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  • 251.
    Weitoft, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Manivel, Vivek A
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Lysholm, Jörgen
    Clinic of Rheumatology, Falun Hospital, Falun.
    Knight, Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Cathepsin S and cathepsin L in serum and synovial fluid in rheumatoid arthritis with and without autoantibodies2015Inngår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 54, nr 10, s. 1923-1928Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Cathepsin S and cathepsin L are endosomal proteolytic enzymes involved in the degradation of extracellular matrixes, angiogenesis and antigen presentation. Cathepsins could thus play several roles in the disease process of RA. The aim of this study was to examine differences in cathepsin S and cathepsin L levels in serum and SF of RA patients with and without ACPA and RF.

    METHODS: In this study 121 patients with RA and clinical signs of knee synovitis were recruited. Patient characteristics were collected and matched samples of serum and SF were analysed for cathepsin S, cathepsin L, ACPA, IgA and IgM RF, CRP and MMP3.

    RESULTS: SF levels of cathepsin L, cathepsin S and MMP3 were significantly higher than in serum. Serum levels of both cathepsins were significantly higher in patients with ACPA, IgM-RF and IgA-RF compared with patients without these antibodies. SF levels of both cathepsins correlated with DAS28 and CRP in ACPA- and RF-positive but not in seronegative patients.

    CONCLUSION: The differences in cathepsin S and cathepsin L between RA patients with and without autoantibodies indicate that these cathepsins have a specific role in the disease process of seropositive RA. In this phenotype, cathepsin serum levels may reflect the autoimmune activity, whereas the levels in SF may reflect the local inflammatory and matrix degrading process in the joint.

  • 252.
    Weitoft, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Manivel, Vivek
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Lysholm, J.
    Knight, A.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Cathepsin S and cathepsin L in serum and synovial fluid in rheumatoid arthritis with and without autoantibodies2014Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr S127, s. 53-53Artikkel i tidsskrift (Annet vitenskapelig)
  • 253.
    Weitoft, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Knight, Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Lysholm, Jörgen
    Saxne, Tore
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Outcome predictors of intra-articular glucocorticoid treatment for knee synovitis in patients with rheumatoid arthritis: a prospective cohort study2014Inngår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 16, nr 3, s. R129-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION:

    Intra-articular glucocorticoid treatment (IAGC) is widely used for symptom relief in arthritis. However, knowledge of factors predicting treatment outcome is limited. The aim of the present study was to identify response predictors of IAGC for knee synovitis in patients with rheumatoid arthritis (RA).

    METHODS:

    In this study 121 RA patients with synovitis of the knee were treated with intra-articular injections of 20 mg triamcinolone hexacetonide. They were followed for 6 months and the rate of clinical relapse was studied. Non-responders (relapse within 6 months) and responders were compared regarding patient characteristics and knee joint damage as determined by the Larsen-Dale index. In addition, matched samples of serum and synovial fluid were analyzed for factors reflecting the inflammatory process (C-reactive protein, interleukin 6, tumour necrosis factor alpha, vascular endothelial growth factor), joint tissue turnover (cartilage oligomeric matrix protein, metalloproteinase 3), and autoimmunity (antinuclear antibodies, antibodies against citrullinated peptides, rheumatoid factor).

    RESULTS:

    During the observation period, 48 knees relapsed (40%). Non-responders had more radiographic joint damage than responders (p = 0.002) and the pre-treatment vascular endothelial growth factor (VEGF) level in synovial fluid was significantly higher in non-responders (p = 0.002).

    CONCLUSIONS:

    Joint destruction is associated with poor outcome of IAGC for knee synovitis in RA. In addition, higher levels of VEGF in synovial fluid are found in non-responders, suggesting that locally produced VEGF is a biomarker for recurrence of synovial hyperplasia and the risk for arthritis relapse.

