and circulating levels of adiponectin, leptin and ghrelin in humans.

    METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), fat mass and fat distribution were determined in 70-year-old men and women (n=890) by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) (n=287). Serum levels of BPA were analyzed using isotope liquid chromatography/tandem mass spectrometer (API4000LC-MS/MS). Hormone levels were analyzed with radioimmunoassays (RIA) or enzyme-linked immunosorbent assay (ELISA). Imaging was performed approximately two years following collection of other data.

    RESULTS: Serum concentrations of BPA were not related to adipose tissue measurements by DXA or MRI. BPA associated positively with adiponectin and leptin, but negatively with ghrelin, following adjustments for sex, height, fat mass, lean mass, smoking, alcohol consumption, physical activity, energy intake, and educational levels (p<0.001, p=0.009, p<0.001, respectively). The relationship between BPA and ghrelin was stronger in women than in men.

    CONCLUSION: Although no relationships between BPA levels and measures of fat mass were seen, BPA associated strongly with the adipokines adiponectin and leptin and with the gut-hormone ghrelin suggesting that BPA may interfere with hormonal control of hunger and satiety.

  • 343.
    Salihovic, Samira
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Stubleski, Jordan
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Kärrman, Anna
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study2018In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 117, p. 196-203Article in journal (Refereed)
    Abstract [en]

    Background: While it is known that perfluoroalkyl substances (PFASs) induce liver toxicity in experimental studies, the evidence of an association in humans is inconsistent.

    Objective: The main aim of the present study was to examine the association of PFAS concentrations and markers of liver function using panel data.

    Methods: We investigated 1002 individuals from Sweden (50% women) at ages 70, 75 and 80 in 2001-2014. Eight PFASs were measured in plasma using isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). Bilirubin and hepatic enzymes alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) were determined in serum using an immunoassay methodology. Mixed-effects linear regression models were used to examine the relationship between the changes in markers of liver function and changes in PFAS levels.

    Results: The changes in majority of PFAS concentrations were positively associated with the changes in activity of ALT, ALP, and GGT and inversely associated with the changes in circulating bilirubin after adjustment for gender and the time-updated covariates LDL- and HDL-cholesterol, serum triglycerides, BMI, statin use, smoking, fasting glucose levels and correction for multiple testing. For example, changes in perfluorononanoic acid (PFNA) were associated with the changes liver function markers beta(BILIRUBIN) = -1.56, 95% confidence interval (CI) -1.93 to -1.19, beta(ALT)= 0.04, 95% CI 0.03-0.06, and beta(ALP)= 0.11, 95% CI 0.06-0.15.

    Conclusion: Our longitudinal assessment established associations between changes in markers of liver function and changes in plasma PFAS concentrations. These findings suggest a relationship between low-dose background PFAS exposure and altered liver function in the general population.

  • 344.
    Schultze, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lind, Monica P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Whole blood and serum concentrations of metals in a Swedish population-based sample2014In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 74, no 2, p. 143-148Article in journal (Refereed)
    Abstract [en]

     Objective

    While the potential toxicity of metals in humans is a well-established field of research, there are few studies that examine circulating concentrations of metals in large population-based samples. The aim of this study was to analyze levels of heavy metals and trace elements in both whole blood and serum in an elderly population, and to examine if gender, kidney function, haemoglobin or serum albumin could impact the distribution of metals between whole blood and serum.

    Methods

    Whole blood and serum samples from 1016 70-year-olds living in Uppsala, Sweden, were analyzed for aluminium, cadmium, cobalt, copper, chromium, mercury, manganese, molybdenum, nickel, lead, and zinc using inductively coupled plasma-sector field mass spectrometry (ICP-SFMS). Distribution between whole blood and serum was evaluated by the ratio between whole blood and serum concentration (B/S-ratio).

    Results

    Concentrations differed significantly between whole blood and serum measurements for all 11 metals (p < 0.00001). The highest B/S-ratios were found for lead (27), zinc (9), manganese (6), and nickel (4). Copper (0.86), cobalt (0.84), and molybdenum (0.86) showed B/S-ratios < 1. Especially the B/S-ratios for chromium, mercury and nickel correlated with kidney function (GFR) (r = 0.21, - 0.21 and - 0.36 respectively, p < 0.0001).

    Conclusions

    The distribution between whole blood and serum varied considerably for different metals. This distribution correlated with physiological factors, mainly with kidney function, for several of the metals.

  • 345.
    Simm, Mikael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Söderberg, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Castegren, Markus
    Department of Anaesthesia, Intensive Care & Surgical Services, Karolinska University Hospital, Huddinge, Stockholm, Sweden..
    Nilsen, Tom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study2016In: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 10, no 8, p. 811-818Article in journal (Refereed)
    Abstract [en]

    AIM: To determine the performance of plasma calprotectin as a marker of sepsis on intensive care unit (ICU) admission and as a marker of mortality day 30 post-ICU admission.

    MATERIALS & METHODS: Consecutive ICU patients were allocated to: sepsis (n = 15), postoperative inflammation (n = 23) and intoxication without inflammation (n = 7) groups.

    RESULTS: Calprotectin was 4.3 (2.6-8.2; mg/l; median [interquartile range]) in the sepsis, 2.8 (1.6-4.4) in the postoperative and 0.7 (0.4-1.6) in the intoxication groups. Area under the receiver operating characteristic curve for sepsis versus intoxication group was: 0.95, for sepsis versus postoperative groups: 0.65 and for survivors versus nonsurvivors: 0.70.

    CONCLUSION: Calprotectin was a sensitive marker of systemic inflammation, is a potential sepsis marker and performed well as mortality predictor in this pilot study.