  • 254.
    Wide, Leif
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Eriksson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Dynamic changes in glycosylation and glycan composition of serum FSH and LH during natural ovarian stimulation2013Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, nr 3, s. 153-164Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Glycosylation and glycan composition are of fundamental importance for the biological properties of FSH and LH. The aim of this study was to determine the glycosylation, sialylation, and sulfonation of serum FSH and LH throughout the normal menstrual cycle. Methods. Serum samples were collected from 79 healthy women with regular menstrual cycles. The mean numbers of anionic monosaccharide (AMS), sialic acid (SA), and sulfonated N-acetylgalactosamine (SU) residues per FSH and LH molecule were estimated for all sera with methods based on electrophoreses, neuraminidase treatments, and fluoroimmunoassays of the gonadotrophins. Results. Di-glycosylated glycoforms (FSHdi, LHdi) were detected in serum in addition to tetra-glycosylated FSH (FSHtetra) and tri-glycosylated LH (LHtri). FSHdi exhibited two peaks: one on day 5 to 7 and one, more pronounced, at midcycle. FSHtetra plateaued at a high concentration from day 5 to 15, without a midcycle peak. There were lower concentrations of LHdi than LHtri, except at midcycle when the opposite occurred. The mean numbers of SA and SU residues per molecule of FSH and LH in serum showed four different patterns during the cycle, all with highly significant (P < 0.0001) differences between levels at different phases of the cycle. The pattern of SA residues on FSH was 'M'-shaped, and that of SU on LH 'V'-shaped. Conclusion. Serum FSH and LH governing the natural ovarian stimulation process exhibited dynamic changes of glycosylation and glycan composition. This new information on the FSH and LH molecular structures may lead to more successful mono-ovulatory treatment regimens for ovulation induction in anovulatory women.

  • 255.
    Wikström, Anna-Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Hagmar, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Ronquist, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Evaluation of a Plasma hCG Method for Point of Care Testing with the Aim of Shortening Test-Turnaround-Times2015Inngår i: Open Journal of Obstetrics and Gynecology, ISSN 2160-8792, E-ISSN 2160-8806, Vol. 5, nr 6, s. 341-343Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To examine the correlation between plasma hCG results obtained with the new i-STAT® hCG point of care test with those concomitantly obtained from the central hospital laboratory utilizing the same patient samples.

    Methods: Prospective cross-sectional laboratory test evaluation. We compared plasma hCG results obtained with the i-STAT® hCG test (Abbott Point of Care, Princeton, NJ, USA) with Architect Ci8200 (Abbott Laboratories, Abbott Park, IL, USA). We also calculated the total coefficient of variation (CV) for the i-STAT® method.

    Results: The two methods showed a good linear correlation (R2 = 0.994; slope 1.03) and CV for the i-STAT® method was 2.1% - 5.2%.

    Conclusion: We suggest that the i-STAT® hCG blood assay could be used as a complement to urine hCG assays in clinical situations when rapid test results are needed and urine is not available.

  • 256. Winkel, P
    et al.
    Jakobsen, J
    Hilden, J
    Lange, T
    Jensen, G
    Kjøller, E
    Sajadieh, A
    Kastrup, J
    Kolmos, H
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gluud, C
    Predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC): Statistical analysis plan for data originating from the CLARICOR (clarithromycin for patients with stable coronary heart disease) trial.2017Inngår i: Diagnostic and Prognostic Research, Vol. 1, s. 10-Artikkel i tidsskrift (Fagfellevurdert)
  • 257. Witasp, Anna
    et al.
    Carrero, Juan Jesús
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Adamsson, Viola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Stenvinkel, Peter
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Inflammatory biomarker pentraxin 3 (PTX3) in relation to obesity, body fat depots, and weight loss2014Inngår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 22, nr 5, s. 1373-1379Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: The relation between inflammatory markers, adiposity and disease is under extensive study. Here we tested the hypothesis that the immunomodulatory protein pentraxin 3 (PTX3) is associated with adiposity in the general population.

    DESIGN AND METHODS: Serum PTX3 concentrations, body mass index (BMI), waist circumference (WC) and fat depots, as quantified by dual-energy X-ray absorptiometry and magnetic resonance imaging, were assessed in three community-based cohorts: ULSAM, n = 790, mean age 78 years; PIVUS, n = 1003, mean age 70 years, women 50%; and the NORDIET-trial, n = 86, mean age 53 years, women 63%. Participants were re-examined after 5 years (PIVUS, n = 804) or following a 6-week randomized controlled dietary intervention (NORDIET).

    RESULTS: PTX3 levels were inversely associated with BMI and WC as well as with total and visceral fat (P < 0.05 for all; adjusted for age, inflammatory biomarkers and cardiovascular risk factors). The association between PTX3 and BMI appeared even stronger in nonobese individuals. A decrease in BMI over 5 years as well as weight loss following the NORDIET intervention were associated with increased serum PTX3 concentrations (P < 0.001).

    CONCLUSIONS: These consistent data support an inverse association between circulating PTX3 and anthropometrical measures, calling for further mechanistic studies of the link between PTX3 and fat.

  • 258.
    Wu, Di
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Yan, Junhong
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sun, Yu
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ronquist, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Cavalli, Marco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Oelrich, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Wadelius, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Landegren, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kamali-Moghaddam, Masood
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Profiling individual protein complexes by proximity-dependent barcodingManuskript (preprint) (Annet vitenskapelig)
  • 259.
    Xu, Shengyuan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Zhao, Linshu
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik.
    Lindahl, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Plasma Prolylcarboxypeptidase (Angiotensinase C) Is Increased in Obesity and Diabetes Mellitus and Related to Cardiovascular Dysfunction2012Inngår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 58, nr 7, s. 1110-1115Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Prolylcarboxypeptidase (PRCP) (angiotensinase C) has 3 major targets, angiotensin II, prekallikrein, and alpha-melanocyte stimulating hormone(1-13). The truncation of the latter leads to loss in appetite regulation and obesity in experimental animals. The objectives of this study were to purify PRCP from a native source, establish a sensitive immunoassay for PRCP, and relate plasma PRCP concentrations to signs and symptoms of obesity, diabetes mellitus, and cardiovascular dysfunction.

    METHODS: Purification of PRCP from human neutrophils and establishment of a sensitive ELISA was carried out with the use of samples from study participants. Three cohorts were studied: healthy individuals (n = 40); a chest pain cohort (Fast Assessment of Thoracic Pain by Neural Networks) (n = 165); and a community-based cohort [Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS)] (n = 1004).

    RESULTS: PRCP was purified to homogeneity. Mean (SD) plasma concentrations in healthy individuals were 12.9 (3.2), mu g/L and were increased in patients with chest pain and in patients with obesity and/or diabetes mellitus (P < 0.0001). In the PIVUS cohort the concentrations were related to several measures of arterial plaque formation, thickness of arterial intima media and posterior wall of the heart (P = 0.04-0.000005); the Framingham score (r = 0.14, P < 0.0001); and concentrations of C-reactive protein (r = 0.16, P < 0.0001) and N-terminal pro B-type natriuretic peptide (r = -0.13, P < 0.0001).

    CONCLUSIONS: Plasma concentrations of PRCP may be used to reflect metabolic conditions in individuals with obesity and diabetes mellitus. The associations of PRCP concentrations with signs of cardiovascular dysfunction and cardiovascular abnormalities suggest a pivotal role of the enzyme in disease. (c) 2012 American Association for Clinical Chemistry