  • 346. Sjöberg, B
    et al.
    Qureshi, A R
    Heimbürger, O
    Stenvinkel, P
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Bárány, P
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Association between levels of pentraxin 3 and incidence of chronic kidney disease in the elderly2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, no 2, p. 173-179Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Higher levels of the novel inflammatory marker pentraxin 3 (PTX3) predict cardiovascular mortality in patients with chronic kidney disease (CKD). Yet, whether PTX3 predicts worsening of kidney function has been less well studied. We therefore investigated the associations between PTX3 levels, kidney disease measures and CKD incidence.

    METHODS: Cross-sectional associations between serum PTX3 levels, urinary albumin/creatinine ratio (ACR) and cystatin C-estimated glomerular filtration rate (GFR) were assessed in two independent community-based cohorts of elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 768, 51% women, mean age 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 651, mean age 77 years). The longitudinal association between PTX3 level at baseline and incident CKD (GFR <60 mL( ) min(-1)  1.73 m(-) ²) was also analysed (number of events/number at risk: PIVUS 229/746, ULSAM 206/315).

    RESULTS: PTX3 levels were inversely associated with GFR [PIVUS: B-coefficient per 1 SD increase -0.16, 95% confidence interval (CI) -0.23 to -0.10, P < 0.001; ULSAM: B-coefficient per 1 SD increase -0.09, 95% CI -0.16 to -0.01, P < 0.05], but not ACR, after adjusting for age, gender, C-reactive protein and prevalent cardiovascular disease in cross-sectional analyses. In longitudinal analyses, PTX3 levels predicted incident CKD after 5 years in both cohorts [PIVUS: multivariable odds ratio (OR) 1.21, 95% CI 1.01-1.45, P < 0.05; ULSAM: multivariable OR 1.37, 95% CI 1.07-1.77, P < 0.05].

    CONCLUSIONS: Higher PTX3 levels are associated with lower GFR and independently predict incident CKD in elderly men and women. Our data confirm and extend previous evidence suggesting that inflammatory processes are activated in the early stages of CKD and drive impairment of kidney function. Circulating PTX3 appears to be a promising biomarker of kidney disease.

  • 347.
    Skorup, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Maudsdotter, Lisa
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Jonsson, Ann-Beth
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Beneficial Antimicrobial Effect of the Addition of an Aminoglycoside to a β-Lactam Antibiotic in an E. coli Porcine Intensive Care Severe Sepsis Model.2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 2, p. e90441-Article in journal (Refereed)
    Abstract [en]

    This study aimed to determine whether the addition of an aminoglycoside to a ß-lactam antibiotic increases the antimicrobial effect during the early phase of Gram-negative severe sepsis/septic shock. A porcine model was selected that considered each animal's individual blood bactericidal capacity. Escherichia coli, susceptible to both antibiotics, was given to healthy pigs intravenously during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either cefuroxime alone (n = 9), a combination of cefuroxime+tobramycin (n = 9), or saline (control, n = 9). Blood samples were collected hourly for cultures and quantitative polymerase chain reaction (PCR). Bacterial growth in the organs after 6 h was chosen as the primary endpoint. A blood sample was obtained at baseline before start of bacterial infusion for ex vivo investigation of the blood bactericidal capacity. At 1 h after the administration of the antibiotics, a second blood sample was taken for ex vivo investigation of the antibiotic-induced blood killing activity. All animals developed severe sepsis/septic shock. Blood cultures and PCR rapidly became negative after completed bacterial infusion. Antibiotic-induced blood killing activity was significantly greater in the combination group than in the cefuroxime group (p<0.001). Growth of bacteria in the spleen was reduced in the two antibiotic groups compared with the controls (p<0.01); no difference was noted between the two antibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (p<0.05). High blood bactericidal capacity at baseline was associated with decreased growth in the blood and spleen (p<0.05). The addition of tobramycin to cefuroxime results in increased antibiotic-induced blood killing activity and less bacteria in the liver than cefuroxime alone. Individual blood bactericidal capacity may have a significant effect on antimicrobial outcome.

  • 348.
    Skorup, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Maudsdotter, Lisa
    Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Mode of Bacterial Killing Affects the Inflammatory Response and Associated Organ Dysfunctions in a Porcine E. coli Intensive Care Sepsis ModelManuscript (preprint) (Other academic)
  • 349.
    Skorup, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Wilske, Frida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Hanslin, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Enhanced Bacterial Clearance at a Secondary Sepsis Challenge in an Endotoxin-tolerant Porcine Intensive Care ModelManuscript (preprint) (Other academic)
  • 350.
    Sohrabian, Azita
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Mathsson Alm, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Thermo Fisher Sci, ImmunoDiagnost Div, Uppsala, Sweden..
    Hansson, M.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Lysholm, J.
    Falun Cent Hosp, Clin Rheumatol, Falun, Sweden..
    Cornillet, M.
    Toulouse Univ, INSERM, U1056, Epithelial Differentiat & Rheumatoid Autoimmun, Toulouse, France..
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Skriner, K.
    Charite, Dept Med, Berlin, Germany..
    Serre, G.
    Toulouse Univ, INSERM, U1056, Epithelial Differentiat & Rheumatoid Autoimmun, Toulouse, France..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Weitoft, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Number Of Peptide-Specific Anti-Citrullinated Peptide Antibodies In Synovial Fluid And In Synovial Fluid Immune Complexes Associate With Degree Of Radiological Destruction And Response To Triamcinolone Hexacetonide For Knee Synovitis In Rheumatoid Arthritis2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. 509-510Article in journal (Other academic)
456789 301 - 350 of 415
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