  • 260.
    Yu, Zhang
    et al.
    Changchun Brother Biotech Co Ltd, Changchun 130062, Peoples R China..
    Jing, Huang
    Jilin Univ, Affiliated Hosp 1, Dept Lab, Changchun 130021, Peoples R China..
    Hongtao, Pan
    Furong, Jia
    Yuting, Jin
    Xu, Shengyuan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Distinction between bacterial and viral infections by serum measurement of human neutrophil lipocalin (HNL) and the impact of antibody selection2016Inngår i: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 432, s. 82-86Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The distinction between acute infections of bacterial or viral causes is clinically important, but often very difficult even for experienced doctors. Previous studies indicated that serum measurements of HNL (Human Neutrophil Lipocalin) might be a superior diagnostic means in this regard, but also indicated that the antibody conformation of the HNL assay might have an impact on the diagnostic performance. The aim of the present report was to examine this further. Methods: Several different (n = 24) HNL ELISA assays were developed using different combinations of monoclonal and polyclonal HNL antibodies. Sera were collected from healthy persons (n = 188) and from 155 patients with acute infections.before any antibiotics treatment. The patients were diagnosed as having bacterial (n = 69) or viral causes (n = 86) of their infections. Plasma and serum were also examined by Western blotting using HNL-specific polyclonal antibodies. Results: The optimal assay format for the distinction between bacterial and viral infection resulted in an area under the receiver operating characteristics curve (AuROC) for S-HNL of 0.98. (95% CI 0.94-1.00) as compared to 0.83 (0.76-0.88) for blood neutrophil counts and 0.69 (0.61-0.76) for S-CRP. Results also showed that different assay formats of HNL identified monomeric and dimeric HNL differently, the monomeric HNL being elevated in viral infections and the dimeric HNL being elevated in bacterial infections. Conclusion: We conclude that serum theasurement of HNL is a superior diagnostic means to distinguish between acute infections caused by bacteria or virus. For optimal clinical performance the immunoassay should address conformational epitopes in the dimeric HNL.

  • 261. Zhulina, Yaroslava
    et al.
    Hahn-Stromberg, Victoria
    Shamikh, Alia
    Peterson, Christer G. B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Gustavsson, Anders
    Nyhlin, Nils
    Wickbom, Anna
    Bohr, Johan
    Bodin, Lennart
    Tysk, Curt
    Carlson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Halfvarson, Jonas
    Subclinical Inflammation with Increased Neutrophil Activity in Healthy Twin Siblings Reflect Environmental Influence in the Pathogenesis of Inflammatory Bowel Disease2013Inngår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 19, nr 8, s. 1725-1731Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background:The mechanisms behind increased fecal calprotectin (FC) in healthy relatives of patients with inflammatory bowel disease (IBD) are unknown. Our aims were to explore if there is a subclinical inflammation with increased neutrophil activity in healthy twin siblings in discordant twin pairs with IBD and to assess the influence of genetics in this context.Methods:Nuclear factor kappa B (NF-B) and neutrophil activity, based on myeloperoxidase (MPO) and FC, were analyzed in healthy twin siblings in discordant twin pairs with IBD and compared with healthy controls. NF-B and MPO were assessed by immunohistochemistry and FC by enzyme-linked immunosorbent assay.Results:In total, 33 of 34 healthy twin siblings were histologically normal. Increased NF-B was more often observed in healthy twin siblings in discordant twin pairs with Crohn's disease (13/18 [73%]) and with ulcerative colitis (12/16 [75%]) than in healthy controls (8/45 [18%]). MPO was more often increased in healthy twin siblings in discordant pairs with Crohn's disease (12/18 [67%]) than in healthy controls (11/45 [24%]) and FC more often in healthy twin siblings in discordant pairs with ulcerative colitis (14/21 [67%]) than in healthy controls (6/31 [19%]). Interestingly, the observed differences remained when healthy monozygotic and dizygotic twin siblings were analyzed separately.Conclusions:We observed increased NF-B, MPO, and FC in healthy twins in both monozygotic and dizygotic discordant pairs with IBD. These novel findings speak for an ongoing subclinical inflammation with increased neutrophil activity in healthy first-degree relatives.

  • 262. Ziegler-Heitbrock, Loems
    et al.
    Frankenberger, Marion
    Heimbeck, Irene
    Burggraf, Dorothe
    Wjst, Matthias
    Haeussinger, Karl
    Brightling, Chris
    Gupta, Sumit
    Parr, David
    Subramanian, Deepak
    Singh, Dave
    Kolsum, Umme
    Boschetto, Piera
    Potena, Alfredo
    Gorecka, Dorota
    Nowinski, Adam
    Barta, Imre
    Doeme, Balazs
    Strausz, Janos
    Greulich, Timm
    Vogelmeier, Claus
    Bals, Robert
    Hohlfeld, Jens M.
    Welte, Tobias
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Gut, Ivo
    Boland, Anne
    Olaso, Robert
    Hager, Joerg
    Hiemstra, Pieter
    Rabe, Klaus F.
    Unmuessig, Martina
    Mueller-Ouernhelm, Joachim
    Prasse, Antje
    The EvA study: aims and strategy2012Inngår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 40, nr 4, s. 823-829Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The EvA study is a European Union-funded project under the Seventh Framework Programme (FP7), which aims at defining new markers for chronic obstructive pulmonary disease (COPD) and its subtypes. The acronym is derived from emphysema versus airway disease, indicating that the project targets these two main phenotypes of the disease. The EvA study is based on the concept that emphysema and airway disease are governed by different pathophysiological processes, are driven by different genes and have differential gene expression in the lung. To define these genes, patients and non-COPD controls are recruited for clinical examination, lung function analysis and computed tomography (CT) of the lung. CT scans are used to define the phenotypes based on lung density and airway wall thickness. This is followed by bronchoscopy in order to obtain samples from the airways and the alveoli. These tissue samples, along with blood samples, are then subjected to genome-wide expression and association analysis and markers linked to the phenotypes are identified. The population of the EvA study is different from other COPD study populations, since patients with current oral glucocorticoids, antibiotics and exacerbations or current smokers are excluded, such that the signals detected in the molecular analysis are due to the distinct inflammatory process of emphysema and airway disease in COPD.

  • 263.
    Ärnlöv, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Carlsson, Axel C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ingelsson, Erik
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Tobias E
    Higher fibroblast growth factor-23 increases the risk of all-cause and cardiovascular mortality in the community2013Inngår i: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 83, nr 1, s. 160-166Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fibroblast growth factor-23 (FGF23), a regulator of mineral metabolism, has been linked to cardiovascular disease in chronic kidney disease. As community-based data of the longitudinal association between FGF23 and cardiovascular events are lacking, we investigated a possible relationship in 727 men of the Uppsala Longitudinal Study of Adult Men population-based cohort (mean age 77 years). During a median follow-up of 9.7 years, 110 participants died of cardiovascular causes. In Cox regression models adjusted for age and established cardiovascular risk factors, higher serum FGF23 was associated with a significantly increased risk for cardiovascular mortality (hazard ratio (HR) per increased s.d. of 1.36). This relationship remained significant, albeit attenuated, after adjustment for glomerular filtration rate (GFR) (HR 1.21). FGF23 was also associated with all-cause mortality, although the association was weaker than that with cardiovascular mortality, and it was nonsignificant in fully adjusted multivariate models. Spline analysis suggested a log-linear relationship between FGF23 and outcome. Participants with a combination of high FGF23 (>60 pg/ml), low GFR (<60 ml/min), and micro-/macro-albuminuria (albumin/creatinine ratio above 3 mg/ml) had an almost eightfold increased risk compared with participants without these abnormalities. Thus, a higher FGF23 level is associated with an increased cardiovascular mortality risk in the community. Clinical trials are needed to determine whether FGF23 is a modifiable risk factor.

  • 264.
    Ärnlöv, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 20132015Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 386, nr 9995, s. 743-800Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.

    METHODS: Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries.

    FINDINGS: Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2·4 billion and 1·6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537·6 million in 1990 to 764·8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114·87 per 1000 people to 110·31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21·1% in 1990 to 31·2% in 2013.

    INTERPRETATION: Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.

    FUNDING: Bill & Melinda Gates Foundation.

  • 265.
    Ärnlöv, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ruge, Toralph
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Serum endostatin and risk of mortality in the elderly: findings from 2 community-based cohorts2013Inngår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 33, nr 11, s. 2689-2695Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    Experimental data imply that endostatin, a proteolytically cleaved fragment of collagen XVIII, could be involved in the development of cardiovascular disease and cancer. Prospective data concerning the relation between circulating endostatin and mortality are lacking. Accordingly, we aimed to study associations between circulating endostatin and mortality risk.

    APPROACH AND RESULTS:

    Serum endostatin was analyzed in 2 community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n=931; mean age, 70 years; median follow-up, 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=748; mean age, 77 years; median follow-up, 9.7 years). During follow-up, 90 participants died in PIVUS (1.28/100 person-years at risk), and 417 participants died in ULSAM (6.7/100 person-years at risk). In multivariable Cox regression models adjusted for age and established cardiovascular risk factors, 1 SD higher ln(serum endostatin level) was associated with a hazard ratio of mortality of 1.39 and 95% confidence interval, 1.26 to 1.53, on average in both cohorts. In the ULSAM cohort, serum endostatin was also associated with cardiovascular mortality (177 deaths; hazard ratio per SD of ln[endostatin] 1.45, 95% confidence interval [1.25-1.71]) and cancer mortality (115 deaths; hazard ratio per SD of ln[endostatin] 1.35, 95% confidence interval [1.10-1.66]).

    CONCLUSIONS:

    High serum endostatin was associated with increased mortality risk in 2 independent community-based cohorts of the elderly. Our observational data support the importance of extracellular matrix remodeling in the underlying pathophysiology of cardiovascular disease and cancer.

  • 266.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Helmersson, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Weitoft, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Seasonal variations of urate in a Swedish adult population2017Inngår i: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 36, nr 7, s. 1595-1598Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Seasonality in the incidence and prevalence of gout has previously been reported but the cause of this seasonality in gout is not explained. The aim of this study was to evaluate possible seasonal variations of urate in a large unselected Swedish adult population. We analyzed 170,915 urate test results from patients at a tertiary care hospital between 2000 and 2016. The results were divided according to sex and sampling month of the year. The median urate values were overall higher in males compared to females and both males and females had peak urate concentrations in the summer months (June-August). There is a seasonal pattern for urate concentrations in a large Swedish population similar to the previously reported seasonality for gout. This may be clinically important and could contribute to the circannual variation of gout. The seasonal pattern should be recognized when evaluating patient results both in clinical practice and in research studies.

  • 267.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Flodin, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Comparison between cystatin C and creatinine estimated GFR in cardiology patients2015Inngår i: Cardiorenal medicine, ISSN 1664-5502, Vol. 5, nr 4, s. 289-296Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Estimation of the glomerular filtration rate (GFR) is essential for identification, evaluation and risk prediction in patients with kidney disease. Estimated GFR (eGFR) is also needed for the correct dosing of drugs eliminated by the kidneys and to identify high-risk individuals in whom coronary angiography or other procedures may lead to kidney failure. Both cystatin C and creatinine are used for the determination of GFR, and we aimed to investigate if eGFR by the two methods differ in cardiology patients.

     Methods: We compared cystatin C and creatinine (CKD-EPI) eGFR calculated from the same request from a cardiology outpatient unit (n = 2,716), a cardiology ward (n = 980), a coronary care unit (n = 1,464), and an advanced coronary care unit (n = 518) in an observational, cross-sectional study. 

    Results: The median creatinine eGFR results are approximately 10 ml/min/1.73 m2 higher than the median cystatin C eGFR that is up to 90 ml/min/1.73 m2, irrespective of the level of care. Creatinine eGFR resulted in a less advanced eGFR category in the majority of patients with a cystatin C eGFR <60 ml/min/1.73 m2.

    Conclusions: Our study demonstrates a difference between creatinine and cystatin C eGFR in cardiology patients. It is important to be aware of which marker is used for the reported eGFR to minimize erroneous interpretations of the test results, as this could lead to under- or overmedication. Further studies are needed to determine the best method of estimating the GFR in cardiology units.

  • 268.
    Åkerfeldt, Torbjörn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Gunningberg, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Leo Swenne, Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Ronquist, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Elective orthopedic and cardiopulmonary bypass surgery causes a reduction in serum endostatin levels2014Inngår i: European Journal of Medical Research, ISSN 0949-2321, E-ISSN 2047-783X, Vol. 19, s. 61-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Endostatin is an endogenous inhibitor of angiogenesis that inhibits neovascularisation. The aim of the study was to evaluate the effect of elective surgery on endostatin levels.

    Methods: Blood samples were collected prior to elective surgery and 4 and 30 days postoperatively in 2 patient groups: orthopedic surgery (n =27) and coronary bypass patients (n =21). Serum endostatin levels were measured by ELISA.

    Results: Serum endostatin was significantly reduced 30 days after surgery in comparison with presurgical values in both the orthopedic (P =0.03) and cardiopulmonary surgery (P =0.04) group.

    Conclusion: Serum endostatin is reduced 30 days after surgery. This reduction would favor angiogenesis and wound-healing.

  • 269.
    Åkerfeldt, Torbjörn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Circulating Human Fractalkine is Decreased Post-operatively After Orthopedic and Coronary Bypass Surgery2014Inngår i: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 28, nr 2, s. 185-188Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fractalkine is an important chemokine involved in resolving normal inflammatory processes such as wound healing. Soluble fractalkine acts as a chemoattractant bringing cytotoxic and cytokine-producing cells to areas of inflammation. The aim of the present study was to investigate circulating fractalkine during inflammatory response induced by surgery.

    MATERIALS AND METHODS: Fractalkine was analyzed in serum samples from orthopedic surgery patients (n=29) and coronary bypass patients (n=21). The samples were collected prior to surgery and 4 and 30 days after surgery, respectively.

    RESULTS: Fractalkine concentrations decreased from pre-operative levels of 1,764 (1,330-2,434) pg/mL to 1,520 (1,330-2,434) pg/mL at 4 days after surgery, and to 1,285 (1,099-1,462) pg/mL 30 days after surgery in patients undergoing orthopedic procedures (p<0.01, 30 days post-operatively versus pre-operatively). Furthermore, fractalkine concentrations decreased significantly from pre-operative levels of 1,856 (1,520-2,434) pg/mL to 1,338 (964-1,650) pg/mL 4 days post-operatively and to 1,266 (1,080-1,338) pg/mL 30 days post-operatively in patients undergoing coronary bypass surgery (p<0.01, 30 days post-operative versus pre-operative values).

    CONCLUSION: A significant and persistent decrease in circulating fractalkine was observed after orthopedic and coronary bypass surgery despite a marked inflammatory response.

  • 270.
    Åkerfeldt, Torbjörn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Gunningberg, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Swenne, Christine Leo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Postsurgical Acute Phase Reaction is Associated with Decreased Levels of Circulating Myostatin2015Inngår i: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 38, nr 4, s. 1727-1730Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Muscle strength is of importance for postsurgical rehabilitation. Myostatin is a growth factor that regulates the size of muscles and could thus influence muscle mass and function in the postsurgical period. The aim of the present study was to study the changes in myostatin levels during the postsurgical inflammatory period. Myostatin was analysed in serum samples from two elective surgery groups, orthopaedic surgery (n = 24) and coronary bypass patients (n = 21). The samples were collected prior to surgery and 4 and 30 days after surgery. In the orthopaedic group, the median myostatin levels decreased from 3582 ng/L prior to surgery to 774 ng/L at day 4 (p < 0.001) and to 2016 ng/L at day 30 (p < 0.001). Median CRP increased from 2.35 mg/L preoperatively to 117 mg/L at day 4 and decreased to 5.5 mg/L at day 30 in the same group. The coronary bypass group showed a similar pattern with a decrease in myostatin from 4212 ng/L to 2574 ng/L at day 4 (p < 0.001) and to 2808 ng/L at day 30 (p = 0.002). Median CRP increased from 1.80 mg/L preoperatively to 136 mg/L at day 4 and returned to 6.12 mg/L at day 30 in the coronary bypass group. There was a significant decrease in myostatin concentrations both in the early and late postsurgical period. The lowest myostatin concentration time point coincided with the highest CRP concentration time point.

  • 271. Öhrvik, Veronica
    et al.
    Warensjö, Eva
    Science DepartmentNational Food AgencyUppsalaSweden.
    Nälsén, Cecilia
    Becker, Wulf
    Ridefelt, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lindroos, Anna Karin
    Dietary intake and biomarker status of folate in Swedish adults2018Inngår i: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 57, nr 2, s. 451-462Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: National data on folate status are missing in Sweden, and regional data indicate folate insufficiency in up to more than 25% of the study populations. The objectives were to determine folate intake and status in the adult Swedish population as well as identifying dietary patterns associated with beneficial folate status.

    METHODS: Folate intake was estimated using a web-based 4-d food record in adults aged 18-80 years (n = 1797). Folate status was measured as erythrocyte (n = 282) and plasma folate concentrations (n = 294). Factor analysis was used to derive a dietary pattern associated with a higher folate status.

    RESULTS: Median folate intake was 246 µg/day (Q 1 = 196, Q 3 = 304, n = 1797) and for women of reproductive age 227 µg/day (Q 1 = 181, Q 3 = 282, n = 450). As dietary folate equivalents (DFE), median intake was 257 µg/day (Q 1 = 201, Q 3 = 323) and for women of reproductive age 239 µg/day (Q 1 = 185, Q 3 = 300). Low blood folate concentrations were found in 2% (erythrocyte concentrations <317 nmol/L) and 4% (plasma concentrations <6.8 nmol/L) of the participants, respectively. None of the women of reproductive age had erythrocyte folate concentrations associated with the lowest risk of neural tube defects. Dietary patterns associated with higher folate status were rich in vegetables, pulses and roots as well as cheese and alcoholic beverages, and low in meat.

    CONCLUSIONS: Prevalence of low erythrocyte folate concentrations was low in this population, and estimated dietary intakes are well above average requirement. However, to obtain a folate status optimal for prevention of neural tube defects major dietary changes are required and folic acid supplements recommended prior to conception.

  • 272.
    Österroos, Albin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Kashif, Muhammad
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Haglund, Caroline
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Blom, Kristin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Andersson, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Gustafsson, Mats G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Eriksson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Larsson, R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Combination screening in vitro identifies synergistically acting KP372-1 and cytarabine against acute myeloid leukemia2016Inngår i: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 118, s. 40-49Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cytogenetic lesions often alter kinase signaling in acute myeloid leukemia (AML) and the addition of kinase inhibitors to the treatment arsenal is of interest. We have screened a kinase inhibitor library and performed combination testing to find promising drug-combinations for synergistic killing of AML cells. Cytotoxicity of 160 compounds in the library InhibitorSelect (TM) 384-Well Protein Kinase Inhibitor I was measured using the fluorometric microculture cytotoxicity assay (FMCA) in three AML cell lines. The 15 most potent substances were evaluated for dose-response. The 6 most cytotoxic compounds underwent combination synergy analysis based on the FMCA readouts after either simultaneous or sequential drug addition in AML cell lines. The 4 combinations showing the highest level of synergy were evaluated in 5 primary AML samples. Synergistic calculations were performed using the combination interaction analysis package COMBIA, written in R, using the Bliss independence model. Based on obtained results, an iterative combination search was performed using the therapeutic algorithmic combinatorial screen (TACS) algorithm. Of 160 substances, cell survival was <= 50% at <0.5 mu M for Cdk/Crk inhibitor, KP372-1, synthetic fascaplysin, herbimycin A, PDGF receptor tyrosine kinase inhibitor IV and reference-drug cytarabine. KP372-1, synthetic fascaplysin or herbimycin A obtained synergy when combined with cytarabine in AML cell lines MV4-11 and HL-60. KP372-1 added 24 h before cytarabine gave similar results in patient cells. The iterative search gave further improved synergy between cytarabine and KP372-1. In conclusion, our in vitro studies suggest that combining KP372-1 and cytarabine is a potent and synergistic drug combination in AML.

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